Pathologic response to neoadjuvant chemotherapy in HPV positive oropharyngeal squamous cell carcinoma

Presentation: AHNS-025
Topic: Mucosal - HPV Positive
Type: Oral
Date: Wednesday, May 1, 2019
Session: 4:05 PM - 5:00 PM Scientific Session 4 - HPV Positive
Authors: Sarah Khalife1, Marco Mascarella1, Agnihotram V Ramanakumar1, Keith Richardson1, Robert Siegel2, Arjun Joshi2, Reza Taheri2, Andrew Fuson2, Nader Sadeghi1
Institution(s): 1McGill University Health Centre, 2George Washington University

Background: A paradigm shift is gradually making way in the treatment of HPV positive oropharyngeal squamous cell carcinoma (OPSCC). Neoadjuvant chemotherapy followed by definitive surgery is currently being investigated for treatment naïve HPV positive OPSCC by our group. Feasibility of the approach is previously reported.  The objective of this study is to ascertain the response to neoadjuvant chemotherapy in an expanded group of patients and the association of tumor volume reduction on imaging to predict pathologic response in such patients.

Methods: A prospective observational study of patients with loco-regionally advanced, non-metastatic, HPV positive, and treatment naive OPSCC enrolled in a clinical trial of neoadjuvant chemotherapy followed by surgery was performed. All patients underwent three cycles of induction chemotherapy (cisplatin/docetaxel); pre and post-chemotherapy imaging wereobtained. Receiver operating characteristic (ROC) curves and logistic regression analyses were used to assess the diagnostic utility of imaging in predicting the complete pathologic response (CR) at the primary and nodal sites.

Results: Of the 55 patients included in the study, 24 (43.6%) patients had a complete pathologic response following neoaadjuvant chemotherapy at all sites. The CR rate at the primary and nodal sites were 70.1% (39 patients) and 56.4% (31 patients), respectively. An estimated volume reduction of the primary tumor at 90% cut-off predicted the complete pathologic response of the primary tumor with a sensitivity of 82% (95% CI 70.2-96.4), specificity of 73% (95% CI 56.6-88.7) and area under the curve (AUC) of 0.79 (95% CI 0.62-0.96). Metastatic lymph node volume reduction by 83% predicted the complete pathologic response of the nodal site with a sensitivity of 64% (95% CI 29.9-80.1), specificity of 76% (95% CI 35.7-98.7) and AUC 0.76 (95% CI 0.61-0.91). After adjusting for age, sex, and Charlson co-morbidity index, tumor volume reduction predicts complete pathologic response reasonably as the logistic odds ratio was 18.6 (95% CI= 2.99-191).

Conclusion: Patients with loco-regionally advanced HPV positive OPSCC show a goodresponse to neoadjuvant chemotherapy. Tumor volume reduction of 90% or more following induction chemotherapy predicts the complete pathologic response of the primary tumor. Neoadjuvant chemotherapy followed by definitive transoral robotic surgery and neck dissection is a new paradigm worthy of further investigation.