Author: Neil Osterweil, Oncology Report Digital Network
Concurrent chemoradiation offered better overall survival and disease-free survival than accelerated radiotherapy in patients with moderately advanced squamous cell carcinomas of the head and neck, investigators reported at the Multidisciplinary Head and Neck Symposium.
Actuarial rates of 2-year overall survival and disease-free survival in patients treated with concurrent chemoradiation (CCR) were significantly better than for patients treated with accelerated radiotherapy alone, reported Dr. Krzysztof Skladowski of the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Gliwice, Poland.
“CCR with conventional 7 weeks of fractionation and at least two courses of high-dose cisplatin is more effective than 6 weeks of accelerated radiotherapy alone,” he said.
Even if patients can tolerate only a single course of cisplatin, CCR is still superior to accelerated radiation, he added.
The findings suggest that accelerated radiation protocols should be reserved for patients with more favorable prognosis, such as those with stage T2 disease with limited nodal involvement, and those who are positive for the human papillomavirus (HPV) p16 protein, Dr. Skladowski said at the symposium cosponsored by the American Society for Radiation Oncology and the American Society of Clinical Oncology.
The findings are “concordant with data that has been emerging now over approximately 10-14 years of the value of concurrent chemoradiation in head and neck cancer for a substantial cohort of patients over radiation alone,” said Dr. Paul Harari of the University of Wisconsin, Madison, and the invited discussant.
Although a previous meta-analysis (Lancet 2006; 368:843-54) suggested that accelerated or hyperfractionated radiotherapy was associated with a 3.4% advantage in overall survival, compared with conventional radiotherapy over 5 years, there have been no randomized studies comparing accelerated radiotherapy protocols with concurrent chemoradiation in this population, Dr. Skladowski said.
He and colleagues compared the two modalities in 101 patients with moderately advanced cancers of the oropharynx (46 patients), hypopharynx (19), and larynx (36).
They defined moderately advanced cancers as stage T2N1-2, T3N0-2, or T4AN0-2 if the involved nodes are not larger than 3 cm in diameter. Patients with oropharyngeal cancers were tested for expression of the human papillomavirus (HPV) p16 protein.
Patients were randomly assigned to receive either concurrent chemoradiation with intensity-modulated radiation therapy–delivered doses of 66-70 Gy divided into 33-35 daily fractions over 45-49 days plus cisplatin 100 mg/m2, delivered on days 1, 2 and 43, or to accelerated radiotherapy delivered via intensity-modulated radiation therapy in 1.8 Gy fractions 7 days/week to a total dose of 66.2-72 Gy.
Five patients in the CCR arm received only one dose of cisplatin, 30 received two doses, and 13 received the planned three doses.
At a median follow-up of 30 months, actuarial rates of 2-year overall survival of patients treated with CCR were 81%, compared with 62% for patients treated with accelerated radiation (P = .02). Disease-free survival rates were 75% and 60%, respectively (P = .05).
Acute adverse events were similar, with approximately 80% of patients in each treatment arm experiencing confluent mucositis, and about 10% having grade 3 dysphagia. There were no grade 4 toxicities.
The majority of treatment failures in each group were local, occurring in 21 of 52 patients treated with radiation alone, and in 11 of 49 patients treated with CCR (P = .03).
Significantly more deaths occurred in the radiation alone arm: 20 vs. 9 (P =.02).
The 2-year disease-free survival rate among patients in the CCR arm was dose dependent, at 60% of patients who received one course of cisplatin, 77% of those who received two courses, and 79% for those who received all three.
At the time of the analysis, all patients with oropharyngeal cancer who were positive for HPV p16 (five treated with accelerated radiation and six with CCR) were alive with no treatment failure. The overall survival rate for HPV-positive patients was 60% in the radiation only arm, and 80% in the CCR arm.
The study was supported by the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology. Dr. Skladowski reported having no financial disclosures. Dr. Harari has received research funding from Amgen.