Treatment implications of postoperative chemoradiotherapy for squamous cell carcinoma of the oral cavity with minor and major extranodal extension

Almeida, John R. de; Truong, Tra; Khan, Nazir Mohemmed; Su, Jie; Irish, Jonathan C.; Gilbert, Ralph W.; Goldstein, David P.; Huang, Shao Hui; Hosni, Ali; Hope, Andrew; Waldron, John; Hansen, Aaron Richard; Spreafico, Anna; Siu, Lillian L.; Perez-Ordoñez, Bayardo; Xu, Wei; Weinreb, Ilan

doi:10.1016/j.oraloncology.2020.104845

Cited by 21 publications

(27 citation statements)

References 29 publications

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“…Our results add to the emerging body of literature suggesting that for patients with HPV-negative HNSCC with ENE mi , adding chemotherapy concurrent with adjuvant RT does not improve OS. 10…”

Section: Discussionmentioning

confidence: 99%

“…[6][7][8][9] Since these landmark trials, emerging evidence has suggested an association between the extent of ENE and prognosis in the HPV-negative setting. [10][11][12] Grading systems to characterize the amount of ENE (beyond present/absent) have been developed. 13,14 In addition, AJCC8 and College of American Pathologist (CAP) guidelines recommend categorizing ENE as absent, microscopic (ENE mi) (2 mm), or macroscopic (.2 mm beyond the lymph node [LN] capsule).…”

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confidence: 99%

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Microscopic Extranodal Extension in HPV‐Negative Head and Neck Cancer and the Role of Adjuvant Chemoradiation

Yan

Almeida

et al. 2021

Otolaryngol.--head neck surg.

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Objective Pathologic extranodal extension (ENE) is an important adverse feature for human papillomavirus (HPV)–negative head and neck squamous cell carcinoma (HNSCC), but the prognostic significance of microscopic ENE (ENEmi) and role of adjuvant concurrent chemoradiation (CRT) for ENEmi remain unclear. This study evaluates (1) the prognostic significance of ENEmi in HPV-negative HNSCC and (2) whether adjuvant CRT is associated with improved overall survival (OS) for these patients. Study Design Retrospective cohort study. Setting Commission on Cancer (CoC)–accredited facilities. Methods This retrospective cohort study included patients in the National Cancer Database from 2009 to 2015 with pathologic node-positive (pN+) HPV-negative HNSCC with either pathologic ENEmi or no ENE who had undergone margin-negative surgery. The association of ENEmi with OS was evaluated using Cox proportional hazard analyses. Analyses were repeated in patients with ENEmi receiving adjuvant therapy to evaluate the association of adjuvant CRT with OS. Results We included 5483 patients with pN+ HPV-negative HNSCC, of whom 24% had ENEmi. On multivariable analysis, ENEmi was associated with decreased OS relative to no ENE (adjusted hazard ratio [aHR], 1.43; 95% CI, 1.28-1.59). Among patients with ENEmi who received ≥60 Gy of adjuvant radiation therapy (RT) (n = 617), adjuvant CRT was not associated with improved OS relative to RT (aHR, 0.91; 95% CI, 0.66-1.27). Conclusion For patients with HPV-negative HNSCC, pN+ with ENEmi is associated with worse OS than pN+ without ENE. However, for patients with ENEmi, concurrent CRT is not associated with improved OS relative to RT. The optimal adjuvant paradigm for ENEmi requires additional investigation.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Microscopic Extranodal Extension in HPV‐Negative Head and Neck Cancer and the Role of Adjuvant Chemoradiation

Yan

Almeida

et al. 2021

Otolaryngol.--head neck surg.

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“…In a meta-analysis with 1620 patients, the five-year overall survival rate in patients with encapsulated lymph node metastases was 58.1%. In patients with ENE, the survival rate was only 30.7% [8] . A comparative analysis of the EORTC (#22931) and RTOG (#9501) trials showed that addition of concomitant chemotherapy to postoperative radiotherapy seems to improve the outcome of patients with ENE [9,10] .…”

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confidence: 96%

“…factor in these patients [2,3] . Prognosis further decreases with the presence of extranodal extension (ENE) in lymph node metastases [4][5][6][7][8] . The incidence of ENE varies between 21% and 85% [8] .…”

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Radiological assessment of extranodal extension in patients with head and neck squamous cell carcinoma

Dankbaar¹,

Pameijer²

2021

JCMT

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The prognosis of patients with head and neck squamous cell cancer (HNSCC) decreases with the presence of extranodal extension (ENE) in lymph node metastases. Therefore, ENE was introduced in the 8th Edition TNM Classification (TNM8) for Head and Neck Cancer as a staging variable in all HPV-negative HNSCC. Patients with ENE may benefit from adjuvant or even primary chemotherapy and/or radiotherapy. There is a clear discrepancy between the definition of clinical ENE and pathological ENE. In TNM8, the radiological evaluation of ENE only plays a supportive role. Since not all patients with advanced disease will undergo a neck dissection, histologic proof of ENE will not always be available. In these cases, it would be of great help to be able to accurately determine ENE with radiological imaging. In this review, an update is given of the ability of radiological imaging to identify and grade ENE.

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Development and validation of a novel TNM staging N‐classification of oral cavity squamous cell carcinoma

de Almeida,

Su,

Kolarski

et al. 2023

Cancer

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BackgroundFor oral cavity squamous cell carcinoma (OSCC), extent of extranodal extension (ENE) (minor, ≤2 mm; major, >2 mm) is differentially prognostic, whereas limitations exist with the 8th edition of American Joint Committee on Cancer/International Union Against Cancer TNM N‐classification (TNM‐8‐N).MethodsResected OSCC patients at four centers were included and extent of ENE was recorded. Thresholds for optimal overall survival (OS) discrimination of lymph node (LN) features were established. After dividing into training and validation sets, two new N‐classifications were created using 1) recursive partitioning analysis (RPA), and 2) adjusted hazard ratios (aHRs) and were ranked against TNM‐8‐N and two published proposals.ResultsA total of 1460 patients were included (pN0: 696; pN+: 764). Of the pN+ cases, 135 (18%) had bilateral/contralateral LNs; 126 (17%) and 244 (32%) had minor and major ENE, and two (0.3%) had LN(s) >6 cm without ENE (N3a). LN number (1 and >1 vs. 0: aHRs, 1.92 [95% confidence interval (CI), 1.44–2.55] and 3.21 [95% CI, 2.44–4.22]), size (>3 vs. ≤3 cm: aHR, 1.88 [95% CI, 1.44–2.45]), and ENE extent (major vs. minor: aHR, 1.40 [95% CI, 1.05–1.87]) were associated with OS, whereas presence of contralateral LNs was not (aHR, 1.05 [95% CI, 0.81–1.36]). The aHR proposal provided optimal performance with these changes to TNM‐8‐N: 1) stratification of ENE extent, 2) elimination of N2c and 6‐cm threshold, and 3) stratification of N2b by 3 cm threshold.ConclusionA new N‐classification improved staging performance compared to TNM‐8‐N, by stratifying by ENE extent, eliminating the old N2c category and the 6 cm threshold, and by stratifying multiple nodes by size.

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Treatment implications of postoperative chemoradiotherapy for squamous cell carcinoma of the oral cavity with minor and major extranodal extension

Cited by 21 publications

References 29 publications

Microscopic Extranodal Extension in HPV‐Negative Head and Neck Cancer and the Role of Adjuvant Chemoradiation

Microscopic Extranodal Extension in HPV‐Negative Head and Neck Cancer and the Role of Adjuvant Chemoradiation

Radiological assessment of extranodal extension in patients with head and neck squamous cell carcinoma

Development and validation of a novel TNM staging N‐classification of oral cavity squamous cell carcinoma

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