Purpose Radiotherapy quality assurance (RTQA) is essential for ensuring adherence to trial protocols. This paper summarizes the individual case review (ICR) results from the PEACE-1 trial, a phase-III study investigates standard of care (androgen deprivation therapy with or without docetaxel) with or without local radiotherapy; and with or without abiraterone acetate plus prednisone in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Materials and methods Participating institutions submitted radiotherapy (RT) plans for central review, assessing protocol compliance in target volume and organs at risk (OARs) delineation, as well as dose specifications. ICRs were conducted either retrospectively (r-ICRs), after starting RT, or prospectively (p-ICRs), before RT initiation. Case reviews were categorized as acceptable per protocol, acceptable variation, or unacceptable variation based on delineation and dose and plan parameters. Results Out of 585 patients in the RT arms, 527 (90%) had r-ICRs, primarily using intensity-modulated radiotherapy (IMRT). Delineation review approved 417 (87%) r-ICRs and 44 (92%) p-ICRs. The main reasons for unacceptable delineation were erroneous clinical target volume (CTV) delineation. In dose and plan reviews, 399 (96%) r-ICRs cases and 46 (96%) p-ICRs were approved, with unacceptable cases primarily due to PTV dose distribution issues. Conclusion RTQA is crucial in prostate cancer trials, primarily for proper target volume delineation. It is recommended to omit r-ICRs due to resource demands and lack of impact on RTQA outcomes, using limited p-ICRs with early feedback for site deviations and reserving full p-ICRs for trails with new techniques or dose regimens.ClinicalTrials.gov: NCT01957436.

365 Background: The aim of this study was to report the efficacy and toxicity of salvage stereotactic body radiation therapy (SBRT) for local prostate cancer recurrence after radiotherapy. Methods: We retrospectively reviewed a total of 108 medical records of patients treated with salvage SBRT for prostate cancer recurrence, between July 2015 and February 2021 in our institution. Patients who had initial radical prostatectomy were excluded. The median time interval between the two radiation treatments was 9 years (range, 3-20 years). All the patients had biochemical recurrence, with a PSA of 3.5 ng/mL (range, 1.8-43 ng/mL). Local recurrence was to be proven by biopsies, without distant lymph node or metastasis. The local recurrence was visible in 82% and 99% of patients on mpMRI and choline/PSMA PET/CT, respectively. The salvage treatment consisted in SBRT at a total dose of 36 Gy in six fractions delivered every other day, associated with androgen deprivation therapy in 44% of patients. We reported efficacy and toxicity (according to CTCAE v 4.03 classification) after salvage SBRT. Results: Median follow-up was 19.6 months (range, 2.3-67 months). Two year biochemical recurrence-free survival and lymph node/metastases free survival rates were 76% (95% CI: 66-87%) and 88% (95% CI: 80-96%), respectively. Regarding acute toxicity, rates of grade 2 and 3 GU toxicities were 27% and 2%, respectively. Rate of grade 2 GI toxicity was 2%, without grade ≥3. Regarding late toxicity, 2 year rates of grade 2 and 3 GU toxicities were 50% (95% CI: 44-56%) and 8% (95% CI: 2-14%), respectively. One patient experimented a grade 4 GU toxicity (bladder necrosis requiring a cystectomy) 8 months after SBRT. Two year rate of grade 2 GI toxicity was 2 (95% CI: 0-5%), without grade ≥3. Conclusions: The main toxicity of prostate salvage SBRT is GU. With a short follow-up, a subset of patients may be controlled by the salvage treatment.

Background: Management of macroscopic local recurrence (MLR) after radical prostatectomy is a challenging situation with no standardized approach.Objective: The objective of our study was to assess the efficacy and safety of functional image-guided salvage radiotherapy (SRT) in patients with MLR in the prostate bed.Design, setting, and participants: In this international multicenter retrospective study across 16 European centers, eligible patients were initially treated by radical prostatectomy (RP) with or without pelvic lymph node dissection for localized or locally advanced adenocarcinoma of the prostate.Outcome measurements and statistical analysis: Prostate-specific antigen (PSA) measured 4 wk after RP was <0.1 ng/ml. All patients presented a biochemical relapse after RP defined by an increase in PSA level of >0.2 ng/ml on two successive measures. Only patients with an MLR lesion in the prostatectomy bed visualized on functional imaging (multiparametric magnetic resonance imaging, positron emission tomography/ computed tomography [PET/CT] choline, or PET/CT prostate-specific membrane antigen) were eligible. Patients with lymph node, bone, or visceral dissemination at restaging imaging (CT and/or bone scintigraphy and/or magnetic resonance imaging and/or PET) were excluded. Dose escalation was defined as a dose of >66 Gy prescribed to the prostate bed or to MLR. Toxicities were classified using the Common Terminology Criteria for Adverse Events scale, version 4.03. The primary endpoint was progression free survival (PFS). Secondary outcomes were metastasis-free survival (MPFS), biochemical progression-free survival, and overall survival. Genitourinary (GU) and gastrointestinal (GI) toxicities were analyzed.Results and limitations: Between January 2000 and December 2019, 310 patients received at least one dose escalation on MLR and 25 patients did not receive any dose escalation. The median PSA level before SRT was 0.63 ng/ml (interquartile range [IQR], 0.27-1.7). The median follow-up was 54 mo (IQR, 50-56). Five-year PFS and MPFS were 70% (95% confidence interval [CI]: [64; 75]) and 84% (95% CI: [78; 88]), respectively. Grade >2 GU and GI late toxicities were observed in 43 (12%) and 11 (3%) patients, respectively. When the prescribed dose on the MLR lesion was >72 Gy, an improvement in 5-yr PFS was found for patients received at least one dose escalation (73% [95% CI: 65- 79]) vs 60% [95% CI: 48; 70]; p = 0.03).Conclusions: In this contemporary study integrating functional imaging data, we found potential efficacy of SRT with dose escalation >72 Gy for patients with MLR in the prostate bed and with an acceptable toxicity profile. Prospective data exploring this MLR dose escalation strategy are awaited.Patient summary: In this report, we looked at the outcomes from salvage radiotherapy for prostate cancer and macroscopic relapse in a large European population. We found that outcomes varied with prostate-specific antigen at relapse, Gleason score, and dose escalation. We found potential efficacy of salvage radiotherapy with dose escalation for macroscopic relapse in the prostate bed, with an acceptable toxicity profile.& COPY; 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.

4015 Background: Preoperative CRT with a FU/platinum regimen has been used for years for esophageal or junctional cancer before the CP regimen became a standard of care following the results of the CROSS study (van Hagen 2012). We aimed at evaluating the complete resection (R0) rate and severe postoperative morbidity rate associated with these 2 neoadjuvant regimens, each being combined with the radiation (RT) regime used in the CROSS trial. Methods: PROTECT is a multicenter, randomized, non-comparative, phase 2 trial (NCT02359968) in patients (pts) with resectable esophageal or Siewert type I-II junctional cancer, stage II (T1-2N1 or T3N0) or stage III (T3N1 or T4anyN) tumors (UICC-7 classification), and ECOG PS ≤2. Following randomization (balanced by ECOG PS 0 vs 1-2, stage II vs III, squamous-cell (SCC) vs adenocarcinoma (ADK), center), pts received CP (AUC2 CBP plus PCL 50mg/m² / week x 5 weeks), or Fx (FU 400 mg/m² bolus Day 1, then FU 1600 mg/m² continuous infusion over 2 days, plus OX 85 mg/m², and Folinic acid 200 mg/m², 2-h infusion, Day 1; 3 cycles every 2 weeks). RT technique was similar in both arms: 3D-conformal as published in the CROSS trial or IMRT (n = 35); total dose of 41.4Gy, 5 fractions of 1.8Gy / week, starting at Day 1 of chemotherapy. Surgery was performed 4 to 8 weeks after completion of CRT through a transthoracic or mini-invasive approach with a two field extended lymphadenectomy. Co-primary endpoints were R0 (failure: R1 or disease progression under CRT), and severe postoperative morbidity rate ≤30 days after surgery (Clavien-Dindo grade ≥ III). Based on a Bryant and Day 2-stage design (p0 = 75% and p1 = 90% for resection; p0 = 45% and p1 = 25% for morbidity; α = 10% and β = 15%), 48 evaluable pts were required by arm. Results: 100/104 pts recruited from 02/2015 to 08/2020, started the study treatment: 50 CP & 50 Fx. Overall, median age = 64 (range, 33-79); 82/100 males; 62 ADK and 38 SCC; 66 esophageal and 34 junctional site; 31 stage II; 68 stage III, 1 Nx. R0 resection was obtained in 46/50 CP pts (92.0%, 95% CI: 80.8-97.8%), and in 42/48 Fx pts (87.5%, 74.8-95.3%); 2 non evaluable pts because of event unrelated to disease progression. Severe postoperative adverse events (AEs) occurred in 34/91 pts who underwent surgery: 21/48 CP (43.8%, 29.5-58.8%) and 13/43 Fx (30.2%, 17.2-46.1%). Severe AEs were respiratory disorders (CP 26%; Fx 26%), esophageal fistula (CP 18%; Fx 6%), infection (CP 5%; Fx 3%), haemorrhage (CP 5%; Fx 0%) and gastric tube necrosis (CP 6%; Fx 3%). 5 pts died from AEs (3 CP, 2 Fx). A TRG1-2 was observed in 29/48 (60.4%, 95% CI: 44.3-74.2%) CP pts, and in 19/43 (44.2%, 29.1-60.1%) Fx pts. Conclusions: When combined to preoperative radiation therapy at 41.4Gy, both regimens (CP and Fx) provided short-term benefit on R0 resection; however, CP is associated with a severe postoperative morbidity rate higher than expected. Clinical trial information: NCT02359968.

251 Background: For prostate cancer (Pca), salvage radiotherapy (sRT) with or without androgen deprivation therapy (ADT) is currently the only curative treatment option in case of post-radical prostatectomy (RP) biochemical relapse (BR). Functional imaging techniques have shown that macroscopic recurrence (MR) in the prostate bed (PB) are frequent. In this study, we aimed to assess efficacy and safety of sRT in patients with MR inside the PB proven by functional imaging. Methods: A multicenter retrospective study was conducted in 16 European centers. Patients were included if they displayed BR after RP for Pca, with MR only in the PB proven by functional imaging. All patients had to be eligible for sRT. The overall population was divided along 4 groups according to the delivered treatment: dose escalation on MR (A), dose escalation on PB (B), double dose escalation MR+PB (C), no dose escalation (D). The primary endpoint was progression-free survival (PFS). Secondary outcomes included the metastasis-free survival (MFS), biochemical PFS (bPFS) and overall survival (OS). Grade ≥2 genito-urinary (GU) and gastro-intestinal (GI) acute and late toxicities were collected. Results: Between January 2000 and December 2019, 363 patients with isolated MR after RP for Pca were treated by sRT. The median pre-sRT PSA level was 0.63ng/mL (range, 0.2-23.6). At the time of BR, 266 (73%) patients presented MR in the PB proven by magnetic resonance imaging, and 110 (30%) by positron emission tomography. The median follow-up was 53.6 months (range, 47.52; 58.32). The 5-year PFS and MFS were 70% (95%CI [63.8-75.4]) and 83.7% (95%CI [78.4-87.8]), respectively. Grade ≥2 GU and GI late toxicities were found in 43 (12%) and 11 (3%) patients, respectively. A 5-year PFS benefit was highlighted for groups A, B and C (313 patients) when the MR dose was ≥72Gy: 72,8% (95%CI 64.6-79.4) versus 60.3% (95%CI 48,4-70,3), p = 0.03. Conclusions: In a modern series integrating functional imaging data, we confirmed that sRT is effective in the event of MR inside the PB, with an acceptable toxicity profile. Prospective data should further investigate the correlation between MR-targeted dose escalation and PFS.

Background and purpose: The relevance of metastasis-directed stereotactic body radiation therapy (SBRT) remains to be demonstrated through phase III trials. Multiple SBRT procedures have been published potentially resulting in a disparity of practices. Therefore, the french society of urological radiation oncolgists (GETUG) recognized the need for joint expert consensus guidelines for metastasis-directed SBRT in order to standardize practice in trials carried out by the group. Materials and methods: After a comprehensive literature review, 97 recommendation statements were created regarding planning and delivery of spine bone (SBM) and non-spine bone metastases (NSBM) SBRT. These statements were then submitted to a national online two-round modified Delphi survey among main GETUG investigators. Consensus was achieved if a statement received >= 75 % agreements, a trend to consensus being defined as 65-74 % agreements. Any statement without consensus at round one was re-submitted in round two. Results: Twenty-one out of 29 (72.4%) surveyed experts responded to both rounds. Seventy-five statements achieved consensus at round one leaving 22 statements needing a revote of which 16 achieved consensus and 5 a trend to consensus. The final rate of consensus was 91/97 (93.8%). Statements with no consensus concerned patient selection (3/19), dose and fractionation (1/11), prescription and dose objectives (1/9) and organs at risk delineation (1/15). The voting resulted in the writing of step-by-step consensus guidelines. Conclusion: Consensus guidelines for SBM and NSBM SBRT were agreed upon using a validated modified Delphi approach. These guidelines will be used as per-protocole recommendations in ongoing and further GETUG clinical trials.

In prostate cancer radiotherapy, biochemical recurrence has been traditionally predicted using radiomics approaches with however limited performance. The purpose of this work was to use a mechanistic in silico model of tumor growth and response to irradiation to obtain better predictions. A cohort of 76 patients with localized prostate adenocarcinoma having undergone external beam radiotherapy was used. Analogous digital tissues were built from pre-treatment MRI. The prescribed irradiation protocols were simulated using the mechanistic model. Logistic regression was then performed to predict recurrence i) directly from MRI features following a conventional radiomics approach, ii) from intermediate parameters and iii) from the number of tumor cells at t = 8 weeks output given by the mechanistic model. Significant improvement in prediction (p-value <= 0.0001) was achieved using the simulation-based marker (AUC = 0.85) compared to predictions based on the MRI features without and with oversampling (AUC = 0.77 and 0.80, respectively).

La radiothérapie en conditions stéréotaxiques peut être proposée comme traitement de rattrapage pour des récidives locales sélectionnées de cancer de prostate après une première irradiation. Si les résultats cliniques sont encourageants, l’expérience est encore limitée. Une question cruciale est en particulier le choix des contraintes dose–volume appropriées lors de la planification. Le premier objectif de cette étude dosimétrique était de quantifier la proportion de patients respectant effectivement les contraintes dose–volume définies selon l’essai du Gétug-31, testant le schéma de dose 36 Gy en six fractions. Le deuxième objectif était d’expliquer pourquoi ces contraintes ne pouvaient potentiellement pas être respectées. Le dernier objectif était de proposer des contraintes dose–volume plus adaptées. Les dossiers de 141 patients, pris en charge entre 2011 et 2020 dans deux centres français experts par réirradiation stéréotaxique prostatique avec CyberKnife®, ont été analysés rétrospectivement. Le schéma de dose de 36 Gy en six fractions était prescrit. Les contraintes dose–volume à respecter selon le Gétug-31 étaient les suivantes : V95 % ≥ 95 % pour le volume cible prévisionnel, V12Gy < 20 % et V27Gy < 2 cm3 pour la paroi rectale, V12Gy < 15 % et V27Gy < 5 cm3 pour la paroi vésicale, et Dmax(35 mm3) < 39 Gy et V24Gy < 30 % pour l’urètre + 3 mm. Le pourcentage de patients ne respectant pas les contraintes dose–volume a été quantifié. Des corrélations entre les contraintes dose–volume et les volumes des différentes structures ont été recherchées. De nouvelles contraintes dose–volume ont été finalement proposées permettant d’être suivies plus largement (à plus de 85 %). Le pourcentage de patients respectant toutes les contraintes dose–volume n’était que de 19 %. Ces patients avaient un volume cible prévisionnel moyen de 18,5 cm3, alors qu’il était de 40,5 cm3 dans toute la série. Un pourcentage de 98 % des patients ayant un ratio contraintes dose–volume/prostate supérieur à 0,5 ne pouvaient pas respecter les contraintes dose–volume dans les organes à risque. La couverture du volume cible et l’épargne des organes à risque diminuaient significativement avec l’augmentation du volume cible prévisionnel, du volume cible anatomoclinique, du ratio volume cible anatomoclinique/prostate, des volumes d’intersection entre le volume cible prévisionnel et la paroi vésicale et entre le volume cible prévisionnel et la paroi rectale. Des valeurs seuils de volume cible prévisionnel inférieures à 20 cm3 et 40 cm3 permettaient de respecter respectivement la couverture dans le volume cible prévisionnel et les contraintes de dose dans la paroi vésicale. Afin d’améliorer le respect des contraintes dose–volume en cas de volume cible important, les paramètres suivants ont été identifiés pour les organes à risque : V12Gy < 25 % et V27Gy < 2 cm3 pour la paroi rectale, et V12G < 25 % et V27Gy < 5 cm3 pour la paroi vésicale. En cas de réirradiation prostatique à une dose de 36 Gy, les contraintes dose–volume du Gétug-31 semblent réalisables uniquement pour de petits volumes cibles (volume cible anatomoclinique inférieur à la moitié de la prostate). Dans le cas où le volume cible est trop important, de nouvelles contraintes ont été proposées. L’autre alternative, dans cette situation, est de s’orienter vers d’autres techniques de rattrapage.

Dose escalated chemoradiotherapy delivering 66Gy is not more toxic than 50Gy but did not improve locoregional progression-free survival. Chemoradiotherapy delivering 50Gy should be definitely admitted as a standard dose.

Hepatocellular carcinoma (HCC) is the sixth more frequent cancer worldwide. This type of cancer has a poor overall survival rate mainly due to underlying cirrhosis and risk of recurrence outside the treated lesion. Quantitative imaging within a radiomics workflow may help assessing the probability of survival and potentially may allow tailoring personalized treatments. In radiomics a large amount of features can be extracted, which may be correlated across a population and very often can be surrogates of the same physiopathology. This issues are more pronounced and difficult to tackle with imbalanced data. Feature selection strategies are therefore required to extract the most informative with the increased predictive capabilities. In this paper, we compared different unsupervised and supervised strategies for feature selection in presence of imbalanced data and optimize them within a machine learning framework. Multi-parametric Magnetic Resonance Images from 81 individuals (19 deceased) treated with stereotactic body radiation therapy (SBRT) for inoperable (HCC) were analyzed. Pre-selection of a reduced set of features based on Affinity Propagation clustering (non supervised) achieved a significant improvement in AUC compared to other approaches with and without feature pre-selection. By including the synthetic minority over-sampling technique (SMOTE) for imbalanced data and Random Forest classification this workflow emerges as an appealing feature selection strategy for survival prediction within radiomics studies.

published or not.The documents may come from teaching and research institutions in France or abroad, or from public or private research centers.L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.How to find the best radiomics features for prediction of overall survival in SBRT for HCC?

Radiomics refers to the quantification of images by the extraction and analysis of a large number of features from different modalities, aiming to establish potential links between them and disease phenotypes. It can potentially predict the free-disease survival or allow the selection of patients at risk, thereby leading to the development of more personalized treatments. The development of robust prediction models is cumbersome as we deal with a high multidimensional problem, where a high number of features can be available but with a low number of individuals. To cope with this problem, we propose in this paper the use of Multiple Kernel Learning (MKL), which allows a selection of more relevant features and its optimal combination in a classification model. The method was evaluated on a dataset of patients of prostate cancer treated with radiotherapy, which is the second most prevalent cancer in men worldwide, for whom we predicted the risk of recurrence. MKL allowed the selection of 7 features out of 98 to build a reliable model with an accuracy of 94.7%, Sensitivity of 75%, and specificity of 97.78%. Compared to other classification methods, MKL achieved significantly higher performance, emerging like a suited methodology within radiomic studies.

Adaptive radiotherapy (ART) is a complexe image-guided radiotherapy modality that comprises multiple planning to account for anatomical variations occurring during irradiation. Schematically, two strategies of RTA can be distinguished and combined according to tumor locations. One or more replanning can be proposed to correct systematic variations such as tumor shrinkage. A library of treatment plans with day-to-day plan selection from cone-beam CT imaging can also be proposed to correct random variations such as uterine motion or bladder/rectum volume changes. Because of strong anatomical variations occurring during irradiation, RTA appears therefore particularly justified in head and neck, lung, bladder, cervical and rectum and pancreas tumors, and to a lesser extent for prostate tumors and other digestive tumors. For these tumor locations, ART provides a fairly clear dosimetric benefit but a clinical benefit not yet formally demonstrated. ART cannot be proposed in a routine practice but must be evaluated medico-economically in the context of prospective trials. A rigorous quality control must be associated.

Purpose. - Literature review reporting results of salvage brachytherapy and stereotactic body radiotherapy for prostate recurrence only after radiotherapy for prostate cancer. Materials and methods. - A total of 38 studies (including at least 15 patients per study) were analysed: 19 using low-dose-rate brachytherapy, nine high-dose-rate brachytherapy and ten stereotactic body radiotherapy. Only five studies were prospective. The median numbers of patients were 30 for low-doserate brachytherapy, 34 for high-dose-rate brachytherapy, and 30 for stereotactic body radiotherapy. The median follow-up were 47 months for low-dose-rate brachytherapy, 36 months for high-dose-rate brachytherapy and 21 months for stereotactic body radiotherapy. Results. - Late genitourinary toxicity rates ranged, for grade 2: from 4 to 42% for low-dose-rate brachytherapy, from 7 to 54% for high-dose-rate brachytherapy and from 3 to 20% for stereotactic body radiotherapy, and for grade 3 or above: from 0 to 24% for low-dose-rate brachytherapy, from 0 to 13% for high-dose-rate brachytherapy and from 0 to 3% for grade 3 or above (except 12% in one study) for stereotactic body radiotherapy. Late gastrointestinal toxicity rates ranged, for grade 2: from 0 to 6% for low-doserate brachytherapy, from 0 to 14% for high-dose-rate brachytherapy and from 0 to 11% for stereotactic body radiotherapy, and for grade 3 or above: from 0 to 6% for low-dose-rate brachytherapy, and from 0 to 1% for high-dose-rate brachytherapy and stereotactic body radiotherapy. The 5-year biochemical disease-free survival rates ranged from 20 to 77% for low-dose-rate brachytherapy and from 51 to 68% for high-dose-rate brachytherapy. The 2- and 3-year disease-free survival rates ranged from 40 to 82% for stereotactic body radiotherapy. Prognostic factors of biochemical recurrence have been identified. Conclusion. - Despite a lack of prospective data, salvage reirradiation for prostate cancer recurrence can be proposed to highly selected patients and tumours. Prospective comparative studies are needed. (C) 2019 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.

La radiothérapie adaptative est une modalité de radiothérapie guidée par l’image avancée intégrant plusieurs planifications pour prendre en compte les variations anatomiques survenant en cours d’irradiation. Schématiquement, deux stratégies de radiothérapie adaptative peuvent être distinguées et combinées selon les localisations tumorales. Une ou plusieurs nouvelles planifications peuvent être proposées pour corriger les variations systématiques telles qu‘une fonte tumorale. Une librairie de plans de traitement avec sélection du plan du jour à partir d’une imagerie d’avant le traitement peut par ailleurs être proposée pour corriger les variations aléatoires telles que les bascules de l’utérus ou les variations de volumes de vessie et/ou de rectum. Du fait de fortes variations anatomiques en cours d’irradiation, la radiothérapie adaptative apparaît ainsi particulièrement justifiée pour les tumeurs de la sphère ORL, bronchiques, de la vessie, du col utérin, du rectum, du pancréas, et dans une moindre mesure pour les tumeurs de la prostate et d’autres tumeurs digestives. Pour ces localisations, la radiothérapie adaptative apporte un bénéfice dosimétrique clairement quantifié mais un bénéfice clinique non encore formellement démontré. De ce fait, la radiothérapie adaptative ne peut être proposée dans une pratique de routine clinique mais doit être évaluée sur le plan médicoéconomique dans le cadre d’essais prospectifs. Un contrôle qualité rigoureux doit y être associé.