<h3>Purpose/Objective(s)</h3> We aim to evaluate the role of neoadjuvant chemotherapy followed by hypofractionated radiotherapy in locally advanced unresectable OCSCC in terms of acute toxicity and efficacy. <h3>Materials/Methods</h3> 10 patients with locally advanced (T4a-T4b and N0 or N1-N2) inoperable OCSCC with good performance status were recruited in this single arm prospective study between December 2020-january 2022. All patients received 2 cycles of NACT (paclitaxel 175 mg /m<sup>2</sup> on D-1, cisplatin 75 mg / m<sup>2</sup> on D1 and D2 in divided doses) every three weekly followed by Hypofractionated Radiotherapy (RT), delivered by 3-dimensional conformal radiotherapy plan with a dose of 55Gray (Gy) in 22 fractions at 2.5Gy per fraction delivered 5 days a week in two phases. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and response was evaluated by WHO response criteria. The primary and secondary endpoints were clinical response rate and acute toxicity, respectively. Statistical analysis was done using statistical software. <h3>Results</h3> All patients received 2 cycles of NACT. Median RT dose was 55Gy. overall treatment time (OTT) was 98 days (95-120). Median Duration of follow up was 10 months (8-13 months). Patients' characteristics are summarized in table 1. All the patients completed their treatment as per protocol. Weekly assessment of toxicity was done and recorded during radiotherapy. Patients having dysphagia (grade >2) was 40% (4) and patients having dysphagia (grade ≤ 2) was 60% (6). Patients having oral mucositis (grade >2) was 50% (5) and those having (grade ≤ 2) was 50% (5). Radiation dermatitis more than grade 2 was not observed in any patient. No patient developed grade-4 radiation toxicity. All patients were regularly followed up for response assessment both clinically and radiologically. At median follow up of 10 month, 20% (2) patients had complete response (CR), 70% (7) patients had partial response (PR) and 10% (1) had progressive disease (PD). <h3>Conclusion</h3> Neoadjuvant chemotherapy followed by hypofractionated radiotherapy in locally advanced unresectable OCSCC shows acceptable acute radiation toxicity and good efficacy.
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