Postoperative Concurrent Chemoradiotherapy Versus Postoperative Radiotherapy in High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck: The Randomized Phase III TROG 05.01 Trial.

Purpose To report the results of the Trans Tasman Radiation Oncology Group randomized phase III trial designed to determine whether the addition of concurrent chemotherapy to postoperative radiotherapy (CRT) improved locoregional control in patients with high-risk cutaneous squamous cell carcinoma of the head and neck. Patients and Methods The primary objective was to determine whether there was a difference in freedom from locoregional relapse (FFLRR) between 60 or 66 Gy (6 to 6.5 weeks) with or without weekly carboplatin (area under the curve 2) after resection of gross disease. Secondary efficacy objectives were to compare disease-free survival and overall survival. Results Three hundred twenty-one patients were randomly assigned, with 310 patients commencing allocated treatment (radiotherapy [RT] alone, n = 157; CRT, n = 153). Two hundred thirty-eight patients (77%) had high-risk nodal disease, 59 (19%) had high-risk primary or in-transit disease, and 13 (4%) had both. Median follow-up was 60 months. Median RT dose was 60 Gy, with 84% of patients randomly assigned to CRT completing six cycles of carboplatin. The 2- and 5-year FFLRR rates were 88% (95% CI, 83% to 93%) and 83% (95% CI, 77% to 90%), respectively, for RT and 89% (95% CI, 84% to 94%) and 87% (95% CI, 81% to 93%; hazard ratio, 0.84; 95% CI, 0.46 to 1.55; P = .58), respectively, for CRT. There were no significant differences in disease-free or overall survival. Locoregional failure was the most common site of first treatment failure, with isolated distant metastases as the first site of failure seen in 7% of both arms. Treatment was well tolerated in both arms, with no observed enhancement of RT toxicity with carboplatin. Grade 3 or 4 late toxicities were infrequent. Conclusion Although surgery and postoperative RT provided excellent FFLRR, there was no observed benefit with the addition of weekly carboplatin.

Predictors of acute grade 4 swallowing toxicity in patients with stages III and IV squamous carcinoma of the head and neck treated with radiotherapy alone.

PURPOSE: The purpose of the study was to investigate the predictive factors for acute grade 4 swallowing toxicity in an attempt to identify which patients may benefit from early intervention with enteral feeding during curative radiation treatment for localised Stages 3-4 squamous cell carcinoma of the head and neck. It was hypothesised that craniocaudal length of the treatment field to the upper neck and pharynx would correlate with grade 4 swallowing toxicity due to the increased volume of pharynx irradiated. PATIENTS AND METHODS: Toxicity data were collected prospectively as part of a phase III randomised trial (TROG 91:01) that assigned patients to either conventional (CRT) or accelerated radiotherapy (ART). Patients were randomly assigned to either CRT, using a single 2 Gy per day to a dose of 70 Gy in 35 fractions in 49 days or to ART, using 1.8 Gy twice a day to a dose of 59.4 Gy in 33 fractions in 24 days. Treatment allocation was stratified for site and stage. Accrual commenced in 1991 and the trial was closed in 1998 when the target of 350 patients was reached. Potential factors were analysed that predicted for Grade IV swallowing toxicity. RESULTS: The treatment field lengths >82mm for the second phase increased the probability of requiring intervention with percutaneous endoscopic gastrostomy (PEG) or Nasogastric tube (NGT). The probability of grade 4 swallowing was 36% if the phase 2 treatment length was >82mm vs 16% for less < or = 82mm(p=0.0001). A predictive enteral grading score (PEG score) was derived using the Cox regression coefficients: Field length of the boost volume >82mm scored 3 points, Stage grouping greater than 1 scored 1 point, altered fractionation scored 2 points, ECOG greater than 1 scored 1 point. The PEG score was 45% if the score was 6 and 19% if the score was <6 (p=0.0). CONCLUSIONS: More attention needs to be focused on developing robust dose and volume constraints for the pharyngeal mucosa and the musculature in order to reduce the need for enteral feeding. Patients with PEG score of 6 or greater are at high risk of requiring enteral feeding during radiation treatment and should be considered for prophylactic PEG or NG feeding.