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.

BACKGROUND: We 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. METHODS: In 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. FINDINGS: Between 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. INTERPRETATION: Panitumumab 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. FUNDING: Amgen

Pre- And postoperative capecitabine without or with oxaliplatin in locally advanced rectal cancer: PETACC 6 trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD

Purpose: The PETACC 6 trial investigates whether the addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative capecitabine improves disease-free survival (DFS) in locally advanced rectal cancer. Methods: Between November 2008 and September 2011, patients with rectal adenocarcinoma within 12 cm from the anal verge, T3/4 and/or node positive, were randomly assigned to 5 weeks preoperative capecitabine-based chemoradiation (45-50.4 Gy) followed by six cycles of adjuvant capecitabine, both without (control arm, 1) or with (experimental arm, 2) oxaliplatin. The primary end point was improvement of 3-year DFS by oxaliplatin from 65% to 72% (hazard ratio [HR], 0.763). Results: A total of 1,094 patients were randomly assigned (intention to treat), and 1,068 eligible patients started their allocated treatment (arm 1, 543; arm 2, 525), with completion of protocol treatment in 68% (arm 1) v 54% (arm 2). A higher rate of grade 3/4 adverse events was reported in the experimental arm (14.4% v 37.3% and 23.4% v 46.6% for neoadjuvant and adjuvant treatment, respectively). At a median follow-up of 68 months (interquartile range, 58-74 months), 157 and 156 DFS events were observed in arms 1 and 2, respectively (adjusted HR, 1.02; 95% CI, 0.82 to 1.28; P = .835). Three-year DFS rate was not different, with 76.5% (95% CI, 72.7% to 79.9%) in arm 1, which is higher than anticipated, and 75.8% (95% CI, 71.9% to 79.3%) in arm 2. The 7-year DFS and overall survival (OS) rates were not different as well, with DFS of 66.1% v 65.5% (HR, 1.02) and OS of 73.5% v 73.7% (HR, 1.19) in arms 1 and 2, respectively. Subgroup analyses revealed heterogeneity in treatment effect according to German versus non-German site location, without detectable confounding factors in multivariable analysis. Conclusion: The addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative adjuvant chemotherapy impairs tolerability and feasibility and does not improve efficacy.Hans-Joachim Schmoll, Alexander Stein, Eric Van Cutsem, Timothy Price, Ralf D. Hofheinz, Bernard Nordlinger, Jean-François Daisne, Jos Janssens, Baruch Brenner, Hans Reinel, Stephan Hollerbach, Karel Caca, Florian Fauth, Carla V. Hannig, John Zalcberg, Niall Tebbutt, Murielle E. Mauer, Sandrine Marreaud, Manfred P. Lutz, and Karin Hausterman

ANOCEF Consensus Guideline on Target Volume Delineation for Meningiomas Radiotherapy

Purpose/Objective(s)Meningiomas are the most common primary intracranial tumor. They are developed at the expense of the dura, with an overall incidence which has increased over the past decade. To date, there is no published specific guideline about meningiomas target volume. No prospective study has defined a consensus for delineation in meningiomas’ radiotherapy. Therefore, target volume definition is mainly based on retrospective studies, with a heterogeneous population of patients. The aim of this paper is to describe delineation guidelines for meningiomas’ radiotherapy as an adjuvant or definitive treatment with Intensity Modulated Radiation Therapy (IMRT) and stereotactic radiation therapy (SRT) techniques.Materials/MethodsThis guideline is based on a consensus endorsed by a global multidisciplinary group of brain tumor experts’ member of the ANOCEF (French neuro-oncology association). A two round modified Delphi consensus was achieved, and the consensus was adopted by the RAND/UCLA method. The third round was carried out in videoconference, in order to allow experts to debate and argue on remaining uncertain proposals.ResultsTwenty experts from 17 radiotherapy center participated. After 3 rounds, all the proposals resulted in a consensus. The ANOCEF guideline committee proposed to perform an unenhanced planning CT scan, merged with a post-contrast MRI obtained at the time of radiotherapy and preoperative MRI in case of adjuvant treatment. GTV is defined by T1 contrast-enhancing lesion, thickened meninges, and directly invaded bone. For IMRT, the CTV include: Grade I: No margin around the GTV. Grade II: Margin of 5mm to expand GTV in normal brain tissue, hyperostosis, along the unthickened meninges and venous sinuses if the GTV is coming into contact. Grade III: Margin of 10mm to expand GTV in normal brain tissue, hyperostosis, along the unthickened meninges, and optic or cranial nerves in contact with GTV. In case of bone invasion, a margin of 5 or 10mm in the healthy bone around the GTV is recommended, for grade II or III respectively. Otherwise, it is considered as an anatomical barrier and does not need to be included in the target volume. In case of post-operative radiotherapy, no additional margin is required for CTV for grade I around tumor bed. A 5 and 10mm margin is required for grade II and III. The cranial flap should only be included in the CTV only over 5 or 10mm for grades II or III, in case of initially invaded bone. The drill holes and osteotomy areas should be included if they come into contact with target volume. SRT is not recommended for grades II and III, excluding relapse situation. CTV corresponds to GTV without additional margin.ConclusionThe current consensus provides a detailed delineation guideline for meningioma, suggesting smaller margins than the major studies published to date