From the start of the organization, the EORTC Head & Neck Cancer Group (HNCG) has always been in the forefront of Head and Neck clinical research. The HNCG was a pioneer in the field of organ preservation starting with the initiation of the first larynx preservation trial in 1989. EORTC trial 24891 compared PF (cisplatin and 5-FU, PF) induction chemotherapy followed by radiation therapy (RT) versus total laryngectomy, radical neck dissection, and postoperative RT in patients with locally advanced hypopharyngeal cancer [J Natl Cancer Institute 1996, 88: 890-899]. A recently published ten-year follow up study confirmed that the larynx preservation strategy provides similar overall survival rates as compared with conventional treatment with total laryngectomy and allowed two third of the survivors to retain their larynx [Ann Oncol 2012, 23(10): 2708-2714].
In a follow-up study, this regimen was compared to a regimen alternating radiotherapy (20 Gy in 2 weeks) and 1 course of chemotherapy (same regimen as above) up to a total dose of 60 Gy and 4 courses of chemotherapy (EORTC 24954). With a median follow-up of 6.5 years, larynx preservation, progression-free survival and overall survival were similar, as were the rate of acute and late toxicity [JNCI 2009, 101(3): 142-152]. An update of these results with a median follow-up of 10.2 years was identical [paper under submission].
Along the previous line, the role of neoadjuvant chemotherapy was further evaluated in patients with non-resectable locally advanced head and neck cancer (EORTC 24971). Patients were randomly assigned to receive PF based induction chemotherapy or TPF (Docetaxel, cisplatin and 5-FU) based chemotherapy followed by radiotherapy alone. TPF-induction chemotherapy showed superior outcome with regard to loco-regional tumor control and survival in comparison with the PF regimen and was shown to have a better tolerance and quality of life [N Engl J Med 2007;357(17):1695-1704]. The long term follow up with a median of eight years was presented at ASCO 2011 [J Clin Oncol 2011;29(15):367s, abs. 5530]. In the framework of larynx preservation protocols, this EORTC neo-adjuvant triple drug is a standard treatment in locally advanced unresectable laryngeal and hypopharyngeal tumors.
In parallel to the validation of the role of induction chemotherapy for organ preservation in locally advanced laryngeal and hypopharyngeal tumors, the HNCG contributed to the validation of alternated fractionation radiotherapy regimen in collaboration with the Radiation Oncology Group (ROG) of EORTC. EORTC trial 22971 demonstrated that hyperfractionated radiotherapy (80.5 Gy in 7 weeks) translated into a 19% improved loco-regional control rate in patients with T2-T3, N0-N1 oropharyngeal squamous cell carcinoma compared to standard fractionation (70 Gy in 7 weeks), with no increase in late radiation morbidity [Radiother. Oncol. 1992, 25: 231-241]. Similarly, the EORTC 22851 trial demonstrated that accelerated radiotherapy (72 Gy in 5 weeks) translated into a significant 13% increase in 5-year loco-regional control rate in patients with locally advanced squamous cell carcinoma compared to standard fractionation (70 Gy in 7 weeks) [Radiother. Oncol. 1997, 44: 111-121].
Head and Neck surgery remains a standard therapeutic option for squamous cell carcinoma originating in the oral cavity, as well as for early pharyngo-laryngeal disease. In locally very advanced laryngeal tumors, it is probably the best treatment option as no vocal function is to be retained. A large proportion of these patients will require postoperative radiotherapy. In this setting, the EORTC trial 22931 compared post-operative radiotherapy (66 Gy in 6.5 weeks) to the same radiotherapy with concurrent administration of high dose cisplatin (100 mg/m2, weeks 1, 2 and 3). The latter was proven to increase the 5-year overall survival by 13% in patients with locally advanced head and neck squamous cell carcinoma, without increasing the rate of late complications [N Engl J Med 2004, 350(19):1945-1952]. A combined analysis with a similarly designed RTOG trial demonstrated that patients with R1 resection and/or with extra-capsular nodal spread were the ones benefiting from this combined approach [Head Neck 2005, 27: 843-850]. This strategy is now adopted as state of the art treatment for post-operative radiotherapy.