Metastatic Non-Small Cell Lung Cancer Treated With Chemotherapy Combined With Concurrent Radiation Therapy to the Primary Tumor: Characterization of Long-term Survivor and Prognostic Value of Lung Immune Prognostic Index in Two Prospective Studies.

Purpose/objective(s) The role of radiotherapy, in addition to chemotherapy, has not been thoroughly determined in metastatic non-small cell lung cancer (mNSCLC). The purpose of the study was to investigate clinical characterization and treatment-related parameter of long-term survival in mNSCLC patients treated with concurrent chemotherapy with thoracic radiation therapy. In our previous study, the count of CD4-positive and CD8-positive T cells was associated with overall survival (OS). We speculated that baseline lung immune prognostic index (LIPI) based on pretreatment neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and lactate dehydrogenase (LDH) level may be associated with OS. Thus, the prognostic value of LIPI level was also evaluated in this study. Materials/methods We retrospectively analyzed 243 eligible patients with mNSCLC who were treated with chemotherapy and concurrent radiation to the primary tumor in two prospective studies. These patients had received at least two chemotherapy cycles and a thoracic radiation dose of at least 40 Gy in 2-Gy fractions, and did not receive targeted therapy or immunotherapy during lifetime. According to previous publications, dNLR greater than 3 and LDH greater than upper limit of normal was developed, characterizing 3 groups (good, 0 factors; intermediate, 1 factor; poor, 2 factors). Prognostic factors for OS were identified by using univariate and multivariate analysis. Propensity-score matching (PSM) were performed to further adjust for confounding. OS≥ 18 months was defined as long-term survival (LTS). Results According to LIPI, 141 patients were classified into good group, 83 patients in intermediate, and 19 patients in poor group. The number of patients was small in poor group. Thus, intermediate group and poor group were merged into the same risk group (intermediate-poor group). A total of 78 patients with long-term survival, 57 (40.4%) patients in good group, and 21 (20.6%) patients in intermediate-poor group. Univariate analysis showed that KPS score, T status, number of metastatic organs, brain metastasis, bone metastasis, radiation dose, and number of chemotherapy cycles, and LIPI were significant difference between LTS and non-LTS. Multivariate analysis showed that good LIPI and radiation dose (≥60 Gy) independently predicted long-term survival (P = 0.006, P = 0.012). After PSM, good LIPI remained to be correlated with long-term survival; the median survival time for good and intermediate-poor group were 13.7 months (95% CI, 11.37 - 16.02) and 11.0 months (95% CI, 9.52 - 12.48); the 1-, 2-, and 3-year OS rates were 59.8%, 21.2%, and 15.5% versus 41.5%, 10.2%, and 7.0% (χ2 = 5.603, P = 0.018). Conclusion For mNSCLC patients treated with chemotherapy in combination with thoracic radiation, LTS patients had good LIPI and receiving higher radiation dose to primary tumor. LIPI might be useful for identifying a subgroup that may benefit from thoracic radiotherapy with concurrent chemotherapy.