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Objective: Brachytherapy of the vaginal dome is the recommended adjuvant treatment for intermediate-risk endometrial cancer. This study assessed the results of dosimetric planning of high-dose-rate brachytherapy exclusively in the first treatment session., Study Design: This retrospective study included all patients who underwent hysterectomy for endometrial cancer followed by adjuvant brachytherapy of the vaginal dome between 2012 and 2015. Local recurrence rates, overall survival (OS) rates, recurrence-free survival (RFS) rates, and related acute and late toxicity rates were evaluated., Results: This analysis included 250 patients, of whom 208 were considered to be at high-intermediate risk of disease recurrence. After a median follow-up of 56 months, the cumulative incidence of local recurrence was 4.8% at 3 years [95% confidence interval (CI) 2.8-8.3] and 7.8% at 5 years (95% CI 4.8-12.6). The 5-year OS rate was 86.2% (95% CI 80.6-90.3), and the 5-year RFS rate was 77.5% (95% CI 71.1-82.7). Acute toxicity occurred in 20 (8%) patients, of which two patients had grade ≥3 toxicity. Only one patient (0.4%) presented with late grade ≥3 toxicity., Conclusion: These findings confirm the tolerability of this brachytherapy approach, indicating minimal cases of late grade ≥3 toxicity, associated with a good 5-year OS rate. With the advent of molecular prognostic factors, the current focus revolves around discerning those individuals who gain the greatest benefit from adjuvant therapy, and tailoring treatment more effectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background and Purpose: Stereotactic radiotherapy potentially treats unresectable recurrences of previously irradiated head and neck (H&N) cancer. This study aimed to assess its efficacy and safety and evaluate prognostic factors., Materials and Methods: We conducted a large retrospective series that included 110 patients who had undergone 36-Gy, six-fraction stereotactic reirradiation (CyberKnife®) for recurrent/secondary H&N cancer between 2007 and 2020 at the Oscar Lambret Center. Patient characteristics and toxicities were assessed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method., Results: Median follow-up time was 106.3 months. The 2-year OS rate was 43.8 % (95 % confidence interval, 95 % CI, 34.3-52.9) and the median survival was 20.8 months (95 % CI, 16.5-26.3). The cumulative 2-year local-recurrence, regional-recurrence, and distant-metastasis rates were 52.2 % (95 % CI, 42.4-61.1 %), 12.8 % (95 % CI, 7.4-19.8 %), and 11 % (95 % CI, 6.0-17.6 %), respectively. 73 patients received concomitant cetuximab, and it was not significantly beneficial (HR = 1.34; 95 % CI, 0.80-2.26; p = 0.26). The cumulative incidences of grade ≥ 2 late toxicity was 42 % (CI95%: 33-51) at 24 months. Two grade 4 bleedings and no treatment-related deaths were reported., Conclusion: In a large retrospective series of SBRT reirradiation for recurrent or second primary H&N cancers, we observed a median OS of 20.8 months, with a cumulative incidence of grade ≥ 2 late toxicity of 42 % at 24 months. Such a treatment is feasible. However, local recurrence rates remain non-negligible, warranting further research. Radiosensitizer use is currently under study. Therefore, establishing a balance between therapeutic modifications and toxicity is essential., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Purpose: Standard treatment of squamous cell carcinoma of the anus (SCCA)is 5-fluorouracil (5FU) and mitomycin C (MMC) based chemoradiotherapy (CRT). This phase II study (EudraCT: 2011-005436-26) assessed the tolerance and complete response (CR) rate at 8 weeks of panitumumab (Pmab) combined with MMC-5FU-based CRT., Methods: Patients with locally advanced tumors without metastases (T2 > 3 cm, T3-T4, or N + whatever T stage) were treated with IMRT up to 65 Gy and concomitant CT according to the doses defined by a previous phase I study (MMC: 10 mg/m 2 ; 5FU: 400 mg/m 2 ; Pmab: 3 mg/kg). The expected CR rate was 80%., Results: Forty-five patients (male: 9, female: 36; median age: 60.1 [41.5-81]) were enrolled in 15 French centers. The most common related grade 3-4 toxicities observed were digestive (51.1%), hematologic (lymphopenia: 73.4%; neutropenia: 11.1%), radiation dermatitis (13.3%), and asthenia (11.1%) with RT interruption in 14 patients. One patient died because of mesenteric ischemia during the CRT, possibly related to treatment. In ITT analysis, the CR rate at 8 weeks after CRT was 66.7% [90%CI: 53.4-78.2]. Median follow-up was 43.6 months [IC 95%: 38.61-47.01]. Overall survival, recurrence-free and colostomy-free survival at 3 years were 80% [95%CI: 65.1-89], 62.2% [IC95%: 46.5-74.6] and 68.8 % [IC95%: 53.1-80.2] respectively., Conclusion: Panitumumab in combination with CRT for locally advanced SCCA failed to meet the expected CR rate and exhibited a poor tolerance. Furthermore, late RFS, CFS, and OS did not suggest any outcome improvement to justify further clinical trials., Clinicaltrials: gov identifier: NCT01581840., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Several molecules are being investigated for their ability to enhance the anti-tumor effect of radiotherapy. The widely prescribed antidiabetic drug metformin has been suggested to possess anti-cancer activity; data indicate that metformin could also enhance radiation sensitivity. The purpose of this review is to summarize current knowledge on the specific effect of metformin in the field of RT, while also discussing the many unknowns that persist. Preclinical models point to multiple mechanisms involved in the radiosensitizing effects of metformin that are mainly linked to mitochondrial complex I inhibition and AMP-activated protein kinase. Transposition of results from bench to bedside will be discussed through the lens of the drug concentration, its potential limits in human settings, and possible alternatives. Clinical data suggest metformin improves progression-free and overall survival in patients for many different cancers treated with RT; nevertheless, the results are not always consistent. The main limitations of the reviewed literature are the retrospective nature of studies, and most of the time, a lack of information on MTF treatment duration and the administered dosages. Despite these limitations, the possible mechanisms of the role of metformin and its utility in enhancing radiotherapy treatments are analyzed. Ongoing clinical trials are also discussed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: Standard treatment of epidermoid anal cancer is 5-fluorouracil (5FU) and mitomycin C (MMC) based chemoradiotherapy (CRT). This phase I study aims to evaluate the addition of panitumumab (Pmab) to CRT and to determine the maximum tolerated dose (MTD) of Pmab and 5-FU in combination with CRT., Materials and Methods: Immunocompetent patients with locally advanced tumour without metastases (Stage T2, T3 or T4, whatever N stage; Stage N1-N3 whatever T stage) followed two RT periods (45 Gy in 5 weeks and 20 Gy in 2 weeks, separated by a 2-week break) with concomitant CT sessions of 5FU/MMC at RT weeks 1, 5 and 8. Pmab was administered on RT weeks 1, 3, 5, 8 and 10 according to a predefined dose escalation schedule., Results: Ten patients were enroled. One was excluded due to unmet dose constraints respect. Three patients received dose level (DL) 0 (Pmab 3 mg/kg + 5FU 600 mg/m 2 /day) and six received DL-1 (Pmab 3 mg/kg + 5FU 400 mg/m 2 /day). Dose-limiting toxicities occurred in all patients at DL 0 and 2 at DL-1. Most common grade 3-4 toxicities observed at DL 0 were haematologic (100%), dermatitis (67%), and anaemia (67%). No death occurred. Four months after ending CRT, five and two patients had a local complete response and a partial response, respectively. One patient had a colostomy with abdomino-perineal amputation due to a tumour recurrence., Conclusions: The MTD is 5FU at 400 mg/m 2 /day, MMC at 10 mg/m 2 and Pmab at 3 mg/kg. The effect of the MTD on tumour response is evaluated in the phase 2 study., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Purpose: Baseline contrast-enhanced computed tomography (CT)-derived texture analysis in locally advanced rectal cancer could help offer the best personalized treatment. The purpose of this study was to determine the value of baseline-CT texture analysis in the prediction of downstaging in patients with locally advanced rectal cancer., Patients and Methods: We retrospectively included all consecutive patients treated with neoadjuvant chemoradiation therapy (CRT) followed by surgery for locally advanced rectal cancer. Tumor texture analysis was performed on the baseline pre-CRT contrast-enhanced CT examination. Based on the selected model of downstaging with a penalized logistic regression in a training set, a radiomics score (Radscore) was calculated as a linear combination of selected features. A multivariable prognostic model that included Radscore and clinical factors was created., Results: Of the 121 patients included in the study, 109 patients (90%) had T3-T4 cancer and 99 (82%) had N+ cancer. A downstaging response was observed in 96 patients (79%). In the training set (79 patients), the best model (ELASTIC-NET method) reduced the 36 texture features to a combination of 6 features. The multivariate analysis retained the Radscore (odds ratio [OR] = 13.25; 95% confidence interval [95% CI], 4.06-71.64; p < 0.001) and age (OR = 1.10/1 year; 1.03-1.20; p = 0.008) as independent factors. In the test set, the area under the curve was estimated to be 0.70 (95% CI, 0.48-0.92)., Conclusion: This study presents a prognostic score for downstaging, from initial computed tomography-derived texture analysis in locally advanced rectal cancer, which may lead to a more personalized treatment for each patient., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: To carry out a prognosis study of the prospective studies KANAL 2 and ACCORD 03 in order to highlight new prognostic factors of colostomy-free survival in patients with locally advanced anal canal carcinoma., Patients and Methods: KANAL 2 and ACCORD 03 were phase 2 and phase 3 multicenter trials with same inclusion criteria: anal canal squamous cell carcinoma of ≥4 cm or pelvic node involvement treated with conformal radiotherapy (45 Gy/25 fractions plus a boost) and concomitant fluorouracyl and cisplatin at weeks 1 and 5. A multivariate analysis of potential factors (patients, tumors, and treatments) was carried out through Cox proportional hazard model. Results were presented as hazard ratio (HR)., Results: 387 patients were included. In multivariate analysis, age over 55 years (HR = 0.62, p = 0.013), the increase of circumferential tumor spread (between 1/3 and 2/3 and more than 2/3 compared to less than 1/3) (respectively 1.97, p = 0.015 and 2.94, p < 0.001), the skin ulceration (1.57, p = 0.03), the inguinal node involvement (1,98, p < 0.001) and the total radiotherapy dose above 60 Gy (between 60 and 65 Gy (HR = 0.37, p < 0.001) and >65 Gy (HR = 0.61, p = 0.028)) were associated with colostomy-free survival., Conclusion: Our study highlights new favorable prognostic factors such as circumferential tumor damage of less than two thirds, age over 55 years, dose escalation boost irradiation and possibly a total radiation dose between 60 and 65 Gy (but the BED dose depends on the overall treatment time). These results could be considered for better selection or stratification of the target population in future trials., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Purpose: The TRENDY trial is an international multi-center phase-II study, randomizing hepatocellular carcinoma (HCC) patients between transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) with a target dose of 48-54 Gy in six fractions. The radiotherapy quality assurance (QA) program, including prospective plan feedback based on automated treatment planning, is described and results are reported., Materials and Methods: Scans of a single patient were used as a benchmark case. Contours submitted by nine participating centers were compared with reference contours. The subsequent planning round was based on a single set of contours. A total of 20 plans from participating centers, including 12 from the benchmark case, 5 from a clinical pilot and 3 from the first study patients, were compared to automatically generated VMAT plans., Results: For the submitted liver contours, Dice Similarity Coefficients (DSC) with the reference delineation ranged from 0.925 to 0.954. For the GTV, the DSC varied between 0.721 and 0.876. For the 12 plans on the benchmark case, healthy liver normal-tissue complication probabilities (NTCPs) ranged from 0.2% to 22.2% with little correlation between NCTP and PTV-D95% (R 2  < 0.3). Four protocol deviations were detected in the set of 20 treatment plans. Comparison with co-planar autoVMAT QA plans revealed these were due to too high target dose and suboptimal planning. Overall, autoVMAT resulted in an average liver NTCP reduction of 2.2 percent point (range: 16.2 percent point to -1.8 percent point, p = 0.03), and lower doses to the healthy liver (p < 0.01) and gastrointestinal organs at risk (p < 0.001)., Conclusions: Delineation variation resulted in feedback to participating centers. Automated treatment planning can play an important role in clinical trials for prospective plan QA as suboptimal plans were detected., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Purposes: Early biomarkers of tumour response are needed to discriminate between responders and non-responders to radiotherapy. We evaluated the ability of ceramide, a bioactive sphingolipid, to predict tumour sensitivity in patients treated by hypofractionated stereotactic body radiation therapy (SBRT) combined with irinotecan chemotherapy., Materials and Methods: Plasma levels of total ceramide and of its subspecies were measured before and during treatment in 35 patients with liver and lung oligometastases of colorectal cancer included in a phase II trial. Cer levels were quantified by LC-ESI-MS/MS and compared to tumour volume response evaluated one year later by CT-scan., Results: Pretreatment plasma ceramide levels were not indicative of tumour response. Nevertheless, the levels of total ceramide and of its 4 main subspecies were significantly higher at days 3 and 10 of treatment in objective responders than in non-responders. According to Kaplan-Meier curves, almost complete tumour control was achieved at 1year in patients with increased total ceramide levels whereas 50% of patients with decreased levels experienced an increase in tumour volume., Conclusions: Total plasma ceramide is a promising biomarker of tumour response to SBRT combined with irinotecan that should enable to segregate patients with high risk of tumour escape., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

The relatively recent introduction of CyberKnife® in the field of radiotherapy has prompted the question of accessibility and usefulness of this technique for seniors. From June 2007 to June 2009, we treated 345 patients of all ages with CyberKnife as part of a single-center study. Median age was 61 years (range, 8-86 years). Ninety-eight patients were over 70 and 17 were older than 80. The treatment could not be completed with 2% (2/98) patients over 70 vs. 3.6% (9/247) among the younger (ns). Physiologic or psychologic problems in maintaining position for a long time were not more frequent among those over 70. The same was true with those over 80. Patients over 70 years old are able to tolerate CyberKnife treatment as efficiently as their younger counterparts. Elderly patients should not be restricted from access to CyberKnife radiosurgery with curative intent., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: The aim of this study was to prospectively assess the quality of life (QOL) of patients treated by concomitant chemo radiation for locally advanced anal canal carcinoma., Materials and Methods: We report on a subgroup of 119 patients enrolled in a 306-patient therapeutic intensification prospective trial (ACCORD 03). This trial evaluated the impact on colostomy-free survival of induction chemotherapy and/or high dose radiotherapy (factorial design 2 *2 treatment arms). QOL was assessed both before and 2 months after treatment using the EORTC QLQ-C30 questionnaire as well as a questionnaire relating to anal sphincter conservative treatment (AS-CT)., Results: Compared to pre-treatment scores, patients reported significant improvement in their emotional function (+8.4 points p=0.002), global health status (+5.9 points p=0.0007), as well as a decrease in insomnia (-13.8 points p<0.0001), constipation (-12.0 points p<0.0001), appetite loss (-10.3 points p<0.0001) and pain (-9.6 points p=0.0002). The AS-CT degree of satisfaction with intestinal functions score was increased (+11.2 points p<0.0001)., Conclusion: This is the first prospective study comparing QOL of patients with advanced anal canal carcinoma, before and 2 months after conservative treatment. Two months after treatment, QOL was improved. Induction chemotherapy and/or high dose radiotherapy did not provide a negative impact on QOL.

Between 1979 and 1990, 149 patients with non-metastatic thymomas were treated in ten French cancer centers. Patients were staged according to the 'GETT' classification, derived from that of Masaoka. There were 13 stage I patients, 46 stage II, 58 stage III and 32 stage IVA. Gross total resections were performed in 63 cases, subtotal resections in 31 cases and in 55 cases a biopsy alone was performed. All patients received radiotherapy and 74 were given post-operative chemotherapy. Median follow-up was 7.7 years. Local control was achieved in 117 cases (78.5%) and was influenced by the stage of the disease (p < 0.01) and the extent of surgery (p < 0.01). Twenty-six patients developed metastatis after a median period of 9 months. Five- and ten-year disease-free survival rates were 59.5% (51-67%) and 49.5% (39-60%), respectively, and were influenced by the stage of the disease (p < 0.01), the extent of surgery (p < 0.001) and a mediastinal compression on presentation (p = 5 x 10(-6)). Four factors could predict a worse overall survival in the multivariate analysis: mediastinal compression on presentation (p < 0.001), absence of chemotherapy (p < 0.001), biopsy alone (p = 0.003), and young age (p = 0.013). A worse DFS was predicted by mediastinal compression on presentation (p < 0.001), absence of chemotherapy (p < 0.001), young age (p = 0.006), and stages III-IVA (p = 0.04). Future therapeutic strategies are discussed and the literature is reviewed.