Impact of tumor volume and systemic therapy on outcome in patients undergoing IMRT for large volume head neck cancer

BACKGROUND: Former prospective analyses revealed gross tumor volume (GTV) as the most reliable parameter to statistically significantly predict disease control in head neck cancer (HNC) patients treated with definitive intensity modulated radiation therapy (IMRT) +/-concomitant systemic therapy. The most 'unfavourable' subgroup was characterized by total GTV (tGTV) of > 70 cc, translating in ~50 and 65% 3-year disease free (DFS) and overall survival (OAS, vs 68% and 88% in tGTV < 70 cc, p = 0.001 and 0.0001), and ~25% distant spread (vs 6% for tGTV < 70 cc, p < 0.0001). The aim of this report was to analyze whether there is a subgroup out of patients with tGTV > 70 cc, which only marginally benefits from intensive curative treatment. RESULTS: Between 03/2002-03/2011, 112 HNC patients with tGTV > 70 cc were definitively irradiated with curative intention. Mean tGTV was 104 cc (71-251). 98/112 (88%) patients underwent systemic therapy. Parameters with potential impact on disease outcome were retrospectively tested. The 3-year local-regional control (LRC), DFS and OAS rates were 61%, 50%, and 58%. The used cut-off value of 130 cc revealed an inverse association between tGTV and outcome. Patients able to undergo any systemic therapy (n = 98, mean tGTV0 103 cc, mean age 60 years) showed a satisfying and significantly superior outcome compared to the subgroup with radiation alone (n = 14, mean tGTV 99 cc, mean age 73 years), with 53% vs 17% 3-year DFS (p = 0.01). Radiation alone for tGTV > 130 cc failed to aim its curative goal in 3/3 patients. CONCLUSION: Patients with tGTV > 70 cc unable to undergo any systemic therapy represented a subgroup in which disease control was achievable in < 20% following curatively intended IMRT. Prospective testing of a larger sample size is needed to evaluate, if radiation alone for tGTV >~130 cc fails to meet its curative aim.