In a single-institution phase II trial reported in the Journal of Clinical Oncology, Nancy Y. Lee, MD, and colleagues found that tumor hypoxia is a promising marker for radiotherapy dose among patients receiving chemoradiotherapy for human papillomavirus (HPV)-related oropharyngeal carcinoma.
As stated by the investigators, “Standard curative-intent chemoradiotherapy for HPV-related oropharyngeal carcinoma results in significant toxicity. Since hypoxic tumors are radioresistant, we posited that the aerobic state of a tumor could identify patients eligible for de-escalation of chemoradiotherapy while maintaining treatment efficacy.”
Nancy Y. Lee, MD
Study Details
In the trial, 152 patients at Memorial Sloan Kettering Cancer Center with T0-2/N1-N2c disease underwent surgical removal of primary site disease, but not of gross disease in the neck. Patients underwent a fluorine-18–fluoromisonidazole positron-emission tomography (FMISO PET) scan to measure tumor hypoxia at baseline and at 1 to 2 weeks intratreatment.
Patients with nonhypoxic tumors received radiotherapy at 30 Gy over 3 weeks with chemotherapy; those with hypoxic tumors received standard chemoradiotherapy to 70 Gy over 7 weeks with chemotherapy. Chemotherapy consisted of cisplatin at 100 mg/m2 or carboplatin at AUC 5 and fluorouracil at 2,400 mg/m2 over 4 days. The primary objective was achieving a 2-year locoregional control of 95% with a 7% noninferiority margin.
Key Findings
At baseline, 110 patients had hypoxic tumors and 42 had nonhypoxic tumors; at intratreatment measurement, hypoxia persisted in 24 patients and resolved in 86. Thus, 24 patients received a boost of 40 Gy/2 Gy/fraction to gross nodal disease to a total of 70 Gy and three cycles of chemotherapy, and 128 patents received radiotherapy of 30 Gy and two cycles of chemotherapy.
Among all patients, 2-year locoregional control was 94.7% (95% confidence interval [CI] = 89.8%–97.7%), meeting the study objective. With a median follow-up of 38.3 months (range = 22.1–58.4) months, 2-year progression-free survival and overall survival rates among all patients were 94% and 99%, respectively, including rates of 94% and 100% in the 30-Gy cohort and 96% and 96% in the 70-Gy cohort.
Acute grade 3 or 4 adverse events were more common in the 70-Gy cohort vs the 30-Gy cohort (58.3% vs 32%, P = .02). Late grade 3 or 4 adverse events occurred only in the 70-Gy cohort, consisting of dysphagia in 4.5% of patients.
The investigators concluded, “Tumor hypoxia is a promising approach to direct dosing of curative-intent chemoradiotherapy for HPV-related carcinomas, with preserved efficacy and substantially reduced toxicity that requires further investigation.”
Dr. Lee, of the Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute and others. For full disclosures of the study authors, visit ascopubs.org.
