Evaluating the feasibility and acceptability of an adapted fencing intervention in breast cancer surgery post-operative care: the RIPOSTE pilot randomized trial.

Background: Adapted physical activity programs have shown promising results in reducing the physical, social and psychological side effects associated with breast cancer, but the extent to which they can be effectively adopted, implemented and maintained is unclear. The aim of this study is to use the framework to guide the planning and evaluation of programs according to the 5 following keys: Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework to evaluate a fencing program under the French acronym RIPOSTE (Reconstruction, Image de soi, Posture, Oncologie, Santé, Thérapie, Escrime) literally in English (Reconstruction, Self-Image, Posture, Oncology, Health, Therapy, Fencing). This program is an innovative intervention focused on improving the quality of life (QoL) of breast cancer surgery patients through fencing. Methods: A convergent mixed methods pilot study was conducted to preliminary evaluate the different RE-AIM dimension of the pilot program. Twenty-four participants who have just undergone surgery for invasive breast cancer were randomly allocated in two groups: one group started immediately after their inclusion (Early RIPOSTE group) and the other started 3 months following their inclusion (Delayed RIPOSTE group). Participants answered a questionnaire at inclusion and at the end of the program on QoL, shoulder functional capacity, fatigue, anxiety-depression and physical activity. Results: RIPOSTE program was able to reach mainly young and dynamic participants, attracted by the originality of fencing and keen to improve their physical condition. Regarding effectiveness, our results suggest a trend to the improvement of QoL, shoulder functional capacity, fatigue and anxiety-depression state, even without any significant differences between the Early RIPOSTE group and the Delayed RIPOSTE group. Discussions: The cooperation, exchanges and cohesion within the group greatly facilitated the adoption of the program, whereas interruptions during school vacations were the main barriers. The intervention was moderately well implemented and adherence to the protocol was suitable. Conclusion: RIPOSTE is an acceptable and effective program for involving breast cancer survivors in physical activity, that needs to be tested at a larger scale to investigate its effectiveness, but has the potential to be transferred and scaled up worldwide.

Adjuvant pulse-dose-rate brachytherapy for oral cavity and oropharynx carcinoma: Outcome and toxicity assessment of 66 patients.

Purpose: Brachytherapy (BT) is a validated radiation technique for treatment of early stage tumors of oral cavity and oropharynx. This study aimed to analyze the results of our institute's patients after replacing low-dose-rate (LDR) with pulse-dose-rate (PDR) brachytherapy. Material and methods: We retrospectively collected data from all patients treated between 2009 and 2020 for squamous cell carcinoma (floor of the mouth, tongue, and oropharynx) using adjuvant interstitial BT with or without external RT. Primary outcome was local control. Secondary outcomes were regional control rate and toxicity. Statistical analysis of local and regional recurrences were described using Kaplan-Meier method. Prognostic value of each factor for recurrence or toxicity was evaluated with bivariate Fine-Gray model. Results: Data from 66 patients were analyzed. Local and regional recurrences were reported in 11% and 20% of the patients, respectively. No significant factors were identified in the present study. Grade 2 and 3 acute mucositis were reported in 21% of patients, and were more frequent in the BT only group. Almost half (47%) of the patients described acute pain following BT, and 26% required stage 2 or 3 analgesics. Trophic disorders were observed in 16 patients. Five patients presented with soft tissue necrosis (STN) and required medical treatment, of whom one subsequently required hyperbaric oxygen therapy. No predictive factors were identified for STN risk. Two patients developed osteoradionecrosis. Conclusions: Oral and oropharyngeal PDR-BT as adjuvant treatment is safe and effective for well-defined indications.

Brachytherapy for favorable prognostic prostate cancer in men up to 60 years of age: Long term follow-up.

PURPOSE: Brachytherapy (BT) is a standard treatment for low- and favorable intermediate-risk prostate adenocarcinoma. Few studies have focused on young patients. We therefore evaluated long-term efficacy and toxicity of BT in patients aged ≤ 60 years with low- and favorable intermediate-risk prostate cancer. MATERIALS AND METHODS: This retrospective study included patients aged ≤60 years with low- or favorable intermediate-risk prostate adenocarcinoma treated with iodine BT alone between 1999 and 2014 at the Institut de Cancérologie de Lorraine. Follow-up assessment included incidence of biochemical failure (BF) at 10 and 15 years after BT, as well as survival data and late toxicities. RESULTS: A total of 177 patients of median age 56 years (54-58) were analyzed, with a median follow-up of 126 months (97-172). Incidence of BF at 10 and 15 years after BT was 5.4% and 11.7% respectively. PSA nadir (HR = 51.8 [95% CI 6.69-277], p < 0.001), age at treatment (HR = 1.78 [95% CI 1.19-2.65], p = 0.005) and prostate D90% (HR = 1.08 [95% CI 1.01-1.15], p < 0.021) were identified as predictive factors of BF. Overall survival at 10 and 15 years after BT was 92.8% and 84.4% respectively. Cancer-specific survival at 10 and 15 years after BT was 99.3% and 97.7% respectively. No major toxicity was recorded. CONCLUSIONS: Exclusive BT is a long-term effective treatment for patients aged ≤ 60 years with low- or favorable intermediate-risk prostate adenocarcinoma.

Association between baseline hemodynamic indices, cardiotoxicity risk, and survival in women with breast cancer.

BACKGROUND: The outcome of breast cancer (BrCa) women monitored by low-dose equilibrium radionuclide angiography (ERNA) remains challenging to predict. AIM: This study aims to determine whether heart rate (HR)/blood pressure (BP) ratio-based indexes, previously confirmed to predict outcomes of various diseases, also predict BrCa-therapy-related cardiotoxicity and survival. METHODS: Predictors of cardiotoxicity and survival were determined among pre-therapy variables, including shock index ([SI HR/systolic BP) and age-adjusted SI (ASI), in a female BrCa cohort with normal baseline ERNA-left ventricular ejection fraction (LVEF). RESULTS: We included 274 women with a median age of 54.8 (interquartile range: 45.5-65.4) years, 271 treated with anthracyclines and 96 with trastuzumab. During a median follow-up of 25.9 (18.6-33.5) months, 31 women developed cardiotoxicity (LVEF: <50% and ≥10% drop from baseline), and 25 died. Baseline ASI was a multivariate predictor (p < 0.001) of (i) cardiotoxicity, in association with trastuzumab treatment (p = 0.010), and LV end-diastolic volume (p = 0.001) and (ii) survival, in association with metastasis (p < 0.001) and estimated glomerular filtration rate (p = 0.008). Cardiotoxicity poorly impacted survival (p = 0.064). The 36-month cardiotoxicity and mortality rates were markedly higher for patients in the upper half of baseline ASI values (ASI: >30 years min-1.mmHg-1, 16.5% and 20.7%, respectively) than in the lower half (7.6% and 4.5%, respectively, both p < 0.05). CONCLUSIONS: In BrCa women with normal baseline ERNA-LVEF, HR/BP ratio-based indexes unmask hemodynamic profiles associated with increased cardiotoxicity risk and decreased survival, highlighting the need for a comprehensive assessment of cardiac- and vascular-related risks in BrCa women monitored by ERNA. CONDENSED ABSTRACT: In a cohort of 274 women BrCa women who were monitored by ERNA for potentially cardiotoxic drugs (anthracyclines or trastuzumab) and who had no history of cardiac disease and a normal left ventricular ejection fraction before treatment, baseline indexes based on HR/BP ratios unmask hemodynamic profiles strongly associated with an increased risk of cardiotoxicity and subsequently decreased survival. Although further validations in other cohorts are needed, these findings highlight the need for a more comprehensive assessment of the cardiac- and vascular-related risk in BrCa women monitored by ERNA.

Prospective results for 5-year survival and toxicity of moderately hypofractionated radiotherapy with simultaneous integrated boost (SIB) in (very) high-risk prostate cancer.

Purpose: High-risk (HR) prostate cancer patients usually receive high-dose radiotherapy (RT) using a two-phase sequential technique, but data on a simultaneous integrated boost (SIB) technique are lacking. We prospectively evaluated the long-term results of urinary (GU) and digestive (GI) toxicity and survival data for high-dose RT using a SIB technique in HR and very high-risk (VHR) prostate cancer. Methods: Patients were treated using an SIB technique in 34 fractions, at a dose of 54.4 Gy to the pelvis and seminal vesicles and 74.8 Gy to the prostate, combined with 36 months of androgen-depriving therapy in a prospective multicenter study. Acute and late GU and GI toxicity data were collected. Overall survival (OS), biochemical-relapse-free survival (bRFS), loco-regional-relapse-free survival (LRRFS), metastasis-free-survival (MFS) and disease-free-survival (DFS) were assessed. Results: We recruited 114 patients. After a median follow-up of 62 months, very few patients experienced acute (M0-M3) (G3-4 GU = 3.7 %; G3-4 GI = 0.9 %) or late (M6-M60) severe toxicity (G3-4 GU = 5.6 %; G3-4 GI = 2.8 %). The occurrence of acute G2 + GU or GI toxicity was significantly related to the consequential late G2 + toxicity (p < 0.01 for both GU and GI). Medians of OS, bRFS, LRRFS, MFS and DFS were not reached. At 60 months, OS, bRFS, LRRFS, MFS and DFS were 88.2 % [82.1; 94.7], 86.0 % [79.4 %;93.2 %], 95.8 % [91.8 %;99.9 %], 87.2 % [80.9 %;94.0 %] and 84.1 % [77.2 %;91.6 %] respectively. Conclusion: SIB RT at a dose of 54.4 Gy to the pelvis and 74.8 Gy to the prostate is feasible, leading to satisfying tumor control and reasonable toxicity in HR and VHR prostate cancer.

CyberKnife® stereotactic radiation therapy for stage I lung cancer and pulmonary oligometastases: is fiducial implantation still relevant?-a cohort study.

Background: Few studies have investigated whether there is a difference in local control or overall survival rates following treatment with robotic stereotactic body radiation therapy (SBRT) with or without prior fiducial marker implantation. Our study aimed to investigate this in patients with primary or secondary lung tumors. Methods: A retrospective study was conducted at the Institut de Cancérologie de Lorraine of patients treated for primary lung cancer or pulmonary oligometastases with SBRT from January 2013 to July 2016. We included patients at least 18 years old who had stage I non-small cell lung cancer (NSCLC) or lung metastases and a follow-up of at least 1 month. Results: A total of 294 patients were included. Tumors included 122 lung metastases, 89 stage I NSCLC, and 83 non-histologically confirmed lung lesions. The tracking methods were Synchrony® in 191 cases (119 gold seeds and 72 coils) and Xsight® Spine with 4D computed tomography in 103 cases. Median follow-up was 31.6 months [interquartile range (IQR), 18.1-50.2 months]. The two- and five-year probability of local control were respectively 92.22% [95% confidence interval (CI): 0.89-0.95] and 85.35% (95% CI: 0.79-0.99). The two- and five-year probability of overall survival were respectively 87.46% and 72.77% (P=0.586). Local control rates did not significantly differ between techniques at 2 and 5 years (P=0.685) (gold seeds, coils or Xsight® Spine) within tumors grouped by location, gross tumor volume (GTV) (respectively P=0.9, P=0.7, and P=0.4), planning target volume (PTV) (respectively P=0.4, P=0.9, and P=0.7), or PTV/GTV ratio (respectively P=0.6, P=0.6, and P=0.5). Metastasis-free survival and Overall survival rates did not significantly differ between techniques at 2 and 5 years (P=0.664 and P=0.586, respectively). There were no grade 4 or 5 toxicities and only one grade 3 pneumonitis and one grade 3 pneumothorax. Conclusions: Fiducial-less SBRT using Xsight® Spine is a safe alternative to Synchrony® using gold seeds or coils, with comparable local control and overall survival rates and a similar toxicity profile.

A Multicenter Phase 2 Study of Ultrahypofractionated Stereotactic Boost After External Beam Radiotherapy in Intermediate-risk Prostate Carcinoma: A Very Long-term Analysis of the CKNO-PRO Trial.

Background: Genitourinary (GU) or gastrointestinal (GI) complications and tumor relapse can occur in the long term after radiotherapy for prostate cancer. Objective: To assess the late tolerance and relapse-free survival (RFS) in patients undergoing hypofractionated stereotactic boost therapy after external beam radiotherapy (EBRT) for intermediate-risk prostate cancer. Design setting and participants: Seventy-six patients with intermediate-risk prostate carcinoma between August 2010 and April 2013 were included. The first course delivered a dose of 46 Gy by conventional fractionation; the second course was a boost of 18 Gy (3 × 6 Gy) within 10 d. Outcome measurements and statistical analysis: GU and GI toxicities were evaluated as the primary outcomes. The secondary outcomes were overall survival and RFS. The cumulative incidence of toxicity was calculated using a competing-risk approach. Overall survival and RFS were estimated using the Kaplan-Meier method. Results and limitations: The median follow-up period was 88 mo (range, 81-99 mo). Sixty (79%) patients were treated with the CyberKnife and 16 (21%) using a linear accelerator. The cumulative incidences of GU and GI grade ≥2 toxicities at 120 mo were 1.4% (95% confidence interval [CI]: 0.1-6.6%) and 11.0% (95% CI: 5.1-19.4%), respectively. The overall survival and RFS rates at 8 yr were 89.1% (95% CI: 77-95%) and 76.9% (95% CI: 63.1-86.1), respectively. Conclusions: A very long follow-up showed low GU and GI toxicities after a hypofractionated stereotactic boost after EBRT for intermediate-risk prostate cancer. Dose escalation of the boost delivered by hypofractionated radiation therapy appears safe for use in future trials. Patient summary: We found low toxicity and good survival rates after a short and high-precision boost after external beam radiotherapy for intermediate-risk prostate cancer, with a long-term follow-up of 88 mo. This long-term treatment is safe and should be considered in future trials.

Prognostic factors of local control and progression-free survival in AJCC stages T1 and T2 cervical cancer patients treated with adjuvant brachytherapy after chemoradiotherapy.

Purpose: We assessed prognostic factors of local control and progression-free survival (PFS) of patients treated for AJCC stages T1 and T2 cervical cancer using utero-vaginal brachytherapy after chemoradiotherapy. Material and methods: This retrospective single-institution analysis included patients who underwent brachytherapy after radiochemotherapy between 2005 and 2015 at the Institut de Cancérologie de Lorraine. Adjuvant hysterectomy was optional. A multivariate analysis of prognostic factors was carried out. Results: Of 218 patients, 81 (37.2%) were AJCC stage T1, and 137 (62.8%) were AJCC stage T2. 167 (76.6%) patients had squamous cell carcinoma, 97 (44.5%) patients had pelvic nodal disease, and 30 (13.8%) patients had para-aortic nodal disease. One hundred eighty-four patients (84.4%) underwent concomitant chemotherapy, while adjuvant surgery was performed in 91 patients (41.9%) and 42 (46.2%) patients had pathological complete response. Median follow-up was 4.2 years, and local control was reported in 87.8% (95% CI: 83.0-91.8) and 87.2% (95% CI: 82.3-91.3) of patients at 2 and 5 years, respectively. In multivariate analysis, T stage (hazard ratio [HR] = 3.65, 95% CI: 1.27-10.46, p = 0.016) was associated with local control. PFS was reported in 67.6% (95% CI: 60.9-73.4) and 57.4% (95% CI: 49.3-64.2) of patients at 2 and 5 years, respectively. In multivariate analysis, para-aortic nodal disease (HR = 2.03, 95% CI: 1.16-3.54, p = 0.012), pathological complete response (HR = 0.33, 95% CI: 0.15-0.73, p = 0.006), and intermediate-risk clinical tumor volume of > 60 cc (HR = 1.90, 95% CI: 1.22-2.98, p = 0.005) were associated with PFS. Conclusions: Lower dose brachytherapy may benefit AJCC stages T1 and T2 tumors, whereas higher doses are required for larger tumors and para-aortic nodal disease involvement, respectively. Pathological complete response should be associated with better local control and not surgery.

Treatment, outcome, and prognostic factors in non-metastatic anal cancer: The French nationwide cohort study FFCD-ANABASE.

INTRODUCTION: International guidelines regarding the treatment of squamous cell carcinoma of the anus (SCCA) recommend intensity-modulated radiotherapy (IMRT) combined with mitomycin-based chemotherapy (CT). The French FFCD-ANABASE cohort aimed at evaluating clinical practices, treatment, and outcomes of SCCA patients. METHODS: This prospective multicentric observational cohort included all non-metastatic SCCA patients treated in 60 French centers from January 2015 to April 2020. Patients and treatment characteristics, colostomy-free survival (CFS), disease-free survival (DFS), overall survival (OS), and prognostic factors were analyzed. RESULTS: Among 1015 patients (male: 24.4 %; female: 75.6 %; median age: 65 years), 43.3 %presented with early-stage(T1-2, N0) and 56.7 % with locally advanced stage (T3-4 or N + ) tumors. IMRT was used for 815 patients (80.3 %) and a concurrent CT was administered in 781 patients, consisting of mitomycin-based CT for 80 %. The median follow-up was 35.5 months. DFS, CFS, and OS at 3 years were 84.3 %, 85.6 %, and 91.7 % respectively in the early-stage group compared to 64.4 %, 66.9 %, and 78.2 % in the locally-advanced group (p < 0.001). In multivariate analyses, male gender, locally-advanced stage, and ECOG PS ≥ 1 were associated with poorer DFS, CFS, and OS. IMRT was significantly associated with a better CFS in the whole cohort and almost reached significance in the locally-advanced group. CONCLUSION: Treatment of SCCA patients showed good respect for current guidelines. Significant differences in outcomes advocate for personalized strategies by either de-escalation for early-stage tumors or treatment intensification for locally-advanced tumors.

Dosimetric predictive factors for facial nerve paralysis after cyberknife® stereotactic radiotherapy for vestibular schwannomas: A single institution experience of 88 patients.

PURPOSE: To identify dosimetric predictive factors of facial nerve paralysis for patients with vestibular schwannomas (VS) treated in a single institution with Cyberknife® (CK) hypofractionated stereotactic radiotherapy (SRT). METHODS AND MATERIALS: Eighty-eight patients were treated from 2010 to 2020. Different treatment schedules were used over that period, some prescribed to the 80% isodose line (4 × 5 Gy, 3 × 7 Gy, 3 × 8 Gy and 5 × 5 Gy) and one to the 70% isodose line (3 × 7.7 Gy). Local control tumor and facial nerve toxicity were recorded, as well as various dosimetric indicators. RESULTS: Median follow-up 37 months (range, 7-96). Of the 88 stereotactic treatments, 20 patients (23%) developed objectively diagnosed radiation-induced facial nerve paralysis. The 2-year and 5-year local tumor control were respectively 95% and 88%, and the overall 2-year facial nerve preservation was 76%. Prescriptions with a maximum dose point (Dmax) of 33 Gy were at a substantially higher risk of facial paralysis than prescriptions with a Dmax less than or equal to 30 Gy (HR = 4.51, 95% CI = [1.04;19.6], p = 0.045). The 2-years cumulative incidences of facial paralysis were 32% [20%;44%] in the case of a 33 Gy Dmax, against 7% [1%;21%] otherwise. We identified four significative dosimetric predictive factors for radiation-induced facial nerve dysfunction: a GTV minimal dose over 22 Gy (EQD2 = 45.5 Gy, p = 0.019), a GTV mean dose over 29 Gy (EQD2 = 73.5 Gy, HR = 2.84, 95% CI = [1.10;7.36], p = 0.024), a PTV mean dose over 27 Gy (EQD2 = 64.8 Gy, HR = 10.52, 95% CI = [1.39;79.76], p = 0.002) and a PTV maximal dose of 32 Gy (EQD2 = 87.5 Gy,HR = 5.09, 95% CI = [1.17;22.15], p = 0.013). CONCLUSION: We identified four dosimetric predictive factors for post-treatment facial paralysis. Increasing the doses of hypofractionated stereotactic radiotherapy for vestibular schwannomas leads to higher facial nerve toxicity and may lead to lower local control rates than other published series. Our three-hypofractionated regimens may have also played a role in these results.

The Safety and Efficacy of Salvage Stereotactic Radiation Therapy in Patients with Intraprostatic Tumor Recurrence After Previous External Radiation Therapy: Phase 1 Results from the GETUG-AFU 31 Study.

BACKGROUND: There is no consensus on the best local salvage treatment for prostate cancer recurrence after primary external beam radiotherapy. Prospective data on stereotactic body radiation therapy (SBRT) are very scarce. OBJECTIVE: To determine the optimal dose regimen for salvage SBRT. DESIGN, SETTING, AND PARTICIPANTS: The present report concerns the phase 1 part of the GETUG-AFU 31 multicenter open-label study. The main inclusion criteria were histologically proven biochemical recurrence, clinical stage T1-T2 upon relapse, multiparametric magnetic resonance imaging data, prostate-specific antigen (PSA) level ≤10 ng/ml prior to salvage SBRT, PSA doubling time >10 mo, and an International Prostate Symptom Score of ≤12. INTERVENTION: Five or six fractions of 6 Gy were delivered using focal SBRT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Dose-limiting toxicity (DLT) was defined as grade ≥3 gastrointestinal or genitourinary tract toxicity, or any grade 4 toxicity (according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03) occurring in the first 18 wk following treatment initiation. A time-to-event continual reassessment method was used to select the dose regimen. RESULTS AND LIMITATIONS: Twenty-one patients were treated (median [interquartile range] age: 76.8 yr [72.2-80.8]), including 12 at 6 × 6 dose level. No DLT was observed. The acute grade 2 genitourinary tract toxicity rate was 19%. With a median follow-up of 12.3 mo, the estimated cumulative incidence of late grade 2 genitourinary toxicity was 41.2% (95% confidence interval: 18.1-63.1%). No grade >2 genitourinary toxicity and no grade ≥2 gastrointestinal toxicity were reported. All treated patients were alive and relapse free at the last follow-up. CONCLUSIONS: A 6 × 6 Gy dose regimen was selected for our phase 2 study of salvage SBRT. With a short follow-up period, the level of toxicity appears to be acceptable. PATIENT SUMMARY: There is no consensus on the best local treatment for patients with local relapse after radiotherapy for prostate cancer. Prospective data are very scarce. Our early phase trial allowed us to recommend six fractions of 6 Gy using high-precision radiotherapy for further studies.

Outcomes following brachytherapy boost for intermediate- and high-risk prostate cancer: A retrospective bicenter study by the SFRO brachytherapy group.

INTRODUCTION: Radiotherapy dose escalation improves biochemical control in intermediate- or high-risk prostate cancer. Brachytherapy boost was shown to further improve biochemical control compared to radiotherapy alone in three randomized trials. The SFRO brachytherapy group sought to evaluate the efficacy and toxicity of BT-boost for intermediate and high-risk prostate cancer in real life, and to determine prognostic factors for efficacy and toxicity. MATERIAL AND METHOD: A retrospective study was conducted, including all patients with intermediate- or high-risk prostate cancer treated with a combination of external beam radiotherapy (EBRT) and high dose-rate brachytherapy boost (HDR-BB), from 2006 until December 2019 at two centers. Patient characteristics, initial disease, treatment and follow-up were collected. RESULTS: 709 patients from two centers were analyzed given a short follow-up in the other centers. Out of those, 277 were intermediate risk (170 favorable and 107 unfavorable) and 432 were high risk. The median EBRT and HDR-BB doses were 46 Gy (35-50) and 14 Gy (10-20). After a median follow-up of 62 months, biochemical control at 5 years was 87.5 % for the overall population, 91 % and 85 % for intermediate- and high-risk cancers, respectively. At 5 years, biochemical and clinical relapse-free survival, metastasis-free survival and local control rates were 83 %, 90 % and 97 % respectively. 5-years overall survival was 94 %. Late grade 2 or higher GU or GI toxicity was found in 36 patients (5 %) and 9 patients (1.3 %). CONCLUSION: This bicenter analysis shows the efficacy and tolerability of HDR-BB as a complement to external radiotherapy. Further improvements such as combination with new hormonal agents or new brachytherapy-radiotherapy fractionation regimens are warranted to improve further the outcomes and therapeutic ratio.

Acute skin toxicity of conventional fractionated versus hypofractionated radiotherapy in breast cancer patients receiving regional node irradiation: the real-life prospective multicenter HYPOBREAST cohort.

BACKGROUND: Large-scale trials have shown that hypofractionated adjuvant breast radiotherapy was as effective in terms of survival and local control as conventional fractionated radiotherapy, and acute toxicity was reduced with hypofractionated radiotherapy. However, there is a lack of data about the toxicity of breast with regional nodal irradiation (RNI). The aim of this study was to assess the effect of fractionation on radiation-related acute skin toxicity in patients receiving RNI in addition to whole-breast or chest wall irradiation, using real-life data. METHODS: We conducted a prospective, multicenter cohort study with systematic computerized data collection integrated into Mosaiq®. Three comprehensive cancer centers used a standardized form to prospectively collect patient characteristics, treatment characteristics and toxicity. RESULTS: Between November 2016 and January 2022, 1727 patients were assessed; 1419 (82.2%) and 308 (17.8%) patients respectively received conventional fractionated and hypofractionated radiation therapy. Overall, the incidence of acute grade 2 or higher dermatitis was 28.4% (490 patients). Incidence was lower with hypofractionated than with conventional fractioned radiation therapy (odds ratio (OR) 0.34 [0.29;0.41]). Two prognostic factors were found to increase the risk of acute dermatitis, namely 3D (vs IMRT) and breast irradiation (vs chest wall). CONCLUSION: Using real-life data from unselected patients with regional nodal irradiation, our findings confirm the decreased risk of dermatitis previously reported with hypofractionated radiation therapy in clinical trials. Expansion of systematic data collection systems to include additional centers as well as dosimetric data is warranted to further evaluate the short- and long-term effects of fractionation in real life.

Adapted Fencing for Patients With Invasive Breast Cancer: The RIPOSTE Pilot Randomized Controlled Trial.

Introduction: Even if indications for mastectomy have been progressively reduced in loco-regional breast cancer (BC) treatment, the harmful effects of surgery are still numerous and can impact physical and psychological wellbeing of women. The RIPOSTE (Reconstruction, self-Image, Posture, Oncology, "Santé"-Health, Therapy, "Escrime"-Fencing) program aimed to propose adapted fencing to patients with BC. This study aims to investigate the effect and conditions of effectiveness of the RIPOSTE program. Methods and analysis: This is a prospective randomized controlled trial including 24 patients with invasive BC who have just undergone surgery. The study will be proposed to the patient and if interested, the patient will be referred to a sports physician for a medico-sportive evaluation. At the end the evaluation, if the patient meets the inclusion criteria, she will be randomly assigned to one of the 2 groups based on a 1:1 principle: Early RIPOSTE group (receive one fencing session per week for 3 months immediately after their inclusion), Delayed RIPOSTE group (receive one fencing session per week for 3 months but within the 3 months following their inclusion). Patients will be included for 6 months with 3 follow-up times (0, 3, and 6 months) by a sport physician. The primary outcome is the evolution of quality of life score. Secondary outcomes are disability score, fatigue, anxiety-depression, cost-effectiveness and process evaluation. Ethics and dissemination: The study protocol has been approved by a French ethics committee (CPP Sud Méditerranée IV, N°ID-RCB: 2020-A01916-33). Results will be submitted for publication, at scientific conferences and through press releases. Trial Registration: NCT04627714.

Resident training in brachytherapy in France: A 10-year update after the first survey of SFJRO members.

Purpose: A previous survey conducted in 2012 showed that 82% of radiation oncology residents felt they were not receiving optimal brachytherapy training. With almost 10 years of hindsight, the aim was to update these results. Material and methods: An anonymized questionnaire based on the 2012 survey was submitted to the 161 French residents enrolled in the 2021 French Society of Young Radiation Oncologists (Société Française des Jeunes Radiothérapeutes Oncologues - SFJRO) national brachytherapy courses. Results: With a participation rate of 73%, 86% of the residents were interested in brachytherapy, but 80% consider their training in brachytherapy insufficient. 88% and 69% of the residents stated that they knew gynecological and prostate brachytherapy indications correctly, respectively. The residents have achieved proficiency in the technique of brachytherapy of vaginal vault in 36% (compared with 21% in 2012), utero-vaginal in 13% (12% in 2012), including 4% with interstitial implants, and prostate in only 4% (4% in 2012). In their brachytherapy internships, 18% of the residents declared having no role or an observational role. The main obstacles to training were the need to go to several centers to see several indications (85%), lack of brachytherapy activity in the center (72%), and the difficulty of freeing themselves from hospital duties (71%). Conclusions: With results globally stable compared with 2012, brachytherapy training needs improvement. In the absence of a mandatory internship in a reference center or dedicated fellowships, residents must have protected access to training sites by favoring inter-hospital exchanges.

OLIGOPELVIS GETUG P07, a Multicenter Phase II Trial of Combined High-dose Salvage Radiotherapy and Hormone Therapy in Oligorecurrent Pelvic Node Relapses in Prostate Cancer.

BACKGROUND: Oligorecurrent pelvic nodal relapse in prostatic cancer is a challenge for regional salvage treatments. Androgen depriving therapies (ADTs) are a mainstay in metastatic prostate cancer, and salvage pelvic radiotherapy may offer long ADT-free intervals for patients harboring regional nodal relapses. OBJECTIVE: To assess the efficacy of the combination of ADT and salvage radiotherapy in men with oligorecurrent pelvic node relapses of prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: We performed an open-label, phase II trial of combined high-dose intensity-modulated radiotherapy and ADT (6 mo) in oligorecurrent (five or fewer) pelvic node relapses in prostate cancer, detected by fluorocholine positron-emission tomography computed tomography imaging. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was 2-yr progression-free survival defined as two consecutive prostate-specific antigen levels above the level at inclusion and/or clinical evidence of progression as per RECIST 1.1 and/or death from any cause. RESULTS AND LIMITATIONS: Between August 2014 and July 2016, 67 patients were recruited in 15 centers. Half of the patients had received prior prostatic irradiation. The median age was 67.7 yr. After a median follow-up of 49.4 mo, 2- and 3-yr progression-free survival rates were 81% and 58%, respectively. Median progression-free survival was 45.3 mo. The median biochemical relapse-free survival (BRFS) was 25.9 mo. At 2 and 3 yr, the BRFS rates were 58% and 46%, respectively. Grade 2 + 2-yr genitourinary and gastrointestinal toxicities were 10% and 2%, respectively. CONCLUSIONS: Combined high-dose salvage pelvic radiotherapy and ADT appeared to prolong tumor control in oligorecurrent pelvic node relapses in prostate cancer with limited toxicity. After 3 yr, nearly half of patients were in complete remission. Our study showed initial evidence of benefit, but a randomized trial is required to confirm this result. PATIENT SUMMARY: In this report, we looked at the outcomes of combined high-dose salvage pelvic radiotherapy and 6-mo-long hormone therapy in oligorecurrent pelvic nodal relapse in prostatic cancer. We found that 46% of patients presenting with oligorecurrent pelvic node relapses in prostate cancer were in complete remission after 3 yr following combined treatment at the cost of limited toxicity.

Locoregional relapses in the ACCORD 12/0405-PRODIGE 02 study: Dosimetric study and risk factors.

PURPOSE: The aim of this study is to correlate locoregional relapse with radiation therapy volumes in patients with rectal cancer treated with neoadjuvant chemoradiation in the ACCORD 12/0405-PRODIGE 02 trial. PATIENTS AND METHODS: We identified patients who had a locoregional relapse included in ACCORD 12's database. We studied their clinical, radiological, and dosimetric data to analyze the dose received by the area of relapse. RESULTS: 39 patients (6.5%) presented 54 locoregional relapses. Most of the relapses were in-field (n = 21, 39%) or marginal (n = 13, 24%) with only six out-of-field (11%), 14 could not be evaluated. Most of them happened in the anastomosis, the perirectal space, and the usual lymphatic drainage areas (presacral and posterior lateral lymph nodes). Only patients treated for a lower rectum adenocarcinoma had a relapse outside of the treated volume. 2 patients with T4 tumors extending into anterior pelvic organs had relapses in anterior lateral and external iliac lymph nodes. CONCLUSIONS: Lowering the upper limit of the treatment field for low rectal tumors increased the risk of out of the field recurrence. For very low tumors, including the inguinal lymph nodes in the treated volume should be considered. Recording locoregional involvement, treated volumes, and relapse areas in future prospective trials would be of paramount interest to refine delineation guidelines.

A NGS-based Blood Test For the Diagnosis of Invasive HPV-associated Carcinomas with Extensive Viral Genomic Characterization.

PURPOSE: Use of circulating tumor DNA (ctDNA) for diagnosis is limited regarding the low number of target molecules in early-stage tumors. Human papillomavirus (HPV)-associated carcinomas represent a privileged model using circulating viral DNA (ctHPV DNA) as a tumor marker. However, the plurality of HPV genotypes represents a challenge. The next-generation sequencing (NGS)-based CaptHPV approach is able to characterize any HPV DNA sequence. To assess the ability of this method to establish the diagnosis of HPV-associated cancer via a blood sample, we analyzed ctHPV DNA in HPV-positive or HPV-negative carcinomas. EXPERIMENTAL DESIGN: Patients (135) from France and Senegal with carcinoma developed in the uterine cervix (74), oropharynx (25), oral cavity (19), anus (12), and vulva (5) were prospectively registered. Matched tumor tissue and blood samples (10 mL) were taken before treatment and independently analyzed using the CaptHPV method. RESULTS: HPV prevalence in tumors was 60.0% (81/135; 15 different genotypes). Viral analysis of plasmas compared with tumors was available for 134 patients. In the group of 80 patients with HPV-positive tumors, 77 were also positive in plasma (sensitivity 95.0%); in the group of 54 patients with HPV-negative tumors, one was positive in plasma (specificity 98.1%). In most cases, the complete HPV pattern observed in tumors could be established from the analysis of ctHPV DNA. CONCLUSIONS: In patients with carcinoma associated with any HPV genotype, a complete viral genome characterization can be obtained via the analysis of a standard blood sample. This should favor the development of noninvasive diagnostic tests providing the identification of personalized tumor markers. See related commentary by Rostami et al., p. 5158.

High-dose-rate brachytherapy for facial skin cancer: Outcome and toxicity assessment for 71 cases.

PURPOSE: In France, the reference technique for skin cancer was low-dose-rate brachytherapy (BT) delivered via iridium wire. At the end of their commercialization in 2015 we have replaced them by high-dose-rate (HDR) BT via interstitial catheters. We assessed efficacy and tolerance as soon as this technique was implemented. METHODS AND MATERIALS: Patients received 7 Gy on the first day, followed by 8 × 4 Gy over the next 4 days for exclusive BT and 9 × 4 Gy over 5 days for post-operative BT. RESULTS: Sixty-six patients of median age 81 years received a total of 58 primary BT and 13 post-operative BT for non-melanoma facial skin cancers. Implantation was without difficulty. Median follow up was 15.3 months. Two patients died of intercurrent diseases before first follow up. For the others, 98.5% showed complete response and 3% local recurrence after a median of 20.5 months. Four patients had grade 3 acute dermatitis and three patients had grade 3 mucositis. All the Grade 3 toxicities were resolved within 3 months. A late significant hypopigmentation occurred in 4 patients. CONCLUSIONS: HDR BT is efficient and well-tolerated with good cosmetic results. HDR catheters are similar with iridium wires in terms of technical difficulty.