Grace Mhango

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.

Survival After Segmentectomy and Wedge Resection in Stage I Non–Small-Cell Lung Cancer

Introduction: Although lobectomy is considered the standard surgical treatment for stage IA non–small-cell lung cancer (NSCLC), wedge resection or segmentectomy are frequently performed on patients who are not lobectomy candidates. The objective of this study was to compare survival among patients with stage IA NSCLC, who are undergoing these procedures. Methods: Using the Surveillance, Epidemiology and End Results registry, we identified 3525 patients. We used logistic regression to determine propensity scores for patients undergoing segmentectomy, based on the patient’s preoperative characteristics. Overall and lung cancer-specific survival of patients treated with wedge resection versus segmentectomy was compared after adjusting, stratifying, or matching patients based on propensity score. Results: Overall, 704 patients (20%) underwent segmentectomy. Analyses, adjusting for propensity scores, showed that segmentectomy was associated with significant improvement in overall (hazard ratio: 0.80, 95% confidence interval: 0.69–0.93) and lung cancer-specific survival (hazard ratio: 0.72, 95% confidence interval: 0.59–0.88) compared with wedge resection. Similar results were obtained when stratifying and matching by propensity score and when limiting analysis to patients with tumors sized less than or equal to 2 cm, or aged 70 years or younger. Conclusions: These results suggest that segmentectomy should be the preferred technique for limited resection of patients with stage IA NSCLC. The study findings should be confirmed in prospective studies.

The Number of Lymph Node Metastases as a Prognostic Factor in Patients With N1 Non-small Cell Lung Cancer

BACKGROUND Lymph node (LN) status is an important component of staging; it provides valuable prognostic information and influences treatment decisions. However, the prognostic significance of the number of positive LNs in N1 non-small cell lung cancer (NSCLC) remains unclear. In this study we evaluated whether a higher number of positive LNs results in worse survival among patients with N1 disease. METHODS The Surveillance, Epidemiology, and End Results database was used to identify 3,399 patients who underwent resection for N1 NSCLC. Subjects were categorized into groups based on the number of positive nodes: one, two to three, four to eight, and more than eight positive LNs. The prognostic significance of the number of positive LNs in relation to survival was evaluated using the Kaplan-Meier method. Stratified and Cox regression analysis were used to evaluate the relationship between the number of positive LNs and survival after adjusting for potential confounders. RESULTS Unadjusted survival analysis showed that a greater number of N1 LNs was associated with worse lung cancer-specific (P < .0001) and overall (P < .0001) survival. Mean lung cancer-specific survival was 8.8, 8.2, 6.0, and 3.9 years for patients with one, two to three, four to eight, and more than eight positive LNs, respectively. Stratified and adjusted analysis also showed the number of N1 LNs was an independent predictor of survival after controlling for potential confounders. CONCLUSION The number of positive LNs is an independent prognostic factor of survival in patients with N1 NSCLC. This information may be used to further stratify patients with respect to risk of recurrence in order to determine postoperative management.

Postoperative radiotherapy for elderly patients with stage III lung cancer

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.

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.

Comparative Outcomes of Elderly Stage I Lung Cancer Patients Treated with Segmentectomy via Video-Assisted Thoracoscopic Surgery versus Open Resection

Introduction: Video-assisted thorcacic surgery (VATS) is considered an alternative to open lobectomy for the treatment of non–small-cell lung cancer (NSCLC). Limited data are available, however, regarding the equivalence of open versus VATS segmental resections, particularly among elderly patients. Methods: From the Surveillance, Epidemiology, and End Results–Medicare database we identified 577 stage I NSCLC patients aged more than 65 years treated with VATS or open segmentectomy. We used propensity score methods to control for differences in the baseline characteristics of patients treated with VATS versus open segmentectomy. Outcomes included perioperative complications, need for intensive care unit, extended hospital stay, perioperative mortality, and survival. Results: Overall, 27% of patients underwent VATS. VATS-treated patients had lower rates of postoperative complications (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.37–0.83), intensive care unit admissions (OR: 0.18, 95% CI: 0.12–0.28), and decreased length of stay (OR: 0.41, 95% CI: 0.21–0.81) after adjusting for propensity scores. Postoperative outcomes were not significantly different across groups after adjusting for surgeon characteristics. Overall (hazard ratio: 0.80, 95% CI: 0.60–1.06) and lung cancer–specific (hazard ratio: 0.71, 95% CI: 0.45–1.12) survival was similar across groups. Conclusions: VATS segmentectomy can be safely performed among elderly NSCLC patients and is associated with equivalent postoperative and oncologic outcomes.

Outcomes of elderly patients with stage IIIB-IV non-small cell lung cancer admitted to the intensive care unit

BACKGROUND Although the prognosis of elderly patients with stage IIIB and IV non-small cell lung cancer (NSCLC) is poor, it remains a common cause of cancer related admissions to the intensive care unit (ICU). The objective was to evaluate short and long-term outcomes of a population-based sample of elderly patients with advanced NSCLC who require ICU care. METHODS Using combined data from the Surveillance, Epidemiology and End Results registry and Medicare files, we identified 1134 patients >65 years of age with stage IIIB and IV NSCLC admitted to an ICU with a diagnosis of respiratory, cardiac, or neurologic complications, renal failure, or sepsis. We assessed rates and predictors of death during hospitalization. The Kaplan-Meier method was used to estimate mortality rates at 90 days and 1 year post hospital discharge. RESULTS In-hospital mortality was 33% (95% CI: 30-36%). The 90-day and 1-year mortality rate was 71% and 90%, respectively. Patients with an admitting diagnosis of sepsis had the highest rate of in-hospital mortality (59%). Of those who were alive at discharge, 52% were transferred to a skilled nursing facility, 6% to hospice, and 42% returned home. CONCLUSION We found that one-third of elderly patients with advanced NSCLC admitted to the ICU do not survive hospitalization. Among survivors, most patients required continued institutionalization with a very low likelihood of surviving >1 year from discharge. This data should help patients, families, and health care providers of elderly patients with advanced NSCLC make decisions regarding ICU utilization.

Limited Resection Versus Lobectomy for Older Patients With Early-Stage Lung Cancer: Impact of Histology

PURPOSE Limited resection has been increasingly used in older patients with stage IA lung cancer. However, the equivalency of limited resection versus lobectomy according to histology is unknown. METHODS We identified patients older than 65 years with stage IA invasive adenocarcinoma or squamous cell carcinoma ≤ 2 cm who were treated with limited resection (wedge or segmentectomy) or lobectomy in the Surveillance, Epidemiology, and End Results-Medicare database. We estimated propensity scores that predicted the use of limited resection and compared survival of patients treated with limited resection versus lobectomy. Treatments were considered equivalent if the upper 95th percentile of the hazard ratio (HR) for limited resection was ≤ 1.25. RESULTS Overall, 27% of 2,008 patients with adenocarcinoma and 32% of 1,139 patients with squamous cell carcinoma underwent limited resection. Survival analyses, adjusted for propensity score by using inverse probability weighting, showed that limited resection was not equivalent to lobectomy in patients with adenocarcinoma (HR, 1.21; upper 95% CI,1.34) or squamous cell carcinoma (HR, 1.21; upper 95% CI, 1.39). Although patients with adenocarcinomas treated with segmentectomy had equivalent survival rates to those treated with lobectomy (HR, 0.97; upper 95% CI, 1.07), outcomes of those treated with wedge resection (HR, 1.29; upper 95% CI, 1.42) did not. Among patients with squamous cell carcinoma, neither wedge resection (HR, 1.34; upper 95% CI, 1.53) nor segmentectomy (HR, 1.19; upper 95% CI, 1.36) were equivalent to lobectomy. CONCLUSION We found generally that limited resection is not equivalent to lobectomy in older patients with invasive non-small-cell lung cancer ≤ 2 cm in size, although segmentectomy may be equivalent in patients with adenocarcinoma.

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.

Metformin Improves Survival in Patients with Pancreatic Ductal Adenocarcinoma and Pre-Existing Diabetes: A Propensity Score Analysis

OBJECTIVES:Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease. Diabetes mellitus (DM) is both a risk factor for and a sequela of PDAC. Metformin is a commonly prescribed biguanide oral hypoglycemic used for the treatment of type II DM. We investigated whether metformin use before PDAC diagnosis affected survival of patients with DM, controlling confounders such as diabetic severity.METHODS:We used the Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database to identify patients with PDAC diagnosed between 2007 and 2011. The diabetic TO comorbidity severity index (DCSI) controlled for DM severity. Inverse propensity weighted Cox Proportional-Hazard Models assessed the association between metformin use and overall survival adjusting for relevant confounders.RESULTS:We identified 1,916 patients with PDAC and pre-existing DM on hypoglycemic medications at least 1 year before cancer diagnosis. Of these, 1,098 (57.3%) were treated with metformin and 818 (42.7%) with other DM medications. Mean survival for those on metformin was 5.5 months compared with 4.2 months for those not on metformin (P<0.01). After adjusting for confounders including DCSI, Charlson score, and chronic kidney disease (CKD), patients on metformin had a 12% decreased risk of mortality compared with patients on other medications (hazard ratio (HR): 0.88, 95% confidence interval (CI): 0.81–0.96, P<0.01). In stratified analysis, differences persisted regardless of the Charlson score, the DCSI score, the presence of kidney disease, or the use of insulin/other hypoglycemic medications (P<0.01 for all).CONCLUSIONS:Metformin is associated with increased survival among diabetics with PDAC. If confirmed in a prospective study, then these results suggest a possible role for metformin as an adjunct to chemotherapy among diabetics with PDAC.