HPV+ Oropharyngeal Cancer Recurrence Typically Detected Within 6 Months of Treatment

Jessica Frakes, MD

In patients treated with definitive radiation therapy (RT) for HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), most recurrences can be detected via imaging at 3 months and physical examinations during the first 6 months after treatment, according to research presented at the 2016 Multidisciplinary Head and Neck Cancer Symposium.

Most recurrences and toxicities were detected by posttreatment imaging at 3 months and physical examinations during the 6 months after treatment. Patients experienced low rates of permanent toxicity, potentially because a multidisciplinary team delivered treatment. Minimizing posttreatment tests without compromising outcomes might reduce patient stress and financial burden.

Previous retrospective and prospective studies have shown that while HPV-associated cases of OPSCC are increasing in frequency, treatments result in decreased toxicities and increased survival. As the number of patients with HPV-positive oropharyngeal cancer and the number of survivors grows, best follow-up care practices need to consider typical time to recurrence and the most effective methods for recurrence detection.

“The purpose of our study is really to determine when these patients fail and also when they have side effects so we know how to guide our optimal follow-up schedule. If you look at the NCCN guidelines, it’s a one-size-fits-all. So whether you’re HPV-associated or not associated, the follow-up recommendations are the same,” said lead study author Jessica Frakes, MD, an assistant professor in the department of Radiation Oncology at the H. Lee Moffitt Cancer Center and Research Institute, during a presscast.

This study examined data from 245 patients diagnosed with either HPV-positive or p16-positive OPSCC. These patients all received definitive RT, and most patients (85%) also received concurrent chemotherapy.

Median follow-up was 36 months. Every patient received a 3-month posttreatment PET/CT scan. Every patient also received physical examinations every 3 months in the first year after treatment, every 4 months in the second year, every 6 months in years 3 to 5, and then annually. Local control was achieved in 239 of 245 patients (98%).

“As you can see from our results here, they’re excellent. Our local control was 98% at 3 years,” said Frakes.

Six local failures were all detected by physical examination via either direct visualization (n = 2) or flexible laryngoscopy (n = 4). Regional failures in the neck (n = 9) were largely detected (89%) by posttreatment imaging. Patients who suffered regional failure were more likely to have had ≥5 nodes or the presence of level 4 lymph nodes upon initial diagnosis and treatment. By 3 years, regional control maintained in 95.3% of patients.

Of distant metastases (n = 21), 71% (n = 15) were discovered by patient symptoms or 3-month posttreatment imaging. An increased risk of distant metastases occurred in patients with lymph nodes >6 cm in diameter, bilateral lymph node carcinomas, ≥5 nodes, or level 4 nodes upon initial diagnosis and treatment. For all patients, 3-year overall survival was 91%.

Late toxicity of grade ≥3 occurred initially in 9% of patients. Late toxicity was defined as side effects that occurred 3 months posttreatment or later. These severe late effects included 19 grade 3 toxicities and 2 grade 4 toxicities with the majority (76%; 16 /21) resolved at the time of last follow-up. Since most cases of late toxicity were resolved, the overall toxicity rate was 2%.

“In conclusion, what we gathered from our study was that the majority of the recurrences and toxicities can be detected by posttreatment imaging at 3 months and physical examinations during that first 6 months following treatment. Regardless of those patients who are at higher risk for regional or distant failures, they still had that same time course of toxicity and/or recurrence,” explained Frakes.

Frakes suggested that excessive posttreatment surveillance and imaging could increase anxiety and financial burden to the patients. These results indicated that no further imaging is warranted if posttreatment PET/CT scans are negative.

“Minimizing these tests that do not compromise outcomes [might] help decrease patient anxiety and stress as well as the financial burden for our patients. And lastly, our outcomes are excellent with lower rates of permanent toxicity, and we think this is partly due to the fact that they are treated with specialized, multidisciplinary teams,” concluded Frakes.

Frakes JM, Naghavi AO, Strom T, et al. Detection of recurrence in HPV associated oropharynx squamous cell carcinoma. Presented at: 2016 Multidisciplinary Head and Neck Cancer Symposium; February 18-20, 2016; Scottsdale, AZ. Abstract 6.

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