Prognostic importance of radiologic extranodal extension in HPV-positive oropharyngeal carcinoma and its potential role in refining TNM-8 cN-classification. (March 2020)

• Record Type: Journal Article
• Authors: Huang, Shao Hui; O'Sullivan, Brian; Su, Jie; Bartlett, Eric; Kim, John; Waldron, John N.; Ringash, Jolie; de Almeida, John R.; Bratman, Scott; Hansen, Aaron; Bayley, Andrew; Cho, John; Giuliani, Meredith; Hope, Andrew; Hosni, Ali; Spreafico, Anna; Siu, Lillian; Chepeha, Douglas; Tong, Lt; Xu, Wei; Yu, Eugene
• Is Part Of: Radiotherapy and oncology. Volume 144(2020)
• Page Start: 13
• Page End: 22
• Publication Date: 2020-03
• Subjects: HPV -- Oropharyngeal carcinoma -- Staging -- cN-classification -- Outcome -- Prognosis; Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2019.10.011
• Languages: English
• ISSNs: 0167-8140

Abstract

Highlights: Radiologic extranodal extension (rENE) is a strong prognostic factor in HPV+ OPC. Inclusion of rENE in TNM-8 cN-classification improves outcome prediction. HPV+ OPC Patients with rENE is not suitable for deintensification trials. rENE can be reliably ascertained with satisfactory inter-/intra-rater concordance. Abstract: Purpose: This study examines outcome heterogeneity and potential to refine the TNM-8 cN-classification using radiologic extranodal extension (rENE) in a contemporary HPV-positive (HPV+) oropharyngeal carcinoma (OPC) cohort. Methods: All HPV+ OPC treated with definitive IMRT from 2010-2015 were included. Pre-treatment CT/MR of cN+ cases were reviewed by a head-neck radiologist for rENE. Overall survival (OS) and disease-free survival (DFS) were compared between rENE-positive (rENE+) vs rENE-negative (rENE−). Multivariable analysis (MVA) for OS confirmed the prognostic value of rENE. Refined cN-classifications for new TNM staging proposals were evaluated against TNM-8 using established criteria. Results: A total of 517 cN+ (rENE+: 97; rENE−: 420) and 41 cN0 cases were identified. The rENE+ proportion increased with rising N-category (N1/N2/N3: 11%/19%/84%, p < 0.001). Median follow-up was 5.1 years. Compared to rENE−, rENE+ patients had a lower 5-year OS (56% vs 85%) and DFS (46% vs 83%) overall, and in N1 (OS: 57% vs 89%; DFS: 51% vs 87%) and N2 subsets (OS: 45% and 76%; DFS: 33% vs 74%) (all p < 0.001). MVA confirmed the prognostic value of rENE for OS (HR = 3.86, p < 0.001) and DFS (HR = 3.89, p < 0.001). We proposed two new cN-classifications: Schema1 reclassified any N_rENE+ as New_N3 ; Schema2 reclassified N1_rENE+ as New_N2 and N2_rENE+ as New_N3 . Stage incorporating either Schema1 (ranked 1st) or Schema2 (ranked 2nd) cN- categories outperformed TNM-8. Conclusion: This study confirms that rENE is prognostically important and facilitates understanding of known outcome heterogeneity within TNM-8 in HPV+ OPC patients. rENE is a promising parameter to refine the TNM-8 cN-classifications.