PIK3CA mutation in HPV-associated OPSCC patients receiving deintensified chemoradiation

PIK3CA is the most frequently mutated gene in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Prognostic implications of such mutations remain unknown. We sought to elucidate the clinical significance of PIK3CA mutations in HPV-associated OPSCC patients treated with definitive chemoradiation (CRT). Seventyseven patients with HPV-associated OPSCC were enrolled on two phase II clinical trials of deintensified CRT (60 Gy intensitymodulated radiotherapy with concurrent weekly cisplatin). Targeted next-generation sequencing was performed. Of the 77 patients, nine had disease recurrence (two regional, four distant, three regional and distant). Thirty-four patients had mutation( s) identified; 16 had PIK3CA mutations. Patients with wild-type-PIK3CA had statistically significantly higher 3-year disease-free survival than PIK3CA-mutant patients (93.4%, 95% confidence interval [CI] = 85.0% to 99.9% vs 68.8%, 95% CI = 26.7% to 89.8%; P=.004). On multivariate analysis, PIK3CA mutation was the only variable statistically significantly associated with disease recurrence (hazard ratio = 5.71, 95% CI = 1.53 to 21.3; P=.01). PIK3CA mutation is associated with worse diseasefree survival in a prospective cohort of newly diagnosed HPV-associated OPSCC patients treated with deintensified CRT

Outcomes after Intensity-Modulated Compared with 3-Dimensional Conformal Radiotherapy with Chemotherapy for Squamous Cell Carcinoma of the Anal Canal

Purpose: We report our institution’s treatment techniques, disease outcomes, and complication rates after radiotherapy for the management of anal canal carcinoma with intensity-modulated radiotherapy (imrt) and concurrent chemotherapy relative to prior cases managed with 3-dimensional conformal radiotherapy (3D-crt). Methods: In a retrospective review of the medical records of 21 patients diagnosed with biopsy-proven stage i (23%), stage ii (27%), or stage iii (50%) squamous-cell carcinoma of the anal canal treated with curative chemotherapy and imrt between July 2009 and December 2014, patient outcomes were determined. Results for patients treated with 3D-crt by the same group were previously reported. The median initial radiation dose to the pelvic and inguinal nodes at risk was 45 Gy (range: 36–50.4 Gy), and the median total dose, including local anal canal primary tumour boost, was 59.4 Gy (range: 41.4–61.2 Gy). Patients received those doses over a median of 32 fractions (range: 23–34 fractions). Chemotherapy consisted of 2 cycles of concurrent fluorouracil–cisplatin (45%) or fluorouracil–mitomycin C (55%). Results: Median follow-up was 3.1 years (range: 0.38–6.4 years). The mean includes a patient who died of septic shock at 38 days. The 3-year rates of overall survival, metastasis-free survival, locoregional control, and colostomy-free survival were 95%, 100%, 100%, and 100% respectively. No patients underwent abdominoperitoneal resection after chemoradiotherapy or required diverting colostomy during or after treatment. Those outcomes compare favourably with the previously published series that used 3D-crt with or without brachytherapy in treating anal canal cancers. Of the 21 patients in the present series, 10 (48%) experienced acute grade 3, 4, or 5 toxicities related to treatment. Conclusions: The recommended use of imrt with concurrent chemotherapy as an improvement over 3D-crt for management of anal canal carcinoma achieves a high probability of local control and colostomy-free survival without excessive risk for acute or late treatment-related toxicities