MRI in rectal cancer: An institutional real life analysis of technical parameters.

INTRODUCTION: MRI plays a key role in the preoperative staging of rectal cancers and choice of neoadjuvant radiochemotherapy. Yet, the acquisition and interpretation of rectum magnetic resonance imaging (MRI) turn out to be unequal, impacting patients'care. The present study aims at evaluating the quality of the acquisition of technical parameters of the rectal MRI performed by comparing them according to the various guidelines. METHODS: The medical MRI reports of all consecutive patients with locally advanced rectal cancer treated in a curative intent, by preoperative RCT and completion surgery were retrospectively reviewed over two periods (January 2010-December 2014 and January 2018 and December 2020) according to international 2012 and 2016 ESGAR and 2017 SAR MRI recommendation reports. RESULTS: During the first period (69 MRI performed), 58% of these MRI abided by the recommendations and 75% of essential criteria could be found in 25.5% of MRI reportings. During the second period (73 MRI performed), the protocol used by 6.8% of MR images abided by the 2016 Society of Gastrointestinal and Abdominal Radiology (ESGAR) recommendations and 39.7% abided by the Society of Abdominal Radiology (SAR) recommendations. 75% of essential criteria could be found in 52.3% of MRI reportings and 90% of essential criteria could be found in 6.2% of MRI reportings. DISCUSSION: In an era of increasing individualized patient care and conservative treatment focused on tumour response and prognostic factors, the present study showed that compliance to MRI protocols and reporting guidelines needs improving to upgrade patient care.

Therapeutic optimization in head and neck radiotherapy planning: Advocacy for 18FDG PET-CT in treatment condition.

INTRODUCTION: The necessity to perform 18FDG PET-CT both for initial tumour staging and for target volume delineation in head and neck cancers seems well established. The aim of the present study is to advocate the place and role of 18FDG PET-CT acquired in planning treatment position (18FDG PET-CT/RT). METHODS: Between March 2018 and July 2019, 22 patients with a squamous cell head and neck carcinoma treated by EBRT were included in the analysis. All these consecutive patients had a 18FDG PET-CT/RT. Three GTV volumes were defined. First, "GTV 40%" corresponded to 40% of SUVmax. "Visual GTV" was defined as the tumor volume obtained from the PET the nuclear medicine physician interpreted. The radiation oncologist used the medical record, clinical anatomy, CT simulation and 18FDG PET-CT/RT data ("GTV40%" and "visual GTV") to draw the GTV. RESULTS: Mean GTVs and mean "GTVs40%" were significantly different (P<0.001) with an intraclass index of 0.734. Mean "GTV40%" and mean "visual GTVs" were also significantly different (P<0.001) with an intraclass index of 0.72. Conversely, the difference between mean GTVs and mean "visual GTVs" were not significant (P=0.11) with an intraclass index of 0.91. Mean DICE between "GTVs40%" and GTV was 0.7 (ranging from 0.2 to 0.9). The mean intersection between GTVs and "visual GTVs" volumes was 0.8 (ranging from 0.4 to 1). The difference between DICES was significant (P=0.015), "visual GTV"/GTV DICE was the smallest. CONCLUSION: 18FDG PET-CT/RT definitely remains the imaging modality that individualized/customized head and neck cancer treatment needs.

Prognostic factors of pelvic MRI at the initial workflow in locally advanced rectal cancer: Focus on extra mural venous invasion and tumour deposits.

INTRODUCTION: Tumour deposits (TD) and extramural venous invasion (EMVI) are key anatomopathology prognostic criteria in rectal cancer. According to the 2018 ESGAR recommendations, they should be included in every MRI report. The present study aimed at identifying pelvic MRI survival prognostic factors in locally advanced rectal cancers before neo-adjuvant treatment, with a focus on EMVI and TD (mrEMVI and mrTD). METHODS: Between 2010 and 2014, we conducted a retrospective study about 69 patients who underwent a pre-operative radiotherapy for a non-metastatic rectal cancer. All MR images were acquired on machines with a 1.5 or 3.0 Tesla field strength and were interpreted in compliance with the 2018 ESGAR recommendations. RESULTS: Out of the 27 patients who were mrEMVI+ (39.1%), MRF was involved in 77.7% of the cases vs. 33.3% for the mrEMVI- tumours. Fifteen (55.5%) out of the 27 mrEMVI+ tumours were mrTD+. This represents 21.7% of our population. mrEMVI/mrTD+ tumours were more RCT resistant, their downstaging happened in 6.7% of cases. In case of tumour downstaging, DFS increased significantly (P=0.02) unlike OS (P=0.2). DISCUSSION: The present study supports the fact that both mrEMVI and mrTD status are important pelvic MRI prognostic factors. Future studies could focus on relating mrTD tumours status to pathological results to define if post-RCT downstaging of TD has an impact on OS.

Robot-Assisted Surgery vs Robotic Stereotactic Body Radiotherapy in Prostate Cancer: A Cost-Utility Analysis.

Prostate cancer is the most common men cancer in France. Continuous progress in oncology led to develop robot-assisted Radical Prostatectomies (rRP) and robot-assisted stereotactic body radiotherapy (rSBRT). The present study aims at comparing economic and clinical impacts of prostate cancer treatments performed either with rSBRT or rRP in France. A Markov model using TreeAge Pro software was chosen to calculate annual costs; utilities and transition probabilities of localized prostate cancer treatments. Patients were eligible for radiotherapy or surgery and the therapeutic decision was a robot-assisted intervention. Over a 10-year period, rSBRT yielded a significantly higher number of quality-adjusted life years than rRP (8.37 vs 6.85). In France, rSBRT seemed more expensive than rRP (€19,475 vs €18,968, respectively). From a societal perspective, rRP was more cost-saving (incremental cost effectiveness ratio = €332/QALY). The model was sensitive to variations of costs of the initial and recurrence state in one-way sensitivity analyses. Robot-assisted stereotactic body radiotherapy seems more cost-effective than Radical Prostatectomy in terms of QALY despite the slightly higher initial cost due to the use of radiotherapy. It would be interesting to conduct comparative quality of life studies in France over longer periods of time.

Preservation of organs related to future sexual function during prostate stereotactic body radiotherapy: feasibility analysis through a re-optimization process.

Preserving the quality of life and sexual function of patients with a localized prostate cancer remains a challenge for physicians and a major issue for patients. The present study aimed at demonstrating the feasibility of a dosimetric preservation of the sexual organs during prostate stereotactic radiotherapy planning. Patients from a single centre were retrospectively included in the RPAH-2 trial and randomized in Arm B if they presented with either a low- or intermediate- risk prostate cancer. A 37.5Gy in 5 fractions stereotactic body radiotherapy was delivered on the prostate gland. The corpus cavernosum, penile bulb and internal pudental arteries were retrospectively delineated before a re-optimization process. During this process, RPAH-2 trial dose constraints were respected on Gross Tumor Volume (GTV), Planning Target Volume and usual organs at risk. Pre-defined dose setting delivered to corpus cavernosum, penile bulb and internal pudental arteries were collected and compared before and after the re-optimization process. Nine patients were included in the study. A decrease of the median of each investigated dose setting (except D90% for corpus cavernosum) was reported after the re-optimization for corpus cavernosum, penile bulb and internal pudental arteries. Our study demonstrated the feasibility of a dosimetric preservation of structures considered as relevant to preserve sexual function after prostate stereotactic radiotherapy.

Head and neck radiotherapy-induced carotid toxicity: Pathophysiological concepts and clinical syndromes.

This review aims at offering a concise cross-section of head and neck radiotherapy-induced carotid toxicity for pathological concepts to emerge and become part of clinical routine. Radiation-induced carotid toxicities such as atherosclerosis, arterial stiffness and arterioradionecrosis result from radiation dose limitation. Atherosclerosis is related to lesions in the epithelial wall. Such lesions are early radiotherapy-related toxicities and depend on the radiation dose. Atherosclerosis may lead to carotid stenosis and stroke. Arterial stiffness and arterioradionecrosis are late toxicities of the connective tissue that have a low alpha/beta ratio. They are risk factors of pseudoaneurysm and carotid blowout syndrome or stroke in some cases. Because all these pathophysiological mechanisms interfere, post-radiation vascular diseases remain particularly severe and difficult to understand.

Dose to pelvic lymph nodes in locally advanced cervical cancer during high-dose-rate brachytherapy with tandem-ring applicators.

Purpose: The present study aimed to assess the correlation between dose to pelvic lymph nodes and to point B with tandem-ring (TR) applicators for intra-cavitary brachytherapy treatment of locally advanced cervical cancer. Material and methods: Cervical cancer patients treated at brachytherapy department of Lucien Neuwirth Cancer Center, from 2015 to 2018, were included. Target delineation was performed in compliance with GEC-ESTRO guidelines. Revised American Brachytherapy Society (ABS) point A was determined (ARN (right) and ALN (left)) as well as Manchester point B. Prescription dose was 25-35 Gy in 5 fractions. Pelvic lymph nodes were delineated, then dose to points A and B, and dose-volume histogram (DVH) parameters of delineated lymph nodes were extracted. Significant relationships or correlations between lymph nodes reference points, dosage to points B, and their DVH parameters were investigated. Results: The mean dose and mean percentage of the prescription dose to the left and right points B were 4.6 ±0.18 Gy and 82.08 ±0.72%, respectively. Pearson correlation coefficient R = 0.81 (p-value = 0.00) between dose to ARN and ALN points and prescription dose was obtained. Negative correlation between CTVHR volume and difference between French and ABS prescription points was found. Conclusions: Dose to point B can be a moderate surrogate for maximum, minimum, and median dose to the internal iliac and presacral lymph node, but cannot be for maximum dose to the obturator lymph node. Points B cannot be a reliable substitute for common and external iliac chains.

Cardiovascular Diseases Following Breast Cancer: Towards a Case-by-Case Assessment Through a Prediction Risk Score Model in 943 Patients.

OBJECTIVES: To identify patients at high risk of developing cardiovascular disease through the identification of risk factors among a large population of breast cancer women and to assess the performance of Abdel-Qadir risk prediction model score. MATERIALS AND METHODS: The medical records and baseline characteristics of all patients/tumors diagnosed with breast cancer from 2010 to 2011 in a French comprehensive cancer center were collected. Cardiovascular events were defined as arterial and cardiac events, atrial fibrillation and venous thromboembolism occurring during the 5-year follow-up. Abdel-Qadir multivariable prediction model for major adverse cardiovascular events were used with the concordance index (c-index) score to assess calibration by comparing predicted risks to observed probabilities. RESULTS: Among the 943 breast cancer patients included, 83 patients (8.8%) presented with at least one cardiovascular event, leading to a cumulative incidence of 0.07 at 5 years (95% confidence interval [CI], 0.055-0.088). The cumulative incidence of atrial fibrillation at 5 years was 0.01 (95% CI, 0.005-0.018). Factors associated with the occurrence of cardiovascular events were pre-existing cardiovascular diseases including high blood pressure (hazard ratio [HR]=1.78, 95% CI=1.07-2.97, P=0.028), acute coronary syndrome (HR=5.28, 95% CI: 2.16-12.88, P<0.05) and grade 3 Scarff-Blool-Richardson (HR=1.95, 95% CI: 1.21-3.15, P=0.006). With a c-index inferior to 0.7, the Abdel-Qadir score was not fully validated in our population. CONCLUSION: These findings call for the assessment of the performance of risk prediction models such as Abdel-Qadir score coupled with other factors such as Scarff Bloom and Richardson grading in order to identify patients at high risk of experiencing cardiotoxicity.

Breast cancer treatment-related cardiovascular disturbances: advocacy for a watchful attitude in this never-ending story.

INTRODUCTION: Thanks to the emergence of new therapeutics, prognosis and outcome of breast cancer patients (any subtype) have improved significantly. This raises the issue of the interactions and side effects related to the use of multiple drugs. Thus, to decide on a treatment, the optimal benefit risk-ratio should be carefully watched as toxicities such as cardiac ones effect on long-term survival. Indeed, nowadays in France, cardiovascular diseases rank first as causes of death in women. AREAS COVERED: This non-exhaustive review aims to report the currently available data on cardiac side effects caused by the use of emerging drugs in breast cancer, in localized or metastatic diseases alike. We will focus on HER2-inhibitors, cyclin-dependent-kinase 4/6 and PARP inhibitors, chemotherapy and immunotherapy, before discussing the means of prevention. EXPERT OPINION: Although this issue has largely been studied, the recent emergence of new drugs emphasizes the necessity for oncologists to adapt their practice to a multidisciplinary model that includes cardio-oncology.

Toxicity and efficacy of stereotactic body radiotherapy for ultra-central lung tumours: a single institution real life experience.

OBJECTIVES: The use of stereotactic body radiotherapy (SBRT) to treat ultra-central lung tumours remains more controversial than for peripheral and central tumours. Our objective was to assess toxicities, local control (LC) rate and survival data in patients with ultra-central lung tumours treated with SBRT. METHODS: We conducted a retrospective and monocentric study about 74 patients with an ultra-central lung tumour, consecutively treated between 2012 and 2018. Ultra-central tumours were defined as tumours whose planning target volume overlapped one of the following organs at risk (OARs): the trachea, right and left main bronchi, intermediate bronchus, lobe bronchi, oesophagus, heart. RESULTS: Median follow-up was 25 months. Two patients (2.7%) showed Grade 3 toxicity. No Grade 4 or 5 toxicity was observed. 11% of patients experienced primary local relapse. LC rate was 96.7% at 1 year and 87.6% at 2 years. Median progression free survival was 12 months. Median overall survival was 31 months. CONCLUSION: SBRT for ultra-central tumours remains safe and effective as long as protecting organs at risk is treatment-planning priority. ADVANCES IN KNOWLEDGE: The present study is one of the rare to describe exclusively ultra-central tumours through real-life observational case reports. Globally, literature analysis reveals a large heterogeneity in ultra-central lung tumours definition, prescribed dose, number of fractions. In our study, patients treated with SBRT for ultra-central lung tumours experienced few Grade 3 toxicities (2.7%) and no Grade 4 or 5 toxicities, due to the highest compliance with dose constraints to OARs. LC remained efficient.

Local treatment in the setting of de novo metastatic rectal cancer: reappraisal of prognostic factors.

BACKGROUND: This retrospective study was conducted to: (1) provide more modern data on real-life local management of metastatic rectal cancer; (2) compare therapeutic strategies; and (3) identify prognostic factors of local failure, overall survival and progression-free survival. METHODS: Data about efficacy and acute toxicity were collected. Patients were diagnosed with metastatic rectal cancer between 2004 and 2015, and were treated at least with radiotherapy. Local failure, overall survival and progression-free survival were correlated with patient, tumour and treatment characteristics using univariate and multivariate analyses. RESULTS: Data of 148 consecutive patients with metastatic rectal cancer were analysed. Median follow-up was 19 months. Median overall survival was 16 months. All patients received local radiotherapy, with a median equivalent 2 Gy per fraction dose of 47.7 Gy. Rectal surgery was performed in 97 patients (65.6%). The majority of patients (86/97, 88.7%) received pre-operative chemoradiation. In multivariate analysis, rectal surgery was found to be the only independent predictor of increased overall survival (24.6 vs 7.1 months, p <0.001). Of the patients undergoing surgical treatment, 22.8% presented with significant complications that required a delay of systemic treatment. Grade 3-4 acute radiation therapy-related toxicities were observed in 6.1% of patients, mainly gastrointestinal toxicities (5.4%). CONCLUSION: Rectal surgery was a key predictive factor of increased progression-free survival and overall survival in patients receiving at least local radiotherapy. In our series of real-life patients, local surgery and radiation seemed as well tolerated as reported in selected phase III non-metastatic rectal cancer patients. These data suggested that local management could be beneficial for metastatic rectal cancer patients.

A Review of the Role of Hypoxia in Radioresistance in Cancer Therapy.

Hypoxia involves neoplastic cells. Unlike normal tissue, solid tumors are composed of aberrant vasculature, leading to a hypoxic microenvironment. Hypoxia is also known to be involved in both metastasis initiation and therapy resistance. Radiotherapy is the appropriate treatment in about half of all cancers, but loco-regional control failure and a disease recurrence often occur due to clinical radioresistance. Hypoxia induces radioresistance through a number of molecular pathways, and numerous strategies have been developed to overcome this. Nevertheless, these strategies have resulted in disappointing results, including adverse effects and limited efficacy. Additional clinical studies are needed to achieve a better understanding of the complex hypoxia pathways. This review presents an update on the mechanisms of hypoxia in radioresistance in solid tumors and the potential therapeutic solutions.

MRI accuracy and interobserver agreement in locally advanced cervix carcinoma.

OBJECTIVES: The main standard of care for locally advanced cervix carcinoma (LACC) is radiochemotherapy (RCT) followed by brachytherapy. A surgical approach may still be discussed based on pelvic MRI-derived residual tumour evaluation. As no interobserver agreement study has ever been conducted to our knowledge, the aim of the present study was to report on pelvic MRI accuracy and interobserver agreement in LACC. METHODS: We carried out a retrospective study in a French university hospital. Medical records of all consecutive patients treated with curative intent for LACC by RCT followed by brachytherapy and completion pelvic surgery between January 2014 and January 2020 were reviewed. Local response was assessed through pelvis MRI and histological analysis after completion surgery. MRI data were independently evaluated by two radiologists with varying experience. The two main interobserving criteria we used were complete response and residual tumour. RESULTS: 23 patients fulfilled the inclusion criteria. Agreement between the junior and senior radiologist was moderate to strong. Indeed, regarding main criteria, κ was 0.65 for complete response and 0.57 for residual tumour. Interestingly, the present study shows a lower sensitivity whatever the radiologists than in the international literature. CONCLUSION: The present study highlights a low interobserver variability regarding pelvic MRI in the assessment of RCT followed by brachytherapy in LACC. Yet, sensitivity was lower than in literature. ADVANCES IN KNOWLEDGE: Radiology is part of treatment decision-making, the issue of heterogeneity regarding radiologists' training and experience to cancer (sensitivity and specificity) turns essential, so does MRI accuracy.

Second-generation hormonotherapy in prostate cancer and bone microenvironment.

Prostate cancer (Pca) is the most commonly diagnosed cancer affecting men in France. Before the age of 75 years old, 1 in 8 French men will have Pca. Androgen deprivation therapies (ADT) remain the standard of care. Such therapies induce significant bone loss. The bone-remodelling cycle depends on the androgen synthesis signalling pathways. Furthermore, age-specific hormonal decline plays a key role in the decrease in bone mass. As a result, the older the patients, the more likely they are to have osteoporosis if they are treated with hormone therapy. Their risk of osteoporotic fracture has an impact on their quality of life and their capacity of independent living. In recent years, newer hormone therapies (acetate abiraterone, enzalutamide, apalutamide and darolutamide) have proved efficient in metastatic castration-resistant Pca (mCRPC) patients as well as in hormone naïve patients, and actually in nonmetastatic diagnosis. The combination of these treatments with ADT highly inhibit androgen production pathways. They are prescribed to aged patients undergoing bone density loss after first-generation antiandrogen treatment. Specific recommendations for bone health management in Pca patients are currently lacking. To date, bone mineral density in patients treated with second-generation hormone therapy has never been assessed in a prospective study. This review aims at reviewing what is known about the impact of second-generation hormonotherapy on bone microenvironment.

Focus on the expected quality of reporting in SBRT/radiosurgery prospective studies: how far have we come in 30 years?

OBJECTIVES: We aimed at describing and assessing the quality of reporting in all published prospective trials about radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). METHODS: The Medline database was searched for. The reporting of study design, patients' and radiotherapy characteristics, previous and concurrent cancer treatments, acute and late toxicities and assessment of quality of life were collected. RESULTS: 114 articles - published between 1989 and 2019 - were analysed. 21 trials were randomised (18.4%). Randomisation information was unavailable in 59.6% of the publications. Data about randomisation, ITT analysis and whether the study was multicentre or not, had been significantly less reported during the 2010-2019 publication period than before (respectively 29.4% vs 57.4% (p < 0.001), 20.6% vs 57.4% (p < 0.001), 48.5% vs 68.1% (p < 0.001). 89.5% of the articles reported the number of included patients. Information about radiation total dose was available in 86% of cases and dose per fraction in 78.1%. Regarding the method of dose prescription, the prescription isodose was the most reported information (58.8%). The reporting of radiotherapy characteristics did not improve during the 2010 s-2019s. Acute and late high-grade toxicity was reported in 37.7 and 30.7%, respectively. Their reporting decreased in recent period, especially for all-grade late toxicities (p = 0.044). CONCLUSION: It seems necessary to meet stricter specifications to improve the quality of reporting. ADVANCES IN KNOWLEDGE: Our work results in one of the rare analyses of radiosurgery and SBRT publications. Literature must include necessary information to first, ensure treatments can be compared and reproduced and secondly, to permit to decide on new standards of care.

CDK 4/6 inhibitors combined with radiotherapy: A review of literature.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) namely palbociclib, ribociclib and abemaciclib were granted approval by the European Medicines Agency (EMA) between 2017 and 2018. They are currently prescribed in combination with hormone therapy to treat hormone receptor positive, HER2 negative metastatic or locally advanced breast cancer. Their combination with radiotherapy raises safety concerns as preclinical data enlightened their possible synergistic effect. Moreover, data about toxicity when combining CDK4/6i with radiotherapy are scarce. This review of literature focused on the use of CDK4/6i combined with radiotherapy. It aimed at listing every published data about such combination so as to understand its possible resulting toxicity in metastatic breast cancer.

Positron emission tomography for radiotherapy planning in head and neck cancer: What impact?

PET-computed tomography (CT) plays a growing role to guide target volume delineation for head and neck cancer in radiation oncology. Pretherapeutic [18F]FDG PET-CT adds information to morphological imaging. First, as a whole-body imaging modality, it reveals regional or distant metastases that induce major therapeutic changes in more than 10% of the cases. Moreover, it allows better pathological lymph node selection which improves overall regional control and overall survival. Second, locally, it allows us to define the metabolic tumoral volume, which is a reliable prognostic feature for survival outcome. [18F]FDG PET-CT-based gross tumor volume (GTV) is on average significantly smaller than GTV based on CT. Nevertheless, the overlap is incomplete and more evaluation of composite GTV based on PET and GTV based on CT are needed. However, in clinical practice, the study showed that using GTV PET alone for treatment planning was similar to using GTVCT for local control and dose distribution was better as a dose to organs at risk significantly decreased. In addition to FDG, pretherapeutic PET could give access to different biological tumoral volumes - thanks to different tracers - guiding heterogeneous dose delivery (dose painting concept) to resistant subvolumes. During radiotherapy treatment, follow-up [18F]FDG PET-CT revealed an earlier and more important diminution of GTV than other imaging modality. It may be a valuable support for adaptative radiotherapy as a new treatment plan with a significant impact on dose distribution became possible. Finally, additional studies are required to prospectively validate long-term outcomes and lower toxicity resulting from the use of PET-CT in treatment planning.

How to improve clinical research in a department of radiation oncology.

INTRODUCTION: Radiation therapy is a core modality for cancer treatment. Around 40% of cancer cures include the use of radiotherapy, either as a single strategy or combined with other treatments. In the past decade, substantial technical advances and novel insights into radiobiological properties have considerably improved patients' outcomes. This study overviewed the landscape of clinical research at our radiotherapy department. METHODS: We surveyed our institutional database of clinical trials to collect information for completed or ongoing radiation therapy clinical trials, from 2005 to December 2017 at the Lucien Neuwirth cancer institute. RESULTS: A total of 31 clinical trials were undertaken during the study period, of which 4 studies (12.9%) were industry-sponsored and 3 studies (9.7%) were launched by our radiotherapy unit. The vast majority of clinical trials (83.9%) were dedicated to unique organ localization, especially urological cancer (prostate or bladder) (42%). We also observed a shift towards more phase II trials during the study period as well as a special focus on elderly population. Over the last decade, the number of included patients increased by a 5.3 fold input, with 135 inclusions before 2011 and 720 inclusions after 2011. DISCUSSION: This study provided an observational and comprehensive analysis of radiotherapy research. From a monocentric point-of-view, these results reflected the on-going progress of worldwide radiotherapy research. Based on a 13-years' experience, this study aimed at highlighting essential cues to ensure efficient and perennial research.

Survival after hypofractionation in glioblastoma: a systematic review and meta-analysis.

BACKGROUND: Glioblastoma multiforme (GBM) has a poor prognosis despite a multi modal treatment that includes normofractionated radiotherapy. So, various hypofractionated alternatives to normofractionated RT have been tested to improve such prognosis. There is need of systematic review and meta-analysis to analyse the literature properly and maybe generalised the use of hypofractionation. The aim of this study was first, to perform a meta-analysis of all controlled trials testing the impact of hypofractionation on survival without age restriction and secondly, to analyse data from all non-comparative trials testing the impact of hypofractionation, radiosurgery and hypofractionated stereotactic RT in first line. MATERIALS/METHODS: We searched Medline, Embase and Cochrane databases to identify all publications testing the impact of hypofractionation in glioblastoma between 1985 and March 2020. Combined hazard ratio from comparative studies was calculated for overall survival. The impact of study design, age and use of adjuvant temozolomide was explored by stratification. Meta-regressions were performed to determine the impact of prognostic factors. RESULTS: 2283 publications were identified. Eleven comparative trials were included. No impact on overall survival was evidenced (HR: 1.07, 95%CI: 0.89-1.28) without age restriction. The analysis of non-comparative literature revealed heterogeneous outcomes with limited quality of reporting. Concurrent chemotherapy, completion of surgery, immobilization device, isodose of prescription, and prescribed dose (depending on tumour volume) were poorly described. However, results on survival are encouraging and were correlated with the percentage of resected patients and with patients age but not with median dose. CONCLUSIONS: Because few trials were randomized and because the limited quality of reporting, it is difficult to define the place of hypofactionation in glioblastoma. In first line, hypofractionation resulted in comparable survival outcome with the benefit of a shortened duration. The method used to assess hypofractionation needs to be improved.

CBCT evaluation of inter- and intra-fraction motions during prostate stereotactic body radiotherapy: a technical note.

BACKGROUND: In most clinical trials, gold fiducial markers are implanted in the prostate to tune the table position before each radiation beam. Yet, it is unclear if a cone-beam computed tomography (CBCT) should be performed before each beam to monitor a possible variation of the organs at risk (OARs) fullness, especially in case of recto-prostatic spacer implantation. The present study aimed at assessing the inter- and intra-fraction movements of prostate, bladder and rectum in patients implanted with a hyaluronic acid spacer and undergoing prostate stereotactic body radiotherapy (SBRT). METHODS: Data about consecutive patients undergoing prostate SBRT were prospectively collected between 2015 and 2019. Inter-and intra-fraction prostate displacements and volume variation of organs at risk (OARs) were assessed with CBCTs. RESULTS: Eight patients were included. They underwent prostate SBRT (37.5Gy, 5 fractions of 7.5Gy) guided by prostate gold fiducial markers. Inter-fraction variation of the bladder volume was insignificant. Intra-fraction mean increase of the bladder volume was modest (29 cc) but significant (p < 0.001). Both inter- and intra-fraction variations of the rectum volume were insignificant but for one patient. He had no rectal toxicity. The magnitude of table displacement necessary to match the prostate gold fiducial marker frequently exceeded the CTV/PTV margins (0.4 cm) before the first (35%) and the second arc (15%). Inter- and intra-fraction bladder and rectum volume variations did not correlate with prostate displacement. CONCLUSION: Major prostate position variations were reported. In-room kV fiducial imaging before each arc seems mandatory. Intra-fraction imaging of the OARs appears unnecessary. We suggest that only one CBCT is needed before the first arc. TRIAL REGISTRATION: NCT02361515, February 11th, 2015.