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Radiology Dissertation topics – Based on Latest Study and Research

Published by Ellie Cross at December 29th, 2022 , Revised On August 16, 2023

A dissertation is an essential part of the radiology curriculum for an MD, DNB, or DMRD degree programme. Dissertations in radiology can be very tricky and challenging due to the complexity of the subject.

Students must conduct thorough research to develop a first-class dissertation that makes a valuable contribution to the file of radiology. The first step is to choose a well-defined and clear research topic for the dissertation.

We have provided some interesting and focused ideas to help you get started. Choose one that motivates so you don’t lose your interest in the research work half way through the process.

List of Radiology Dissertation Topics

The use of computed tomography and positron emission tomography in the diagnosis of thyroid cancer
MRI diffusion tensor imaging is used to evaluate the traumatic spinal injury
Analyzing digital colour and subtraction in comparison patients with occlusive arterial disorders and doppler
Functional magnetic resonance imaging is essential for ensuring the security of brain tumour surgery
Doppler uterine artery preeclampsia prediction
Utilizing greyscale and doppler ultrasonography to assess newborn cholestasis
MRI’s reliability in detecting congenital anorectal anomalies
Multivessel research on intrauterine growth restriction (arterial, venous) doppler speed
Perfusion computed tomography is used to evaluate cerebral blood flow, blood volume, and vascular permeability for brain neoplasms
In post-radiotherapy treated gliomas, compare perfusion magnetic resonance imaging with magnetic resonance spectroscopy to identify recurrence
Using multidetector computed tomography, pediatric retroperitoneal masses are evaluated. Tomography
Female factor infertility: the role of three-dimensional multidetector CT hysterosalpingography
Combining triphasic computed tomography with son elastography allows for assessing localized liver lesions
Analyzing the effects of magnetic resonance imaging and transperineally ultrasonography on female urinary stress incontinence
Using dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging, evaluate endometrial lesions
For the early diagnosis of breast lesions, digital breast tomosynthesis and contrast-enhanced digital mammography are also available
Using magnetic resonance imaging and colour doppler flow, assess portal hypertension
Magnesium resonance imaging enables the assessment of musculoskeletal issues
Diffusion magnetic resonance imaging is a crucial diagnostic technique for neoplastic or inflammatory brain lesions
Children with chest ailments that are HIV-infected and have a radiological spectrum high-resolution ultrasound for childhood neck lumps
Ultrasonography is useful when determining the causes of pelvic discomfort in the first trimester
Magnetic resonance imaging is used to evaluate diseases of the aorta or its branches. Angiography’s function
Children’s pulmonary nodules can be distinguished between benign and malignant using high-resolution ct
Research on multidetector computed urography for treating diseases of the urinary tract
The evaluation of the ulnar nerve in leprosy patients involves significantly high-resolution sonography
Utilizing computed tomography and magnetic resonance imaging, radiologists evaluate musculoskeletal tumours that are malignant and locally aggressive before surgery
The function of MRI and ultrasonography in acute pelvic inflammatory disorders
Ultrasonography is more efficient than computed tomographic arthrography for evaluating shoulder discomfort
For patients with blunt abdominal trauma, multidetector computed tomography is a crucial tool
Compound imaging and expanded field-of-view sonography in the evaluation of breast lesions
Focused pancreatic lesions are assessed using multidetector CT and perfusion ct
Ct virtual laryngoscopy is used to evaluate laryngeal masses
In the liver masses, triple phase multidetector computed tomography
The effect of increasing the volume of brain tumours on patient survival
Colonic lesions can be diagnosed using perfusion computed tomography
A role for proton MRI spectroscopy in the diagnosis and management of temporal lobe epilepsy
Functions of multidetector CT and doppler ultrasonography in assessing peripheral arterial disease
There is a function for multidetector computed tomography in paranasal sinus illness
In neonates with an anorectal malformation, transperineal ultrasound
Using multidetector CT, comprehensive imaging of an acute ischemic stroke is performed
The diagnosis of intrauterine neurological congenital disorders requires the use of fetal MRI
Children with chest masses may benefit from multidetector computed angiography
Multimodal imaging for the evaluation of palpable and non-palpable breast lesions
As measured by sonography and relation to fetal outcome, fetal nasal bone length at 11–28 gestational days
Relationship between bone mineral density, diffusion-weighted MRI imaging, and vertebral marrow fat in postmenopausal women
A comparison of the traditional catheter and CT coronary imaging angiogram of the heart
Evaluation of the descending colon’s length and diameter using ultrasound in normal and intrauterine-restricted fetuses
Investigation of the hepatic vein waveform in liver cirrhosis prospectively. A connection to child pugh’s categorization
Functional assessment of coronary artery bypass graft patency in symptomatic patients using CT angiography
MRI and MRI arthrography evaluation of the labour-ligamentous complex lesion in the shoulder
The evaluation of soft tissue vascular abnormalities involves imaging
Colour doppler ultrasound and high-resolution ultrasound for scrotal lesions
Comparison of low-dose computed tomography and ultrasonography with colour doppler for diagnosing salivary gland disorders
The use of multidetector CT to diagnose lesions of the salivary glands
Low dose CT venogram and sonography comparison for evaluating varicose veins: a pilot study
Comparison of dynamic contrast-enhanced MRI and triple phase CT in patients with liver cirrhosis
Carotid intima-media thickness and coronary artery disease are examined in individuals with coronary angiography for suspected CAD
Unenhanced computed tomography assessment of hepatic fat levels in fatty liver disease
Bone mineral density in postmenopausal women and vertebral marrow fat on spectroscopic and diffusion-weighted MRI images are correlated
Evaluation of CT coronary angiography against traditional catheter coronary angiography in comparison
“High-frequency ultrasonography and colour doppler evaluation of the median nerve in carpal tunnel syndrome in contrast to nerve conduction tests”
Role of MR urethrography in the surgical therapy of obliterative urethral stricture compared to conventional urethrography
“High resolution computed tomography evaluation of the temporal bone in cholesteatoma patients.”
“Ultrasonographic assessment of sore shoulders and linkage of clinical examination and rotator cuff diseases”
“A Study to Evaluate the Performance of Magnetization Transfer Ratio in Distinguishing Neurocysticercosis from Tuberculoma”

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You can use or get inspired by our selection of the best radiology diss. You can also check our list of critical care nursing dissertation topics and biology dissertation topics because these areas also relate to the discipline of medical sciences.

Choosing an impactful radiology dissertation topic is a daunting task. There is a lot of patience, time and effort that goes into the whole process. However, we have tried to simplify it for you by providing a list of amazing and unique radiology dissertation topics for you. We hope you find this blog helpful.

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Advances in Radiation Oncology for the Treatment of Cervical Cancer

Background: Over the past two decades, there has been significant advancement in the management of cervical cancer, particularly in the domain of definitive chemoradiotherapy for locally advanced cervical cancer (LACC). Indeed, radiation treatment paradigms have shifted from a two-dimensional (2D) approach solely based on anatomical bony landmarks, to an image-guided three-dimensional (3D) approach, with the goal of delivering doses more precisely to clinical targets with an increased sparing of organs-at-risk. Methods: This is a narrative review on the advances in radiation technologies for the treatment of cervical cancer. Using the PubMed database, we identified articles published in English up until November 18, 2021 on the treatment of LACC with external beam radiotherapy (EBRT) and brachytherapy. A search of the Clinicaltrials.gov and Clinicaltrialsregister.eu retrieved information on ongoing clinical trials on the topic of combined immunotherapy and radiotherapy in cervical cancer. Results: We highlight the historical evolution from the use of 2D radiotherapy to 3D-conformal radiotherapy, and then intensity modulated radiotherapy (IMRT) for the delivery of EBRT. We also discuss advances in brachytherapy, notably the transition to 3D image-guided adaptive brachytherapy (3D-IGABT). In this context, we highlight large cohort studies that were recently constructed and have shown significant improvement in local control and treatment-related toxicities with 3D-IGABT. Finally, we discuss other advances in the field, notably the use of stereotactic body radiotherapy (SBRT) as a substitute to brachytherapy, and the addition of immunotherapy to chemoradiation. Conclusions: The use of IG-IMRT and 3D-IGABT have considerably improved treatment outcomes and toxicity profiles for patients with LACC, and are now considered the gold standard in many countries. The use of SBRT boost as a replacement for brachytherapy has been associated with increased toxicity and decreased efficacy and should be used with caution in the context of clinical trials. New experimental approaches include the addition of immunotherapy to chemoradiation regimens.

1. Introduction

Cervical cancer is the fourth most common cancer in women worldwide [ 1 , 2 ]. The majority of cervical cancers in developed countries are diagnosed early at stage I and 5-year overall survival (OS) for all stages remains above 73% [ 3 , 4 ]. However, outcomes for those with locally advanced cervical cancer remain quite poor. The 5-year OS for patients with regional disease is around 55% [ 3 , 5 ]. The addition of concurrent chemotherapy to radiotherapy (RT) has improved the prognosis of these patients; however treatment-related toxicity and distant recurrence remain a challenge [ 6 ]. Thus, there is much room for improvement in the treatment of locally advanced cervical cancer and new strategies are needed to further improve outcomes.

Standard treatment of locally advanced cervical cancer (LACC) consists of concurrent chemoradiotherapy (CCRT) with external beam radiotherapy (EBRT), followed by brachytherapy (BT) [ 7 ]. CCRT has been the standard of care for LACC since 1999, based on the results of five Phase III randomized controlled trials (RCT) showing a 30% to 50% survival advantage by adding cisplatin-based chemotherapy to radiation (GOG 85, GOG 120, GOG 123, SWOG 8797/Intergroup 0107, RTOG 9001) [ 8 , 9 , 10 , 11 , 12 ]. In the past two decades, radiation treatment paradigms have shifted from a two-dimensional (2D) approach, solely based on anatomical bony landmarks, to an image-guided three-dimensional (3D) approach, taking into account variations in tumour size and position, with the goal of delivering doses more precisely to clinical targets with an increased sparing of organs-at-risk (OARs).

In this narrative review, we discuss the advances in external beam radiotherapy (EBRT) and brachytherapy (BT) for the treatment of locally advanced cervical cancer. We highlight the historical evolution from the use of 2D radiotherapy to 3D-conformal radiotherapy (3DCRT), and then to intensity modulated radiotherapy (IMRT) that has now become a standard for the planning and delivery of EBRT. We also discuss advances in brachytherapy, notably the evolution from a Manchester system delivery of BT, to now widespread use of 3D image-guided adaptive brachytherapy (3D-IGABT). In this context, we highlight recently conducted large cohort studies that have shown significant improvement in local control (LC) and treatment-related toxicities with 3D-IGABT. Finally, we highlight other technological advances in the field, notably the use of stereotactic body radiotherapy (SBRT) as a potential substitute when brachytherapy is contraindicated, and future directions such as the addition of immunotherapy to chemoradiation.

2. Material and Methods

A literature search was performed in the PubMed database for articles on radiotherapy for the treatment of LACC. The following keywords were used in various search algorithms: “cervical cancer”, “radiotherapy,” “radiation therapy,” “chemoradiation”, “IMRT”, “brachytherapy”, “SBRT”, “immunotherapy,” and “immune checkpoint inhibitors”. Original research, review papers, or meeting abstracts published on the topic up to 18 November 2021 were considered. Articles published in languages other than English were excluded. Further references found within the articles and relevant to the subject were also used. A search query was also performed in Clinicaltrials.gov and Clinicaltrialsregister.eu to retrieve information on ongoing clinical trials on combined immunotherapy and RT in cervical cancer.

2.1. Advances in External Beam Radiotherapy

2.1.1. from 2d radiotherapy to 3d-conformal radiotherapy (3dcrt).

Historically, the treatment of LACC with RT has been performed with 2D external beam radiotherapy, solely based on empirically defined anatomical landmarks. These anatomical bony landmarks were defined based on X-rays to be able to largely cover the primary disease as well as any potential extent of the tumour to the adjacent soft tissues and draining lymph nodes. The most rudimentary technique of EBRT consists of two parallel opposed fields (AP-PA). This was followed by the use of Biaxial Telecobalt pendular irradiation of the pelvic lymph nodes combined with 226 Radium-BT to treat cervical cancer in the 1960s, especially in the recurrent setting [ 13 ]. Later, the “four-field box” technique was introduced and achieved better OARs sparing. It consists of four large treatment fields, with the anterior border placed anteriorly to the pubic symphysis, posterior border covering the sacrum at the S3/S4 level, superior border at the level of the aortic bifurcation around the L3-L5 vertebral body levels, or at the level of T12 in the case of extended fields, when the para-aortic lymph nodes are involved. The inferior border is defined as the bottom of the obturator foramen and finally the lateral borders are placed 1.5 to 2 cm lateral to the pelvic brim. Although easily applicable, the use of standardized fields based only on bony landmarks has the caveat of not being adaptable to variations in individual patients’ anatomy and has been associated with geographical misses leading to decreased LC [ 14 , 15 ].

The computerized tomography (CT) scanner was invented in 1971 by Hounsfield and Cormack, but it was not until the 1990s that it was used in the planning and delivery of RT [ 16 ], marking the evolution from 2D-RT to 3DCRT. Indeed, 3DCRT takes advantage of the soft tissue and anatomical information obtained from a CT scan of the patient in a reproducible treatment position, to delineate the target disease and the neighboring OARs. Based on this information, gross tumour volume (GTV), clinical target volume (CTV) and planning target volume (PTV) are delineated as defined by the ICRU 50 and 62 reports [ 17 , 18 ]. This allowed for the use of the “four field box” technique based on anatomical rather than empirical bony landmarks, and the use of field blocks or multileaf collimators (MLCs) to better shape the dose distribution to the PTV while limiting the dose delivered to the OARs [ 19 , 20 ]. Compared to a 2D technique, 3DCRT also provides the advantage of recording volumetric dosimetry, correlating it with treatment outcomes and toxicities.

2.1.2. Intensity Modulated Radiotherapy (IMRT) for the Treatment of Locally Advanced Cervical Cancer

IMRT is a radiotherapy technique that allows for the delivery of highly conformal dose distribution compared to conventional techniques of 2D or 3DCRT, while minimizing the dose to nearby OARs. It achieves this through the use of multiple static beamlets or of volumetric intensity-modulated arcs (VMAT) and inverse planning software that can optimize the dose distribution, based on set constraints and target priorities. The trade-off is an increased volume of normal tissues receiving low doses of radiation. The success of IMRT at achieving such highly conformal dose distributions relies on the accuracy of target volume delineation and the quality of the imaging used. Thus, simulation CT scans are often fused with available diagnostic CT, MRI and PET/CT imaging to aid accurate target and OAR delineation. When available, MRI and/or PET/CT simulation is also favored to capture the anatomy in the treatment position. IMRT also allows for dose escalation to grossly involved pelvic and para-aortic lymph nodes by sequential or simultaneous integrated boost techniques when the planning CT is fused with diagnostic images such as a PET scan [ 21 ]. Multiple consensus contouring guidelines exist to help in the delineation of targets and OARs for cervical cancer [ 22 , 23 ] and have been extensively reviewed elsewhere [ 24 ].

Initial reports of the use of IMRT for the treatment of gynecological cancers were published in the early 2000s. In 2001, Portelance et al. showed that normal tissue sparing is superior with IMRT in a cohort of 10 patients with cervical cancer planned with IMRT vs. conventional techniques [ 25 ]. They showed that the volumes of bladder, rectum and small bowel receiving the prescribed dose of 45 Gy or higher was significantly decreased when using IMRT compared to conventional RT [ 25 ]. In 2002, Mundt et al. [ 26 ] reported their experience with intensity-modulated whole pelvic radiotherapy (IM-WPRT) in 40 women with gynecologic malignancies. They showed adequate coverage of the target volumes compared to conventional RT, with 98.1% of the PTV receiving the prescription dose. There was also an improved toxicity profile, with a decrease in grade 2 acute gastrointestinal toxicity in the IMRT group compared to the conventional whole pelvis RT group (60 vs. 91%, p = 0.002), and no patient developing grade 3 toxicity [ 26 ]. Since then, several other studies have shown a decrease in acute toxicities, notably of gastrointestinal (GI), genitourinary (GU) and hematological toxicities when using IMRT in the treatment of LACC compared to 2D or 3DCRT, without compromising tumour control [ 27 , 28 , 29 , 30 , 31 ]. Notably, a meta-analysis by Lin et al. [ 32 ] on the outcomes of IMRT use for the definitive treatment of cervical cancer included a total of 1008 patients (IMRT = 350, 3DCRT/2D-RT = 658) and showed a significant decrease in the incidence of acute GI and GU toxicities in patients treated with IMRT compared to 3DCRT/2D-RT. Odds ratios (OR) were 0.55 (95% CI: 0.32–0.95, p = 0.03 ) for grade ≥3 acute GI toxicities and 0.31 (95% CI: 0.14–0.67, p = 0.003) for acute GU toxicities [ 32 ]. Moreover, there were no difference in 3-year PFS and OS when comparing the two techniques [ 32 ], showing that IMRT confers equivalent efficacy compared to conventional techniques with a lower toxicity profile.

In the post-operative setting, RTOG 0418 was the first multi-institutional phase II study that evaluated the use of IMRT to the pelvis vs. four-field box conventional RT. The study included 83 patients, 43 with endometrial cancer and 40 with cervical cancer. Patients with endometrial cancer received IMRT alone, whereas patients with cervical cancer received IMRT and weekly cisplatin. The RT dose was 50.4 Gy in 28 fractions to the pelvic lymph nodes and vagina. An analysis of hematological toxicities from this cohort showed that patients with cervical cancer treated with IMRT had grades 1, 2 and 3 hematological toxicities of 23%, 33% and 25%, respectively and no grade 4–5 toxicities [ 33 ]. Importantly, the volume of bone marrow receiving 40 Gy correlated with acute hematological toxicities, as 75% of patients with a V40 > 37% experienced grade 2 or higher hematological toxicities compared to 40% of patients with a V40 ≤ 37% ( p = 0.025). A median bone marrow dose of >34.2 Gy was also significantly associated with higher rates of grade ≥ 2 hematological toxicities; however, bone marrow is highly radiosensitive and keeping doses lower than 34.2 Gy is not sufficient to maintain hematopoiesis, as 43% of patients with a median bone marrow dose ≤34.2 Gy still experienced hematological toxicities [ 33 ]. The role of IMRT in the post-operative setting is equally advantageous to reduce acute GI toxicities, because with the uterus and ovaries removed, there is more room for the small bowel to shift downwards and occupy the pelvis, thus being more at risk of toxicity from RT. The TIME-C trial (NRG/RTOG 1203) is a phase III RCT that evaluated patient-reported acute GI toxicity from baseline to the end of RT, for 278 patients with cervical or endometrial cancer, randomized to post-operative RT using IMRT or a four-field box [ 34 ]. Secondary endpoints included a change in patient-reported urinary toxicity and quality of life. IMRT was associated with a significantly smaller decline in patient-reported bowel and urinary symptom scores, less frequent or constant diarrhea, and fewer use of anti-diarrhea medications [ 34 ].

2.1.3. Adaptive External Beam Radiotherapy

The uterus and cervix are highly susceptible to changes in position during RT delivery, mainly due to variations in bladder and rectal filling and tumour regression during RT [ 35 ]. The reported mean interfractional cervical motion varies between 2.3 and 16 mm in the anterior-posterior direction, 2.7 and 8 mm in the superior-inferior direction and between 0.3 and 10 mm in the lateral direction [ 36 ]. Thus, the concept of internal target volume (ITV) has been introduced to account for such variations in position [ 37 ]. The ITV is generated by doing simulation CT scans on a full and empty bladder and combining the CTV drawn on each of these scans to account for every position change between these two bladder-filling extremes. A PTV margin of 5–7 mm is then added to this ITV to account for setup and position in errors. However, cone beam CT (CBCT) is recommended so as to ensure adequate coverage of the CTV and PTV daily prior to RT delivery. Moreover, this approach has the benefit of decreasing the volume of OARs exposed to higher doses of RT and the use of image-guided IMRT has been associated with a decrease in GI and hematological toxicities compared with IMRT alone [ 38 ]. Other adaptive RT technologies have emerged over the past few years to further improve image guidance during EBRT delivery, notably the “plan of the day” approach or the “online adaptive RT” that include same day replanning and are the subject of a recently published review article [ 39 ].

2.2. Advances in Brachytherapy for the Treatment of Locally Advanced Cervical Cancer

Brachytherapy (BT) is a type of RT in which small, sealed radioactive sources are placed in or near a tumour volume to deliver a therapeutic dose. It is an integral part of the treatment algorithm for LACC as it helps in boosting the RT dose to the local disease to a curative level. The addition of BT to the treatment of LACC is independently associated with a significantly higher survival rate, with up to a 12% absolute improvement in 4-year OS (from 46% to 58%, p < 0.001) with hazard ratios (HR) of 0.66 (95% CI, 0.60–0.74) [ 5 ]. In this SEER database analysis, BT was also associated with significantly improved cancer-specific survival (CSS) with a 4-year CSS of 64.3% vs. 51.5% for those who did not receive BT ( p < 0.001) and HR of 0.64 (95% CI, 0.57–0.71).

2.2.1. From 2D-Brachytherapy (2D-BT) to 3D Image Guided Adaptive Brachytherapy (3D-IGABT)

Historically, BT for LACC was delivered through a 2D technique, whereby a 2 Gy equivalent cumulative dose (EQD2) of 80 to 85 Gy was delivered according to the Manchester system, to point A defined on X-ray. First introduced in 1938, the Manchester system defined point A as a point 2 cm superior to the external OS and 2 cm lateral and perpendicular to the applicator tandem, anatomically representing where the uterine vessels cross the ureter [ 40 , 41 ]. Thus, 2D-BT delivers a known dose to point A bilaterally, generating a pear-shaped distribution, but without factoring in patient-specific factors such as tumour size, anatomy, or doses to OARs, as these cannot be readily identified on an X-ray. However, with the advent of CT and MRI imaging during the procedure, the delivery of BT has evolved to a volume-based approach, taking into account variations in tumour size and position over the treatment course. This allows for conformal treatment of a high-risk clinical target volume (HR-CTV) while simultaneously sparing OARs.

In 2005, the Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology (GEC-ESTRO) published the first recommendations on the basic concepts of terms utilized for a 3D image-based BT approach [ 42 ]. Since then, several consensus contouring guidelines and protocols have been developed for target delineation in cervical cancer brachytherapy [ 43 , 44 , 45 ]. Briefly, 3D-BT can be either CT-guided or MRI-guided, with the latter being considered the gold standard, as it is required for visualizing and contouring the residual GTV after EBRT. For instance, the EMBRACE-II protocol [ 46 ] defines the residual GTV (GTV-Tres) as the residual macroscopic tumour at the time of the BT boost, after treatment that is assumed sufficient to control microscopic disease, and based on clinical examination and imaging (MRI, PET/CT). The adaptive High Risk CTV-T (CTV-T HRadapt) includes the GTV-Tres, the whole cervix and adjacent residual pathologic tissue as defined by clinical examination and imaging at the time of BT ( Figure 1 ). It is the volume bearing the highest risk for recurrence and should receive at least 90 Gy of cumulative EQD2 as per the EMBRACE-II dose targets (D90 CTV-T HR > 90–95 Gy EQD2 10 ). The Intermediate Risk CTV-T (CTV-T IR) represents the area of the GTVinit superimposed on the topography at the time of brachytherapy and a margin surrounding the anatomical cervical borders in areas without an initial GTV-T. Dose distribution and optimization is achieved using different types of applicators that are MRI compatible. Intracavitary applicators can be used for smaller tumours (<31 cc) but are limited at covering the CTV-T HRadapt to doses >85 Gy, in case of larger tumours or asymmetrical local tumour extension for example to the parametria, vagina, bladder or rectal wall [ 47 , 48 ]. For such cases, a combined intracavitary-interstitial (IC/IS) approach is favoured and allows for improved conformality and target-dose escalation without increasing the doses received by the OARs [ 47 , 48 , 49 , 50 ].

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Residual gross tumour volume at brachytherapy (GTV-Tres: yellow) and adaptive High Risk CTV-T (CTV-T HRadapt: red) contoured at the time of brachytherapy on axial T2 MRI.

2.2.2. Outcomes of 3D Image-Guided Brachytherapy (3D-IGABT)

Several studies have reported improved LC and survival outcomes, and decreased toxicities with the use of 3D-IGABT compared to 2D-BT. Initiated in 2005, the French STIC trial was the first prospective, non-randomized trial to compare 2D- vs. 3D-BT in the treatment of LACC [ 51 ]. A total of 705 LACC patients were treated as per Group 1: BT (2D or 3D) followed by surgery; Group 2: chemoradiation, BT (2D or 3D) followed by surgery, or Group 3: chemoradiation then BT (2D or 3D), for which the 3D-BT was mostly CT-guided. At 24 months, improved LC was observed in all three groups, as well as a 50% reduction in grade 3 and 4 morbidity with 3D-BT compared to 2D-BT [ 51 ]. The RetroEMBRACE study is the largest retrospective, multi-institutional study of its kind reporting on the outcomes of 731 women with LACC, treated with CCRT and 3D-IGABT (either by CT or MRI) [ 52 ]. With a median follow-up of 43 months, Sturdza et al. reported excellent 5-year LC rates of 89%, pelvic control (PC) of 84%, cancer-specific survival (CSS) of 73% and OS of 65%, which is an improvement of ~10% compared to historic controls using 2D-BT. They also reported limited morbidity with grade ≥3 late toxicity rates of 5%, 7%, and 5%, respectively, for the bladder, gastrointestinal tract and vagina [ 52 ]. Importantly, for patients treated with MRI-based IGABT, 5-year LC was 94% for those with tumours <5 cm compared to 81% for tumours ≥5 cm ( p ≤ 0.001), thus showing how tumour size impacts on LC. The recently published EMBRACE-I prospective, multicentre cohort study evaluated local tumour control and morbidity after chemoradiotherapy and MRI-based IGABT in LACC. They reported an actuarial 5-year LC of 92.0% (95% CI, 90–93) at a median follow-up of 51 months, 5-year PC of 87.0% (95% CI, 85–89) and 5-year nodal control of 87.0% (95% CI, 85–89). The 5-year disease-free survival (DFS) in this cohort was 68% (95%, CI 65–70) and 5-year OS was 74% (95%, CI 72–77) [ 53 ]. LC was similar across all of the stage groups; however there was a 14-17% absolute improvement in LC in FIGO stage IIIB disease compared to the RetroEmbrace cohort (92% LC vs. 75% in RetroEmbrace) [ 52 , 53 ]. This could be due to an increase in the use of MRI planning (100% vs. 19%) and interstitial needles (43% vs. 23%) in EMBRACE-I compared to RetroEmbrace. The initially reported late grade ≥3 bowel and bladder toxicity from the EMBRACE-I cohort were 5.9% and 5.3%, respectively, [ 54 , 55 ] but the most recent report showed an actuarial cumulative 5-year incidence of grade ≥3 GI toxicity of 8.5% (6.9–10.6), grade ≥3 GU toxicity of 6.8% (95% CI 5.4–8.6), 5.7% (4.3–7.6) vaginal toxicity and 3.2% (2.2–4.5) fistula events [ 53 ].

Taken together, these studies show the superior safety profile and efficacy, at least in terms of LC, of 3D-IGABT compared to 2D-BT techniques. This has been corroborated by a recent systematic review and meta-analysis by Kim et al. that reported a pooled hazard ratio (HR) for grade ≥3 toxicities of 0.54 for 3D-IGABT compared to 2D-BT (95% CI 0.37–0.77) [ 56 ]. There was also a significant improvement in locoregional recurrence-free survival (HR = 0.61; 95% CI, 0.40–0.93) and PFS (HR = 0.75; 95% CI, 0.59–0.96) favoring 3D-IGABT, but not in OS (HR = 0.65; 95% CI 0.40–1.06). Though MRI-guided IGABT is now considered the gold standard for brachytherapy boost in the treatment of LACC in most European and North American centres, the lack of clear OS benefit in this meta-analysis raises questions as to its widespread adoption, specifically in developing countries where access to MRI planning may be limited. However, the lack of clear OS benefit in this meta-analysis may be because 40% of patients in the pooled analysis were treated with CT-guided BT and only a few patients received interstitial BT, which could have negatively impacted OS rates. Moreover, a cost-effectiveness analysis performed in the US showed that 3D-IGABT is a cost-effective option compared 2D-BT, thus supporting its routine use in the treatment of LACC [ 57 ].

2.3. Stereotactic Body Radiotherapy in the Treatment of Locally Advanced Cervical Cancer

Stereotactic body radiotherapy (SBRT) is a type of EBRT whereby high doses of radiation per fraction (usually > 5Gy/fraction) are precisely delivered to a target in one or a few fractions. In recent years, SBRT has been considered as a conformal RT boost alternative to BT, particularly in patients unable to undergo BT due to unfavorable anatomy or medical comorbidities. A National Cancer Database registry analysis showed that from 2004 to 2011, the use of BT in LACC decreased from 96.7% to 86.1%, whereas the use of IMRT and SBRT as a radiation boost increased from 3.3% to 13.9% in the same period ( p < 0.01). However, IMRT or SBRT boost were associated with inferior OS (HR = 1.86; 95% CI, 1.35-2.55; p <0.01), and this decrease was even more significant than that observed when excluding chemotherapy (HR = 1.61, 95% CI, 1.27–2.04, p < 0.01) [ 58 ]. Another National Cancer Database study later showed no significant difference in OS between the SBRT boost and brachytherapy boost after propensity score matching (HR = 1.477, 95% CI 0.746–2.926, p = 0.263), but there was a significant decrease in OS for patients who received IMRT boost vs. brachytherapy boost (HR = 1.455, 95% CI 1.300–1.628, p < 0.001) [ 59 ]. However, a recent single-arm phase II trial of SBRT boost (28 Gy in 4 fractions) as an alternative for intracavitary/interstitial BT boost for LACC was closed prematurely after 15 patients were enrolled, owing to concerns of toxicity [ 60 ]. Indeed, 2-year cumulative grade ≥ 3 toxicity was 26.7%, with predominantly rectal ulcers/fistulas. Two of the grade 3 patients died of complications from fistulas, resulting in a grade 5 toxicity rate of 13% [ 60 ]. Moreover, the efficacy of SBRT was inferior with 2-year LC, PFS, and OS of 70.1%, 46.7%, and 53.3%, respectively, although the authors argue that larger tumour size and patient comorbidities may have contributed to these inferior outcomes [ 60 ]. Another prospective study of SBRT boost for 25 gynecological patients with pelvic relapse or primary disease, of which seven were cervical cancer patients treated with definitive radiotherapy, reported a 1-year in-field RFS of 64.5% and 90.0% for the salvage and definitive group, respectively, and a 1-year OS of 80.8% and 49.1%, respectively [ 61 ]. One patient developed an entero-vaginal fistula, one developed sigmoid perforation and no patients experienced grade ≥ 3 genitourinary complications [ 61 ]. Taken together, it appears that SBRT boost in LACC results in inferior efficacy compared to BT, but more importantly, it can be associated with serious adverse effects. Thus, caution should be taken when considering this technique in LACC patients that cannot undergo brachytherapy and should only be attempted in the context of a clinical trial with special attention to the dose distribution to the bowel. In their dosimetric analysis, Albuquerque et al. showed that the percentage of rectal circumference receiving 15 Gy (PRC15) was associated with development of a grade 3 ulcer or rectovaginal fistula ( p < 0.04), with PRC15 >62.7% being the strongest predictor of toxicity [ 60 ].

On the other hand, when SBRT is used for the treatment of oligometastic cervical cancer, it is associated with favorable response rates and LC. A meta-analysis of 17 studies on SBRT for oligometastic gynecological cancers, including 671 patients, 27.1% of which had cervical cancer, showed response rates ranging from 49% to 97% and LC ranging from 71% to 100% [ 62 ]. Disease progression occurred most commonly outside of the SBRT radiation field. Toxicity rates ranged from 2.6% to 10% and the majority of studies (9 out of 16 studies, 56%) did not report any grade ≥ 3 toxicities [ 62 ].

2.4. Immunotherapy as an Adjunct to Chemoradiation

Advances in chemoradiation for the treatment of LACC, notably the use of MRI-based IGABT, have translated into improved LC and toxicity profile. However, the OS for patients with advanced disease remains dismal, and this is thought to be mainly driven by distant failures rather than local recurrences. Thus, new systemic treatments are needed to improve OS for patients with LACC. One of such treatment adjuncts is immunotherapy. Indeed, cervical cancers are thought to be highly immunogenic, as a virus-driven type of cancer (HPV), thus amenable to respond to immunotherapy. Cervical cancer ranks amongst the tumours with the most somatic mutations, neoantigen formation and immune cell infiltrates [ 63 , 64 ]. Furthermore, a landmark Cancer Genome Atlas study on invasive cervical cancer identified several targetable mutations in this type of cancer, notably amplifications in the immune checkpoint regulators programmed death ligand (PD-L1 and PD-L2 [ 65 ]. Finally, several studies have shown that HPV positivity is associated with increased PD-L1 expression [ 66 , 67 ]. Taken together, all these factors argue for the rationale that cervical cancer tumours would respond to checkpoint-inhibitor targeted therapy.

To date, a few studies have investigated the role of targeted anti PD1/PD-L1 therapy in cervical cancer. The Keynote-28 ( {"type":"clinical-trial","attrs":{"text":"NCT02054806","term_id":"NCT02054806"}} NCT02054806 ) was a single-arm, phase IB basket trial of 477 patients from 20 different cohorts with advanced or metastatic PD-L1-expressing solid tumours, including 24 cervical cancer patients. Patients received pembrolizumab every two weeks for up to 24 months. The primary endpoint was overall response rate as per RECIST v1.1 criteria and secondary endpoint was safety. With a median follow-up of 11 months, the objective response rate (ORR) in the cervical cancer cohort was 17% (95% CI, 5% to 37%) with four patients achieving a partial response and median duration of response was 5.4 months (4.1 to 7.5 months) [ 68 ]. The 6-month PFS was 13% and 6-month OS was 66.7%. Treatment-related adverse events (AEs) were reported in 18 patients (75%) with five patients experiencing grade 3 treatment-related AEs. There were no grade 4 treatment-related AEs or deaths [ 68 ].

Furthermore, KEYNOTE-158 ( {"type":"clinical-trial","attrs":{"text":"NCT02628067","term_id":"NCT02628067"}} NCT02628067 ) is an ongoing phase II trial including 1595 patients with advanced (unresectable and/or metastatic) solid tumours who have progressed to standard of care therapy and treated with pembrolizumab [ 69 ]. This included a total of 98 patients with previously treated advanced cervical cancer, of which 82 patients (83.7%) had PD-L1-positive tumours. Pembrolizumab monotherapy was administered every 3 weeks for 2 years until progression. The primary endpoint was ORR as per RECIST v1.1 criteria and secondary endpoints included PFS and OS. With a median follow-up of 10.2 months, ORR was 12.2% (95% CI, 6.5–20.4), with three complete and nine partial responses. All 12 responses were observed in patients with PD-L1-positive tumours. Median duration of response was not reached (range, ≥ 3.7 to ≥ 18.6 months) at time of interim analysis. Median OS was 9.4 months for the entire cohort and 11.0 months for the PD-L1-positive patients. Treatment-related AEs occurred in 65.3% of patients with grade 3 and 4 treatment-related AEs occurring in 12.2% of patients. The most common AEs were hypothyroidism (10.2%), decreased appetite (9.2%), and fatigue (9.2%) [ 69 ]. These two trials showed that pembrolizumab had durable anti-tumour activity in cervical cancer with acceptable toxicity. Based on this, the Food and Drug Administration (FDA) approved, in June 2018, the use of pembrolizumab for the second-line treatment of PD-L1-positive metastatic or recurrent cervical cancer.

Nivolumab was also shown to have efficacy in advanced/metastatic cervical cancer in the second-line setting. In the phase I/II CHECKMATE 358 ( {"type":"clinical-trial","attrs":{"text":"NCT02488759","term_id":"NCT02488759"}} NCT02488759 ), 24 patients with recurrent or metastatic gynecological cancers (19 cervical, 5 vaginal/vulvar) who had received no more than two previous lines of treatment, were treated with nivolumab every two weeks regardless of PD-L1 status [ 70 ]. With a median follow-up of 19.2 months, ORRs were 26.3% (95% CI, 9.1–51.2) for cervical cancer and 20.0% (95% CI, 0.5–71.6) for vaginal/vulvar cancers. The median duration of response (DOR) was not reached (range, 23.3 to 29.5+ months) at the time of analysis in the five responding patients in the cervical cohort. Median OS was 21.9 months (95% CI, 15.1–not reached) for cervical cancer patients. Treatment-related AEs were reported in 12/19 patients (63.2%) in the cervical cohort and all five patients in the vaginal/vulvar cohort, with 21.1% ( n = 4) being of grade 3 and 4 [ 70 ].

In June 2021, Merck announced that a Phase 3 double-blind, randomized trial KEYNOTE-826 ( {"type":"clinical-trial","attrs":{"text":"NCT03635567","term_id":"NCT03635567"}} NCT03635567 ) met its primary endpoint of OS and PFS for the first-line treatment of patients with persistent, recurrent or metastatic cervical cancer. A total of 548 patients with a PD-L1 combined positive score of 1 or more received in a 1:1 ratio pembrolizumab or placebo every 3 weeks plus platinum-based chemotherapy and, per investigator discretion, bevacizumab. Primary endpoints were PFS and OS. The results of the first interim analysis were just published in the November 2021 edition of the New England Journal of Medicine, and showed a median PFS of 10.4 months in the pembrolizumab group and 8.2 months in the placebo group (HR for disease progression or death of 0.62; 95% CI, 0.50–0.77; p < 0.001) [ 71 ]. The 2 year-OS was 53.0% in the pembrolizumab group and 41.7% in the placebo group (HR for death of 0.64; 95% CI, 0.50–0.81; p < 0.001) [ 71 ]. Grade 3 to 5 AEs occurred in 81.8% of patients in the pembrolizumab group and in 75.1% of patients in the placebo group, with grade 5 events occurring in 14 patients in each group (4.6% and 4.5%, respectively) [ 71 ].

In the definitive setting, ENGOT-cx11/KEYNOTE-A18 ( {"type":"clinical-trial","attrs":{"text":"NCT04221945","term_id":"NCT04221945"}} NCT04221945 ) is a phase III, randomized trial evaluating the combination of pembrolizumab with concurrent CRT for the treatment of locally advanced cervical cancer [ 72 ]. It is still ongoing and aims to recruit 980 patients with high-risk LACC (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA) who have not received prior treatments, randomized 1:1 to receive either 5 cycles of pembrolizumab vs. placebo every 3 weeks plus CRT followed by 15 cycles of pembrolizumab vs. placebo every 6 weeks. The CRT regimen is as per the standard practice, including 5–6 cycles of cisplatin 40 mg/m 2 weekly + EBRT followed by brachytherapy (IGABT). Randomization will be stratified based on the EBRT technique (IMRT or VMAT vs. non-IMRT), cancer stage at screening (stage IB2-IIB vs. III-IVA) and planned total RT dose. The primary endpoints are PFS as per RECIST v1.1 and OS. The secondary endpoints are 2-year PFS, 3-year OS, complete response at 12 weeks, ORR, PFS and OS in PD-L1–positive patients, EORTC QLQ-C30 and QLQ-CX24, and safety. Results of this trial are highly anticipated and will further elucidate whether immunotherapy combined with definitive CRT can improve LC, PC and survival in patients with LACC. Currently, there are ten clinical trials assessing the combination of immunotherapy and definitive chemoradiation in the treatment of cervical cancer ( Table 1 ). Results from all these trials are eagerly awaited to assess whether immunotherapy could improve distant control as well as survival rates in LACC without significantly increasing toxicities.

Clinical trials combining immunotherapy with definitive radiotherapy in the treatment of locally advanced cervical cancer.

RT: radiotherapy; EBRT: external beam radiotherapy; IMRT: intensity modulated radiotherapy; BT: brachytherapy; SoC CRT: standard of care chemoradiation consisting of weekly cisplatin concurrent with pelvic +/− para-aortic EBRT (45Gy/25Fx) followed by BT (to 80–90 Gy EQD2); EFRT: extended field radiotherapy, WPRT: whole pelvic radiation therapy; N+: node positive, LNs: lymph nodes, PA: para-aortic, adenoCa: adenocarcinoma; SCC: squamous cell carcinoma; ORR: objective response rate; PFS: progression-free survival; OS: overall survival; DFS: Disease Free Survival; MTD: maximum tolerated dose; dose-limiting toxicities (DLTs); AEs: adverse events; SAEs: serious adverse events.

3. Conclusions and Perspectives

RT plays a primordial role in the treatment of LACC. Radiation oncology technologies have progressed rapidly in the past two decades. Notably, the use of IG-IMRT and 3D-IGABT have considerably improved treatment outcomes and toxicity profiles for patients with LACC and are now considered the gold standard in many countries. However, there is still room for improvement, and new experimental perspectives include the addition of immunotherapy to chemoradiation regimens, or a move towards an even more personalized approach to treatment with the identification of risk factors and biomarkers that can be used to de-escalate or intensify treatments according to individual patients’ risk group (EMBRACE III). Other technological innovations such as the use of the SBRT boost to replace BT boost have been associated with increased toxicity and decreased efficacy and so should be used with caution and only in the context of clinical trials.

Author Contributions

Both authors have contributed equally in the conception and design of the work; Writing—original draft preparation, M.D.F. Writing—critical review and editing, J.A. All authors have read and agreed to the published version of the manuscript.

This research received no external funding.

Conflicts of Interest

The authors declare no conflict of interest.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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The evolving role of radiotherapy for pediatric cancers with advancements in molecular tumor characterization and targeted therapies.

1 Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC, United States
2 Department of Radiation Oncology, University of Minnesota, Minneapolis, MN, United States

Ongoing rapid advances in molecular diagnostics, precision imaging, and development of targeted therapies have resulted in a constantly evolving landscape for treatment of pediatric cancers. Radiotherapy remains a critical element of the therapeutic toolbox, and its role in the era of precision medicine continues to adapt and undergo re-evaluation. Here, we review emerging strategies for combining radiotherapy with novel targeted systemic therapies (for example, for pediatric gliomas or soft tissue sarcomas), modifying use or intensity of radiotherapy when appropriate via molecular diagnostics that allow better characterization and individualization of each patient’s treatments (for example, de-intensification of radiotherapy in WNT subgroup medulloblastoma), as well as exploring more effective targeted systemic therapies that may allow omission or delay of radiotherapy. Many of these strategies are still under investigation but highlight the importance of continued pre-clinical and clinical studies evaluating the role of radiotherapy in this era of precision oncology.

Introduction

In the early history of pediatric cancer treatment, surgical resection and then radiation therapy served as the primary treatment modalities ( 1 , 2 ). Subsequent introduction of chemotherapy regimens resulted in combination therapies with reduction in radiotherapy dose in many cases ( 3 , 4 ). Further refinement of chemotherapy regimens and significant advancements in radiotherapy techniques have led to improvements in disease outcomes while limiting late toxicities, critical for treatment of childhood cancers. Recently, dramatic and rapid advancements in precision medicine, which we define here as more precise genomic and molecular characterization of individual tumors, development of targeted anti-tumor drugs, and improved accuracy and conformality of radiotherapy, have enabled treatment approaches that may be better tailored to each patient ( 5 – 8 ). Radiotherapy has remained a mainstay and one of the most effective anti-cancer treatments; however, these advances in precision medicine require constant re-evaluation of the role of radiotherapy in this evolving landscape. A critical goal in the treatment of pediatric malignancies is to maintain effective cancer control while minimizing late toxicities as much as possible. On one hand, it can be tempting to try to omit or limit the use of radiotherapy for childhood cancers given potential late effects in an era of improvements in targeted systemic therapies. In some cases, this may be appropriate for select patients, as long as disease control can be maintained. On the other hand, the potential for radiotherapy to synergize with targeted drugs should be explored and fully utilized. Significant advancements in radiotherapy techniques have also been made in this era of precision medicine, via improvements in conformality with intensity-modulated radiotherapy (IMRT) and proton therapy, better precision with image guidance, and reductions of dose and treatment volumes where appropriate, allowing for reduced toxicity and an improved therapeutic ratio with radiotherapy.

Role of Radiotherapy With Advances in Targeted Systemic Therapies

Better molecular and genomic characterization of tumors, along with advances in targeted drug development, have resulted in more specific systemic therapies for pediatric tumors, which in some cases may have better anti-tumor efficacy and in many cases are associated with less toxicity compared to standard chemotherapy regimens. In some cases, these targeted systemic therapies can be used upfront, delaying local radiotherapy and reserving it for progression, while in others, these targeted therapies may be given concurrently with or following radiotherapy, or in the recurrent or metastatic setting.

Management of Pediatric Low-Grade Gliomas With Advances in Targeted Therapies

Low-grade gliomas (LGG) are among the pediatric tumor types for which novel targeted agents have demonstrated promising potential. While malignant progression is rare in pediatric LGG (in contrast to adult LGG) and 5-year overall survival is greater than 90% ( 9 ), patients whose tumors cannot be fully resected often end up requiring multiple courses of therapy, with associated late effects and long-term reduction in quality of life ( 10 ). For LGG that cannot be managed by surgery alone, current management is controversial: conventional cytotoxic chemotherapy is typically the recommended initial approach for pediatric patients, deferring radiotherapy to limit late toxicities ( 11 ). However, advances in radiotherapy techniques that can reduce late toxicities, including IMRT and proton therapy, may make radiotherapy a more viable earlier-line option. Further, it is now fairly established that the majority of pediatric LGG arise from an alteration in the mitogen-activated protein kinase (MAPK) signaling pathway, including BRAF mutation (most commonly V600E point mutation) or fusion (most commonly BRAF : KIAA1549), NF1 mutation, NTRK family fusion, and FGFR1 mutation or rearrangement, along with other less common alterations ( Figures 1 , 2 ) ( 5 , 6 , 13 – 16 ). Thus, targeted agents including MEK1/2 (an upstream kinase of MAPK), BRAF, and TRK inhibitors have been evaluated and have demonstrated promising activity in pediatric gliomas ( 17 – 22 ).

Figure 1 Schematic of MAPK signaling pathway and potential targets and therapeutics for pediatric LGG. FGFR, fibroblast growth factor receptor; LGG, low-grade glioma; MAPK, mitogen-activated protein kinase; RTK, receptor tyrosine kinase; TRK, tropomyosin receptor kinase.

Figure 2 Distribution of pediatric LGG histologies and genetic alterations by location in the brain. Reproduced with permission from Filbin and Sturm ( 12 ). DA, diffuse astrocytoma; DNT, dysembryoplastic neuroepithelial tumors; GG, ganglioglioma; LGG, low-grade glioma; PA, pilocytic astrocytoma; PXA, pleomorphic xanthoastrocytomas; SEGA, subependymal giant cell astrocytoma.

The most mature data in this setting exist for the MEK1/2 inhibitor selumetinib. In a multicenter phase 2 study by the Pediatric Brain Tumor Consortium, pediatric patients with recurrent, refractory, or progressive LGG after at least one line of standard therapy were treated with selumetinib ( 18 ). Response and survival outcomes compare favorably to prior studies of recurrent or progressive pediatric LGG treated with chemotherapy regimens including carboplatin/vincristine and vinblastine monotherapy ( Table 1 ) ( 18 , 23 – 27 ). We note that data regarding the efficacy of selumetinib for patients without NF1- or BRAF alteration-associated LGG from this study are still pending, and prior studies of chemotherapy did not stratify or have information regarding NF1 or BRAF status. Nonetheless, these promising results have led to the current Children’s Oncology Group (COG) randomized studies ACNS1831 [NCT03871257] and ACNS1833 [NCT04166409], which are evaluating selumetinib versus standard carboplatin/vincristine chemotherapy in the upfront setting for patients with NF1-associated or non-NF1-associated low grade gliomas, respectively.

Table 1 Prospective studies of systemic therapies for recurrent/progressive/refractory pediatric low-grade glioma.

Studies of other targeted agents are also complete or underway, including a phase 2 study (TRAM-01, NCT03363217) of the MEK1/2 inhibitor trametinib (the first FDA-approved MEK inhibitor) in patients with progressing/refractory LGG or plexiform neurofibroma with activation of the MAPK pathway ( 28 ), and a phase 1/2 study of the BRAF V600 inhibitor dabrafenib in pediatric patients with BRAF V600-mutant relapsed or refractory LGG ( Table 1 ) ( 19 , 29 ). BRAF V600E mutation has been identified in nearly 20% of pediatric LGG across a range of histologies and sites and confers a worse prognosis than BRAF wild-type tumors when treated with conventional adjuvant therapies (including chemotherapy and radiotherapy) ( 15 ). While TRK fusions are less commonly identified in pediatric gliomas, robust responses to TRK kinase inhibitors have been seen in pediatric solid tumors harboring TRK fusions, including high grade gliomas ( 20 , 21 , 30 ). Thus, when feasible, pediatric LGG should be evaluated for potentially targetable alterations, as MEK1/2, BRAF, and TRK inhibitors have demonstrated promising activity in pediatric gliomas and can be considered for patients who have failed upfront chemotherapy.

The timing of use of radiotherapy for LGG is controversial and continues to evolve with developments in targeted systemic therapies and radiotherapy techniques. Radiotherapy has for years demonstrated effective control of unresectable, progressive LGG, with 10-year PFS and overall survival (OS) of approximately 70% and 80%, respectively ( 31 – 33 ). However, concerns of late toxicity, including neurocognitive deficits, stroke, endocrine dysfunction, and secondary malignancy, especially in younger patients treated with radiotherapy ( 32 – 35 ), led to a shift toward initial treatment with systemic therapy and avoidance or delay of radiotherapy ( 36 – 38 ). In many cases, treatment with multiple lines of systemic therapy, deferring radiotherapy, has resulted in significant morbidity from tumor progression ( 39 ). Advances in radiotherapy techniques since the 1990s have allowed for more precise and conformal delivery of radiotherapy, maintaining tumor control while reducing normal tissue toxicity ( Table 2 ). An early study of stereotactic radiotherapy for pediatric low-grade gliomas in the 1990s at the Dana Farber Cancer Institute used magnetic resonance imaging (MRI)-based treatment planning and smaller radiotherapy target margins and demonstrated maintained PFS and OS (65% and 82%, respectively, at 8 years), with no marginal failures ( 40 ). A subsequent phase 2 trial was conducted at the St. Jude Children’s Research Hospital of conformal radiotherapy for pediatric low-grade gliomas using primarily 3-dimensional conformal radiotherapy (3D-CRT) with a 10mm clinical target volume (CTV) margin and MRI-based planning. Disease control was similarly maintained, with 10-year EFS and OS of 74% and 96%, respectively ( 41 ). Late effects were overall limited compared to patients treated with less conformal techniques, although cognitive deficits and risk of vasculopathy were greater in patients younger than age 5 at the time of treatment ( 41 , 45 ). More recently, the COG study ACNS0221 (2006–2010) evaluated conformal radiotherapy for pediatric LGG, using a smaller 5mm CTV margin with the majority (71%) of patients receiving IMRT, the current standard radiotherapy technique. This study also demonstrated favorable disease control (5-year PFS and OS of 71% and 93%, respectively) with limited toxicity ( 42 ). Finally, treatment with proton therapy, which can often further spare normal tissues for pediatric brain tumors compared to IMRT ( 46 ), has demonstrated reduced toxicity while maintaining excellent disease control for pediatric LGG. A study from the Massachusetts General Hospital demonstrated 8-year PFS and OS of 83% and 100%, respectively, and no significant declines in intelligence quotient (IQ), although a subset analysis suggested more neurocognitive decline in patients <7 years and those with significant dose to the left temporal lobe/hippocampus ( 43 ). More recently, a report on a large series of patients (n=174) treated with proton therapy for LGG at the University of Florida Health Proton Therapy Institute also demonstrated excellent disease control (5-year PFS and OS of 84% and 92%, respectively), with <5% developing serious late toxicity at a median follow-up of 4.4 years ( 44 ).

Table 2 Studies of advanced radiotherapy techniques for pediatric low-grade glioma.

In this context of reduced toxicity from newer radiotherapy techniques, recent studies suggest that delayed radiotherapy may be associated with worse outcomes in some patients with pediatric LGG. A study of pediatric patients treated with radiotherapy for optic pathway and hypothalamic LGG at St. Jude found that receipt of chemotherapy prior to radiotherapy was associated with worse EFS (hazard ratio 3.1, 95% CI: 1.4-7.0, P=0.007) and that younger age <6 years at the time of radiotherapy (patients who were typically treated first with chemotherapy) had worse EFS and OS ( 32 ). A very recent study by investigators at St. Jude reviewed pediatric patients with unresectable LGG treated with radiotherapy and identified low- and high-risk groups based on OS [10-year OS of 96% (95% CI: 89-98%) versus 76% (95% CI: 59-87%) respectively] ( 47 ). Within the high-risk group, which included diffuse astrocytoma or location within the thalamus/midbrain, delayed radiotherapy (after at least one line of chemotherapy) was associated with worse PFS (hazard ratio 2.5, 95% CI: 1.4-4.4, P=0.001). Thus, early radiotherapy should be considered for LGG patients with higher risk disease, those at risk of functional impairment with progression, older patients, and those without targetable alterations.

Several questions arise from these studies regarding the management of pediatric LGG: can novel targeted agents be combined with radiotherapy, and can modifications in radiotherapy dose be considered? The studies of MEK1/2 and BRAF inhibitors for pediatric LGG have been for recurrent, refractory, or progressive disease and not in combination (whether concurrent or sequential) with radiotherapy. Pre-clinical data have suggested synergy between MEK1/2 and BRAF inhibitors with radiotherapy for pediatric gliomas ( 48 – 50 ), but concerns regarding toxicity of concurrent treatment exist ( 51 , 52 ). The standard radiotherapy dose for pediatric LGG (~54 Gy) is largely derived from adult studies, where dose escalation above 45-50 Gy has not been associated with improved outcomes in randomized trials, but retrospective data in both adult and pediatric studies suggest better survival with treatment to ≥53 Gy ( 44 , 53 – 55 ). As recent studies of radiotherapy for pediatric LGG have focused on reduced margins and more conformal delivery techniques (reviewed above), the standard dose has remained ~54 Gy. While improvements in conformality may lessen the benefits of dose reduction for LGG, there would likely still be significant benefit for patients with larger tumors or those near critical structures such as the hippocampi ( 56 ). Further, combination with MEK1/2 and/or BRAF inhibitors may allow for reduction of radiotherapy dose while maintaining tumor control. Future investigations could evaluate these combinations, with standard versus reduced-dose radiotherapy and with targeted therapy and radiotherapy delivered concurrently versus sequentially as in ACNS1723 for high-grade glioma (discussed in the next section) to minimize toxicities of combined therapy.

Management of Pediatric High-Grade Gliomas With Advances in Targeted Therapies

While pediatric high-grade gliomas (HGG) are standardly treated with conventional radiotherapy and temozolomide chemotherapy based on adult data ( 57 ), this treatment approach as studied in ACNS0126 and ACNS0423 did not improve outcomes in children with HGG compared to prior treatments with radiotherapy and other chemotherapy regimens ( 58 – 60 ). Pediatric diffuse midline gliomas, including diffuse intrinsic pontine glioma (DIPG), are typically considered high grade given aggressive behavior even with lower grade histology ( 61 ) and are treated with radiotherapy and best supportive care. Outcomes overall are still very poor for these tumors, and thus novel treatment approaches are desperately needed. Multiple studies have now established a different molecular genetic profile underlying pediatric HGG compared to adult disease, with frequent somatic mutations in histone H3 genes, TP53, and ATRX; focal amplification of PDGFRA; chromosome 1q gain; NTRK and other targetable gene fusions in infant HGG; and infrequent IDH1 hotspot mutations ( 14 , 21 , 62 – 65 ). Approximately 5-10% of pediatric HGGs harbor BRAF V600E mutations and have a slightly better clinical outcome, potentially accounting for some of the long-term survivors in pediatric HGG trials ( 66 , 67 ).

Therapeutically, these advances in molecular characterization will allow tailoring of treatment approaches for pediatric HGG instead of a single standard paradigm for all patients. Unfortunately, in contrast to LGG, a single drug is unlikely to benefit a large number of patients given the heterogeneity of these tumors, and radiotherapy will likely remain a critical component of upfront treatment for these patients. Infant HGG may be one subset where targeted therapies are used upfront, deferring radiotherapy, as these tumors more frequently exhibit targetable MAPK alterations and gene fusions targeting ALK, NTRK, ROS1, and MET ( 14 , 21 ) and have demonstrated rapid clinical responses to targeted therapies in case reports ( 20 , 68 ). For older children with HGG, two ongoing COG trials are evaluating novel systemic therapies together with radiotherapy depending on tumor molecular features: for patients with BRAF V600 mutant-HGG, ACNS1723 [NCT03919071] is a phase 2 trial evaluating treatment with the BRAF V600 inhibitor dabrafenib and MEK 1/2 inhibitor trametinib following radiotherapy. For those without BRAF V600 or H3 K27M mutations, ACNS1721 [NCT03581292] is a phase 2 trial evaluating concurrent radiotherapy with the poly (ADP-ribose) polymerase (PARP) inhibitor veliparib, followed by maintenance chemotherapy with veliparib and temozolomide. PARP inhibitors, as DNA damage response inhibitors, can effectively synergize with radiotherapy ( 69 , 70 ) and have demonstrated radio- and chemo-sensitization in pre-clinical studies of glioblastoma ( 71 ). PARP inhibition has been evaluated clinically in combination with temozolomide in recurrent adult glioblastoma and recurrent pediatric brain tumors ( 72 , 73 ), as well as in combination with radiation and temozolomide in the Pediatric Brain Tumor Consortium (PBTC) study PBTC-033 for newly diagnosed DIPG but did not improve survival compared to historical series ( 74 ) (thus patients with H3 K27M mutations are excluded from ACNS1721). Along similar lines, Wee1 is a cell cycle regulator that is also involved in the DNA damage repair pathway. Based on promising pre-clinical data ( 75 ), the COG is conducting a phase 1 trial of the Wee1 inhibitor adavosertib with radiotherapy for newly diagnosed DIPG (COG-ADVL1217, NCT01922076).

Management of Pediatric Sarcomas and Other Extracranial Solid Tumors With Advances in Targeted Therapies

Outside of the central nervous system (CNS), targeted systemic therapies are increasingly incorporated in the treatment of pediatric sarcomas, as well as other tumors based on specific molecular and genetic alterations. These are typically included concurrently with radiotherapy as part of definitive treatment, or following standard of care therapy in the recurrent or refractory setting. Based on clinical efficacy in the treatment of adult soft tissue sarcoma (STS) and renal cell carcinoma, pazopanib, a multikinase angiogenesis inhibitor targeting vascular endothelial growth factor receptors (VEGFR), c-kit, and platelet-derived growth factor receptors (PDGFR), was initially evaluated in a phase 1 trial by the COG for children with STS and other refractory solid tumors. This study demonstrated pazopanib was well tolerated in children, had evidence of anti-angiogenic effect, and had potential clinical benefit in pediatric sarcoma ( 76 ). Subsequently, the COG together with the adult cooperative group NRG Oncology conducted a randomized phase 2 trial, ARST1321, evaluating the addition of pazopanib to pre-operative chemoradiotherapy for children and adults with large, unresectable, intermediate- or high-grade STS. Initial results after the second interim analysis have recently been published and demonstrated improvement in the pathological near-complete response rate with addition of pazopanib (≥90% pathological response in 58% of patients in the pazopanib group versus 22% of patients in the control group) ( 77 ). Longer-term follow-up will be required to compare survival outcomes.

Targeted therapy is also being evaluated for newly diagnosed metastatic Ewing sarcoma. Prior phase 1 and phase 2 studies demonstrated favorable responses to ganitumab, an insulin-like growth factor receptor (IGFR) inhibitor, in patients with relapsed or refractory Ewing sarcoma ( 78 , 79 ). Based on these data, the COG randomized phase 3 trial AEWS1221 is evaluating addition of ganitumab to standard multi-agent chemotherapy for newly diagnosed metastatic Ewing sarcoma [NCT02306161]. Local control with surgery and/or radiotherapy after induction chemotherapy, as well as metastatic site radiotherapy following consolidation chemotherapy, remain components of treatment on this study.

In the relapsed or refractory setting, multiple agents targeting VEGFR, PDGFR, mechanistic target of rapamycin (mTOR), and IGFR, among others, are being evaluated for pediatric sarcomas ( 80 , 81 ). While multi-agent chemotherapy regimens are standard for rhabdomyosarcoma (RMS) and Ewing sarcoma, targeted therapies are increasingly being evaluated for recurrent or refractory disease. For example, a phase 1/2 trial conducted by the National Cancer Institute is evaluating the IGF-1R antibody ganitumab in combination with the Src family kinase inhibitor dasatinib in patients with embryonal or alveolar RMS refractory to other standard treatments [NCT03041701]. For patients with relapsed or refractory Ewing sarcoma, a prior phase 2 trial demonstrated partial response or stable disease following treatment with ganitumab in 55% of patients ( 79 ), and a phase 2 trial is currently being conducted to evaluate ganitumab in combination with the cyclin-dependent kinase (CDK) 4/6 inhibitor palbociclib [NCT04129151].

Desmoplastic small round cell tumor (DSRCT), a rare and aggressive STS that is characterized by translocation between EWSR1 and WT1, is typically treated with intensive multimodal therapy including alkylator-based chemotherapy, cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (HIPEC), and whole abdominopelvic radiotherapy ( 82 ). However, survival outcomes remain dismal (5-year OS ~25%) ( 82 ), and novel therapeutic approaches are critically needed. Currently, targeted systemic therapies are usually considered at progression after first- or second-line chemotherapy, and data are limited to small case series or trials of Ewing sarcoma that include DSRCT ( 83 ). Pazopanib is one of the agents with more clinical experience that has demonstrated clinical activity in DSRCT, with partial response observed in a small subset of patients and at least stable disease observed in the majority of patients in the largest study of 22 patients with heavily pre-treated DSRCT ( 76 , 84 ). Other reports have shown stable response to mTOR inhibitors and other PDGFR and VEGFR inhibitors, and a few ongoing studies are evaluating therapies targeting these and other pathways ( 83 ).

Advances in molecular and genetic tumor evaluation have allowed identification of a small subset of pediatric solid tumors that harbor targetable NTRK gene fusions and BRAF alterations (introduced above) ( 16 , 85 ). A phase 1 study of the TRK kinase inhibitor larotrectinib for pediatric solid tumors harboring NTRK gene fusions demonstrated an ORR of 93% with predominantly grade 1 adverse events. Tumors included infantile fibrosarcoma, other STS, and papillary thyroid cancer ( 30 , 86 ). Five patients on this phase 1 study were treated preoperatively with larotrectinib for locally advanced sarcomas, and all had radiographic partial response. Three of the five patients had R0 resections and complete or near-complete pathological responses ( 87 ). Thus, robust responses to these agents have led to their incorporation primarily for recurrent, refractory, or metastatic disease but may also be considered earlier in the course of treatment and, in rare cases, may provide an alternative to pre- or post-operative radiotherapy for management of pediatric sarcomas.

The incorporation of hypofractionated radiotherapy for local control in advanced disease settings is evolving. Stereotactic body radiotherapy (SBRT) is increasingly being utilized and studied for oligometastatic and recurrent disease, as a more convenient treatment that can minimize interruption of systemic therapy, and with possibly less toxicity than conventional radiotherapy. For sarcomas, which are typically more radioresistant, SBRT may also offer increased local control efficacy. However, the relevance and success of SBRT, which delivers high biologically effective doses to focal areas of disease, relies on improvements in micrometastatic disease control with systemic therapy. Thus, SBRT may become increasingly relevant with effective targeted systemic therapies. Several retrospective and early phase prospective studies (summarized in Table 3 ) have evaluated SBRT for metastatic and recurrent sarcomas ( 88 – 91 ). These have generally shown good local control outcomes, but increased toxicity when given with concurrent systemic therapy or in the re-irradiation setting. The prospective phase II study by Elledge et al. importantly suggested that survival outcomes may be improved with consolidation of all known metastatic sites with SBRT ( 90 ), consistent with data from the EURO-EWING trial indicating improved EFS with local therapy to primary and metastatic sites ( 92 ). Current COG trial AEWS1221 is evaluating SBRT for treatment of osseous metastatic sites, to a dose of 40 Gy in 5 fractions [NCT02306161]. Additional data are still needed to evaluate the safety of SBRT with newer targeted systemic therapies.

Table 3 Studies of stereotactic body radiotherapy for pediatric sarcomas.

Role of Immunotherapy in Management of Pediatric Cancers

While immunotherapy has revolutionized the treatment of several adult cancers, its role in pediatric malignancies has thus far been limited, in large part due to how most pediatric cancers arise: typically from embryonal cells through transcriptional abnormalities, chromosomal rearrangements, and copy number variants, as opposed to accumulation of genetic mutations in epithelial cells ( 93 , 94 ). Thus, most pediatric tumors have low mutational burden and limited neoantigen expression and are non- or weakly immunogenic, with the rare exception of cancers arising from mismatch repair deficiencies ( 94 , 95 ). However, a few immunotherapies have been FDA-approved for treatment of pediatric cancers. Blinatumomab, a bispecific antibody targeting the B lymphocyte antigen CD19, and tisagenlecleucel, a chimeric antigen receptor (CAR)-T cell therapy targeting CD19, are approved for treatment of relapsed/refractory B-cell acute lymphoblastic leukemia ( 93 , 96 , 97 ). Dinutuximab is an antibody specific for disialoganglioside (GD2), a glycolipid antigen highly expressed on the surface of neuroblastoma and other embryonal tumors. The Fc portion of anti-GD2 antibodies engages receptors on monocytes, macrophages, neutrophils, and natural killer cells, which then triggers antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity ( 93 , 98 ). Based on promising initial phase I data of dinutuximab alone and in combination with granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-2 (IL-2) to enhance ADCC ( 99 – 101 ), the COG conducted the randomized phase 3 study ANBL0032 to evaluate the addition of dinutuximab with GM-CSF and IL-2 to standard isotretinoin post-consolidation therapy for high-risk neuroblastoma patients. The study was stopped early due to the superiority of the dinutuximab arm at 2 years, with significant improvements in EFS (66 ± 5% vs . 46 ± 5%, P =0.01) and OS (86 ± 4% vs . 75 ± 5%, P =0.02) ( 102 ). Thus, dinutuximab is FDA-approved for treatment of high-risk neuroblastoma patients with response to frontline multi-modal therapy (including consolidative radiotherapy) and is a standard component of post-consolidation therapy on the current COG trial ANBL1531 [NCT03126916] ( 93 ). Finally, immune checkpoint inhibitors, which have had significant success in the treatment of adult cancers, have not yet been widely adopted in the pediatric setting. Pembrolizumab, an antibody specific for programmed cell death protein 1 (PD-1) expressed on activated T and B lymphocytes, is approved for the treatment of refractory or relapsed Hodgkin lymphoma based on data extrapolated from adult studies ( 93 , 103 ). Ipilimumab, an antibody targeting cytotoxic T lymphocyte antigen 4 (CTLA-4), is approved for treatment of unresectable or metastatic melanoma in pediatric patients ≥12 years of age ( 104 , 105 ).

Ongoing clinical trials evaluating various immunotherapies (including immune checkpoint inhibitors, CAR-T cell therapies, cancer vaccines, and oncolytic virus therapies, among others) across a spectrum of pediatric cancers are summarized in Hutzen et al. ( 93 ) A handful of trials incorporate radiotherapy, either in combination with immunotherapy or as consolidative therapy after upfront systemic therapy. For patients ≥12 years of age with newly diagnosed stage III-IV classic Hodgkin lymphoma, a randomized phase 3 trial is evaluating immunotherapy (nivolumab, an anti-PD-1 antibody, versus brentuximab vedotin, an antibody-drug conjugate targeting CD30 on the surface of Hodgkin lymphoma cells) with standard combination chemotherapy followed by consolidative radiotherapy as clinically indicated [SWOG S1826, NCT03907488]. A few studies are investigating combinations of immunotherapy and radiotherapy for progressive or recurrent primary brain tumors. Indoximod is an inhibitor of the indoleamine 2,3-dioxygenase (IDO) pathway, which serves multiple immunomodulatory functions but ultimately results in immune tolerance to tumor antigens ( 106 ). A phase 1 trial of indoximod combined with temozolomide or radiotherapy for pediatric patients with progressive brain tumors (or with radiotherapy for patients with newly diagnosed DIPG) has completed enrollment [NCT02502708], and a phase 2 trial is now underway [NCT04049669]. Other studies are investigating intratumoral virus injection together with radiotherapy for malignant gliomas or recurrent ependymomas [NCT02457845, NCT00634231], as well as adoptive cellular therapy with radiotherapy (with or without temozolomide) for patients with brainstem gliomas [NCT03396575]. Finally, based on pre-clinical and clinical data suggesting more robust systemic immune responses to combinations of focal radiotherapy and immunotherapy ( 107 – 113 ), a few early studies are evaluating this combination in extracranial solid tumors and lymphomas [NCT03445858].

Tailoring Radiotherapy With Advancements in Molecular Characterization

Dose-reduced radiotherapy for patients with low risk medulloblastoma.

Medulloblastoma is standardly treated with an aggressive multi-modal regimen of maximal safe resection followed by post-operative craniospinal irradiation (CSI) and multi-agent chemotherapy. However, as the median age at diagnosis is ~6 years of age and the majority of patients are long-term survivors (5-year OS ~80% for patients with standard risk disease and ~60% for patients with high risk disease), all patients experience late toxicities, including neurocognitive impairment, neuroendocrine dysfunction, impact on growth, infertility, and secondary malignancies, and strategies to decrease late effects from treatment while maintaining survival rates are constantly being evaluated ( 114 ). Patients with standard risk disease per traditional definitions (≤1.5cm 2 residual disease, ≥3 years old, and no metastatic disease) are treated with lower dose CSI (23.4 Gy) with an involved field boost to 54 Gy total, while patients with high risk disease per traditional definitions (>1.5cm 2 residual disease or metastatic disease present) are treated with higher dose CSI (36 Gy) with a posterior fossa boost to 54 Gy total and metastatic site boost to 45-54 Gy total. CSI has been an essential component of treatment for medulloblastoma, as cure was rare before the use of CSI, and early efforts to omit or reduce the dose of CSI resulted in worse outcomes ( 115 , 116 ). Based on early studies of medulloblastoma demonstrating significant and often unacceptable neurocognitive deficits attributed to high dose radiotherapy in children under the age of 3 ( 1 , 117 , 118 ), radiotherapy is typically delayed for infants and young children with medulloblastoma until age 3 or older. Surgical resection is usually followed by adjuvant chemotherapy, delaying radiotherapy until progression (the “acceptable” age for proceeding with CSI varies across studies, from 18 months to 6 years) ( 119 – 121 ). The COG trial ACNS0334 [NCT00336024] is evaluating two high-dose chemotherapy regimens followed by peripheral blood stem cell rescue for infants up to age 2 with high-risk medulloblastoma or CNS embryonal tumors, and preliminary results suggest that while focal radiotherapy may be reasonable upfront for select patients, omission of CSI upfront does not appear to compromise survival ( 122 ).

Newer radiotherapy techniques, including IMRT and proton therapy, as well as reduction in the boost margin, have resulted in steadily lower doses to normal tissues without compromising disease control ( 123 – 125 ). Specifically for proton therapy, dosimetric studies indicate reduction of dose to anterior organs, including heart, gastrointestinal tract, lungs, kidneys, and thyroid, with proton CSI ( 126 ), and evaluation of long-term toxicity of proton therapy for medulloblastoma suggests decreased cardiac, pulmonary, and gastrointestinal toxicity compared to photon-based treatments ( 127 ). While neurocognitive impairment will always occur with CSI regardless of treatment modality, especially with younger age at the time of treatment ( 128 ), a recent study suggests that better intellectual outcomes may still be achieved with proton versus photon radiotherapy for medulloblastoma based on the boost treatment ( 129 ). Thus, even with standard-dose radiotherapy for medulloblastoma, advancements in radiotherapy techniques are resulting in improvements in the late toxicity profile.

More recently, the management of medulloblastoma has been revolutionized by advancements in tumor molecular characterization, moving from previous risk definitions based on amount of residual disease, age, and presence of metastatic disease to current stratifications based on molecular subgroups: WNT, sonic hedgehog (SHH), Group 3, and Group 4. With standard treatments, the WNT subgroup is most favorable, with >90% 5-year PFS, followed by intermediate outcomes in the SHH and Group 4 subgroups (5-year PFS of 70-80%), and poor outcomes for Group 3 (5-year PFS of 50-60%) ( 8 , 114 , 130 ). Thus, current studies are evaluating whether patients in low risk subgroups may be eligible for de-intensified treatment regimens, whether avoiding radiotherapy altogether or reducing the dose or volume of radiotherapy ( Figure 3 ) ( 7 , 130 ). COG study ACNS1422 [NCT02724579] is evaluating whether both chemotherapy intensity and CSI dose (18 Gy) can be reduced in patients with average risk WNT-driven tumors who have positive β-catenin and presence of CTNNB1 [exon 3] mutation and without large cell/anaplastic medulloblastoma or MYC/MYCN amplification. SJMB12 [NCT01878617] is evaluating a reduced CSI dose of 15 Gy in the same population. However, a pilot study omitting CSI entirely for WNT-driven medulloblastoma has closed due to inferior outcomes [NCT02212574]. In Europe, the ongoing International Society of Paediatric Oncology (SIOP) PNET-5 study is investigating the possibility to deliver, within a combined modality approach, a reduced CSI dose of 18 Gy to a selected subgroup of children with a low-risk biological profile [NCT02066220]. At the same time, SJMB12 is investigating intensified treatment regimens for patients in higher risk subgroups, including the addition of gemcitabine and pemetrexed for those with high risk Group 3 or Group 4 medulloblastoma and targeted SHH inhibitor therapy for those with SHH-medulloblastoma ( Figure 3 ).

Figure 3 Current treatment paradigms for medulloblastoma, as well as approaches under investigation in clinical trials incorporating molecular risk stratification. Investigational approaches are indicated in red. CSI, craniospinal irradiation; GTR, gross total resection; NTR, near total resection; SHH, sonic hedgehog; STR, subtotal resection.

Risk-Adapted Radiotherapy for Patients With Rhabdomyosarcoma

Rhabdomyosarcoma is standardly treated with a combined modality regimen of surgery (if resectable), multi-agent chemotherapy, and radiotherapy. Use and dose of radiotherapy for rhabdomyosarcoma is typically based on clinical group, FOXO1 fusion status, and site (primary/metastatic). Patients with clinical group I, FOXO1 negative or indeterminate tumors do not receive radiotherapy, while all others receive radiotherapy with dose based on the factors above. Given the young age of many of these patients and significant risk of late toxicity from radiotherapy ( 131 – 134 ), there is always a question of whether radiotherapy can be safely omitted or reduced and thereby minimize treatment-related toxicity for appropriately selected patients. An analysis of ARST0331 and ARST0531 suggests worse local control and survival outcomes when “individualized local therapy” (typically omission or delay of radiotherapy) as opposed to protocol-specified radiotherapy is given to infants with rhabdomyosarcoma ( 135 ). Thus, attempting to select for more favorable risk patients, the current protocol ARST1431 [NCT02567435] permits deviations for patients ≤2 years of age only if they are FOXO1 fusion negative. Histologic and radiographic response to initial chemotherapy is another measure that has been used to guide radiotherapy usage and dose (used in D9602/D9803 and ARST0331/ARST0531, as well as in ARST1431). Second-look procedures after initial chemotherapy largely correlate with clinical/radiographic complete response; however, ~40% of patients without clinical/radiographic complete response have no viable tumor histologically, and thus post-chemotherapy biopsies/DPE may be helpful for selecting patients for radiotherapy dose reduction ( 136 ). On the other end, ARST1431 is evaluating higher doses of radiotherapy in patients at greater risk of local failure by increasing the boost dose to 59.4 Gy total for tumors >5cm at diagnosis.

Future studies will need to incorporate our evolving understanding of molecular and genetic features of rhabdomyosarcoma that are associated with favorable or adverse outcomes, such that patients can be appropriately selected for potential treatment de-escalation or escalation. For instance, recent histological and molecular analysis of infant rhabdomyosarcoma suggests favorable prognosis of the spindle cell subtype associated with alterations in VGLL2, NTRK, and BRAF, and potential consideration of de-intensified treatment for this subset of patients ( 137 ). Conversely, MYOD1-mutant spindle cell and sclerosing rhabdomyosarcoma is associated with an aggressive clinical course and poor outcomes ( 138 , 139 ) and, together with tumors with anaplasia and TP53 mutation, should be excluded from consideration of de-escalated therapy and perhaps considered for augmented therapy.

Radiotherapy has remained an integral component in the treatment of pediatric cancers over several decades. However, its role has continued to evolve with the introduction of chemotherapy regimens and now molecularly targeted therapies in an era of rapid advances in precision medicine. In particular, MEK1/2, BRAF, and TRK inhibitors have demonstrated significant promise in pediatric gliomas and extracranial solid tumors harboring these alterations and warrant further investigation in larger trials, as well as clinical consideration when these alterations are present. Developments in molecular diagnostics and targeted systemic therapies are providing opportunities for potentially more effective and specific but less toxic therapies, critical for treatment of pediatric patients. At the same time, advances in radiotherapy techniques are improving the precision and conformality of local therapy. Together, these developments are leading to novel synergistic combinations of radiotherapy and systemic therapy, as well as potential avenues to select patients for treatment de-escalation, leading to more tailored treatments with improved therapeutic ratio for pediatric cancer patients.

Author Contributions

CS and ST contributed to conception of the manuscript. CS wrote the first draft of the manuscript. All authors contributed to the article and approved the submitted version.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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121. Dhall G, Grodman H, Ji L, Sands S, Gardner S, Dunkel IJ, et al. Outcome of Children Less Than Three Years Old at Diagnosis With non-Metastatic Medulloblastoma Treated With Chemotherapy on the “Head Start” I and II Protocols. Pediatr Blood Cancer (2008) 50(6):1169–75. doi: 10.1002/pbc.21525

122. Aridgides PD, Kang G, Mazewski C, Merchant TE. Outcomes After Radiation Therapy for Very Young Children With High-Risk Medulloblastoma or Supratentorial Primitive Neuroectodermal Tumor Treated on COG Acns0334. Int J Radiat Oncol (2019) 105(1, Supplement):S109. doi: 10.1016/j.ijrobp.2019.06.602

123. Merchant TE, Kun LE, Krasin MJ, Wallace D, Chintagumpala MM, Woo SY, et al. Multi-Institution Prospective Trial of Reduced-Dose Craniospinal Irradiation (23.4 Gy) Followed by Conformal Posterior Fossa (36 Gy) and Primary Site Irradiation (55.8 Gy) and Dose-Intensive Chemotherapy for Average-Risk Medulloblastoma. Int J Radiat Oncol Biol Phys (2008) 70(3):782–7. doi: 10.1016/j.ijrobp.2007.07.2342

124. Moxon-Emre I, Bouffet E, Taylor MD, Laperriere N, Scantlebury N, Law N, et al. Impact of Craniospinal Dose, Boost Volume, and Neurologic Complications on Intellectual Outcome in Patients With Medulloblastoma. J Clin Oncol Off J Am Soc Clin Oncol (2014) 32(17):1760–8. doi: 10.1200/JCO.2013.52.3290

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128. Pulsifer MB, Duncanson H, Grieco J, Evans C, Tseretopoulos ID, MacDonald S, et al. Cognitive and Adaptive Outcomes After Proton Radiation for Pediatric Patients With Brain Tumors. Int J Radiat Oncol (2018) 102(2):391–8. doi: 10.1016/j.ijrobp.2018.05.069

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131. Paulino AC, Simon JH, Zhen W, Wen B-C. Long-Term Effects in Children Treated With Radiotherapy for Head and Neck Rhabdomyosarcoma. Int J Radiat Oncol (2000) 48(5):1489–95. doi: 10.1016/S0360-3016(00)00799-9

132. Paulino AC. Late Effects of Radiotherapy for Pediatric Extremity Sarcomas. Int J Radiat Oncol (2004) 60(1):265–74. doi: 10.1016/j.ijrobp.2004.02.001

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Keywords: precision medicine & genomics, pediatric cancer, targeted therapies, molecular diagnostics, radiation therapy (radiotherapy), pediatric glioma, medulloblastoma, pediatric sarcomas

Citation: Shen CJ and Terezakis SA (2021) The Evolving Role of Radiotherapy for Pediatric Cancers With Advancements in Molecular Tumor Characterization and Targeted Therapies. Front. Oncol. 11:679701. doi: 10.3389/fonc.2021.679701

Received: 12 March 2021; Accepted: 26 August 2021; Published: 16 September 2021.

Reviewed by:

Copyright © 2021 Shen and Terezakis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Colette J. Shen, [email protected]

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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Radiology Thesis – More than 400 Research Topics (2022)!

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Introduction

A thesis or dissertation, as some people would like to call it, is an integral part of the Radiology curriculum, be it MD, DNB, or DMRD. We have tried to aggregate radiology thesis topics from various sources for reference.

Not everyone is interested in research, and writing a Radiology thesis can be daunting. But there is no escape from preparing, so it is better that you accept this bitter truth and start working on it instead of cribbing about it (like other things in life. #PhilosophyGyan!)

Start working on your thesis as early as possible and finish your thesis well before your exams, so you do not have that stress at the back of your mind. Also, your thesis may need multiple revisions, so be prepared and allocate time accordingly.

Tips for Choosing Radiology Thesis and Research Topics

Keep it simple silly (kiss).

Retrospective > Prospective

Retrospective studies are better than prospective ones, as you already have the data you need when choosing to do a retrospective study. Prospective studies are better quality, but as a resident, you may not have time (, energy and enthusiasm) to complete these.

Choose a simple topic that answers a single/few questions

Original research is challenging, especially if you do not have prior experience. I would suggest you choose a topic that answers a single or few questions. Most topics that I have listed are along those lines. Alternatively, you can choose a broad topic such as “Role of MRI in evaluation of perianal fistulas.”

You can choose a novel topic if you are genuinely interested in research AND have a good mentor who will guide you. Once you have done that, make sure that you publish your study once you are done with it.

Get it done ASAP.

In most cases, it makes sense to stick to a thesis topic that will not take much time. That does not mean you should ignore your thesis and ‘Ctrl C + Ctrl V’ from a friend from another university. Thesis writing is your first step toward research methodology so do it as sincerely as possible. Do not procrastinate in preparing the thesis. As soon as you have been allotted a guide, start researching topics and writing a review of the literature.

At the same time, do not invest a lot of time in writing/collecting data for your thesis. You should not be busy finishing your thesis a few months before the exam. Some people could not appear for the exam because they could not submit their thesis in time. So DO NOT TAKE thesis lightly.

Do NOT Copy-Paste

Reiterating once again, do not simply choose someone else’s thesis topic. Find out what are kind of cases that your Hospital caters to. It is better to do a good thesis on a common topic than a crappy one on a rare one.

Books to help you write a Radiology Thesis

Event country/university has a different format for thesis; hence these book recommendations may not work for everyone.

How to Write the Thesis and Thesis Protocol: A Primer for Medical, Dental, and Nursing Courses: A Primer for Medical, Dental and Nursing Courses

Amazon Kindle Edition
Gupta, Piyush (Author)
English (Publication Language)
206 Pages - 10/12/2020 (Publication Date) - Jaypee Brothers Medical Publishers (P) Ltd. (Publisher)

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List of Radiology Research /Thesis / Dissertation Topics

State of the art of MRI in the diagnosis of hepatic focal lesions
Multimodality imaging evaluation of sacroiliitis in newly diagnosed patients of spondyloarthropathy
Multidetector computed tomography in oesophageal varices
Role of positron emission tomography with computed tomography in the diagnosis of cancer Thyroid
Evaluation of focal breast lesions using ultrasound elastography
Role of MRI diffusion tensor imaging in the assessment of traumatic spinal cord injuries
Sonographic imaging in male infertility
Comparison of color Doppler and digital subtraction angiography in occlusive arterial disease in patients with lower limb ischemia
The role of CT urography in Haematuria
Role of functional magnetic resonance imaging in making brain tumor surgery safer
Prediction of pre-eclampsia and fetal growth restriction by uterine artery Doppler
Role of grayscale and color Doppler ultrasonography in the evaluation of neonatal cholestasis
Validity of MRI in the diagnosis of congenital anorectal anomalies
Role of sonography in assessment of clubfoot
Role of diffusion MRI in preoperative evaluation of brain neoplasms
Imaging of upper airways for pre-anaesthetic evaluation purposes and for laryngeal afflictions.
A study of multivessel (arterial and venous) Doppler velocimetry in intrauterine growth restriction
Multiparametric 3tesla MRI of suspected prostatic malignancy.
Role of Sonography in Characterization of Thyroid Nodules for differentiating benign from
Role of advances magnetic resonance imaging sequences in multiple sclerosis
Role of multidetector computed tomography in evaluation of jaw lesions
Role of Ultrasound and MR Imaging in the Evaluation of Musculotendinous Pathologies of Shoulder Joint
Role of perfusion computed tomography in the evaluation of cerebral blood flow, blood volume and vascular permeability of cerebral neoplasms
MRI flow quantification in the assessment of the commonest csf flow abnormalities
Role of diffusion-weighted MRI in evaluation of prostate lesions and its histopathological correlation
CT enterography in evaluation of small bowel disorders
Comparison of perfusion magnetic resonance imaging (PMRI), magnetic resonance spectroscopy (MRS) in and positron emission tomography-computed tomography (PET/CT) in post radiotherapy treated gliomas to detect recurrence
Role of multidetector computed tomography in evaluation of paediatric retroperitoneal masses
Role of Multidetector computed tomography in neck lesions
Estimation of standard liver volume in Indian population
Role of MRI in evaluation of spinal trauma
Role of modified sonohysterography in female factor infertility: a pilot study.
The role of pet-CT in the evaluation of hepatic tumors
Role of 3D magnetic resonance imaging tractography in assessment of white matter tracts compromise in supratentorial tumors
Role of dual phase multidetector computed tomography in gallbladder lesions
Role of multidetector computed tomography in assessing anatomical variants of nasal cavity and paranasal sinuses in patients of chronic rhinosinusitis.
magnetic resonance spectroscopy in multiple sclerosis
Evaluation of thyroid nodules by ultrasound elastography using acoustic radiation force impulse (ARFI) imaging
Role of Magnetic Resonance Imaging in Intractable Epilepsy
Evaluation of suspected and known coronary artery disease by 128 slice multidetector CT.
Role of regional diffusion tensor imaging in the evaluation of intracranial gliomas and its histopathological correlation
Role of chest sonography in diagnosing pneumothorax
Role of CT virtual cystoscopy in diagnosis of urinary bladder neoplasia
Role of MRI in assessment of valvular heart diseases
High resolution computed tomography of temporal bone in unsafe chronic suppurative otitis media
Multidetector CT urography in the evaluation of hematuria
Contrast-induced nephropathy in diagnostic imaging investigations with intravenous iodinated contrast media
Comparison of dynamic susceptibility contrast-enhanced perfusion magnetic resonance imaging and single photon emission computed tomography in patients with little’s disease
Role of Multidetector Computed Tomography in Bowel Lesions.
Role of diagnostic imaging modalities in evaluation of post liver transplantation recipient complications.
Role of multislice CT scan and barium swallow in the estimation of oesophageal tumour length
Malignant Lesions-A Prospective Study.
Value of ultrasonography in assessment of acute abdominal diseases in pediatric age group
Role of three dimensional multidetector CT hysterosalpingography in female factor infertility
Comparative evaluation of multi-detector computed tomography (MDCT) virtual tracheo-bronchoscopy and fiberoptic tracheo-bronchoscopy in airway diseases
Role of Multidetector CT in the evaluation of small bowel obstruction
Sonographic evaluation in adhesive capsulitis of shoulder
Utility of MR Urography Versus Conventional Techniques in Obstructive Uropathy
MRI of the postoperative knee
Role of 64 slice-multi detector computed tomography in diagnosis of bowel and mesenteric injury in blunt abdominal trauma.
Sonoelastography and triphasic computed tomography in the evaluation of focal liver lesions
Evaluation of Role of Transperineal Ultrasound and Magnetic Resonance Imaging in Urinary Stress incontinence in Women
Multidetector computed tomographic features of abdominal hernias
Evaluation of lesions of major salivary glands using ultrasound elastography
Transvaginal ultrasound and magnetic resonance imaging in female urinary incontinence
MDCT colonography and double-contrast barium enema in evaluation of colonic lesions
Role of MRI in diagnosis and staging of urinary bladder carcinoma
Spectrum of imaging findings in children with febrile neutropenia.
Spectrum of radiographic appearances in children with chest tuberculosis.
Role of computerized tomography in evaluation of mediastinal masses in pediatric
Diagnosing renal artery stenosis: Comparison of multimodality imaging in diabetic patients
Role of multidetector CT virtual hysteroscopy in the detection of the uterine & tubal causes of female infertility
Role of multislice computed tomography in evaluation of crohn’s disease
CT quantification of parenchymal and airway parameters on 64 slice MDCT in patients of chronic obstructive pulmonary disease
Comparative evaluation of MDCT and 3t MRI in radiographically detected jaw lesions.
Evaluation of diagnostic accuracy of ultrasonography, colour Doppler sonography and low dose computed tomography in acute appendicitis
Ultrasonography , magnetic resonance cholangio-pancreatography (MRCP) in assessment of pediatric biliary lesions
Multidetector computed tomography in hepatobiliary lesions.
Evaluation of peripheral nerve lesions with high resolution ultrasonography and colour Doppler
Multidetector computed tomography in pancreatic lesions
Multidetector Computed Tomography in Paediatric abdominal masses.
Evaluation of focal liver lesions by colour Doppler and MDCT perfusion imaging
Sonographic evaluation of clubfoot correction during Ponseti treatment
Role of multidetector CT in characterization of renal masses
Study to assess the role of Doppler ultrasound in evaluation of arteriovenous (av) hemodialysis fistula and the complications of hemodialysis vasular access
Comparative study of multiphasic contrast-enhanced CT and contrast-enhanced MRI in the evaluation of hepatic mass lesions
Sonographic spectrum of rheumatoid arthritis
Diagnosis & staging of liver fibrosis by ultrasound elastography in patients with chronic liver diseases
Role of multidetector computed tomography in assessment of jaw lesions.
Role of high-resolution ultrasonography in the differentiation of benign and malignant thyroid lesions
Radiological evaluation of aortic aneurysms in patients selected for endovascular repair
Role of conventional MRI, and diffusion tensor imaging tractography in evaluation of congenital brain malformations
To evaluate the status of coronary arteries in patients with non-valvular atrial fibrillation using 256 multirow detector CT scan
A comparative study of ultrasonography and CT – arthrography in diagnosis of chronic ligamentous and meniscal injuries of knee
Multi detector computed tomography evaluation in chronic obstructive pulmonary disease and correlation with severity of disease
Diffusion weighted and dynamic contrast enhanced magnetic resonance imaging in chemoradiotherapeutic response evaluation in cervical cancer.
High resolution sonography in the evaluation of non-traumatic painful wrist
The role of trans-vaginal ultrasound versus magnetic resonance imaging in diagnosis & evaluation of cancer cervix
Role of multidetector row computed tomography in assessment of maxillofacial trauma
Imaging of vascular complication after liver transplantation.
Role of magnetic resonance perfusion weighted imaging & spectroscopy for grading of glioma by correlating perfusion parameter of the lesion with the final histopathological grade
Magnetic resonance evaluation of abdominal tuberculosis.
Diagnostic usefulness of low dose spiral HRCT in diffuse lung diseases
Role of dynamic contrast enhanced and diffusion weighted magnetic resonance imaging in evaluation of endometrial lesions
Contrast enhanced digital mammography anddigital breast tomosynthesis in early diagnosis of breast lesion
Evaluation of Portal Hypertension with Colour Doppler flow imaging and magnetic resonance imaging
Evaluation of musculoskeletal lesions by magnetic resonance imaging
Role of diffusion magnetic resonance imaging in assessment of neoplastic and inflammatory brain lesions
Radiological spectrum of chest diseases in HIV infected children High resolution ultrasonography in neck masses in children
with surgical findings
Sonographic evaluation of peripheral nerves in type 2 diabetes mellitus.
Role of perfusion computed tomography in the evaluation of neck masses and correlation
Role of ultrasonography in the diagnosis of knee joint lesions
Role of ultrasonography in evaluation of various causes of pelvic pain in first trimester of pregnancy.
Role of Magnetic Resonance Angiography in the Evaluation of Diseases of Aorta and its Branches
MDCT fistulography in evaluation of fistula in Ano
Role of multislice CT in diagnosis of small intestine tumors
Role of high resolution CT in differentiation between benign and malignant pulmonary nodules in children
A study of multidetector computed tomography urography in urinary tract abnormalities
Role of high resolution sonography in assessment of ulnar nerve in patients with leprosy.
Pre-operative radiological evaluation of locally aggressive and malignant musculoskeletal tumours by computed tomography and magnetic resonance imaging.
The role of ultrasound & MRI in acute pelvic inflammatory disease
Ultrasonography compared to computed tomographic arthrography in the evaluation of shoulder pain
Role of Multidetector Computed Tomography in patients with blunt abdominal trauma.
The Role of Extended field-of-view Sonography and compound imaging in Evaluation of Breast Lesions
Evaluation of focal pancreatic lesions by Multidetector CT and perfusion CT
Evaluation of breast masses on sono-mammography and colour Doppler imaging
Role of CT virtual laryngoscopy in evaluation of laryngeal masses
Triple phase multi detector computed tomography in hepatic masses
Role of transvaginal ultrasound in diagnosis and treatment of female infertility
Role of ultrasound and color Doppler imaging in assessment of acute abdomen due to female genetal causes
High resolution ultrasonography and color Doppler ultrasonography in scrotal lesion
Evaluation of diagnostic accuracy of ultrasonography with colour Doppler vs low dose computed tomography in salivary gland disease
Role of multidetector CT in diagnosis of salivary gland lesions
Comparison of diagnostic efficacy of ultrasonography and magnetic resonance cholangiopancreatography in obstructive jaundice: A prospective study
Evaluation of varicose veins-comparative assessment of low dose CT venogram with sonography: pilot study
Role of mammotome in breast lesions
The role of interventional imaging procedures in the treatment of selected gynecological disorders
Role of transcranial ultrasound in diagnosis of neonatal brain insults
Role of multidetector CT virtual laryngoscopy in evaluation of laryngeal mass lesions
Evaluation of adnexal masses on sonomorphology and color Doppler imaginig
Role of radiological imaging in diagnosis of endometrial carcinoma
Comprehensive imaging of renal masses by magnetic resonance imaging
The role of 3D & 4D ultrasonography in abnormalities of fetal abdomen
Diffusion weighted magnetic resonance imaging in diagnosis and characterization of brain tumors in correlation with conventional MRI
Role of diffusion weighted MRI imaging in evaluation of cancer prostate
Role of multidetector CT in diagnosis of urinary bladder cancer
Role of multidetector computed tomography in the evaluation of paediatric retroperitoneal masses.
Comparative evaluation of gastric lesions by double contrast barium upper G.I. and multi detector computed tomography
Evaluation of hepatic fibrosis in chronic liver disease using ultrasound elastography
Role of MRI in assessment of hydrocephalus in pediatric patients
The role of sonoelastography in characterization of breast lesions
The influence of volumetric tumor doubling time on survival of patients with intracranial tumours
Role of perfusion computed tomography in characterization of colonic lesions
Role of proton MRI spectroscopy in the evaluation of temporal lobe epilepsy
Role of Doppler ultrasound and multidetector CT angiography in evaluation of peripheral arterial diseases.
Role of multidetector computed tomography in paranasal sinus pathologies
Role of virtual endoscopy using MDCT in detection & evaluation of gastric pathologies
High resolution 3 Tesla MRI in the evaluation of ankle and hindfoot pain.
Transperineal ultrasonography in infants with anorectal malformation
CT portography using MDCT versus color Doppler in detection of varices in cirrhotic patients
Role of CT urography in the evaluation of a dilated ureter
Characterization of pulmonary nodules by dynamic contrast-enhanced multidetector CT
Comprehensive imaging of acute ischemic stroke on multidetector CT
The role of fetal MRI in the diagnosis of intrauterine neurological congenital anomalies
Role of Multidetector computed tomography in pediatric chest masses
Multimodality imaging in the evaluation of palpable & non-palpable breast lesion.
Sonographic Assessment Of Fetal Nasal Bone Length At 11-28 Gestational Weeks And Its Correlation With Fetal Outcome.
Role Of Sonoelastography And Contrast-Enhanced Computed Tomography In Evaluation Of Lymph Node Metastasis In Head And Neck Cancers
Role Of Renal Doppler And Shear Wave Elastography In Diabetic Nephropathy
Evaluation Of Relationship Between Various Grades Of Fatty Liver And Shear Wave Elastography Values
Evaluation and characterization of pelvic masses of gynecological origin by USG, color Doppler and MRI in females of reproductive age group
Radiological evaluation of small bowel diseases using computed tomographic enterography
Role of coronary CT angiography in patients of coronary artery disease
Role of multimodality imaging in the evaluation of pediatric neck masses
Role of CT in the evaluation of craniocerebral trauma
Role of magnetic resonance imaging (MRI) in the evaluation of spinal dysraphism
Comparative evaluation of triple phase CT and dynamic contrast-enhanced MRI in patients with liver cirrhosis
Evaluation of the relationship between carotid intima-media thickness and coronary artery disease in patients evaluated by coronary angiography for suspected CAD
Assessment of hepatic fat content in fatty liver disease by unenhanced computed tomography
Correlation of vertebral marrow fat on spectroscopy and diffusion-weighted MRI imaging with bone mineral density in postmenopausal women.
Comparative evaluation of CT coronary angiography with conventional catheter coronary angiography
Ultrasound evaluation of kidney length & descending colon diameter in normal and intrauterine growth-restricted fetuses
A prospective study of hepatic vein waveform and splenoportal index in liver cirrhosis: correlation with child Pugh’s classification and presence of esophageal varices.
CT angiography to evaluate coronary artery by-pass graft patency in symptomatic patient’s functional assessment of myocardium by cardiac MRI in patients with myocardial infarction
MRI evaluation of HIV positive patients with central nervous system manifestations
MDCT evaluation of mediastinal and hilar masses
Evaluation of rotator cuff & labro-ligamentous complex lesions by MRI & MRI arthrography of shoulder joint
Role of imaging in the evaluation of soft tissue vascular malformation
Role of MRI and ultrasonography in the evaluation of multifidus muscle pathology in chronic low back pain patients
Role of ultrasound elastography in the differential diagnosis of breast lesions
Role of magnetic resonance cholangiopancreatography in evaluating dilated common bile duct in patients with symptomatic gallstone disease.
Comparative study of CT urography & hybrid CT urography in patients with haematuria.
Role of MRI in the evaluation of anorectal malformations
Comparison of ultrasound-Doppler and magnetic resonance imaging findings in rheumatoid arthritis of hand and wrist
Role of Doppler sonography in the evaluation of renal artery stenosis in hypertensive patients undergoing coronary angiography for coronary artery disease.
Comparison of radiography, computed tomography and magnetic resonance imaging in the detection of sacroiliitis in ankylosing spondylitis.
Mr evaluation of painful hip
Role of MRI imaging in pretherapeutic assessment of oral and oropharyngeal malignancy
Evaluation of diffuse lung diseases by high resolution computed tomography of the chest
Mr evaluation of brain parenchyma in patients with craniosynostosis.
Diagnostic and prognostic value of cardiovascular magnetic resonance imaging in dilated cardiomyopathy
Role of multiparametric magnetic resonance imaging in the detection of early carcinoma prostate
Role of magnetic resonance imaging in white matter diseases
Role of sonoelastography in assessing the response to neoadjuvant chemotherapy in patients with locally advanced breast cancer.
Role of ultrasonography in the evaluation of carotid and femoral intima-media thickness in predialysis patients with chronic kidney disease
Role of H1 MRI spectroscopy in focal bone lesions of peripheral skeleton choline detection by MRI spectroscopy in breast cancer and its correlation with biomarkers and histological grade.
Ultrasound and MRI evaluation of axillary lymph node status in breast cancer.
Role of sonography and magnetic resonance imaging in evaluating chronic lateral epicondylitis.
Comparative of sonography including Doppler and sonoelastography in cervical lymphadenopathy.
Evaluation of Umbilical Coiling Index as Predictor of Pregnancy Outcome.
Computerized Tomographic Evaluation of Azygoesophageal Recess in Adults.
Lumbar Facet Arthropathy in Low Backache.
“Urethral Injuries After Pelvic Trauma: Evaluation with Uretrography
Role Of Ct In Diagnosis Of Inflammatory Renal Diseases
Role Of Ct Virtual Laryngoscopy In Evaluation Of Laryngeal Masses
“Ct Portography Using Mdct Versus Color Doppler In Detection Of Varices In
Cirrhotic Patients”
Role Of Multidetector Ct In Characterization Of Renal Masses
Role Of Ct Virtual Cystoscopy In Diagnosis Of Urinary Bladder Neoplasia
Role Of Multislice Ct In Diagnosis Of Small Intestine Tumors
“Mri Flow Quantification In The Assessment Of The Commonest CSF Flow Abnormalities”
“The Role Of Fetal Mri In Diagnosis Of Intrauterine Neurological CongenitalAnomalies”
Role Of Transcranial Ultrasound In Diagnosis Of Neonatal Brain Insults
“The Role Of Interventional Imaging Procedures In The Treatment Of Selected Gynecological Disorders”
Role Of Radiological Imaging In Diagnosis Of Endometrial Carcinoma
“Role Of High-Resolution Ct In Differentiation Between Benign And Malignant Pulmonary Nodules In Children”
Role Of Ultrasonography In The Diagnosis Of Knee Joint Lesions
“Role Of Diagnostic Imaging Modalities In Evaluation Of Post Liver Transplantation Recipient Complications”
“Diffusion-Weighted Magnetic Resonance Imaging In Diagnosis And
Characterization Of Brain Tumors In Correlation With Conventional Mri”
The Role Of PET-CT In The Evaluation Of Hepatic Tumors
“Role Of Computerized Tomography In Evaluation Of Mediastinal Masses In Pediatric patients”
“Trans Vaginal Ultrasound And Magnetic Resonance Imaging In Female Urinary Incontinence”
Role Of Multidetector Ct In Diagnosis Of Urinary Bladder Cancer
“Role Of Transvaginal Ultrasound In Diagnosis And Treatment Of Female Infertility”
Role Of Diffusion-Weighted Mri Imaging In Evaluation Of Cancer Prostate
“Role Of Positron Emission Tomography With Computed Tomography In Diagnosis Of Cancer Thyroid”
The Role Of CT Urography In Case Of Haematuria
“Value Of Ultrasonography In Assessment Of Acute Abdominal Diseases In Pediatric Age Group”
“Role Of Functional Magnetic Resonance Imaging In Making Brain Tumor Surgery Safer”
The Role Of Sonoelastography In Characterization Of Breast Lesions
“Ultrasonography, Magnetic Resonance Cholangiopancreatography (MRCP) In Assessment Of Pediatric Biliary Lesions”
“Role Of Ultrasound And Color Doppler Imaging In Assessment Of Acute Abdomen Due To Female Genital Causes”
“Role Of Multidetector Ct Virtual Laryngoscopy In Evaluation Of Laryngeal Mass Lesions”
MRI Of The Postoperative Knee
Role Of Mri In Assessment Of Valvular Heart Diseases
The Role Of 3D & 4D Ultrasonography In Abnormalities Of Fetal Abdomen
State Of The Art Of Mri In Diagnosis Of Hepatic Focal Lesions
Role Of Multidetector Ct In Diagnosis Of Salivary Gland Lesions
“Role Of Virtual Endoscopy Using Mdct In Detection & Evaluation Of Gastric Pathologies”
The Role Of Ultrasound & Mri In Acute Pelvic Inflammatory Disease
“Diagnosis & Staging Of Liver Fibrosis By Ultraso Und Elastography In
Patients With Chronic Liver Diseases”
Role Of Mri In Evaluation Of Spinal Trauma
Validity Of Mri In Diagnosis Of Congenital Anorectal Anomalies
Imaging Of Vascular Complication After Liver Transplantation
“Contrast-Enhanced Digital Mammography And Digital Breast Tomosynthesis In Early Diagnosis Of Breast Lesion”
Role Of Mammotome In Breast Lesions
“Role Of MRI Diffusion Tensor Imaging (DTI) In Assessment Of Traumatic Spinal Cord Injuries”
“Prediction Of Pre-eclampsia And Fetal Growth Restriction By Uterine Artery Doppler”
“Role Of Multidetector Row Computed Tomography In Assessment Of Maxillofacial Trauma”
“Role Of Diffusion Magnetic Resonance Imaging In Assessment Of Neoplastic And Inflammatory Brain Lesions”
Role Of Diffusion Mri In Preoperative Evaluation Of Brain Neoplasms
“Role Of Multidetector Ct Virtual Hysteroscopy In The Detection Of The
Uterine & Tubal Causes Of Female Infertility”
Role Of Advances Magnetic Resonance Imaging Sequences In Multiple Sclerosis Magnetic Resonance Spectroscopy In Multiple Sclerosis
“Role Of Conventional Mri, And Diffusion Tensor Imaging Tractography In Evaluation Of Congenital Brain Malformations”
Role Of MRI In Evaluation Of Spinal Trauma
Diagnostic Role Of Diffusion-weighted MR Imaging In Neck Masses
“The Role Of Transvaginal Ultrasound Versus Magnetic Resonance Imaging In Diagnosis & Evaluation Of Cancer Cervix”
“Role Of 3d Magnetic Resonance Imaging Tractography In Assessment Of White Matter Tracts Compromise In Supra Tentorial Tumors”
Role Of Proton MR Spectroscopy In The Evaluation Of Temporal Lobe Epilepsy
Role Of Multislice Computed Tomography In Evaluation Of Crohn’s Disease
Role Of MRI In Assessment Of Hydrocephalus In Pediatric Patients
The Role Of MRI In Diagnosis And Staging Of Urinary Bladder Carcinoma
USG and MRI correlation of congenital CNS anomalies
HRCT in interstitial lung disease
X-Ray, CT and MRI correlation of bone tumors
“Study on the diagnostic and prognostic utility of X-Rays for cases of pulmonary tuberculosis under RNTCP”
“Role of magnetic resonance imaging in the characterization of female adnexal pathology”
“CT angiography of carotid atherosclerosis and NECT brain in cerebral ischemia, a correlative analysis”
Role of CT scan in the evaluation of paranasal sinus pathology
USG and MRI correlation on shoulder joint pathology
“Radiological evaluation of a patient presenting with extrapulmonary tuberculosis”
CT and MRI correlation in focal liver lesions”
Comparison of MDCT virtual cystoscopy with conventional cystoscopy in bladder tumors”
“Bleeding vessels in life-threatening hemoptysis: Comparison of 64 detector row CT angiography with conventional angiography prior to endovascular management”
“Role of transarterial chemoembolization in unresectable hepatocellular carcinoma”
“Comparison of color flow duplex study with digital subtraction angiography in the evaluation of peripheral vascular disease”
“A Study to assess the efficacy of magnetization transfer ratio in differentiating tuberculoma from neurocysticercosis”
“MR evaluation of uterine mass lesions in correlation with transabdominal, transvaginal ultrasound using HPE as a gold standard”
“The Role of power Doppler imaging with trans rectal ultrasonogram guided prostate biopsy in the detection of prostate cancer”
“Lower limb arteries assessed with doppler angiography – A prospective comparative study with multidetector CT angiography”
“Comparison of sildenafil with papaverine in penile doppler by assessing hemodynamic changes”
“Evaluation of efficacy of sonosalphingogram for assessing tubal patency in infertile patients with hysterosalpingogram as the gold standard”
Role of CT enteroclysis in the evaluation of small bowel diseases
“MRI colonography versus conventional colonoscopy in the detection of colonic polyposis”
“Magnetic Resonance Imaging of anteroposterior diameter of the midbrain – differentiation of progressive supranuclear palsy from Parkinson disease”
“MRI Evaluation of anterior cruciate ligament tears with arthroscopic correlation”
“The Clinicoradiological profile of cerebral venous sinus thrombosis with prognostic evaluation using MR sequences”
“Role of MRI in the evaluation of pelvic floor integrity in stress incontinent patients” “Doppler ultrasound evaluation of hepatic venous waveform in portal hypertension before and after propranolol”
“Role of transrectal sonography with colour doppler and MRI in evaluation of prostatic lesions with TRUS guided biopsy correlation”
“Ultrasonographic evaluation of painful shoulders and correlation of rotator cuff pathologies and clinical examination”
“Colour Doppler Evaluation of Common Adult Hepatic tumors More Than 2 Cm with HPE and CECT Correlation”
“Clinical Relevance of MR Urethrography in Obliterative Posterior Urethral Stricture”
“Prediction of Adverse Perinatal Outcome in Growth Restricted Fetuses with Antenatal Doppler Study”
Radiological evaluation of spinal dysraphism using CT and MRI
“Evaluation of temporal bone in cholesteatoma patients by high resolution computed tomography”
“Radiological evaluation of primary brain tumours using computed tomography and magnetic resonance imaging”
“Three dimensional colour doppler sonographic assessment of changes in volume and vascularity of fibroids – before and after uterine artery embolization”
“In phase opposed phase imaging of bone marrow differentiating neoplastic lesions”
“Role of dynamic MRI in replacing the isotope renogram in the functional evaluation of PUJ obstruction”
Characterization of adrenal masses with contrast-enhanced CT – washout study
A study on accuracy of magnetic resonance cholangiopancreatography
“Evaluation of median nerve in carpal tunnel syndrome by high-frequency ultrasound & color doppler in comparison with nerve conduction studies”
“Correlation of Agatston score in patients with obstructive and nonobstructive coronary artery disease following STEMI”
“Doppler ultrasound assessment of tumor vascularity in locally advanced breast cancer at diagnosis and following primary systemic chemotherapy.”
“Validation of two-dimensional perineal ultrasound and dynamic magnetic resonance imaging in pelvic floor dysfunction.”
“Role of MR urethrography compared to conventional urethrography in the surgical management of obliterative urethral stricture.”

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Proofreading Your Thesis:

Make sure you use Grammarly to correct your spelling , grammar , and plagiarism for your thesis. Grammarly has affordable paid subscriptions, windows/macOS apps, and FREE browser extensions. It is an excellent tool to avoid inadvertent spelling mistakes in your research projects. It has an extensive built-in vocabulary, but you should make an account and add your own medical glossary to it.

Grammarly spelling and grammar correction app for thesis

Guidelines for Writing a Radiology Thesis:

These are general guidelines and not about radiology specifically. You can share these with colleagues from other departments as well. Special thanks to Dr. Sanjay Yadav sir for these. This section is best seen on a desktop. Here are a couple of handy presentations to start writing a thesis:

Read the general guidelines for writing a thesis (the page will take some time to load- more than 70 pages!

A format for thesis protocol with a sample patient information sheet, sample patient consent form, sample application letter for thesis, and sample certificate.

Resources and References:

Guidelines for thesis writing.
Format for thesis protocol
Thesis protocol writing guidelines DNB
Informed consent form for Research studies from AIIMS
Radiology Informed consent forms in local Indian languages.
Sample Informed Consent form for Research in Hindi
Guide to write a thesis by Dr. P R Sharma
Guidelines for thesis writing by Dr. Pulin Gupta.
Preparing MD/DNB thesis by A Indrayan
Another good thesis reference protocol

Hopefully, this post will make the tedious task of writing a Radiology thesis a little bit easier for you. Best of luck with writing your thesis and your residency too!

More guides for residents :

Guide for the MD/DMRD/DNB radiology exam!
Guide for First-Year Radiology Residents
FRCR Exam: THE Most Comprehensive Guide (2022)!
Radiology Practical Exams Questions compilation for MD/DNB/DMRD !
Radiology Exam Resources (Oral Recalls, Instruments, etc )!
Tips and Tricks for DNB/MD Radiology Practical Exam
FRCR 2B exam- Tips and Tricks !

FRCR exam preparation – An alternative take!

Why did I take up Radiology?

Radiology Conferences – A comprehensive guide!

ECR (European Congress Of Radiology)
European Diploma in Radiology (EDiR) – The Complete Guide!
Radiology NEET PG guide – How to select THE best college for post-graduation in Radiology (includes personal insights)!
Interventional Radiology – All Your Questions Answered!
What It Means To Be A Radiologist: A Guide For Medical Students!
Radiology Mentors for Medical Students (Post NEET-PG)
MD vs DNB Radiology: Which Path is Right for Your Career?
DNB Radiology OSCE – Tips and Tricks

More radiology resources here: Radiology resources This page will be updated regularly. Kindly leave your feedback in the comments or send us a message here . Also, you can comment below regarding your department’s thesis topics.

Note: All topics have been compiled from available online resources. If anyone has an issue with any radiology thesis topics displayed here, you can message us here , and we can delete them. These are only sample guidelines. Thesis guidelines differ from institution to institution.

Image source: Thesis complete! (2018). Flickr. Retrieved 12 August 2018, from https://www.flickr.com/photos/cowlet/354911838 by Victoria Catterson

About The Author

Dr. amar udare, md, related posts ↓.

7 thoughts on “Radiology Thesis – More than 400 Research Topics (2022)!”

Amazing & The most helpful site for Radiology residents…

Thank you for your kind comments 🙂

Dr. I saw your Tips is very amazing and referable. But Dr. Can you help me with the thesis of Evaluation of Diagnostic accuracy of X-ray radiograph in knee joint lesion.

Wow! These are excellent stuff. You are indeed a teacher. God bless

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A List Of Interesting Radiotherapy Dissertation Ideas

Among the many miraculous transformations that modern medicine has made in our lives, the ones concerning technologies from waves like radio waves, x rays and gamma rays. In the same vein, radiotherapy has emerged to be a boon of sorts. If you are into the study of medicine, there will be a time when you may be asked to write a paper on radiotherapy.

When writing on a topic as complex as radiotherapy, one of the first things that you will have to consider is the topic of the essay. There are several people that get it wrong in this place and there are several others that can plan their way ahead with the right topic at the helm. Also, your topic largely determines if you are on safe waters or treading slippery grounds with the essay.

List of interesting topics

6GY and 8GY Single Radiotherapy Dose: evaluation and comparison of the two procedures in treating bone metastases
The prospect: Breast cancer in elderly women and its treatment with hypo fractioned radiotherapy
Cross Section Study: Chemo radiation in concurrence with accelerated concomitant and cell carcinomas
Rectal and bladder radiation evaluation: Carcinoma dose, cervix patients and intravaginal balloon catheters
Radiotherapy and administration of concomitant pilocarpine: preventing xerostomia
Conventional radiotherapy: low dose concomitant cell carcinoma in the neck and head
The prospect and comparative analysis of palliative radiotherapy in different regimens of advanced carcinoma oh the head and the neck
Radiotherapy hypo fractioned in the treatment of neck and head cancer
Chemo boost and conventional radiotherapy: marking the new trends in cancer prevention of the head and neck
External beam radiotherapy: an assessment into the efficacy of the procedure
Intraluminal brachytherapy: the following up of external beam therapy into in dysphagia palliation
Head and neck carcinoma: the benefits of chemo radiations addressing the locally squamous cells

Sensitivity of topic

While you are free to choose among the above mentioned topics, you may also research your own topic on radiotherapy. Please bear in mind to encourage and promote the sensitivity of the topic as you move along the selection of topic. The topic must be both sensible and applicable to the genre you are preparing.

You may consult several websites while you decide o the sensitivity of a topic. Here is another website that has a few nonpareil pearls of wisdom on choosing topics related to radiotherapy. You may visit the website to find out more about the subject and aligned topics.

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Radiography is the scientific technology of producing images of internal body organs and tissues. This revolutionary imaging technique of science has been widely used to diagnose issues of a body’s internal structure. Radiography is a helpful field for the medical diagnosis that requires extensive research. Students need to find exciting and up-to-date radiography dissertation topics .

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Top thesis topics in radiography topics 2024, trending research topics in radiography dissertation topics, a methodical approach to choose a good radiography dissertation topic.

Selecting radiology research topics involves a methodical approach. Start by identifying your specific interests within radiography, such as diagnostic imaging, radiation therapy, or advancements in technology. Formulate a clear research aim and methodology, ensuring a focused and insightful exploration of your chosen area to contribute meaningfully to the field of radiography.

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Research Papers/Topics in Radiotherapy

Sonographic assessment of renal parenchymal and medullary pyramid thicknesses among healthy children in selected schools in enugu, nigeria.

ABSTRACT Renal parenchymal thickness (RPT) and renal medullary pyramid thickness (MPT) are important renal size parameters and there is no existing ultrasound normogram for RPT and MPT among children in our locality. Thus, this study was aimed at establishing normal values for RPT and MPT among children in Enugu metropolis; establishing the relationship between RPT and MPT with age, height, body weight, body mass index (BMI) and body surface area (BSA) among the subjects; establishing the rel...

Assessing Cancer Patients’ Quality of Life and Coping Mechanisms in Radiotherapy Department of the University College Hospital, Ibadan

ABSTRACT Background: Cancer is often associated with a lot of pain and suffering. These suggest that coping with the symptoms, diagnosis and treatment of cancer is a major life stressor that is capable of inﬂuencing patients’ quality of life (QoL). Purpose: The purpose of the study is to assess the relationship between cancer patients QoL dimensions and coping strategies in the Radiotherapy Department of the University College Hospital Ibadan, Nigeria. Methods: Data were collected on cl...

Dissertations / Theses on the topic 'Cancer - Radiotherapy treatment'

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Consult the top 50 dissertations / theses for your research on the topic 'Cancer - Radiotherapy treatment.'

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Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.

Cha, Kyungduck. "Cancer treatment optimization." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/22604.

Williamson, Raymond Allan. "An experimental study of the use of hyperbaric oxygen treatment to reduce the side effects of radiation treatment for malignant disease." University of Western Australia. School of Anatomy and Human Biology, 2007. http://theses.library.uwa.edu.au/adt-WU2007.0063.

Wey, Mark Tao Teong. "DNA repair in bladder cancer predisposition and radiotherapy treatment response." Thesis, University of Leeds, 2012. http://etheses.whiterose.ac.uk/8087/.

Fokas, Emmanouil. "Targeting the PI3K/mTOR and ATK/Chk1 pathways to improve radiation efficacy for cancer therapy." Thesis, University of Oxford, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.572788.

Murray, Louise Janet. "Optimising treatment outcomes using Stereotactic Body Radiotherapy (SBRT) for prostate cancer." Thesis, University of Leeds, 2014. http://etheses.whiterose.ac.uk/8666/.

Elder, Eric Scott. "A method and treatment device for non-coplanar radiotherapy of the pancreas." Diss., Georgia Institute of Technology, 1997. http://hdl.handle.net/1853/17656.

Olausson, Kristina. "Patient experiences of the radiotherapy process and treatment." Doctoral thesis, Umeå universitet, Onkologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-127456.

Tse, Ka-ho, and 謝家豪. "A comparison of contralateral breast dose from primary breast radiotherapy using different treatment techniques." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206498.

Wu, Wing-cheung Vincent, and 胡永祥. "Dose analysis of 2-dimensional and 3-dimensional radiotherapy techniques in the treatment of nasopharyngeal carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1997. http://hub.hku.hk/bib/B31220149.

胡寶文 and Po-man Wu. "The application of the tumor control probability model of nasopharyngeal carcinoma in three dimensional conformal treatment planevaluation." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B31241232.

Jagannathan, Rupa. "A case-based reasoning system for radiotherapy treatment planning for brain cancer." Thesis, University of Nottingham, 2013. http://eprints.nottingham.ac.uk/29318/.

Mackenzie, Christine. "Emotional functioning of patients before, during and after radiotherapy treatment for cancer." Thesis, Middlesex University, 2003. http://eprints.mdx.ac.uk/13386/.

Della, Gala Giuseppe. "A method for automated generation of radiotherapy treatment plans for lung cancer." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amslaurea.unibo.it/9549/.

Wilson, Elena McNaught. "Three dimensional conformal radiotherapy treatment planning for non-small cell lung cancer." Thesis, University College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404897.

Eardley, A. "The care of urological cancer patients : Delay in obtaining treatment and problems following radiotherapy." Thesis, University of Manchester, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.234189.

Neal, Anthony James. "Optimisation of radiotherapy treatment planning for tumours of the breast, prostate and brain." Thesis, King's College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306922.

Johansson, Jonas. "Comparative Treatment Planning in Radiotherapy and Clinical Impact of Proton Relative Biological Effectiveness." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6593.

Orvehed, Hiltunen Erik. "Robust optimization of radiotherapy treatment plans considering time structures of the delivery." Thesis, Uppsala universitet, Avdelningen för datalogi, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-355628.

Brock, Juliet. "Advanced technology of radiotherapy in the treatment of non-small cell lung cancer." Thesis, Institute of Cancer Research (University Of London), 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538697.

Lilley, Francis. "An optical 3D body surface measurement system to improve radiotherapy treatment of cancer." Thesis, Liverpool John Moores University, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313092.

Delaney, Geoffrey Paul SWSAHS Clinical School UNSW. "The Development of a New Measure of Linear Accelerator Throughput in Radiation Oncology Treatment Delivery - The Basic Treatment Equivalent (B.T.E.)." Awarded by:University of New South Wales. SWSAHS Clinical School, 2001. http://handle.unsw.edu.au/1959.4/33381.

Bailie, Karen E. M. "Quality in clinical decision making : the treatment of breast cancer in Northern Ireland." Thesis, Queen's University Belfast, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343063.

Fridriksson, Jon Örn. "Adverse effects of curative treatment of prostate cancer." Doctoral thesis, Umeå universitet, Urologi och andrologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-128709.

Uitterhoeve, Apollonia Léonie Joséphine. "Radiotherapy and Cisplatin: outcome of combined modality treatment in non-small cell lung cancer." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2007. http://dare.uva.nl/document/47061.

Pijls-Johannesma, Madelon. "Optimization of radiotherapy in lung cancer treatment balance between survival and quality of life /." Maastricht : Maastricht : Universitaire Pers ; University Library, Universiteit Maastricht [host], 2008. http://arno.unimaas.nl/show.cgi?fid=13773.

Christian, Judith Ann. "Evaluation of new techniques in the radiotherapy treatment of non-small cell lung cancer." Thesis, Institute of Cancer Research (University Of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.411594.

Lee, W. M. Anne, and 李詠梅. "Therapeutic benefits of concurrent chemoradiotherapy for advanced nasopharyngeal carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41290677.

Barton, Michael Clinical School South Western Sydney Faculty of Medicine UNSW. "The improvement of cancer management by the application of the currently available knowledge." Awarded by:University of New South Wales, 2008. http://handle.unsw.edu.au/1959.4/39210.

Stewart, Grant Duncan. "Novel survival factors and approaches to the treatment of hypoxic prostate cancer." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/4390.

Owusu, Miriam Sekyere. "Lymphedema, post breast cancer treatment at Komfo Anokye Teaching Hospital, Kumasi, Ghana." Thesis, Cape Peninsula University of Technology, 2011. http://hdl.handle.net/20.500.11838/2262.

Knight, Kellie Ann. "Daily Image Guided Radiation Therapy for Prostate Cancer: An assessment of treatment plan reproducibility." University of Sydney, 2006. http://hdl.handle.net/2123/1628.

Wirth, Manfred P., and Michael Fröhner. "Perspectives in Adjuvant Treatment of Prostate Cancer." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133839.

McGowan, Stacey Elizabeth. "Incorporating range uncertainty into proton therapy treatment planning." Thesis, University of Cambridge, 2015. https://www.repository.cam.ac.uk/handle/1810/248787.

Ayles, Michael. "Minimizing errors in treatment planning and delivery during external beam radiotherapy for lung cancer patients." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=40731.

Ryalat, Mohammad. "Automatic construction of immobilisation masks for use in radiotherapy treatment of head-and-neck cancer." Thesis, University of East Anglia, 2017. https://ueaeprints.uea.ac.uk/66573/.

Nakamura, Akira. "Analysis of Dose Intensification for the Improvement of Treatment Outcomes of Radiotherapy for Pancreatic Cancer." Kyoto University, 2013. http://hdl.handle.net/2433/174808.

Wirth, Manfred P., and Michael Fröhner. "Perspectives in Adjuvant Treatment of Prostate Cancer." Karger, 2002. https://tud.qucosa.de/id/qucosa%3A27540.

Wirth, Manfred P., and Michael Fröhner. "Adjuvant Hormonal Treatment for Prostate Cancer: The Bicalutamide Early Prostate Cancer Program." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133551.

Sandberg, Linnea. "Quality assurance of a radiotherapy registry." Thesis, Umeå universitet, Institutionen för fysik, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-176779.

Wirth, Manfred P., and Michael Fröhner. "Adjuvant Hormonal Treatment for Prostate Cancer: The Bicalutamide Early Prostate Cancer Program." Karger, 2003. https://tud.qucosa.de/id/qucosa%3A27515.

suh, yelin. "DEVELOPMENT AND INVESTIGATION OF INTENSITY-MODULATED RADIATION THERAPY TREATMENT PLANNING FOR FOUR-DIMENSIONAL ANATOMY." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1827.

Kyei, Kofi Adesi. "Assessment of Anxiety and Depression Among Breast Cancer Patients Undergoing Treatment in Ghana." ScholarWorks, 2017. https://scholarworks.waldenu.edu/dissertations/4526.

Svensson, Sara. "Variations in the target definition on CT and MR based treatment plans for radiotherapy." Thesis, Umeå universitet, Centrum för medicinsk teknik och fysik (CMTF), 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-96753.

De, Armas Ricardo Eduardo. "Impact of intrafractional prostate motion on the accuracy and efficiency of prostate cancer treatment on CyberKnife radiotherapy." Thesis, Massachusetts Institute of Technology, 2015. http://hdl.handle.net/1721.1/98920.

Kishi, Takahiro. "Comparative evaluation of respiratory-gated and ungated FDG-PET for target volume definition in radiotherapy treatment planning for pancreatic cancer." 京都大学 (Kyoto University), 2017. http://hdl.handle.net/2433/225447.

Marcu, Loredana Gabriela. "Deterministic modelling of kinetics and radiobiology of radiation-cisplatin interaction in the treatment of head and neck cancers." Title page, contents and abstract only, 2004. http://hdl.handle.net/2440/37961.

De, Pomeroy-Legg Jeanita. "Prevalence of side-effects and change in nutritional status during radical radiotherapy for head and neck malignancies at Tygerberg Academic Hospital, Western Cape, South Africa." Thesis, Link to the online version, 2008. http://hdl.handle.net/10019/1492.

Filipov, Danielle. "Avaliação da dose fetal em radioterapia de mama, com câmara de ionização cilíndrica, usando blindagem e filtros físico e dinâmico." Universidade Tecnológica Federal do Paraná, 2010. http://repositorio.utfpr.edu.br/jspui/handle/1/1311.

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March 18, 2024

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Hypofractioned post-prostatectomy radiotherapy new acceptable practice standard based on NRG Oncology trial findings

by NRG Oncology

Results from the Phase III NRG Oncology NRG-GU003 clinical trial comparing hypofractioned post-prostatectomy radiotherapy (HYPORT) to conventionally fractioned post-prostatectomy radiotherapy (COPORT) determined that HYPORT was non-inferior to COPORT in terms of late gastrointestinal (GI) or genitourinary (GU) toxicity for patients primarily treated with prostatectomy for their prostate cancer.

HYPORT was not associated with significantly higher patient-reported GU or GI symptoms at 1-2 years following radiotherapy, thus indicating HYPORT can be used as an acceptable new practice standard. There was greater short-term GI toxicity, mostly rectal irritation, associated with HYPORT as one would expect with the shorter regimen, but this difference resolved at 6 months following radiotherapy.

These results were recently published in the JAMA Oncology .

"This study confirms what many doctors have suspected, which is a shorter course of 25 treatments doesn't compromise quality-of-life compared to 37 treatments. The shorter course only requires a simple adjustment, which means any radiation oncology center can make the switch."

"Now, many more patients are expected to be offered radiation because it is less burdensome. This is a big win for patients because radiation is often curative." stated Mark K. Buyyounouski, MD, a radiation oncologist at the Stanford University Cancer Center and the lead author of the NRG-GU003 manuscript.

NRG-GU003 accrued a total of 296 patients with prostate cancer . Patients were stratified according to baseline EPIC score using four tiers based on GU and GI scores and androgen deprivation therapy use. Patients were then randomly assigned to receive either COPORT at 66.6 Gy in 37 fractions or HYPORT at 62.5 Gy in 25 fractions.

The trial's co-primary endpoint was the two-year change score from baseline in the bowel and urinary domains of the patient-reported Expanded Prostate Cancer Index Composite (EPIC) questionnaire.

The COPORT treatment arm included 152 patients, and the HYPORT treatment arm included 144 patients. At the end of radiotherapy, the HYPORT and COPORT mean GU change scores were neither clinically significant nor significantly different and remained so at 6 and 12 months.

The mean GI change scores for HYPORT and COPORT were both clinically significant and significantly different at the end of RT (HYPORT mean GI = ‐15.0 vs. COPORT mean GI = ‐6.8 p < 0.01). However, the clinically and statistically significant differences in HYPORT and COPORT mean GI change scores were resolved at 6 and 12 months.

The 24‐month differences in mean GU and GI change scores for HYPORT and COPORT were not significantly greater than the non‐inferiority margins of ‐5 and ‐6, respectively (HYPORT mean GU = ‐5.0 vs. COPORT mean GU = ‐4.1, p = 0.98; HYPORT mean GI = ‐4.2 vs. COPORT mean GI = ‐1.4, p = 0.99).

With a median follow‐up for censored patients of 2.1 years, there was no difference between HYPORT versus COPORT for biochemical failure defined as a PSA ≥ 0.4 ng/mL and rising (2‐yr rate, 12% vs. 8%, p = 0.29).

NRG-GU003 had an 83% compliance rate at 2 years for the bowel and urinary domains of the EPIC. Future research in HYPORT versus COPORT could benefit from examining any potential long-term differences in cancer control between the treatments or can test this in a larger sample size.

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