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To evaluate potential synergistic effect of pembrolizumab with radiotherapy (RT) compared with a standard-of-care (SOC) cetuximab-RT in patients with locally advanced-squamous cell carcinoma of head and neck (LA-SCCHN).Patients with nonoperated stage III-IV SCC of oral cavity, oropharynx, hypopharynx, and larynx and unfit for receiving high-dose cisplatin were enrolled. Patients received once-daily RT up to 69.96 Gy in 33 fractions with weekly cetuximab (cetuximab-RT arm) or 200 mg Q3W pembrolizumab during RT (pembrolizumab-RT arm). The primary endpoint was locoregional control (LRC) rate 15 months after RT. To detect a difference between arms of 60%-80% in 15-month LRC, inclusion of 66 patients per arm was required to achieve a power of at least 0.85 at two-sided significance level of 0.20.Between May 2016 and October 2017, 133 patients were randomized to cetuximab-RT (n = 66) and pembrolizumab-RT (n = 67). Two patients (one in each arm) were not included in the analysis (a consent withdrawal and a progression before treatment start). The median age was 65 years (interquartile range 60-70 years), 92% were smokers, 60% were oropharynx (46% of oropharynx with p16+) and 75% were stage IV. Median follow-up was 25 months in both arms. The 15-month LRC rate was 59% with cetuximab-RT and 60% with pembrolizumab-RT ]odds ratio 1.05, 95% confidence interval (CI) 0.43-2.59; P = 0.91]. There was no significant difference between arms for progression-free survival (hazard ratio 0.85, 95% CI 0.55-1.32; P = 0.47) and for overall survival (hazard ratio 0.83, 95% CI 0.49-1.40; P = 0.49). Toxicity was lower in the pembrolizumab-RT arm than in the cetuximab-RT arm: 74% versus 92% patients with at least one grade ≥3 adverse events (P = 0.006), mainly due to mucositis, radiodermatitis, and rash.Compared with the SOC cetuximab-RT, pembrolizumab concomitant with RT did not improve the tumor control and survival but appeared less toxic in unfit patients with LA-SCCHN.

Purpose This phase I study assessed the safety of first-in-class radioenhancer nanoparticles, NBTXR3, in elderly or frail patients with locally advanced head and neck squamous cell carcinoma (HNSCC), ineligible for chemoradiation. Methods Patients with stage III or IVA (American Joint Committee on Cancer (AJCC) guidelines, 7th edition, 2010) HNSCC of the oral cavity or oropharynx, aged ≥70 or ≥65 years and ineligible to receive cisplatin, amenable to radiotherapy (RT) with curative intent, received NBTXR3 as a single intratumoural (IT) injection followed by activation by intensity-modulated radiation therapy (IMRT; 70 Gy). The NBTXR3 dose corresponded to a percentage of the baseline tumour volume, measured by magnetic resonance imaging. The primary objectives were to determine the recommended phase II dose (RP2D), dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Safety and tolerability were assessed using National Cancer Institute CTCAE version 4.0. Antitumour activity was assessed by Response Evaluation Criteria in Solid Tumours 1.1. Results Nineteen patients were enrolled: 3 at the dose level of 5%, 3 at the dose level of 10%, 5 at the dose level of 15% and 8 at the dose level of 22% of the tumour volume. The MTD was not reached, and no DLTs or serious adverse event (SAEs) related to NBTXR3 were observed. Four adverse events related to NBTXR3 and/or the IT injection were reported (grade I–II). NBTXR3 remained in the injected tumour throughout RT, with no leakage in the surrounding healthy tissues. Specific RT-related toxicity was as expected with IMRT. The RP2D was determined as 22% baseline tumour volume. Preliminary signs of antitumour activity were observed. Conclusion Intratumoural injection of NBTXR3 followed by IMRT is feasible and demonstrated a good safety profile, supporting further evaluation at the RP2D in this patient population. Trial registration ClinicalTrials.gov NCT01946867 .

PurposeTo assess the feasibility, safety and tolerability of CareMin650, a new photobiomodulation device, in patients treated by radiotherapy (RT). To collect preliminary data on efficacy for prevention and treatment of oral mucositis (OM) and radiation dermatitis (RD).MethodsFrench, multicentric, prospective, non-comparative study. Inclusion of patients with head and neck cancer (H&NC, cohort A) or breast cancer (BC, cohort B) treated in prophylactic (cohorts A1 and B1) or curative setting (cohort A2 and B2). Prophylactic treatment was administered from D1 to end of RT, at a dose of 3 J/cm2. Curative treatment started when a grade 1 to grade 3 lesion had occurred and was pursued until end of RT. Primary endpoint was incidence of device-related adverse events (AEs). OM and RD lesions were graded according to CTCAE V3.ResultsOverall, 72 patients were included (22, 9, 23 and 18 in cohorts A1, A2, B1 and B2 respectively). No device-related AE was reported after 1,312 CareMin650 sessions. In cohorts A1 and B1, median time to first OM or RD lesion was 20 days. One BC patient developed G3 RD after completion of RT and discontinuation of CareMin650. Four H&NC patients developed G3 OM. In cohorts A2 and B2, lesions improved or stabilized in 71% of patients. Rates of satisfaction were high among patients and users. ConclusionCareMin650 is feasible, safe and well tolerated for preventive or curative treatment of OM and RD in cancer patients treated with RT. Preliminary efficacy results are promising.

Hypofractionated radiotherapy of early-stage squamous cell carcinoma of the glottic larynx is a promising treatment option. This can be divided into radiotherapy with moderate hypofractionation (up to 2.5Gy per fraction), more intense hypofractionation (between 2.5 and 4.5Gy per fraction) and stereotactic radiotherapy (above 4.5Gy per fraction). Most studies evaluating moderate hypofractionation show a local control rate between 85 and 95%. Acute laryngeal toxicity is superior to conventional treatment, but only for grades 1 and 2, with no significant difference reported for severe toxicity. Stereotactic radiotherapy in this pathology is also an emerging entity, but some authors have reported significant toxicity. There are currently no standardized guidelines for treatment and management regimen. We conducted a systemic review of published prospective and retrospective trials to evaluate efficacy, toxicity, and discuss future directions.

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.

Background: There is no evidence to support surgery or radiotherapy as the best treatment for resectable oropharyngeal cancers with a negative HPV status. Predictive algorithms may help to decide which strategy to choose, but they will only be accepted by caregivers and European authorities if they are interpretable. As a proof of concept, we developed a predictive and interpretable algorithm to predict locoregional relapse at 18 months for oropharyngeal cancers as a first step towards that goal. Methods: The model was based on clinical and Pyradiomics features extracted from the dosimetric CT scan. Intraclass correlation was used to filter out features dependant on delineation. Correlated redundant features were also removed. An XGBoost model was cross-validated and optimised on the HN1 cohort (79 patients), and performances were assessed on the ART ORL cohort (45 patients). The Shapley Values were used to provide an overall and local explanation of the model. Results: On the ART ORL cohort, the model trained on HN1 yielded a precision&mdash, or predictive positive value&mdash, of 0.92, a recall of 0.42, an area under the curve of the receiver operating characteristic of 0.68 and an accuracy of 0.64. The most contributory features were shape Voxel Volume, grey level size zone matrix Small Area Emphasis (glszmSAE), gldm Dependence Non Uniformity Normalized (gldmDNUN), Sex and Age. Conclusions: We developed an interpretable and generalizable model that could yield a good precision&mdash, positive predictive value&mdash, for relapse at 18 months on a different test cohort.

PURPOSE/OBJECTIVE(S) Concurrent radiotherapy (RT) with high-dose cisplatin, or cetuximab in case of intolerance to cisplatin, are the non-surgical standard treatment for locally advanced head and neck squamous cell carcinoma (LA HNSCC). However, elderly patients, patients with poor performance status, comorbidities, and/or intolerance may not benefit from these treatments and represent a high unmet medical need. New approaches are thus needed to improve the patient clinical outcomes without adding toxicity. NBTXR3, composed of functionalized hafnium oxide nanoparticles, is injected once intratumorally and activated by RT. NBTXR3 increases the RT energy deposit inside tumor cells and subsequently increases tumor cell death compared to RT alone, without adding toxicity to healthy tissues. We present here current results of the dose expansion part of the phase I study evaluating NBTXR3 plus intensity modulated radiation therapy (IMRT) in this population (ClinicalTrials.gov: NCT01946867). MATERIALS/METHODS Patients with stage III-VA or T3/T4 (AJCC/UICC TNM staging system 8th ed.) HNSCC of the oropharynx or oral cavity, ineligible to cisplatin or cetuximab and amenable for RT, received a single intratumoral injection of NBTXR3 and IMRT (70 Gy in 35 fractions /7 weeks). A classical 3 + 3 dose escalation design has tested four doses of NBTXR3, equivalent to 5, 10, 15, and 22% of baseline theoretical tumor volume. The RP2D established as 22% of baseline tumor volume is further tested in the dose expansion part of the study. The primary endpoints of the dose expansion part are objective response rate (ORR) and complete response rate (CRR) of the primary tumor, by imaging according to RECIST v1.1. Safety is also evaluated. RESULTS As of August 13, 2020, 43 patients have been treated in the dose expansion part of the study. The median age was 70.7 years old (range: 50.7- 89.9), 70% of patients had cardiac disorder risk, 44% had gastrointestinal disorder risk and 44% metabolic and nutrition disorder risk. The median tumor volume was 42.8 mL (range: 1.3 - 222.3). In the evaluable population for efficacy (N = 31), the ORR of the primary lesion was 83.9% and the CRR 67.7% at a median time of 7.8 months after NBTXR3 injection. Three patients (7%) experienced at least one serious adverse event (AE) related to the injection procedure and/or NBTXR3 which represented less than 1% of all reported AEs. RT-related toxicity was as expected with IMRT. Three deaths due to AEs related to RT and other causes were reported. The recruitment is ongoing and updated efficacy and safety results will be presented. CONCLUSION NBTXR3 intratumoral administration followed by IMRT may represent an option in elderly in elderly patients or patients with multiple comorbidities with LA-HNSCC who have limited therapeutic options. NBTXR3 activated by RT showed promising anti-tumor efficacy, supporting further evaluation in a phase III randomized trial.

Introduction et but de l’etude La photobiomodulation est recommandee pour prevenir la mucite orale au cours du cancer de la tete et du cou traite par irradiation et a montre des resultats encourageants sur la radiodermite au cours du cancer du sein. Les dispositifs actuels ne permettent pas une administration reproductible ni standardisee. CareMin650 permet l’illumination des tissus par des applicateurs souples, faits de fibres optiques tissees, places au contact des tissus (peau ou muqueuse), delivrant une lumiere rouge a 650nm. Materiel et methodes Il s’agissait d’une etude francaise multicentrique prospective chez des patients pris en charge par radiotherapie pour un cancer de la tete et du cou (cohorte A) ou du sein (cohorte B), en situation preventive (A1 et B1) ou curative (A2 et B2). Une prophylaxie (3j/cm2) a ete debutee a j1 de la radiotherapie (trois a cinq seances par semaine), un traitement curatif (6j/cm2, cinq seances par semaine) a ete debute a l’apparition d’une lesion, les seances ont ete realisees juste avant ou apres la radiotherapie. Le critere principal etait la tolerance (CTCAEv4). Les criteres secondaires etaient l’efficacite, la satisfaction du patient et de l’operateur. Resultats et analyse statistique Soixante-douze patients ont ete inclus dans l’analyse en ITT (22 A1, neuf A2, 23 B1 et 18 B2) pour un total de 1312 sessions de CareMin650. Il y a eu 17 sorties prematurees de l’etude, principalement liees a la pandemie de covid-19. Les traitements sont resumes dans le Tableau 1. La tolerance etait tres bonne, aucun evenement indesirable lie au dispositif n’a ete observe. Le Tableau 2 resume les donnees des patients ayant recu le traitement prophylactique. En ce qui concerne l’efficacite (population per protocole), en situation preventive, le delai median d’apparition des lesions etait de 20jours (intervalle : 3–50jours). En situation curative, le nombre median etait de deux lesions (intervalle : 1–4) en debut de traitement, de grade maximal 1 (70,4 %), 2 (25,9 %) ou 3 (3,7 %). A la fin de la radiotherapie, il etait observe pour une majorite de patients une stabilisation (52 %) ou une amelioration (19 %). En ce qui concerne la satisfaction, la majorite des patients ont trouve le traitement non contraignant (81,3 %), non douloureux (87,5 %), satisfaisant (93,6 %) et 89,1 % ont pu tenir les applicateurs seuls pendant les sessions. La satisfaction globale des operateurs etait de 96 %. Conclusion CareMin650 est un nouveau dispositif tres bien tolere et simple d’utilisation qui peut ameliorer la faisabilite de la photobiomodulation chez les patients recevant un traitement pour un cancer.

Introduction et but de l’etude Les recommandations de la medecine par les preuves reposent sur 5 % des donnees medicales, essentiellement issues des essais cliniques. Les 95 % restantes dites de “vie reelle” restent largement inexploitees alors qu’elles peuvent completer les connaissances. Nous rapportons ici une adaptation libre et gratuite d’un logiciel de radiotherapie (Mosaiq®) permettant d’enregistrer et de restituer les donnees issues des soins courant en radiotherapie. Cette production de donnees est « structuree », c’est-a-dire creee et restituee dans un format directement exploitable pour la recherche. Cette adaptation est progressivement utilisee par cinq centres et permet un partage multicentrique des donnees. Materiel et methodes En 2016 un parametrage comprenant 37 formulaires de types e-CRF (electronic case report form) utilises en consultation a ete defini puis synchronise entre les centres. Ces formulaires sont adaptes aux tumeurs et a la prise en charge pour un usage quotidien. Leur utilisation permet la saisie des donnees structurees au fil de la consultation et leur ergonomie associee a des courriers automatises permet une baisse de la charge de travail des medecins. Une copie hebdomadaire de 421 elements pertinents est realisee de Mosaiq® vers une base de donnees relationnelle. Ces elements couvrent le traitement (doses, seances, etc.), la tumeur (CIM10, etc.) et les donnees des formulaires (toxicite selon les Common Terminology Criteria for Adverse Events [CTCAE], controle tumoral). Ces outils en production dans cinq etablissements permettent une production continue de donnees. Les bases de donnees relationnelles sont securisees, accessibles uniquement dans l’etablissement et ne communiquent pas entre elles. Cependant, leur structure identique permet une analyse par une seule requete informatique appliquee localement, et valable pour tous les centres avec un cout en ressource infime. Le resultat d’une requete peut etre ensuite analyse localement ou partage avec une autre equipe pour un projet de recherche en respectant le reglement general sur la protection des donnees (RGPD). Une documentation de la structure des bases de donnees relationnelles permet leur exploitation par des personnes sans formation en oncologie. Resultats et analyse statistique Plusieurs requetes ont ete creees a l’Icans (Unicancer Strasbourg) et appliquees en fevrier 2020 dans les instituts Jean-Godinot, Gustave-Roussy, Antoine-Lacassagne et Oscar-Lambret sans mobilisation de ressources humaines informatiques locales. Les fichiers Excel® des resultats sont automatiquement mis a jour toutes les semaines. Le partage puis l’analyse des resultats a montre que les cas de 11343 patients ont ete evalues lors de 50374 consultations. Deux etudes « preuve de concept » sur les traitements mammaires portant sur 2991 patientes ont ete realisees et publiees (Societe francaise de radiotherapie oncologique [SFRO] en 2019, European Society for Radiotherapy and Oncology [ESTRO] en 2020). Conclusion L’adaptation d’un logiciel de radiotherapie pour recueillir et mettre a disposition les donnees de vie reelle est possible. Leur exploitation multicentrique a faible cout ouvre de nouveaux horizons pour la recherche et viendra completer les connaissances. Cette production quotidienne constitue le socle d’etudes en cours dans les centres participants.

Introduction Reconstructive surgery in head and neck cancers frequently involves the use of autologous flaps to improve functional outcomes. However, the literature suggests that postoperative radiotherapy deteriorates functional outcomes due to flap atrophy and fibrosis. Data on patterns of relapse after postoperative radiotherapy with a flap are lacking, resulting in heterogenous delineation of postoperative clinical target volumes (CTV). Flap delineation is unusual in routine practice and there are no guidelines on how to delineate flaps. Therefore, we aim to propose a guideline for flap delineation in head and neck cancers to assess dose-effects more accurately with respect to flaps. Material and methods Common flaps were selected. They were delineated by radiation oncologists and head and neck surgeons based on operative reports, on contrast-enhanced planning CTs and checked by a radiologist. Each flap was divided into its vascular pedicle and its soft tissue components (fat, fascia/ muscle, skin, bone). Results Delineation (body and pedicle) of Facial Artery Musculo-Mucosal, pectoralis, radial forearm, anterolateral thigh, fibula and scapula flaps was performed. Based on information provided in operative reports, i.e. tissue components, size and location, flaps can be identified. The various tissue components of each flap can be individualized to facilitate the delineation. Conclusion This atlas could serve as a guide for the delineation of flaps and may serve to conduct studies evaluating dose-effects, geometric patterns of failure or functional outcomes after reconstructive surgery. Changes in postoperative CTV definitions might be needed to improve risk/benefit ratio in the future based on surgery-induced changes.

6051 Background: The non-surgical standard of care (SOC) for the treatment of locally advanced head and neck squamous cell carcinoma (LA HNSCC) patients is concurrent chemoradiation with high dose cisplatin or cetuximab in case of contra-indication to cisplatin. However elderly patients, and those with poor performance status, comorbidities, and/or intolerance, may not benefit from these SOC treatments and represent a high unmet need. New approaches are thus needed to improve clinical outcomes without adding toxicity. NBTXR3, a novel radioenhancer, composed of functionalized hafnium oxide nanoparticles, is injected once intratumorally and activated by radiotherapy (RT).NBTXR3 increases the RT energy deposit inside tumor cells and subsequently increases tumor cell death compared to RT alone, while sparing healthy tissues. We present here the results of the dose expansion part of the phase I study evaluating NBTXR3 plus intensity modulated radiation therapy (IMRT) in this population. Methods: Patients with stage III-IVA or T3/T4 (AJCC/UICC TNM staging system 8th ed.) HNSCC of the oropharynx or oral cavity, ineligible to cisplatin or cetuximab and amenable for RT, received a single intratumoral injection of NBTXR3 and IMRT (70 Gy in 35 fractions /7 weeks). A classical 3 + 3 dose escalation design has tested four doses of NBTXR3, equivalent to 5, 10, 15, and 22% of baseline theoretical tumor volume. The RP2D established as 22% of baseline tumor volume is further tested in the dose expansion part. The primary endpoints of the dose expansion part are objective response rate (ORR) and complete response rate (CRR) of the primary tumor, by imaging according to RECIST 1.1. Safety is also evaluated. Results: As of August 13, 2020, 43 patients have been treated in the phase I dose expansion part. The median age was 70.7 years old (range: 50.7- 89.9), 70% of patients had cardiac disorder risk, 44% had gastrointestinal disorder risk and 44% metabolic and nutrition disorder risk. The median tumor volume was 42.8 mL (range: 1.3 - 222.3). At a median time of 7.8 months after NBTXR3 injection, the ORR of the primary lesion was 83.9% and the CRR 67.7% in the evaluable population for efficacy (N = 31). Three patients (7%) experienced at least one serious adverse event (AE) related to the injection procedure and/or NBTXR3 which represented less than 1% of all reported AEs. RT-related toxicity was as expected with IMRT. Three deaths due to AEs related to RT and other causes were reported. The recruitment is ongoing and updated efficacy and safety results will be presented. Conclusions: NBTXR3 intratumoral administration followed by IMRT may represent an option in elderly patients or patients with multiple comorbidities with LA-HNSCC who have limited therapeutic options. NBTXR3 activated by RT showed promising anti-tumor efficacy, supporting further evaluation in a phase III randomized trial. Clinical trial information: NCT01946867.

6573 Background: The standard of care non-surgical approach for locally advanced head and neck squamous cell carcinoma (LA HNSCC) patients (pts) is concurrent chemoradiation with high dose cisplatin or cetuximab in case of contra-indication. Older age is a contra-indication to cisplatin, and cetuximab might not improve survival in older pts. It is therefore urgently needed to develop new treatment options for elderly pts with LA HNSCC. NBTXR3 are hafnium oxide nanoparticles that can enhance the efficacy of radiotherapy (RT) by increasing locally the deposited dose. In this phase I clinical trial we aimed to evaluate the feasibility and safety of NBTXR3 administered as intratumoral (IT) injection prior to RT in LA HNSCC elderly pts. Methods: Pts with stage III-IV LA HNSCC of the oropharynx or oral cavity ineligible for platinum-based chemoradiation received a single IT injection of NBTXR3 into a selected primary tumor and intensity modulated RT (IMRT; 70 Gy/35 fractions/7 weeks) [NCT01946867]. A 3+3 dose escalation design, tested NBTXR3 dose levels equivalent to 5, 10, 15, and 22% of baseline tumor volume, followed by a dose expansion at the Recommended Phase II Dose (RP2D). Primary endpoints included RP2D determination, and early dose limiting toxicities (DLT). NBTXR3 intratumoral bioavailability and anti-tumor activity (RECIST 1.1) were also evaluated. Results: Enrollment was completed at all dose escalation levels: 5% (3 pts), 10% (3 pts), 15% (5 pts), and 22% (8 pts). No early DLT or SAE related to NBTXR3 or injection were observed. The median follow-up from NBTXR3 administration is 7.6 months. One AE (Grade 1) related to NBTXR3 and four AEs (Grade 1-2) related to the injection were observed. RT-related toxicity was as expected with IMRT. CT-scan assessment showed a good dispersion of NBTXR3 throughout the injected tumor and not in surrounding healthy tissues. The RP2D was determined to be 22%. Preliminary efficacy was evaluated in pts who received the intended dose of NBTXR3 and RT. A complete response of the injected lesion was observed in 9/13 (69%) evaluable pts at doses ≥10% (2 unconfirmed) and an overall complete response in 5/13 (38%) evaluable pts at doses ≥10%. Preliminary safety and efficacy data of the dose expansion cohort at the RP2D will also be presented. Conclusions: NBTXR3 activated by RT was well tolerated at all tested doses and demonstrated promising preliminary anti-tumor activity. Recruitment is ongoing in the dose expansion cohort. These results demonstrate that further testing of NBTXR3 in this population is warranted. Clinical trial information: NCT01946867 .

Background Based on the hypothesis of a synergistic effect of the anti-PDL1 avelumab when combined with cetuximab (cetux) and RT, this new combination is tested in a large scale randomized trial against two well established SoC in LA-SCCHN pts. Methods This randomized multicenter phase III trial comprises two cohorts of pts deemed fit (Cohort 1) to receive high dose cisplatin (CDDP 100 mg/m², Q3W) or unfit (Cohort 2) to receive CDDP. The SoC is IMRT (69.96 Gy, 33 fractions) combined with CDDP in Cohort 1 (arm A) and with cetux (arm D) in Cohort 2 (400 mg/m² Day-7 and 250 mg/m² weekly). In both cohorts, experimental (exp) arms are IMRT concomitant with cetux (same schedule as in SoC) and avelumab (10 mg/kg Day-7 and every 2 weeks) followed by avelumab 10 mg/kg bi-monthly for 12 months (arms B and C). The primary objective is to test whether exp arm is superior to SoC for progression-free survival in each cohort, with 400 and 268 pts to be randomized to Cohort 1 and 2 respectively. Monitoring of grade ≥4 acute adverse events (AE) in both exp arms was planned with null and alternative hypotheses of 15% and 35%, 1-sided α error = 0.10, Lan-DeMets α spending function, power 95%. This safety phase was approved by the Independent Data and Safety Monitoring Committee (IDSMC) and planned to be run on the first 41 pts randomized in exp arms, in 3 steps, after 8 weeks follow-up of 14, 27 and 41 pts. Results Between September 2017 and August 2018, 82 pts with LA-SCCHN were randomized including 41 in the exp arms. All pts of exp arms received the entire RT, except one in arm C with early stop after 55 Gy. In exp arms, 36 pts (88%) and 31 pts (76%) received the expected number of avelumab and cetux administrations during RT. In the exp arms, the most common grade ≥3 AE were radiation dermatitis, mucositis and dysphagia. Grade ≥4 AEs occurred in 5/41 (12%) pts in the exp arms (all in arm C), in 3/21 (14%) pts in arm A and 2/20 (10%) in arm D. Only one grade 5 AE occurred in arm A. Conclusions The combination of avelumab, cetuximab and RT is tolerable for pts with LA-SCCHN in the safety phase of this ongoing phase 3 trial and an approval to continue the trial was given by IDSMC. Clinical trial identification NCT02999087. Legal entity responsible for the study GORTEC. Funding Merck Serono. Disclosure Y. Tao: Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Serono; Research grant / Funding (institution): Debiopharma; Research grant / Funding (institution): Pfizer. J. Thariat: Advisory / Consultancy: BMS; Advisory / Consultancy: Nanobiotix. J. Guigay: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: Innate pharma; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Serono. J. Bourhis: Advisory / Consultancy: Merck Serono; Advisory / Consultancy: BMS; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: MSD. All other authors have declared no conflicts of interest.

International audience; Purpose: Radiation-induced sarcoma (RIS) is a rare but serious event. Its occurrence has been discussed during the implementation of new radiation techniques and justified appropriate radioprotection requirements. New approaches targeting intrinsic radio-sensitivity have been described, such as radiation-induced CD8 T-lymphocyte apoptosis (RILA) able to predict late radio-induced toxicities. We studied the role of RILA as a predisposing factor for RIS as a late adverse event following radiation therapy (RT).Patients and methods: In this prospective biological study, a total of 120 patients diagnosed with RIS were matched with 240 control patients with cancer other than sarcoma, for age, sex, primary tumor location and delay after radiation. RILA was prospectively assessed from blood samples using flow cytometry.Results: Three hundred and forty-seven patients were analyzed (118 RIS patients and 229 matched control patients). A majority (74%) were initially treated by RT for breast cancer. The mean RT dose was comparable with a similar mean (± standard deviation) for RIS (53.7 ± 16.0 Gy) and control patients (57.1 ± 15.1 Gy) (p = .053). Median RILA values were significantly lower in RIS than in control patients with respectively 18.5% [5.5–55.7] and 22.3% [3.8–52.2] (p = .0008). Thus, patients with a RILA >21.3% are less likely to develop RIS (p

Introduction et but de l’etude La mucite orale radiochimio induite est un effet secondaire redoutable, et expose a des risques de complications. Notre etude visait a decrire les pratiques de prise en charge de mucite orale radiochimio-induite afin d’identifier les difficultes et l’interet d’elaborer un referentiel simplifie. Materiel et methodes Il s’agissait d’une etude prospective observationnelle et descriptive d’evaluation des pratiques par l’envoi de questionnaires ciblant les praticiens des Hauts-de-France (oncologues, radiotherapeutes, hematologues et specialistes d’organes pratiquant l’oncologie et la chimiotherapie) des hopitaux publics et des cliniques privees. Resultats et analyse statistique Soixante-dix-sept praticiens sur 316 sollicites ont repondu. Quatre-vingt-quinze pour cent des praticiens ont repondu a plus de 90 % du questionnaire. Respectivement, 23, 37 et 46 % consideraient maitriser « pas du tout », « moyennement bien » et « bien » les recommandations de prise en charge de la mucite orale radiochimio induite (Association francophone des soins oncologiques de support [Afsos], Multinational Association of Supportive Care in Cancer [MASCC]/International Society of Oral Oncology [ISOO]). A titre preventif, 91 % des praticiens utilisaient les bains de bouche au bicarbonate de sodium, 24 % des melanges, 22 % des bains de bouche antifongiques et 11 % antiseptiques. La secheresse buccale etait recherchee pour 46 % d’entre eux. Dans leur centre de travail, 71 % des praticiens ne disposaient pas de referentiel de prise en charge et 50 % utilisaient alors les recommandations internationales. Parmi les difficultes identifiees, il s’agissait essentiellement du manque de traitements efficaces et pres d’un tiers des praticiens suggeraient le manque formation. Quatre-vingt-huit pour cent ont trouve un interet en ce questionnaire et 86 % iraient chercher des informations supplementaires pour completer leurs connaissances. Enfin, 83 % indiquaient que le support le plus utile pour ameliorer et simplifier la pratique serait un referentiel de prise en charge sous forme de tableau. Conclusion Dans une population selectionnee d’oncologues exposees aux mucites, 40 % considerent bien maitriser en la gestion. Il existe un interet a l’elaboration d’un referentiel simplifie de prise en charge de la mucite orale radiochimio induite pour faciliter la pratique.

6069 Background: New therapeutic approaches are needed for elderly or frail head and neck squamous cell carcinoma (HNSCC) patients (pts) ineligible for standard of care treatment. NBTXR3, a crystalline solution of hafnium oxide nanoparticles may represent such an option. Injected intratumorally, NBTXR3 enters tumor cells and yields an increased cell-localized energy deposit upon exposure to radiotherapy (RT), leading to increased tumor cell death compared to the same dose of RT alone. Methods: Phase I study of NBTXR3 activated by RT in pts ≥70 years old or ≥65 years old and unable to receive cisplatin, eligible for exclusive RT with stage III or IV HNSCC of the oral cavity or oropharynx [NCT01946867]. A 3+3 dose escalation design was implemented with dose levels corresponding to 5%, 10%, 15% and 22% of baseline tumor volume, followed by an expansion phase. Pts received an intratumoral (IT) injection of NBTXR3 and intensity modulated RT (IMRT; 70 Gy/35 fractions/7 weeks). Determination of Recommended Phase 2 Dose (RP2D) and Dose Limiting Toxicities (DLT) were primary endpoints of phase I. Absence of NBTXR3 leakage and preliminary efficacy using RECIST 1.1 principles were also evaluated. Results: The dose-escalation is complete. Nineteen pts were enrolled: 3 at 5%, 3 at 10%; 5 at 15% and 8 at 22% with no observed DLT or SAE related to NBTXR3 or IT injection. One grade 1 NBTXR3-related AE (asthenia at 22%) and four IT injection-related AE (grade 2 oral pain; grade 1 tumor hemorrhage; grade 1 asthenia, and grade 1 injection site hemorrhage) were reported. RT-related toxicity was as expected with IMRT. RP2D has been determined to be 22%. CT-scan assessment between 24h and 7 weeks post-IT injection demonstrated absence of NBTXR3 leakage in the surrounding tissues. Among 13 evaluable pts treated at doses ≥10%, 9 achieved a complete response of the injected lesion. Conclusions: These results show that NBTXR3 activated by RT is safe and well tolerated at all doses with preliminary encouraging efficacy results. It thus represents a promising future treatment for frail and elderly pts with locally advanced HNSCC with limited therapeutic options. Expansion phase has started at the RP2D. Clinical trial information: NCT01946867.

Resume Objectif Evaluer les resultats cliniques et dosimetriques de la tomotherapie helicoidale adjuvante avec boost integre apres mastectomie partielle. Patientes et methodes Les dossiers de 20 patientes ayant recu une tomotherapie apres tumorectomie ont ete analyses. L’âge median etait de 49 ans. Les doses prescrites ont ete de 63,8 Gy par fraction de 2,2 Gy dans le lit operatoire, 52,2 Gy par fraction de 1,8 Gy dans le sein et 50,4 Gy par fractions de 1,74 dans les aires ganglionnaires, soit par 29 fractions. La reproductibilite a ete analysee en mesurant les decalages quotidiens dans les axes x, y, z et en rotation roll. La toxicite a ete decrite selon la Common Terminology Criteria of Adverse Effects v3.0. Resultats Vingt-deux tumeurs ont ete irradiees, 68 % etaient situees dans les quadrants internes, 90 % des patientes ont ete irradiees dans les aires sus-claviculaire et mammaire interne. Le volume recevant 107 % de la dose prescrite (V107 %) etait pour le volume cible previsionnel du boost de 0,3 % ± 0,50 (deviation standard), celui recevant 95 % (V95 %) de 98,4 % ± 1,9. Le volume cible previsionnel du sein recevant 107 % de la dose prescrite etait de 7,8 % ± 17,3, le V95 % de 96,8 % ± 2,2. Le volume cible previsionnel des aires ganglionnaires recevant 107 % de la dose prescrite etait de 2,5 % ± 4,2, le V95 % de 92,7 % ± 13,2. Le volume recevant 20 Gy (V20) du poumon homolateral etait de 18,9 % ± 3,5. Pour les lesions gauches, le volume moyen recevant 30 Gy (V30) du cœur etait de 0,9 % ± 0,8. Les volumes moyens recevant 5 Gy etaient pour le poumon homolateral de 73,1 % ± 11,8, pour le poumon controlateral de 38,9 % ± 21, pour le cœur (lesions gauches) de 57,3 % ± 21, et pour le sein controlateral de 15,5 % ± 9,6. Les decalages moyens ont ete pour l’axe x de –0,04 mm (intervalle de confiance a 95 % [IC95] : –0,40 +0,38), pour l’axe y de –0,37 mm (IC95 : −0,88 +0,14) et pour l’axe z de 2,90 mm (IC95 : 2,4–3,4), le rotation roll de 0,22° (IC95 : –0,10 +0,32). Le suivi median etait 9,7 mois. La tolerance a ete acceptable avec une seule interruption de traitement et trois arrets temporaires pour toxicite cutanee. Aucun cas de toxicite de grades 3–4 n’a ete observe, pour 95 % des patientes une toxicite cutanee de grade 2 pour 45 %. Il y a eu trois cas d’œsophagite. Conclusion La radiotherapie helicoidale permet un traitement bien tolere, qui autorise une couverture adequate des volumes cible en protegeant le cœur et le poumon homolateral. Cependant, les faibles doses dans les etudes suivantes doivent etre reduites.

La radiotherapie est un moyen therapeutique majeur dans la prise en charge des cancers pour assurer leur curabilite. Ces modalites ont connu un veritable essor ces dernieres annees avec des avancees therapeutiques et technologiques majeures. La radiotherapie conformationnelle en trois dimensions (RC3D) est passee dans la routine avec la delineation des volumes tumoraux et celle des organes a risque puis realisation d’une dosimetrie integrant les contraintes de dose a travers les histogrammes dose-volumes. La technique enmodulation d’intensite a permis de sculpter la dose autour des volumes de traitement pour epargner davantage de tissu sain. L’arrivee de la radiotherapie guidee par l’image (IGRT) est une etape supplementaire permettant de controler a chaque seance la position de la cible. Les techniques en arctherapie dynamique integrent desormais ces deux parametres pour optimiser la precision et le gain de temps. Les concepts en radiotherapie sont forts et devront se deployer sur tous les plateaux techniques. L’oncologie radiotherapie n’est probablement qu’a l’aube et a la maitrise de ces innovations; l’avenir est grand ouvert et les perspectives vastes. (2012).

6018Background: Based on the hypothesis of a potential synergistic effect of the anti-PD1 pembrolizumab when combined with RT, this new combination was tested in a phase II randomized trial against...

To evaluate the dosimetry and acute toxicity of helical tomotherapy for locoregional irradiation of patients after breast-conserving surgery.Twenty breast cancer patients with breast-conserving surgery treated by helical tomotherapy have been studied. The median age was 49 (min: 25, max: 69). The whole breast, tumour bed and lymph nodes were prescribed 52.2 Gy, 63.8 Gy and 50.4 Gy, all in 29 fractions. The dose per fraction was 2.2 Gy to the boost, 1.8 Gy to the breast and 1.74 Gy to the lymph node volumes. The reproducibility was analysed by recording the daily shifts in x, y and z directions and roll rotation. All toxicities were described using the Common Terminology Criteria for Adverse Effects v3.0.Twenty-two tumours were irradiated. Six-eight percent were located in the inner quadrant. In 90 % of patients supraclavicular and internal mammary nodes were treated. The coverage of planning target volumes (PTV) was as follows: PTV boost: V107 = 0.3 % ± 0.5 SD, V95 = 98.4 % ± 1.9 SD; PTV breast: -V107 = 7.8 % ± 17.3 SD, V95 = 96.8 % ± 2.2 SD; PTV LN: V107 = 2.5 % ± 4.2 SD, V95 = 92.7 % ± 13.2 SD. The mean V20 of the homolateral lung was 18.9 % ± 3.5 SD. For left side lesion, the mean V30 of the heart was 0.9 % ± 0.8 SD. The mean V5 was: V5 homolateral lung: 73.1 % ± 11.8 ET, controlateral lung: 38.9 % ± 21, heart (left side breast): 57.3 % ± 21, controlateral breast: 15.5 % ± 9.6. Median shifts were as follow: x-axis -0.04 mm (IC 95: -0.4 +0.38), y-axis -0.37 mm ± 5.51 (IC 95: -0.88 +0.14), z-axis 2.90 mm ± 5.42 (IC 95:+2.4+3.4) and roll rotation 0.22 ± 1.10 (IC 95: -0.1+0.32). The treatment tolerance was acceptable with 1 definitive interruption couple of fractions before the end and 3 temporal interruptions for skin toxicity. No grade 3 or 4 toxicity. Ninety-five percent of patients experienced skin toxicity: 45 % grade 2. There were 3 cases of oesophagitis. The median follow-up of presented series is 9.7 months and all of the patients are free of disease without any residual early or late toxicity.Helical tomotherapy can achieve full target coverage while protected to the heart and ipsilateral lung. This treatment was well tolerated and reproducible. However, the low doses to normal tissue volumes need to be reduced in future studies.

In this paper, we experiment a new robotic concept for the brachytherapy of prostate, using adaptive tracking of mobile targets under ultrasound control of industrial robot. Contours detection' method of the prostate from ultrasound images is presented. The targets to be achieved safely by the robot, are defined from a virtual and adaptive grid. A virtual simulator is used firstly, to transfer the coordinates of the targets from the image to the robot frame, then secondly to supervise by comparing between the theoritical and experimental trajectories, in order to improve the accuracy of the robot control. Experimental results applied on a prostate phantom from one access point, can show the advantage of the proposed concept in the context of reducing trauma and recovery times for real patients.

e11540 Background: Neoadjuvant chemotherapy rarely induces a complete pathological response in LBC. Nevertheless, adjuvant chemotherapy is used in lobular as well as in other tumor types. Methods: ...