At 10 years, the cumulative incidence of radiation-induced second malignancies in patients receiving definitive radiation therapy for human papillomavirus (HPV)–associated oropharyngeal cancers was 1.74%, according to findings culled from the Cleveland Clinic Cancer Institute database. These findings were presented in a poster at the 2025 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract 2731).
“The patient population with HPV-positive disease has a very high likelihood of cure with the right treatment. It is also a younger population who likely has decades of life ahead of them. As such, not only is the goal to cure these patients but also for them to live well for the long term. As the number of treatment options proliferates and as we start to figure out how to de-escalate therapy for select patients, we need to have a sense of the full spectrum of benefit and risk over their future lifetime. That includes risks of secondary malignancies,” stated senior study author Neil M. Woody, MD, a radiation oncologist at Cleveland Clinic.
Rationale and Study Methods
The study authors sought to determine the rate of radiation-induced second malignancies among a large cohort of patients with oropharyngeal cancer who were treated with radiation therapy, so patients considering their treatment options could be accurately counseled on the risks and benefits of radiation therapy vs transoral robotic surgery. Davies et al reviewed patient data, tumor characteristics, and clinical outcomes from patients diagnosed with HPV-positive cancers of the oropharynx who received intensity-modulated radiation therapy between 2009 and 2020 at the Cleveland Clinic Cancer Institute.
For the study, radiation-induced second malignancy was defined as a tumor arising within the line of the treated tumor with features of being histopathologically distinct from the primary tumor, occurring at a geographically distinct site or subsite, and/or occurring more than 5 years from the completion of radiation therapy.
Key Study Findings
A total of 662 patients met the eligibility criteria. These patients were followed for a median of 58.4 months.
Eight patients developed a radiation-induced second malignancy between 19.4 and 140 months after radiation therapy, for cumulative incidence rates of 0.37% (95% confidence interval [CI] = 0.08%–1.28%) at 5 years and 1.74% (95% CI = 0.70%–3.65%) at 10 years. Among these eight patients, radiation doses ranged from 70 to 74 Gy, six received concurrent chemotherapy, and all eight underwent neck dissection.
“For patients with early-stage disease, these findings will enable clinicians to have a more comprehensive discussion about the risks and benefits of radiation therapy,” stated lead study author Erik Davies, MD, a resident in radiation oncology at Cleveland Clinic.
Of note, the patients who developed a radiation-induced second malignancy were more likely to have an extensive smoking history than patients who did not develop a secondary cancer.
In the overall cohort of patients with HPV-positive oropharyngeal cancer treated with radiation therapy, the overall survival rate at 5 years was 83%, and it was 69% at 10 years. Disease recurrence was reported in 16.6% of patients.
“Based on our data, a patient in the early stages might preferentially be recommended for surgery,” Dr. Davies said. However, patient selection is still crucial, and some patients may still need chemoradiotherapy following surgery for an optimal chance of cure.
The study authors noted that further analysis is needed in larger patient cohorts for competing risk analysis to identify the patients most at risk for radiation-induced second malignancies.
Disclosure: For full disclosures of the study authors, visit amportal.astro.org.
