No multicenter study has validated cochlear dose constraints for hearing preservation in pediatric brain tumor patients in a real-world setting. Although the PENTEC review proposed a 35 Gy mean cochlear dose threshold, supporting evidence from heterogeneous, multicenter pediatric cohorts remains scarce. To evaluate dosimetric, therapeutic, and clinical risk factors for sensorineural hearing loss (SNHL) after pediatric cranial radiotherapy in a national multicenter cohort, with a specific focus on validating the clinical relevance of the 35 Gy mean cochlear dose threshold. We retrospectively analyzed 88 children treated with cranial radiotherapy between 2014 and 2024 across four French pediatric radiotherapy centers participating in the national PediaRT registry. All patients had baseline and at least two post-radiotherapy audiograms graded according to the Chang Ototoxicity Scale, with SNHL defined as Chang grade ≥ 1a. Mean (Dmean) and minimum (Dmin) cochlear doses were extracted and analyzed using Kaplan–Meier estimates and Cox proportional hazards models. Over a median follow-up of 37 months, 17 patients (19.3
Total neoadjuvant therapy (TNT) has become a cornerstone in the treatment of locally advanced rectal cancer, improving systemic control and increasing the potential for organ preservation. However, current trials and guidelines continue to treat rectal cancer as a homogeneous entity, overlooking the significant anatomic and therapeutic differences between mid- and low-rectal tumors. This uniform approach fails to reflect the impact of tumor location on both oncologic outcomes and functional consequences. Low-rectal cancers-defined as tumors located < 1 cm from the anal ring-pose distinct anatomic and functional challenges. These include more complex lymphatic drainage, higher risks of positive margins, and greater impact on continence. By contrast, mid-rectal tumors are generally more amenable to standard resection with preserved function and may benefit from treatment deintensification, particularly regarding radiotherapy. Drawing on data from over 80 studies and clinical trials, this review argues that mid- and low-rectal cancers should be considered distinct clinical entities requiring tailored treatment strategies. We examine evidence supporting radiotherapy de-escalation for mid-rectal tumors and intensified TNT for low-rectal tumors when organ and sphincter preservation is essential. Adopting a location-specific, patient-centered approach can better align treatment intensity with oncologic risk and individual functional priorities, ultimately improving both outcomes and quality of life.
BACKGROUND:The standard treatment for older patients (aged ≥70 years) with localised, unresectable head and neck squamous-cell carcinoma is standard fractionated radiotherapy (SF-RT). However, its high toxicity and multiple fractions lead physicians to deliver tailored hypofractionated split-course radiotherapy (HSC-RT). The aim of the study was to compare these two radiotherapy methods in older patients. METHODS:This non-inferiority, multicentre, open-label, randomised controlled trial was done in 30 treating centres (cancer centres, university and general hospitals, and private clinics) across France and Monaco. Patients aged 70 years or older, assessed as frail by geriatric evaluation, with stage II-IV head and neck squamous-cell carcinoma and in curative intent were randomly assigned (1:1) to receive either SF-RT (70 Gy, 35 fractions over 7 weeks) or HSC-RT (55 Gy, 20 fractions, two courses of 2 weeks with 2 weeks stop). Randomisation was done by minimisation, and physicians and patients were not masked to the treatment group. The primary endpoint was the proportion of patients alive with complete locoregional response at 6 months, analysed in all randomly assigned patients (intention-to-treat population). The non-inferiority margin was set at 16%. The study was sponsored by the Groupe d'Oncologie Radiothérapie Tête et Cou (GORTEC) and is registered with ClinicalTrials.gov, NCT01864850. FINDINGS:Between Oct 21, 2013, and Aug 22, 2018, 102 patients were randomly assigned to the HSC-RT group and 100 patients to the SF-RT group. One patient in the HSC-RT group refused treatment and follow-up and so was excluded, resulting in 101 patients in the HSC-RT group. Median age was 82 years (IQR 77-86); 145 (72%) were male and 56 (28%) were female. Median follow-up for overall survival was 56·6 months (IQR 41-69). In the intent-to-treat population, 35 (35%) of 101 patients were alive with complete locoregional response at 6 months in the HSC-RT group versus 33 (33%) of 100 patients in the SF-RT group (difference +2%, 95% CI -11 to 15). In the per-protocol population, 35 (36%) of 97 patients were alive with complete locoregional response at 6 months in the HSC-RT group versus 33 (35%) of 95 patients in the SF-RT group (difference +1%, -12 to 15). Median overall survival was 13·0 months (95% CI 10·3 to 17·0) in the HSC-RT group versus 18·9 months (14·3 to 30·9) in the SF-RT group (hazard ratio 1·32, 95% CI 0·97 to 1·81). Eight patients died between radiotherapy start and 30 days after radiotherapy end (five [5%] in the HSC-RT group and three [3%] in the SF-RT group). One patient in the HSC-RT group had a grade 4 adverse event (kidney failure), as did four in the SF-RT group (two mucositis, one septic shock, and one hemiplegia). Acute adverse events grade 3-5 occurred in 33 (36%) of 91 patients in the HSC-RT group and in 44 (47%) of 93 patients in the SF-RT group (p=0·13; difference -11%, 95% CI -25 to 3). INTERPRETATION:Compared with SF-RT, HSC-RT did not decrease the 6-month complete locoregional response rate and could be an option for frail older patients. However, given the survival results, it should only be offered to patients deemed unsuitable for SF-RT after geriatric assessment. FUNDING:French programme PAIR-VADS 2011 (sponsored by the French National Cancer Institute, Fondation ARC, and Ligue Contre le Cancer), GEMLUC, and GEFLUC.
INTRODUCTION:Trimodal therapy (TMT) is a viable option for muscle-invasive bladder cancer (MIBC), but the optimal chemotherapy regimen remains unclear. This phase II randomized trial (NCT01495676) compared cisplatin (CDDP) with twice-weekly gemcitabine (GEM) and radiation therapy (RT) with CDDP plus RT. METHODS:Patients with pT2-pT3N0M0 MIBC, after macroscopically complete transurethral resection (TURBT), received RT (63 Gy to the bladder, 45 Gy to the pelvis, 1,8 Gy/ fraction) with chemotherapy (CDDP 20 mg/m2/day for 4 days every 21 days alone or plus GEM 25 mg/m2 twice weekly). The primary endpoint was 2-year disease-free survival (DFS); secondary endpoints included overall survival (OS) and toxicities. A 1:2 randomization was planned to include 36 patients in the control arm and 73 patients in the experimental arm. RESULTS:Sixty-nine patients were included: 24 in the RT/CDDP arm and 45 in the RT/CDDP/GEM arm. The median follow-up was 63 months. Two-year DFS was similar between groups (58.3% CI95% [36.6-77.9] vs. 60.0% CI95% [44.3-74.3]), with median DFS of 29.8 (RT/CDDP) vs. 37.4 (RT/CDDP/GEM) months. OS at 24 and 60 months was 91.3% [IC 95% 69.5-97.8] and 66.8% [IC 95% 39.6-83.9] (RT/CDDP) vs. 66.7% % [IC 95% 50.2 - 78.8] and 53.7% [IC 95% 37.2 - 67.6] (RT/CDDP/GEM). Toxicity profiles were comparable except for increased cytopenias in the GEM arm. CONCLUSIONS:Adding GEM to CDDP did not improve 2-year DFS in MIBC patients treated with TMT. Results should be interpreted cautiously due to early study termination and insufficient accrual.
BACKGROUND:Several publications have shown that cancers of the colon and of the rectum are significantly different, and tumor location is a major prognostic factor for survival. However, colorectal peritoneal metastases (CRPM) is still considered as a homogeneous and a single disease without differentiating between colonic or rectal origin. We asked whether the primary tumor location influences the survival and surgical outcomes of patients with colonic (C_PM) and rectal peritoneal metastases (R_PM) following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS:Between January 2013 and March 2024, data from 1237 CRS/HIPEC procedures in 1152 patients with CRPM were analysed (C_PM, n = 1129; R_PM, n = 108). Overall survival (OS), recurrence-free survival (RFS), and day-30 morbi-mortality were compared. RESULTS:The 3-year and 5-year OS rates were 68.9% and 52.5% respectively and were significantly better for C_PM than for R_PM patients: (69.8% vs 61%; p = 0.036) and (53.4% vs 43.6%; p = 0.031) respectively. Stratification according to left (LC_PM) and right colonic (RC_PM) subgroups resulted in better 3-year OS for LC_PM than for RC_PM (73.9% vs 63.2%; p ≤ 0.001). Multivariate analysis of 5-year survival identified PCI >15 (HR = 2.09), R_PM (HR = 1.46) and RC_PM (HR = 1.29) as significant risk factors of death. The C_PM group had fewer re-interventions at day-30 (17.6% vs 36.1%; p ≤ 0.001) and shorter surgery time (330 vs 390 min; p ≤ 0.001), ICU-stay (3 vs 4 days; p ≤ 0.001) and hospital length-of-stay (14 vs 17 days; p = 0.002). CONCLUSION:Patients presenting with colonic PM have significantly better OS at 3 and 5 years with fewer re-interventions at day-30 and, shorter surgery time, ICU and hospital stay than those presenting rectal PM. Left-side colonic PM has a significantly better OS at 3-years than right-side colonic PM. PCI >15, rectal and right colonic origin are linked to earlier mortality. When deciding on CRS/HIPEC treatment, designing a study, or reporting data, the CRPM primary tumour site should be taken into account.
