Background: Concomitant Chemoradiotherapy (CRT) is standard approach for treating locally advanced head and neck squamous cell carcinoma (HNSCC). Altered fractionation such as hyperfractionated radiotherapy (HF) has also shown similar survival benefits as compared to conventional CRT. To determine whether addition of concomitant chemotherapy to hyperfractionated radiotherapy further improves outcome in HNSCC patients treated with modern volumetric arc modulated radiotherapy (VMAT).Methods: From January 2018 to March 2019, thirty four patients with stage III-IV HNSCC (excluding oral cavity, nasopharynx and paranasal sinus) were randomly assigned to hyperfractionated HFCRT (VMAT) with concomitant chemotherapy arm with radiation dose 81.6Gy/68 fractions,1.2Gy/fraction, twice daily, 5days/week or Conventional CRT (VMAT) arm with radiation dose 70GY/35 fractions, 2Gy/fraction, once daily, 5days/week, seventeen patients in each arm. Concurrent cisplatin 40mg/m 2 /week was given in both arm from first week. Overall survival (OS), Disease free survival (DFS) and toxicities were assessed. Results:The cisplatin full dose was received by 94.1% and 82.4% patients in HFCRT (VMAT) and CRT (VMAT) arm respectively. High grade (3-4) acute skin and mucosal were higher in HFCRT (VMAT) arm (47.1%) in comparison to CRT (VMAT) arm (17.6%) with no statistical significance (p = 0.067). Late toxicity was similar in both arms. The OS was better in HFCRT (VMAT) arm with median overall survival-17 months as compared to CRT (VMAT) arm with median overall survival -12 months, however, difference did not reach significance (log-rank test, p = 0.341), with similar trend in DFS. Conclusion:Hyperfractionated HFCRT (VMAT) with concomitant chemotherapy showed an encouraging trend for OS and DFS with acceptable toxicity profile. A larger study with longer follow up needed to elucidate possible superiority of HFCRT over CRT.
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