Alissa S. Marr

Lung cancer in women: role of estrogens

The incidence of lung cancer in females is increasing, in contrast to that seen in males. In addition, the proportion of lung cancer cases in women attributable to smoking is approximately half of that seen in males. Female sex hormones, especially estrogen, may play a key role in this. Estrogen receptors ERα and ERβ have been detected on lung cancer cells and there is new evidence suggesting that hormone-replacement therapy may increase both the incidence of, and mortality from, lung cancer in women. Laboratory evidence lends credence to the carcinogenic effects of estrogens in lung cancer. This article summarizes the current evidence on their role in lung cancer.

Predictive ability of Charlson comorbidity index on outcomes from lung cancer.

BackgroundThe effect of age and/or comorbidities on management decisions in lung cancer patients has been debated. The Charlson Comorbidity Index (CCI) was developed to help predict mortality from chronic medical conditions. This study was undertaken to evaluate whether CCI is correlated with survival in lung cancer. Patients and MethodsA retrospective chart review of 617 lung cancer patients diagnosed between 1994 and 2007 was conducted. CCI was calculated for each patient with and without the inclusion of age. Multivariate Cox proportional hazard regression analysis was used to evaluate the relationship between CCI and survival while adjusting for other prognostic factors. ResultsSix patients were excluded from the final analysis due to missing outcome or comorbidity data. The median age at diagnosis was 64 years (range, 16-89 y). Five hundred fourteen patients (84%) had nonsmall cell lung cancer and 97 patients (16%) had small cell lung cancer. Using multivariate analysis, no correlation was found between CCI and risk of death whether or not age was included in the index score. ConclusionsCCI did not provide predictive validity for survival of lung cancer patients. Development of accurate and predictive prognostic models to help estimate a patients prognosis is needed.

Epidermal Growth Factor Receptor Mutational Status and Brain Metastases in Non–Small-Cell Lung Cancer

Introduction Epidermal growth factor receptor (EGFR) mutations in non–small-cell lung cancers (NSCLC) may be more common in patients with brain metastases. Previous studies, however, did not adjust for effects of confounding variables. Methods This retrospective study included 1,522 consecutive patients with NSCLC, whose tumors were diagnosed and tested for EGFR mutations at the University of Nebraska Medical Center (Omaha, NE) and Tata Memorial Hospital (Mumbai, India). Multivariate logistic regression was used to identify any association between EGFR status and clinical factors. Results EGFR mutations were more common in females than males (38.7% v 24.8%), Asians than whites (31.3% v 13.4%), nonsmokers than smokers (40.2% v 14.6%), alcohol nonconsumers than users (32.4% v 15.8%), adenocarcinoma than other histology types (32.7% v 10.3%), and patients with brain metastases than extracranial or no metastases (39.4% v 29.8% v 15.1%; P < .001 for all comparisons). There was a higher likelihood of an EGFR mutation among patients with brain metastases (odds ratio, 1.8; P < .001). The median overall survival (OS) was 19.8 months. Patients with brain metastases had a shorter median OS (15 v 20.6 months; P = .02). However, in the cohort of EGFR mutation–positive patients, there was no difference in median OS between patients with and without brain metastases (20.8 v 25.1 months; P = .11). Conclusion There is a nearly two-fold higher incidence of EGFR mutations in NSCLC among patients with brain metastases at diagnosis. EGFR mutations did not predict for outcomes from brain metastases.

Weekly vinorelbine and paclitaxel in older patients with advanced non-small cell lung cancer: A phase II Fred and Pamela Buffet Cancer Center Clinical Trials Network study.

OBJECTIVE Platinum-based doublet chemotherapy is the standard for most patients with advanced non-small cell lung cancer (NSCLC). Toxicity concerns limit chemotherapy for patients over 70years. Vinorelbine and paclitaxel are effective as single agents in advanced NSCLC. This phase II study evaluates safety and efficacy of a combination of these two agents in patients >70years with advanced NSCLC. MATERIALS AND METHODS Patients with treatment naïve metastatic NSCLC received two cycles comprising 6 weekly doses of vinorelbine and paclitaxel, with restaging scans at week 8. Patients with radiographic progression came off study. The estimated sample size was 29. Toxicity analyses were conducted after 10 patients and again after 19 patients were enrolled. Outcomes were safety and efficacy, progression free (PFS) and overall survival (OS) and quality of life (QOL). RESULTS The study closed at second interim analysis as 6/19 patients had ≥grade 4 non-hematologic toxicity (respiratory failure, sepsis, ischemic encephalopathy, pneumonia, hypoxemia, cardiopulmonary arrest, neutropenic fever, death). Of the 16 evaluable patients, 7 completed the study. Disease control rate (partial response+stable disease) was 47% (n=9); 37% (n=7) progressed. No complete responses were seen. Median PFS was 3.5months (95% CI: 1.4, 5.5) and OS 7.8months (95% CI: 1.9, 13.6). QOL did not change compared to baseline, at week 9, but increased at week 17. CONCLUSIONS Although the combination met its response end points, increased toxicity makes this combination unsuitable for older patients. While QOL improved over the study, the small sample hinders interpretation.

Resected small cell lung cancer—time for more?

Small cell lung cancer (SCLC) often presents with either regional or systemic metastases, but approximately 4% of patients present with a solitary pulmonary nodule. Surgical resection can be an option for these patients and is endorsed by the National Comprehensive Cancer Network (NCCN) guidelines. There are no prospective randomized clinical trials evaluating the role of adjuvant systemic therapy in these resected SCLC patients. A recent National Cancer Database analysis found that the receipt of adjuvant chemotherapy alone [hazard ratio (HR), 0.78; 95% CI, 0.63-0.95] or with brain radiation (HR, 0.52; 95% CI, 0.36-0.75) was associated with significantly improved survival as compared to surgery alone. As it is unlikely that a randomized prospective clinical trial addressing this question will be completed, these data should assist with decision making in these patients.

Resected small cell lung cancer—what do we do next?

Small cell lung cancer (SCLC) accounts for only 15% of lung cancers diagnosed in the United States; however it represents the 5th leading cause of cancer related mortality (1). Cytotoxic chemotherapy, with or without radiation therapy, is the primary modality for the treatment of SCLC as this particular histology is exquisitely chemosensitive with initial response rates around 65% (2).

Advanced lung cancer in the older patient: is there a role for bevacizumab?

There is ongoing discussion about the most appropriate treatment for lung cancer in elderly patients. Many trials exclude this age group; and those that include elderly, often do not distinguish between age groups. The advent of targeted agents in cancer therapy has raised the hope that older cancer patients could be treated as effectively as younger patients and without added toxicities.

Early-stage non-small cell lung cancer: A SEER database analysis.

e17501 Background: Surgery is the main treatment of early stage non small cell lung cancer (NSCLC). Radiation (XRT) can be used for patients who are not surgical candidates. Recent advances in XRT techniques have put the management of early stage NSCLC in flux. This study was conducted to evaluate outcomes from the two treatment modalities. METHODS Patients with stage I and II (AJCC 6th Ed) NSCLC diagnosed between 1988 and 2005 were identified in the SEER database. Data abstracted included: age, gender, year of diagnosis, treatment and overall survival (OS). Data were grouped in three intervals based on year of diagnosis (1988-1992, 1992-1997, post-1997) to evaluate changes in outcomes over time. OS was analyzed using Kaplan-Meier curves and log-rank statistics. Cox proportional hazards model was used for multivariate analysis of OS. Statistical significance was estimated at the 0.05 level. RESULTS Of the 8097 patients identified, 6,410 had stage I disease and 1,687 had stage II. Most patients (5,214 - stage I; 832 - stage II) received surgery alone, while 753 (516 - stage I; 237 - stage II) patients received XRT alone and 407 (315 - stage I; 92 - stage II) received no treatment. On multivariate analysis factors that predicted for OS in stage I were age, race, year of diagnosis, gender, histology, tumor grade and treatment (p<0.001). For stage II, age, gender, year of diagnosis and treatment predicted OS (p<0.0001). Median OS (years) following surgery for stage I NSCLC was similar in the three time periods (6.33, 6.58, 6.75) but a significant improvement following XRT (1.33, 1.25, 1.92; p<0.0001) and no treatment (0.5, 0.75, 1.25; p<0.0001) was identified. Patients who refused surgery in favor of XRT had a worse OS compared to those who received surgery (1.83 vs. 6.25 yrs; p<0.0001 - stage I and 0.42 vs. 2.67 years; p<0.0001 - stage II). These differences persisted in each of the three time periods. Caucasians, females, adenocarcinomas and grade 1 tumors had better outcomes. CONCLUSIONS Patients treated with radiation have experienced improved survival in early stage NSCLC between 1998 and 2005. Appropriate candidates should be made aware of the differences in outcomes between surgery and XRT, since XRT has significantly inferior outcomes despite advances in technology.