Phase 2 trial indicates viability of half the standard dose for appropriately selected patients with oropharynx cancer following surgery.

For certain patients with oropharyngeal cancer caused by the human papilloma virus (HPV), an aggressive reduction of radiation therapy after surgery may provide excellent cancer control while simultaneously reducing post-treatment side effects, improving quality of life and lowering treatment costs, according to research presented at the 59th Annual Meeting of the American Society for Radiation Oncology (ASTRO).

Patients in the phase 2 clinical trial received half the standard radiation dose but achieved equally high cure rates at two years following treatment.

Standard treatment for oropharyngeal squamous cell carcinoma (OPSCC) can include surgery to remove the cancer followed by radiation therapy with or without chemotherapy. While cure rates are excellent following therapy, treating the sensitive throat and neck regions often causes serious and potentially life-altering side effects.

Quality of life considerations have become even more salient in the past several decades, as today’s average OPSCC patient is younger and will live a longer time with any side effects of treatment. Between 1988 and 2004, the rates of HPV?associated OPSCC more than doubled, while the rates of HPV?negative disease—which is typically caused by smoking and alcohol consumption—dropped by half. HPV-related disease also is biologically more responsive to radiation and chemotherapy, leading to high cure rates for these patients.

“The profile of the typical oropharynx cancer patient has changed, which means that our approach to treating this disease needs to change, as well,” said Daniel Ma, MD, lead author of the study and an assistant professor of radiation oncology at the Mayo Clinic in Rochester, Minnesota. “Several research groups are pursuing an incremental approach to de-escalating treatment, such as using 15% less radiation dose. Our trial took a different approach—testing whether we could cut the dose by half. Our findings indicate that this more aggressive approach toward treatment reduction can be viable for appropriately selected patients.”

MC1273 was a single-arm phase 2 trial for HPV-related OPSCC testing clinical outcomes and quality of life with a de-escalated course of radiation therapy following surgery to remove the disease. Patients received two weeks of twice-daily radiation therapy to the oropharynx for a total dose of 30-36 Gray (Gy), a 50% reduction of the standard radiation dose of 60-66 Gy. Patients also received two courses of chemotherapy (docetaxel 15 mg/m^2), delivered on days one and eight. The 43 patients with extracapsular extension (ECE), a marker of particularly aggressive disease, received an additional, simultaneous radiation boost to the areas with ECE, for a total dose (including primary treatment) of 36 Gy.

Eighty patients were accrued between September 2013 and June 2016 with all patients completing treatment. Eligible patients included those with HPV-related OPSCC who had no evidence of residual disease following surgery and a minimal smoking history (e.g., less than one pack per day for 10 years or less). The median patient age was 60.5 years (range 25-77 years). All patients had stage III or IV disease. The median follow-up for this report was 24 months (range 12-46 months).

At a median follow-up of two years after de-escalated treatment, the rate of tumor control in the oropharynx and surrounding region was 95%. Of the 80 patients in the trial, three experienced a local recurrence and one patient experienced a regional recurrence. Disease-free survival (DFS) following the dose-reduced treatment was 89%. By comparison, the RTOG 0234 clinical trial reported a two-year DFS rate of 86.4% for patients with HPV-related cancers.

Grade 2 or higher side effects were reported in 1% of patients at one year following treatm