HPV-Associated Squamous Cell Carcinomas of the Oropharynx Treated with Curative Intent Radiotherapy: Patterns of Failure Analysis Using a Deformable Registration Methodology

Abstract

<h3>Purpose/Objective(s)</h3> Although human papillomavirus (HPV)-associated squamous cell carcinomas of the oropharynx (SCCOP) have high locoregional control rates, understanding spatial patterns of recurrence remains important in the IMRT era. A standardized methodology, using deformable registration, has been proposed to more accurately assess recurrent disease volumes in the context of initial treatment dose distributions. In this study we used this methodology to analyze recurrent malignancies in HPV-associated SCCOP. <h3>Materials/Methods</h3> A single institution database was retrospectively assessed for p16 (+) SCCOP treated with curative intent, either definitively or adjuvantly, using IMRT. Recurrence required either pathologic confirmation or clinically conclusive imaging. The earliest image indicative of recurrence was identified (either CT, MRI or PET-CT) and a "recurrent GTV" (rGTV) was contoured. Local and regional recurrences in the same patient were analyzed separately. This image was deformed onto the initial CT simulation, and the deformed rGTV was categorized into five types (A-E). In Types A/B the rGTV centroid was inside the prescribed high dose distribution, and delineated "A" if the dose to 95% of the failure volume (fD95%) was ≥ 95%, versus "B" if < 95%. In Types C/D the rGTV centroid was inside the elective dose distribution, and delineated "C" if fD95% was ≥ 95%, versus "D" if < 95%. In Type E the rGTV centroid was outside the elective and high dose volume. All deformable registrations were performed using MIM treatment planning software. <h3>Results</h3> A total of 140 patients met inclusion criteria, of which 114 were treated definitively and 26 were treated adjuvantly. 17 locoregional recurrences in 16 patients were identified; 8 failed at the primary, 7 failed regionally, and 1 failed both at the primary and regionally. Recurrence was confirmed by pathology in 14 patients. Five patients were AJCC 8^th Stage I, three were Stage II, and eight were Stage III. The mean rGTV was 9.2 cc (0.1 to 60.7). Of the 17 recurrences, 11 (65%) were Type A, two (12%) were Type B, one (6%) was Type C, and three (18%) were Type E. The only Type C recurrence occurred in a patient treated on the radiotherapy alone arm on NRG HN002 within the 48 Gy elective nodal volume. Type E failures occurred in level VI-A in a Stage II base of tongue malignancy, the contralateral neck in a patient treated ipsilaterally for a Stage I tonsillar malignancy, and the base of skull in a Stage III tonsillar malignancy. <h3>Conclusion</h3> In HPV-associated SCCOP locoregional recurrences occur primarily within the high dose volume, indicating a need for improved stratification and potential intensification in a small subset of patients. Deformable registration-based patterns of failure analysis are feasible, and should be the standard reporting methodology.