Pulmonary Adenosquamous Cell Carcinoma With Systemic Lymphadenopathy due to Immunoglobulin G4-Related Disease: A Case Report.

A 75-year-old man with diabetes mellitus showed elevated C-reactive protein (CRP) level at his regular visit. Computed tomography scan showed a lung tumor in his left lower lobe and systemic lymphadenopathy including abdominal lymph nodes. The patient was diagnosed as primary pulmonary squamous cell carcinoma with systemic lymph node metastasis. Thereafter, unexpected steroid pulse therapy for accidental acute exacerbation of interstitial pneumonia rapidly shrank lymphadenopathy. At this time, we also found elevated serum immunoglobulin G4 (IgG4) level (385 mg/dL). Considering these findings, we doubted the lymph nodes metastases at the initial staging, and then corrected cancer-staging (C-staging) from inferior vena cava (IVC) to inferior abdomen (IA). In addition, during the steroid tapering, sudden onset and uncontrollable left pneumothorax required surgical approach. Curative-intent left lower lobectomy with lymphadenectomy was performed for the lung cancer. Pathological findings revealed coexistence of adenosquamous carcinoma and infiltration of IgG4-positive plasma cells in the resected mediastinal lymph node. We detected 384 IgG4-positive cells per high power field. IgG4/IgG-positive cell ratio was 54%. Based on these findings, the diagnosis of IgG4-related disease with primary adenosquamous carcinoma (p-stage IIIA) was confirmed. The patient died 24 days after surgery because of another acute exacerbation of interstitial pneumonia. Our case alerts oncologists to IgG4-related disease as a possible underlying comorbidity which may confuse pretreatment clinical stage.

Durvalumab-Induced Diffuse Alveolar Hemorrhage: An Autopsy Case Report.

Durvalumab, a programmed cell death ligand 1 inhibitor, induces various immune-related adverse events (irAEs), including lung injury. However, diffuse alveolar hemorrhage (DAH) is a rare type of lung injury due to immune checkpoint inhibitors. A 76-year-old man with c-stage IIIA squamous cell carcinoma of the lung received maintenance durvalumab therapy after chemoradiotherapy. He developed dyspnea and malaise after 11 cycles of durvalumab. Chest computed tomography showed rapidly spreading bilateral ground-glass opacity in the lungs. We diagnosed DAH by hemosiderin-laden macrophages in bloody bronchoalveolar lavage fluid. Despite mechanical ventilation, steroids, and cyclophosphamide, he died of respiratory failure. The autopsy revealed that fresh and old bleeding areas coexisted, and neither pulmonary vasculitis nor diffuse alveolar damage was detected microscopically. Furthermore, CD3+ and CD8+ lymphocytes were observed in the lung interstitium, whereas CD20+ and CD4+ lymphocytes were scarcely detected. We report the first case of durvalumab-induced DAH. We should be alert to irAEs with DAH as a potential differential diagnosis of lung injury during durvalumab treatment.

Real-world osimertinib for EGFR mutation-positive non-small-cell lung cancer with acquired T790M mutation.

Aim: Osimertinib is a key drug for EGFR mutation-positive non-small-cell lung cancer (NSCLC). As the hazards ratio of overall survival in comparison with first-generation EGFR-tyrosine kinase inhibitors was almost similar between FLAURA and ARCHER 1050, salvage use of osimertinib is still a treatment option. Patients & methods: We retrospectively analyzed the clinical courses of EGFR mutation-positive NSCLC patients who were potential candidates for salvage osimertinib. Results: Among 524 patients enrolled from five hospitals, 302 patients underwent biopsy, with 52.6% detection rate of T790M. Osimertinib was administered in 93.6% of the T790M-positive patients. The overall response rate and median progression-free survival time of osimertinib were calculated with 147 patients, to be 55.6% and 17.2 months, respectively. Conclusion: Osimertinib is active for T790M-driven acquired resistance in EGFR-mutant NSCLC, but the detection of T790M was unsatisfactory. Clinical Trial Registration: UMIN000028989 (UMIN Clinical Trials Registry).

Gustave Roussy Immune Score and Royal Marsden Hospital Prognostic Score Are Prognostic Markers for Extensive Disease of Small Cell Lung Cancer.

BACKGROUND: The Royal Marsden Hospital prognostic score (RMH score) and the Gustave Roussy immune score (GRIm-score) were developed in order to select more suitable patient for phase I trials. Lactate dehydrogenase (LDH) and serum albumin concentration are common risk factors to these two systems. As the third risk factor, the RMH score and the GRIm-score adopt number of metastatic sites and neutrophil-to-lymphocyte ratio (NLR), respectively. We aimed to investigate whether these two systems are also useful for extensive disease of small cell lung cancer (ED-SCLC). METHODS: We retrospectively collected 128 patients who had initiated platinum-based chemotherapy at our hospital between September 2007 and March 2018. We divided our patients into low (score 0 - 1) and high (2 - 3) score groups, and compared overall survival (OS) and progression-free survival (PFS) between them. Multivariate Cox proportional hazard analyses found prognostic factors of survival times. RESULTS: Regarding GRIm-score, OS was significantly shorter in high score group than in low score group (median 6.1 vs. 11.4 months, P < 0.01), while no significant difference was observed in PFS (median 4.7 vs. 5.0 months, P = 0.12). Both OS (median 6.9 vs. 12.4 months, P < 0.01) and PFS (median 4.4 vs. 5.4 months, P = 0.01) were significantly shorter in high RMH score group than in low group. Multivariate analyses detected both high GRIm-score (hazard ratio (HR) 1.80, 95% confidence interval (CI) 1.20 - 2.72, P < 0.01) and high RMH score (HR 1.93, 95% CI 1.27 - 2.92, P < 0.01) as independent worse prognostic factors of OS, and then only high RMH score (HR 1.53, 95% CI 1.04 - 2.25, P = 0.03) as independent worse prognostic factor of PFS. CONCLUSIONS: Both RMH score and GRIm-score are useful as independent prognostic factors of OS in ED-SCLC. However, only RMH score is an independent prognostic factor of PFS.

Sarcopenia and Visceral Adiposity Did Not Affect Efficacy of Immune-Checkpoint Inhibitor Monotherapy for Pretreated Patients With Advanced Non-Small Cell Lung Cancer.

BACKGROUND: This study aimed to investigate the association of computed tomography (CT)-assessed sarcopenia and visceral adiposity with efficacy and prognosis of immune-checkpoint inhibitor (ICI) therapy for pretreated non-small cell lung cancer (NSCLC). METHODS: We retrospectively collected 74 patients with pretreated NSCLC who had initiated programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitor monotherapy between December 2015 and November 2018 at our hospital. As CT-assessed pretreatment markers, we used psoas muscle index (PMI), intramuscular adipose tissue content (IMAC), visceral-to-subcutaneous ratio (VSR) and visceral fat area (VFA) at lumbar vertebra L3 level. We divided 74 patients into high and low groups according to each Japanese sex-specific cut-off value. Using Kaplan-Meier curves and log-rank tests, we compared overall survival (OS) and progression-free survival (PFS). Adjusted by serum albumin, neutrophil-to-lymphocyte ratio, performance status and driver mutations, multivariate Cox proportional hazard analyses evaluated various variables as independent prognostic factors of OS and PFS. RESULTS: We could not find significant difference in response rate (RR) and disease control rate (DCR) between low and high groups according to any factors. The OS of patients with body mass index (BMI) < 18.5 was significantly shorter than that of patients with BMI ≥ 18.5 (median 3.3 vs. 15.8 months, P < 0.01), while there was no significant difference in OS and PFS according to PMI, IMAC, VSR and VFA. Multivariate analyses detected no significant prognostic factor in OS and PFS, except for low IMAC (hazard ratio 0.43, 95% confidence interval 0.18 - 0.998, P = 0.0496) as a favorable prognostic factor of longer OS. CONCLUSIONS: Neither PMI nor VSR, VFA might be a significant prognostic factor of PFS and OS of ICI monotherapy for pretreated NSCLC. According to our multivariate analyses, IMAC was a significant prognostic factor of OS, but not of PFS. Thus, neither sarcopenia nor visceral adiposity may be associated with the efficacy of ICI therapy.

Gustave Roussy Immune Score and Royal Marsden Hospital Prognostic Score Are Biomarkers of Immune-Checkpoint Inhibitor for Non-Small Cell Lung Cancer.

BACKGROUND: The Gustave Roussy Immune Score (GRIm-Score) and the Royal Marsden Hospital prognostic score (RMH score) were recently developed in order to improve a better participant selection for phase I trials. The GRIm-Score is formed by combination of lactate dehydrogenase (LDH), serum albumin concentration, and neutrophil-to-lymphocyte ratio (NLR). The RMH score is calculated by LDH, albumin, and number of metastases. These two scores have been validated only in phase I trials. The purpose of this study was to assess whether these scores are useful for practical treatment of immune-checkpoint inhibitor (ICI) monotherapy in pretreated non-small cell lung cancer (NSCLC). METHODS: This was a retrospective and single-centered study of 76 NSCLC patients treated with ICI monotherapy between December 2015 and October 2018 at our hospital. We divided 76 patients into high and low GRIm-Score and RMH score groups. Comparison of overall survival (OS) and progression free survival (PFS) was performed by Kaplan-Meier curves and log-rank tests. Independent prognostic factors of OS and PFS were analyzed by multivariate Cox proportional hazard analyses. RESULTS: The OS of the high GRIm-Score group was significantly shorter than that of the low score group (low vs. high; median 19.9 vs. 3.2 months, P < 0.01), while no significant difference was observed in PFS (2.6 vs. 2.1 months, P = 0.13). The PFS of the high RMH score was significantly shorter than that of the low score group (low vs. high; 2.6 vs. 1.8 months, P = 0.01), while there was no significant difference in OS (16.0 vs. 10.4, P = 0.24). Multivariate analyses detected high GRIm-Score (hazard ratio (HR) 3.93, 95% confidence interval (CI) 2.04 - 7.58, P < 0.01), and high RMH score (HR 1.76, 95% CI 1.03 - 3.02, P = 0.04) as poor prognostic factors of OS and PFS, respectively. CONCLUSIONS: Baseline GRIm-Score and RMH score were independent prognostic factors of OS and PFS of ICI monotherapy for pretreated NSCLC patients, respectively. These two scores are not only selection biomarkers for patients in experimental trials, but also useful prognostic biomarkers for NSCLC patients practically treated with ICI therapy.

Pretreatment Lung Immune Prognostic Index Is a Prognostic Marker of Chemotherapy and Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor.

BACKGROUND: Lung immune prognostic index (LIPI) was recently developed on the basis of the combination of baseline derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH). This index was demonstrated as a specific biomarker of immune checkpoint inhibitors for non-small cell lung cancer (NSCLC). We aimed to show that LIPI may be a useful biomarker of cytotoxic chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for NSCLC. METHODS: We retrospectively collected 175 wild-type EGFR adenocarcinomas, 131 NSCLCs harboring mutant EGFR and 110 squamous cell carcinomas. All patients initiated first-line cytotoxic chemotherapy or EGFR-TKI monotherapy between July 2007 and August 2017 at our hospital. These patients were divided into good, intermediate and poor LIPI groups. We compared their overall survival (OS) and progression-free survival (PFS). Multivariate analyses detected prognostic and predictive factors of OS and PFS. RESULTS: The good LIPI group survived longer than the intermediate and poor LIPI groups in wild-type EGFR adenocarcinoma (good, intermediate and poor LIPI groups: median 19.6, 11.5 and 3.3 months, P < 0.01, respectively) and mutant EGFR NSCLC (45.4, 25.6 and 15.7 months, P < 0.01). The PFS of good LIPI group was significantly longer that those of the other two groups in mutant EGFR NSCLC (16.6, 12.6 and 8.3 months, P < 0.01). The intermediate group (hazard ratio (HR) 1.49, 95% confidential interval (CI) 1.03 - 2.15, P = 0.04) of wild-type EGFR adenocarcinoma, intermediate (HR 2.30, 95% CI 1.33 - 3.99, P < 0.01) and poor (HR 2.76, 95% CI 1.03 - 7.42, P = 0.04) groups of mutant EGFR NSCLC were independent prognostic factors of poor OS. The intermediate (HR 1.57, 95% CI 1.01 - 2.44, P = 0.04) and poor (HR 2.63, 95% CI 1.14 - 6.07, P = 0.02) groups were significant prognostic factors of PFS of mutant EGFR NSCLC. CONCLUSIONS: LIPI was an independent prognostic factor of chemotherapy for adenocarcinoma with wild-type EGFR and of EGFR-TKI for NSCLC harboring mutant EGFR. Thus, LIPI was not a specific biomarker for ICI therapy, but a useful biomarker for chemotherapy and EGFR-TKI therapy in specific subsets of NSCLC.

Gustave Roussy Immune Score Is a Prognostic Factor for Chemotherapy-Naive Pulmonary Adenocarcinoma With Wild-Type Epidermal Growth Factor Receptor.

BACKGROUND: The Gustave Roussy Immune Score (GRIm-Score) was developed based on the Royal Marsden Hospital (RMH) prognostic score for the purpose of a better patient selection for immunotherapy phase I trials. This scoring system is simply calculated by neutrophil-to-lymphocyte ratio, lactate dehydrogenase (LDH), and serum albumin concentration. The aim of our study was to determine whether GRIm-Score is a practically useful prognostic biomarker for advanced non-small cell lung cancer (NSCLC) patients treated with cytotoxic chemotherapy or epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). METHODS: This retrospective and single institutional study collected 185 adenocarcinomas without active EGFR mutation, 115 squamous cell carcinomas treated with first-line cytotoxic chemotherapy, and 140 NSCLCs with mutant EGFR treated with first- or second-generation EGFR-TKI monotherapy. These treatments were initiated between July 2007 and March 2018 at our hospital. We compared overall survival (OS) and progression-free survival (PFS) between high and low GRIm-Score groups. Using multivariate Cox proportional hazard analyses, we also found prognostic factors of survival times. RESULTS: The OS and PFS of low GRIm-Score group were significantly longer than those of high-score group in wild-type EGFR adenocarcinoma (low vs. high; median OS, 18.4 vs. 5.1 months, P < 0.01, and median PFS, 5.8 vs. 3.7 months, P = 0.01) and EGFR-mutant NSCLC (median OS, 38.9 vs. 10.4 months, P < 0.01, and median PFS, 15.9 vs. 5.0 months, P < 0.01). Subsequent multivariate analyses detected high GRIm-Score in wild-type EGFR adenocarcinoma as a poor prognostic factor of OS (hazard ratio (HR) 2.20, 95% CI 1.47 - 3.31, P < 0.01), and in the EGFR-mutant NSCLC as a poor prognostic factor of PFS (HR 1.89, 95% CI 1.00 - 3.55, P = 0.049). CONCLUSIONS: High GRIm-Score was an independent prognostic biomarker of OS of first-line cytotoxic chemotherapy for wild-type EGFR adenocarcinoma and of PFS of first- or second-generation EGFR-TKI for EGFR-mutant NSCLC. Therefore, GRIm-Score is not only a specific selection marker for experimental immunotherapy trials, but may also be a promising and useful pretreatment prognostic maker for specific NSCLC subsets in the real-world practice.

Low Body Mass Index Is an Independent Prognostic Factor in Patients With Non-Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor.

BACKGROUND: Sarcopenia and obesity have been suspected as factors associated with efficacy of treatment and prognosis in various malignancies. This study aimed to investigate the association of pretreatment sarcopenia and visceral obesity with efficacy and prognosis of first- and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for patients with non-small cell lung cancer (NSCLC) and positive EGFR mutation. METHODS: We retrospectively collected 167 NSCLC patients with mutant EGFR who had started EGFR-TKI monotherapy between October 2007 and August 2018 at our hospital. We classified 167 patients into two groups, according to the definition of underweight based on the World Health Organization (WHO) body mass index (BMI) classification and the Japanese sex-specific cut-off values of the following computed tomography (CT) images-assessed markers of pretreatment sarcopenia or visceral obesity, such as psoas muscle index (PMI), intramuscular adipose tissue content (IMAC) and visceral-to-subcutaneous fat ratio (VSR) at lumbar vertebra L3 level. We compared overall survival (OS) and progression-free survival (PFS) of two groups by Kaplan-Meier curves and log-rank tests. Using multivariate Cox proportional hazard analyses adjusted by age, neutrophil-to-lymphocyte ratio, performance status, EGFR mutation types and EGFR-TKI lines, and extra-pulmonary metastases or three or more than 3 metastatic sites, we searched independent prognostic factors of OS and PFS of EGFR-TKI therapy. RESULTS: The OS (median 26.0 vs. 32.3 months, P = 0.02) and PFS (9.1 vs. 14.8 months, P = 0.03) of patients with BMI < 18.5 were significantly shorter than those of patients with BMI ≥ 18.5. However, there was no significant difference in OS and PFS according to PMI, IMAC and VSR. The multivariate analyses detected only BMI < 18.5 as an unfavorable prognostic factor of shorter OS (hazard ratio (HR) 1.70, 95% confidence interval (CI) 1.03 - 2.81, P = 0.04) and PFS (HR 1.72, 95% CI 1.11 - 2.67, P = 0.02). CONCLUSIONS: Pretreatment underweight was a significant prognostic factor of poor PFS and OS of EGFR-TKI therapy. However, neither pretreatment sarcopenia nor visceral obesity was associated with prognosis of EGFR-TKI. Underweight may be a surrogate for advanced disease burden.

Pretreatment Lymphocyte to Monocyte Ratio as a Prognostic Marker for Advanced Pulmonary Squamous Cell Carcinoma Treated With Chemotherapy.

BACKGROUND: Lower lymphocyte to monocyte ratio (LMR), higher neutrophil to lymphocyte ratio (NLR) and modified Glasgow prognostic score (mGPS) 2 have been demonstrated as independent prognostic markers for poor prognosis of advanced non-small cell lung cancer (NSCLC). However, little is known about these three markers as prognostic markers for a specific histological subset of NSCLC, squamous cell carcinoma (SCC). This study aimed to evaluate the prognostic significance of LMR, NLR and mGPS for advanced SCC. METHODS: We retrospectively collected 107 patients who met the following criteria: pathologically confirmed SCC, chemo-naive patients who had initiated first-line cytotoxic chemotherapy between September 2007 and February 2017 at our institution, and c-stage IIIB, IV or recurrence after curative-intent surgery or thoracic radiotherapy. In order to demonstrate these three markers as significant prognostic factors, we compared overall survival (OS) between two groups divided by LMR, NLR and mGPS 0 - 1 versus 2, and performed univariate and multivariate Cox proportional hazard analyses. RESULTS: Groups with low LMR (< 2.07) and high NLR (≥ 5.28) experienced shorter OS (LMR: 6.5 versus 15.6 months in median, P < 0.01; NLR: 8.2 versus 15.6 months, P < 0.01) than groups with high LMR (≥ 2.07) and low NLR (< 5.28). However, no significant difference was detected in OS between mGPS 0 - 1 and 2 (13.0 versus 13.7 months, P = 0.61). As significant poor prognostic factors, our multivariate Cox hazard analysis detected ECOG PS 2 - 4 (hazard ration (HR): 3.09, 95% confidence interval (CI): 1.77 - 5.40; P < 0.01) and LMR < 2.07 (HR: 0.39, 95% CI: 0.21 - 0.79; P < 0.01). However, NLR was not selected in the multivariate analysis. CONCLUSION: LMR is an independent prognostic factor for advanced pulmonary SCC. Neither NLR nor mGPS is useful as prognostic factor for this histology. The optimal prognostic markers may differ from each subset of NSCLC.

Lymphocyte to Monocyte Ratio and Modified Glasgow Prognostic Score Predict Prognosis of Lung Adenocarcinoma Without Driver Mutation.

BACKGROUND: Neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR) and modified Glasgow prognostic score (mGPS) are useful prognostic markers based on host-related systemic inflammatory response. They have been shown as independent prognostic biomarkers in various cancers, including non-small cell lung cancer. However, there has been little evidence for a specific population of pulmonary adenocarcinoma without active epidermal growth factor receptor (EGFR) mutation. METHODS: We retrospectively reviewed 159 patients who met the following criteria: histologically or cytologically diagnosed adenocarcinoma, confirmed wild-type EGFR, started first-line cytotoxic chemotherapy between July 2007 and March 2017 at our hospital, and c-stage IIIB or IV. We compared overall survival (OS) between dichotomized groups by the optimal cut-off points of NLR and LMR, and mGPS 0 - 1 vs. 2. Univariate and multivariate Cox proportional hazard analyses also detected prognostic factors for OS. RESULTS: As favorable prognostic factors for OS, multivariate analysis detected Eastern Cooperative Oncology Group performance status (ECOG PS) 0 - 1 (hazard ratio (HR) 3.43, 95% confidence interval (CI): 2.12 - 5.53; P < 0.01), LMR ≥ 1.97 (HR 0.39, 95% CI: 0.21 - 0.72; P < 0.01) and mGPS 0 - 1 (HR 1.95, 95% CI: 1.20 - 3.16; P < 0.01). The OS of LMR ≥ 1.97 and mGPS 0 - 1 groups were significantly longer than those of LMR < 1.97 and mGPS 2 groups, respectively. We divided 159 patients into three groups, both LMR ≥ 1.97 and mGPS 0 - 1, either LMR ≥ 1.97 or mGPS 0 - 1 and both LMR < 1.97 and mGPS 2. The OS of both LMR < 1.97 and mGPS 2 was significantly shorter than the other two groups. After adjustment for age, sex, ECOG PS, sodium, alkaline phosphatase and NLR, multivariate analysis found both LMR < 1.97 and mGPS 2 as an independent poor prognostic combination in comparison with both LMR ≥ 1.97 and mGPS0-1 (HR 5.98, 95% CI: 2.64 - 13.5; P < 0.01). CONCLUSIONS: LMR and mGPS are independent prognostic markers for pulmonary adenocarcinoma with wild-type EGFR. Combination of LMR and mGPS can stratify patients according to prognosis.

Pretreatment Glasgow prognostic score and prognostic nutritional index predict overall survival of patients with advanced small cell lung cancer.

BACKGROUND: Various biomarkers have been shown to predict prognosis in various types of cancers. However, these biomarkers have not been studied in advanced small cell lung cancer (SCLC). The modified Glasgow prognostic score (mGPS) is based on serum albumin level and C-reactive protein (CRP). The prognostic nutritional index (PNI) is a combination of serum albumin level and absolute lymphocyte count. This study aimed to evaluate the prognostic value of mGPS and PNI in SCLC. METHODS: We retrospectively reviewed and calculated mGPS and PNI for patients with stage IIIB or IV SCLC who initiated platinum-based combination chemotherapy between November 2007 and June 2016. We compared overall survival (OS) and progression-free survival (PFS) between high and low groups of these two biomarkers. Univariate and multivariate Cox hazard analyses assessed the prognostic value of these biomarkers. RESULTS: We reviewed 97 SCLC patients. The OS of patients with mGPS 0-1 and higher PNI was significantly longer than that of those with mGPS 2 and lower PNI. The PFS of mGPS 0-1 was significantly longer than that of mGPS 2, while there was no significant difference in PFS according to PNI. Multivariate analyses found mGPS 0-1 (hazard ratio [HR] 2.34, 95% confidence interval [CI] 1.27-4.31, P<0.01) and higher PNI (HR 0.50, 95% CI 0.31-0.78, P<0.01) as prognostic factors for longer OS. However, neither biomarker was predictive of PFS. CONCLUSION: Our study was a small retrospective study; however, the data demonstrate that pretreatment mGPS and PNI are independent predictors of OS in patients with advanced SCLC. The pretreatment assessment of mGPS and PNI may be useful for identification of patients with poor prognosis. We recommend pretreatment measurement of serum albumin, C-reactive protein, and absolute lymphocyte count.

Trajectory of chemotherapy for patients with EGFR wild-type advanced pulmonary adenocarcinoma: a single-institution retrospective study.

BACKGROUND: Pulmonary adenocarcinoma, recently benefited by new cytotoxic and molecularly targeted drugs, has been classified by driver mutations, such as EGFR mutations. The aim of this study was to research the proportions of patients treated with first- to third-line chemotherapy and to find influential factors for the introduction of chemotherapy and survival benefit from chemotherapy. MATERIALS AND METHODS: Data were collected retrospectively on patients who met the following criteria: adenocarcinoma, diagnosed between June 2007 and March 2015 at our hospital, stage IIIB or IV, and EGFR wild type. A nonchemotherapy group of patients who did not receive chemotherapy was compared with a chemotherapy group of patients who received it. The patients who had received first- to third-line chemotherapy between June 2007 and November 2015 at our hospital were also analyzed. RESULTS: During the study period, 46 patients did not receive chemotherapy, while 148, 89, and 48 received first-, second- and third-line chemotherapy, respectively. As predictive factors for unlikely chemotherapy, multivariate logistic analysis detected Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2, hemoglobin <13.2 g/dL, creatinine clearance (Ccr) <50.4 mL/min, and CRP ≥0.53 mg/dL. As factors predicting shorter survival after chemotherapy, multivariate Cox proportional-hazard analyses detected age ≥75 years, ECOG PS ≥2, lower lymphocyte counts, and higher CRP for the first line; female, higher neutrophil counts, lower lymphocyte counts, reduced Ccr, hyponatremia, and shorter interval between first- and second-line chemotherapy for the second line; and age ≥75 years, body mass index <18.5 kg/m2, higher neutrophil counts, lower lymphocyte counts, hyponatremia, higher lactate dehydrogenase, and higher CRP for the third line. CONCLUSION: Approximately 76% of patients were treated with first-line chemotherapy. Of those patients, 61% and 34% proceeded to second- and third-line chemotherapy, respectively. For patients with poor PS, anemia, reduced Ccr, and higher CRP, it is difficult to introduce chemotherapy.

Neutrophil-to-Lymphocyte Ratio Predicts Overall Survival of Advanced Non-Small Cell Lung Cancer Harboring Mutant Epidermal Growth Factor Receptor.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) have been demonstrated to be prognostic biomarkers in various cancers, including non-small cell lung cancer (NSCLC). However, little has been known about these two ratios for a specific population of NSCLC harboring active epidermal growth factor receptor (EGFR) mutation. METHODS: We retrospectively reviewed electrical medical records of 152 patients who met the following criteria: NSCLC harboring mutant EGFR, EGFR-tyrosine kinase inhibitor (EGFR-TKI) monotherapy initiated between October 2007 and February 2017 at our hospital, stage III-IV or post-surgical recurrence. We compared overall survival (OS) and progression-free survival (PFS) between dichotomized groups by the optimal cut-off points of the two biomarkers. Univariate and multivariate Cox hazard analyses also searched for prognostic factors of survival time. RESULTS: OSs of NLR < 2.11 (median 38.6 vs. 24.1 months, P < 0.01) and LMR ≥ 5.09 (median 39.4 vs. 26.4 months, P < 0.01) were significantly longer than those of NLR ≥ 2.11 and LMR < 5.09. Multivariate analyses found lower NLR (hazard ratio (HR) 1.07, 95% CI: 1.01 - 1.14; P = 0.03) as an independent prognostic factor for longer OS, in addition to Eastern Cooperative Oncology Group performance status 0 - 1, first-line EGFR-TKI, higher serum sodium concentration and lower lactate dehydrogenase. However, LMR was not detected as a significant prognostic factor for OS. None of these two biomarkers was selected as an independent prognostic factor for PFS. CONCLUSIONS: This study demonstrated that elevated NLR is an independent prognostic factor for poor survival of patients with EGFR mutant NSCLC. NLR is a useful and simple biomarker for these patients.

Retrospective analysis of outcomes and prognostic factors of chemotherapy for small-cell lung cancer.

BACKGROUND: Small-cell lung cancer (SCLC) is responsive to initial chemotherapy but becomes resistant to cytotoxic drugs. The aim of this study was to evaluate what proportion of patients with SCLC had received the first- and further-line chemotherapy and which patients had benefited from chemotherapy. METHODS: We retrospectively reviewed medical records of patients with SCLC who had been treated with the best supportive care alone and the first-, second-, or third-line chemotherapy at the Osaka Police Hospital from June 2007 until March 2015. RESULTS: Among 145 patients diagnosed with SCLC and eligible for analysis, 118 patients received chemotherapy. We added five patients who initiated the second-line chemotherapy during the study period at our institution. Sixty-five and 31 patients received the second- and third-line chemotherapies, respectively. Multivariate logistic regression analysis detected age ≥75 years (odds ratio, 2.80; 95% confidence interval, 1.01-7.75; P=0.047) and European Clinical Oncology Group Performance Status (ECOG PS) 3-4 (14.3; 4.86-41.9; P<0.01) as factors disturbing the introduction of chemotherapy. Multivariate Cox hazard analyses also detected ECOG PS 2-4 (3.34; 2.00-5.58; P<0.01) as a factor decreasing overall survival after the first-line chemotherapy, and C-reactive protein level ≥1.0 mg/dL (2.67; 1.30-5.47; P<0.01) and progression-free survival after the first-line chemotherapy ≥6 months (2.85; 1.50-5.43; P<0.01) as factors influencing overall survival after the second-line chemotherapy. CONCLUSION: Approximately two-thirds and one-third of the patients who receive chemotherapy proceed to the second- and third-line chemotherapies, respectively. Several factors, such as age, ECOG PS, C-reactive protein level, and progression-free survival after previous treatment may be useful when considering the introduction of further-line chemotherapy.

Outcomes and prognostic factors of chemotherapy for patients with locally advanced or metastatic pulmonary squamous cell carcinoma.

BACKGROUND: Pulmonary squamous cell carcinoma has not benefited from improvements in chemotherapy over the past decade, compared with non-squamous non-small-cell lung cancer. Nowadays, treatment strategies differ between squamous and non-squamous non-small-cell lung cancers. This study aimed to investigate the percentage of patients treated with first-, second-, or third-line chemotherapy and the characteristics of patients for whom chemotherapy has been beneficial. METHOD: Data on patients with stage IIIB or IV squamous cell carcinoma diagnosed between June 2007 and March 2015, and on patients who had received first-, second-, or third-line chemotherapy between June 2007 and November 2015 at our hospital, were retrospectively extracted from our institutional medical charts. We also compared patients who were treated with chemotherapy (chemotherapy group) and patients who were not (non-chemotherapy group) using multivariate logistic regression and multivariate Cox hazard analyses, respectively. RESULTS: During the study period, 103, 63, and 32 patients received first-, second-, and third-line chemotherapy, respectively. Fifty-one patients did not receive chemotherapy. Factors predicting unlikely chemotherapy included age ≥75 years, Eastern Cooperative Oncology Group (ECOG)-performance status (PS) ≥2, Charlson comorbidity index ≥2, hemoglobin <12.2 g/dL, red cell distribution width ≥13.9%, and serum sodium <140 mEq/L. Factors predicting survival for each line of chemotherapy included the following: ECOG-PS ≥2 for first-line; ECOG-PS ≥2 and lymphocyte count for second-line; and ECOG-PS ≥2, body mass index <18.5 kg/m2, and hemoglobin and lactate dehydrogenase levels for third-line. CONCLUSION: Approximately 66% of patients received first-line chemotherapy. Of those, 66% and 33% received second- and third-line chemotherapy, respectively. ECOG-PS was always an essential prognostic factor when considering introducing chemotherapy and proceeding with additional chemotherapy. Other markers, such as lymphocyte count, body mass index, anemia, and lactate dehydrogenase level, may be useful depending on the patient and line of chemotherapy.