Effect of treatment center volume on outcomes in gastroenteropancreatic neuroendocrine tumor patients.

BACKGROUND: Medical centers with varying levels of expertise treat gastroenteropancreatic neuroendocrine tumors (GEP-NETs), which are relatively rare tumors. This study assesses the impact of center volume on GEP-NET treatment outcomes. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) registry linked to Medicare claims data. The data includes patients diagnosed between 1995 and 2010 who had no health maintenance organization (HMO) coverage, participated in Medicare parts A and B, were older than 65 at diagnosis, had tumor differentiation information, and had no secondary cancer. We identified medical centers at which patients received GEP-NET treatment (surgery, chemotherapy, somatostatin analogues, or radiation therapy) using Medicare claims data. Center volume was divided into 3 tiers - low, medium, and high - based on the number of unique GEP-NET patients treated by a medical center over 2 years. We used Kaplan-Meier curves and Cox regression to assess the association between volume and disease-specific survival. RESULTS: We identified 899 GEP-NET patients, of whom 37, 45, and 18% received treatment at low, medium volume, and high-volume centers, respectively. Median disease-specific survival for patients at low and medium tiers were 1.4 years and 5.3 years, respectively, but was not reached for patients at high volume centers. Results showed that patients treated at high volume centers had better survival than those treated in low volume centers (HR: 0.63, 95% CI: 0.4-0.9), but showed no difference in outcomes between medium and high-volume centers. CONCLUSIONS: Our results suggest that for these increasingly common tumors, referral to a tertiary care center may be indicated. Physicians caring for GEP-NET patients should consider early referral to high volume centers.

Racial Disparities in Resection of Early Stage Non-Small Cell Lung Cancer: Variability Among Surgeons.

BACKGROUND: Racial disparities in resection of non-small cell lung cancer (NSCLC) are well documented. Patient-level and system-level factors only partially explain these findings. Although physician-related factors have been suggested as mediators, empirical evidence for their contribution is limited. OBJECTIVE: To determine if racial disparities in receipt of thoracic surgery persisted after patients had a surgical consultation and whether there was a physician contribution to disparities in care. METHODS: The authors identified 19,624 patients with stage I-II NSCLC above 65 years of age from the Surveillance-Epidemiology and End-Results-Medicare database. They studied black and white patients evaluated by a surgeon within 6 months of diagnosis. They assessed for racial differences in resection rates among surgeons using hierarchical linear modeling. Our main outcome was receipt of NSCLC resection. A random intercept was included to test for variability in resection rates across surgeons. Interaction between patient race and the random surgeon intercept was used to evaluate for heterogeneity between surgeons in resection rates for black versus white patients. RESULTS: After surgical consultation, black patients were less likely to undergo resection (adjusted odds ratio, 0.57; 95% confidence interval, 0.47-0.69). Resection rates varied significantly between surgeons (P<0.001). A significant interaction between the surgeon intercept and race (P<0.05) showed variability beyond chance across surgeons in resection rates of black versus white patients. When the model included thoracic surgery specifalization the physician contribution to disparities in care was decreased. CONCLUSIONS: Racial disparities in resection of NSCLC exist even among patients who had access to a surgeon. Heterogeneity between surgeons in resection rates between black and white patients suggests a physician's contribution to observed racial disparities. Specialization in thoracic surgery attenuated this contribution.

The effect of radiographic emphysema in assessing lung cancer risk.

PURPOSE: Lung cancer risk models optimise screening by identifying subjects at highest risk, but none of them consider emphysema, a risk factor identifiable on baseline screen. Subjects with a negative baseline low-dose CT (LDCT) screen are at lower risk for subsequent diagnosis and may benefit from risk stratification prior to additional screening, thus we investigated the role of radiographic emphysema as an additional predictor of lung cancer diagnosis in participants with negative baseline LDCT screens of the National Lung Screening Trial. METHODS: Our cohorts consist of participants with a negative baseline (T0) LDCT screen (n=16 624) and participants who subsequently had a negative 1-year follow-up (T1) screen (n=14 530). Lung cancer risk scores were calculated using the Bach, PLCOm2012 and Liverpool Lung Project models. Risk of incident lung cancer diagnosis at the end of the study and number screened per incident lung cancer were compared between participants with and without radiographic emphysema. RESULTS: Radiographic emphysema was independently associated with nearly double the hazard of lung cancer diagnosis at both the second (T1) and third (T2) annual LDCT in all three risk models (HR range 1.9-2.0, p<0.001 for all comparisons). The number screened per incident lung cancer was considerably lower in participants with radiographic emphysema (62 vs 28 at T1 and 91 vs 40 at T2). CONCLUSION: Radiographic emphysema is an independent predictor of lung cancer diagnosis and may help guide decisions surrounding further screening for eligible patients.

Assessing the extent of non-aggressive cancer in clinically detected stage I non-small cell lung cancer.

BACKGROUND: Overdiagnosis among clinically detected lung cancers likely consists of cases that are non-aggressive and slowly progressive and will never disseminate, cause symptoms or be a threat to a subject's survival, even if untreated. In this study, we estimate the prevalence of non-aggressive lung cancers from a large, population-based cancer registry. METHODS: We identified individuals ≥65 years with histologically confirmed, untreated stage I non-small cell lung cancers (NSCLCs) from the Surveillance, Epidemiology, and End Results-Medicare registry. We estimated the rate of non-aggressive lung cancers by determining the point at which the cumulative lung cancer-specific survival curve no longer changed (ie, the slope approaches zero). At this point, there are no additional deaths due to progressive lung cancer observed among untreated patients after adjusting for deaths from competing risks (these long-term survivors can be considered 'non-aggressive cases). RESULTS: The overall rate of non-aggressive cancers among 2197 clinically detected cases of untreated stage I NSCLC was 2.4%, 95% CI: 1.0% to 3.8%. The rate of non-aggressive cancer was 1.9% (95% CI: 0.0% to 4.9%) for women and 2.4% (95% CI: 0.7% to 4.1%) for men (p=0.84). When stratifying by tumour size, non-aggressive cancer rates were 10.2% (95% CI: 0.0% to 29.3%), 2.1% (95% CI: 0.0% to 9.2%), 4.9% (95% CI: 0.0% to 10.3%), 1.8% (95% CI: 0.0% to 5.2%) and 0.0% (95% CI: 0.0% to 1.0%) for tumour sizes <15 mm, 15-24 mm, 25-34 mm, 35-44 mm and ≥45 mm, respectively. In comparison with the smallest tumour sizes (<15 mm), the rates of non-aggressive cancers were not statistically significantly different for tumour sizes 15-24 mm (p=0.36), 25-34 mm (p=0.57), 35-44 mm (p=0.38) and tumour sizes >45 mm (p=0.30). DISCUSSION: We found relatively low rates of non-aggressive cancers among clinically detected, stage I NSCLC regardless of sex or size. Our findings suggest that most clinically diagnosed early stage cancers should be treated with curative intent.

Assessing the association of obesity and asthma morbidity in older adults.

BACKGROUND: Obesity is a robust predictor of poor asthma control in younger adults. Given the high prevalence of asthma and obesity in older Americans, weight reduction could benefit asthma management in this population. OBJECTIVE: To assess the association between obesity and asthma outcomes among older adults. METHODS: We recruited from urban primary care clinics a prospective cohort of nonsmoking individuals with asthma who were 60 years or older without a history of other respiratory diseases. At baseline, body mass index (BMI) measurements were classified as normal (BMI, 18-25), overweight (BMI, 25-30), or obese (BMI, >30). Measures of asthma morbidity (Asthma Control Questionnaire [ACQ], and Mini Asthma Quality of Life Questionnaire [Mini-AQLQ]) and asthma-related resource utilization (inpatient or outpatient) were taken at baseline and at 3- and 12-month interviews. We used generalized estimating equation models to assess associations between obesity and asthma outcomes after controlling for potential confounders. RESULTS: Of the 437 older adults with asthma in the study, 17% had a normal BMI, 32% were overweight, and 51% were obese. Unadjusted analyses revealed that obesity was associated with lower ACQ scores (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.09-1.31) and poorer Mini-AQLQ scores (OR, 1.21; 95% CI, 1.11-1.33). Adjusted analyses revealed no significant association between obesity and ACQ (OR, 1.05; 95% CI, 0.96-1.15) and Mini-AQLQ (OR, 1.08; 95% CI, 0.99-1.19). CONCLUSION: Our study suggests that obesity is not independently associated with worse asthma outcomes in older adults, reflecting potential differences in the mechanisms that link obesity with asthma control in older vs younger populations.

Survival of patients with stage IV lung cancer with diabetes treated with metformin.

RATIONALE: Prior studies have shown an anticancer effect of metformin in patients with breast and colorectal cancer. It is unclear, however, whether metformin has a mortality benefit in lung cancer. OBJECTIVES: To compare overall survival of patients with diabetes with stage IV non-small cell lung cancer (NSCLC) taking metformin versus those not on metformin. METHODS: Using data from the Surveillance, Epidemiology, and End Results registry linked to Medicare claims, we identified 750 patients with diabetes 65-80 years of age diagnosed with stage IV NSCLC between 2007 and 2009. We used propensity score methods to assess the association of metformin use with overall survival while controlling for potential confounders. MEASUREMENTS AND MAIN RESULTS: Overall, 61% of patients were on metformin at the time of lung cancer diagnosis. Median survival in the metformin group was 5 months, compared with 3 months in patients not treated with metformin (P < 0.001). Propensity score analyses showed that metformin use was associated with a statistically significant improvement in survival (hazard ratio, 0.80; 95% confidence interval, 0.71-0.89), after controlling for sociodemographics, diabetes severity, other diabetes medications, cancer characteristics, and treatment. CONCLUSIONS: Metformin is associated with improved survival among patients with diabetes with stage IV NSCLC, suggesting a potential anticancer effect. Further research should evaluate plausible biologic mechanisms and test the effect of metformin in prospective clinical trials.

Inequalities in lung cancer care of elderly patients with schizophrenia: an observational cohort study.

OBJECTIVE: Cancer mortality is higher in individuals with schizophrenia, a finding that may be due, in part, to inequalities in care. We evaluated gaps in lung cancer diagnosis, treatment, and survival among elderly individuals with schizophrenia. METHODS: The Surveillance, Epidemiology, and End Results database linked to Medicare records was used to identify patients 66 years or older with primary non-small cell lung cancer. Lung cancer stage, diagnostic evaluation, and rates of stage-appropriate treatment were compared among patients with and without schizophrenia using unadjusted and multiple regression analyses. Survival was compared among groups using Kaplan-Meier methods. RESULTS: Of the 96,702 patients with non-small cell lung cancer in the Surveillance, Epidemiology, and End Results database, 1303 (1.3%) had schizophrenia. In comparison with the general population, patients with schizophrenia were less likely to present with late-stage disease after controlling for age, sex, marital status, race/ethnicity, income, histology, and comorbidities (odds ratio = 0.82, 95% confidence interval = 0.73-0.93) and were less likely to undergo appropriate evaluation (p < .050 for all comparisons). Adjusting for similar factors, patients with schizophrenia were also less likely to receive stage-appropriate treatment (odds ratio = 0.50, 95% confidence interval = 0.43-0.58). Survival was decreased among patients with schizophrenia (mean survival = 22.3 versus 26.3 months, p = .002); however, no differences were observed after controlling for treatment received (p = .40). CONCLUSIONS: Elderly patients with schizophrenia present with earlier stages of lung cancer but are less likely to undergo diagnostic evaluation or to receive stage-appropriate treatment, resulting in poorer outcomes. Efforts to increase treatment rates for elderly patients with schizophrenia may lead to improved survival in this group.

Outcomes after adjuvant platinum-based chemotherapy in elderly NSCLC patients with T4 disease.

BACKGROUND: The postoperative management of elderly patients with T4, N0-1, M0 non-small cell lung cancer (NSCLC) remains controversial. The objective of this study was to evaluate the association of adjuvant chemotherapy with survival and toxicity among these patients. METHODS: Using surveillance, epidemiology and end results registry data linked to Medicare claims, we identified 389 elderly patients with resected T4, N0-1, M0 NSCLC diagnosed between 1992 and 2007. We compared survival of patients treated with and without platinum-based chemotherapy using a Cox regression adjusting for propensity scores for chemotherapy use and use of radiotherapy. We used logistic regression to assess the risk of adverse events in patients receiving chemotherapy. RESULTS: No benefit was noted in overall survival with adjuvant chemotherapy after PS adjustment for both N0 (hazard ratio 0.78, 95% confidence interval 0.50-1.23) and N1 (hazard ratio 1.01, 95% confidence interval 0.67-1.53) cancers. Patients receiving adjuvant chemotherapy experienced severe adverse events more frequently than patients who did not receive chemotherapy. CONCLUSIONS: Use of adjuvant chemotherapy in elderly patients with T4, N0-1, M0 NSCLC was not associated with a survival advantage and was associated with higher rates of severe toxicity.

Clinical and sociodemographic risk factors associated with the development of second primary cancers among postmenopausal breast cancer survivors.

BACKGROUND: Advancement in breast cancer (BC) diagnosis and treatment have increased the number of long-term survivors. Consequently, primary BC survivors are at a greater risk of developing second primary cancers (SPCs). The risk factors for SPCs among BC survivors including sociodemographic characteristics, cancer treatment, comorbidities, and concurrent medications have not been comprehensively examined. The purpose of this study is to assess the incidence and clinicopathologic factors associated with risk of SPCs in BC survivors. METHODS: We analyzed 171, 311 women with early-stage primary BC diagnosed between January 2000 and December 2015 from the Medicare-linked Surveillance Epidemiology and End Results (SEER-Medicare) database. SPC was defined as any diagnosis of malignancy occurring within the study period and at least 6 months after primary BC diagnosis. Univariate analyses compared baseline characteristics between those who developed a SPC and those who did not. We evaluated the cause-specific hazard of developing a SPC in the presence of death as a competing risk. RESULTS: Of the study cohort, 21,510 (13%) of BC survivors developed a SPC and BC was the most common SPC type (28%). The median time to SPC was 44 months. Women who were white, older, and with fewer comorbidities were more likely to develop a SPC. While statins [hazard ratio (HR) 1.066 (1.023-1.110)] and anti-hypertensives [HR 1.569 (1.512-1.627)] increased the hazard of developing a SPC, aromatase inhibitor therapy [HR 0.620 (0.573-0.671)] and bisphosphonates [HR 0.905 (0.857-0.956)] were associated with a decreased hazard of developing any SPC, including non-breast SPCs. CONCLUSION: Our study shows that specific clinical factors including type of cancer treatment, medications, and comorbidities are associated with increased risk of developing SPCs among older BC survivors. These results can increase patient and clinician awareness, target cancer screening among BC survivors, as well as developing risk-adapted management strategies.

Impact of diabetes on stage I lung cancer treatment patterns and prognosis in older adults: A population-based cohort study.

Background: Diabetes is a common comorbidity in patients with early-stage non-small cell lung cancer (NSCLC), a growing population due to increased LC screening. However, it is unknown if diabetes is associated with less aggressive NSCLC treatment and worse NSCLC outcomes. This study aimed to investigate treatment patterns and outcomes of older patients with Stage I NSCLC and diabetes. Methods: Using national cancer registry data linked to Medicare, we identified patients ≥65 years old with Stage I NSCLC. Patients were categorized as having no diabetes, diabetes without severe complications (DM-c), or diabetes with ≥1 severe complication (DM + c). We used multinomial logistic regression to assess the association of diabetes and NSCLC treatment. The association of diabetes category with NSCLC and non-NSCLC survival was analyzed with Fine-Grey competing-risks regression. Results: In 25,358 patients (75% no diabetes, 12% DM-c and 13% had DM + c), adjusted analyses showed that DM-c and DM + c were associated with increased odds of receiving limited resection rather than lobectomy (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.07-1.37 and OR 1.42, 95% CI 1.26-1.59, respectively). Competing risk regression showed diabetes was associated with increased risk of non-NSCLC death (DM-c hazard ratio [HR] 1.16, 95% CI: 1.08-1.25, DM + c HR 1.49, 95% CI: 1.40-1.59), but not NSCLC-specific death. Conclusion: This study uncovers critical information on how diabetes is associated with less aggressive early-stage NSCLC care in older patients. This study also confirms that diabetes increases death from non-lung cancer causes and managing comorbidities is crucial to improving outcomes in older early-stage NSCLC survivors.

Outcomes Following SBRT vs. IMRT and 3DCRT for Older Patients with Stage IIA Node-Negative Non-Small Cell Lung Cancer > 5 cm.

BACKGROUND: To describe outcomes and compare the effectiveness of stereotactic body radiotherapy (SBRT) versus 3-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) in patients with stage IIA lymph node-negative (N0) non-small cell lung cancer (NSCLC) tumors > 5 cm. METHODS: We used the SEER-Medicare database (2005-2015) to identify patients > 65 years with stage IIA (AJCC TNM7) N0 NSCLC > 5 cm tumors who were treated with SBRT, IMRT, and 3DCRT. We used propensity score methods with inverse probability weighting to compare lung cancer-specific survival (LCSS), overall survival (OS), and toxicity. RESULTS: Of 584 patients, 88 (15%), 140 (24%), and 356 (61%) underwent SBRT, IMRT, and 3DCRT, respectively. The SBRT group was older (P = .004), had more comorbidities (P = .02), smaller tumors (P = .03), and more adenocarcinomas (P < .0001). We found a trend towards higher median unadjusted OS with SBRT compared to IMRT and 3DCRT (19 vs. 13 and 14 months, respectively, P = .37). In our propensity score-adjusted analyses, SBRT was significantly associated with better OS and LCSS compared to IMRT (HROS: 0.78, 95% CI: 0.68-0.89, HRLCSS: 0.70, 95% CI: 0.60-0.81) and 3DCRT (HROS: 0.81, 95% CI: 0.72-0.93, HRLCSS: 0.80, 95% CI: 0.68-0.93). SBRT-treated patients also had lower overall adjusted complication rates compared to IMRT (OR: 0.74, 95% CI: 0.55-0.99) and 3DCRT (OR: 0.53, 95% CI: 0.40-0.71). CONCLUSION: For patients with NSCLC tumors > 5 cm, SBRT trends towards fewer toxicities and improved survival compared to other forms of radiotherapy. Our findings support SBRT as an appropriate treatment strategy for older patients with larger inoperable NSCLC tumors.

Postoperative radiotherapy for elderly patients with stage III lung cancer.

BACKGROUND: The potential role of postoperative radiation therapy (PORT) for patients who have completely resected, stage III nonsmall cell lung cancer (NSCLC) with N2 disease remains controversial. By using population-based data, the authors of this report compared the survival of a concurrent cohort of elderly patients who had N2 disease treated with and without PORT. METHODS: By using the Surveillance, Epidemiology, and End Results (SEER) registry linked to Medicare records, 1307 patients were identified who had stage III NSCLC with N2 lymph node involvement diagnosed between 1992 and 2005. Propensity scoring methods and instrumental variable analysis were used to compare the survival of patients who did and did not receive PORT after controlling for selection bias. RESULTS: Overall, 710 patients (54%) received PORT. Propensity score analysis indicated that PORT was not associated with improved survival in patients with N2 disease (hazard ratio [HR], 1.11; 95% confidence interval [CI], 0.97-1.27). Analyses that were limited to patients who did or did not receive chemotherapy, who received intermediate-complexity or high-complexity radiotherapy planning, or adjusted for time trends produced similar results. The instrumental variable estimator for the absolute improvement in 1-year and 3-year survival with PORT was -0.04 (95% CI, -0.15 to 0.08) and -0.08 (95% CI, -0.24 to 0.15), respectively. CONCLUSIONS: The current data suggested that PORT is not associated with improved survival for elderly patients with N2 disease. These findings have important clinical implications, because SEER data indicate that a large percentage of elderly patients currently receive PORT despite the lack of definitive evidence about its effectiveness. The potential effectiveness of PORT should be evaluated further in randomized controlled trials.

Radiotherapy and chemotherapy for elderly patients with stage I-II unresected lung cancer.

Radiotherapy (RT) is the standard therapy for unresected stage I-II nonsmall cell lung cancer (NSCLC). Using population-based data, we compared survival and toxicity among unresected elderly patients treated with combined chemoradiotherapy (CRT) or RT alone. Using the Surveillance, Epidemiology and End Results (SEER) registry (National Cancer Institute, Bethesda, MD, USA) we identified 3,006 cases of unresected stage I-II NSCLC. We used propensity score methods to compare survival and rates of toxicity of patients treated with RT versus CRT. Overall, 844 (28%) patients received CRT. Adjusted analyses showed that CRT was associated with improved survival (hazard ratio 0.85, 95% CI 0.78-0.94). Combination therapy was also associated with better survival among stage I patients treated with intermediate complexity RT (HR 0.80, 95% CI 0.70-0.90); however, no difference in survival was observed among patients treated with complex RT. In stage II patients, CRT was associated with improved survival regardless of the RT technique (HR 0.61-0.72). CRT was associated with increased odds of toxicity. Despite increased toxicity, CRT may improve survival of elderly unresected patients with stage II disease as well as stage I NSCLC treated with intermediate RT complexity. Randomised trials are needed to clarify the balance of benefits and risk of CRT in unresected patients.

Assessment of treatment strategies for stage I non-small cell lung cancer in patients with comorbidities.

INTRODUCTION: Non-small cell lung cancer (NSCLC) patients frequently have major comorbidities but there is scarce data regarding the impact of these conditions on management strategies. We used simulation modeling to compare different treatments for stage I NSCLC for patients with common major comorbidities. METHODS: We used data on NSCLC patinet outcomes and quality of life from: (1) the Surveillance Epidemiology and End Results (SEER) database linked to Medicare claims; (2) Kaiser Permanente Southern California electronic health records; and (3) SEER-Medical Health Outcomes Survey to parameterize a novel simulation model of management and outcomes for stage I NSCLC. Relative efficacy of treatment modalities (lobectomy, segmentectomy, wedge resection and stereotactic body radiotherapy [SBRT]) was collected from existing literature and combined using evidence synthesis methods. We then simulated multiple randomized trials comparing these treatments in a variety of scenarios, estimating quality adjusted life expectancy (QALE) according to age, tumor size, histologic subtype, and comorbidity status. RESULTS: Lobectomy and segmentectomy yielded the greatest QALE gains among all simulated age, tumor size and comorbidity groups. Optimal treatment strategies differed by patient sex and age; wedge resection was among the optimal strategies for women aged 80-84 with tumors 0-2 cm in size. SBRT was included in some optimal strategies for patients aged 80-84 with multimorbidity. CONCLUSIONS: In simulated comparative trials of four common treatments for stage I NSCLC, aggressive surgical management was typically associated with the greatest projected QALE gains despite the presence of comorbidities, although less aggressive strategies were predicted to be non-inferior in some older comorbid patient groups.

The benefits and harms of adjuvant chemotherapy for non-small cell lung cancer in patients with major comorbidities: A simulation study.

BACKGROUND: Randomized controlled trials (RCTs) have demonstrated a survival benefit for adjuvant platinum-based chemotherapy after resection of locoregional non-small cell lung cancer (NSCLC). The relative benefits and harms and optimal approach to treatment for NSCLC patients who have major comorbidities (chronic obstructive pulmonary disease [COPD], coronary artery disease [CAD], and congestive heart failure [CHF]) are unclear, however. METHODS: We used a simulation model to run in-silico comparative trials of adjuvant chemotherapy versus observation in locoregional NSCLC in patients with comorbidities. The model estimated quality-adjusted life years (QALYs) gained by each treatment strategy stratified by age, comorbidity, and stage. The model was parameterized using outcomes and quality-of-life data from RCTs and primary analyses from large cancer databases. RESULTS: Adjuvant chemotherapy was associated with clinically significant QALY gains for all patient age/stage combinations with COPD except for patients >80 years old with Stage IB and IIA cancers. For patients with CHF and Stage IB and IIA disease, adjuvant chemotherapy was not advantageous; in contrast, it was associated with QALY gains for more advanced stages for younger patients with CHF. For stages IIB and IIIA NSCLC, most patient groups benefited from adjuvant chemotherapy. However, In general, patients with multiple comorbidities benefited less from adjuvant chemotherapy than those with single comorbidities and women with comorbidities in older age categories benefited more from adjuvant chemotherapy than their male counterparts. CONCLUSIONS: Older, multimorbid patients may derive QALY gains from adjuvant chemotherapy after NSCLC surgery. These results help extend existing clinical trial data to specific unstudied, high-risk populations and may reduce the uncertainty regarding adjuvant chemotherapy use in these patients.

Lymph node ratio as a prognostic factor in elderly patients with pathological N1 non-small cell lung cancer.

BACKGROUND: Lymph node (LN) metastasis is an important predictor of survival for patients with non-small cell lung cancer (NSCLC). However, the prognostic significance of the extent of LN involvement among patients with N1 disease remains unknown. A study was undertaken to evaluate whether involvement of a higher number of N1 LNs is associated with worse survival independent of known prognostic factors. METHODS: Using the Surveillance, Epidemiology and End Results-Medicare database, 1682 resected patients with N1 NSCLC diagnosed between 1992 and 2005 were identified. As the number of positive LNs is confounded by the total number of LNs sampled, the cases were classified into three groups according to the ratio of positive to total number of LNs removed (LN ratio (LNR)): ≤0.15, 0.16-0.5 and >0.5. Lung cancer-specific and overall survival was compared between these groups using Kaplan-Meier curves. Stratified and Cox regression analyses were used to evaluate the relationship between the LNR and survival after adjusting for potential confounders. RESULTS: Lung cancer-specific and overall survival was lower among patients with a high LNR (p<0.0001 for both comparisons). Median lung cancer-specific survival was 47 months, 37 months and 21 months for patients in the ≤0.15, 0.16-0.5 and >0.5 LNR groups, respectively. In stratified and adjusted analyses, a higher LNR was also associated with worse lung cancer-specific and overall survival. CONCLUSIONS: The extent of LN involvement provides independent prognostic information in patients with N1 NSCLC. This information may be used to identify patients at high risk of recurrence who may benefit from aggressive postoperative therapy.

Association between somatostatin analogues and diabetes mellitus in gastroenteropancreatic neuroendocrine tumor patients: A Surveillance, Epidemiology, and End Results-Medicare analysis of 5235 patients.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are increasingly common malignancies and tend to have favorable long-term prognoses. Somatostatin analogues (SSA) are a first-line treatment for many NETs. Short-term experiments suggest an association between SSAs and hyperglycemia. However, it is unknown whether there is a relationship between SSAs and clinically significant hyperglycemia causing development of diabetes mellitus (DM), a chronic condition with significant morbidity and mortality. AIM: In this study, we aimed to compare risk of developing DM in patients treated with SSA vs no SSA treatment. METHODS AND RESULTS: Using the Surveillance, Epidemiology, and End Results (SEER) database and linked Medicare claims (1991-2016), we identified patients age 65+ with no prior DM diagnosis and a GEP-NET in the stomach, small intestine, appendix, colon, rectum, or pancreas. We used χ2 tests to compare SSA-treated and SSA-untreated patients and multivariable Cox regression to assess risk factors for developing DM. Among 8464 GEP-NET patients, 5235 patients had no prior DM and were included for analysis. Of these, 784 (15%) patients received SSAs. In multivariable analysis, the hazard ratio of developing DM with SSA treatment was 1.19, which was not statistically significant (95% CI 0.95-1.49). Significant risk factors for DM included black race, Hispanic ethnicity, prior pancreatic surgery, prior chemotherapy, tumor size >2 cm, pancreas tumors, and higher Charlson scores. CONCLUSION: DM was very common in GEP-NET patients, affecting 53% of our cohort. Despite prior studies suggesting an association between SSAs and hyperglycemia, our analysis found similar risk of DM in SSA-treated and SSA-untreated GEP-NET patients. Further studies are needed to better understand this relationship. As NET patients have increasingly prolonged survival, it is crucial to identify chronic conditions such as DM that these patients may be at elevated risk for.

The Relationship Between Asthma and Cardiovascular Disease: An Examination of the Framingham Offspring Study.

BACKGROUND: Although asthma has been suggested as a risk factor for cardiovascular disease (CVD), robust longitudinal evidence of this relationship is limited. RESEARCH QUESTION: Using Framingham Offspring Cohort data, the goal of this study was to longitudinally examine the association between asthma and lifetime risk of CVD while controlling for cardiovascular risk factors included in the Framingham Risk Score. STUDY DESIGN AND METHODS: Data were analyzed from a prospective population-based cohort of 3,612 individuals, ages 17 to 77 years, who participated in Framingham Offspring Study examinations from 1979 to 2014. Asthma was defined based on physician diagnosis during study interviews. Incident CVD included myocardial infarction, angina, coronary insufficiency, stroke, transient ischemic attack, and heart failure. Time-dependent Cox regression models were used to evaluate the relationship between asthma and CVD incidence. RESULTS: Overall, 533 (15%) participants had a diagnosis of asthma and 897 (25%) developed CVD during the course of the study. Unadjusted analyses revealed that asthma was associated with increased CVD incidence (hazard ratio, 1.40; 95% CI, 1.17-1.68). Cox regression also showed an adjusted association between asthma and CVD incidence (hazard ratio, 1.28; 95% CI, 1.07-1.54) after controlling for established cardiovascular risk factors. INTERPRETATION: This prospective analysis with > 35 years of follow-up shows that asthma is a risk factor for CVD after adjusting for potential confounders. When assessing risk of cardiovascular disease, asthma should be evaluated and managed as a risk factor contributing to morbidity and mortality.

Lung Cancer Risk among Patients with Asthma-Chronic Obstructive Pulmonary Disease Overlap.

Rationale: Chronic obstructive pulmonary disease (COPD) is a well-established independent risk factor for lung cancer; however, the literature on the association between asthma and lung cancer is mixed. Whether asthma-COPD overlap (ACO) is associated with lung cancer has not been studied. Objectives: We aimed to compare lung cancer risk among patients with ACO versus COPD and other conditions associated with airway obstruction. Methods: We studied 13,939 smokers from the National Lung Cancer Screening Trial who had baseline spirometry and used spirometric indices and history of childhood asthma to categorize participants into five specific airway disease subgroups. We used Poisson regression to compare unadjusted and adjusted lung cancer risk. Results: The incidence rate of lung cancer per 1,000 person-years was as follows: ACO, 13.2 (95% confidence interval [CI], 8.1-21.5); COPD, 11.7 (95% CI, 10.5-13.1); asthmatic smokers, 1.8 (95% CI, 0.6-5.4); Global Initiative for Chronic Obstructive Lung Disease-Unclassified, 7.7 (95% CI, 6.4-9.2); and normal spirometry smokers, 4.1 (95% CI, 3.5-4.8). Patients with ACO had increased adjusted risk of lung cancer compared with patients with asthma (incidence rate ratio [IRR], 4.5; 95% CI, 1.3-15.8) and normal spirometry smokers (IRR, 2.3; 95% CI, 1.3-4.2) in models adjusting for other risk factors. Adjusted lung cancer incidence in patients with ACO and COPD were not found to be different (IRR, 1.2; 95% CI, 0.7-2.1). Conclusions: The risk of lung cancer among patients with ACO is similar to those with COPD and higher than other groups of smokers. These results provide further evidence that COPD, with or without a history of childhood asthma, is an independent risk factor for lung cancer.

Comparative Effectiveness of Robotic-Assisted Surgery for Resectable Lung Cancer in Older Patients.

BACKGROUND: Robotic-assisted surgery (RAS) is a novel surgical approach increasingly used for patients with non-small cell lung cancer (NSCLC). However, data comparing the effectiveness and costs of RAS vs open thoracotomy and video-assisted thoracoscopic surgery (VATS) for NSCLC are limited. METHODS: Patients > 65 years old with stage I to IIIA NSCLC treated with RAS, VATS, or open thoracotomy were identified from the Surveillance, Epidemiology, and End Results-Medicare database and matched according to age, sex, stage, and extent of resection. Propensity score methods were used to compare adjusted rates of postoperative complications, adequate lymph node staging, survival, and treatment-related costs. RESULTS: In this matched study cohort of 2,766 patients with resected NSCLC, RAS was associated with lower complication rates (OR, 0.57; 95% CI, 0.42-0.79) compared with open thoracotomy, and similar complication rates (OR, 1.02; 95% CI, 0.76-1.37) compared with VATS. Patients undergoing RAS were as likely to have adequate lymph node sampling as those undergoing open thoracotomy (OR, 1.28; 95% CI, 0.94-1.74) or VATS (OR, 0.88; 95% CI, 0.66-1.18). There was no significant difference in overall survival after RAS vs open thoracotomy (hazard ratio, 0.81; 95% CI, 0.63-1.04) or VATS (hazard ratio, 0.91; 95% CI, 0.70-1.18). Costs were similar for RAS ($54,702) vs open thoracotomy ($57,104; P = .08), and higher compared with VATS ($48,729; P = .02). CONCLUSIONS: RAS led to improved operative outcomes compared with open thoracotomy but may not offer an advantage over VATS. The comparative effectiveness of RAS should be further evaluated prior to widespread adoption.