Neutrophil-to-Lymphocyte Ratio Helps Predict Survival in Stage III NSCLC

Neutrophil-to-lymphocyte ratio (NLR) appeared to be a significant predictor of overall survival (OS) in stage III locally-advanced non-small cell lung cancer (NSCLC), according to findings presented at the International Association for the Study of Lung Cancer (IASLC) 2019 North America Conference on Lung Cancer.1

The median base line neutrophil and lymphocyte counts were 5.5 and 1.9, respectively – meaning baseline NLR was significant for OS on a multivariable analysis (P <.0001). The nadir NLR was also found to be a significant correlate to OS (P = .004). Moreover, baseline NLR demonstrated a trend for improved progression-free survival, (P <.006) after adjusting for age, sex, race, body mass index, and other factors.

“This is a large randomized data base of locally advanced non-squamous NSCLC patients undergoing CRT showing pre-treatment NLR to be a significant predictor of OS and a trend toward PFS,” the researchers concluded in the study abstract. “In addition, the nadir NLR value has shown significant predictor for OS.”

They noted that locally-advanced NSCLC continues to be a challenge given its poor outcomes. “Only about 14% of stage IIIA and 5% (of) IIIB lung cancer patients survive 5 years. However, there is no proven predictor for survival outcomes in this population to guide treatment decisions in order to improve outcomes,” they wrote, adding that increased systemic inflammatory response has been demonstrated to play an important role in cancer initiation, progression, and prognosis.

“Based on this knowledge, there has been renewed focus on identifying inflammatory biomarkers and indices that are associated with the prognosis of cancer patients, including neutrophil to lymphocyte ratio, platelet to lymphocyte ratio (PLR), and lymphocyte nadir value (LNV) during treatment.”

In the randomized PROCLAIM trial, researchers compared cisplatin plus pemetrexed with cisplatin plus etoposide with concurrent radiation. Enrollment for the study, sponsored by Eli Lilly and Company, was “stopped early due to futility,” according to the 2016 results published in the Journal of Clinical Oncology.2

But the secondary analysis of the inflammatory biomarkers, especially pre-treatment and nadir NLR, and its impact on survival outcomes, has now proven to show important results in survival prediction, according to the investigators, led by Tithi Biswas, MD, clinical associate profession, University Hospitals Seidman Cancer Center, Case Western Reserve University.

In total, 586 patients were randomized to receive either regimen – cisplatin plys pemetrexed or cisplatin plus etoposide. Researchers collected the baseline neutrophil and lymphoctye counts, among other clinical observations. OS and PFS served as the primary endpoint.

Along the course of the trial, the nadir NLR counts were also calculated after extractions during CRT, resulting in a sample size of 550 patients.

The median age of patients was 59 year, and the median follow-up was 24 months. Among other factors: 60% of patients were male, 71% were white, 60% were past smokers, and 13% were never-smokers.

References:

1. Biswas T, Kang K, Bajor D, et al. Prognostic Role of NLR in Stage III NSCLC Undergoing Chemoradiation: Secondary Analysis of PROCLAIM Trial. Presented at: IASLC 2019 North America Conference on Lung Cancer; October 11, 2019; Chicago, Ill. Abstract OA01.03.
2. Senan S, Brade A, Wang L, et al. PROCLAIM: Randomized Phase III Trial of Pemetrexed-Cisplain or Etoposide-Cisplatin Plus Thoracic Radiation Therapy Followed by Consolidation Chemotherapy in Locally Advanced NonSquamous Non-small-Cell Lung Cancer. Journal of Clinical Oncology. 34 (9) March 20, 2016. 953-962.