For patients treated with definitive radiation therapy for oropharyngeal cancer caused by human papillomavirus (HPV), the majority of recurrences can be detected by post-treatment imaging at 3 months and physical exams during the 6 months following treatment, according to research presented by Frakes et al at the 2016 Multidisciplinary Head and Neck Cancer Symposium (Abstract 6).
The number of oropharyngeal squamous cell carcinoma cases associated with HPV has climbed dramatically in the past several decades, according to the American Cancer Society, and survival rates following definitive radiation therapy have risen, as well. As the number of oropharyngeal cancer patients and survivors grows, so does the need to determine general time to recurrence and the most effective modes of recurrence detection, to guide standards for optimal follow-up care by oncology teams.
To examine patterns in recurrence detection, researchers in this study examined all 246 cases of HPV- or p16-positive non-metastatic oropharyngeal squamous cell carcinoma treated with definitive radiation therapy at a single, large-volume cancer center between 2006 and 2014. Most patients received radiation therapy and a concurrent systemic therapy (n = 209, 84.6%); fewer patients received definitive radiotherapy alone (n = 38, 15.4%).
For follow-up care, patients received a positron-emission tomography/comuted tomography (PET/CT) scan 3 months after completing treatment, as well as physical exams every 3 months in the first year following treatment, every 4 months in the second year, and every 6 months in years 3 to 5.
Median follow-up care length for all patients was 36 months. Patient outcomes, including recurrence and survival rates, were calculated using the Kaplan-Meier method from the end of radiation therapy.
Most recurrences were detected either by persistent disease appearing on 3-month post-treatment imaging or by patients presenting with symptoms at follow-up exams. All six local failures were detected by direct visualization or flexible laryngoscopy in physical exams. Eight of the nine regional recurrences (89%), 12 of the 13 locoregional failures (92%), and 15 of the 21 distant recurrences (71%) were found due to symptoms or a PET/CT scan 3 months following treatment.
Findings also indicated that some disease characteristics increase the likelihood of recurrence. Both regional and distant failure were more common among patients who presented with five or more nodes or who had level four lymph nodes (P < .05). Risk of developing distant metastases also was greater in patients with a lymph node larger than 6 cm or with bilateral lymphadenopathy (P < .05).
“For most patients with HPV-associated oropharynx cancer, after a negative 3-month PET scan, physical exams with history and direct visualization are sufficient to find recurrences,” said Jessica M. Frakes, MD, Assistant Member of the Department of Radiation Oncology at the H. Lee Moffitt Cancer Center. “Minimizing the number of unnecessary tests may alleviate the financial and emotional burden on these patients, including overall health-care costs, time spent away from work and family, and the anxiety of waiting for scan results.”
In addition to examining patterns of recurrence and detection, this study lends support to the effectiveness of specialist teams in treating HPV-positive oropharyngeal squamous cell carcinoma with definitive radiation therapy. Within 3 years, local control was achieved in 97.8% of all patients in the study; regional control in 95.3%; locoregional control in 94%; and freedom from distant metastases in 91.4%. The 3-year overall survival rate was 91%.
Nine percent of patients experienced severe late toxicities, including 19 grade 3 toxicities and two grade 4 toxicities with resolution in the majority (76%, 16 of 21 toxicities) at the time of last follow-up. Sixty-four percent of toxicities and/or recurrences occurred within the first 6 months following treatment; only four events occurred more than 2 years following treatment.
“We were pleasantly surprised by the high cure rates and the low permanent side-effect rates for these patients,” said Dr. Frakes. “These findings demonstrate that individuals with HPV-associated oropharyngeal cancer who are treated with definitive radiation therapy and cared for by multidisciplinary specialists have excellent outcomes.”
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