The HNCG is conducting and developing trials/projects in 5 main research lines, i.e. 1) the early stage oropharyngeal squamous cell carcinoma, 2) the locally advanced pharyngo-laryngeal squamous cell carcinoma, 3) the pre-operative oral cavity squamous cell carcinoma, 4) the recurrent and/or metastatic salivary gland tumors and 5) the Quality of Life.
For all the trials listed below, the HNCG is working in close collaboration with other EORTC groups, especially the Radiation Oncology, the Quality of Life, the Imaging and the Pathobiology groups. For all these studies involving surgery and radiotherapy, comprehensive quality assurance (QA) programs are put in place to reduce treatment heterogeneity and ensure optimal patient care. For example, in the EORTC 1219 trial, an individual review of target volume selection and delineation, and of dose distribution is performed for every patients included in the trial. A similar review will be performed for the EORTC 1420 “Best-Off” trial where a quality assurance program in Surgery will also be developed.
Early stage oropharyngeal tumors
In early stage (stage I and II) oropharyngeal squamous cell carcinoma, retrospective clinical studies have shown that radiotherapy or surgery achieved similar local tumor control. It’s however still unclear which of these 2 options provides the best functional outcome in term of swallowing function, especially in the area of modern treatments, i.e. IMRT and trans-oral surgery. In this framework, the HNCG is launching a randomized phase III study assessing the “best of” radiotherapy compared to the “best of” surgery (trans-oral surgery, TOS) in patients with T1-T2, N0 oropharyngeal carcinoma (EORTC 1420; coordinator: Prof. Ch. Simon). This study will include stage I and II tonsil, glosso-tonsilar sulcus, lateralized base of tongue and lateral pharyngeal wall squamous cell carcinoma. Treatment of the neck will be done by surgery or radiotherapy depending on the randomization. The primary endpoint will be the assessment of the swallowing function (using the MDADI score) within the first year after the two treatment strategies. Secondary endpoints will include loco-regional tumor control rate at 1 and 2 years, overall survival at 1, 2 and 5 years, functional assessment at 2 years, complication rate at 2 years, QOL up to 2 years and cost-effectiveness. One hundred and seventy patients will be randomized to demonstrate a difference of at least 8 points in the MDADI swallowing scale between the 2 treatment arms.
The study is expected to start accruing patients around mid-2016.
Locally advanced pharyngo-laryngeal tumors
At the end of 2014, the HNCG launched, in collaboration with the Danish group DAHANCA, a double blind randomized multicenter study of accelerated fractionated chemo-radiotherapy (IMRT, 70 Gy in 6 weeks with cddp 100 mg/m2, weeks 1 and 4) with or without the hypoxic cell radiosensitizer nimorazole (Nimoral) for the treatment of HPV/p16 negative squamous cell carcinoma of the oropharynx, larynx and hypopharynx (EORTC 1219 – DAHANCA; coordinators: Prof. V. Grégoire and Prof. J. Overgaard). In this trial, a 15-gene signature specific for tumor hypoxia is used as a stratification factor. There are two primary objectives in this study: the first is to evaluate whether the hypoxic cell radiosensitizer nimorazole can improve the loco-regional control probability of concomitant chemo-radiotherapy; the second is to investigate if the patients and tumors that may have such benefit can be predicted by the use of a hypoxic gene profile, i.e. if the treatment benefit is larger and essentially restricted to the subset of patients who are hypoxic cell signature positive. The secondary objective is to evaluate the feasibility and morbidity of such treatment.
This is a randomized superiority trial where the number of patients enrolled is planned as 640, 320 in each treatment arm. After one year of accrual, 92 patients have been randomized from 11 participating institutions (10 European centers and one Canadian center) in alignment with the expected accrual curve. Six centers from Australia and New- Zealand will soon join the study groups, and during the course of 2016, additional new centers are expected to be further activated in Europe.
This trial is conducted along with a strong translational research program including the use of the FAZA-hypoxic PET tracer in selected centers, and also the exploratory investigation of additional gene signatures and their possible predictive role.
“Window of opportunity” study in oral cavity tumors
The EORTC 90111-24111 (coordinator: Prof. JP Machiels) early phase-II trial is a concept study aiming at discovering the activity of targeted agents using molecular biology and molecular imaging techniques such as FDGPET/ CT and DW-MRI as well as to identify predictive biomarkers for activity or resistance. Patients with squamous cell carcinoma of the head and neck (SCCHN) scheduled for primary surgery with curative intend are randomized (5:1) between neo-adjuvant afatinib treatment versus “no neo-adjuvant treatment”. The study included an early monitoring of the surgical co-morbidities for patients treated with afatinib, and the possibility to interrupt accrual prematurely according to pre-defined safety constraints. A total of 30 eligible patients have been randomized, out of which 25 patients received afatinib treatment. Data analysis is currently ongoing.
Recurrent and/or metastatic salivary gland tumors
The HNCG wants to address the treatment of rare tumors in the head and neck using novel treatments. In this direction, the HNCG initiated a randomized phase II study to evaluate the efficacy and safety of chemotherapy versus androgen deprivation therapy (1:1 randomization) in patients with recurrent and/or metastatic, androgen receptor expressing, salivary gland cancer (EORTC 1206; coordinator, Prof. L. Licitra). It is planned to randomize a total of 76 eligible patients, 38 in each arm. For this project, the EORTC HNCG is part of a larger international consortium called IRCI. The first centers have recently been activated.
Quality of Life
In close collaboration with the EORTC Quality of Life group (QLG), the HNCG is developing a new questionnaire for patients with thyroid cancer to measure their QOL (EORTC QLQ-THY, coordinator: Prof. S Singer). In the pilottesting, 131 patients have been enrolled out of the 150 planned. The HNCG also decided, together with the QLG, to revise the current version of the head and neck module EORTC QLQ-H&N35 (EORTC QLQ-HN, coordinator: Prof. S Singer). This revision became necessary as side effects of modern treatments were not covered by the module that was developed in the 1990s. The pilot-testing of this revised version is completed and the validation phase is ongoing.