Clinical Outcome of Nivolumab Plus Ipilimumab in Patients with Locally Advanced Non-Small-Cell Lung Cancer with Relapse after Concurrent Chemoradiotherapy followed by Durvalumab.

Nivolumab plus ipilimumab showed promising efficacy in patients with metastatic non-small-cell lung cancer (NSCLC). The efficacy of the nivolumab plus ipilimumab combination regimen in NSCLC patients who relapse after durvalumab consolidation following concurrent chemoradiotherapy (CCRT) has not been determined. Between January 2021 and June 2022, clinical data were retrospectively extracted from the medical records of patients with NSCLC who received nivolumab plus ipilimumab after CCRT and durvalumab consolidation. A total of 30 patients were included in this analysis. The median number of durvalumab treatment cycles was 11. Median PFS and OS with nivolumab plus ipilimumab were 4.2 months (95% confidence interval [CI]: 0.7-7.7) and 18.5 months (95% CI: 3.5-33.5), respectively. The 6-month and 12-month PFS rates were 46.7% (95% CI: 28.8-64.5) and 36.4% (95% CI: 19.0-53.7). In multivariate analysis, a significant correlation was observed between a durvalumab treatment duration of 6 months or more and PFS (p = 0.04) as well as OS (p = 0.001). Grade 3 adverse events, including pneumonitis, dermatitis, and colitis, occurred in 10% of the patients. This study suggests that nivolumab plus ipilimumab is effective, especially in patients who have received durvalumab for 6 months or more, and tolerable for patients who relapsed after durvalumab following CCRT.

Membranous Nephropathy as a Paraneoplastic Syndrome in Cancer of Unknown Primary.

BACKGROUND/AIM: Membranous nephropathy (MN) is a nephrotic syndrome with both idiopathic and secondary etiologies. The mechanism of cancer-associated MN is presumed to involve the immunological production of antibodies against a tumor antigen, although little is known about the detailed mechanism. Lung cancer is a major neoplasm associated with cancer-associated MN. However, the simultaneous occurrence of secondary MN in patients with cancer of unknown primary (CUP) remains unclear. CASE REPORT: Here, we present a case of secondary MN in a 72-year-old female as a paraneoplastic syndrome in CUP. Thoracic radiotherapy up to a total of 60 Gy was initially performed on the right subclavian and mediastinal lymph nodes. Computed tomography revealed marked shrinking of these lymph nodes, and the secondary MN also improved without any symptoms. CONCLUSION: The presence of proteinuria in patients with CUP suggests the possibility of secondary MN as a rare differential diagnosis.

Progression to Lymph Node Metastasis After Spontaneous Regression of Pulmonary Adenocarcinoma Following Biopsy.

BACKGROUND/AIM: Spontaneous regression (SR) of cancer, which indicates the natural disappearance of malignant tumors, is rare. Little is known about the mechanisms underlying SR; however, immunological reactions, infections, injuries, and medications have been presumed. Among previously reported cases of SR, lung cancer cases have been extremely limited. CASE REPORT: Here, we present a case of lymph node metastasis exacerbation after SR of a primary adenocarcinoma following a biopsy. After complete disappearance of the primary site tumor, metastatic lymph nodes in the mediastinum gradually increased in size as a single lesion. Local treatment with resection and radiotherapy was effective for this metastasis, without recurrence for >3 years. CONCLUSION: This is an interesting case of SR of pulmonary adenocarcinoma with inconsistent features in the primary and metastatic lesions. When physicians encounter exacerbation of metastatic sites with SR of the primary site in lung cancer, local intervention may be considered as a curative treatment.

Metabolic Tumor Volume as Significant Predictor for Chemotherapy Containing PD-L1 Blocker in Extensive Stage Small Cell Lung Cancer.

BACKGROUND/AIM: Chemo-immunotherapy, including the programmed death ligand 1 (PD-L1) antibody, is an effective treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC). However, no biomarker has been established for the prediction of chemo-immunotherapy. Therefore, we investigated the potential of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) as a predictive marker. PATIENTS AND METHODS: Forty-six patients with ES-SCLC who received 18F-FDG-PET immediately before combined platinum-based chemotherapy with PD-L1 blockade as a first-line treatment were eligible, and the maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on 18F-FDG uptake were evaluated. RESULTS: PD-L1 and tumor infiltrative lymphocytes (TILs) were immunohistochemically analyzed in 36 of the 46 patients. A high MTV was significantly associated with poor performance status and low albumin levels, and there was a significant association between low albumin and high TLG. Univariate analysis identified sex, Brinkman index, and MTV as significant predictors of progression-free survival (PFS), and sex, SUVmax, MTV, and TLG as significant factors of overall survival (OS). Multivariate analysis revealed that sex, Brinkman index, and MTV were independent prognostic factors for PFS, and sex, SUVmax, MTV, and TLG were significant predictors of OS. SUVmax was significantly higher in patients with positive PD-L1 expression than in those with negative expression but was not significantly different between positive and negative TILs. Moreover, the levels of MTV and TLG were not closely associated with the levels of PD-L1 and TILs. CONCLUSION: MTV or TLG metabolic tumor activity is suitable for the prediction of chemo-immunotherapy outcomes in patients with ES-SCLC.

Immunotherapy for non-small cell lung cancer.

Immune checkpoint inhibitors (ICI) bind to programmed cell death-1 (PD-1)/PD-1 ligand-1 (PD-L1) and Cytotoxic T-lymphocyte antigen-4 (CTLA-4), which suppress T-cell function and inhibit their inhibitory function, resulting in T-cell activation. ICI have been approved for a wide range of cancers, including malignant melanoma, renal cell carcinoma, non-small cell lung cancer, head and neck cancer, Hodgkin's disease, small-cell lung cancer, malignant pleural mesothelioma, gastric cancer, esophageal cancer, breast cancer, uterine cancer, and hepatocellular carcinoma, and the number of indications continues to grow. In addition to the treatment of advanced disease, the anti-tumor effect has been demonstrated across disease stages, from locally advanced disease to early-stage operative disease. The treatment of lung cancer is at the forefront of this trend and long-term durable responses and survival benefits in lung cancer have been exhibited that were unimaginable when cytotoxic anticancer agents were the only treatment options. However, treatment efficacy varies greatly from case to case, and no biomarkers have been developed to accurately predict efficacy. In this article, we discuss the past and future of ICI therapy for lung cancer, based on clinical and basic evidence accumulated to-date.

Investigating the immunological function of alpha-2-glycoprotein 1, zinc-binding in regulating tumor response in the breast cancer microenvironment.

BACKGROUND: Alpha-2-glycoprotein 1, zinc-binding (ZAG), a secreted protein encoded by the AZGP1 gene, is structurally similar to HLA class I. Despite its presumed immunological function, little is known about its role in tumor immunity. In this study, we thus aimed to determine the relationship between the expression of AZGP1/ZAG and the immunological profiles of breast cancer tissues at both the gene and protein level. METHODS: Using a publicly available gene expression dataset from a large-scale breast cancer cohort, we conducted gene set enrichment analysis (GSEA) to screen the biological processes associated with AZGP1. We analyzed the correlation between AZGP1 expression and immune cell composition in breast cancer tissues, estimated using CIBERSORTx. Previously, we evaluated the infiltration of 11 types of immune cells for 45 breast cancer tissues using flow cytometry (FCM). ZAG expression was evaluated by immunohistochemistry on these specimens and analyzed for its relationship with immune cell infiltration. The action of ZAG in M1/M2 polarization models using primary cultures of human peripheral blood mononuclear cells (PBMC)-derived macrophage (Mφ) was analyzed based on the expression of M1/M2 markers (CD86, CD80/CD163, MRC1) and HLA class I/II by FCM. RESULTS: AZGP1 expression was negatively correlated with multiple immunological processes and specific immune cell infiltration including Mφ M1 using GSEA and CIBERSORTx. ZAG expression was associated with decreased infiltration of monocytes/macrophages, non-classical monocytes, and myeloid-derived suppressor cells in tumor tissues assessed using FCM. In in vitro analyses, ZAG decreased the expression of CD80, CD163, MRC1, and HLA classes I/II in the M1 polarization model and the expression of CD163 and MRC1 in the M2 polarization model. CONCLUSION: ZAG is suggested to be a novel immunoregulatory factor affecting the Mφ phenotype in breast cancer tissues.

Clinical impact of inflammatory and nutrition index based on metabolic tumor activity in non­small cell lung cancer treated with immunotherapy.

The aim of the present study was to explore the relationship between tumor metabolic glycolysis and inflammatory or nutritional status in patients with advanced non-small cell lung cancer (NSCLC) who received programmed death-1 (PD-1) blockade. A total of 186 patients were registered in the present study. All of patients underwent 18F-FDG PET imaging before initial PD-1 blockade, and maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were assessed as indicators of 18F-FDG uptake. As inflammatory and nutritional index, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ration (PLR), systemic immune inflammation index (SII), prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI) and Glasgow prognostic score (GPS) were evaluated based on previous assessment. 18F-FDG uptake by MTV and TLG significantly correlated with the scores of NLR, PLR, SII, PNI and ALI, in addition to the level of albumin, lactate dehydrogenase, C-reactive protein, white blood cells, neutrophils, lymphocytes and body mass index. The count of NLR, PLR and SII was significantly higher in patients with <1 year overall survival (OS) compared with in those with ≥1 year OS, and that of PNI and ALI was significantly lower in those with <1 year OS compared with those with ≥1 year OS. High MTV under the high PLR, SII and low ALI were identified as significant factors for predicting the decreased PFS and OS after PD-1 blockade in a first-line setting. In second or more lines, high MTV was identified as a significant prognostic predictor regardless of the levels of PLR, SII, ALI and GPS. In conclusion, metabolic tumor glycolysis determined by MTV was identified as a predictor for the outcome of PD-1 blockade under the high inflammatory and low nutritional conditions, in particular, when treated with a first-line PD-1 blockade. A high MTV under high PLR and SII and low ALI in the first-line setting could be more predictive of ICI treatment than other combinations.

A phase II study of atezolizumab with bevacizumab, carboplatin, and paclitaxel for patients with EGFR-mutated NSCLC after TKI treatment failure (NEJ043 study).

INTRODUCTION: Treatment options for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after EGFR-tyrosine kinase inhibitor (TKI) treatment failure are limited. An exploratory analysis of 26 patients in the IMpower150 study indicated that treatment with atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) was effective in patients with EGFR-mutated NSCLC. This phase II study was conducted to assess the efficacy of ABCP in EGFR-mutated NSCLC patients after TKI treatment. METHODS: Patients with non-squamous NSCLC harboring sensitizing EGFR mutations were enrolled. ABCP therapy was administered every 3 weeks for four cycles, followed by maintenance therapy with atezolizumab and bevacizumab. The primary endpoint was progression-free survival (PFS) according to extramural review (ER). Key secondary endpoints and preplanned analysis included overall survival (OS), overall response rate (ORR), and differences in the efficacy of ABCP according to prior EGFR-TKI administration, liver metastases, and brain metastases. RESULTS: Sixty patients from 26 centers were enrolled. Median PFS was 7.4 months (95% confidence interval [CI]: 5.7-8.2). The median OS was 23.1 months (95% CI: 13.1-not reached), and the ORR was 55.9%. PFS was significantly shorter in patients who had received osimertinib as a first-line treatment (7.2 months vs. 7.4 months, hazard ratio [HR] 1.932, p = 0.023), those with brain metastases (5.7 months vs. 8 months, HR 1.86, p = 0.032), or those with liver metastases (5.4 months vs. 7.9 months, HR 2.779, p = 0.003). CONCLUSIONS: Although this study did not meet the primary endpoint, ABCP showed clinically meaningful efficacy in EGFR-mutated NSCLC patients.

Clinical Utility of Inflammatory and Nutritious Index as Therapeutic Prediction of Nivolumab plus Ipilimumab in Advanced Non-Small Cell Lung Cancer.

INTRODUCTION: Biomarkers for predicting the outcome of ipilimumab plus nivolumab (Nivo-Ipi) treatment in cancer patients have not been identified. Herein, we investigated the prognostic significance of inflammatory and nutritional markers in patients with advanced non-small cell lung cancer (NSCLC) receiving Nivo-Ipi. METHODS: Our study retrospectively analyzed 101 patients with advanced NSCLC who received Nivo-Ipi at a single institution. Inflammatory and nutritional indices were correlated with patient outcomes and included the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), prognostic nutritional index (PNI), advanced lung cancer inflammation index (ALI), and Glasgow prognostic score (GPS). RESULTS: The NLR significantly correlated with the PLR, SII, PNI, ALI, and GPS. Regarding therapeutic efficacy, the NLR, SII, and PNI predicted a partial response, and all indices predicted progressive disease. In subgroup analyses, the SII, PNI, and ALI predicted the outcome of patients with adenocarcinoma, whereas only the PNI predicted the outcome of patients with non-adenocarcinoma. The PNI and SII were the most useful indices in patients with a programmed death ligand-1 expression level of <1% and ≥1%, respectively. CONCLUSION: The NLR, PLR, SII, PNI, ALI, and GPS were significantly associated with the outcome of Nivo-Ipi treatment in patients with NSCLC. The PNI was the most suitable marker regardless of histological type. The SII and PNI were the most promising markers for patients with and without PD-L1 expression, respectively.

Prognostic Potential of the Prognostic Nutritional Index in Non-Small Cell Lung Cancer Patients Receiving Pembrolizumab Combination Therapy with Carboplatin and Paclitaxel/Nab-Paclitaxel.

INTRODUCTION: Pembrolizumab (Pemb) therapy in conjunction with carboplatin and paclitaxel (PTX)/nab-PTX has been efficacious in treating non-small cell lung cancer (NSCLC). However, the response predictors of this combination therapy (Pemb-combination) remain undetermined. We aimed to evaluate whether Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), body mass index (BMI), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) are potential factors in prognosticating the response to Pemb-combination therapy in advanced NSCLC patients. METHODS: We retrospectively recruited 144 NSCLC patients receiving first-line treatment with Pemb-combination therapy from 13 institutions between December 1, 2018, and December 31, 2020. GPS, NLR, BMI, PLR, and PNI were assessed for their efficacy as prognostic indicators. Cox proportional hazard models and the Kaplan-Meier method were used to compare the progression-free survival (PFS) and overall survival (OS) of the patients. RESULTS: The treatment exhibited a response rate of 63.1% (95% confidence interval [CI]: 55.0-70.6%). Following Pemb-combination administration, the median PFS and OS were 7.3 (95% CI: 5.3-9.4) and 16.5 (95% CI: 13.9-22.1) months, respectively. Contrary to PNI, NLR, GPS, BMI, and PLR did not display substantially different PFS in univariate analysis. However, multivariate analysis did not identify PNI as an independent prognostic factor for PFS. Furthermore, univariate analysis revealed that GPS, BMI, and PLR exhibited similar values for OS but not NLR and PNI. Patients with PNI ≥45 were predicted to have better OS than those with PNI <45 (OS: 23.4 and 13.9 months, respectively, p = 0.0028). Multivariate analysis did not establish NLR as an independent prognostic factor for OS. CONCLUSION: The PNI evidently predicted OS in NSCLC patients treated with Pemb-combination as first-line therapy, thereby validating its efficiency as a prognostic indicator of NSCLC.

Clinical significance of antinuclear antibody as prognostic marker for first-line pembrolizumab in advanced non-small cell lung cancer.

BACKGROUND: The relationship between antinuclear antibody (ANA) and the efficacy of programmed death-1 (PD-1) blockade remains controversial. Here, we investigated the prognostic significance of ANA titer in patients with non-small cell lung cancer (NSCLC) receiving pembrolizumab monotherapy as the first-line treatment, compared with that of platinum-based chemotherapy with PD-1 blockade. METHODS: Our clinical data based on the ANA titer (1:80) were retrospectively reviewed for patients with advanced NSCLC, who were treated with first-line pembrolizumab monotherapy and platinum-based chemotherapy with PD-1 blockade. Immunohistochemical staining for tumor-infiltrating lymphocytes such as CD4, CD8 and Foxp3 was performed. RESULTS: Among 106 patients treated with pembrolizumab, 19 (17.9%) tested high for ANA. Progression-free survival (PFS) and overall survival (OS) were significantly better in patients with high ANA than in those with low ANA, and high ANA was identified as an independent prognostic predictor, particularly in the subgroup with programmed death ligand-1 (PD-L1) ≥ 50%. However, no statistically significant difference in PFS and OS based on the ANA titer was observed in 59 patients treated with combinational chemotherapy and immunotherapy. High numbers of intratumoral Foxp3 and stromal CD8 were significantly associated with low ANA. CONCLUSIONS: Assessment of preexisting ANA titers was useful to prognose PD-1 blockade as a first-line setting, particularly for the PD-L1 ≥ 50% subgroup, but not in the case of combined immunotherapy and chemotherapy.

Predictive significance of circulating tumor DNA against patients with T790M-positive EGFR-mutant NSCLC receiving osimertinib.

Circulating tumor DNA (ctDNA) provides molecular information on tumor heterogeneity. The prognostic usefulness of ctDNA after first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are limited. Therefore, the present study evaluated ctDNA during osimertinib administration as a second-line or more setting to identify the relationship between EGFR mutation levels and outcomes in patients with advanced non-small cell lung cancer (NSCLC). Forty patients with EGFR T790M-positive NSCLC receiving osimertinib after prior EGFR-TKI treatment were registered. Plasma samples were collected at osimertinib pretreatment, after 1 month of treatment, and at the time of progressive disease (PD). ctDNA analysis was performed by digital polymerase chain reaction. The detection rate of copy numbers of exon 19 deletion, L858R, and T790M in plasma samples was significantly lower 1 month after osimertinib than at pretreatment, and significantly higher at PD than at 1 month, whereas that of C797S was significantly higher at PD than at 1 month. No statistically significant difference was observed in the copy numbers of exon 19 deletion, L858R, T790M, and C797S between complete response or partial response and stable disease or PD. The detection of T790M at PD after osimertinib initiation was a significant independent prognostic factor for predicting shorter prognosis, and the presence of major EGFR mutations at pretreatment and PD was closely linked to worse survival after osimertinib initiation. Molecular testing based on ctDNA is helpful for predicting outcomes of osimertinib treatment in T790M-positive NSCLC after previous EGFR-TKI treatment.

Clinicopathological impact of VEGFR2 and VEGF-C in patients with EGFR-major mutant NSCLC receiving osimertinib.

BACKGROUND: Vascular endothelial growth factor (VEGF) has been identified as one of the resistant mechanisms to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). However, the relationship between the efficacy of osimertinib and protein expression of VEGF family members in patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations remains unclear. METHODS: A total of 76 patients with advanced NSCLC with EGFR major mutations (del19 or L858R) receiving first-line osimertinib were eligible as the osimertinib (Osi) group, whereas 43 patients receiving first- or second-generation EGFR-TKIs were compared with the control group. The expression of vascular endothelial growth factor receptor 2 (VEGFR2) and vascular endothelial growth factor C (VEGF-C) in the tumor specimens was analyzed using immunohistochemistry. RESULTS: VEGFR2 and VEGF-C were highly expressed in 65.8% and 51.3% of patients, respectively, in the Osi group, and 69.7% and 76.7%, respectively, in the control group. High VEGFR2 and VEGF-C levels were significantly associated with poor performance status (PS) and female sex, respectively. In the Osi group, patients with co-high expression of VEGFR2 and VEGF-C showed significantly worse progression-free survival (PFS) and overall survival (OS) than those without co-high expression. In del19, VEGFR2 was a significant predictor of PFS and OS and independent predictor of OS in multivariate analysis. In L858R, co-high expression of VEGFR2 and VEGF-C was identified as a significant predictor of PFS and OS and independent predictor of PFS. CONCLUSION: VEGFR2 and VEGF-C are highly expressed in EGFR-mutant NSCLC cells. Increased expression of VEGFR2 was identified as a significant prognostic factor in patients with EGFR del19 mutation who received osimertinib, whereas co-high expression of VEGFR2 and VEGF-C was a significant predictor for those with EGFR L858R mutation.

A Th1-like CD4+ T-cell Cluster That Predicts Disease-free Survival in Early-stage Lung Cancer.

Perioperative immune checkpoint inhibitors have been shown to improve prognosis in early-stage lung cancer. However, no biomarkers are known to indicate the requirement for treatment. This study aimed to identify T-cell clusters responsible for antitumor immunity in patients with early-stage lung cancer. Preoperative blood samples from 50 consecutive patients with lung cancer who were diagnosed as operable and underwent complete resection were analyzed by mass cytometry. Patients were divided into two groups: no recurrence at a minimum observation period of 851 days (median observation period: 1,031.5 days) and recurrence by the last observation date. Mass cytometry and single-cell RNA sequencing analysis of lymph nodes (LN) and tumor-infiltrating T cells were also performed. CCR4-CCR6+ Th7R showed discriminative ability between recurrence and non-recurrence patients with lung cancer. Patients with more than 3.04% Th7R showed significantly favorable disease-free survival. Th7R was a major component of CD4+ T cells in tumor microenvironments and LNs adjacent to lung cancer tissues and was the only cluster that decreased in peripheral blood after the removal of cancer tissues, suggesting that Th7R was primed and proliferated in tumor-draining LNs in the presence of cancer tissues. Th7R had the kinetics that antitumor T cells should have, as indicated by the cancer immunity cycle; thus, peripheral blood Th7R could represent the potency of tumor immunity by reflecting priming and proliferation in tumor-draining LNs and Th7R in the tumor microenvironment. Prediction using peripheral Th7R before surgery could allow the selection of patients who require perioperative drug therapy and optimize therapeutic interventions with clinical implications. Significance: Peripheral Th7R, a Th1-like CD4+ T-cell cluster reflecting priming status in draining LNs and immune status in the tumor microenvironment, predicts disease-free survival after complete resection and has significant clinical relevance in selecting appropriate therapeutic interventions in patients with early-stage lung cancer.

Using the neutrophil-to-lymphocyte ratio to predict the outcome of individuals with nonsquamous non-small cell lung cancer receiving pembrolizumab plus platinum and pemetrexed.

BACKGROUND: Factors predicting the response to pembrolizumab plus platinum and pemetrexed combination therapy (Pemb-Plt-PEM) in nonsquamous non-small cell lung cancer (non-sq NSCLC) are unclear. We investigated the Glasgow Prognostic (GP) score, neutrophil-to-lymphocyte ratio (NLR), and body mass index (BMI) as predictors of response to initial treatment with combination therapy in individuals with advanced non-sq NSCLC. METHODS: We retrospectively reviewed 236 patients who received initial treatment with combination therapy for non-sq NSCLC at 13 institutions between December 2018 and December 2020. The usefulness of the GP score, NLR, and BMI as prognostic indicators was assessed. Cox proportional hazard models and the Kaplan-Meier method were used to compare progression-free survival (PFS) and overall survival (OS). RESULTS: The response rate was 51.2% (95% CI: 44.9-57.5%). The median PFS and OS after beginning Pemb-Plt-PEM were 8.8 (95% CI: 7.0-11.9) months and 23.6 (95% CI: 18.7-28.6) months, respectively. The NLR independently predicted the efficacy of Pemb-Plt-PEM-the PFS and OS were more prolonged in individuals with NLR <5 than in those with NLR ≥5 (PFS: 12.8 vs. 5.3 months, p = 0.0002; OS: 29.4 vs. 12.0 months, p < 0.0001). BMI predicted the treatment response-individuals with BMI ≥22.0 kg/m2 had longer OS than did those with BMI < 22.0 kg/m2 (OS: 28.4 vs. 18.4 months, p = 0.0086). CONCLUSIONS: The NLR significantly predicted PFS and OS, whereas BMI predicted OS, in individuals who initially received Pemb-Plt-PEM for non-sq NSCLC. These factors might be prognosis predictors in non-sq NSCLC.