Meta-analysis of Treatment Modalities for Locally Advanced Head and Neck Cancer

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In an individual patient data network meta-analysis reported in The Lancet Oncology, Petit et al identified treatment modalities associated with improved overall survival vs locoregional treatment alone in nonmetastatic head and neck squamous cell cancer, with hyperfractionated radiotherapy and concomitant chemotherapy appearing to provide the best outcome.

Study Details

The analysis included 115 randomized trials that enrolled patients between January 1980 and April 2012, yielding 154 comparisons between treatments that included 28,978 patients with 19,253 deaths and 20,579 progression events. Treatments were grouped into 16 modalities that permitted 35 types of direct comparison.

Overall survival was the primary endpoint, with treatment modalities being compared with locoregional therapy (surgery, radiotherapy, or both) as the reference category. Treatments were ranked for effectiveness using a P score (higher score indicates more effective therapy).

Key Findings

Median follow-up based on all trials was 6.6 years (interquartile range = 5.0–9.4 years).

Hyperfractionated radiotherapy with concomitant chemotherapy (HFCRT) was ranked as the best treatment for overall survival (P score = 97%; hazard ratio [HR] vs locoregional therapy = 0.63, 95% confidence interval [CI] = 0.51–0.77). HFCRT was followed in order according to P score by:

  • Induction chemotherapy with taxane, cisplatin, and fluorouracil followed by locoregional therapy (ICTaxPF-LRT; 89%, HR = 0.69, 95% CI = 0.56–0.85)
  • Accelerated radiotherapy with concomitant chemotherapy (ACRT; 82%, HR = 0.75, 95% CI = 0.66–0.85)
  • ICTaxPF followed by locoregional therapy with concomitant chemoradiotherapy (ICTaxPF-CLRT; 80%, HR = 0.75, 95% CI = 0.62–0.9.2)
  • Locoregional therapy with concomitant chemoradiotherapy with platinum-based chemotherapy (CLRTP; 78%, HR = 0.77, 95% CI = 0.72–0.83).

The overall survival hazard ratio for HFCRT vs CLRTP was 0.82 (95% CI = 0.66–1.01). Compared with CLRTP, hazard ratios also favored the other top three modalities: ICTaxPF-LRT (HR = 0.90, 95% CI = 0.72–1.12), ACRT (HR = 0.97, 95% CI = 0.86–1.10), and ICTaxPF-CLRT (HR = 0.98, 95% CI = 0.81–1.19).

The absolute overall survival benefit at 5 years vs locoregional therapy alone was 16.7% for HFCRT, 13.4% for ICTaxPF-LRT, 10.4% for ACRT, 10.3% for ICTaxPF-CLRT, and 9.5% for CLRTP.

For event-free survival, the five highest ranked modalities vs locoregional therapy alone were: HFCRT (P score = 97%, HR = 0.60, 95% CI = 0.49–0.73), ICTaxPF-CLRT (89%, HR = 0.66, 95% CI = 0.55–0.80), ACRT (82%, HR = 0.71, 95% CI = 0.63–0.80), ICTaxPF-LRT (80%, HR = 0.71, 95% CI = 0.59–0.87), and CLRTP (75%, HR = 0.74, 95% CI = 0.70–0.79). Of the five treatments, only HFCRT was associated with significantly better outcome vs CLRTP (HR = 0.80, 95% CI = 0.65–0.98).

The investigators concluded, “The results of this network meta-analysis suggest that further intensifying chemoradiotherapy, using hyperfractionated radiotherapy with concomitant chemotherapy or induction chemotherapy with taxane, cisplatin, and fluorouracil followed by locoregional therapy with concomitant chemoradiotherapy, could improve outcomes over chemoradiotherapy for the treatment of locally advanced head and neck cancer.”

Pierre Blanchard, MD, of the Department of Radiation Oncology, Gustave Roussy, Villejuif, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by the French Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC. For full disclosures of the study authors, visit

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