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Evidence on the efficacy of postoperative radiotherapy (PORT) in low-intermediate risk squamous cell carcinoma of the oral cavity (OSCC) remains inconclusive. Members of a task force from two national radio-oncology Associations (AIRO and GORTEC) defined 14 clinically relevant questions to identify "gray areas" pertinent to the indication for PORT in this clinical setting. Consequently, a literature review was performed on the topic. The resulting statements were then rated by an Expert Panel (EP) using a modified Delphi method. Only radiation oncologists were part of the discussion and voting on the scenarios. There was agreement on the 14 statements at the first round of voting. The task force then decided to propose clinical cases for the two more controversial statements that had received a lower agreement to better capture the Experts' attitudes. The clinical cases highlighted a more significant decisional heterogeneity. However, the good level of consensus reached among the two Associations gives relevant support in informing clinical choices while acknowledging general indications cannot fit all clinical situations and do not replace multidisciplinary discussion.

International audience; 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 unresected 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 cycle 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. placebo 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. placebo 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 demonstrated superior efficacy benefits, including markedly improved 5-year survival in patients with unresected LA SCCHN.

Purpose A Benchmark Case (BC) was performed as part of the quality assurance process of the randomized phase 2 GORTEC 2014-14 OMET study, testing the possibility of multisite stereotactic radiation therapy (SBRT) alone in oligometastatic head and neck squamous cell carcinoma (HNSCC) as an alternative to systemic treatment and SBRT. Material and methods Compliance of the investigating centers with the prescription, delineation, planning and evaluation recommendations available in the research protocol was assessed. In addition, classical dosimetric analysis was supplemented by quantitative geometric analysis using conformation indices. Results Twenty centers participated in the BC analysis. Among them, four major deviations (MaD) were reported in two centers. Two (10%) centers in MaD had omitted the satellite tumor nodule and secondarily validated after revision. Their respective DICE indexes were 0.37 and 0 and use of extracranial SBRT devices suboptimal There were significant residual heterogeneities between participating centers, including those with a similar SBRT equipment, with impact of plan quality using standard indicators and geometric indices. Conclusion A priori QA using a BC conditioning the participation of the clinical investigation centers showed deviations from good SBRT practice and led to the exclusion of one out of the twenty participating centers. The majority of centers have demonstrated rigorous compliance with the research protocol. The use of quality indexes adds a complementary approach to improve assessment of plan quality.

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.

Introduction Head and neck reconstructive surgery using a flap is increasingly common. Best practices and outcomes for postoperative radiotherapy (poRT) with flaps have not been specified. We aimed to provide consensus recommendations to assist clinical decision-making highlighting areas of uncertainty in the presence of flaps. Material and methods Radiation, medical, and surgical oncologists were assembled from GORTEC and internationally with the Head and Neck Cancer International Group (HNCIG). The consensus-building approach covered 59 topics across four domains: (1) identification of postoperative tissue changes on imaging for flap delineation, (2) understanding of tumor relapse risks and target volume definitions, (3) functional radiation-induced deterioration, (4) feasibility of flap avoidance. Results Across the 4 domains, international consensus (median score ≥ 7/9) was achieved only for functional deterioration (73.3%); other consensus rates were 55.6% for poRT avoidance of flap structures, 41.2% for flap definition and 11.1% for tumor spread patterns. Radiation-induced flap fibrosis or atrophy and their functional impact was well recognized while flap necrosis was not, suggesting dose-volume adaptation for the former. Flap avoidance was recommended to minimize bone flap osteoradionecrosis but not soft-tissue toxicity. The need for identification (CT planning, fiducials, accurate operative report) and targeting of the junction area at risk between native tissues and flap was well recognized. Experts variably considered flaps as prone to tumor dissemination or not. Discrepancies in rating of 11 items among international reviewing participants are shown. Conclusion International GORTEC and HNCIG-endorsed recommendations were generated for the management of flaps in head and neck radiotherapy. Considerable knowledge gaps hinder further consensus, in particular with respect to tumor spread patterns.

Purpose Naloxegol, an oral once-daily peripherally acting mu-opioid receptor antagonist, is indicated for the treatment of opioid-induced constipation (OIC) with inadequate response to laxative(s), in cancer and non-cancer patients. This study mainly aimed to assess in real-life conditions the efficacy and safety of naloxegol in cancer pain patients and the evolution of their quality of life. Methods A non-interventional, 4-week follow-up study was conducted in 24 French oncology and pain centers between 2018 and 2019. Eligible patients were aged ≥ 18 years, treated with opioids for cancer pain, and started naloxegol for OIC with inadequate response to laxatives. The rate of the response to naloxegol (primary criterion) was assessed at W4. The evolution of quality of life was measured using the Patient Assessment of Constipation Quality of Life (PAC-QOL). Results A total of 124 patients were included (mean age, 62 ± 12 years; ECOG ≤ 2, 79%; primary cancer, lung 18%, breast 16%, prostate 11%, head and neck 9%, digestive 9%…; metastatic stage, 80%). At inclusion, the median opioid dosage was 60 mg of oral morphine or equivalent. At W4, the response rate was 73.4% (95% CI [63.7–83.2%]), and 62.9% (95% CI [51.5–74.2%]) of patients had a clinically relevant change in quality of life (decrease in PAC-QOL score ≥ 0.5 point). Adverse events related to naloxegol were reported in 8% of patients (7% with gastrointestinal events; one serious diarrhea). Conclusion This real-world study shows that naloxegol is effective and well tolerated in cancer pain patients with OIC and that their quality of life improves under treatment.

BACKGROUND Older adults suffering from cancer receive a treatment that, in most cases, causes symptoms such as fatigue, weakness, sleep disturbances, and lethargy. Moreover, the toxicity of the chemotherapy itself can also affect the physical function and the quality of life of cancer patients. Since a poor general health status reduces the chances of survival and these patients are most likely to also suffer from sarcopenia, it is therefore important to be able to improve their physical function through adapted physical activity (APA) as part of a supportive care management. Unfortunately, APA is too often saved for patients in an advanced stage of blood cancer. As a result, there is a lack of data regarding the impact of a regular practice of physical activity (that is concomitant to the administration of chemotherapy) on cancer survival. OBJECTIVE The aim of this study is to assess a new and open rehabilitation program suitable for a frail population of patients that are treated for diffuse large B-cell lymphoma (DLBCL). METHODS PHARAOM (Physical Activity program for the survival of elderly patients with lymphoma) is a phase 3 (1:1) randomized study focusing on a frail population of patients treated for DLBCL. It will include a total of 186 elderly DLBCL patients (aged over 65 years) receiving rituximab plus cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R-CHOP); of these, 93 patients (the investigational group) will receive APA that will be supervised by a dedicated qualified kinesiologist, in addition to chemotherapy. The primary endpoint of this study will be the patients’ event-free survival. Secondary endpoints will include the overall survival, the progression-free survival, the prevalence rates of sarcopenia and undernutrition, as well as the patients’ quality of life. RESULTS The study has been approved by the internal Ethical Committee, and was registered as a clinical trial (NCT04670029) on December 16, 2020. The study will be undertaken in accordance with the Declaration of Helsinki. CONCLUSIONS This study will highlight the benefits of regular APA on the survival of patients treated for a DLBCL. This study could also contribute to our understanding of how an adapted physical program can reduce sarcopenia in cancer patients, and improve their quality of life. By documenting the prevalence and the relationship between sarcopenia and exercise load, we might be able to help physicians to plan better interventions in DLBCL patients. CLINICALTRIAL Clinical Trial: NCT04670029

International audience; Background: Concurrent chemoradiotherapy (CRT) is the standard of care (SoC) in locally advanced (LA) head and neck squamous cell carcinomas (HNSCC). This trial was designed to test whether dose-escalated IMRT and cisplatin could improve locoregional control without increasing complications over 3D-radiotherapy.Methods: Patients were randomized between 70 Gy/35F in 7 weeks with 3D-RT (Arm A) versus 75 Gy/35F with IMRT (Arm B). Both arms received 50 Gy in 25 fractions followed by a sequential boost of 20 Gy/10F in Arm A and 25 Gy/10F to gross tumor volume in Arm B, as well as 3 cycles of cisplatin at 100 mg/m2 during RT. The primary endpoint was locoregional progression (LRP).Results: 188 patients were randomized: 85% oropharynx and 73% stage IVa. P16 status was documented for 137 oropharyngeal tumors with P16+ in 53 (39%) patients; and 90% were smokers. Median follow-up was 60.5 months. Xerostomia was markedly decreased in arm B (p < 0.0001). The 1-year grade ≥2 xerostomia (RTOG criteria) was 63% vs 23% and 3-year 45% vs 11% in arms A and B, respectively. Xerostomia LENT-SOMA scale was also reduced in arm B. Dose-escalated IMRT did not reduce LRP with an adjusted HR of 1.13 [95%CI = 0.64-1.98] (p = 0.68). Survival was not different (adjusted HR: 1.19 [95%CI = 0.78-1.81], p = 0.42). No interaction between p16 and treatment effect was found.Conclusion: Dose-escalated IMRT did not improve LRC in LA-HNSCC patients treated with concomitant CRT over standard 3D-RT. This trial reinforces the evidence showing IMRT reduces xerostomia in LA-HNSCC treated with radiotherapy. Clinicaltrial.gov: NCT00158678.

Summary Background Debio 1143 is an orally available antagonist of inhibitor of apoptosis proteins with the potential to enhance the antitumour activity of cisplatin and radiotherapy. The radiosensitising effect of Debio 1143 is mediated through caspase activation and TNF, IFNγ, CD8 T cell-dependent pathways. We aimed to investigate the efficacy and safety of Debio 1143 in combination with standard chemoradiotherapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck. Methods This double-blind, multicentre, randomised, phase 2 study by the French Head and Neck Radiotherapy Oncology Group (GORTEC) was run at 19 hospitals in France and Switzerland. Eligible patients were aged 18–75 years with locoregionally advanced, squamous cell carcinoma of the head and neck (characterised as non-metastatic, measurable stage III, IVa, or IVb [limited to T ≥2, N0–3, and M0] disease), Eastern Cooperative Oncology Group performance status of 0 or 1, a history of heavy tobacco smoking (>10 pack-years) with no previous or current treatment for invasive head and neck cancer, and no previous treatment with inhibitor of apoptosis protein antagonists. Patients were randomly assigned (1:1) to receive oral Debio 1143 (200 mg per day on days 1–14 of 21-day cycles, for three cycles) or oral placebo (20 mg/mL, administered at the same dosing schedule) using a stochastic minimisation technique according to node involvement and primary tumour site, and HPV-16 status in patients with an oropharyngeal primary tumour site. All patients received standard high-dose cisplatin chemoradiotherapy. The primary endpoint was the proportion of patients with locoregional control 18 months after chemoradiotherapy, analysed in the intention-to-treat population (primary analysis), and repeated in the per-protocol population. Responses were assessed according to Response Evaluation Criteria in Solid Tumors (version 1.1). This trial is registered with ClinicalTrials.gov , NCT02022098 , and is still active but not recruiting. Findings Between Jan 25, 2016, and April 24, 2017, 48 patients were randomly assigned to the Debio 1143 group and 48 to the placebo group (one patient in the placebo group did not receive the study drug and was not included in the safety analysis). Median duration of follow-up was 25·0 months (IQR 19·6–29·4) in the Debio 1143 group and 24·2 months (6·6–26·8) in the placebo group. Locoregional control 18 months after chemoradiotherapy was achieved in 26 (54%; 95% CI 39–69) of 48 patients in the Debio 1143 group versus 16 (33%; 20–48) of 48 patients in the placebo group (odds ratio 2·69 [95% CI 1·13–6·42], p=0·026). Grade 3 or worse adverse events were reported in 41 (85%) of 48 patients in the Debio 1143 group and in 41 (87%) of 47 patients in the placebo group. The most common grade 3–4 adverse events were dysphagia (in 24 [50%] patients in the Debio 1143 group vs ten [21%] in the placebo group), mucositis (in 15 [31%] vs ten [21%]), and anaemia (in 17 [35%] vs 11 [23%]). Serious treatment-emergent adverse events were recorded in 30 (63%) of 48 patients in the Debio 1143 group and 28 (60%) of 47 in the placebo group. In the placebo group, two (4%) deaths were due to adverse events (one multiple organ failure and one asphyxia; neither was considered to be related to treatment). No deaths due to adverse events occurred in the Debio 1143 group. Interpretation To our knowledge, this is the first treatment regimen to achieve superior efficacy in this disease setting against a high-dose cisplatin chemoradiotherapy comparator in a randomised trial. These findings suggest that inhibition of inhibitor of apoptosis proteins is a novel and promising approach in this poor prognostic population and warrant confirmation in a phase 3 study with the aim of expanding the therapeutic options for these patients. Funding Debiopharm.

Objective The severity of breakthrough cancer pain (BTcP) impacts patients' quality of life, increases the risk of anxiety and depression, lowers functional capacities, and may lead to poor compliance with cancer treatments. The aim of the current study was to assess, in a real-life setting, patient satisfaction with a fentanyl-pectin-nasal-spray (FPNS) for BTcP management in head and neck (H&N) cancer patients treated by radiotherapy. Materials and Methods This non-interventional, prospective study was conducted in 92 adult H&N-cancer patients undergoing radiotherapy and who started FPNS treatment for BTcP. Throughout the radiotherapy period, the patients completed self-diaries to assess their BTcP episodes, FPNS use, satisfaction on FPNS efficiency (primary outcome), tolerability and ease of use. Results Prior to FPNS treatment, 86% of the patients were experiencing ≤4 BTcP episodes/day. During the radiotherapy period, the BTcP episodes were treated with a median dose of 100µg of FPNS. Patients were "satisfied/very-satisfied" with the efficiency (73% of assessments), ease of use (87% of assessments) and tolerability (87% of assessments) of FPNS. In total, 27% of patients reported at least one adverse event related to FPNS and 4% of patients discontinued treatment due to adverse events. None of the adverse events were serious. Patient quality of life was maintained throughout the radiotherapy period. Conclusion This study showed, in a real-life setting, that a clear majority of H&N cancer patients treated with FPNS for BTcP throughout radiotherapy expressed satisfaction with this analgesic treatment.

Background: Several reports have suggested that radiotherapy after reconstructive surgery for head and neck cancer (HNC), could have deleterious effects on the flaps with respect to functional outcomes. To predict and prevent toxicities, flap delineation should be accurate and reproducible. The objective of the present study was to evaluate the interobserver variability of frequent types of flaps used in HNC, based on the recent GORTEC atlas.Materials and methods: Each member of an international working group (WG) consisting of 14 experts delineated the flaps on a CT set from six patients. Each patient had one of the five most commonly used flaps in HNC: a regional pedicled pectoralis major myocutaneous flap, a local pedicled rotational soft tissue facial artery musculo-mucosal (FAMM) (2 patients), a fasciocutaneous radial forearm free flap, a soft tissue anterolateral thigh (ALT) free flap, or a fibular free flap. The WG's contours were compared to a reference contour, validated by a surgeon and a radiologist specializing in HNC. Contours were considered as reproducible if the median Dice Similarity Coefficient (DSC) was > 0.7.Results: The median volumes of the six flaps delineated by the WG were close to the reference contour value, with approximately 50 cc for the pectoral, fibula, and ALT flaps, 20 cc for the radial forearm, and up to 10 cc for the FAMM. The volumetric ratio was thus close to the optimal value of 100% for all flaps. The median DSC obtained by the WG compared to the reference for the pectoralis flap, the FAMM, the radial forearm flap, ALT flap, and the fibular flap were 0.82, 0.40, 0.76, 0.81, and 0.76, respectively.Conclusions: This study showed that the delineation of four main flaps used for HNC was reproducible. The delineation of the FAMM, however, requires close cooperation between radiologist, surgeon and radiation oncologist because of the poor visibility of this flap on CT and its small size.

152 Background: In castrate-resistant oligo metastatic prostate Cancer (CRoligoMPC), the benefit of metastases-directed ablative radiotherapy (MDRT) is poorly investigated. Our study retrospectively reviewed the cases of CR oligoMPC treated with MDRT. Methods: Patients receiving MDRT in CRoligoMPC were retrospectively reviewed. Patients were included if: they had < 5 metastases on metabolic work-up, testosterone is < 50 ng/mL, metastases received MDRT. Patients and disease's data were collected: age, Gleason score, time to metastases, time to castration resistance; medical treatments, metastases location (bone versus node); radiotherapy regimens, PSA (PSA doubling time PSADT at the time of MDRT and PSA response). Progression was assessed according to PCWG criteria. PFS and OS are defined as the time from MDRT to first progression, for PFS and death date for OS. Kaplan-Meier analysis was used to summarize time-to-event variables and curves were compared with the log-rank test. A logistic regression was used to identify predictive factors of PFS. Results: the median follow up is 25.6 months.107 patients met inclusion criteria, among those 197 metastases received MDRT. Median age at MDRT time was 73 years. Median hormonosensitivity duration was 38 months (4-225). Forty six patients had metastases at the time of hormonosensitivity and 61 developed metastases in the castration resistance (CR)period (spartan-like population). PSA doubling time at the time of MDT RT was < 12 months in 88%. A median number of 2 metastases per patient was treated (1-4), 54% had RT on bony metastases only, 38% on nodes, 8% on bone + node. In 61 patients with metastases at the time of CRPC, 34.5% received a CR systemic medication before or concomitantly to MDRT, 39% received CR medication at progression, 23.5% never received CR treatment (unknown in 3%). OS is 93% at 2 years and 81.4% at 3 years. For node-only metastases, 2y OS is 100% versus 89% for bone metastases. Median PFS is 12.6 months (IC 95% [9.6; 17]). Metastases location, grade group, PSA or hormonosensitivity duration were not related to PFS in a univariate survival analysis. PFS was 10.2 months when PSA Doubling time was < 6 months, versus 18.2 months when it exceeded 6 months (NS). The PSA 50% response was studied in the Spartan like population, it was 83.4% in patients receiving MDRT AND new generation hormonotherapy; 31% in those who received MDRT without new generation hormonotherapy, and 20% in those who received MDRT at the time of progression of oligometastases occurring under new generation hormonotherapy. Conclusions: In a population of CR oligoM PC with short PSA DT, MDRT leads to a PFS of 12.6 months and to a 3y OS of 81.4%. In this setting, androgen receptor targeting agents are the standard of care. Whether adding MDRT could improve prognosis should be prospectively evaluated.

Resume Objectif de l’etude Pour faciliter la formation a la delineation, la Societe francaise de radiotherapie oncologique (SFRO) et l’association de formation continue en oncologie radiotherapie (Afcor) ont cree en 2008 un site Internet de radioanatomie et d’aide a la delineation. Materiel et methodes Entre 2015 et 2017, une mise a jour du site a ete entreprise, necessitant la mise en place de deux parties : des cours theoriques d’une part, et des ateliers de delineation en ligne d’autre part. Resultats Un nouveau site exploitant l’ensemble des nouvelles technologies numeriques a ete mis en ligne. Les cours ont ete realises sous forme de videos commentees et consultables a tout moment. La partie pratique offre une interface de delineation en ligne qui genere a la fin de l’exercice un rapport permettant de quantifier la qualite de sa delineation. Conclusion Siriade 2.0 est un outil numerique innovant qui s’inscrit en complement des formations initiales et continues deja disponibles.

Background Prognostic factors can impact the quality of life and overall survival in metastatic situations: sarcopenia and nutritional status disorders. Methods We conducted a non-interventional, observational prospective study during 3 consecutive months (SPACE trial, ClinicalTrials.gov identifier: NCT04714203). Performance status, lumbar skeletal muscle index (by CT scan), albumin, C-reactive protein, or LDH, were collected from medical records in the classic balance sheet at inclusion and then at 3 and 6 months after the day of inclusion. Results 38 patients were included with a median age of 68 years old and 31 were evaluable for sarcopenia. 58.1% of patients with metastatic cancer were sarcopenic at the diagnosis and 61% at 6 months. At the inclusion, 87.5% of sarcopenic patients were men (p

Purpose Endoscopic endonasal surgery (EES) is becoming a standard for most malignant sinonasal tumours. Margin analysis after piecemeal resection is complex and optimally relies on accurate histosurgical mapping. Postoperative radiotherapy may be adapted based on margin assessment mapping to reduce the dose to some sinonasal subvolumes. We assessed the use of histosurgical mapping by radiation oncologists (RO). Material and methods A French practice survey was performed across 29 ENT expert RO (2 did not answer) regarding integration of information on EES, as well as quality of operative and pathology reportsto refine radiotherapy planning after EES. This was assessed through an electronic questionnaire. Results EES was ubiquitously performed in France. Operative and pathology reports yielded accurate description of EES samples according to 66.7% of interviewed RO. Accuracy of margin assessment was however insufficient according to more than 40.0% of RO. Additional margins/biopsies of the operative bed were available in 55.2% (16/29) of the centres. In the absence of additional margins, quality of resection after EES was considered as microscopically incomplete in 48.3% or dubious in 48.3% of RO. As performed, histosurgical mapping allowed radiotherapy dose and volumes adaptation according to 26.3% of RO only. Conclusions Standardized histosurgical mapping with margin and additional margin analysis could be more systematic. Advantages of accurate EES reporting could be dose painting radiotherapy to further decrease morbidity in sinonasal tumours.

It is proposed to delineate the anatomo-clinical target volumes of primary tumor (CTV-P) in ethmoid cancers treated with post-operative radiotherapy. This concept is based on the use of radioanatomy and the natural history of cancer. It is supported by the repositioning of the planning scanner with preoperative imaging for the replacement of the initial GTV and the creation of margins around it extended to the microscopic risk zones according to the anatomical concept. This article does not discuss the indications of external radiotherapy but specifies the volumes to be delineated if radiotherapy is considered.

Contains fulltext : 235407.pdf (Publisher’s version ) (Closed access) BACKGROUND: Randomised, controlled trials and meta-analyses have shown the survival benefit of concomitant chemoradiotherapy or hyperfractionated radiotherapy in the treatment of locally advanced head and neck cancer. However, the relative efficacy of these treatments is unknown. We aimed to determine whether one treatment was superior to the other. METHODS: We did a frequentist network meta-analysis based on individual patient data of meta-analyses evaluating the role of chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC]) and of altered fractionation radiotherapy (Meta-Analysis of Radiotherapy in Carcinomas of Head and Neck [MARCH]). Randomised, controlled trials that enrolled patients with non-metastatic head and neck squamous cell cancer between Jan 1, 1980, and Dec 31, 2016, were included. We used a two-step random-effects approach, and the log-rank test, stratified by trial to compare treatments, with locoregional therapy as the reference. Overall survival was the primary endpoint. The global Cochran Q statistic was used to assess homogeneity and consistency and P score to rank treatments (higher scores indicate more effective therapies). FINDINGS: 115 randomised, controlled trials, which enrolled patients between Jan 1, 1980, and April 30, 2012, yielded 154 comparisons (28 978 patients with 19 253 deaths and 20 579 progression events). Treatments were grouped into 16 modalities, for which 35 types of direct comparisons were available. Median follow-up based on all trials was 6·6 years (IQR 5·0-9·4). Hyperfractionated radiotherapy with concomitant chemotherapy (HFCRT) was ranked as the best treatment for overall survival (P score 97%; hazard ratio 0·63 [95% CI 0·51-0·77] compared with locoregional therapy). The hazard ratio of HFCRT compared with locoregional therapy with concomitant chemoradiotherapy with platinum-based chemotherapy (CLRT(P)) was 0·82 (95% CI 0·66-1·01) for overall survival. The superiority of HFCRT was robust to sensitivity analyses. Three other modalities of treatment had a better P score, but not a significantly better HR, for overall survival than CLRT(P) (P score 78%): induction chemotherapy with taxane, cisplatin, and fluorouracil followed by locoregional therapy (IC(TaxPF)-LRT; 89%), accelerated radiotherapy with concomitant chemotherapy (82%), and IC(TaxPF) followed by CLRT (80%). INTERPRETATION: The results of this network meta-analysis suggest that further intensifying chemoradiotherapy, using HFCRT or IC(TaxPF)-CLRT, could improve outcomes over chemoradiotherapy for the treatment of locally advanced head and neck cancer. FUNDINGS: French Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC.

Background Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated. Patients and Methods In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and June 11, 2020. The primary endpoint was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary endpoints. Results From April 4 to June 11, 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), ECOG PS ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except cytotoxic chemotherapy in the subgroup of patients with detectable SARS-CoV-2 by RT-PCR, which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment interrupted or stopped following diagnosis of COVID-19. Conclusions Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis., Highlights • A total of 1289 patients with solid tumours and COVID-19 were analysed. • Mortality and COVID-19 severity were mainly driven by patient general characteristics. • Overall, we found no deleterious effects of recent anticancer treatments on mortality. . • Systemic anticancer treatment was interrupted or stopped in 39% of patients.

Background In Europe, induction chemotherapy (ICT) followed by radiotherapy is preferred to conventional chemoradiotherapy to avoid total laryngectomy in patients with laryngeal/hypopharyngeal cancer. In comparison with conventional radiotherapy, bioradiotherapy with cetuximab significantly improves locoregional control rates (LCRs) and overall survival (OS) without any increase in unmanageable toxicity. Methods Patients included had untreated non-metastatic stage III–IV laryngeal/hypopharyngeal invasive squamous cell carcinoma. Good responders after three cycles of docetaxel-cisplatin-5-fluorouracil (TPF)-ICT (docetaxel and cisplatin, 75 mg/m2 each on day 1, and 5-fluorouracil, 750 mg/m2/day on days 1–5) every 3 weeks were randomised to receive radiotherapy (70 Gy) with concurrent cisplatin (100 mg/m2/day on days 1, 22 and 43 of radiotherapy) or cetuximab (400 mg/m2 of loading dose, 250 mg/m2/week during radiotherapy). The primary end-point was larynx preservation. The secondary end-points were laryngo-oesophageal dysfunction-free survival (LEDFS), LCR and OS. Results A total of 153 patients were enrolled. Among 126 TPF-ICT responders, 116 were randomised to receive either cisplatin (n = 60) or cetuximab (n = 56). The median follow-up was 77.5 months. Five-year OS rates were 66.6% (95% confidence interval [CI]: 0.54–0.79) versus 66.9% (95% CI: 0.54–0.79) (p = 0.9), respectively. Five-year LCRs were 79.8% (95% CI: 69.5–90.0) versus 67.8% (95% CI: 55.1–80.5%) (p = 0.18). Five-year LEDFS was 62.2% (95% CI: 49.7–74.8%) versus 56.2% (95% CI: 43.0–69.4) (p = 0.38). Late grade III/IV salivary gland and laryngeal toxicity occurred in 10.3% versus 9.8% and 6.8% versus 11.8% of patients receiving cisplatin-radiotherapy versus cetuximab, respectively. Conclusions No significant difference in LEDFS was observed between the two arms. TPF-ICT followed by conventional chemoradiotherapy or cetuximab was feasible, and long-term toxicity was not statistically different between the two arms. LEDFS appears as a relevant end-point.

Purpose Both concurrent chemoradiotherapy (CT-RT) and cetuximab radiotherapy (cetux-RT) have been established as the standard of care for the treatment of locally advanced squamous cell carcinoma of the head and neck. It was not known whether the addition of induction chemotherapy before cetux-RT could improve outcomes compared with standard of care CT-RT. Patients and Methods The current trial was restricted to patients with nonmetastatic N2b, N2c, or N3 squamous cell carcinoma of the head and neck and fit for taxotere, cisplatin, fluorouracil (TPF). Patients were randomly assigned to receive three cycles of TPF followed by cetux-RT versus concurrent carboplatin fluorouracil and RT as recommended in National Comprehensive Cancer Network guidelines. The trial was powered to detect a hazard ratio (HR) of 0.66 in favor of TPF plus cetux-RT for progression-free survival at 2 years. The inclusion of 180 patients per arm was needed to achieve 80% power at a two-sided significance level of .05. Results Between 2009 and 2013, 370 patients were included. All patients and tumors characteristics were well balanced between arms. There were more cases of grade 3 and 4 neutropenia in the induction arm, and the induction TPF was associated with 6.6% treatment-related deaths. With a median follow-up of 2.8 years, 2-year progression-free survival was not different between both arms (CT-RT, 0.38 v TPF + cetux-RT, 0.36; HR, 0.93 [95% CI, 0.73 to 1.20]; P = .58). HR was 0.98 (95% CI, 0.74 to 1.3; P = .90) for locoregional control and 1.12 (95% CI, 0.86 to 1.46; P = .39) for overall survival. These effects were observed regardless of p16 status. The rate of distant metastases was lower in the TPF arm (HR, 0.54 [95% CI, 0.30 to 0.99]; P = .05). Conclusion Induction TPF followed by cetux-RT did not improve outcomes compared with CT-RT in a population of patients with advanced cervical lymphadenopathy.

Purpose To investigate the effect of adding concurrent chemotherapy (CT) to cetuximab plus radiotherapy (RT; CT-cetux-RT) compared with cetuximab plus RT (cetux-RT) in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Patients and Methods In this phase III randomized trial, patients with N0-2b, nonoperated, stage III or IV (nonmetastatic) LA-SCCHN were enrolled. Patients received once-daily RT up to 70 Gy with weekly cetuximab or with weekly cetuximab and concurrent carboplatin and fluorouracil (three cycles). To detect a hazard ratio (HR) of 0.64 for progression-free survival (PFS) with 85% power at a two-sided significance level of P = .05, 203 patients needed to be included in each arm. Results Four hundred six patients were randomly assigned to either CT-cetux-RT or cetux-RT. Patient and tumor characteristics were well balanced between arms, including p16 status. With a median follow-up of 4.4 years, the HR for PFS favored the CT-cetux-RT arm (HR, 0.73; 95% CI, 0.57 to 0.94; P = .015), with 3-year PFS rates of 52.3% and 40.5% and median PFS times of 37.9 and 22.4 months in the CT-cetux-RT and cetux-RT arms, respectively. The HR for locoregional control was 0.54 (95% CI, 0.38 to 0.76; P < .001) in favor of CT-cetux-RT. These benefits were observed regardless of p16 status for oropharynx carcinomas. Overall survival (HR, 0.80; P = .11) and distant metastases rates (HR, 1.19; P = .50) were not significantly different between the two arms. The CT-cetux-RT arm, compared with cetux-RT, had a higher incidence of grade 3 or 4 mucositis (73% v 61%, respectively; P = .014) and of hospitalizations for toxicity (42% v 22%, respectively; P < .001). Conclusion The addition of concurrent carboplatin and fluorouracil to cetux-RT improved PFS and locoregional control, with a nonsignificant gain in survival. To our knowledge, this is the first evidence of a clinical benefit for treatment intensification using cetux-RT as a backbone in LA-SCCHN.

We aimed to investigate whether patient self-evaluated symptoms transmitted via Internet is feasible between planned visits to provide an early management of fever and neutropenia induced by chemotherapy, and if it can reduce hospitalizations for severe neutropenia. Patients who received a chemotherapy regimen with an overall risk of febrile neutropenia ≥ 20% had to report daily temperature between physician planned visits using a web application. Fever and clinical signs of seriousness were reported to the physician (if some criteria were fulfilled in a specific algorithm) via automatic email notifications by the web application. Patients could be hospitalized quickly or could take over at home, make blood count, and take predefined oral antibiotics if indicated. Primary outcome was patient’s compliance and satisfaction. The number and the cost of hospitalization were also assessed and compared with an historical cohort of patients with similar clinical conditions and treatment. Among the 41 patients included, 36 (87.8%) used the web application with 88% of daily compliance and 90% (28/33) of satisfaction. One patient (2.7%) had planned hospitalization after the web application alert. In the historical cohort, the rate of unplanned hospitalization for febrile neutropenia was 17% (6 patients) and 2.7% (1 patient) in users of the web application cohort. The cumulative cost of hospitalization for neutropenia was USD 28,827 in the historical cohort and USD 6563 in the web application cohort. Web-mediated follow-up of febrile neutropenia is feasible. It led to high patient satisfaction, high compliance, and a possible reduction of the number and the cost of hospitalizations.

Resume En neuro-oncologie, le nombre de patients irradies avec une esperance de vie prolongee augmente. De plus, la radiotherapie encephalique est associee a un indice therapeutique etroit. La preservation des organes a risque est liee aux techniques d’irradiation, doses et balistiques, mais aussi a la reproductibilite du traitement. L’essor de la stereotaxie et de la protontherapie accentue cette problematique. L’importance de l’utilisation de l’imagerie et du repositionnement est souvent sous-estimee en raison d’une delegation de tâches et d’une revue d’images repetitive et fastidieuse. Pourtant, la radiotherapie guidee par l’image, dans le cas des irradiations intracrâniennes, a permis d’eviter des contentions invasives pour le patient, mais aussi un gain en termes de qualite de repositionnement et de duree des recalages. Les reperes osseux crâniens et le peu de mouvements entre et pendant les fractions des volumes a irradier permettent une automatisation des repositionnements via le guidage par l’image. Neanmoins, les protocoles d’imagerie au poste de traitement sont de la responsabilite du radiotherapeute (qualite, frequence, utilisation). Cet article propose une mise au point de l’utilisation du guidage par l’image au service des irradiations encephaliques, en se focalisant sur son utilisation pour le repositionnement et ses perspectives quant a la radiotherapie adaptative.

Low-level laser therapy (LLLT) also called Photobiomodulation therapy (PBMT) could reduce oral mucositis (OM) incidence and severity in head and neck cancer patients treated by chemoradiotherapy, however randomised data about efficacy and safety are missing with curative dose 4 J/cm2. This phase III trial was conducted in patients with oral cavity, or oro/hypopharyngeal cancers (stage III or IV). Patients were treated by lasertherapy on OM lesions grade ≥ 2 (4 J/cm2 or placebo), during chemoradiotherapy and until recovery. Severity of OM (incidence and duration of grades ≥3) was used as primary endpoint and blindly assessed. Among 97 randomised patients, 83 patients (85.6%) could be assessed finally (erroneous inclusions, chemoradiotherapy interruptions) and 32 patients had no lasertherapy because of unreachable OM lesions. Randomisation and population characteristics (sex ratio, age, chemoradiotherapy procedures, toxicities incidence) were still comparable between the two LLLT/PBMT groups. An acute OM (grade ≥ 3) was observed in 41 patients (49.4%): 23 patients (54.8%) of the active laser group versus 18 (43.9%) in the control group (modified intend to treat, p = 0.32). Median time before occurrence of OM ≥ grade 3 in half of the patients was 8 weeks in active laser group (vs. 9 weeks in control group). However, 95% of patients exhibited a very good tolerance of LLLT/PBMT. This study assessed LLLT/PBMT according to the Multinational Association of Supportive care in Cancer recommendations but lacked power. LLLT/PBMT was well tolerated with a good safety profile, which promotes its use in clinical routine for severe OM treatment. ClinicalTrials.gov Identifier: NCT01772706 . Title: Laser Mucite ORL: Effectiveness of Laser Therapy for Mucositis Induced by a Radio-chemotherapy in Head and Neck Cancer (LaserMucite). Study Start Date: October 2008. Primary Completion Date: October 2016. Responsible Party: Institut de Cancerologie de l’Ouest – Paul Papin. Principal Investigator: Eric Jadaud, M.D., Institut de Cancerologie de l’Ouest – Paul Papin. Funding: French Ministry of Health, French national funding scheme (PHRC 2008).

Resume Le traitement des carcinomes epidermoides des voies aerodigestives localement evolues repose sur la chimioradiotherapie concomitante. Un traitement sequentiel associant chimiotherapie d’induction par association de docetaxel, cisplatine et 5-fluoro-uracile (TPF), suivie d’une (chimio)radiotherapie, est utilise frequemment dans le cadre des strategies de preservation laryngee. En dehors de cette situation particuliere, le benefice en termes de survie d’une chimiotherapie d’induction a ete beaucoup discute ces dernieres annees. Dans cinq essais randomises recents, une chimioradiotherapie a ete comparee a une chimiotherapie d’induction par TPF, suivie d’une chimioradiotherapie. Parmi ces cinq essais, quatre concluent que ces traitements sont similaires. Un seul essai a montre un benefice de la chimiotherapie d’induction mais sa methodologie est tres discutable. Apres la chimiotherapie par TPF, la chimioradiotherapie est moins bien toleree. En cas d’envahissement ganglionnaire important (stade N2b-c-N3), la chimiotherapie d’induction permet de diminuer la survenue de metastases a distance. Le statut selon l’ Human papilloma virus (HPV) ne doit pas influencer la decision therapeutique.

Induction chemotherapy must be integrated in a global approach for locally advanced head and neck cancer. Its use has theoretical advantages but should not compromise locoregional radiotherapy. Induction chemotherapy is a standard for organ preservation with the use of the TPF scheme to avoid total laryngectomy without compromising survival data. It is more controversial in other locally advanced head and neck cancer because concurrent chemoradiotherapy is the standard of care. It may be an option for patients with significant lymph node invasion to reduce the occurrence of distant metastasis.

Resume Cet article passe en revue les grands principes therapeutiques en matiere d’irradiation des cancers de la tete et du cou. La radiotherapie avec modulation d’intensite (RCMI), associee a une chimiotherapie par cisplatine est desormais le standard en situation exclusive hors preservation laryngee. Le cetuximab doit etre privilegie en cas de contre-indications aux sels de platine tandis que l’hyperfractionnement peut etre evoque en cas de contre-indication a un traitement concomitant. En situation postoperatoire, une chimiotherapie par cisplatine est proposee en cas d’effractions capsulaires et d’atteinte des tranches de section, et peut egalement etre discutee en cas de facteurs d’agressivite histologique. Plusieurs etudes de desescalade therapeutique en cas d’infection par les papillomavirus sont en cours. La radiotherapie adaptative, l’immunotherapie, ainsi que l’imagerie pour guider la therapeutique representent egalement des domaines de recherche qui aboutiront certainement a des modifications de prise en charge dans les annees a venir.

To investigate the use of metabolic parameters as early prognostic factors during concomitant chemoradiotherapy for locally advanced cervix carcinoma (LACC). Between February 2008 and January 2012, 34 consecutive patients treated for LACC (International Federation of Gynecology and Obstetrics Staging System stage IB2-IVA) were included in a retrospective study. Treatment was standard of care: total dose of 45 Gy in 1.8 Gy per fraction with concurrent cisplatin followed by brachytherapy. 18F-FDG PET-CT modalities were performed before treatment and per-treatment (at 40 Gy). The analyzed parameters were: maximum standardized uptake value (SUVmax), SUVmax variations of the primary tumor between the 2 investigations (DSUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Survival was assessed according to early metabolic changes during chemoradiotherapy. Median follow-up was 16 months (range, 5.3 to 32.4 mo). Median SUVmax before treatment was 13.15 (5.9 to 31) and was 5.05 (0 to 12) per-treatment. Median DSUVmax was 63.97% (0% to 100%). Median MTV before treatment was 44.16 mL (3.392 to 252.768 mL) and was 5.44 mL (0 to 69.88 mL) per-treatment. Median TLG before treatment was 249.82 mL (13.40 to 1931.10 mL) and was 20.14 mL (0 to 349.99 mL) per-treatment. At 40 Gy, SUVmax≥6, DSUVmax≤40%, MTV≥5.6 mL, and TLG≥21.6 mL were significantly associated with overall survival and progression-free survival reduction. MTV predicted progression with a sensitivity of 80% and a specificity of 87.5% and TLG with a sensitivity of 80% and a specificity of 83.3%. PET-CT imaging could be useful as an early prognostic factor during treatment for LACC. MTV and TLG seem to provide better prognostic information than SUVmax and DSUVmax.

Purpose The main objective of this study was to evaluate the 5-year efficacy of exclusive laryngeal radiotherapy without node prophylactic irradiation for localized cancers of the vocal cords. Patients and methods We retrospectively reviewed charts from 258 patients with T1-T2N0 glottic carcinoma irradiated from April 1987 to March 2015 in four France western centers, including pretreated patients. Toxicity was analyzed according to CTCAE v4.0 classification. Results The median follow-up was 50 months. The median age was 67 years with 87% men and 85.5% had T1 tumor. Five years overall survival was 77.5% (95% confidence interval [95% CI]: 71.4–83.5), 5 years local control was 86.8% (95% CI: 82.3–91.3), specific survival rate was 95% (95% CI: 92.2–97.9) and final laryngectomy-free survival was 87.5% (95% CI: 82.2–92.9). Most toxicities were grade 1 and 2. Grade 3 acute toxicity was 15.5% for the radiation laryngitis, 3.5% for radiodermatitis and 7.7% for dysphonia. Grade 3 chronic toxicity was 3.5% for dysphonia and there were two cases of tracheal stenosis treated by tracheotomy. Conclusion Radiotherapy provides good results in local control of stage I and II vocal cords cancers as well as the toxicity level.

Introduction et but de l’etude Le consensus international de delineation des volumes cible anatomocliniques tumoraux des carcinomes epidermoides des voies aerodigestives superieures a propose l’application de marges d’expansion geometriques autour du volume tumoral macroscopique (5 + 5 mm avec adaptation par localisation) selon le concept du Danish Head and Neck Cancer Group (DAHANCA). Il offre l’avantage d’une standardisation des pratiques mais la methodologie d’obtention de ce consensus fait defaut. Ce changement de pratique a pousse le Groupe d’oncologie radiotherapie tete et cou (Gortec) a la mise en place d’une demarche de validation interne. Materiel et methodes La methode utilisee etait celle du consensus formalise de la Haute autorite de sante (HAS) qui permet de formaliser le degre d’accord et fonder des recommandations par deux phases de cotations iteratives suivies d’une etape de lecture de propositions definitives. Les cotations variaient de 1 a 9. Les propositions etaient jugees appropriees si la mediane des cotations etait superieure ou egale a 7 (extremes : 5-9), inappropriees si elle etait inferieure ou egale a 3,5 (extremes : 1-5) ; incertaines pour les autres valeurs. La cotation sur le degre d’accord selon Lee et al. etait utilisee en complement (≥ 85 % : haut, 75-84 % : modere ; Resultats et analyse statistique Le chapitre « General description of the procedure for the primary tumour (CTV-P) delineation » comportait 13 propositions. Neuf etaient cotees appropriees et quatre incertaines avec des degres d’accord moderes a hauts (77 a 92 %). Le chapitre « Guidelines for the delineation of the primary tumour CTV site by site » precisant la delineation organe par organe selon le stade T comportait 32 propositions. Elles etaient toutes jugees incertaines avec des degres d’accord faibles (47-69 %). Seules les propositions sur les T1 (volumes cible anatomocliniques P1 et P2) avaient un degre d’accord modere (84,5 %). Le chapitre « Discussion : Limit of validity and A word of caution » comportait quatre propositions. Deux etaient jugees appropriees et deux incertaines avec des degres d’accord hauts (92 a 100 %). Les huit items sur les choix proposes par le Gortec etaient appropries pour cinq, incertains pour deux et inapproprie pour un. La proposition d’appliquer strictement le concept geometrique etait jugee inappropriee avec 0 % d’accord. La proposition de s’orienter vers une approche « geoanatomique » consistant a debuter la delineation du volume cible anatomoclinique P2 selon le concept geometrique puis d’etendre cette delineation selon le concept anatomique des voies d’extension tumorale, etait jugee appropriee avec un haut degre d’accord (100 %). Conclusion Les resultats des phases de cotation s’orientent vers une validation interne par le Gortec du consensus complete par une approche « geoanatomique » pour la delineation du volume cible anatomoclinique P2. Les resultats de la derniere etape de lecture devraient etre disponibles le jour du congres.

Patients with cervical lymphadenopathy of unknown primary carcinoma (CUP) usually undergo neck dissection and irradiation. There is an ongoing controversy regarding the extent of nodal and mucosal volumes to be irradiated. We assessed outcomes after bilateral or unilateral nodal irradiation.This retrospective multicentre study included patients with CUP and squamous cellular carcinoma who underwent radiotherapy (RT) between 2000 and 2015.Of 350 patients, 74.5% had unilateral disease and 25.5% had bilateral disease. Of 297 patients with available data on disease and irradiation sides, 61 (20.5%) patients had unilateral disease and unilateral irradiation, 155 (52.2%), unilateral disease and bilateral irradiation and 81 (27.3%), bilateral disease and bilateral irradiation. Thirty-four (9.7%) and 217 (62.0%) patients received neoadjuvant and/or concomitant chemotherapy, respectively. Median follow-up was 37 months. Three-year local, regional, locoregional failure rates and CUP-specific survival were 5.6%, 11.7%, 15.0% and 84.7%, respectively. In patients with unilateral disease, the 3-year cumulative incidence of regional/local relapse was 7.7%/4.3% after bilateral irradiation versus 16.9%/11.1% after unilateral irradiation (hazard ratio = 0.56/0.61, p = 0.17/0.32). The cumulative incidence of CUP-specific deaths was 9.2% after bilateral irradiation and 15.5% after unilateral irradiation (p = 0.92). In multivariate analysis, mucosal irradiation was associated with better local control, whereas no neck dissection, ≥N2b and interruption of RT for more than 4 days were associated with poorer regional control. Toxicity was higher after bilateral irradiation (p 0.05). No positron-emission tomography-computed tomography, largest node diameter, ≥N2b, neoadjuvant chemotherapy and interruption of RT were associated with poorer cause-specific survival.Bilateral nodal irradiation yielded non-significant better nodal and mucosal control rates but was associated with higher rates of severe toxicity.

Resume La radiotherapie conformationnelle avec modulation d’intensite (RCMI) est la technique de reference dans le traitement des cancers des voies aerodigestives superieures. Un des objectifs est la protection des organes a risque tels que les glandes salivaires et la mandibule. Les risques d’hyposialie, de trismus et d’osteoradionecrose doivent etre reduits. La delineation et l’optimisation dosimetrique doivent permettent de ne pas depasser une dose moyenne de 26 Gy dans la parotide, de 39 Gy dans la glande sous-maxillaire, de 60 a 65 Gy dans la mandibule et une dose dans 2 % du volume ( D 2 % ) de moins de 65 Gy pour les articulations temporomandibulaires. Les donnees sur les contraintes de doses restent encore a affiner par des etudes utilisant la RCMI. Ces contraintes sont a integrer dans le contexte clinique et doivent etre ponderees afin de ne pas conduire a un traitement insuffisant de la maladie tumorale.

Given the ballistic opportunities it offers, intensity-modulated radiotherapy has emerged as the gold standard treatment for head and neck cancers. Protection of organs at risk is one of the objectives of optimization during the planning process. The compliance of dose constraints to the nervous system must be prioritized over all others. To avoid complications, it is recommended to respect a maximum dose of 50Gy to the spinal cord, and 60Gy to the brachial plexus using conventional fractionation of 2Gy per fraction. These constraints can be adapted depending on the clinical situation; they will probably be refocused by the follow-up of the IMRT studies.

Radiation-induced damage of ocular, orbital and eyelid structures are mainly reported for the optic nerve, retina, lens and lacrimal gland. Dose-volume relationships are, however, inaccurate due to the small volume of most of the organs at risk involved and limited ability of irradiation techniques to spare these structures in the pre-IMRT (intensity-modulated radiation therapy) era. The ability of newest radiation techniques including IMRT and proton therapy to generate steep dose gradients may yield more accurate models in the future. Some toxicities are severe and irreversible, leading to vision loss, as in the case of radiation-induced optic neuropathy for which curative treatments are suboptimal. Other toxicities can lead to reversible vision loss but can be surgically corrected, as is the case for radiation-induced cataract. In this paper, we will review the dose effects for the ocular; orbital and eyelid structures.

Radio-induced pharyngolaryngeal chronic disorders may challenge the quality of life of head and neck cancer long survivors. Many anatomic structures have been identified as potentially impaired by irradiation and responsible for laryngeal edema, dysphonia and dysphagia. Some dose constraints might be plausible such as keeping the mean dose to the pharyngeal constrictor muscles under 50 to 55Gy, the mean dose to the supra-glottic larynx under 40 to 45Gy and, if feasible, the mean dose to the glottic larynx under 20Gy. A reduction of the dose delivered to the muscles of the floor of the mouth and the cervical esophagus would be beneficial as well. Nevertheless, the publications available do not provide an extensive enough level of proof. One should consider limiting as low as possible the dose delivered to these structures without compromising the quality of irradiation of the target tumor volumes.

Modern techniques such as intensity modulated radiation therapy (IMRT) have been proven to significantly decrease the dose delivered to the cochleovestibular apparatus, limiting consecutive toxicity especially for sensorineural hearing loss. However, recent data still report a 42% rate of radio-induced hypoacusia underscoring the need to protect the cochleovestibular apparatus. Due to the small size of the cochlea, a precise dose-volume analysis could not be performed, and recommendations only refer to the mean dose. Confusing factors such as age, concomitant chemotherapy, primary site and tumor stage should be taken into account at the time of treatment planning. (Non-coplanar) VMAT and tomotherapy have been proven better at sparing the cochlea in comparison with 3D CRT. Brainstem radio-induced injuries were poorly studied because of their infrequency and the difficulty of distinguishing between necrosis and tumor progression in the case of a primary tumor located at the base of skull. The following toxicities have been described: brainstem focal radionecrosis, cognitive disorders without dementia, cranial nerve injuries and sensori motor disability. Maximal dose to the brainstem should be kept to

Background A retrospective study was conducted to analyze interindividual variability of cetuximab pharmacokinetics and its influence on survival (progression-free survival and overall survival [OS]) in a cohort of head and neck squamous cell carcinoma (HNSCC). Methods Thirty-four patients received cetuximab as an infusion loading dose of 400 mg/m followed by weekly infusions of 250 mg/m. Twenty-one patients had locally advanced HNSCC, and 13 had metastatic/recurrent HNSCC. Cetuximab concentrations were measured by the enzyme-linked immunosorbent assay, and its pharmacokinetics was analyzed by a population approach. Survivals were analyzed with the log-rank test. Results Cetuximab pharmacokinetics was best described using a 2-compartment model with both first-order and saturable (zero-order) eliminations. Estimated pharmacokinetic parameters (%CV) were central volume of distribution V1 = 3.18 L (6%), peripheral volume of distribution V2 = 5.4 L (42%), elimination clearance CL = 0.57 L/d (31%), distribution clearance Q = 0.64 L/d, and zero-order elimination rate k0 = 6.72 mg/d (29%). Both V1 and V2 increased with the body surface area. Adjunction of chemotherapy reduced CL and increased k0. OS was inversely related with cetuximab global clearance (P = 0.007) and was higher in patients with severe radiation dermatitis (P = 0.005). Conclusions Cetuximab pharmacokinetics in patients with HNSCC can be described using a 2-compartment model combining linear and nonlinear mechanisms of elimination. OS is associated with both cetuximab global clearance and severe radiation dermatitis.

The intensity-modulated radiotherapy is the gold standard in the treatment of hypopharynx cancers. Early T1 and T2 tumours could be treated by exclusive radiotherapy or surgery. For tumours requiring total pharyngolaryngectomy (T2 or T3), induction chemotherapy followed by exclusive radiotherapy or concurrent chemoradiotherapy are possible. For T4 tumours, surgery must be proposed. The treatment of lymph nodes is based on the initial treatment of the primary tumour. In non-surgical procedure, in case of sequential radiotherapy, curative dose is 70Gy and prophylactic dose is 50Gy. An integrated simultaneous boost radiotherapy is allowed (70Gy in 2Gy per fraction and 56Gy in 1.8Gy per fraction or 70Gy in 2.12Gy per fraction). Postoperatively, radiotherapy is used for locally advanced cancers with dose levels based on pathologic criteria (66Gy for R1 resection, 50 to 54Gy for complete resection). Volume delineation is based on guidelines.

Indication, doses, technique of radiotherapy and concomitant chemotherapy for oropharynx carcinoma are presented. The recommendations for delineation of the target volumes and organs at risk are detailed.

Resume La radiotherapie conformationnelle avec modulation d’intensite (RCMI) est la technique de reference dans le traitement des cancers du larynx (en dehors de ceux de stade T1 du plan glottique). Les tumeurs localisees de stade T1 et T2 peuvent etre traitees soit par irradiation externe (exclusive), soit par chirurgie conservatrice. Pour les tumeurs necessitant une laryngectomie totale (stade T2 ou T3), une chimiotherapie d’induction suivie d’une radiotherapie externe exclusive ou une chimioradiotherapie concomitante exclusive d’emblee peuvent etre proposees. Pour les cancers de stade T4, une chirurgie est proposee. La prise en charge des aires ganglionnaires sera le plus souvent fonction du traitement initial de la tumeur primitive. En cas de tumeur en place, les doses a visee curative sont de 70 Gy et les doses prophylactiques de 50 Gy, en irradiation classique avec 2 Gy par fraction ou avec boost integre (70 Gy par fractions de 2 Gy et 56 Gy par fractions de 1,8 Gy ou 70 Gy par fractions de 2,12 Gy). Apres chirurgie, l’indication est retenue pour les cancers evolues, avec des niveaux de doses selon des criteres anatomopathologiques (66 Gy en cas de resection R1, 50 a 54 Gy en cas de resection complete). La definition des volumes tumoraux et ganglionnaires repose sur des recommandations.

The nasal cavity and parasinusal cancer are rare (10% of tumors of the head and neck) and are mainly represented by squamous cell carcinoma of the nasal cavity or the maxillary sinus and adenocarcinoma of the ethmoid sinus (occupational disease, wood dust). The most common clinical sign is nasal obstruction, but tumors can also manifest as rhinorrhea and/or epistaxis (usually unilateral signs). A magnetic resonance imaging of the facial structure is systematic for staging before treatment. The treatment consists of a first surgery if the patient is operable with a resectable tumor. If it is not the case, the treatment consists of radiotherapy (RT) associated with chemotherapy (CT) according to the initial data (T3/T4 or N+). After first surgery, RT is indicated (except T1N0 with complete resection) associated with a CT based on postoperative data (capsular effraction or incomplete resection). Lymph node irradiation is considered case by case, but is indicated in any nodal involvement. RT must be an intensity modulated RT (IMRT), static or dynamic, and must be imagery guided (IGRT). According to ICRU 83, doses to organs at risk and target volumes must be carried. Finally, after a post-treatment baseline imaging between 2 and 4 months, monitoring will be alternated with the ENT surgeon every 2 or 3 months for 2 years, then every 4 to 6 months for 5 years.