Neoadjuvant Chemotherapy Followed by Hypofractionated Radiotherapy in Inoperable Oral Cavity Squamous Cell Carcinoma: A Prospective Single-Arm Study

Abstract

Background: Locally advanced, inoperable oral cavity squamous cell carcinoma (OCSCC) carries a dismal prognosis, and optimal non-surgical management remains undefined. Hypofractionated radiotherapy (HypoRT) offers the dual advantages of biological dose intensification and treatment efficiency. This study prospectively evaluated the efficacy and tolerability of neoadjuvant chemotherapy (NACT) followed by HypoRT in this difficult-to-treat population.
Methods: Fifteen patients with histologically confirmed, inoperable OCSCC (AJCC 7th edition; T4a–T4b, N0–N2) who remained unresectable after NACT (paclitaxel 175 mg/m² Day 1, cisplatin 75 mg/m² Days 1–2; 2–3 cycles, 3-weekly) received hypofractionated external beam radiotherapy (55 Gy in 22 fractions, 2.5 Gy per fraction over 4.5 weeks) without concurrent chemotherapy. Primary endpoint was objective response rate (ORR) at 3 months post-radiotherapy by WHO criteria. Secondary endpoints included acute toxicity (CTCAE v5.0), progression-free survival (PFS), and overall survival (OS).
Results: Median age was 50 years; 73.3% were male. The tongue was the commonest primary site (66.7%). T4b disease was present in 73.3% and N2 disease in 53.3%. All patients achieved partial response (ORR 100%) at 3 months, with median tumour volume reduction of 78.8% from baseline (range 58–88.1%). No patient had complete response, stable disease, or progression. Grade 3 dysphagia and oral mucositis each occurred in 60% of patients at peak (weeks 4–5), with Grade 3 radiation dermatitis in 20%. All patients completed the planned radiotherapy course without treatment interruption. Median PFS was 9.1 months (95% CI 8.0–10.3 months) and median OS was 13.7 months (95% CI 7.0–20.5 months).
Conclusion: NACT followed by hypofractionated radiotherapy (55 Gy/22 fractions) is a feasible, efficacious, and tolerable treatment strategy for inoperable OCSCC. This regimen merits further validation in larger prospective trials as a resource-efficient option for this challenging patient cohort.