Jean Francois Daisne

Panitumumab plus radiotherapy versus chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-2): a randomised, controlled, open-label phase 2 trial.

BACKGROUNDnWe aimed to compare panitumumab, a fully human monoclonal antibody against EGFR, plus radiotherapy with chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck.nnnMETHODSnIn this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 22 sites in eight countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥ 10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (two cycles of cisplatin 100 mg/m(2) during radiotherapy) or to radiotherapy plus panitumumab (three cycles of panitumumab 9 mg/kg every 3 weeks administered with radiotherapy) using a stratified randomisation with a block size of five. All patients received 70-72 Gy to gross tumour and 54 Gy to areas of subclinical disease with accelerated fractionation radiotherapy. The primary endpoint was local-regional control at 2 years, analysed in all randomly assigned patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This study is registered with ClinicalTrials.gov, number NCT00547157.nnnFINDINGSnBetween Nov 30, 2007, and Nov 16, 2009, 152 patients were enrolled, and 151 received treatment (61 in the chemoradiotherapy group and 90 in the radiotherapy plus panitumumab group). Local-regional control at 2 years was 61% (95% CI 47-72) in the chemoradiotherapy group and 51% (40-62) in the radiotherapy plus panitumumab group. The most frequent grade 3-4 adverse events were mucosal inflammation (25 [40%] of 62 patients in the chemoradiotherapy group vs 37 [42%] of 89 patients in the radiotherapy plus panitumumab group), dysphagia (20 [32%] vs 36 [40%]), and radiation skin injury (seven [11%] vs 21 [24%]). Serious adverse events were reported in 25 (40%) of 62 patients in the chemoradiotherapy group and in 30 (34%) of 89 patients in the radiotherapy plus panitumumab group.nnnINTERPRETATIONnPanitumumab cannot replace cisplatin in the combined treatment with radiotherapy for unresected stage III-IVb squamous-cell carcinoma of the head and neck, and the role of EGFR inhibition in locally advanced squamous-cell carcinoma of the head and neck needs to be reassessed.nnnFUNDINGnAmgen.

Reduction of the dose of radiotherapy to the elective neck in head and neck squamous cell carcinoma; a randomized clinical trial. Effect on late toxicity and tumor control.

BACKGROUND AND PURPOSEnA multi-center prospective randomized clinical trial has been performed investigating whether a reduction of the dose to the elective nodal sites in head and neck cancer delivered by intensity modulated radiotherapy (IMRT) would result in a reduction of late side effects without compromising tumor control.nnnMATERIALS AND METHODSnTwo hundred patients were included. The prescription dose to the elective nodal volumes was a normalized iso-effective dose in 2Gy fractions (NID2Gy) of 50Gy in the standard arm and of 40Gy in the experimental arm. Late toxicity was scored at 6, 12, 18 and 24months using the RTOG scoring system.nnnRESULTSnWe observed a trend toward less dysphagia at 6months in the experimental arm, however this was not confirmed after longitudinal analysis. Regarding moderate salivary gland toxicity we observed lower incidence of salivary gland toxicity ⩾grade 1, at 6 (p=0.01) and 18months (p=0.03). After two years of follow up, we did not observe significant differences in estimated local failure rate (14.1% in the 40Gy arm vs 14.4% in the 50Gy arm), estimated regional failure rate (13.0% vs 5.5% in the 40 and the 50Gy arm respectively), estimated metastatic recurrence (13.4% vs 18.5% in the 40 and the 50Gy arm respectively), estimated disease-free survival (57.9% vs 65.3% in the 40 and the 50Gy arm respectively) nor estimated overall survival (72.0% vs 73.2% in the 40 and the 50Gy arm respectively).nnnCONCLUSIONSnIn our study population there was no statistically significant difference regarding survival and estimated recurrence rates between both arms of this study. We found a trend toward less dysphagia at 6months (however not significant after longitudinal analysis) and found a significant reduction of any salivary gland toxicity at 6 and 18months in the 40Gy arm.

Radiotherapy induced dermatitis is a strong predictor for late fibrosis in head and neck cancer. The development of a predictive model for late fibrosis

PURPOSEnTo determine if the severity of radiodermatitis at the end of radio(chemo)therapy (R(C)T) for head and neck cancer (HNC) is a predictive factor for late fibrosis of the neck and to find a model to predict neck fibrosis grade⩾2 (fibrosis RTOG2-4) at 6months following R(C)T for HNC.nnnMATERIAL/METHODSn161 patients were prospectively included. We correlated radiodermatitis at the end of RCT, age, sex, T/N stage, tumor site, concomitant chemotherapy, upfront neck dissection, neo-adjuvant chemotherapy, accelerated RT, smoking, alcohol consumption, HPV status and the dose prescribed to the elective neck with fibrosis RTOG2-4 6months after the end of treatment.nnnRESULTSnRadiodermatitis at the end of R(C)T ⩾grade 3 proved to be associated with the incidence of fibrosis RTOG2-4 at 6months (p<0.01). Furthermore, upfront neck dissection (p<0.01), increasing N stage (p<0.01) and tumor site (p=0.02) are significantly associated in univariate analysis with fibrosis RTOG2-4 at 6months of follow-up. Upfront neck dissection and radiodermatitis grade⩾3 at the end of R(C)T were identified by our multivariate model. Additionally, increasing N stage was selected as an independent predictor variable. The AUC for this model was 0.92.nnnCONCLUSIONnA model for the prediction of fibrosis RTOG2-4 following R(C)T for head and neck cancer is presented with an AUC of 0.92. Interestingly, radiodermatitis grade⩾3 at the end of R(C)T is associated with RTOG2-4 fibrosis at 6months.

Validation of the total dysphagia risk score (TDRS) in head and neck cancer patients in a conventional and a partially accelerated radiotherapy scheme

BACKGROUND AND PURPOSEnA risk model, the total dysphagia risk score (TDRS), was developed to predict which patients are most at risk to develop grade ⩾2 dysphagia at 6 months following radiotherapy (RT) for head and neck cancer. The purpose of this study was to validate this model at 6 months and to investigate the power at earlier and later time-points. A second aim was to see if this model can be used in a partially accelerated RT regimen.nnnMATERIALS AND METHODSn164 patients from 3 different centres treated with RT between 2008 and 2014 were included in the current study. Both physician-scored dysphagia and QoL data were prospectively obtained. The TDRS of all patients was correlated with the physician-scored dysphagia and the QoL data. To validate this prediction model, we tested the validity in terms of calibration and discrimination.nnnRESULTSnPartial acceleration had no influence on the TDRS. Regarding physician-scored dysphagia, there was a significant correlation with dysphagia grade ⩾2 at 1, 3, 6 and 9 months. The area-under-the-curve at 1 month was 0.85; at 3 months 0.80; at 6 months 0.85; at 9 months 0.86 and 0.79 at 12 months. Regarding QoL, TDRS correlates with PEG-tube usage at 6 and 12 months.nnnCONCLUSIONnWe found significant correlations between TDRS and dysphagia grade ⩾2 and PEG-tube usage.

PO-0638: Adaptive dose painting by numbers for head and neck cancer: interim analysis of a randomised trial

ESTRO 35 2016 ______________________________________________________________________________________________________ studies, topical clonidine shown activity in reducing NF-κB activation and incidence of severe OM (SOM). In a randomized double blind, placebo-controlled study, a novel mucoadhesive buccal tablet (MBT) containing clonidine reduced the incidence of SOM in HNC patients being treated with CRT. We now report overall survival (OS), tolerability and systemic exposure of clonidine of study subjects.

OC-0141: Reduction of the dose to the elective CTV in HNSCC using IMRT. Dosimetrical analysis and effect on acute toxicity

Purpose/Objective: To evaluate patterns-of-care and patterns-ofoutcome after stereotactic body radiotherapy (SBRT) for stage I nonsmall cell lung cancer (NSCLC). Materials and Methods: The working group Extracranial Stereotactic Radiotherapy of the German Society of Radiation Oncology (DEGRO) performed a multi-center analysis of practice and outcome after SBRT for stage I NSCLC: 16 German and Austrian centers with experience in pulmonary SBRT were asked for participation. Results: Data of 582 patients treated in 13 institutions between 19982011 were collected; all but one institution were academic hospitals. In 2010, the last full year covered in this analysis, 95 patients in total were treated with SBRT. The median number of patients per institution was 39 (range 8-110) and the median number of patients per institution and year was 5 (range 1-29). Median patient age was 72 years (range 31-92) and median pre-treatment FEV1 was 58% (range 16-129%). Median maximum tumor diameter was 2.5cm. NSCLC was biopsy confirmed in 84.5% of the patients. A time trend to more advanced radiotherapy technologies (nodal staging using FDG-PET, advanced type B dose calculation algorithm, in-room image guidance) was observed. The PTV encompassing dose was increased continuously and reached a plateau of 94Gy±26Gy BED (α/β=10Gy) on average in 2006-2011. Patient characteristics (age, performance status, pulmonary function) remained stable over time. Inter-institutional variability was substantial in all treatment characteristics. In contrast, there was no inter-institutional variability in pre-treatment patient age and pulmonary function. After average follow-up of 21 months, three-years freedom from distant recurrence (FFDR), regional recurrence (FFRR) and local progression (FFLP) were 63.4%, 75.4% and 79.6% for all 582 patients, respectively. Three-years overall survival (OS) was 47.1%. The biological effective dose (BED) was the most significant factor influencing all patterns of failure and OS in uniand multivariate analysis. After ≥106Gy BED as planning target volume encompassing dose (n=164), three-years FFDR, FFRC, and FFLP were 74.8%, 90.4% and 92.5%, respectively; three-years OS was 62.2%. The figure below shows OS depending on stage and irradiation dose.