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The aim of this retrospective national cohort study is to assess the association between various radiation heart dosimetric parameters (RHDPs), acute myocardial infarct (AMI) and overall survival (OS) outcomes in non-small cell lung cancer (NSCLC) patients treated with post-operative thoracic radiotherapy (PORT) using contemporary radiation techniques.We identified patients with stage I to III NSCLC treated with PORT at the 2 national cancer institutions from 2007 to 2014. We linked their electronic medical records to the national AMI and death registries. Univariable Cox regression was performed to assess the association between various RHDPs, AMI, and OS.We included 43 eligible patients with median follow-up of 36.6 months. Median age was 64 years. Majority of the patients had pathological stage III disease (72%). Median prescription dose was 60Gy. Median mean heart dose (MHD) was 9.4Gy. There were no AMI events. The 5-year OS was 34%. Univariable Cox regression showed that age was significantly associated with OS (hazard ratio, 1.06; 95% confidence interval, 1.01 to 1.10; P = .008). Radiation heart doses, including MHD, volume of heart receiving at least 5, 25, 30, 40, 50Gy and dose to 30% of heart volume, were not significantly associated with OS.There is insufficient evidence to conclude that RHDPs are associated with OS for patients with NSCLC treated with PORT in this study. Studies with larger sample size and longer term follow-up are needed to assess AMI outcome.

Background: The survival benefit of PCI in ES-SCLC reported by a European randomized trial (RCT) in 2007 was not replicated by a Japanese RCT published in 2017. This study aimed to evaluate the uptake of PCI before and after publication of the European RCT and its association with survival in ES-SCLC., Methods: We identified eligible patients in the only two Singapore national cancer centres from 2003 to 2010. We linked their electronic medical records to the national death registry. We described the utilization of PCI in patients diagnosed from 2003 to 2006 (pre-adoption cohort) with patients diagnosed from 2007 to 2010 (post-adoption cohort). We performed univariable and multivariable Cox regression analysis to assess the association between PCI and survival., Results: We identified 224 patients with ES-SCLC with no brain metastases. Among the 71 patients who had at least stable disease after first line chemotherapy, there was an increase in the use of PCI from the period 2007 to 2010 compared with 2003 to 2006 (32% versus 10%, P = 0.044). PCI was associated with improved OS (hazard ratio 0.22, 95% CI 0.10 to 0.47, P < 0.001) compared to no PCI in the multivariable analysis., Conclusion: There was an increase in the adoption of PCI for ES-SCLC since 2007. PCI was associated with improved survival in patients who did not have mandatory MRI brain imaging prior to PCI and had stable disease or better after first line chemotherapy, suggesting that the results of the European RCT are reproducible in the real-world practice.

Objectives: This purpose of this study was to examine clinical-pathologic factors--particularly smoking and brain metastases--in EGFR mutation positive (M(+)) lung adenocarcinoma (ADC) to determine their impact on survival in patients treated with first line EGFR TKI., Methods: A retrospective review of EGFR mutation reflex testing experience for all ADC diagnosed at a tertiary Asian cancer centre from January 2009 to April 2013. Amongst this cohort, patients with advanced EGFR M(+) ADC treated with first line EGFR TKI were identified to determine factors that influence progression free and overall survival., Results: 444/742 (59.8%) ADC reflex tested for EGFR mutations were EGFR M(+.) Amongst never-smokers (n=468), EGFR M(+) were found in 74.5% of females and 76.3% of males, and amongst ever smokers (n=283), in 53.3% of females and 35.6% of males. Exon 20 mutations were found more commonly amongst heavy smokers (> 50 pack years and > 20 pack years, Pearson's chi square p=0.044, and p=0.038 respectively). 211 patients treated with palliative first line TKI had a median PFS and OS of 9.2 and 19.6 months respectively. 26% of patients had brain metastasis at diagnosis. This was significantly detrimental to overall survival (HR 1.85, CI 1.09-3.16, p=0.024) on multivariate analysis. There was no evidence that smoking status had a significant impact on survival., Conclusions: The high prevalence of EGFR M(+) in our patient population warrants reflex testing regardless of gender and smoking status. Smoking status and dosage did not impact progression free or overall survival in patients treated with first line EGFR TKI. The presence of brain metastasis at diagnosis negatively impacts overall survival.

This is phase II study evaluating a non-platinum-containing regimen, used in conjunction with radiotherapy, in patients with locally advanced non-small cell lung cancer (NSCLC). Patients with non-resectable stage III NSCLC were treated with two cycles of induction gemcitabine (1000mg/m(2)) and vinorelbine (25mg/m(2)) given on D(1,8) every 21 days, followed by thoracic radiotherapy (60-66Gy) with concurrent weekly vinorelbine (15mg/m(2)). The primary objective was to assess response rate and secondary objectives to assess tolerability and to determine the progression-free survival (PFS) and overall survival (OS). Of the 42 patients enrolled on the study, 15 (36%) achieved a partial response (PR) after induction chemotherapy. After chemo-radiotherapy, five patients had complete response (CR) and 19 patients had PR, giving an overall response rate of 52%. The median PFS was 8 months and median OS was 17 months. The regimen was tolerable, with a 21% grade 3/4 neutropenia rate and 38% grade 2/3 esophagitis rate.

Introduction: The aim of this study was to assess the outcome of radical treatment for stage I non-small cell lung cancer (NSCLC) with external beam radiation therapy., Materials and Methods: A retrospective series of 23 patients with stage I NSCLC treated radically with radiotherapy from September 1997 to December 2004 at the National Cancer Centre, Singapore. Eighteen patients had 3D conformal radiotherapy and 5 patients had 2D planning. The median radiation dose delivered was 55 Gy (range, 50 to 67.5 in 20 to 33 fractions). The estimated median BED(10) was 63.9 Gy (range, 57.6 to 70.1). Complete response (CR) rates, overall survival and cause-specific survival rates were analysed for evaluation of treatment results. Local regional failure was defined as disease in the ipsilateral lung and entire mediastinum. Recurrence at the contralateral lung and other distal organs was defined as distant metastases. Survival data were calculated using the Kaplan-Meier method and tested for significance with log-rank statistics., Results: A total of 23 patients (16 males, 7 females) with a median age of 73 years (range, 45 to 88) were analysed. Six (26%) had stage IA and 17 (74%) had stage IB disease. Eleven patients refused surgery and 12 patients were medically inoperable. The median follow-up was 18.9 months (range, 6.2 to 117.4). The overall survival at 2 years and 3 years was 54.7% and 24.3% respectively. The overall cause-specific survival was 57.4% at 2 years and 25.6% at 3 years. Radiological CR was obtained in 6/23 patients (26%) and the median survival was 24.8 months as compared to 20 months in patients who attained partial response (PR) or unknown response (P = 0.24). The median survival for 12 patients who received a BED(10) of > or =63.9Gy was not reached as compared to 20 months in 11 patients with BED(10) of <63.9 Gy (P = 0.03). Sixteen patients died, 14 due to disease recurrence or progression and 2 of unrelated causes. Seven patients (29.2%) remained alive. The longest surviving patient had a follow-up time of 117.4 months. Four of these 7 patients were disease-free and 3 were alive with disease (2 with bone metastases and 1 with recurrence in the primary site)., Conclusion: Our data are consistent with the reported literature for stage I NSCLC treated with radical radiotherapy. Patients who received a higher dose of radiation have a better outcome. The 3-year cause-specific survival of 25.6% is less than ideal and further investigations into dose escalation with modern radiotherapy techniques and perhaps the addition of chemotherapy or new targeted agents to radiation are warranted to improve the outcome.

It is known that smoking increases the risk for all histological subtypes of lung cancer. To date, the factors that determine why some patients develop small-cell lung cancer (SCLC) while others develop non-small-cell lung cancer (NSCLC) remain unknown. We compared the characteristics of 774 smokers with SCLC and NSCLC diagnosed during the period January 1999 till December 2002. Multivariate logistic regression was used to estimate the odds ratio (OR) with 95% CI. Testing of linear trend across categories of pack-years was also conducted. Six hundred and sixty-five NSCLC were compared to 109 SCLC. Among SCLC, there were significantly more females (20.2% versus 12.8%), current-smokers (81.7% versus 71.9%) as well as smokers who had smoked more than 40 pack-years (75.6% versus 50.3%). Comparing SCLC with NSCLC among the men only, having smoked more than 40 pack-years was associated with a significantly elevated odds ratio (OR) of 3.71 of developing SCLC (95% CI, 1.05-13.1; p=0.041). There was a decreasing trend in OR with increasing smoking cessation period. When comparing SCLC with adenocarcinoma, the women had a higher OR of 2.37 of developing SCLC (95% CI, 1.05-5.31; p=0.037) compared to the men. Our findings suggest that cumulative smoking exposure in terms of pack-years smoked is an important determining factor for the preferred development of SCLC among smokers.

Introduction: The survival and epidemiology of small-cell lung cancer (SCLC) in Singapore has not been described. We aim to present the characteristics as well as determine the survival outcome and important prognostic factors for SCLC patients., Materials and Methods: A retrospective analysis of SCLC patients diagnosed from 1999 to 2002 was conducted at the Outram campus, Singapore. Clinical characteristics and treatment data were obtained from case records and survival data were checked with the registry of births and deaths on 30 May 2005., Results: One hundred and eleven patients were analysed. There were 38 (34.2%) limited-disease (LD) patients and 73 (65.8%) extensive-disease (ED) patients. The majority were current or former smokers (94.7% among LD and 94.5% among ED). More patients with LD had good performance status (92% versus 63%, P = 0.0003) and were treated with combined chemotherapy and radiotherapy (82% versus 48%, P = 0.012). The median survival time of LD patients treated with curative chemoradiotherapy was 14.2 months (95% CI, 10.96 to 17.44). Those given prophylactic cranial irradiation had a median survival time of 16.9 months (95% CI, 11.83 to 21.97). For ED patients, the median survival time was 8.17 months (95%CI, 5.44 to 10.89). None of the factors analysed were significant prognostic factors for LD patients while performance status and type of treatment given were significant among ED patients., Conclusions: We found that the characteristics and survival of SCLC patients in Singapore are fairly similar to that of other countries.

Purpose: Tobacco smoke is a definite causative agent for lung cancer. It is increasingly being recognized that never-smokers can be afflicted with non-small-cell lung cancer (NSCLC). We aim to assess survival differences between smokers and never-smokers with NSCLC., Patients and Methods: We analyzed 975 NSCLC patients who presented from January 1999 to December 2002. Clinical characteristics among current-, former- and never-smokers were tested using chi2 or Kruskal-Wallis test. The hazard ratio (HR) for death and its 95% CI were calculated by Cox regression., Results: Of 975 patients, 59 had no smoking history and 33 had no quit time recorded. Of 883 patients analyzed, 286 patients (32.4%) were never-smokers. One hundred ninety-six never-smokers (68.5%) were females compared with 12% among current- and 13% among former-smokers (P < .001). There was a significant difference in histologic subtype between never-smokers and smokers: 69.9% with adenocarcinoma versus 39.9% (current-smokers) versus 47.3% (former-smokers); 5.9% with squamous cell carcinoma versus 35.7% (current-smokers) versus 28% (former-smokers; P < .001). Smokers had significantly poorer performance status (P = .002) and higher median age at diagnosis (P < .001) while more never-smokers presented with advanced disease (P = .002). Eight hundred and five patients (82.6%) died by May 30, 2005. The HR for smokers was significantly higher on both univariate and multivariate analysis (HR, 1.297; 95% CI, 1.040 to 1.619)., Conclusion: Never-smokers comprised a high proportion of NSCLC patients in Singapore. Definite epidemiologic differences exist between never-smokers and smokers. Differences in survival outcome further suggest that the biology underlying the pathogenesis and behavior of the disease may be different for never-smokers.