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Characterization of tumour mutation burden in patients with non-small cell lung cancer and interstitial lung disease.

ABSTRACT: BACKGROUND AND OBJECTIVE:The efficacy expectation of immune checkpoint inhibitors against NSCLC in patients with ILD seems to be high because these populations are supposed to have high TMB. However, information about the characterization of TMB in patients with NSCLC and ILD is limited. Therefore, this study aimed to evaluate TMB in samples of NSCLC with ILD and clarify factors that influence TMB values. METHODS:The medical records of patients with NSCLC who underwent thoracic surgery at our institution between January 2014 and January 2017 were retrospectively reviewed. Whole-exome sequencing with an Ion Proton system and gene expression profiling of fresh surgical specimens were performed. RESULTS:Among 367 patients with NSCLC, 62 (16.9%) were diagnosed with ILD. All samples were collected from primary tumours with a median TMB of approximately 2.1 (range: 0.1-64.4) mutation/Mb. Among 81 squamous cell carcinomas, we compared 27 tumours with concomitant ILD and 54 tumours without ILD. Univariate analyses revealed that tumours with concomitant ILD showed lower TMB values than those without ILD. Multivariate analysis revealed that concomitant ILD was significantly associated with low TMB values. Conversely, no difference was noted in the TMB value of adenocarcinoma between patients with and without ILD. CONCLUSION:Squamous cell carcinoma and adenocarcinoma with ILD do not have high TMB values. Therefore, considering the risk of severe pneumonitis, immune checkpoint inhibitors should not be used routinely against patients with NSCLC and ILD based on the expectation of high TMB values.

SUBMITTER: Kobayashi H

PROVIDER: S-EPMC7496253 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Characterization of tumour mutation burden in patients with non-small cell lung cancer and interstitial lung disease.

Kobayashi Haruki H Serizawa Masakuni M Naito Tateaki T Konno Hayato H Kojima Hideaki H Mizuno Tetsuya T Isaka Mitsuhiro M Endo Masahiro M Nagashima Takeshi T Kusuhara Masatoshi M Urakami Kenichi K Ohshima Keiichi K Yamaguchi Ken K Ohde Yasuhisa Y Takahashi Toshiaki T

Respirology (Carlton, Vic.) 20191106 8

<h4>Background and objective</h4>The efficacy expectation of immune checkpoint inhibitors against NSCLC in patients with ILD seems to be high because these populations are supposed to have high TMB. However, information about the characterization of TMB in patients with NSCLC and ILD is limited. Therefore, this study aimed to evaluate TMB in samples of NSCLC with ILD and clarify factors that influence TMB values.<h4>Methods</h4>The medical records of patients with NSCLC who underwent thoracic su ...[more]

PMID: 31694070

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Project description:BackgroundInterstitial lung disease (ILD) in patients with non-small cell lung cancer (NSCLC) worsens the prognosis for overall survival (OS) due to chemotherapy-triggered acute exacerbation (AE)-ILD. The Glasgow Prognostic Score (GPS), which is based on serum C-reactive protein and albumin levels, has been suggested as a reliable prognostic tool for mortality in cancer patients, including NSCLC. In this study, we investigated whether GPS is a predictor for chemotherapy-triggered AE-ILD and the prognosis in patients with NSCLC and pre-existing ILD.MethodsWe conducted a retrospective review on 56 NSCLC and ILD patients at our hospital who received platinum agent-based treatment as first-line chemotherapy between June 2010 and May 2019. We categorized these patients according to their GPS (0-2) and compared the incidence of chemotherapy-triggered AE-ILD and OS.ResultsThe GPS 0, 1, and 2 groups included 31, 16, and nine patients, respectively, out of 56. A total of 12 (21.4%) patients showed chemotherapy-triggered AE-ILD. The median OS was at 11.5 months (95% confidence interval: 8.0-15.1). The incidence of chemotherapy-triggered AE-ILD within the first year of chemotherapy in the GPS 0, 1, and 2 groups was three (9.6%), four (25.0%), and five (55.5%), and the median OS time was 16.9, 9.8 and 7.6 months, respectively. Univariate and multivariate analyses indicated that only GPS 2 could predict both chemotherapy-triggered AE-ILD and OS (P < 0.05).ConclusionsGPS assessment of patients with NSCLC and pre-existing ILD is a valuable prognostic tool for predicting chemotherapy-triggered AE-ILD and OS.Key pointsSIGNIFICANT FINDINGS OF THE STUDY: We found that GPS 2 was an independent risk factor for chemotherapy-triggered AE-ILD and prognosis in patients with ILD associated with NSCLC.What this study addsGPS may potentially enable the discrimination of patients tolerant of chemotherapy from those at an increased risk of AE-ILD and predict the prognosis in patients with NSCLC and ILD receiving chemotherapy.

Dataset Information

Characterization of tumour mutation burden in patients with non-small cell lung cancer and interstitial lung disease.

Publications

Characterization of tumour mutation burden in patients with non-small cell lung cancer and interstitial lung disease.

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