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ABSTRACT: : Despite its common occurrence, the influence of malignant pleural effusion (MPE) on the outcomes of patients with advanced non-small-cell lung cancer (NSCLC) with distant metastasis (M1b) is unknown. We evaluated the clinical characteristics associated with MPE at presentation and the prognostic impact of MPE at presentation in patients with stage M1b NSCLC.
: We extracted data from the Surveillance Epidemiology and End Results (SEER) registry from patients with NSCLC diagnosed between 2004 and 2005. Odds-ratio estimates were calculated using logistic regression, and the Kaplan-Meier method was used to estimate the overall survival. Cox proportional hazard model was used to evaluate whether MPE was an independent risk for outcome.
: Among the 57,685 patients, MPE was present in 9170 (15.9%), including 3944 out of 31,506 (12.5%) without distant metastases and 5226 (20.0%) out of 26,179 with M1b. The probability of MPE was higher in patients with larger tumors, mediastinal lymph node involvement, and adenocarcinoma, NSCLC not otherwise specified, or large-cell histology. In patients with stage M1b, median overall survival (3 months versus 5 months), estimated 1-year survival (12.6% versus 24.8%), and 2-year survival (5.4% versus 11.3%) were significantly lower in patients with MPE compared with those without MPE (hazards ratio 1.49, 95% confidence interval 1.44-1.54, p < 0.0001). MPE was also an independent factor for worse survival in multivariate analysis (hazards ratio 1.36, 95% confidence interval1.30-1.43, p < 0.001).
: MPE is a common complication in patients with NSCLC and is associated with decreased survival in patients with distant metastases. If these data are validated, subsequent studies in patients with advanced NSCLC may consider stratification according to the MPE status.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2012; 7(10):1485-9. · 4.55 Impact Factor
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ABSTRACT: : Increased tumor size is a known risk for poor outcomes in patients with stage I and II non-small cell lung cancer (NSCLC), who are treated with surgery or radiotherapy. However, there is limited information regarding the impact of tumor size on the outcomes of patients with mediastinal lymph node involvement. We conducted a Surveillance, Epidemiology, and End Results (SEER) database analysis to evaluate the prognostic significance of tumor size in patients with unresected stage III NSCLC.
: The SEER registry was queried for patients with unresected NSCLC stage III and no malignant pleural effusion, aged 21 years or older, and diagnosed between 1998 and 2003. Tumor size was defined as S1 (0.1-3cm), S2 (3.1-5cm), S3 (5.1-7cm), and S4 (7.1-20cm). Demographic variables included age, sex, race and histology. Overall survival (OS) and disease-specific survival (DSS) were estimated by the Kaplan-Meier method, and the Cox proportional hazard model was used to evaluate whether tumor size remained an independent risk factor in multivariable analysis.
: A total of 12,315 patients met the eligibility criteria. Median age at diagnosis was 70 years and most patients were men (58.7%) and white (81.3%). Tumor size was an independent predictor for both OS (p < 0.0001) and DSS (p < 0.001) in all subgroups of patients.
: Tumor size is an independent predictor for OS and DSS in patients with unresected stage III NSCLC, and should be considered in the stratification of patients treated in this setting after validation of this finding in additional studies.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2012; 7(10):1479-84. · 4.55 Impact Factor
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Ramaswamy Govindan,
Li Ding,
Malachi Griffith, Janakiraman Subramanian,
Nathan D Dees,
Krishna L Kanchi,
Christopher A Maher,
Robert Fulton,
Lucinda Fulton,
John Wallis, [......],
Jason Walker,
Sandra McDonald,
Ron Bose,
David Ornitz,
Donghai Xiong,
Ming You,
David J Dooling,
Mark Watson,
Elaine R Mardis,
Richard K Wilson
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ABSTRACT: We report the results of whole-genome and transcriptome sequencing of tumor and adjacent normal tissue samples from 17 patients with non-small cell lung carcinoma (NSCLC). We identified 3,726 point mutations and more than 90 indels in the coding sequence, with an average mutation frequency more than 10-fold higher in smokers than in never-smokers. Novel alterations in genes involved in chromatin modification and DNA repair pathways were identified, along with DACH1, CFTR, RELN, ABCB5, and HGF. Deep digital sequencing revealed diverse clonality patterns in both never-smokers and smokers. All validated EFGR and KRAS mutations were present in the founder clones, suggesting possible roles in cancer initiation. Analysis revealed 14 fusions, including ROS1 and ALK, as well as novel metabolic enzymes. Cell-cycle and JAK-STAT pathways are significantly altered in lung cancer, along with perturbations in 54 genes that are potentially targetable with currently available drugs.
Cell 09/2012; 150(6):1121-34. · 32.40 Impact Factor
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The lancet oncology 03/2012; 13(3):216-7. · 14.47 Impact Factor
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Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 03/2012; 7(3):626-8. · 4.55 Impact Factor
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ABSTRACT: In the last several years, we have made slow but steady progress in developing new treatment strategies for patients with lung cancer. The use of molecularly targeted therapy has made a significant impact on the outcomes of patients with lung cancer. Further research is ongoing to identify more effective ways to target lung cancer. In the recently concluded 47 th annual meeting of the American Society of Clinical Oncology, there were several presentations on novel targeted therapies for lung cancer, in addition to the effective and optimal use of existing cytotoxic and targeted therapies for lung cancer. For this review, we have selected presentations that primarily have an impact on clinical practice, and some presentations regarding emerging therapeutic agents.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 01/2012; 7(1):260-5. · 4.55 Impact Factor
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ABSTRACT: This trial focused on optimally combining existing targeted therapies and cytotoxic chemotherapy in the treatment of unselected patients with advanced non-small-cell lung cancer (NSCLC).
Patients with previously untreated advanced-stage nonsquamous NSCLC were eligible for this trial. In module A, patients received up to 4 cycles of erlotinib 150 mg daily and bevacizumab 15 mg/kg every 3 weeks. Patients then received carboplatin (AUC = 6), paclitaxel 200 mg/m2, and bevacizumab 15 mg/kg for 4 cycles in module B. Patients who did not have progressive disease in module A received maintenance erlotinib 150 mg daily and bevacizumab 15 mg/kg every 3 weeks in module C.
Forty-eight patients were enrolled in this multicenter phase II trial. Most patients were male (62.5%) and white (77.1%) with stage IV disease (93.8%) and adenocarcinoma histologic type (66.7%). The overall response rate in module A was 10.4%, in module B it was 15.1%, and in module C it was 5.5%. The study achieved its primary endpoint, with a nonprogression rate of 45.8% in module A. The median overall survival (OS) was 12.6 months.
The novel systemic therapy regimen is feasible in patients with advanced NSCLC. However there is no further role for developing this regimen in unselected patients with NSCLC.
Clinical Lung Cancer 11/2011; 13(2):123-8. · 2.94 Impact Factor
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Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 11/2011; 6(11 Suppl 4):S1786-8. · 4.55 Impact Factor
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ABSTRACT: A number of novel agents are currently being tested in clinical trials in patients with cancer. Results from early-phase trials, often in unselected groups of patients with a wide variety of cancer types, were reported at the 46th annual meeting of the American Society of Clinical Oncology (ASCO). We report on selected studies from the developmental therapeutics track (abstracts 2500-2613 and 3000-3108) that may be of interest to the thoracic oncology community.
Clinical Lung Cancer 03/2011; 12(2):94-9. · 2.94 Impact Factor
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ABSTRACT: Globally, lung cancer remains the most common cause of cancer-related death. In recent years, it has become clear that development of rational molecular targeted therapies is critical to improve the outcomes of patients with lung cancer. A better understanding of the tumor biology is crucial to achieve this goal. Several new findings in the field of tumor biology were presented at the 46th Annual Meeting of the American Society of Clinical Oncology. Novel genetic mutations were identified in pleural mesothelioma using array-based technologies. Several studies on the development and testing of new molecular diagnostic tests to detect epidermal growth factor receptor tyrosine kinase mutations and EML4-ALK (Echinoderm Microtubule-associated Protein like 4 Anaplastic Lymphoma Receptor Tyrosine Kinase) fusion gene were presented as well.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 02/2011; 6(2):399-403. · 4.55 Impact Factor
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ABSTRACT: Angiogenesis is essential for cancer growth and progression. Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis. The addition of bevacizumab, an antibody to vascular endothelial growth factor (VEGF), to paclitaxel and carboplatin improves survival compared with chemotherapy alone in patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC). Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) are a new class of drugs that target the TK domain of the VEGF receptors. To evaluate the role of this class of agents in the treatment of NSCLC, some phase II and phase III studies using these agents alone or in combination with other agents have been completed. This review summarizes the currently available data on VEGFR TKIs in the treatment of NSCLC.
Clinical Lung Cancer 09/2010; 11(5):311-9. · 2.94 Impact Factor
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ABSTRACT: Several new agents are being tested in clinical trials for patients with non-small cell lung cancer (NSCLC). A survey of ongoing clinical trials in NSCLC in the ClinicalTrials.gov website would help identify areas that require further attention in the future.
We conducted a survey of ongoing clinical trials on NSCLC registered in the ClinicalTrials.gov website. The advanced search option was applied using the terms "non small cell lung cancer," "open studies," "interventional," and "adults 18 years or older."
Of the 493 eligible trials, 77 (15.6%) were phase III, 92 (18.7%) were phase I, and 240 (48.7%) were phase II trials. Universities were listed as the primary sponsor for 224 (45.4%) trials and pharmaceutical industry for 166 (33.7%) trials. Majority of the trials were multicenter studies (56.8%) and were being conducted exclusively within the United States (51.3%). A large proportion of phase II and III clinical trials (77.2%) were focused on patients with advanced-stage disease. The most frequently used end points were progression-free survival (27.1%) followed by tumor response rate (22.9%) and overall survival (16.6%). Although biomarker analysis was included in 185 (37.5%) trials, only 39 (7.9%) trials used biomarkers for patient selection.
Progression-free survival is the end point most commonly used to assess the effectiveness of experimental regimens, and biomarker-based patient selection is rarely used in ongoing clinical trials for NSCLC.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2010; 5(8):1116-9. · 4.55 Impact Factor
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Nature Reviews Clinical Oncology 02/2010; 7(2):77-8. · 11.96 Impact Factor
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ABSTRACT: Lung cancer in "never-smokers" constitutes only a small proportion of patients with lung cancer. Nevertheless, the topic has recently attracted a good deal of attention. Initially this was due to the fact that never-smokers with lung cancer had better outcomes with epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitors, compared to tobacco smokers with lung cancer. More recently the identification of molecular changes unique to lung cancer in never-smokers has generated further interest in this disease. These findings have the potential to enhance our knowledge of lung cancer biology and lead to the development of new, more effective treatments for lung cancer. In this review, we summarize the existing body of knowledge on lung cancer in never-smokers.
Oncology (Williston Park, N.Y.) 01/2010; 24(1):29-35. · 1.03 Impact Factor
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ABSTRACT: The median age of patients with newly diagnosed non-small cell lung cancer (NSCLC) at presentation is 71 years. We conducted an analysis of Surveillance, Epidemiology, and End Results data to assess whether the presentation and outcomes of NSCLC in younger patients (age < or =40 years) are different from that in older patients (age >40 years).
We obtained the demographic, clinical, and outcomes data for all patients diagnosed with NSCLC from 1988 to 2003 in the Surveillance, Epidemiology, and End Results registry. Patients were grouped by age at diagnosis into younger than or equal to 40 years (younger cohort) or older than 40 years (older cohort).
During the period analyzed, we identified 2775 patients with NSCLC in the younger cohort and 236,313 patients in the older cohort. Compared with the older group, the younger group had greater proportion of African Americans (19.2% versus 10.9%; p < 0.0001), Asian or Pacific Islander (10.3% versus 5.9%; p < 0.0001), women (48.7% versus 41.9%; p < 0.0001), and patients with stage IV disease (57.4% versus 43.0%; p < 0.0001). Adenocarcinoma was more common in younger patients than in the older patients (57.5% versus 45.2%; p < 0.0001). Squamous cell carcinoma was less prevalent in the younger cohort than in older cohort (12.5% versus 26.4%; p < 0.0001). Five-year overall survival and cancer specific survival were significantly better for younger patients than for older patients across all stages.
There is a greater representation of African Americans, Asians or Pacific Islanders, women, and adenocarcinoma histology in the younger cohort of patients with NSCLC compared with the older cohort. Despite presenting with stage IV disease more often, the overall and cancer-specific survivals are better in younger cohort than in the older cohort.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 11/2009; 5(1):23-8. · 4.55 Impact Factor
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ABSTRACT: Although there has been a significant survival improvement for patients with metastatic NSCLC enrolled in randomized trials, it is not clear whether a similar benefit is seen in an unselected group of patients. Therefore, we conducted a study to evaluate for survival changes in a large national cancer registry database.
The Surveillance, Epidemiology, and End Results (SEER) registry was queried for patients with NSCLC stage IV, aged 21 years or older, and diagnosed between 1990 and 2005. We analyzed four equally divided time periods between 1990 and 2005 (1990 to 1993 or period 1, 1994 to 1997 or period 2, 1998 to 2001 or period 3, and 2002 to 2005 or period 4) to determine changes in overall survival for all patients and according to histology.
We identified 129,337 patients meeting eligibility criteria. There was a significant improvement in overall survival since period 1. One-year and 2-year overall survival increased from 13.2 and 4.5%, respectively, in period 1 to 19.4% and 7.8%, respectively, in period 4. On multivariate analysis, survival for adenocarcinoma was increased compared with squamous cell carcinoma only in period 4 (p = 0.02).
There has been a modest but statistically significant improvement in overall survival for stage IV NSCLC over the past 16 years. The recent differences in outcomes based on histology observed in period 4 may reflect the increased activity of epidermal growth factor receptor tyrosine kinase inhibitors in adenocarcinoma compared with squamous cell carcinoma.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 09/2009; 4(12):1524-9. · 4.55 Impact Factor
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ABSTRACT: Half of all patients with non-small cell lung cancer (NSCLC) are 70 years or older at the time of diagnosis. Surgery is an option for fit elderly patients with early stage disease, but rates of disease recurrence after surgical resection are not well described. We report the outcomes in elderly patients (70 years or older) with stage I NSCLC after surgical resection.
We conducted a retrospective study of patients diagnosed with stage I NSCLC after surgical resection at Washington University School of Medicine-Alvin J. Siteman Cancer Center from 1990 to 2000. Demographic, pathologic, treatment, and follow-up data were collected. Recurrence rates and overall survival were calculated by the Kaplan-Meier method. Multivariate Cox proportional hazards models were used to detect associations between potential prognostic factors and survival and recurrence.
Of the 715 patients with stage I NSCLC, 286 were 70 years or older at diagnosis. In this elderly cohort, the median age was 74 years (range, 70-89 years) and 140 of them were women (49%). Lobectomy was performed in 237 patients (83%) whereas 43 patients (15%) had a wedge or segmental resection, and six patients (2%) underwent pneumonectomy. Clinical and pathologic characteristics were not statistically different between the elderly and younger cohorts, with the exception that older patients were more likely to be white (90% versus 80%, p = 0.0003) and less likely to be smokers (88% versus 95%, p = 0.019) compared with the younger cohort. With a median follow-up of 4.6 years, the overall 5-year survival rate was 52% with a 5-year recurrence rate of 24%. In comparison, the patients younger than 70 years had a 5-year survival rate of 67% (p < 0.001) and a 5-year recurrence rate of 24%.
Although overall survival was worse in elderly patients, estimated disease recurrence rates after resection were identical.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2009; 4(11):1370-4. · 4.55 Impact Factor
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Clinical Lung Cancer 10/2008; 9(5):252-3. · 2.94 Impact Factor
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ABSTRACT: Lung cancer is a major cause of cancer-related mortality in the USA, and tobacco smoke is the major risk factor for this disease. However, many patients with lung cancer have never smoked (never smokers). Patients with lung cancer who have never smoked are more likely to have mutations in epidermal growth factor receptor (EGFR) tyrosine kinase and have better response to its inhibitors than do patients with tobacco-associated lung cancer. Furthermore, the prevalences of mutations in KRAS and P53 differ for patients with lung cancer who have never smoked and those with tobacco-associated lung cancer. Genetic mutations seem to be more common in patients with tobacco-associated lung cancer than in never smokers. Current evidence indicates that the two types of lung cancer are biologically distinct. Here, we review published studies of the molecular genetics of lung cancer in never smokers and identify the specific differences from tobacco-associated lung cancer.
The lancet oncology 08/2008; 9(7):676-82. · 14.47 Impact Factor
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ABSTRACT: Tobacco smoking leads to lung cancer. Approximately 10% of patients with lung cancer are life long never-smokers. There are only limited data available on the clinical characteristics and outcomes of lung cancer in never-smokers from the Western hemisphere.
Demographic and survival information was collected on 254 never-smokers with a confirmed pathologic diagnosis of non-small cell lung cancer (NSCLC) by reviewing their medical records and the Social Security database.
The study population consisted of 182 (71.6%) women and 72 (28.3%) men. The median age was 70 years (range: 31-91 years). Adenocarcinoma was the most common histology accounting for 60.8% of all patients, followed by NSCLC not otherwise specified (14.4%), bronchoalveolar carcinoma (13.6%), squamous cell carcinoma (8.8%), and large-cell type (2.4%). Majority of patients presented with stage III or IV disease (62.5%). We compared survival between never-smokers and smokers with NSCLC matched for gender, histology, tumor stage, and years of diagnosis. No significant difference in 5-year survival was seen between never-smokers (27.2%) and smokers with NSCLC (31.3%; p = 0.73).
Two thirds of patients with lung cancer who report no history of tobacco smoking are women. In the matched case-control analysis, we report no significant survival difference between lung cancer in never-smokers and those with history of tobacco smoking and lung cancer.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2007; 2(9):827-30. · 4.55 Impact Factor
