Assessing the Prognostic Significance of Tumor-Infiltrating Lymphocytes in Patients With Melanoma Using Pathologic Features Identified by Natural Language Processing

Jie Yang,Li Zhou,John W Lian,Yen-Po (Harvey) Chin,George F Murphy,Anna Lian,Liqin Wang

doi:10.1001/jamanetworkopen.2021.26337

Jie Yang, Li Zhou + Show 5 more

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https://doi.org/10.1001/jamanetworkopen.2021.26337

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Abstract

Although tumor-infiltrating lymphocytes (TILs) are an important histopathologic characteristic reflecting host immune response in patients with melanoma, their prognostic value remains controversial. Because manual review of medical records is labor intensive, a survival analysis using a large patient cohort with comprehensive clinical and histopathologic characteristics is lacking. To assess the prognostic significance of TILs among patients with cutaneous melanoma using a large cohort established through natural language processing (NLP) algorithms. This retrospective cohort study analyzed the medical records of 14 436 patients with cutaneous melanoma at Brigham and Women's Hospital between June 1, 2004, and December 31, 2019. Patients were followed up to death or censored at their last clinical visit. The primary outcome was overall survival (OS). Survival analysis was conducted using Kaplan-Meier curves, the log-rank test, and Cox proportional hazards regression analysis. A total of 14 436 patients with cutaneous melanoma were identified in the institution's pathology information system. Using NLP, we established a study cohort of 2624 patients (1462 men [55.7%]; median age, 61 years [interquartile range, 50-72 years]) who had vertical growth phase melanoma with TIL status scored. Absent TILs were identified in 434 patients (16.5%), nonbrisk TILs in 1916 patients (73.0%), and brisk TILs in 274 patients (10.4%). The 5-year survival rate was 71.0% (95% CI, 65.5%-76.9%) among patients with an absence of TILs, 73.8% (95% CI, 71.1%-76.5%) among patients with nonbrisk TILs, and 85.2% (95% CI, 80.0%-90.7%) among patients with brisk TILs. Brisk TILs were significantly associated with improved OS (adjusted hazard ratio, 0.63; 95% CI, 0.42-0.95; P = .03; 14.2% OS advantage at 5 years), and nonbrisk TILs were not associated with improved OS (adjusted hazard ratio, 0.87; 95% CI, 0.68-1.11; P = .25), compared with the absence of TILs. This study provides evidence based on a large patient cohort from a single institution that suggests that brisk TILs represent an independent prognostic factor for OS among patients with primary cutaneous melanoma. The study also suggests that NLP is a highly efficient tool to facilitate large-scale analyses that involve free-text clinical data.

Highlights

Despite recent advances, melanoma remains one of the most aggressive and therapy-resistant cancers, with incidence and mortality rates remaining high.[1,2,3] In the United States, more than 100 000 new cases of melanoma are diagnosed annually, and almost 7000 people die of the disease.[3]
Brisk tumorinfiltrating lymphocyte (TIL) were significantly associated with improved overall survival (OS), and nonbrisk TILs were not associated with improved OS, compared with the absence of TILs
This study provides evidence based on a large patient cohort from a single institution that suggests that brisk TILs represent an independent prognostic factor for OS among patients with primary cutaneous melanoma

Summary

Introduction

Melanoma remains one of the most aggressive and therapy-resistant cancers, with incidence and mortality rates remaining high.[1,2,3] In the United States, more than 100 000 new cases of melanoma are diagnosed annually, and almost 7000 people die of the disease.[3]. There have been studies that demonstrated no association between overall survival (OS) and TILs.[18,19] a study conducted by Sinnamon et al[20] showed that the prognostic significance of TILs regarding sentinel lymph node positivity in patients with melanoma is more relevant to men than to women, highlighting that the prognostic value of TILs may vary among patients with different demographic characteristics. The inconsistent findings from different studies on the prognostic value of TILs in melanoma may be associated with small sample sizes, the heterogeneity of the scoring methods used, the inconsistent cutoff of biomarkers, and the limited number of histopathologic characteristics considered.[21]

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