Associations between tumor mutations in cfDNA and survival in non-small cell lung cancer

Anine Larsen Ottestad; Hong Yan Dai; Tarje Onsøien Halvorsen; Elisabeth Fritzke Emdal; Sissel Gyrid Freim Wahl; Bjørn Henning Grønberg

doi:10.1016/j.ctarc.2021.100471

Associations between tumor mutations in cfDNA and survival in non-small cell lung cancer

Cancer Treat Res Commun. 2021:29:100471. doi: 10.1016/j.ctarc.2021.100471. Epub 2021 Sep 29.

Authors

Anine Larsen Ottestad¹, Hong Yan Dai², Tarje Onsøien Halvorsen¹, Elisabeth Fritzke Emdal³, Sissel Gyrid Freim Wahl², Bjørn Henning Grønberg⁴

Affiliations

¹ Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway; Department of Oncology, Cancer Clinic, St. Olav's Hospital, Trondheim University Hospital, 7006, Trondheim, Norway.
² Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway; Department of Pathology, Clinic of Laboratory Medicine, St. Olav's Hospital, Trondheim University Hospital, 7006 Trondheim, Norway.
³ Department of Pathology, Clinic of Laboratory Medicine, St. Olav's Hospital, Trondheim University Hospital, 7006 Trondheim, Norway.
⁴ Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway; Department of Oncology, Cancer Clinic, St. Olav's Hospital, Trondheim University Hospital, 7006, Trondheim, Norway. Electronic address: bjorn.h.gronberg@ntnu.no.

PMID: 34607221
DOI: 10.1016/j.ctarc.2021.100471

Abstract

Introduction: Studies have indicated that detection of mutated KRAS or EGFR in circulating tumor DNA (ctDNA) from pre-treatment plasma samples is a negative prognostic factor for non-small cell lung cancer (NSCLC) patients. This study aims to investigate whether this is the case also for NSCLC patients with other tumor mutations.

Methods: Tumor tissue DNA from 107 NSCLC patients was sequenced and corresponding pre-treatment plasma samples were analyzed using a limited target next-generation sequencing approach validated in this study. Patients without detected mutations in tumor samples were excluded from further analyses.

Results: Mutations were detected in tumor samples from 71 patients. Median age was 68 years, 51% were female, and 88% were current/former smokers, 91% had adenocarcinoma, 4% had squamous cell carcinoma and 6% had other NSCLC. The distribution between stage I, II, III and IV was 33%, 8%, 30%, and 29%, respectively. Between one and three tumor mutation(s) were detected in ctDNA from corresponding plasma samples. Patients with detected ctDNA had shorter PFS (9.6 vs. 41.3 months, HR: 2.9, 95% CI: 1.6-5.2, p = 0.0003) and OS (13.6 vs. 115.0 months, HR: 4.0, 95% CI: 2.1-7.6, p = 0.00002) than patients without detected ctDNA. ctDNA remained a significant negative prognostic factor for OS (HR: 2.5, 95% CI: 1.1-5.7, p=0.0327), but not PFS, in the multivariable analyses adjusting for baseline patient and disease characteristics including stage of disease.

Conclusions: This study adds further evidence supporting that detectable tumor mutations in cfDNA is associated with a worse prognosis in NSCLC harboring a variety of tumor mutations.

Keywords: Next-generation sequencing; Prognosis; Progression-free survival; cfDNA; ctDNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Non-Small-Cell Lung / mortality
Carcinoma, Non-Small-Cell Lung / pathology
Cell-Free Nucleic Acids / genetics*
Female
Humans
Lung Neoplasms / genetics*
Lung Neoplasms / mortality
Lung Neoplasms / pathology
Male
Middle Aged
Mutation
Prognosis
Survival Analysis

Substances

Cell-Free Nucleic Acids