Search

Background: The results of the PRODIGE 42/GERICO 12 study showed that short course radiotherapy had a better tolerance profile than radiochemotherapy, with comparable oncological results. We have included Quality of Life analyses and oncogeriatric evaluations in this study., Patients and Methods: In all, 101 patients ≥75 years of age with resectable T3-T4 rectal adenocarcinoma less than 12 cm from the anal margin received short course radiotherapy (5X5 Gy in one week) or radiochemotherapy (50 Gy, 2 y/f and capecitabine 800 mg/m 2 , 5 days/week) with delayed surgery (7 weeks ± 1) in both groups. The Quality of Life analyses (EORTC QLQ C-30 et ELD14) were conducted upon inclusion, pre-operatively, at 3, 6 and 12 months post-op, together with the oncogeriatric evaluations, including an evaluation of the IADL and ADL scores, walking speed, GDS15, MMSE, MNA., Results: We did not highlight any statistical difference for the global EORTC QLQ-C30 score; several factors are statistically in favor of the short course radiotherapy group at 3 months post-op (cognitive functions, fatigue, appetite). In the case of the ELD14 score, the disease burden is perceived as more negative at 3, 6 and 12 months postop in the radiochemotherapy group. The IADL score deteriorated in 44.8 % of the radiochemotherapy group and 14.8 % of the radiotherapy group (p = 0.032); similarly, the GDS15 depression score was better preserved in the short course radiotherapy group (p = 0.05). An analysis of the other scores: ADL, walking speed, MNA, MMSE did not highlight any statistical difference., Conclusion: Short course radiotherapy achieves better results in terms of Quality of Life and preservation of autonomy in patients aged ≥75 treated for locally advanced rectal cancer., 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 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.)

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., 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.)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Randomized studies have shown low compliance to adjuvant chemotherapy in rectal cancer patients receiving preoperative chemotherapy and external beam radiation (CT/EBRT) with total mesorectal excision. We hypothesize that giving neoadjuvant CT before local treatment would improve CT compliance., Methods: Between 2010-2017, 180 patients were randomized (2:1) to either Arm A (AA) with FOLFOX x6 cycles prior to high dose rate brachytherapy (HDRBT) and surgery plus adjuvant FOLFOX x6 cycles, or Arm B (AB), with neoadjuvant HDRBT with surgery and adjuvant FOLFOX x12 cycles. The primary endpoint was CT compliance to ≥85% of full-dose CT for the first six cycles. Secondary endpoints were ypT0N0, five-year disease free survival (DFS), local control and overall survival (OS)., Results: Patients were randomized to either AA (n = 120, median age (MA) 62 years) or AB (n = 60, MA 63 years). 175/180 patients completed HDRBT as planned (97.2%). In AA, two patients expired during CT; three patients post-randomization received short course EBRT because of progression under CT (n = 2, AA) or personal preference (n = 1, AB). ypT0N0 was 31% in AA and 28% in AB (p = 0.7). CT Compliance was 80% in AA and 53% in AB (p = 0.0002). Acute G3/G4 toxicity was 35.8% in AA and 27.6% in AB (p = 0.23). With a median follow-up of 48.5 months (IQR 33-72), the five-year DFS was 72.3% with AA and 68.3% with AB (p = 0.74), the five-year OS 83.8% for AA and 82.2% for AB (p = 0.53), and the five-year local recurrence was 6.3% for AA and 5.8% for AB (p = 0.71)., Conclusion: We confirmed improved compliance to neoadjuvant CT in this study. Although there is no statistical difference in ypT0N0 rate, local recurrence, and DFS between the two arms, a trend towards favourable oncological outcomes is observed., (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: 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: Rectal cancer predominantly affects the elderly. Unfortunately, this age category is under-represented in clinical trials because clinicians are loath to include patients with a high risk of comorbidity., Patients and Methods: An exploratory analysis of the ACCORD12/PRODIGE 2 phase III trial was carried out to retrospectively compare the benefit of neoadjuvant chemotherapy between the elderly (≥70 years; n=142) and younger patients (<70 years; n=442), this analysis was not preplanned in the study protocol. Patients with histologically confirmed resectable stage T3 or T4 rectal adenocarcinoma were eligible with an age limit of 80 years., Results: Overall, the two age categories did not statistically differ in terms of patient's clinical and tumor baseline characteristics. Preoperative chemoradiotherapy leads to more severe grade 3/4 toxicities (25.6% vs. 15.8%, p=0.01) and more permanent stomas (33.3% vs. 22.8%, p=0.014) in elderly patients who were less often operated on than younger patients (95.8% vs. 99.0%, p=0.008). The relative number of interventions per surgery type (p=0.18), treatment efficacy in terms of R0 resection rate (88.6% vs. 90.6%; p=0.54) and complete pathological response (14.7% vs. 16.9%; p=0.55) were nearly identical between the two categories., Conclusion: Altogether these results warrant the development of specific optimal therapeutic strategies for the elderly., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)