Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis.

BACKGROUND: Several trials have studied the role of unconventional fractionated radiotherapy in head and neck squamous cell carcinoma, but the effect of such treatment on survival is not clear. The aim of this meta-analysis was to assess whether this type of radiotherapy could improve survival. METHODS: Randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic HNSCC were identified and updated individual patient data were obtained. Overall survival was the main endpoint. Trials were grouped in three pre-specified categories: hyperfractionated, accelerated, and accelerated with total dose reduction. FINDINGS: 15 trials with 6515 patients were included. The median follow-up was 6 years. Tumours sites were mostly oropharynx and larynx; 5221 (74%) patients had stage III-IV disease (International Union Against Cancer, 1987). There was a significant survival benefit with altered fractionated radiotherapy, corresponding to an absolute benefit of 3.4% at 5 years (hazard ratio 0.92, 95% CI 0.86-0.97; p=0.003). The benefit was significantly higher with hyperfractionated radiotherapy (8% at 5 years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1.7% with total dose reduction at 5 years, p=0.02). There was a benefit on locoregional control in favour of altered fractionation versus conventional radiotherapy (6.4% at 5 years; p<0.0001), which was particularly efficient in reducing local failure, whereas the benefit on nodal control was less pronounced. The benefit was significantly higher in the youngest patients (hazard ratio 0.78 [0.65-0.94] for under 50 year olds, 0.95 [0.83-1.09] for 51-60 year olds, 0.92 [0.81-1.06] for 61-70 year olds, and 1.08 [0.89-1.30] for over 70 year olds; test for trends p=0.007). INTERPRETATION: Altered fractionated radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation has the greatest benefit.

Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients.

OBJECTIVES: To study the effect of adding chemotherapy to radiotherapy (RT) on overall survival and event-free survival for patients with nasopharyngeal carcinoma. METHODS AND MATERIALS: This meta-analysis used updated individual patient data from randomized trials comparing chemotherapy plus RT with RT alone in locally advanced nasopharyngeal carcinoma. The log-rank test, stratified by trial, was used for comparisons, and the hazard ratios of death and failure were calculated. RESULTS: Eight trials with 1753 patients were included. One trial with a 2 x 2 design was counted twice in the analysis. The analysis included 11 comparisons using the data from 1975 patients. The median follow-up was 6 years. The pooled hazard ratio of death was 0.82 (95% confidence interval, 0.71-0.94; p = 0.006), corresponding to an absolute survival benefit of 6% at 5 years from the addition of chemotherapy (from 56% to 62%). The pooled hazard ratio of tumor failure or death was 0.76 (95% confidence interval, 0.67-0.86; p < 0.0001), corresponding to an absolute event-free survival benefit of 10% at 5 years from the addition of chemotherapy (from 42% to 52%). A significant interaction was observed between the timing of chemotherapy and overall survival (p = 0.005), explaining the heterogeneity observed in the treatment effect (p = 0.03), with the highest benefit resulting from concomitant chemotherapy. CONCLUSION: Chemotherapy led to a small, but significant, benefit for overall survival and event-free survival. This benefit was essentially observed when chemotherapy was administered concomitantly with RT.

Individual patients' data meta-analyses in head and neck cancer.

PURPOSE OF REVIEW: This is a review of the experience obtained at the Institute Gustave Roussy, evaluating the role of chemotherapy and of altered fractionated radiotherapy in locally advanced head and neck cancer. The database included nearly 120 randomized trials, and about 25,000 patients, with a median follow-up of 6 years. RECENT FINDINGS: In the chemotherapy database (Meta-Analysis of Chemotherapy in Head, Neck Cancer and Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma), concomitant cisplatin-based radiotherapy-chemotherapy provided the most significant benefit on locoregional control and survival, both in head and neck squamous cell carcinomas and nasopharyngeal carcinomas. In head and neck squamous cell carcinomas, the benefit of adding concomitant chemotherapy was found to be in the same order of magnitude whether radiotherapy was postoperative or definitive. In the altered radiotherapy database (Meta-Analysis of Radiotherapy in Carcinoma of Head and Neck), among the different types of altered fractionated radiotherapy, hyperfractionation provided the most significant benefit. The benefit associated with altered fractionated radiotherapy and of concomitant chemotherapy markedly decreased with increasing age. SUMMARY: This database provided a unique tool to evaluate long-term effects of chemotherapy and altered fractionated radiotherapy in head and neck cancer. This allowed the oncological community to obtain a reliable characterization of the magnitude of the treatment benefits in this type of cancer and to base patient care and future research on strong evidence.