BACKGROUND AND OBJECTIVE:Few studies have compared short-term androgen deprivation (STADT) combined with high-dose radiotherapy (STADT-RT) versus high-dose radiotherapy (RT) alone in localized prostate cancer. METHODS:The GETUG 14 study randomized 376 patients to RT (n = 191) or STADT-RT (n = 179). The RT dose was 80 Gy in both arms. STADT consisted of monthly triptorelin and daily flutamide for a total duration of 4 mo, starting 2 mo before RT. Disease-free survival (DFS) was the primary endpoint. Secondary endpoints were overall survival (OS), biochemical failure (BF), metastasis failure (MF), toxicity, and quality of life. KEY FINDINGS AND LIMITATIONS:Among the 370 patients in the modified intention-to-treat population, 241 (65%) had intermediate-risk and 107 (28%) high-risk prostate cancer. At median follow-up among surviving patients of 84 mo (interquartile range 62-99 mo), the 5-yr DFS rate was 76% in RT arm versus 84% in STADT-RT arm (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.43-0.94]). ADT addition decreased BF (HR 0.45, 95% CI 0.28-0.72) and MF (HR 0.5, 95% CI 0.23-1.11) but not OS (HR 1.22, 95% CI 0.65-2.29). There were no significant differences for RT versus STADT-RT in the incidence rates for grade ≥2 toxicity in terms of acute gastrointestinal (GI) toxicity (26%, 95% CI 20-32 vs 26%, 95% CI 20-33), acute genitourinary (GU) toxicity (39%, 95% CI 32-46% vs 42%, 95% CI 35-50%), late GI toxicity (21%, 95% CI 16-28% vs 23%, 95% CI 18-30%), or late GU toxicity (30%, 95% CI 24-38% vs 27%, 95% CI 21-34%). CONCLUSIONS AND CLINICAL IMPLICATIONS:STADT is a well-tolerated and effective strategy that can enhance oncological outcomes when combined with high-dose RT, particularly for patients with intermediate- or high-risk prostate cancer.

Purpose/Objective(s) Few studies compared short-term androgen deprivation (STADT) with high-dose radiotherapy (STADT-RT) versus high-dose radiotherapy (RT) alone in localized prostate cancer. Materials/Methods The GETUG 14 study randomized 376 patients between RT (n=191) and STADT-RT (n=179). RT dose was 80 Gy in both arms and STADT was monthly triptorelin and daily flutamide for a total duration of 4 months, starting 2 months before irradiation. Disease-free survival (DFS) was the primary endpoint. Secondary endpoints were overall survival (OS), biochemical failure (BF), metastasis failure (MF), toxicity and quality of life. Results With a median follow-up of 84 months, five-year DFS was 76% in RT arm versus 84% in STADT-RT arm (hazard ratio [HR] = 0.64; [95% CI 0.43 - 0.89]; P = .02). ADT decreased BF (HR = 0.45; P = .001) and MF (HR = 0.5; P = .09) but not OS (HR = 1.22; P = .54). No difference was found in terms of gastrointestinal (26% of grade ≥2 in both arm, P = .97) and genito-urinary acute toxicity (39% for RT and 42% for STADT-RT, P = .55). Similarly, no difference was found in late toxicity and quality of life. Conclusion STADT improves disease-free survival in intermediate and high-risk prostate cancer patients receiving high dose (80 Gy) RT, without any deterioration in the safety profile.

In "Joint EANM/SNMMI/ESTRO Practice Recommendations for the Use of 2-[18F]FDG-PET/CT External Beam Radiation Treatment Planning in Lung Cancer V1.0" clinical indications for PET-CT in (non-)small cell lung cancer are highlighted and selective nodal irradiation is discussed. Additionally, concepts about target definition, target delineation and treatment evaluation are reviewed.

BACKGROUND: PET-CT with F-18-EDG or other radiophannaceuticals is a recommended tool to help the delineation of lung cancers candidate to radiotherapy. The motion artifacts caused by respiratory movements are reduced by 4D acquisitions. We introduced an extended reconstruction algorithm (multiple reconstruct register and average [multi-RRA]) which requires much shorter acquisition times than standard 4D PET-CT. Our aim was to evaluate the interest on multi-RRA images as an alternative of 3D and 4D PET-CT for the delineation of lung lesion. METHODS: PET acquisitions synchronized to the respiratory signal were obtained in 18 patients with mobile lung tumors. We compared the tumor volumes delineated on Multi-RRA images to 3D and 4D PET-CT, considering the 4D CT as a reference. The tumor volumes were delineated and compared with topologic similarity indexes (Dice, Jaccard and overlap). RESULTS: Twenty tumors were delineated. The volumes delineated with multi-RRA and 4D PET were not significantly different (mean difference of 0.2 +/- 0.7 mL). Comparison by pairs (Tukey-Kramer test) showed that 3D-PET volumes were significantly smaller than 4D-PET and multi-RRA volumes (P<0.001). Topologic similarity indexes with 4D-PET were slightly statistically higher with multi-RRA than with 3D-PET (Dice and Jaccard) or 4D-CT (Dice, Jaccard and Overlap). CONCLUSIONS: The tumor volumes delineated on multi-RRA are similar to the volumes obtained with 4D PET, with shorter acquisition time.

2-[18F]FDGPET/CT is of utmost importance for radiation treatment (RT) planning and response monitoring in lung cancer patients, in both non-small and small cell lung cancer (NSCLC and SCLC). This topic has been addressed in guidelines composed by experts within the field of radiation oncology. However, up to present, there is no procedural guideline on this subject, with involvement of the nuclear medicine societies. A literature review was performed, followed by a discussion between a multidisciplinary team of experts in the different fields involved in the RT planning of lung cancer, in order to guide clinical management. The project was led by experts of the two nuclear medicine societies (EANM and SNMMI) and radiation oncology (ESTRO). This guideline results from a joint and dynamic collaboration between the relevant disciplines for this topic. It provides a worldwide, state of the art, and multidisciplinary guide to 2-[18F]FDG PET/CT RT planning in NSCLC and SCLC. These practical recommendations describe applicable updates for existing clinical practices, highlight potential flaws, and provide solutions to overcome these as well. Finally, the recent developments considered for future application are also reviewed.

Introduction:Stereotactic body radiotherapy (SBRT) is a treatment option for spine metastases. The International Spine Radiosurgery Consortium (ISRC) has published consensus guidelines for target delineation in spine SBRT. A new software called Elements™ Spine SRS by Brainlab® that includes the module Elements SmartBrush Spine (v3.0, Munich, Germany) has been developed specifically for SBRT treatment of spine metastases, and the latter provides the ability to perform semiautomatic clinical target volume (CTV) generation based on gross tumor volume (GTV) localization and guidelines. The aims of our study were to evaluate this software by studying differences in volumes between semiautomatic CTV contours compared to manual contouring performed by an expert radiation oncologist and to determine the dosimetric impact of these differences on treatment plans.Methods:A total of 35 volumes ("Expert GTV" and "Expert CTV") from 30 patients were defined by a single expert. A semiautomatic definition of these 35 CTVs based on the location of "Expert GTV" and following ISRC guidelines was also performed in Elements SmartBrush Spine ("Brainlab CTV"). The spatial overlap between "Brainlab" and "Expert" CTVs was calculated using the Dice similarity coefficient (DSC). We considered a threshold of 0.80 or above to indicate that Elements SmartBrush Spine performed very well with adequate contours for clinical use. Two dosimetric treatment plans, each corresponding to a specific planning target volume (PTV; Expert PTV, Brainlab PTV), were created for 11 patients.Results:We showed that "Brainlab CTV" and "Expert CTV" mean volumes were 29.8 ± 16.1 and 28.7 ± 15.7 cm3, respectively (p = 0.23). We also showed that the mean DSC for semiautomatic contouring relative to expert manual contouring was 0.85 ± 0.08 and less than 0.80 in five cases. For metastases involving the vertebral body only (n = 13,37%), the mean DSC was 0.90 ± 0.03, and for ones involving other or several vertebral regions (n = 22.63%), the mean DSC was 0.81 ± 0.08 (p < 0.001). The comparison of dosimetric treatment plans was performed for equivalent PTV coverage. There were no differences between doses received by organs at risk (spinal cord and esophagus) for Expert and Brainlab PTVs, respectively.Conclusion:The results showed that the semiautomatic method had quite good accuracy and can be used in clinical routine even for complex lesions.

Low skeletal muscle mass is a well-known prognostic factor for patients treated for a non-small-cell lung cancer by surgery or chemotherapy. However, its impact in patients treated by exclusive radiochemotherapy has never been explored. Our study tries to evaluate the prognostic value of low skeletal muscle mass and other antropometric parameters on this population. Clinical, nutritional and anthropometric date were collected for 93 patients treated by radiochemotherapy for a NSCLC. Anthropometric parameters were measured on the PET/CT by two methods. The first method was a manual segmentation at level L3, used to define Muscle Body Area (MBA L3 ), Visceral Fat Area (VFA L3 ) and Subcutaneous Fat Area (SCFA L3 ). The second method was an software (Anthropometer3D), allowing an automatic multislice measurement of Lean Body Mass (LBM Anthro3D ), Fat Body Mass (FBM Anthro3D ), Muscle Body Mass (MBM Anthro3D ), Visceral Fat Mass (VFM Anthro3D ), and Sub-Cutaneous Fat Mass (SCFM Anthro3D ) on the PET/CT. All anthropometrics parameters were normalised by the patient's height. The primary end point was overall survival time. Univariate and then stepwise multivariate cox analysis were performed for significant parameters. Finally, Spearman's correlation between MBA L3 and MBM Anthro3D was assessed. Forty-one (44%) patients had low skeletal muscle mass. The median overall survival was 18 months for low skeletal muscle mass patients versus 36 months for non-low skeletal muscle mass patients ( p = 0.019). Low skeletal muscle mass (HR = 1.806, IC95% [1.09–2.98]), serums albumin level < 35 g/l (HR = 2.203 [1.19–4.09]), Buzby Index < 97.5 (HR = 2.31 [1.23–4.33]), WHO score = 0 (HR = 0.59 [0.31–0.86] and MBM Anthro3D < 8.56 kg/m 2 (HR = 2.36 [1.41–3.90]) were the only significant features in univariates analysis. In the stepwise multivariate Cox analysis, only MBM Anthro3D < 8.56 kg/m 2 (HR = 2.16, p = 0.003) and WHO score = 0 (HR = 0.59, p = 0.04) were significant. Finally, muscle quantified by MBA L3 and MBM Anthro3D were found to be highly correlated (Spearman = 0.9). Low skeletal muscle mass, assessed on the pre-treatment PET/CT is a powerful prognostic factor in patient treated by radiochemotherapy for a NSCLC. The automatic software Anthropometer3D can easily identify patients a risk that could benefit an adapted therapy.

Background : Sarcopenia is defined by a loss of skeletal muscle mass with or without loss of fat mass. Sarcopenia has been associated to reduced tolerance to treatment and worse prognosis in cancer patients, including patients undergoing surgery for limited oesophageal cancer. Concomitant chemo-radiotherapy is the standard treatment for locally-advanced tumour, not accessible to surgical resection. Using automated delineation of the skeletal muscle, we have investigated the prognostic value of sarcopenia in locally advanced oesophageal cancer (LAOC) patients treated by curative-intent chemo-radiotherapy. Methods : The clinical, nutritional, anthropometric, and functional-imaging ( 18 FDG-PET/CT) data were collected in 97 patients treated between 2006 and 2012 in our institution. The skeletal muscle area was automatically delineated on cross-sectional CT images acquired at the 3 rd . lumbar vertebra level and divided by the patient’s squared height (SML3/h²) to obtain the Skeletal Muscle Index (SMI). The primary endpoint was overall survival probability. Results : Seventy-six deaths were reported. The median survival time was 27 [95% Confidence Interval 23 – 40] months for the whole population. Univariate analyses (Cox Proportional Hazard Model) showed decreased survival probabilities in patients with reduced SMI, WHO >0, Body Mass Index ≤21, and Nutritional Risk Index ≤97.5. Multivariate analyses showed that sarcopenia was the only significant prognostic factor (HR 2.32 [1.24-4.34], p=0.008). Using Receiver Operating Characteristics curves, the Area Under the Curve (AUC) was 0.73 in males (p=0.0002], the optimal threshold being 51.5 cm²/m². In women, the AUC was 0.65 (p=0.19). Conclusion : Sarcopenia is a powerful independent prognostic factor, associated with a rise of the overall mortality in patients treated exclusively by radiochemotherapy for a locally advanced oesophageal cancer. L3 CT images are easily gathered from 18 FDG-PET/CT acquisitions

In the era of open science, public datasets, along with common experimental protocol, help in the process of designing and validating data science algorithms; they also contribute to ease reproductibility and fair comparison between methods. Many datasets for image segmentation are available, each presenting its own challenges; however just a very few exist for radiotherapy planning. This paper is the presentation of a new dataset dedicated to the segmentation of organs at risk (OARs) in the thorax, i.e. the organs surrounding the tumour that must be preserved from irradiations during radiotherapy. This dataset is called SegTHOR (Segmentation of THoracic Organs at Risk). In this dataset, the OARs are the heart, the trachea, the aorta and the esophagus, which have varying spatial and appearance characteristics. The dataset includes 60 3D CT scans, divided into a training set of 40 and a test set of 20 patients, where the OARs have been contoured manually by an experienced radiotherapist. Along with the dataset, we present some baseline results, obtained using both the original, state-of-the-art architecture U-Net and a simplified version. We investigate different configurations of this baseline architecture that will serve as comparison for future studies on the SegTHOR dataset. Preliminary results show that room for improvement is left, especially for smallest organs.

Purpose: Medulloblastoma has recently been characterized as a heterogeneous disease with 4 distinct molecular subgroups: wingless (WNT), sonic hedgehog (SHH), group 3, and group 4, with a new definition of risk stratification. We report progression-free survival, overall survival, and long-term cognitive effects in children with standard-risk medulloblastoma exclusively treated with hyperfractionated radiation therapy (HFRT), reduced boost volume, and online quality control, and we explore the prognostic value of biological characteristics in this chemotherapy-naiive population. Methods and Materials: Patients with standard-risk medulloblastoma were enrolled in 2 successive prospective multicentric studies, MSFOP 98 and MSFOP 2007, and received exclusive HFRT (36 Gy, 1 Gy/fraction twice daily) to the craniospinal axis followed by a boost at 68 Gy restricted to the tumor bed (1.5 cm margin), with online quality assurance before treatment. Patients with MYC or MYCN amplification were not excluded at the time of the study. We report progression-free survival and overall survival in the global population, and according to molecular subgroups as per World Health Organization 2016 molecular classification, and we present cognitive evaluations based on the Wechsler scale. Results: Data from 114 patients included in the MSFOP 98 trial from December 1998 to October 2001 (n = 48) and in the MSFOP 2007 from October 2008 to July 2013 (n = 66) were analyzed. With a median follow-up of 16.2 (range, 6.4-19.6) years for the MSFOP 98 cohort and 6.5 (1.6-9.6) years for the MSFOP 2007 cohort, 5-year overall survival and progression-free survival in the global population were 84% (74%-89%) and 74% (65%-81%), respectively. Molecular classification was determined for 91 patients (WNT [n = 19], SHH [n = 12], and non-WNT/non-SHH [n = 60]-including group 3 [n = 9], group 4 [n = 29], and not specified [n = 22]). Our results showed more favorable outcome for the WNT-activated subgroup and a worse prognosis for SHH-activated patients. Three patients had isolated extra-central nervous system relapse. The slope of neurocognitive decline in the global population was shallower than that observed in patients with a normofractionated regimen combined with chemotherapy. Conclusions: HFRT led to a 5-year survival rate similar to other treatments combined with chemotherapy, with a reduced treatment duration of only 6 weeks. We confirm the MSFOP 98 results and the prognostic value of molecular status in patients with medulloblastoma, even in the absence of chemotherapy. Intelligence quotient was more preserved in children with medulloblastoma who received exclusive HFRT and reduced local boost, and intelligence quotient decline was delayed compared with patients receiving standard regimen. HFRT may be appropriate for patients who do not consent to or are not eligible for prospective clinical trials; for patients from developing countries for whom aplasia or ileus may be difficult to manage in a context of high cost/effectiveness constraints; and for whom shortened duration of RT may be easier to implement. (C) 2020 Elsevier Inc. All rights reserved.

To use the oxyhaemoglobin dissociation curve (ODC) to non-invasively measure the ventilation perfusion ratio (VA/Q) and right-to-left intrapulmonary vascular shunt before and after liver transplantation (LT) in children with hepatopulmonary syndrome (HPS). To investigate whether the right-to-left shunt derived by ODC correlated with the shunt derived by technetium-99 labelled macroaggregated albumin lung perfusion scan (MAA).A retrospective cohort study at King's College Hospital NHS Foundation Trust, London, UK was performed between 1998 and 2016. The VA/Q and right-to-left shunt were non-invasively measured pre and post LT. The pre-LT right-to-left intrapulmonary shunt was also measured by MAA. The non-invasively derived pre-LT shunt was correlated with the shunt derived by MAA.Fifteen children with HPS were studied with a median (IQR) age at LT of 8.8 (6.6–12.9) years. The median (IQR) pre-LT VA/Q [0.49 (0.42–0.65)] was lower compared to the post-LT VA/Q [0.61 (IQR 0.54–0.72), p = 0.012]. The median (IQR) pre-LT shunt was 19 (3–24) % which decreased to zero in all but one children post-LT, (p = 0.001). The MAA-derived shunt was significantly positively correlated with the ODC-derived shunt (r = 0.783, p = 0.001). The mean (SD) difference between shunt derived by ODC and shunt derived by MAA was 0.5 (7.2) %.Ventilation/perfusion impairment reverses but not completely resolves after liver transplantation in children with hepatopulmonary syndrome. The non-invasive method for estimating intrapulmonary shunting could be used as an alternative to the macroaggregated albumin scan in this population.

In radiotherapy, the dose prescription is currently based on discretized dose-effects records that do not take into fully account for the complexity of the patient-dose-response relationship. Their predictive performance on both anti-tumour efficacy and toxicity can be optimized by integrating radiobiological models. It is with this in mind that the calculation models TCP (Tumor Control Probability) and NTCP (Normal Tissue Complication Probability) have been developed. Their construction involves several important steps that are necessary and important to understand. The first step is based on radiobiological models allowing to calculate according to more or less complexity the rate of surviving cells after irradiation. Two additional steps are required to convert the physical dose into an equivalent biological dose, in particular a 2Gy equivalent biological dose (EQD2): first to take into account the effect of the fractionation of the dose for both the target volume and the organs at risk; second to convert an heterogeneous dose to an organ into an homogeneous dose having the same effect (Niemierko generalized equivalent uniform dose (gEUD)). Finally, the process of predicting clinical effects based on radiobiological models transform doses into tumour control (TCP) or toxicity (NTCP) probabilities using parameters that reflect the radiobiological characteristics of the tissues in question. The use of these models in current practice is still limited, but since the radiotherapy softwares increasingly integrate them, it is important to know the principle and limits of application of these models.

Background Radiotherapy is the standard salvage treatment after radical prostatectomy. To date, the role of androgen deprivation therapy has not been formally shown. In this follow-up study, we aimed to update the results of the GETUG-AFU 16 trial, which assessed the efficacy of radiotherapy plus androgen suppression versus radiotherapy alone. Methods GETUG-AFU 16 was an open-label, multicentre, phase 3, randomised, controlled trial that enrolled men (aged >= 18 years) with Eastern Cooperative Oncology Group performance status of 0 or 1, with histologically confirmed adenocarcinoma of the prostate (but no previous androgen suppression or pelvic radiotherapy), stage pT2, T3, or T4a (bladder neck involvement only) and pN0 or pNx according to the tumour, node, metastasis (TNM) staging system, whose prostate-specific antigen (PSA) concentration increased from 0.1 ng/mL to between 0.2 ng/mL and 2.0 ng/mL after radical prostatectomy, without evidence of clinical disease. Patients were assigned through central randomisation (1:1) to short-term androgen suppression (subcutaneous injection of 10.8 mg goserelin on the first day of irradiation and 3 months later) plus radiotherapy (3D conformal radiotherapy or intensity modulated radiotherapy of 66 Gy in 33 fractions, 5 days a week for 7 weeks) or radiotherapy alone. Randomisation was stratified using a permuted block method (block sizes of two and four) according to investigational site, radiotherapy modality, and prognosis. The primary endpoint was progression-free survival in the intention-to-treat population. This post-hoc one-shot data collection done 4 years after last data cutoff included patients who were alive at the time of the primary analysis and updated long-term patient status by including dates for first local progression, metastatic disease diagnosis, or death (if any of these had occurred) or the date of the last tumour evaluation or last PSA measurement. Survival at 120 months was reported. Late serious adverse effects were assessed. This trial is registered on ClinicalTrials.gov, NCT00423475. Findings Between Oct 19, 2006, and March 30, 2010, 743 patients were randomly assigned, 374 to radiotherapy alone and 369 to radiotherapy plus goserelin. At the time of data cutoff (March 12, 2019), the median follow-up was 112 months (IQR 102-123). The 120-month progression-free survival was 64% (95% CI 58-69) for patients treated with radiotherapy plus goserelin and 49% (43-54) for patients treated with radiotherapy alone (hazard ratio 0.54, 0.43-0.68; stratified log-rank test p<0.0001). Two cases of secondary cancer occurred since the primary analysis, but were not considered to be treatment related. No treatment-related deaths occurred. Interpretation The 120-month progression-free survival confirmed the results from the primary analysis. Salvage radiotherapy combined with short-term androgen suppression significantly reduced risk of biochemical or clinical progression and death compared with salvage radiotherapy alone. The results of the GETUG-AFU 16 trial confirm the efficacy of androgen suppression plus radiotherapy as salvage treatment in patients with increasing PSA concentration after radical prostatectomy for prostate cancer. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

INTRODUCTION:The purpose of our present study was to assess the prognostic impact of FDG PET-CT after induction chemotherapy for patients with inoperable non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS:This retrospective study included 50 patients with inoperable stage II/III NSCLC from January 2012 to July 2015. They were treated for curative intent with induction chemotherapy, followed by concomitant chemoradiation therapy or sequential radiation therapy. FDG PET-CT scans were acquired at initial staging (PET1) and after the last cycle of induction therapy (PET2). Five parameters were evaluated on both scans: SUVmax, SUVpeak, SUVmean, TLG, MTV, and their respective deltas. The prognostic value of each parameter for overall survival (OS) and progression-free survival (PFS) was evaluated with Cox proportional-hazards regression models. RESULTS:Median follow-up was 19 months. PET1 parameters, clinical and histopathological data were not predictive of the outcome. TLG2 and ΔTLG were prognostic factors for OS. TLG2 was the only prognostic factor for PFS. For OS, log-rank test showed that there was a better prognosis for patients with TLG2< 69g (HR = 7.1, 95%CI 2.8-18, p = 0.002) and for patients with ΔTLG< -81% after induction therapy (HR = 3.8, 95%CI 1.5-9.6, p = 0.02). After 2 years, the survival rate was 89% for the patients with low TLG2 vs 52% for the others. We also evaluated a composite parameter considering both MTV2 and ΔSUVmax. Patients with MTV2> 23cc and ΔSUVmax> -55% had significantly shorter OS than the other patients (HR = 5.7, 95%CI 2.1-15.4, p< 0.01). CONCLUSION:Post-induction FDG PET might be an added value to assess the patients' prognosis in inoperable stage II/III NSCLC. TLG, ΔTLG as well as the association of MTV and ΔSUVmax seemed to be valuable parameters, more accurate than clinical, pathological or pretherapeutic imaging data.

Severe hypoxia [oxygen partial pressure (pO(2)) below 5-10 mmHg] is more frequent in glioblastoma multiforme (GBM) compared to lower-grade gliomas. Seminal studies in the 1950s demonstrated that hypoxia was associated with increased resistance to low-linear energy transfer (LET) ionizing radiation. In experimental conditions, the total radiation dose has to be multiplied by a factor of 3 to achieve the same cell lethality in anoxic situations. The presence of hypoxia in human tumors is assumed to contribute to treatment failures after radiotherapy (RT) in cancer patients. Therefore, a logical way to overcome hypoxia-induced radioresistance would be to deliver substantially higher doses of RT in hypoxic volumes delineated on pre-treatment imaging as biological target volumes (BTVs). Such an approach faces various fundamental, technical, and clinical challenges. The present review addresses several technical points related to the delineation of hypoxic zones, which include: spatial accuracy, quantitative vs. relative threshold, variations of hypoxia levels during RT, and availability of hypoxia tracers. The feasibility of hypoxia imaging as an assessment tool for early tumor response to RT and for predicting long-term outcomes is discussed. Hypoxia imaging for RT dose painting is likewise examined. As for the radiation oncologist's point of view, hypoxia maps should be converted into dose-distribution objectives for RT planning. Taking into account the physics and the radiobiology of various irradiation beams, preliminary in silico studies are required to investigate the feasibility of dose escalation in terms of normal tissue tolerance before clinical trials are undertaken.

Results of pooled data from MSFOP 98 and MSFOP 2007 studies testing hyperfractionated radiotherapy without chemotherapy in standard risk medulloblastoma on 114 evaluable patients and correlation with the new biomolecular classification in 93/114 cases. Between 12/98 and 10/01, 48 patients were included in the MSFOP 98 trial and between 10/08 and 07/13, 66 patients were included in the MSFOP 2007 observational study with the same treatment and criteria inclusion. All patients received hyperfractionated radiotherapy (36Gy- 36fraction) on craniospinal axis, boost with conformal therapy restricted to the tumor bed (68Gy- 68 fractions), and no chemotherapy. Pathologic slides were reviewed by a panel of experts .93/114 have been reclassified according the new biomolecular classification: 9 classic non-WNT/nonSHH, group 3; 28 classic non-WNT/nonSHH group 4; 22 classic non-WNT/non SHH ; 22 Classic WNT activated and 12 SHH activated. The median age of our population was 9.9 years and the sex ratio was 1.7. The mean FU is 195 months for MSFOP98 and 78 for MSFOP2007.The 5 y OS according molecular sub groups is 95% (CI95%: 72-99) for WNT activated group, 86% (CI95%:63-95) for non-WNT nonSHH sub group, 78% (CI95%:36-94) for non-WNT nonSHH, group 3sub group, 77% (CI95%:56-89) for non-WNT nonSHH, group 4 sub group, and 67% (CI95%:34-86) for the SHH activated sub group. Regarding cognitive evaluation, at last measurement for every patient, the mean Full Scale Intelligence Quotient (FSIQ) was 88 (40 – 131) with a mean interval from inclusion of 4.3 y (-0.05 – 13.17). Forty-six patients had performed two assessments or more. After a mean of 5 years (0.95 – 13.17) from inclusion, means IQ were 87 (40-131), 97 (45 - 140), 89 (50 - 111), 84 (50 - 115) and 81 (50 -111). Neurocognitive outcome of these patients is in the low average of normal range for both assessments with slowness and a late decrease of working memory over time (after 5 years of follow up). Working memory does not depend on age at diagnosis but working memory continues to decline 10 years after diagnosis The perceptual reasoning/organization index is below the verbal comprehension index measures but FSIQ remained stable with time and do not continue to decline. With time, there is an advantage of HFRT treatment for cognitive functioning (in the normal range; -0.8 DS) compared to high (35 Gys) and standard (25Gys) dose irradiation. These results confirmed that HFRT without chemotherapy could be an alternative treatment for standard risk medulloblastoma and doesn't increase the CNS isolated relapse rate. New biomolecular classification is still prognostic in the chemotherapy naïve population.