Extranodal extension of nodal metastasis is the main prognostic moderator in squamous cell carcinoma of the esophagus after neoadjuvant chemoradiotherapy

Extranodal extension (ENE) of nodal metastasis is defined as the extension of metastatic cells through the nodal capsule into the perinodal tissue. This morphological parameter, recently proposed as an important prognostic factor in different types of malignancy, has not been included in the TNM staging system for non-small cell lung cancer (NSCLC). In this systematic review with meta-analysis, we weighted the prognostic role of ENE in patients with lymph node-positive NSCLC. Two independent authors searched SCOPUS and PubMed through 28 February 2017. Prospective and retrospective studies on NSCLC, comparing patients with presence of ENE (ENE+) ENE+) vs. only intranodal extension (ENE-) and including data regarding prognosis, were considered as eligible. Data were summarized using risk ratios (RR) for the number of deaths/recurrences, and hazard ratios (HR) with 95% confidence intervals (CI) for time-dependent risk related to ENE+, adjusted for potential confounders. We identified 13 studies, including 1709 patients (573 ENE+ and 1136 ENE-) with a median follow-up of 60 months. ENE was associated with a significantly increased risk of mortality of all causes (RR = 1.39, 95% CI: 1.18-1.65, P < 0.0001, I = 70%; HR = 1.30, 95% CI: 1.01-1.67, P = 0.04, I = 0%) and of disease recurrence (RR = 1.32, 95% CI: 1.04-1.68, P = 0.02, I = 42%; HR = 1.93, 95% CI: 1.53-2.44, P < 0.0001, I = 0%). We conclude that in NSCLC, requirements for assessment of ENE should be included in gross sampling and ENE status should be included in the pathology report. Inclusion of ENE status in oncology staging systems will allow further assessment of its role as prognostic parameter.

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Extranodal extension of nodal metastases is a poor prognostic moderator in non-small cell lung cancer: a meta-analysis

Luchini

Veronese

Nottegar

et al. 2018

Virchows Arch

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Assessment of intratumor immune-microenvironment in colorectal cancers with extranodal extension of nodal metastases

et al. 2018

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BackgroundNo data is available on the molecular background of the extra-nodal extension (ENE) of lymph node metastasis (LN) in colorectal cancer (CRC).MethodsA series of 22 ENE-positive CRCs was considered and three samples per case were selected (the primary CRC, an ENE-negative and an ENE-positive metastatic LN). Samples (n = 66) were analysed by immunohistochemistry for PD-L1, CD4, CD8, CD68 and CD80. Fifteen out of twenty-two cases were further profiled through a hotspot multigene mutational custom panel, including 164 hotspot regions of AKT1, APC, BRAF, CTNNB1, KIT, KRAS, NRAS, PDGFRA, PIK3CA, PTEN and TP53 genes.ResultsA significantly higher percentage of CD4-, CD8- and CD68-positive cells was observed at the invasive front of both CRCs and in ENE in contrast with what observed at the core of both CRCs and their matched nodal metastases. ENE was also characterized by a significantly higher number of CD80-positive cells. No significant difference was observed in PD-L1 distribution among the different specimens. Fourteen out of 15 CRCs (93%) showed at least a driver mutation. The most frequently mutated gene was TP53 (n = 8 tumors), followed by APC (n = 6), BRAF (n = 4), KRAS, NRAS and PIK3CA (n = 2). In 11 out of 15 CRCs (73%) the mutational profiling of the primary tumor was consistent with what obtained from the two matched LNs.ConclusionsA heterogeneous intratumor immune-microenvironment has been observed in ENE-positive CRCs, which are characterized by an increased leukocytic infiltration at the ENE invasive front.

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Tri-modality therapy in advanced esophageal carcinoma: long-term results and insights from a developing world, institutional cohort

Chufal

Ahmad

Bajpai

et al. 2023

BJR

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Objectives: To evaluate treatment outcomes in patients from a low-middle income country (LMIC) with esophageal carcinoma who underwent esophagectomy after neoadjuvant chemoradiation (NACRT/S). Methods: Between 2010 and 2020, 254 patients (median follow-up: 53 months) met our inclusion criteria. Out-of-Field nodal regions were determined by reviewing individual radiotherapy plans. Cox regression modelling was performed to analyze overall survival (OS) and recurrence-free survival (RFS), while pathological complete response (pCR) prediction utilized Poisson regression. Results: The median OS was 71.4 months (IQR: 19.6-∞), RFS did not reach the median and pCR rate was 46%. On multivariable Cox regression, BMI [0.93 (0.89–0.98); 0.94 (0.89–0.99)] and absence of out-of-field node with extranodal extension (ENE)[0.22 (0.09–0.53); 0.30 (0.12–0.75)] influenced OS and RFS, respectively. Age [1.03 (1.01–1.06)], nodal stage [cN2-3 vs cN0: 2.67 (1.08–6.57)] and adventitial involvement [2.54 (1.36–4.72)] also influenced OS, while involved margins [3.12 (1.24–7.81)] influenced RFS. On multivariable Poisson regression, non-CROSS-chemotherapy regimens [0.65 (0.44–0.95)] and residual primary disease on pre-surgical imaging [0.73 (0.57–0.93)] were significantly associated with pCR. The most frequently involved in-field and out-of-field nodal regions were the peri-esophageal and peri-gastric (greater and lesser curvature) regions, respectively. Conclusions: NACRT/S is feasible and effective in patients from LMIC. Out-of-field ENE merits further investigation as a prognostic factor since it significantly influenced both OS and RFS. Advances in knowledge: The results of clinical trials are replicable in LMICs. Out-of-field ENE is an independent prognostic factor for OS and RFS.

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Extranodal extension of nodal metastasis is the main prognostic moderator in squamous cell carcinoma of the esophagus after neoadjuvant chemoradiotherapy

Cited by 4 publications

References 24 publications

Extranodal extension of nodal metastases is a poor prognostic moderator in non-small cell lung cancer: a meta-analysis

Extranodal extension of nodal metastases is a poor prognostic moderator in non-small cell lung cancer: a meta-analysis

Assessment of intratumor immune-microenvironment in colorectal cancers with extranodal extension of nodal metastases

Tri-modality therapy in advanced esophageal carcinoma: long-term results and insights from a developing world, institutional cohort

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