Concurrent Weekly Cisplatin and Simultaneous Integrated Boost Intensity Modulated Radiation Therapy (SIB IMRT) of Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LA SCCHN)

Abstract

We conducted a phase I/II trial to investigate concurrent weekly cisplatin and accelerated SIB IMRT in LA SCCHN. Patients in stage III/IVA were treated with SIB IMRT delivering 67,5/60/54 Gy in 30 fractions over 6 weeks to planning target volumes of gross tumor volume/clinical target volume/prophylactic neck with concurrent 2900weekly cisplatin 40 mg/m2. Dose modification of cisplatin was made if a subject experienced significant toxicity. Common Terminology Criteria of Adverse Events version 4.03 was used for toxicity assessment. We included 41 patients (median age 56 years, range 34 – 64 years) with oral cavity (6), larynx (3), hypopharynx (9) and oropharynx (23) in stage III (16) and IVA (25). HPV status assessed by p16 immunohistochemistry was positive in 27% (11) and negative in 73% (30). Median overall treatment time prolongation was 7 days. Cisplatin cumulative dose of at least 80% of the planned dose, i.e. ≥200 mg/m2, was delivered in 83% (34) and less than 200 mg/m2 in 17% (7). With the median follow-up of 21,4 months (range 5 – 33 months), the 2-years overall survival (OS), cancer specific survival (CSS) and local control rates (LCR) were 80,5%, 85,4% and 68,3% respectively. Most prominent grade 3 acute toxicity was bone marrow in 12% (5), mucositis in 12% (5), gastrointestinal in 10% (4), renal in 2% (1), and dermatitis in 2% (1). Cumulative late dysphagia ≥ grade 2 occurred in 24% (10), grade 2 xerostomia in 20% (8) and grade 2 mandibular osteoradionecrosis in 2% (1). On multivariate analysis, LCR was significantly determined by HPV status (100% vs. 57%, P = 0,001). The cumulative dose of cisplatin proved significant impact on LCR in HPV negative patients (63% vs. 33%, P = 0,041). Site of the primary, stage, age, gender, smoking status and overall treatment time prolongation were not significant in OS, CSS or LCR. High proportion of patients with LA SCCHN received adequate cumulative dose of concurrent cisplatin with SIB IMRT. Weekly cisplatin is effective in HPV positive patients. LCR in HPV negative patients with less than 200 mg/m2 cumulative dose of cisplatin was suboptimal.