Risk model-based management for second primary lung cancer among lung cancer survivors through a validated risk prediction model.

BACKGROUND: Recent therapeutic advances and screening technologies have improved survival among patients with lung cancer, who are now at high risk of developing second primary lung cancer (SPLC). Recently, an SPLC risk-prediction model (called SPLC-RAT) was developed and validated using data from population-based epidemiological cohorts and clinical trials, but real-world validation has been lacking. The predictive performance of SPLC-RAT was evaluated in a hospital-based cohort of lung cancer survivors. METHODS: The authors analyzed data from 8448 ever-smoking patients diagnosed with initial primary lung cancer (IPLC) in 1997-2006 at Mayo Clinic, with each patient followed for SPLC through 2018. The predictive performance of SPLC-RAT and further explored the potential of improving SPLC detection through risk model-based surveillance using SPLC-RAT versus existing clinical surveillance guidelines. RESULTS: Of 8448 IPLC patients, 483 (5.7%) developed SPLC over 26,470 person-years. The application of SPLC-RAT showed high discrimination area under the receiver operating characteristics curve: 0.81). When the cohort was stratified by a 10-year risk threshold of ≥5.6% (i.e., 80th percentile from the SPLC-RAT development cohort), the observed SPLC incidence was significantly elevated in the high-risk versus low-risk subgroup (13.1% vs. 1.1%, p < 1 × 10-6 ). The risk-based surveillance through SPLC-RAT (≥5.6% threshold) outperformed the National Comprehensive Cancer Network guidelines with higher sensitivity (86.4% vs. 79.4%) and specificity (38.9% vs. 30.4%) and required 20% fewer computed tomography follow-ups needed to detect one SPLC (162 vs. 202). CONCLUSION: In a large, hospital-based cohort, the authors validated the predictive performance of SPLC-RAT in identifying high-risk survivors of SPLC and showed its potential to improve SPLC detection through risk-based surveillance. PLAIN LANGUAGE SUMMARY: Lung cancer survivors have a high risk of developing second primary lung cancer (SPLC). However, no evidence-based guidelines for SPLC surveillance are available for lung cancer survivors. Recently, an SPLC risk-prediction model was developed and validated using data from population-based epidemiological cohorts and clinical trials, but real-world validation has been lacking. Using a large, real-world cohort of lung cancer survivors, we showed the high predictive accuracy and risk-stratification ability of the SPLC risk-prediction model. Furthermore, we demonstrated the potential to enhance efficiency in detecting SPLC using risk model-based surveillance strategies compared to the existing consensus-based clinical guidelines, including the National Comprehensive Cancer Network.

Prognostic factors in resected pulmonary carcinoid tumors: A retrospective study with 10 years of follow­up.

The objective of the present study was to characterize the difference in 10-year carcinoid-specific survival (CSS) and disease-free survival (DFS) among patients with resected pulmonary typical carcinoid (TC) and atypical carcinoid (AC). Patients diagnosed with pulmonary carcinoid tumors (PCT) between January 1, 1997, and December 31, 2016, were identified. All patients underwent video-assisted thoracoscopic surgery or thoracotomy with thoracic lymphadenectomy. Cumulative CSS was estimated using the Kaplan-Meier model. The analysis of hazard ratios (HRs) and 95% confidence intervals (CIs) was performed using univariate and multivariate Cox proportional hazards models. A total of 404 patients with PCT were included in the present study. The 10-year CSS and DFS rates of patients with AC were significantly worse than those of patients with TC (49.1 vs. 86.8% and 52.2 vs. 92.6%, respectively; P<0.001). In the CSS multivariate analysis, older age and lymph node involvement (HR, 2.45; P=0.022) were associated with worse survival in AC, while age, male sex, M1 stage, cigarette smoking and inadequate N2 lymphadenectomy were associate with worse survival in TC. In the recurrence multivariate analysis, N1-3 stage (HR, 2.62; 95% CI, 1.16-5.95; P=0.018) and inadequate N2 lymphadenectomy (HR, 2.13; 95% CI, 1.04-4.39; P=0.041) were associated with an increase in recurrence in AC, while male sex (HR, 3.72; 95% CI, 1.33-10.42; P=0.010) and M1 stage (HR, 14.93; 95% CI, 4.77-46.77; P<0.001) were associated with an increase in recurrence in TC. In conclusion, patients with AC tumors had significantly worse CSS and DFS rates compared with patients with TC. The degree of nodal involvement in AC was a prognostic marker, in contrast to that in TC. Inadequate lymphadenectomy increased the risk of recurrence in AC and mortality in TC, although surgical approaches did not have a significant impact. The present study therefore emphasizes the importance of mediastinal nodal dissection in patients with PCTs.

Gastroesophageal reflux disease and paraneoplastic neurological syndrome associated with long-term survival in limited stage small-cell lung cancer.

INTRODUCTION: Patients with small-cell lung cancer (SCLC) have a very poor prognosis. However, a subset of SCLC achieves long-term survival. The objective of this study was to investigate factors and pattern of long-term survival in patients with limited-stage small cell lung cancer (LS-SCLC) who achieved a complete response (CR) after chemoradiotherapy. PATIENT AND METHODS: This was a single-center retrospective study. The analysis of hazard ratio (HR) and 95% confidence interval (CI) was performed using Cox proportional hazards model. For pattern analysis, the date of recurrence was used as the endpoint. The nominal categorical variables were analyzed by the χ2 test. Survival was estimated using the Kaplan-Meier model, and the results were reported as the median and interquartile range. RESULTS: We identified 162 patients, median age was 64.7 (56.2-70.2) years, and 94 (58%) were females. Eighty-one patients (50%) had recurrence during follow-up. Gastroesophageal reflux disease (GERD) (HR, 0.65; 95% CI, 0.45-0.93; p = 0.016) and neurological paraneoplastic syndrome (PNS) (HR, 0.46; 95% CI, 0.29-0.72; p < 0.001) were independent factors associated with improved overall survival (OS). Patients with GERD had prolonged recurrence free survival (RFS) compared to patients without GERD (median, 29.1 months vs. 13.9 months, p < 0.001), whereas patients with neurological PNS had a reduced recurrence rate compared to those patients without neurological PNS (No. [%], 8 [20.5] vs. 73 [59.3], p < 0.001). CONCLUSIONS: Patients with LS-SCLC achieving a CR after chemoradiotherapy, GERD, and neurological PNS were associated with improved OS. GERD and neurological PNS were associated with longer RFS and lower recurrence rate, respectively.

Real-world efficacy of osimertinib in previously EGFR-TKI treated NSCLC patients without identification of T790M mutation.

BACKGROUND: The efficacy of osimertinib in previously EGFR-TKI-treated NSCLC without identification of T790M mutational status remains unclear in real-world practice. PATIENTS AND METHODS: 417 patients had stage III-IV NSCLC harboring EGFR mutation and 154 out of 417 patients receiving osimertinib as ≥ second-line EGFR-TKI were identified. The time to treatment failure and risk of death were analyzed. RESULTS: Higher risk of death was found in EGFR-mutant patients with age ≥ 65 years, non-adenocarcinoma, no surgery or radiation, non-exon 19 deletion/exon 21 L858R, higher ECOG PS (2-4), PD-L1 expression ≥ 50%, and bone/liver/adrenal metastasis (all p < 0.05). Osimertinib as ≥ second-line TKI in patients with/without identification of T790M revealed lower risk of death compared to first-line first/second generation TKI without subsequent osimertinib (p = 0.0002; 0.0232, respectively). However, osimertinib-treated patients with T790M did not have superior survival than those without (p = 0.2803). A higher risk of treatment failure for osimertinib was found in males, patients with first-line TKI duration ≤ 12 months, BMI drop > 10%, and PD-L1 expression ≥ 50% (All p < 0.05). Nonetheless, osimertinib as ≥ second-line TKI in patients without identification of 790 M did not have higher risk of treatment failure than those with T790M (p = 0.1236). CONCLUSIONS: This study demonstrates that osimertinib as second line or subsequent TKI in EGFR-TKI-treated patients without identification of T790M revealed lower risk of death compared to first-line first/second generation TKI without subsequent osimertinib, in real-world practice. Additionally, EGFR-mutant patients with PD-L1 expression ≥ 50% had a higher risk of treatment failure for osimertinib and worse overall survival than those with PD-L1 expression < 50%. These results suggest that osimertinib as second line or subsequent TKI may be a potential alternative option for the treatment of patients without identification of T790M and PD-L1 expression ≥ 50% is associated with a significantly poor outcome in patients receiving osimertinib.

Timing of chronic obstructive pulmonary disease diagnosis in lung cancer prognosis: a clinical and genomic-based study.

BACKGROUND: A two-phase study (clinical and genomic-based) was conducted to evaluate the effect of timing of chronic obstructive pulmonary disease (COPD) diagnosis on lung cancer outcomes. METHODS: The prognostic influence of COPD was investigated in a clinical cohort of 1,986 patients who received surgery for stage I lung cancer; 823 (41.4%) of them also had COPD, including 549 (27.6%) incidental COPD (diagnosed within 6-months of lung cancer diagnosis) and 274 (13.8%) prior COPD (>6 months before lung cancer diagnosis). The genomic variations were analyzed from another cohort of 1,549 patients for association with 384 lung cancer-related single nucleotide polymorphisms (SNPs). RESULTS: Older age (≥70 years), smokers, and respiratory symptoms were independent predictors of incidental COPD in lung cancer (all P<0.05). Similar to prior COPD, incidental COPD increased postoperative complications and worsened quality-of-life related to dyspnea (both P<0.05). Multivariate Cox regression analysis showed lung cancer survival decreased significantly in incidental COPD (HR, 1.30; 95% CI, 1.02-1.66), but not in prior COPD (HR, 1.15; 95% CI, 0.87-1.52). Among prior COPD, median survival showed a trend for being better in those with fewer exacerbations (0-1 vs. ≥2 exacerbation/year; 6.1 vs. 4.1 years; P=0.10). The SNP-based analysis identified ADCY2:rs52827085 was significantly associated with risk of incidental COPD (OR, 1.76; 95% CI, 1.30-2.38) and NRXN1:rs1356888 associated with prior COPD complicated with lung cancer (OR, 1.73; 95% CI, 1.29-2.33). CONCLUSIONS: Different long-term survival and genomic variants were observed between lung cancer patients with incidental and with prior COPD, suggesting timing of COPD diagnosis should be considered in lung cancer clinical management and mechanistic research.

Efficient and Accurate Extracting of Unstructured EHRs on Cancer Therapy Responses for the Development of RECIST Natural Language Processing Tools: Part I, the Corpus.

PURPOSE: Electronic health records (EHRs) are created primarily for nonresearch purposes; thus, the amounts of data are enormous, and the data are crude, heterogeneous, incomplete, and largely unstructured, presenting challenges to effective analyses for timely, reliable results. Particularly, research dealing with clinical notes relevant to patient care and outcome is seldom conducted, due to the complexity of data extraction and accurate annotation in the past. RECIST is a set of widely accepted research criteria to evaluate tumor response in patients undergoing antineoplastic therapy. The aim for this study was to identify textual sources for RECIST information in EHRs and to develop a corpus of pharmacotherapy and response entities for development of natural language processing tools. METHODS: We focused on pharmacotherapies and patient responses, using 55,120 medical notes (n = 72 types) in Mayo Clinic's EHRs from 622 randomly selected patients who signed authorization for research. Using the Multidocument Annotation Environment tool, we applied and evaluated predefined keywords, and time interval and note-type filters for identifying RECIST information and established a gold standard data set for patient outcome research. RESULTS: Key words reduced clinical notes to 37,406, and using four note types within 12 months postdiagnosis further reduced the number of notes to 5,005 that were manually annotated, which covered 97.9% of all cases (n = 609 of 622). The resulting data set of 609 cases (n = 503 for training and n = 106 for validation purpose), contains 736 fully annotated, deidentified clinical notes, with pharmacotherapies and four response end points: complete response, partial response, stable disease, and progressive disease. This resource is readily expandable to specific drugs, regimens, and most solid tumors. CONCLUSION: We have established a gold standard data set to accommodate development of biomedical informatics tools in accelerating research into antineoplastic therapeutic response.

Natural language processing for populating lung cancer clinical research data.

BACKGROUND: Lung cancer is the second most common cancer for men and women; the wide adoption of electronic health records (EHRs) offers a potential to accelerate cohort-related epidemiological studies using informatics approaches. Since manual extraction from large volumes of text materials is time consuming and labor intensive, some efforts have emerged to automatically extract information from text for lung cancer patients using natural language processing (NLP), an artificial intelligence technique. METHODS: In this study, using an existing cohort of 2311 lung cancer patients with information about stage, histology, tumor grade, and therapies (chemotherapy, radiotherapy and surgery) manually ascertained, we developed and evaluated an NLP system to extract information on these variables automatically for the same patients from clinical narratives including clinical notes, pathology reports and surgery reports. RESULTS: Evaluation showed promising results with the recalls for stage, histology, tumor grade, and therapies achieving 89, 98, 78, and 100% respectively and the precisions were 70, 88, 90, and 100% respectively. CONCLUSION: This study demonstrated the feasibility and accuracy of automatically extracting pre-defined information from clinical narratives for lung cancer research.

5-year overall survival in patients with lung cancer eligible or ineligible for screening according to US Preventive Services Task Force criteria: a prospective, observational cohort study.

BACKGROUND: The US Preventive Services Task Force (USPSTF) recommends lung cancer screening among individuals aged 55-80 years with a 30 pack-year cigarette smoking history and, if they are former smokers, those who quit within the past 15 years. Our previous report found that two-thirds of newly diagnosed patients with lung cancer do not meet these criteria; they are reported to be either long-term quitters (≥15 years since quitting) or from a younger age group (age 50-54 years). We aimed to assess survival outcomes in these two subgroups. METHODS: For this prospective, observational cohort study we identified and followed up patients aged 50-80 years with lung cancer, with a smoking history of 30 pack-years or more, and included both current smokers and former smokers who quit within the past 30 years. We identified patients from two cohorts in the USA: a hospital cohort (Mayo Clinic, Rochester, MN) and a community cohort (Olmsted County, MN). Patients were divided into those meeting USPSTF criteria (USPSTF group) versus those not meeting USPSTF criteria (long-term quitters or the younger age group). The main outcome was overall survival at 5 years after diagnosis. 5-year overall survival was analysed with and without matching age and pack-years smoked for long-term quitters. The USPSTF group was subdivided into two age subgroups (55-69 years and 70-80 years) for multivariable regression analysis. FINDINGS: Between Jan 1, 1997, and Dec 31, 2017, 8739 patients with lung cancer were identified and followed up. Median follow-up was 6·5 (IQR 3·8-10·0) years, and median overall survival was 16·9 months (95% CI 16·2-17·5). 5-year overall survival was 27% (95% CI 25-30) in long-term quitters, 22% (19-25) in the younger age group, and 23% (22-24) in the USPSTF group. In both cohorts, 5-year overall survival did not differ significantly between long-term quitters and the USPSTF group (hospital cohort: hazard ratio [HR] 1·02 [95% CI 0·94-1·10]; p=0·72; community cohort: 0·97 [0·75-1·26]; p=0·82); matched analysis showed similar results in both cohorts. 5-year overall survival also did not differ significantly between the younger age group and the USPSTF group in both cohorts (hospital cohort: HR 1·16 [95% CI 0·98-1·38], p=0·08; community cohort: 1·16 [0·74-1·82]; p=0·52); multivariable regression analyses stratified by age group yielded similar findings. INTERPRETATION: Patients with lung cancer who quit 15 or more years before diagnosis and those who are up to 5 years younger than the age cutoff recommended for screening, but otherwise meet USPSTF criteria, have a similar risk of death to those individuals who meet all USPSTF criteria. Individuals in both subgroups could benefit from screening, as expansion of USPSTF screening criteria to include these subgroups could enable earlier detection of lung cancer and improved survival outcomes. FUNDING: National Institutes of Health and the Mayo Clinic Foundation.

Small-cell Lung Cancer in Very Elderly (≥ 80 Years) Patients.

BACKGROUND: This analysis was performed to describe the outcome of very elderly (≥ 80 years) patients with small-cell lung cancer (SCLC) as there is no published data regarding these patients. MATERIALS AND METHODS: One hundred forty-six very elderly patients with SCLC were identified from the Institutional Lung Cancer Database ranging in age from 80 to 92 years (median, 82 years). Of these, 47 (32%) patients had limited-stage SCLC (L-SCLC), and 99 (68%) had extensive-stage SCLC (E-SCLC). All were Caucasian, and the majority (64%) were female. Sixty-seven (46%) patients had Zubrod performance status (PS) of 0 to 1. RESULTS: Of the 146 patients, 44 (30%) received no therapy, 65 (45%) received chemotherapy alone, 27 (19%) received chemotherapy plus local therapy (thoracic radiotherapy [TRT] or surgery), and 10 (7%) received local therapy alone. The median survival was 5.4 months. On univariable analysis, age (P = .019), stage (L-SCLC vs. E-SCLC; P = .0002), PS (P < .0001), and treatment option (P < .0001) were associated with survival. On multivariable analysis, stage (P = .011), PS (P = .029), and treatment option (P < .0001) maintained significance. For entire cohort, the median survival was 1.3 months without active therapy, 6 months with local therapy alone, 7.2 months with chemotherapy alone, and 14.4 months with chemotherapy plus local therapy (P < .0001, univariable and multivariable). Similar survival findings in response to treatment were found when the L-SCLC and E-SCLC cohorts were separately analyzed. CONCLUSIONS: The survival of very elderly patients with SCLC was associated with stage (L-SCLC vs. E-SCLC), PS, and treatment option. Very elderly patients with SCLC often have limited functional reserve required to tolerate aggressive multimodality therapy but appeared to benefit from it. Geriatric assessments, careful monitoring, and extra support are warranted in elderly patients. Care should be individualized based on the desires and needs of each patient.

Information Extraction for Populating Lung Cancer Clinical Research Data.

Lung cancer is the second most common cancer and the wide adoption of electronic health records (EHRs) offers a potential of accelerating cohort-related epidemiological studies using informatics approaches. In this study, we developed and evaluated a natural language processing (NLP) system to extract information on stage, histology, grade and therapies (chemotherapy, radiotherapy and surgery) automatically for lung cancer patients from clinical narratives including clinical notes, pathology reports and surgery reports. Evaluation showed promising results with the recalls for stage, histology, grade, and therapies achieving 89%, 98%, 80%, and 100% respectively and the precisions were 71%, 89%, 90%, and 100% respectively. This study demonstrated the feasibility and accuracy of extracting related information from clinical narratives for lung cancer research.

Achievability to Extract Specific Date Information for Cancer Research.

Accurate identification of temporal information such as date is crucial for advancing cancer research which often requires precise date information associated with related cancer events. However, there is a gap for existing natural language processing (NLP) systems to identify dates for specific cancer research studies. Illustrated with two case studies, we investigated the feasibility, evaluated the performances and discussed the challenges of date information extraction for cancer research.

Pulmonary invasive mucinous adenocarcinoma and mixed invasive mucinous/nonmucinous adenocarcinoma-a clinicopathological and molecular genetic study with survival analysis.

Invasive mucinous adenocarcinoma is a variant of lung adenocarcinoma, which may be mixed with nonmucinous adenocarcinoma. KRAS mutations are common, but other clinical and genetic features are not clearly established. Lung adenocarcinomas (n=760) with ≥5 years of follow-up comprised 3 nonoverlapping cohorts for survival analysis. Mucinous tumors were evaluated with Ion AmpliSeq Cancer Hotspot Panel v2. Cases without detected mutations were tested for ALK and ROS1 and by OncoScan array. Fifty-seven invasive mucinous adenocarcinomas and 54 mixed mucinous/nonmucinous adenocarcinomas were identified. Mucinous tumors constituted 27 of 218 nonselected patients (12.4%), 23 of 268 never-smokers (8.6%), and 61 of 274 in a smokers cohort enriched for lepidic growth (22.3%). In the lepidic-enriched smokers, patients with mucinous tumors experienced worse overall survival (P=.006) and progression-free survival (P=.024), which persisted on multivariable analysis. No survival differences were observed in the other cohorts. KRAS mutations were common (76% of invasive mucinous adenocarcinomas, 68% of mixed mucinous/nonmucinous), and 38% of KRAS mutations occurred with other mutations, especially STK11. Six cases had potentially targetable mutations (3 ALK, 2 EGFR, 1 BRAF V600E). All ALK-rearranged tumors were mixed mucinous/nonmucinous. Four of 6 cases without hotspot mutations showed complex copy number/structural abnormalities. Pulmonary invasive mucinous adenocarcinomas and mixed nonmucinous/mucinous adenocarcinomas are clinically and genetically similar, except for a higher rate of ALK rearrangement in mixed tumors. Survival for mucinous tumors is similar to that for nonmucinous tumors in a nonselected cohort, although worse survival was seen in a cohort of smokers enriched for lepidic growth.

T category of non-small cell lung cancer invading the fissure to the adjacent lobe.

BACKGROUND: Dispute arises in the tumor category of non-small cell lung cancer invading the fissure to the adjacent lobe. The purpose of this study is to determine the long-term prognosis of non-small cell lung cancer with such an invasion and to propose an appropriate T category. METHODS: In total, 53 cases of non-small cell lung cancer invading the fissure to the adjacent lobe (fissure group) were identified in patients who underwent pulmonary resection from 1997 to 2014. Propensity score matching was applied to balance known confounders for prognosis between each paired group, resulting in 3 matched sets (fissure vs T2a, fissure vs T2b, and fissure vs T3). The overall survival of the fissure group was compared with the survival of patients with T2a, T2b, and T3 diseases, as classified in the eighth edition of TNM classification. RESULTS: The 5-year survivals of the T2a, T2b, T3, and fissure groups were 64.2% (95% confidence interval, 53.2-72.6), 54.6% (95% confidence interval, 44.7-65.8), 35.8% (95% confidence interval, 22.8-44.2), and 38.6% (95% confidence interval, 25.0-52.2), respectively. Specifically, the difference between the fissure group and T2a is statistically significant at P = .01; between the fissure group and T2b at P = .02; and between the fissure group and T3 at P = .93. Multivariate analyses indicate that the fissure group had a similar risk of dying as the T3 disease group (hazard ratio, 1.10; 95% confidence interval, 0.69-1.37) and was at a significantly higher risk compared with the T2a group (hazard ratio, 2.34; 95% confidence interval, 1.50-3.39) and T2b group (hazard ratio, 1.71; 95% confidence interval, 1.19-2.76). CONCLUSIONS: On the basis of our single-institution study, we propose that non-small cell lung cancer invading the fissure to the adjacent lobe should be further investigated and the impact on patients' prognoses validated as a T3 disease.

Chest wall resection for non-small cell lung cancer: A case-matched study of postoperative pulmonary function and quality of life.

BACKGROUND: To assess the pulmonary function and quality of life (QOL) after chest wall resection for non-small cell lung cancer. MATERIAL AND METHODS: One hundred and thirty-five patients (cases) who underwent pulmonary resection with chest wall removal were identified from January 1997 to December 2015. Propensity score matching (1:3) was applied to balance known confounders for pulmonary function and QOL between the cases and the control group who underwent pulmonary resection without chest wall invasion. Matched analyses were performed to compare perioperative mortality and morbidity, postoperative pulmonary function, overall QOL, and specific symptoms. RESULTS: Perioperative mortality and morbidity did not differ significantly between cases and controls, but the hospital stay was longer in cases than in controls (mean, 12.8 vs 8.9days; p<0.001), The decline of postoperative pulmonary forced vital capacity (FVC) and the percentage of predicted FVC (FVC%) was more obvious in cases than in controls at 6 months and 2 years after surgery, but there was no obvious decline in the forced expiratory volume in one second (FEV1), the percentage of predicted FEV1 (FEV1%), the diffusion capacity of the lung for carbon monoxide (DLCO) and the percentage of predicted DLCO (DLCO%) in cases compared with controls. No significant difference was observed between the two groups in scores for overall QOL, pain, fatigue, cough, dyspnea, appetite, hemoptysis, lung cancer symptoms, and normal activities. CONCLUSIONS: When chest wall resection is inevitable, it does not worse the QOL and pulmonary function of patients who underwent pulmonary resection with chest wall removal obviously compared with patients underwent pulmonary resection without chest wall invasion.

Regional Emphysema Score Predicting Overall Survival, Quality of Life, and Pulmonary Function Recovery in Early-Stage Lung Cancer Patients.

INTRODUCTION: Pulmonary emphysema is a frequent comorbidity in lung cancer, but its role in tumor prognosis remains obscure. Our aim was to evaluate the impact of the regional emphysema score (RES) on a patient's overall survival, quality of life (QOL), and recovery of pulmonary function in stage I to II lung cancer. METHODS: Between 1997 and 2009, a total of 1073 patients were identified and divided into two surgical groups-cancer in the emphysematous (group 1 [n = 565]) and nonemphysematous (group 2 [n = 435]) regions-and one nonsurgical group (group 3 [n = 73]). RES was derived from the emphysematous region and categorized as mild (≤5%), moderate (6%-24%), or severe (25%-60%). RESULTS: In group 1, patients with a moderate or severe RES experienced slight decreases in postoperative forced expiratory volume in 1 second, but increases in the ratio of forced expiratory volume in 1 second to forced vital capacity compared with those with a mild RES (p < 0.01); however, this correlation was not observed in group 2. Posttreatment QOL was lower in patients with higher RESs in all groups, mainly owing to dyspnea (p < 0.05). Cox regression analysis revealed that patients with a higher RES had significantly poorer survival in both surgical groups, with adjusted hazard ratios of 1.41 and 1.43 for a moderate RES and 1.63 and 2.04 for a severe RES, respectively; however, this association was insignificant in the nonsurgical group (adjusted hazard ratio of 0.99 for a moderate or severe RES). CONCLUSIONS: In surgically treated patients with cancer in the emphysematous region, RES is associated with postoperative changes in lung function. RES is also predictive of posttreatment QOL related to dyspnea in early-stage lung cancer. In both surgical groups, RES is an independent predictor of survival.

Genetic Risk Can Be Decreased: Quitting Smoking Decreases and Delays Lung Cancer for Smokers With High and Low CHRNA5 Risk Genotypes - A Meta-Analysis.

BACKGROUND: Recent meta-analyses show that individuals with high risk variants in CHRNA5 on chromosome 15q25 are likely to develop lung cancer earlier than those with low-risk genotypes. The same high-risk genetic variants also predict nicotine dependence and delayed smoking cessation. It is unclear whether smoking cessation confers the same benefits in terms of lung cancer risk reduction for those who possess CHRNA5 risk variants versus those who do not. METHODS: Meta-analyses examined the association between smoking cessation and lung cancer risk in 15 studies of individuals with European ancestry who possessed varying rs16969968 genotypes (N=12,690 ever smokers, including 6988 cases of lung cancer and 5702 controls) in the International Lung Cancer Consortium. RESULTS: Smoking cessation (former vs. current smokers) was associated with a lower likelihood of lung cancer (OR=0.48, 95%CI=0.30-0.75, p=0.0015). Among lung cancer patients, smoking cessation was associated with a 7-year delay in median age of lung cancer diagnosis (HR=0.68, 95%CI=0.61-0.77, p=4.9∗10-10). The CHRNA5 rs16969968 risk genotype (AA) was associated with increased risk and earlier diagnosis for lung cancer, but the beneficial effects of smoking cessation were very similar in those with and without the risk genotype. CONCLUSION: We demonstrate that quitting smoking is highly beneficial in reducing lung cancer risks for smokers regardless of their CHRNA5 rs16969968 genetic risk status. Smokers with high-risk CHRNA5 genotypes, on average, can largely eliminate their elevated genetic risk for lung cancer by quitting smoking- cutting their risk of lung cancer in half and delaying its onset by 7years for those who develop it. These results: 1) underscore the potential value of smoking cessation for all smokers, 2) suggest that CHRNA5 rs16969968 genotype affects lung cancer diagnosis through its effects on smoking, and 3) have potential value for framing preventive interventions for those who smoke.

Multiple-level validation identifies PARK2 in the development of lung cancer and chronic obstructive pulmonary disease.

An important precursor to lung cancer development is chronic obstructive pulmonary disease (COPD), independent of exposure to tobacco smoke. Both diseases are associated with increased host susceptibility, inflammation, and genomic instability. However, validation of the candidate genes and functional confirmation to test shared genetic contribution and cellular mechanisms to the development of lung cancer in patients with COPD remains underexplored. Here, we show that loss of PARK2 (encoding Parkin) increases the expression of proinflammation factors as well as nuclear NF-κB localization, suggesting a role of PARK2 loss in inflammation. Additional exploration showed that PARK2 deficiency promotes genomic instability and cell transformation. This role of PARK2 in inflammation and chromosome instability provides a potential link among Parkin, COPD and lung cancer. A further comprehensive validation of 114 informative single nucleotide polymorphism (SNP) variants of PARK2, in 2,484 cases and controls with well-defined lung cancer and COPD phenotypes, found rs577876, rs6455728 and rs9346917 (p<0.01) to be significantly associated with lung cancer development in people with COPD. Our findings support the evidence that PARK2 might have a tumor suppressor role in the development of COPD and lung cancer.

Impact of self-reported physical activity and health promotion behaviors on lung cancer survivorship.

BACKGROUND: There is some initial evidence that an enhanced physical activity level can improve fquality of life, and possibly survival among patients with lung cancer. The primary aim of this project was to evaluate the impact of physical activity on the quality and quantity of life of lung cancer survivors. METHODS: Between January 1, 1997, and December 31, 2009, a total of 1466 lung cancer survivors completed a questionnaire with patient-reported outcomes for quality of life (QOL), demographics, disease and clinical characteristics, and a measure of physical activity (Baecke Questionnaire). Chi-square tests compared lung cancer survivors who reported being physically active versus not on a variety of the other covariates. Kaplan-Meier estimates and Cox models evaluated the prognostic importance of physical activity level on Overall Survival (OS). RESULTS: Roughly half of the lung cancer survivors had advanced stage disease at the time of survey. Treatment prevalence rates were 61, 54, and 33 % for surgery, chemotherapy and radiotherapy, respectively. The majority (77 %) of survivors reported themselves as physically active. Physically active survivors reported greater activity across all individual Baecke items. Lung cancer survivor-reported QOL indicated the benefits of physical activity in all domains. Survivors receiving chemotherapy or radiation at the time of questionnaire completion were less likely to be physically active (74 and 73 % respectively). In contrast, 84 % of surgical patients were physically active. Disease recurrence rates were the same for physically active and inactive patients (81 % vs 82 %, p = 0.62). Physically active patients survived an average of 4 more years than those who were not physically active (8.4 years versus 4.4 years respectively, log rank p < 0.0001). CONCLUSIONS: Being physically active was related to profound advantages in QOL and survival in a large sample of lung cancer survivors.