Smoking signature is superior to programmed death-ligand 1 expression in predicting pathological response to neoadjuvant immunotherapy in lung cancer patients.

Yang, Haitang; Ma, Wenyan; Sun, Beibei; Fan, Liwen; Xu, Ke; Hall, Sean; Al-Hurani, Mohammad; Schmid, Ralph A.; Peng, Ren-Wang; Hida, Toyoaki; Wang, Zhexin; Yao, Feng (2021). Smoking signature is superior to programmed death-ligand 1 expression in predicting pathological response to neoadjuvant immunotherapy in lung cancer patients. Translational lung cancer research, 10(9), pp. 3807-3822. AME Publishing 10.21037/tlcr-21-734

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Background

There is a paucity of biomarkers that can predict the degree of pathological response [e.g., pathological complete response (pCR) or major response (pMR)] to immunotherapy. Neoadjuvant immunotherapy provides an ideal setting for exploring responsive biomarkers because the pathological responses can be directly and accurately evaluated.

Methods

We retrospectively collected the clinicopathological characteristics and treatment outcomes of non-small cell lung cancer (NSCLC) patients who received neoadjuvant immunotherapy or chemo-immunotherapy followed by surgery between 2018 and 2020 at a large academic thoracic cancer center. Clinicopathological factors associated with pathological response were analyzed.

Results

A total of 39 patients (35 males and 4 females) were included. The most common histological subtype was lung squamous cell carcinoma (LUSC) (n=28, 71.8%), followed by lung adenocarcinoma (LUAD) (n=11, 28.2%). After neoadjuvant treatment, computed tomography (CT) scan-based evaluation showed poor agreement with the postoperatively pathological examination (weighted kappa =0.0225; P=0.795), suggesting the poor performance of CT scans in evaluating the response to immunotherapy. Importantly, we found that the smoking signature displayed a better performance than programmed death-ligand 1 (PD-L1) expression in predicting the pathological response (area under the curve: 0.690 vs. 0.456; P=0.0259), which might have resulted from increased tumor mutational burden (TMB) and/or microsatellite instability (MSI) relating to smoking exposure.

Conclusions

These findings suggest that CT scan-based evaluation is not able to accurately reflect the pathological response to immunotherapy and that smoking signature is a superior marker to PD-L1 expression in predicting the benefit of immunotherapy in NSCLC patients.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Thoraxchirurgie

UniBE Contributor:

Hall, Sean; Al-Hurani, Mohammad; Schmid, Ralph and Peng, Ren-Wang

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2226-4477

Publisher:

AME Publishing

Language:

English

Submitter:

Thomas Michael Marti

Date Deposited:

19 Jan 2022 12:08

Last Modified:

19 Jan 2022 12:13

Publisher DOI:

10.21037/tlcr-21-734

PubMed ID:

34733630

Uncontrolled Keywords:

Neoadjuvant immunotherapy biomarker lung cancer pathological response smoking

BORIS DOI:

10.48350/162940

URI:

https://boris.unibe.ch/id/eprint/162940

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