Disparity in clinical outcomes between pure and combined pulmonary large-cell neuroendocrine carcinoma: A multi-center retrospective study.

OBJECTIVES: The 2015 World Health Organization classification defines pulmonary large-cell neuroendocrine carcinoma (LCNEC) as a high-grade neuroendocrine carcinoma. However, the clinical characteristics and prognostic factors of pure LCNEC and combined LCNEC remain unclear. Hence, we performed a multi-center retrospective study to compare the clinical outcomes of pure versus combined LCNEC. MATERIALS AND METHODS: Data from 381 patients with pulmonary LCNEC admitted to 17 Chinese institutes between 2009 and 2016 were collected retrospectively. Clinical characteristics and prognosis were analyzed among patients receiving adjuvant (adjuvant group; n = 56) and first-line (first-line group; n = 146) chemotherapy, as well as among patients receiving small cell lung cancer (SCLC) and non-SCLC (NSCLC) chemotherapy regimens. The Kaplan-Meier method and multivariable Cox regression were used to identify clinicopathological variables that might influence patient outcomes. RESULTS: Expression levels of neuroendocrine markers (synaptophysin, chromogranin-A, CD56) were associated with patients' prognosis in the total study cohort. In the adjuvant group, median disease-free survival was non-significantly longer for SCLC-based regimens than for NSCLC-based regimens (P = 0.112). In the first-line group, median progression-free survival was significantly longer for SCLC-based regimens than for NSCLC-based regimens (11.5 vs. 7.2 months, P = 0.003). Among patients with combined LCNEC, adenocarcinoma was the most common combined component, accounting for 70.0 % of cases. Additionally, median overall survival was non-significantly shorter for combined LCNEC than for pure LCNEC (P = 0.083). CONCLUSION: The SCLC regimen is a more effective choice, as either first-line or adjuvant chemotherapy, when compared to the NSCLC regimen for LCNEC treatment. Further studies are needed to clarify the survival differences between patients with pure-, and combined LCNEC.

Cardiovascular disease and survival in non-small cell lung cancer: a multicenter prospective assessment.

PURPOSE: Chronic inflammation contributes to cancer development via multiple mechanisms. We hypothesized that cardiovascular diseases (CVD) are also an independent risk factor for survival in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Prospective multicenter data from 345 consecutive NSCLC patients treated from January 2013 to January 2017 were assessed. Median follow-up for all patients was 13 months (range 3-60 months). There were 109 patients with baseline heart disease (HD 32%), 149 with arterial hypertension (43%), 85 with diabetes mellitus (25%), 129 with hyperlipidemia (37%) and 45 with venous thromboembolism events (VTE 13%). A total of 289 patients (84%) were treated with platinum-based chemotherapy (CT), 300 patients (87%) received thoracic radiation therapy (RT; median radiation dose: 60 Gy [range 12-70]); and 50 (15%) patients underwent surgery. RESULTS: Our cohort consisted of 305 men (88%) and 40 (12%) women, with a median age of 67 years (range 31-88 years). Seventy percent had a Karnofsky performance status (KPS) ≥ 80. Multivariate analyses showed a lower OS and higher risk of distant metastasis in patients with advanced stages (p = 0.05 and p < 0.001, respectively) and HD (HR 1.43, p = 0.019; and HR 1.49, p = 0.025, respectively). Additionally, patients with VTE had lower local control (HR 1.84, p = 0.025), disease-free survival (HR 1.64, p = 0.020) and distant metastasis-free survival (HR 1.73, p = 0.025). CONCLUSIONS: HD and VTE are associated with a higher risk of mortality and distant metastasis in NSCLC patients. Chronic inflammation associated with CVDs could be an additional pathophysiologic factor in the development of distant metastasis.

Real-World Treatment Patterns, Overall Survival, and Occurrence and Costs of Adverse Events Associated With Second-Line Therapies for Medicare Patients With Advanced Non-Small-Cell Lung Cancer.

INTRODUCTION: Real-world data on current treatment practices for non-small-cell lung cancer (NSCLC) are needed to understand the place in therapy and potential economic impact of newer therapies. PATIENTS AND METHODS: This retrospective cohort study identified patients ≥ 65 years old in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database with first-time diagnosis of stage IIIB/IV NSCLC from 2007-2011 who received second-line therapy after first-line platinum-based chemotherapy from 2007 through mid-2013. Second-line regimens, health care resource use, adverse events (AEs), and associated costs were analyzed descriptively. Overall survival was determined by Kaplan-Meier test. Costs were adjusted to 2013 US dollars. RESULTS: We identified 4033 patients with advanced NSCLC who received second-line therapy (47% of those who received first-line platinum-based chemotherapy). Mean (SD) age was 73 (5) years, 2246 (56%) were male; 1134 (28%) and 2899 (72%) had squamous and nonsquamous NSCLC, respectively. The 4 most common second-line regimens were pemetrexed (22%), docetaxel (12%), carboplatin/paclitaxel (11%), and gemcitabine (7%). Median overall survival from second-line therapy initiation was 7.3 months (95% confidence interval, 7.0-7.7). Dyspnea and anemia were the most common AEs of interest, affecting 29% and 26% of patients, respectively; atypical pneumonia was associated with the highest AE-related costs (mean, $5339). The mean total per-patient-per-month cost was $10,885; AE-related per-patient-per-month costs totaled $1036 (10%). Costs were highest for pemetrexed-treated patients. CONCLUSION: These real-world data illustrate the variety of second-line regimens, poor prognosis, and high cost of second-line chemotherapy for patients with advanced NSCLC treated before the approval of immunotherapies for these patients.

The effect of non-small cell lung cancer histology on survival as measured by the graded prognostic assessment in patients with brain metastases treated by hypofractionated stereotactic radiotherapy.

BACKGROUND: The purpose of this study was to investigate the impact of histology on survival stratified by the Graded Prognostic Assessment (GPA) for non-small cell lung cancer (NSCLC) in a group of selected patients treated recently. METHODS: A total of 171 NSCLC patients with brain metastases treated by hypofractionated stereotactic radiotherapy with or without whole-brain radiotherapy between 2001 and 2011 were included. The GPA score was calculated for each patient. Tumor histologies were categorized into adenocarcinoma (ADCA) and non-ADCA. Median survival time (MST, in months) was calculated using the Kaplan-Meier method. The log-rank test was used to determine statistical differences. RESULTS: MSTs by histology were: ADCA 15 (n = 92) and non-ADCA 10 (n = 79) (p < 0.001). For all patients, the MSTs by GPA score were: GPA 3.5-4, 24; GPA 2.5-3, 15; GPA 1.5-2, 9 and GPA 0-1, 6 (p < 0.001). The histology of ADCA showed a statistically significant higher MST than non-ADCA for patients with GPA 2.5-4. For GPA 2.5-3, MSTs were: ADCA 18, non-ADCA 10 (p = 0.007); for GPA 3.5-4, MSTs were: ADCA 30, non-ADCA 17 (p = 0.046). For GPA 0-2, MSTs did not differ significantly by histology. For GPA 0-1, MSTs were: ADCA 8, non-ADCA 4 (p = 0.146); GPA 1.5-2, MSTs were: ADCA 10, non-ADCA 8 (p = 0.291). We further found that non-ADCA in upper GPA class (3.5-4) had similar survival with ADCA in lower GPA class (2.5-3) (MSTs were 17 and 18, respectively, p = 0.775). This phenomenon also happened between patients of non-ADCA in upper GPA class (2.5-3) and those of ADCA in lower GPA class (1.5-2) (MSTs were both 10, p = 0.724). CONCLUSIONS: We confirmed that the histology of NSCLC had effect on the GPA in these selected patients treated recently. ADCA showed a statistically significant higher MST than non-ADCA with GPA 2.5-4. The non-ADCA in upper GPA classes (3.5-4 and 2.5-3) had similar survival to ADCA in lower GPA classes (2.5-3 and 1.5-2, respectively). The histology as a new factor should be added to the original GPA for NSCLC.

Adjuvant chemotherapy for elderly patients with stage I non-small-cell lung cancer ≥4 cm in size: an SEER-Medicare analysis.

BACKGROUND: The role of adjuvant chemotherapy for non-small-cell lung cancer (NSCLC) stage I patients with tumors size ≥4 cm is not well established in the elderly. PATIENTS AND METHODS: We identified 3289 patients with stage I NSCLC (T2N0M0 and tumor size ≥4 cm) who underwent lobectomy from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database diagnosed from 1992 to 2009. Overall survival and rates of serious adverse events (defined as those requiring admission to hospital) were compared between patients treated with resection alone, platinum-based adjuvant chemotherapy, or postoperative radiation (PORT) with or without adjuvant chemotherapy. Propensity scores for receiving each treatment were calculated and survival analyses were conducted using inverse probability weights based on the propensity score. RESULTS: Overall, 84% patients were treated with resection alone, 9% received platinum-based adjuvant chemotherapy, and 7% underwent PORT with or without adjuvant chemotherapy. Adjusted analysis showed that adjuvant chemotherapy [hazard ratio (HR), 0.82; 95% confidence interval (CI) 0.68-0.98] was associated with improved survival compared with resection alone. Conversely, the use of PORT with or without adjuvant chemotherapy (HR 1.91; 95% CI 1.64-2.23) was associated with worse outcomes. Patients receiving adjuvant chemotherapy had more serious adverse events compared with those treated with resection alone, with neutropenia (odds ratio, 21.2; 95% CI 5.8-76.6) being most significant. No significant difference was observed in rates of fever, cytopenias, nausea, and renal dysfunction. CONCLUSIONS: Platinum-based adjuvant chemotherapy is associated with reduced mortality and increased serious adverse events in elderly patients with stage I NSCLC and tumor size ≥4 cm.

Adjuvant treatment for elderly patients with early-stage lung cancer treated with limited resection.

OBJECTIVES: Limited resection is commonly used for treating older patients with early-stage non-small cell lung cancer (NSCLC) who cannot tolerate lobectomy. However, parenchymal-sparing procedures leave patients at increased risk of recurrence. The role of postoperative radiotherapy (PORT) and chemotherapy after limited resection is not established. METHODS: We identified 1,929 patients with stage I-II (≤ 5 cm in size) NSCLC who underwent limited resection (wedge or segmentectomy) from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Using propensity score methods, we compared toxicity and survival of patients treated with limited resection alone, PORT, adjuvant chemotherapy, or PORT and chemotherapy. We conducted secondary analysis stratifying the sample by size (>2-5 cm), stage (IA vs. IB/IIA), and type of limited resection (wedge resection vs. segmentectomy). MEASUREMENTS AND MAIN RESULTS: Overall, 1,656 (85.8%), 159 (8.3%), 74 (3.8%), and 40 (2.1%) patients were treated with limited resection alone, PORT, adjuvant chemotherapy, or PORT and chemotherapy, respectively. Adjusted analysis using inverse probability weighting showed that PORT (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.45-1.69), adjuvant chemotherapy (HR, 1.48; 95% CI, 1.36-1.61), and PORT and chemotherapy (HR, 1.73; 95% CI, 1.61-1.86) were associated with worse survival compared with limited resection alone. Similar results were obtained in secondary analyses. Compared with limited resection alone, the adjusted odds ratios for toxicity were 1.97 (95% CI, 1.6-2.4), 3.15 (95% CI, 2.58-3.85), 2.59 (95% CI, 2.0-3.4) for PORT, chemotherapy, and PORT and chemotherapy, respectively. CONCLUSIONS: PORT and adjuvant chemotherapy are not beneficial and appear to be associated with increased toxicity and worse survival after limited resection in elderly patients with early-stage NSCLC. Alternative strategies should be explored to improve local control.

Quality of life, geriatric assessment and survival in elderly patients with non-small-cell lung cancer treated with carboplatin-gemcitabine or carboplatin-paclitaxel: NVALT-3 a phase III study.

BACKGROUND: Elderly patients with advanced non-small-cell lung cancer (NSCLC) may derive similar benefit from platinum-based chemotherapy as younger patients. Quality of life (QoL) and comprehensive geriatric assessment (CGA) is often advocated to assess benefits and risks. PATIENTS AND METHODS: A total of 181 chemotherapy-naive patients [≥70 years, performance score (PS) of 0-2] with stage III-IV NSCLC received carboplatin and gemcitabine (CG) (n = 90) or carboplatin and paclitaxel (CP) (n = 91) every 3 weeks for up to four cycles. Primary end point was change in global QoL from baseline compared with week 18. Pretreatment CGA and mini geriatric assessment during and after treatment were undertaken. A principal component (PC) analysis was carried out to determine the underlying dimensions of CGA and QoL and subsequently related to survival. RESULTS: There were no changes in QoL after treatment. The number of QoL responders (CG arm, 12%; CP arm, 5%) was not significantly different. CGA items were only associated with neuropsychiatric toxicity. Quality-adjusted survival was not different between treatment arms. The PC analysis derived from nine CGA, six QoL and one PS score indicated only one dominant dimension. This dimension was strongly prognostic, and physical and role functioning, Groningen Frailty Indicator and Geriatric Depression Scale were its largest contributors. CONCLUSIONS: Paclitaxel or gemcitabine added to carboplatin did not have a differential effect on global QoL. CGA was associated with toxic effects in a very limited manner. CGA and QoL items measure one underlying dimension, which is highly prognostic.

Time from finding abnormality on mass-screening to final diagnosis of lung cancer.

Mass-screening for lung cancer is rather a unique system in Japan. This study illustrates time from finding abnormality on mass-screening to final diagnosis of lung cancer. Among the 517 patients with lung cancer who were admitted to our hospital over a 10-year period up to December 2001, 83 (16.1%) were detected by mass-screening. We reviewed medical records of the 83 patients and determined the intervals from the mass-screening to the pathological diagnosis with clinical staging. Time from the mass-screening to the date of hospital visit was <2 months in 62 (74.7%) cases. Five (6.0%) patients visited hospital more than 6 months after the mass-screening. With respect to the interval, there was no statistical difference in gender (p=0.0680) and age (p=0.1532). Among 60 patients who were referred from outside, on average, patients visited our hospital 0.5 month after they first sought medical attention at nearby clinic, and at our hospital 0.5 month was required to make a pathological diagnosis of lung cancer with TNM staging. There was a statistical difference in survival between the patients who were diagnosed <4 months and the patients who were diagnosed >4 months from the screening (p=0.0487). The interval in most cases was acceptable. However, further improvements are still needed to minimize the delay and to maximize the benefits of early cancer detection.