BACKGROUND AND PURPOSE:Postoperative target delineation after reconstructive surgery in head and neck cancer (HNC) is heterogeneous; whether to include the flap or focus on the native tissue-flap junction is debated. We quantified patterns of relapse relative to flaps and summarized practice, toxicity and function. MATERIALS AND METHODS:in the retrospective XFLAP1 cohort (2018-2023), patients with HNC underwent tumor resection with flap reconstruction and postoperative radiotherapy (PORT) ± concurrent chemotherapy. Competing-risks (Fine-Gray) estimated locoregional relapse (LRR) and metastases; overall survival (OS) used Kaplan-Meier. Flaps were contoured a posteriori on planning CTs, when available. RESULTS:Of 355 patients across eight centres, free flaps were used in 239 (67%) and regional pedicled flaps in 69 (33%). The entire flap body was encompassed in the CTVs in 66% of plans; median flap-body dose was 65.3 Gy and pedicle Dmax 67.5 Gy for the delineated flaps (N = 153). Median follow-up was 32.9 months, 120/355 (34%) patients relapsed, including 68 (19%) LRR and 71 (20%) metastases. Median time to LRR was 7.35 months; only 3 (1%) of relapses arose within the flap body. Two-year cumulative incidence was 15.8% for LRR and 16.7% for metastases; two-year OS was 74.6%. On multivariable analysis, pN2-3 predicted metastases; LRR, metastases, and ECOG ≥ 1 were associated with worse OS. CONCLUSIONS:relapses in the flap-body epicentre were rare; most local failures involved the native tissue-flap junction or non-flap sites. These data support junction-focused CTVs with reduced emphasis of the flap body to limit morbidity, pending prospective validation.

PURPOSE:Trimodal therapy, combining transurethral resection of the bladder tumour, radiotherapy, and concurrent radiosensitization, is an established bladder-preserving alternative to radical cystectomy in muscle-invasive bladder cancer. Hypofractionated radiotherapy has gained interest due to radiobiological advantages and logistical convenience, yet its efficacy and safety remain under evaluation. METHODS:A review of prospective phase II and III trials published between 2000 and 2025 was conducted in Medline using the search engine PubMed. Studies were included if they assessed hypofractionated radiotherapy (excluding stereotactic body radiotherapy) for non-metastatic muscle-invasive bladder cancer within a curative-intent using a trimodal therapy approach. Key endpoints included progression-free survival, overall survival, and toxicity. RESULTS:Seven prospective trials (five phase II, two phase III) were identified. The largest evidence come from the BC2001 and BCON trials, which demonstrated that a dose of 55Gy delivered in 20 fractions was non-inferior to a dose of 64Gy delivered in 32 fractions in terms of locoregional control and overall survival, with similar genitourinary and gastrointestinal toxicity rates. Additional studies confirmed comparable efficacy between hypofractionated and conventional fractionated radiotherapy regimens. Various concurrent systemic therapies were used, including cisplatin, 5-fluorouracil with mitomycin C, gemcitabine, and carbogen with nicotinamide, though no regimen showed clear superiority. Elective pelvic nodes irradiation remains controversial; one phase III trial showed no benefit, while recent data suggest a potential survival advantage without increased toxicity, even in hypofractionated protocols. CONCLUSION:Hypofractionated chemoradiotherapy is a safe and effective bladder-preserving strategy in selected patients with muscle-invasive bladder cancer. It offers comparable oncological outcomes and toxicity to conventional radiotherapy, with improved treatment efficiency. While systemic radiosensitization remains essential, further research is needed to optimize agents and clarify the role of pelvic nodes irradiation in hypofractionated settings.

We present the updated recommendations of the Société française de radiothérapie oncologique (SFRO; the French society of radiation oncology) regarding the radiotherapy management of laryngeal cancers. Clinical examination in a seated position and nasofibroscopy are essential for accurately assessing laryngeal mobility, a crucial parameter in the therapeutic decision-making process for glottic cancer. In early-stage cancers, treatment selection depends on multiple factors and requires thorough consideration and multidisciplinary discussion. Between surgery and radiotherapy, the decision can be personalized to achieve an optimal balance between tumour control and the preservation of laryngeal function. In advanced-stage laryngeal tumours, the therapeutic approach is mainly based on two strategies: concomitant chemoradiotherapy or induction chemotherapy followed by chemoradiotherapy. However, in some cases where these approaches are not feasible, the treatment relies on upfront total laryngectomy, often followed by adjuvant therapy. With the exception of early-stage glottic tumours, where hypofractionation has proven its efficacy, there is no formal indication to modify the standard fractionation regimen. Due to the movements induced by respiration and swallowing, laryngeal mobility must be taken into account. Three-dimensional volumetric imaging is the gold standard for ensuring accurate daily patient positioning and monitoring weight loss. The follow-up of laryngeal cancers is crucial for the early detection of potential recurrences and for adjusting oncological management when necessary. It also plays a key role in patient rehabilitation, ensuring the best possible preservation of vocal and respiratory functions to optimize quality of life.

Stereotactic radiation therapy (SRT) is on the rise around the world. We aimed to provide recommendations to streamline and assess medical practices in SRT delivery at treatment unit, while complying with legal obligations concerning safety. We conducted an online closed practice survey for heads of radiotherapy departments both nationally in comprehensive cancer centers and university hospitals throughout France, and internationally. The aim was to obtain a better understanding of how the delivery of SRT at treatment unit was managed across different centers according to experience, and to the machines and repositioning techniques used. Radiation oncologists (ROs) were also asked to assess the difficulties of technical implementation in the department, and whether residents were involved in the validation and delivery of SRT. Differences among countries regarding legislation governing the validation of SRT sessions at treatment unit were also collected. A videoconference was then held to draw up proposals for regulatory changes based on the results obtained. Finally, recommendations were drawn up by the steering committee and approved by heads of radiotherapy departments in comprehensive cancer centers and university hospitals throughout France. Thirty-five French centers and 15 centers from 14 foreign countries responded to the questionnaire. The most common stereotactic machines were Varian Truebeam STX® (45

We present the update of the recommendations of the Société française de radiothérapie oncologique on radiotherapy for hypopharynx. Intensity-modulated radiotherapy is the gold standard treatment for hypopharynx cancers. Early T1 and T2 tumours can be treated by exclusive radiation or surgery followed by postoperative radiation in case of high recurrence risk. For locally advanced tumours requiring total pharyngolaryngectomy (T2 or T3) or with significant lymph nodes involvement, they can be treated by chemoradiation or by induction drugs followed by exclusive radiation. For T4 tumour, surgery must be proposed. Different fractionation schedules are possible: for 35 fractions, the curative dose is 70Gy (delivered at 2Gy per fraction) and prophylactic doses are 50 to 56Gy (delivered at 2Gy per fraction in case of sequential radiotherapy or 1.6Gy in case of simultaneous integrated boost radiotherapy; for 33 fractions, the curative dose is 69.96Gy (delivered at 2.12Gy per fraction) and the prophylactic dose is 52.8Gy (delivered at 1.6Gy per fraction in simultaneous integrated boost radiotherapy or 54Gy in 1.64Gy per fraction); for 30 fractions, curative dose is 66Gy (delivered at 2.2Gy per fraction) and prophylactic dose is 54Gy (delivered at 1.8Gy per fraction in simultaneous integrated boost radiotherapy. Doses over 2Gy per fraction can be delivered when chemotherapy is not used regarding potential larynx toxicity. Postoperatively, radiotherapy is used for locally advanced cancer with dose levels based on pathologic criteria, delivering 60 to 66Gy for R1 resection and 57.6 to 60Gy for complete resection in bed tumour; 50 to 66Gy in lymph nodes areas regarding extracapsular spread. Target volume delineation recommendations were based on guidelines cited in this article.

PURPOSE:Reconstructive surgery with a flap is standard practice in advanced oral cavity squamous cell carcinoma to restore essential functions. However, these functions may be compromised by postoperative radiotherapy. This study evaluates relapse patterns and treatment-related toxicity in these patients. METHODS AND MATERIALS:A multicentre 2018-2023 study included 247 patients with oral cavity squamous cell carcinoma. Uni- and multivariate analyses estimated the cumulative incidence of locoregional failures, survival rates, and prognostic factors. RESULTS:Among the patients, 74.0 % had pT3-4 tumours, 78.5 % had free flaps, regional pedicled flaps (12.6 %), or local flaps (8.5 %). Flaps were not delineated on planning CTs. Median follow-up for living patient was 36.8months. Fifty-eight patients (23.0 %) had involved soft-tissue margins; no correlation was found between margin involvement, stage, or flap type. Forty patients experienced local relapse within a median of 8.23months. Local relapse rates were higher in patients with involved (28.6 %) versus clear margins (9.3 %, P<0.004). Two-year locoregional relapse and survival rates were 17.8 %, and 74.3 %, respectively. Performance status greater than 1, locoregional relapse, and distant relapse were associated with poorer survival. Coregistration of planning-relapse CTs is challenging due to flap changes, limiting relapse pattern analysis. Subgroup analysis of locoregional relapses (14 out of 53) at the main contributing centre revealed that five relapses occurred at the native tissue-flap junction, with minor flap involvement in two cases and no intraflap failure. All other relapses occurred outside the flap. CONCLUSIONS:Involved margin rates correlating with increased local relapse risk and were not different according flap type. Further investigation into flap segmentation and planning optimization is needed. The OPTIFLAP trial (NCT06798922, PHRC2024) aims to determine whether radiotherapy can be optimized to spare flaps without increasing the risk of locoregional failure.

Background: Radiotherapy is thought to enhance anti-tumor immunity, particularly when delivered in a hypofractionated and multisite manner. Therefore, we investigated the effects of combining radiotherapy with nivolumab in patients with advanced melanoma. Methods: This was a multicenter, non-randomized, phase 2 trial that enrolled patients with treatment-na & iuml;ve metastatic melanoma. They received nivolumab (240 mg / 2 weeks) plus radiotherapy (day 15, 6 Gy x 3). When feasible, one target from each organ was irradiated (no irradiation of all targets). The primary endpoint was 1year overall survival (OS). Results: This trial included 64 patients between March 2017 and July 2019. The median follow-up was 23.5 (2.3-43.8) months. The median age was 68 (35-95) years, patients were mostly male (67 %) with an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0 (72 %), stage IV-M1c disease (47 %), and were BRAF-wild-type (67 %). The 2-year OS and 1-year PFS rates were 65.2 % and 56 %, respectively (P = 0.22 and P = 0.03, vs. 58 % and 43 %, respectively, in the Checkmate 066 study). Thirty-seven (58 %) and twentyseven (42 %) patients were irradiated at one and multiple targets, respectively. The ECOG-PS (1 vs. 0; HR = 3.5; P = 0.005) was an independent prognostic factor for OS. Irradiating more than one site and irradiating a smaller cumulative tumor volume tended to correlate with better outcome. Grade 3-4 treatment-related adverse events occurred in 21.9 % of the patients (no grade 5). Conclusions: Combined immunotherapy and hypofractionated radiotherapy did not improve survival compared to historical cohorts. The radiotherapy schedule needs to be optimized in order to improve these results.

Purpose. - Trimodal therapy, an organ-sparing alternative, may be proposed for selected patients with muscle-invasive bladder cancer instead of radical cystectomy. In this multicentre retrospective study, we aimed to assess the oncological outcomes of patients who had trimodal therapy for a muscle-invasive bladder cancer. Materials and methods. - Seventy-three patients from four centres treated who had trimodal therapy (maximal transurethral resection of bladder tumour and concomitant chemoradiotherapy) for localized muscle-invasive bladder cancer were included. Patients meeting the optimal trimodal therapy eligibility criteria as per the European Association of Urology guidelines were identified. Overall survival, recurrence-free survival and cancer-specific survival were assessed using the Kaplan-Meier method. The cumulative incidence of recurrence was estimated using the Kalbfleisch-Prentice method. Results. - Median overall survival was 27.0 months (95 % confidence interval [CI]: 20.3-58.3 months), 5-years overall-, cancer-specific- and recurrence-free survival rates were 37.5% (95 % CI: 25.5-49.5 %), 60 % (95 % CI: 48.3-72.0 %), and 17.9 % (95 % CI: 9.3-28.8 %), respectively. There was no significant difference in 5-year overall survival and recurrence-free survival between the trimodal therapy-eligible and non-eligible patients (hazard ratio [HR]: 1.38, P = 0.30 and HR: 0.96, P = 0.90, respectively). The univariate analysis did not reveal any significant prognostic factors associated with recurrence-free or overall survival. Conclusion. - Trimodal therapy offers encouraging specific survival, the prognosis remains poor. Our study highlights the low number and high frailty of patients to whom trimodal therapy is offered in clinical practice. (c) 2024 Societe franc,aise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

It is difficult to distinguish between the brain metastasis progression (BMP) and brain radionecrosis (BRN) on the basis of 18F-3,4-dihydroxyphenylalanine positron emission tomography/computed-tomography (18F-FDOPA PET/CT) data. The advent of silicon photomultiplier (SiPM) PET technology makes it possible to study dynamic volumes and potentially improve diagnostic accuracy. We developed a method for processing 18F-FDOPA PET/CT in the differential diagnosis between BMP and BRN. The method involves a short (3-second) sampling time during a 4-minute acquisition on a SiPM-PET/CT machine. We prospectively included 15 patients and 19 metastases. All acquisitions were performed in list mode acquisition for 25 min on a four-ring SiPM PET/CT system. We calculated the ratios between the maximum activity in the lesion’s voxel and the mean activity in the contralateral region (VOImax/CLmean) or the mean activity in the white matter (VOImax/WMmean). Seven lesions were classified as BMP and twelve were classified as BRN. Statistically significant intergroup differences in the VOImax/CLmean and VOImax/WMmean activity ratios were observed for both the clinical volume and the early acquisition. The best performing quantitative variable was the VOImax/CLmean ratio on early acquisition, with a diagnostic accuracy of 94.7

BackgroundThymomas are rare intrathoracic malignancies that can relapse after surgery. Whether or not Post-Operative Radiotherapy (PORT) should be delivered after surgery remains a major issue. RADIORYTHMIC is an ongoing, multicenter, randomized phase 3 trial addressing this question in patients with completely R0 resected Masaoka-Koga stage IIb/III thymoma. Experts in the field met to develop recommendations for PORT.MethodsA scientific committee from the RYTHMIC network identified key issues regarding the modalities of PORT in completely resected thymoma. A DELPHI-method was used to question 24 national experts, with 115 questions regarding: 1/ Imaging techniques, 2/ Clinical Target Volume (CTV) and margins, 3/ Dose constraints to Organs At Risk, 4/ Dose and fractionation, 5/ Follow-up and records. Consensus was defined when opinions reached ≥ 80% agreement.ResultsWe established the following recommendations: pre-operative contrast-enhanced CT-scan is recommended (94% agreement); optimization of radiation delivery includes either a 4D-CT based planning (82% agreement), a breath-holding inspiration breath-hold-based planning, or daily control CT-imaging (81% agreement); imaging fusion based on cardiovascular structures of pre-operative and planning CT-scan is recommended (82% agreement); right coronary and left anterior descending coronary arteries should be delineated as cardiac substructures (88% agreement); rotational RCMI/VMAT is recommended (88% agreement); total dose is 50Gy (81% agreement) with 1.8-2Gy per fraction (94% agreement); cardiac evaluation, and follow-up for patients with history of cardiovascular disease is recommended (88% agreement) with EKG and evaluation of LVEF at 5 years and 10 years.ConclusionThis is the first consensus for PORT in thymoma. Implementation will help to harmonize practices.

BACKGROUND:A standard treatment for fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) is yet to be established. In the previous EXTREME trial, few older patients were included. We aimed to evaluate the efficacy and tolerance of an adapted EXTREME regimen in fit, older patients with recurrent or metastatic HNSCC. METHODS:This single-arm, phase 2 study was done at 22 centres in France. Eligible patients were aged 70 years or older and assessed as not frail (fit) using the ELAN Geriatric Evaluation (EGE) and had recurrent or metastatic HNSCC in the first-line setting that was not eligible for local therapy (surgery or radiotherapy), and an Eastern Cooperative Oncology Group performance status of 0-1. The adapted EXTREME regimen consisted of six cycles of fluorouracil 4000 mg/m2 on days 1-4, carboplatin with an area under the curve of 5 on day 1, and cetuximab on days 1, 8, and 15 (400 mg/m2 on cycle 1-day 1, and 250 mg/m2 subsequently), all intravenously, with cycles starting every 21 days. In patients with disease control after two to six cycles, cetuximab 500 mg/m2 was continued once every 2 weeks as maintenance therapy until disease progression or unacceptable toxicity. Granulocyte colony-stimulating factor was systematically administered and erythropoietin was recommended during chemotherapy. The study was based on the two-stage Bryant and Day design, combining efficacy and toxicity endpoints. The primary efficacy endpoint was objective response rate at week 12 after the start of treatment, assessed by central review (with an unacceptable rate of ≤15%). The primary toxicity endpoint was morbidity, defined as grade 4-5 adverse events, or cutaneous rash (grade ≥3) that required cetuximab to be discontinued, during the chemotherapy phase, or a decrease in functional autonomy (Activities of Daily Living score decrease ≥2 points from baseline) at 1 month after the end of chemotherapy (with an unacceptable morbidity rate of >40%). Analysis of the coprimary endpoints, and of safety in the chemotherapy phase, was based on the per-protocol population, defined as eligible patients who received at least one cycle of the adapted EXTREME regimen. Safety in the maintenance phase was assessed in all patients who received at least one dose of cetuximab as maintenance therapy. The study is registered with ClinicalTrials.gov, NCT01864772, and is completed. FINDINGS:Between Sept 27, 2013, and June 20, 2018, 85 patients were enrolled, of whom 78 were in the per-protocol population. 66 (85%) patients were male and 12 (15%) were female, and the median age was 75 years (IQR 72-79). The median number of chemotherapy cycles received was five (IQR 3-6). Objective response at week 12 was observed in 31 patients (40% [95% CI 30-51]) and morbidity events were observed in 24 patients (31% [22-42]). No fatal adverse events occurred. Four patients presented with a decrease in functional autonomy 1 month after the end of chemotherapy versus baseline. During chemotherapy, the most common grade 3-4 adverse events were haematological events (leukopenia [22 patients; 28%], neutropenia [20; 26%], thrombocytopenia [15; 19%], and anaemia [12; 15%]), oral mucositis (14; 18%), fatigue (11; 14%), rash acneiform (ten; 13%), and hypomagnesaemia (nine; 12%). Among 44 patients who received cetuximab during the maintenance phase, the most common grade 3-4 adverse events were hypomagnesaemia (six patients; 14%) and acneiform rash (six; 14%). INTERPRETATION:The study met its primary objectives on objective response and morbidity, and showed overall survival to be as good as in younger patients treated with standard regimens, indicating that the adapted EXTREME regimen could be used in older patients with recurrent or metastatic HNSCC who are deemed fit with use of a geriatric evaluation tool adapted to patients with head and neck cancer, such as the EGE. FUNDING:French programme PAIR-VADS 2011 (sponsored by the National Cancer Institute, the Fondation ARC, and the Ligue Contre le Cancer), Sandoz, GEFLUC, and GEMLUC. TRANSLATION:For the French translation of the abstract see Supplementary Materials section.

Background: Chemoradiotherapy with high-dose cisplatin (HD-Cis: 100 mg/m 2 q3w for three cycles) is the standard of care (SOC) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC).Cumulative delivered dose of cisplatin is prognostic of survival, even beyond 200 mg/m 2 but high toxicity compromises its delivery.Aim: Cisplatin fractionation may allow, by decreasing the peak serum concentration, to decrease toxicity.To date, no direct comparison was done of HD-Cis versus fractionated high dose cisplatin (FHD-Cis).Methods: This is a multi-institutional randomized phase II trial, stratified on postoperative or definitive chemoradiotherapy, comparing HD-Cis to FHD-Cis (25 mg/m 2 /d d1-4 q3w for 3 cycles) in patients with LA-HNSCC.The primary endpoint was the cumulative delivered cisplatin dose.Results: Between December 2015 and April 2018, 124 patients were randomized.Median cisplatin cumulative delivered dose was 291 mg/m 2 (IQR: 251;298) in the FHD-Cis arm and 274 mg/m 2 (IQR: 198;295) in the HD-Cis arm (P = 0.054).The proportion of patients receiving a third cycle of cisplatin was higher, with a lower proportion of grade 3-4 acute AEs in the FHD-Cis arm compared to the HD-Cis arm: 81 % vs. 64 % (P = 0.04) and 10 % vs. 17 % (P = 0.002), respectively.With a median follow-up of 48 months (IQR: 41;55), locoregional failure rate, PFS and OS were similar between the two arms.

In this article, we propose a consensus delineation of postoperative clinical target volumes for the primary tumour in maxillary sinus and nasal cavity cancers. These guidelines are developed based on radioanatomy and the natural history of those cancers. They require the fusion of the planning CT with preoperative imaging for accurate positioning of the initial GTV and the combined use of the geometric and anatomical concepts for the delineation of clinical target volume for the primary tumour. This article does not discuss the indications of external radiotherapy (nor concurrent systemic treatment) but focuses on target volumes when there is an indication for radiotherapy.

PurposeRadiotherapy is, with surgery, one of the main therapeutic treatment strategies for meningiomas. No prospective study has defined a consensus for the delineation of target volumes for meningioma radiotherapy. Therefore, target volume definition is mainly based on information from retrospective studies that include heterogeneous patient populations. The aim is to describe delineation guidelines for meningioma radiotherapy as an adjuvant or definitive treatment with intensity-modulated radiation therapy and stereotactic radiation therapy techniques. This guideline is based on a consensus endorsed by a multidisciplinary group of brain tumor experts, members of the Association of French-speaking Neuro-oncologists (ANOCEF).Materials and methodsA 3-step procedure was used. First, the steering group carried out a comprehensive review to identify divergent issues on meningiomas target volume delineation. Second, an 84-item web-questionnaire has been developed to precisely define meningioma target volume delineation in the most common clinical situations. Third, experts members of the ANOCEF were requested to answer. The first two rounds were completed online. A third round was carried out by videoconference to allow experts to debate and discuss the remaining uncertain questions. All questions remained in a consensus.ResultsLimits of the target volume were defined using visible landmarks on computed tomography and magnetic resonance imaging, considering the pathways of tumor extension. The purpose was to develop clear and precise recommendations on meningiomas target volumes.ConclusionNew recommendations for meningiomas delineation based on simple anatomic boundaries are proposed by the ANOCEF. Improvement in uniformity in target volume definition is expected.

Introduction: We report long-term efficacy and overall survival (OS) results from a randomised, double-blind, phase 2 study (NCT02022098) investigating xevinapant plus standard-of-care chemoradiotherapy (CRT) vs. placebo plus CRT in 96 patients with unre-sected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN).Methods: Patients were randomised 1:1 to xevinapant 200 mg/day (days 1-14 of a 21-day cy-cle for 3 cycles), or matched placebo, plus CRT (cisplatin 100 mg/m2 every 3 weeks for 3 cycles plus conventional fractionated high-dose intensity-modulated radiotherapy [70 Gy/35 F, 2 Gy/ F, 5 days/week for 7 weeks]). Locoregional control, progression-free survival, and duration of response after 3 years, long-term safety, and 5-year OS were assessed.Results: The risk of locoregional failure was reduced by 54% for xevinapant plus CRT vs. pla-cebo plus CRT but did not reach statistical significance (adjusted hazard ratio [HR] 0.46; 95% CI, 0.19-1.13; P = .0893). The risk of death or disease progression was reduced by 67% for xevinapant plus CRT (adjusted HR 0.33; 95% CI, 0.17-0.67; P = .0019). The risk of death was approximately halved in the xevinapant arm compared with placebo (adjusted HR 0.47; 95% CI, 0.27-0.84; P = .0101). OS was prolonged with xevinapant plus CRT vs. pla-cebo plus CRT; median OS not reached (95% CI, 40.3-not evaluable) vs. 36.1 months (95% CI, 21.8-46.7). Incidence of late-onset grade >3 toxicities was similar across arms.Conclusions: In this randomised phase 2 study of 96 patients, xevinapant plus CRT demon-strated superior efficacy benefits, including markedly improved 5-year survival in patients with unresected LA SCCHN.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Importance There remains an unmet need to improve clinical outcomes in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Objective To evaluate clinical benefit of first-line nivolumab plus ipilimumab vs nivolumab alone in patients with R/M SCCHN. Design, Setting, and Participants The CheckMate 714, double-blind, phase 2 randomized clinical trial was conducted at 83 sites in 21 countries between October 20, 2016, and January 23, 2019. Eligible participants were aged 18 years or older and had platinum-refractory or platinum-eligible R/M SCCHN and no prior systemic therapy for R/M disease. Data were analyzed from October 20, 2016 (first patient, first visit), to March 8, 2019 (primary database lock), and April 6, 2020 (overall survival database lock). Interventions Patients were randomized 2:1 to receive nivolumab (3 mg/kg intravenously [IV] every 2 weeks) plus ipilimumab (1 mg/kg IV every 6 weeks) or nivolumab (3 mg/kg IV every 2 weeks) plus placebo for up to 2 years or until disease progression, unacceptable toxic effects, or consent withdrawal. Main Outcomes and Measures The primary end points were objective response rate (ORR) and duration of response between treatment arms by blinded independent central review in the population with platinum-refractory R/M SCCHN. Exploratory end points included safety. Results Of 425 included patients, 241 (56.7%; median age, 59 [range, 24-82] years; 194 males [80.5%]) had platinum-refractory disease (nivolumab plus ipilimumab, n = 159; nivolumab, n = 82) and 184 (43.3%; median age, 62 [range, 33-88] years; 152 males [82.6%]) had platinum-eligible disease (nivolumab plus ipilimumab, n = 123; nivolumab, n = 61). At primary database lock, the ORR in the population with platinum-refractory disease was 13.2% (95% CI, 8.4%-19.5%) with nivolumab plus ipilimumab vs 18.3% (95% CI, 10.6%-28.4%) with nivolumab (odds ratio [OR], 0.68; 95.5% CI, 0.33-1.43; P = .29). Median duration of response for nivolumab plus ipilimumab was not reached (NR) (95% CI, 11.0 months to NR) vs 11.1 months (95% CI, 4.1 months to NR) for nivolumab. In the population with platinum-eligible disease, the ORR was 20.3% (95% CI, 13.6%-28.5%) with nivolumab plus ipilimumab vs 29.5% (95% CI, 18.5%-42.6%) with nivolumab. The rates of grade 3 or 4 treatment-related adverse events with nivolumab plus ipilimumab vs nivolumab were 15.8% (25 of 158) vs 14.6% (12 of 82) in the population with platinum-refractory disease and 24.6% (30 of 122) vs 13.1% (8 of 61) in the population with platinum-eligible disease. Conclusions and Relevance The CheckMate 714 randomized clinical trial did not meet its primary end point of ORR benefit with first-line nivolumab plus ipilimumab vs nivolumab alone in platinum-refractory R/M SCCHN. Nivolumab plus ipilimumab was associated with an acceptable safety profile. Research to identify patient subpopulations in R/M SCCHN that would benefit from nivolumab plus ipilimumab over nivolumab monotherapy is warranted. Trial Registration ClinicalTrials.gov Identifier: NCT02823574

IntroductionThe objective of this study was a multicentric evaluation of professional practices, analyzing the irradiation technique itself and its impact on survival and recurrence sites, in primary central nervous system lymphomas (PCNSLs).MethodsWe retrospectively analyzed the technical and clinical records of 79 PCNSL patients included in the database of the national expert network for oculocerebral lymphoma ('LOC') who were treated with brain radiotherapy as first-line treatment for newly diagnosed primary central nervous system lymphoma between 2011 and 2018.ResultsThe number of patients treated with brain radiotherapy gradually decreased over time. The heterogeneity of radiotherapy prescriptions was significant, and 55% of them did not comply with published recommendations in terms of irradiation dose and/or volume. The proportion of complete responders to induction chemotherapy treated with reduced-dose radiotherapy increased over time. Partial brain radiotherapy was associated with significantly lower overall survival in univariate analysis. In partial responders to induction chemotherapy, increasing the total dose to the brain >30 Gy and adding a boost to the WBRT induced a trend toward improved progression-free and overall survival. Five recurrences (13%) occurred exclusively in the eyes, all in patients whose eyes had been excluded from the irradiation target volume and including 2 patients without ocular involvement at diagnosis.ConclusionThe visibility of recommendations for prescribing brain radiotherapy for the treatment of newly diagnosed primary central nervous system lymphoma needs to be improved to harmonize practices and improve their quality. We propose an update of the recommendations.

Anatomical variations occur during head and neck (H&N) radiotherapy (RT) treatment. These variations may result in underdosage to the target volume or overdosage to the organ at risk. Replanning during the treatment course can be triggered to overcome this issue. Due to technological, methodological and clinical evolutions, tools for adaptive RT (ART) are becoming increasingly sophisticated. The aim of this paper is to give an overview of the key steps of an H&N ART workflow and tools from the point of view of a group of French-speaking medical physicists and physicians (from GORTEC). Focuses are made on image registration, segmentation, estimation of the delivered dose of the day, workflow and quality assurance for an implementation of H&N offline and online ART. Practical recommendations are given to assist physicians and medical physicists in a clinical workflow.

Globally, cervical cancers continue to be one of the leading causes of cancer-related deaths. The primary treatment of patients with early-stage disease includes surgery or radiation therapy with or without chemotherapy. The main challenge in treating these patients is to maintain a curative approach and limit treatment-related morbidity. Traditionally, inoperable patients are treated with radiation therapy solely and operable patients undergo upfront surgery followed by adjuvant (chemo) radiotherapy in cases with poor histopathological prognostic features. Patients with locally advanced cervical cancers are treated with concurrent chemoradiotherapy followed by an image-guided brachytherapy boost. In these patients, the main pattern of failure is distant relapse, encouraging intensification of systemic treatments to improve disease control. Ongoing trials are evaluating immunotherapy in locally advanced tumours following its encouraging efficacy reported in the recurrent and metastatic settings. In this article, clinical evidence of neoadjuvant and adjuvant treatments in cervical cancer patients is reviewed, with a focus on potential strategies to improve patients’ outcome and minimize treatment-related morbidity.