Pre‐ and Post‐Radiotherapy Radiologic Nodal Features and Oropharyngeal Cancer Outcomes

Abstract

Objectives: To assess the prognostic value of pre-/post-radiotherapy (pre-/post-RT) radiologic lymph node (LN) features in human papillomavirus (HPV)-positive and HPV-negative oropharyngeal carcinoma (OPC) patients treated with definitive (chemo-)RT. Methods: Clinical node-positive OPCs treated from 2011 to 2015 were reviewed. Nodal features were reviewed by a radiologist on pre-/post-RT computed tomography (CTs). Univariable analysis calculated hazard ratio (HR) for regional failure (RF), distant metastasis (DM), and deaths. Multivariable analysis estimated adjusted HR (aHR) of significant nodal features identified in univariable analysis adjusting for confounders. Results: Pre-RT CT was undertaken in 344 HPV-positive and 94 HPV-negative OPC patients, of whom 242 (70%) HPV-positive and 67 (71%) HPV-negative also had a post-RT CT. Median follow-up was 4.9 years. Pre-RT LN calcification (pre-RT_LN-cal) increased the risk of RF in HPV-negative (aHR: 5.3, P = .007) but not HPV-positive patients (P = .110). Pre-RT radiologic extranodal extension (pre-RT_rENE+) increased the risk of DM and death in both HPV-negative (DM: aHR 6.6, P < .001; death: aHR 2.1, both P = .019) and HPV-positive patients (DM: aHR 4.9; death: aHR 3.0, both P < .001). Increased risk of RF occured with < 20% post-RT LN size reduction in both HPV-negative (HR 6.0, P = .002) and HPV-positive cases (HR 3.0, P = .049). Post-RT_LN-cal did not affect RF, DM, or death regardless of tumor HPV status (all P > .05). Conclusion: Pre-RT_LN-cal is associated with higher RF risk in HPV-negative but not in HPV-positive patients. Pre-RT_rENE increases risk of DM and death regardless of tumor HPV status. Minimal post-RT LN size reduction (< 20%) increases risk of RF in both diseases. Post-RT_LN-cal + has no apparent influence on outcomes in either disease.

Assessment Criteria and Clinical Implications of Extranodal Extension in Head and Neck Cancer

“…56 Therefore, the term coalescent may be a more appropriate description of the Pattern 2b rENE. 50,57…”

“…rENE may be even more powerful than TNM and patient factors in both viral-unrelated 45,[57][58][59] and viral-related head and neck cancer (i.e., nasopharyngeal carcinoma 50,51,56,60,61 and HPV-associated oropharyngeal carcinoma 16,48,53,54,62 ). The adverse effect is mainly caused by the increased risk of distant metastasis rather than reduction in locoregional control (Table 2).…”

Prognostic importance of radiologic extranodal extension in nasopharyngeal carcinoma treated in a Canadian cohort

“…Presence (based on unequivocal radiologic evidence) or absence (including negative, equivocal, or uncertainty) of the following nodal features were recorded: level, size, and side of radiologic overt LNs including retropharyngeal LNs (RPLN), lower neck involvement, and rENE. A radiologically overt LN was defined as nodal size >1.5 cm in largest dimension for level IIA, !8 mm for RPLN, and >1.0 cm for all other levels, or presence of suspicious features (e.g., necrosis, irregular borders, calcification, round shape) [11][12][13][14]. Lower neck LN referred to any involved LN with a border extending into or beyond level IV or VB per consensus definition [3].…”

Augmenting inter‐rater concordance of radiologic extranodal extension in HPV‐positive oropharyngeal carcinoma: A multicenter study

“…The scanning protocols included 2‐mm slice thickness for CT and 3‐mm slice thickness for MRI as described previously 4,8,9 . The rENE assessment results by EY served as the reference for inter‐rater comparison owing to his previous experience in this field 4,7,9–11 …”

“…4,8,9 The rENE assessment results by EY served as the reference for inter-rater comparison owing to his previous experience in this field. 4,7,[9][10][11] The study was carried out in two-phases with interphase group discussion to consolidate rENE definition and share qualitative assessment methods. In Phase-I, rENE ascertainment was performed on pretreatment CT or MRI of 20 randomly selected HPV+ OPC cases (Training_Set_1) by all six radiologists independently (two from PMH, two from MUMC, two from TCI) based on each radiologist's individual appreciation of the existing literature and without knowledge of other radiologists' assessments nor the clinical outcome of the cases.…”