114 - Oncologic Outcomes of a Multicenter Prospective Study Evaluating ctHPVDNA-Adapted Adjuvant Radiotherapy in Patients with HPV-Associated Oropharyngeal Cancer
Presenter(s)
J. E. Bates1, W. A. Stokes1, J. S. Remick2, S. Rudra2, M. W. McDonald3, A. Jethanandani4, A. Simon-Kamm5, M. M. Steininger5, N. A. Lockney6, K. Mannion7, N. F. Saba8, N. C. Schmitt9, J. H. Gross5, C. Steuer5, A. S. Kaka10, X. Ji5, J. Switchenko11, M. Topf12, and M. Patel13; 1Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA, 2Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, 3Winship Cancer Institute of Emory University, Atlanta, GA, 4The University of Tennessee Health Science Center College of Medicine, Memphis, TN, 5Emory University, Atlanta, GA, 6Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, 7Vanderbilt University School of Medicine, Nashville, TN, 8Winship Cancer Institute, Emory University, Atlanta, GA, 9Emory Winship Cancer Institute, Atlanta, GA, 10Department of Otolaryngology, Winship Cancer Institute of Emory University, Atlanta, GA, 11Emory University School of Medicine, Atlanta, GA, 12Vanderbilt University Medical Center, Nashville, TN, 13UNC Chapel Hill School of Medicine, Chapel Hill, NC, United States
Purpose/Objective(s):
Patients with early-stage HPV-associated oropharyngeal cancer (HPV+OPSCC) have excellent outcomes when treated with primary transoral surgery (TOS) followed by pathology-guided adjuvant therapy, however, swallowing difficulty often persists after treatment, especially in patients requiring adjuvant radiotherapy (RT). Circulating tumor HPV DNA (ctHPVDNA) is a strong prognostic marker of tumor recurrence in this patient population. We performed a multi-institutional prospective clinical trial to evaluate if post-operative ctHPVDNA could be used to safely select patients with intermediate pathologic risk for reduced intensity adjuvant RT.Materials/Methods:
Patients with detectable pre-operative ctHPVDNA and no or limited smoking history (<10 pack-year or <30 pack-year if >10 years from cessation) who underwent TOS and neck dissection with intermediate risk pathology (pT0-2N0-1M0 HPV+OPSCC with closest margin <3 mm, perineural invasion, 2 – 4 positive nodes, or single lymph node > 3 cm) were eligible. Patients with any extranodal extension or positive margins were excluded. ctHPVDNA was drawn 2 weeks post-operatively: if undetectable, patients received a de-intensified course of adjuvant RT (36 Gy in daily 2.4 Gy fractions); if detectable, patients received standard of care adjuvant therapy. In patients with a final surgical margin >2 mm, RT could be omitted to the primary site. The primary outcome was 1-year MD Anderson Dysphagia Inventory (MDADI). We report secondary outcomes of oncologic endpoints at the same timepoint.Results:
We enrolled 35 patients at two institutions. The median age was 60 years (range 33 – 76 years). The median follow-up was 19.3 months (0.7 – 37.1 months). 91.4% (n = 32) were male, 74.3% (n = 26) were white. Patients had predominately pT1 disease (57.1%, n = 20) with the remaining having pT2 disease. Almost all patients (94.3%, n = 33) had pN1 disease, with the remaining having pN0 disease. Most were post-operative ctHPVDNA negative (91.4%, n = 32). The 12- and 24-month progression-free survival were 91.4% (95% CI: 75.7% - 97.2%) and 88.4% (95% CI: 71.9% - 95.5%) respectively. The 12- and 24-month overall survival were 97.1% (95% CI: 81.4% - 99.6%) and 93.9% (95% CI: 77.7% - 98.4%) respectively. Two patients, both post-operative ctHPVDNA negative, experienced progression of their HPV+OPSCC; one in the unirradiated contralateral neck who was successfully salvaged with surgery and adjuvant RT, the other with metastatic disease. Two patients passed away of causes unrelated to their HPV+OPSCC.Conclusion:
In this multi-center, prospective study of early-stage HPV+OPSCC TOS patients, ctHPVDNA-adapted adjuvant radiotherapy was associated with acceptable oncologic outcomes. Further prospective study is needed to verify this treatment approach.