High survival and organ function rates after primary chemoradiotherapy for intermediate-stage squamous cell carcinoma of the head and neck treated in a multicenter phase II trial

Abstract

Purpose: Patients with intermediate-stage squamous cell carcinoma of the head and neck traditionally have been treated with initial surgical resection followed by radiotherapy (RT) alone or chemoradiotherapy. A previous study in this patient population reported a 91% locoregional control rate and 65% overall survival (OS) rate at 5 years, with chemoradiotherapy used as primary treatment. This study was undertaken to assess whether shortening treatment duration with hyperfractionated RT would be feasible and improve locoregional control, organ preservation, and progression-free survival.

Methods: Eligible patients with stage II or III disease received fluorouracil, hydroxyurea, and RT given twice daily on a week-on/week-off schedule. Quality-of-life scores were measured using three validated indexes.

Results: All 53 patients enrolled are included in the analysis, with a median follow-up of 42 months (range, 5 to 98 months). Grade 3 or 4 in-field mucositis was observed in 77% and 9%, respectively. No patients required surgical salvage at the primary tumor site (pathological complete response rate, 100%). The 3-year progression-free and OS rates are 67% and 78%, respectively. The 3-year disease-specific mortality rate is 7%. At the time of analysis, 87% of surviving patients do not require enteral feeding support. Quality-of-life and performance assessment indicated that, although acute treatment toxicities were severe, most patients returned to pretreatment function by 12 months.

Conclusion: Concurrent chemoradiotherapy with hyperfractionated RT is feasible in this patient population and yields high local control and cure rates. Compared with our historical control using once-daily fractionation, hyperfractionation is accompanied by increased acute in-field toxicity.

Conflict of interest statement

Authors’ Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

Figures

Fig 1

Mean quality-of-life scores with SE bars from baseline (BL) to 36 months for selected variables. Higher scores represent better functioning. The y-axis represents raw scores obtained on each respective instrument. (A) Diet; (B) pain in mouth; (C) stick saliva; (D) dry mouth; and (E) FACT-G. N, number of patients with available data at each time point; FACT-G, Functional Assessment of Cancer Therapy–General.

Fig 2

(A) Kaplan-Meier curve of progression-free survival. (B) Kaplan-Meier curve of overall survival. (C) Cumulative incidence of disease-related mortality.