Prognostic value of circulating chromogranin A and soluble tumor necrosis factor receptors in advanced nonsmall cell lung cancer

BACKGROUND: Increased levels of chromogranin A (CgA), a protein secreted by many neuroendocrine cells, have been detected in sera of patients with neuroendocrine tumors or renal, hepatic, or heart failure. In patients with heart failure, serum CgA correlates with tumor necrosis factor-alpha (TNF) and soluble TNF receptors (sTNF-Rs), with important prognostic implications. The prognostic value of CgA and sTNF-Rs was investigated in advanced nonsmall cell lung cancer (NSCLC), a histologically heterogeneous group of tumors that may undergo neuroendocrine differentiation. METHODS: CgA and sTNF-Rs were analyzed in the sera of 88 patients with NSCLC before chemotherapy by enzyme-linked immunoadsorbent assay (ELISA) and in tumors by immunohistochemistry. RESULTS: Thirteen percent of patients had CgA values greater than the highest value observed in normal subjects (distribution range, 9-724 ng/mL and 28-196 ng/mL, respectively). Immunohistochemical studies showed no correlation between CgA expression in tumors and serum levels. Conversely, circulating CgA was associated with worse Eastern Cooperative Oncology Group (ECOG) performance status (PS) (P = .0005), more advanced stage (P = .042), and survival, with CgA being an independent prognostic factor of poor outcome (hazards ratio [HR] 1.31 for 100 ng/mL increase; 95% confidence interval [95% CI], 1.08-1.60 [P = .0071]). sTNF-R1 and sTNF-R2 were also associated with ECOG PS (P = .0001 and P = .02, respectively). sTNF-Rs was weakly correlated with circulating CgA (r = 0.39 for TNF-R1 and r = 0.40 for TNF-R2), suggesting a regulatory link between sTNF-Rs and CgA secretion. CONCLUSIONS: Increased serum levels of CgA in NSCLC are independent from protein expression in tumors and more likely related to neuroendocrine response associated with worsening of patient condition. In addition to ECOG PS and stage, CgA is an independent indicator of poor prognosis.     

Independent prognostic value of fascin immunoreactivity in stage I nonsmall cell lung cancer

Fascin-1, the most expressed form of fascin in vertebrate tissues, is an actin-bundling protein that induces cell membrane protrusions and increases motility of normal and transformed epithelial cells. Very few data are available on the role of this protein in nonsmall cell lung cancer (NSCLC). Two hundred and twenty patients with stage I NSCLC and long-term follow-up were evaluated immunocytochemically for fascin expression. Overall, variable fascin immunoreactivity was detected in 98% of 116 squamous cell carcinomas, in 78% of 96 adenocarcinomas, in 83% of six large cell carcinomas, and in the two adenosquamous carcinomas under study. Neoplastic emboli were commonly decorated by the antifascin antibody (P<0.001), also when the surrounding invasive carcinoma was unreactive. Fascin immunoreactivity correlated with high tumour grade (P=0.017) and, in adenocarcinomas, with high Ki-67 labelling index (P=0.021). Adenocarcinomas with a prevalent bronchiolo-alveolar in situ component were less commonly immunoreactive for fascin than invasive tumours (P=0.005). Contralateral thoracic or distant metastases were associated significantly with diffuse (>60% immunoreactive tumour cells) fascin expression in adenocarcinomas (P=0.043), and marginally with strong fascin immunostaining in squamous cell carcinomas (P=0.13). No associations were noted with any other clinicopathological variables tested. Patients with tumours showing diffuse (>60% immunoreactive neoplastic cells) and/or strong immunoreactivity for fascin had a shorter survival (P=0.006 for adenocarcinomas and P=0.026 for squamous cell carcinomas), even after multivariate analysis (P=0.014 and 0.050, respectively). The current study documents for the first time that fascin is upregulated in invasive and more aggressive NSCLC, being an independent prognostic predictor of unfavourable clinical course of the disease. Targetting the fascin pathway could be a novel therapeutic strategy of NSCLC.     

Prognostic implications of cell cycle-related proteins in primary resectable pathologic N2 nonsmall cell lung cancer

BACKGROUND: Patients who have pathologic N2 (pN2) nonsmall cell lung cancer (pN2 NSCLC) represent a heterogeneous group with regard to prognosis and treatment. Molecular features of NSCLC seem to be of interest. For the current study, to select an appropriate therapeutic strategy for each patient, patients with N2 NSCLC were stratified into homogenous subgroups according to the expression profiles of cell cycle-related markers. METHODS: The expression levels of retinoblastoma protein (pRb), cyclin D1, p16, p53, and p21 proteins and values of the Ki-67 labeling index were evaluated in 61 primary surgically resected tumor specimens from patients with pN2 NSCLC using immunohistochemistry. The prognostic impact of these markers on overall survival was analyzed in both univariate and multivariate analyses. RESULTS: In univariate analysis, p21, p16, and Ki-67 were correlated significantly with survival. In multivariate analysis, only p21 and p16 influenced survival. Indeed, the group of patients with pN2 NSCLC who were positive for p21 and p16 had the most favorable overall survival (P = .001) and were correlated significantly with the clinical lymph node (cN) status (cN2 disease; P = .008). Moreover, no significant difference in survival was observed between patients with cN0/cN1 disease and patients with cN2 disease within the group (P = .4333). CONCLUSIONS: Loss of control of cell-cycle checkpoints is a common occurrence in pN2 NSCLC. Functional cooperation between different cell-cycle regulators constitutes another level of regulation in cell growth control and tumor suppression. Preoperative patients with pN2 NSCLC, even those with cN2 disease, who have positive p21 and p16 protein expression in their primary tumors are expected to have a favorable postoperative prognosis and may be candidates for primary resection.     

Prognostic impact of insulin receptor expression on survival of patients with nonsmall cell lung cancer

BACKGROUND:

The purpose of this study was to characterize insulin receptor (IR) and insulin‐like growth factor‐1 receptor (IGF‐1R) expression in patients with nonsmall cell lung cancer (NSCLC).

METHODS:

A total of 459 patients who underwent curative resection of NSCLC were studied (median follow‐up duration, 4.01 years). Expression of the IR and IGF‐1R protein in tumor specimens was assessed immunohistochemically using tissue microarrays.

RESULTS:

The cytoplasmic IR score was higher in patients with adenocarcinoma (ADC) than in those with squamous cell carcinoma (SCC), whereas cytoplasmic IGF‐1R score was higher in patients with SCC than those with ADC. Neither IR nor IGF‐1R expression was associated with sex, smoking history, or clinical stage. Patients with positive IR or IGF‐1R expression levels had poor recurrence‐free (RFS) (3.8 vs 3.3 years; 3.8 vs 2.0 years, respectively), but similar overall survival (OS). Patients with high expression levels of IR and IGF‐1R had shorter RFS and OS compared with those with low levels of IR and/or IGF‐1R expression. Finally, a multivariate analysis revealed the impact of IR, but not of IGF‐1R, as an independent predictive marker of NSCLC survival: hazard ratio (HR) for OS, 1.005 (95% confidence interval [CI], 1.001‐1.010], HR for RFS, 1.005 (95% CI, 1.001‐1.009), when IR score was tested as a continuous variable.

CONCLUSIONS:

Overexpression of IR predicts a poor survival among patients with NSCLC, especially those with SCC. These results might serve as future guidance to the clinical trials involving IR or IGR‐1R targeting agents. Cancer 2012;. © 2011 American Cancer Society.     

Recent developments in the chemotherapeutic options for nonsmall cell lung cancer

Lung cancer is one of the leading causes of cancer deaths in the developed world. It is grossly divided into small cell and nonsmall cell types. Depending on the stage at diagnosis, the principal means of treating nonsmall cell lung cancer are surgery, chemotherapy and/or radiotherapy. However, even when it is diagnosed at an early stage, the progression-free and overall survival rates have been disappointing compared with other cancers. In recent years, there have been a number of developments in the chemotherapeutic options for nonsmall cell lung cancer. The aim of this review is to summarize these developments, in a stage-specific manner, with respect to both standard chemotherapy and also the newer targeted therapies.     

Neighborhood-level socioeconomic determinants impact outcomes in nonsmall cell lung cancer patients in the Southeastern United States

BACKGROUND:

Studies examining the impact of lower socioeconomic status (SES) on the outcomes of patients with nonsmall cell lung cancer (NSCLC) are inconsistent. The objective of this study was to clearly elucidate the association between SES, education, and clinical outcomes among patients with NSCLC.

METHODS:

The study population was derived from a consecutive, retrospective cohort of patients with NSCLC who received treatment within the Duke Health System between 1995 and 2007. SES determinants were based on the individual's census tract and corresponding 2000 Census data. Determinants included the percentage of the population living below poverty, the median household income, and the percentages of residents with at least a high school diploma and at least a bachelor's degree. The SES and educational variables were divided into quartiles. Statistical comparisons were performed using the 25th and 75th percentiles.

RESULTS:

Individuals who resided in areas with a low median household income or in which a high percentage of residents were living below the poverty line had a shorter cancer‐specific 6‐year survival than individuals who resided in converse areas (P = .0167 and P = .0067, respectively). Those living in areas in which a higher percentage of residents achieved a high school diploma had improved disease outcomes compared with those living in areas in which a lower percentage attained a high school diploma (P = .0033). A survival advantage also was observed for inhabitants of areas in which a higher percentage of residents attained a bachelor's degree (P = .0455).

CONCLUSIONS:

Low SES was identified as an independent prognostic factor for poor survival in patients with both early and advanced stage NSCLC. Patients who lived in areas with high poverty levels, low median incomes, and low education levels had worse mortality. Cancer 2012. © 2012 American Cancer Society.     

Expression of multiple epigenetically regulated cancer/germline genes in nonsmall cell lung cancer

Cancer/germline (CG) antigens represent promising targets for widely applicable mono- and multiantigen cancer vaccines for nonsmall cell lung cancer (NSCLC). Since little is known about their composite expression in this tumor type, we analyzed 7 CG genes (MAGE-A3, NY-ESO-1, LAGE-1, BRDT, HOM-TES-85, TPX-1 and LDHC) in 102 human NSCLC specimens. About 81% of NSCLC express at least 1 and half of the specimen at least 2 CG genes. Activation of most of these genes occurs more frequently in squamous cell cancer than in adenocarcinomas. Even though we found all genes but one to be regulated by genomic methylation, not all of them are co-expressed. In particular, combining CG genes not localized on the X-chromosome may provide effective treatment for an extended number of patients.     

Manic fringe inhibits tumor growth by suppressing Notch3 degradation in lung cancer

Notch signaling plays an essential role in development as well as cancer. We have previously shown that Notch3 is important for lung cancer growth and survival. Notch receptors are activated through the interaction with their ligands, resulting in proteolytic cleavage of the receptors. This interaction is modulated by Fringe, a family of fucose-specific β1,3 N-acetylglucosaminyltransferases that modify the extracellular subunit of Notch receptors. Studies in developmental models showed that Fringe enhances Notch’s response to Delta ligands at the expense of Jagged ligands. We observed that Manic Fringe expression is down-regulated in lung cancer. Since Jagged1, a known ligand for Notch3, is often over-expressed in lung cancer, we hypothesized that Fringe negatively regulates Notch3 activation. In this study, we show that re-expression of Manic Fringe down-regulates Notch3 target genes HES1 and HeyL and reduces tumor phenotype in vitro and in vivo. The mechanism for this phenomenon appears to be related to modulation of Notch3 protein stability. Proteasome inhibition reverses Manic Fringe-induced protein turnover. Taken together, our data provide the first evidence that Manic Fringe functions as a tumor suppressor in the lung and that the mechanism of its anti-tumor activity is mediated by inhibition of Notch3 activation.     

Inactivation of LLC1 gene in nonsmall cell lung cancer

Serial analysis of gene expression studies led us to identify a previously unknown gene, c20orf85, that is present in the normal lung epithelium but absent or downregulated in most primary nonsmall cell lung cancers and lung cancer cell lines. We named this gene LLC1 for Low in Lung Cancer 1. LLC1 is located on chromosome 20q13.3 and has a 70% GC content in the promoter region. It has 4 exons and encodes a protein containing 137 amino acids. By in situ hybridization, we observed that LLC1 message is localized in normal lung bronchial epithelial cells but absent in 13 of 14 lung adenocarcinoma and 9 out of 10 lung squamous carcinoma samples. Methylation at CpG sites of the LLC1 promoter was frequently observed in lung cancer cell lines and in a fraction of primary lung cancer tissues. Treatment with 5-aza deoxycytidine resulted in a reduced methylation of the LLC1 promoter concomitant with the increase of LLC1 expression. These results suggest that inactivation of LLC1 by means of promoter methylation is a frequent event in nonsmall cell lung cancer and may play a role in lung tumorigenesis.     

非小细胞肺癌的后程适形放疗疗效

目的探讨后程适形放疗在非小细胞肺癌治疗中的临床价值.方法回顾分析我院1999年后程适形放疗的非小细胞肺癌患者19例.对比同期本院非小细胞肺癌患者常规放疗25例.对后程适形放疗组(1ate course conformal radiotherapy,LCCR)和常规放疗组(conventional radiotherapy,CR)进行比较.结果完全缓解率(CR)和总有效率(CR+PR)LCCR组为31.6%和89.5%;CR组为8%和60%.两组有显著性差异(P＜0.05).12月生存率、局部控制率LCCR组为78.9%、68.4%,18月生存率、局部控制率LCCR组为63.2%、47.4%.CR组分别为48%、24%和32%、16%.两组差异有显著性意义.放射性食管炎、放射性气管炎、放射性肺炎及放射性肺纤维化2个组均无差异.结论后程适形放疗治疗非小细胞肺癌患者的放射毒性反应与常规放疗相似,但疗效优于常规放疗.     

Prognostic model to predict outcomes in nonsmall cell lung cancer patients treated with gefitinib as a salvage treatment

BACKGROUND:

A prognostic model based on clinical parameters for nonsmall cell lung cancer (NSCLC) patients treated with gefitinib (250 mg/day) as a salvage therapy was devised.

METHODS:

Clinical data regarding a total of 316 metastatic or recurrent NSCLC patients who were treated with gefitinib were analyzed.

RESULTS:

Poor prognostic factors for overall survival (OS) by multivariate analysis were an Eastern Cooperative Oncology Group (ECOG) performance status of 2 to 3 (hazards ratio [HR] of 2.07; 95% confidence interval [CI], 1.57‐2.73 [P < .001]), the presence of intra‐abdominal metastasis (HR of 1.76; 95% CI, 1.33‐2.34 [P < .001]), elevated serum alkaline phosphatase (HR of 1.50; 95% CI, 1.13‐2.00 [P = .005]), time interval from diagnosis to gefitinib therapy of ≤12 months (HR of 1.48; 95% CI, 1.12‐1.95 [P = .005]), low serum albumin (HR of 1.45; 95% CI, 1.09‐1.92 [P = .009]), progression‐free interval for previous chemotherapy of ≤12 weeks (HR of 1.40; 95% CI, 1.0‐1.84 [P = .015]), white blood cell >10,000/μL (HR of 1.38; 95% CI, 1.02‐1.85 [P = .032]), and ever‐smoker (HR of 1.33; 95% CI, 1.02‐1.75 [P = .033]). Of the 272 patients applicable to this prognostic model, 41 patients (15%) were categorized as a good prognosis group (0‐1 risk factors), 100 patients (37%) as an intermediate prognosis group (2‐3 risk factors), 81 patients (30%) as a poor prognosis group (4‐5 risk factors), and 50 patients (16%) as a very poor prognosis group (≥6 risk factors). The median OS from the time of gefitinib treatment for the good, intermediate, poor, and very poor prognosis groups were 18.0 months, 11.2 months, 4.0 months, and 1.3 months, respectively (P < .001).

CONCLUSIONS:

This prognostic model based on easily available clinical variables would be useful to identify patients who might derive more benefit from gefitinib treatment and to make decisions in clinical practice. Cancer 2009. © 2009 American Cancer Society.     

Predictive and prognostic impact of primary tumor-bearing lobe in nonsmall cell lung cancer patients treated with anti-PD-1 therapy

Immunotherapy targeting programmed cell death-1 (PD-1) has become a standard pharmacological therapy. Although tumor mutation burden level was reported to depend on the tumor location in nonsmall cell lung cancer (NSCLC), predictive impact of the tumor location on the response to anti-PD-1 therapy is unknown. Two hundred and seventeen advanced or recurrent NSCLC patients treated with anti-PD-1 therapy at Kyushu University Hospital and National Hospital Organization Kyushu Cancer Center were analyzed. To minimize the bias arising from the patients’ background, adjusted Kaplan-Meier survival curves and Cox proportional hazards regression analyses using inverse probability of treatment weights (IPTW) were performed. Of the 217 patients, 132, 27, and 58 had primary NSCLC in upper, middle, and lower lobes, respectively. Patients with NSCLC in upper lobe were significantly associated with younger age (P = .0070) and smoker (P = .0003). The epidermal growth factor receptor-wild type and tumor location in upper lobe were independent predictors of disease control (P = .0175 and P = .0425, respectively). The IPTW-adjusted Kaplan-Meier curves showed that patients with NSCLC in the upper lobes had significantly longer progression-free survival (PFS) and overall survival (OS) than those in middle/lower lobes (P = .0026 and P = .0015, respectively). On IPTW adjusted Cox analysis, NSCLC in the upper lobe was an independent predictor of PFS and OS (P = .0078 and P = .0034, respectively). Patients with primary NSCLC in the upper lobes may be good candidates for anti-PD-1 therapy. These findings should be validated prospectively.     

Prognostic influence of metformin as first-line chemotherapy for advanced nonsmall cell lung cancer in patients with type 2 diabetes

BACKGROUND:

It has been reported that antidiabetic drugs affect the risk of cancer and the prognosis of patients with diabetes, but few studies have demonstrated the influence of different antidiabetic agents on outcomes after anticancer therapy among patients with cancer. The objective of this study was to evaluate the influence of the antidiabetic drugs metformin and insulin on the prognosis of patients with advanced nonsmall cell lung cancer (NSCLC) plus type 2 diabetes who received first‐line chemotherapy.

METHODS:

Data on patients with NSCLC who had diabetes from 5 hospitals in China during January 2004 to March 2009 were reviewed retrospectively. Ninety‐nine patients were included in the final analysis. The influence of metformin and insulin on chemotherapy response rates and survival in these patients was evaluated.

RESULTS:

Chemotherapy with metformin (Group A) produced superior results compared with insulin (Group B) and compared with drugs other than metformin and insulin (Group C) in terms of both progression‐free survival (PFS) (8.4 months vs 4.7 months vs 6.4 months, respectively; P = .002) and overall survival (OS) (20.0 months vs 13.1 months vs 13.0 months, respectively; P = .007). Although no significant differences in the response rate (RR) were observed between these 3 groups, when groups B and C (ie, the nonmetformin group) were combined, there was a tendency for better disease control in Group A than that in nonmetformin group. No significant difference in survival was observed between chemotherapy with insulin (Group B) versus other drugs (Group C).

CONCLUSIONS:

The current data suggested that metformin may improve chemotherapy outcomes and survival for patients who have NSCLC with diabetes. Cancer 2011;. © 2011 American Cancer Society.     

Dose escalation of gemcitabine concomitant with radiation and cisplatin for nonsmall cell lung cancer

BACKGROUND:

The current study was conducted to evaluate the maximum tolerable dose of weekly gemcitabine administered simultaneously with radiation and cisplatin in patients with locally advanced nonsmall cell lung cancer (NSCLC).

METHODS:

Patients with stage IIIA/B NSCLC received concurrently 63 grays radiation and 20 mg/m² cisplatin Day 1 to 3 in Weeks 1 and 5, plus weekly gemcitabine at escalating doses (150‐700 mg/m²) on Fridays after radiation to avoid radiosensitization. The authors assessed dose‐limiting toxicities according to Common Toxicity Criteria. The primary endpoint was maximum tolerated dose (MTD) of gemcitabine. Tumor resectability, survival, and disease‐free survival (DFS) were also determined.

RESULTS:

Forty‐two patients were accrued, of whom 95% received radiation and 66% cisplatin as above. Weekly doses of gemcitabine were escalated to 700 mg/m². Grade 3 dysphagia and 1 case of fatal, probably treatment‐related pulmonary deterioration established the MTD of gemcitabine at 550 mg/m² weekly. Twenty‐five patients underwent surgery, and histopathological complete regression was documented in 26% of these patients. Overall, median actuarial survival and DFS were 23.8 and 12.4 months, respectively.

CONCLUSIONS:

Gemcitabine at doses up to 550 mg/m² weekly can be given simultaneously with radiation and cisplatin to patients with locally advanced NSCLC. Radical resection thereafter is feasible. The impact of this aggressive therapy should be evaluated further. Cancer 2010. © 2010 American Cancer Society.     

KRAS mutation status in primary nonsmall cell lung cancer and matched metastases

BACKGROUND:

The objective of this study was to determine whether the mutation status of the v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and epidermal growth factor receptor (EGFR) differed between primary tumors and matched distant metastases in nonsmall cell lung cancer (NSCLC).

METHODS:

Patients who underwent resection for both primary NSCLC and matched distant metastases were included in the study. KRAS and EGFR mutation status were assessed by polymerase chain reaction (PCR) amplification and direct sequencing on both primary tumors and metastases. For KRAS analysis, mutant‐enriched PCR (ME‐PCR) was performed in case of discordance between a primary tumor and its matched metastasis.

RESULTS:

Twenty‐one patients were included. No EGFR mutations were detected. KRAS mutations were detected in 6 patients (28%). In all patients, the mutations identified by direct sequencing were discordant between the primary tumor and the matched metastasis. The use of ME‐PCR allowed a resolution of the discordance in 3 of the 6 cases by demonstrating the presence of low levels of mutant KRAS in lesions that were negative by direct sequencing.

CONCLUSIONS:

Highly sensitive tools are required to identify biomarkers. The KRAS mutation status mostly was concordant between primary tumors and matched distant metastases. In a few patients, KRAS mutation status differed between different tumor sites. Cancer 2010. © 2010 American Cancer Society.     

Serum fibrinogen is an independent prognostic factor in operable nonsmall cell lung cancer

Serum fibrinogen converted to insoluble fibrin by activated thrombin, plays an important role in the coagulation system. Increased fibrinogen considerably influences cancer cell growth, progression and metastasis. In nonsmall cell lung cancer (NSCLC), however, the association between serum fibrinogen concentration and prognosis has not been fully examined. We enlisted 567 operable NSCLC patients in our study. Preoperative serum fibrinogen was measured by the Clauss method. The association of serum fibrinogen concentration with clinical pathological factors and patient outcome was evaluated. Survival analysis indicated that serum fibrinogen was an independent prognostic factor in operable NSCLC. Patients with hyperfibrinogenemia had an elevated risk of disease progression and death compared to patients with normal fibrinogen levels. The hazard ratio was 1.49 (95% confidence interval [CI] 1.07–2.05) for disease progression and 1.64 (95% CI 1.06–2.53) for death. The trend linking increasing fibrinogen levels with risk was also statistically significant for both outcomes (p < 0.05). These analyses were adjusted for patient age, sex, smoking behavior, disease stage, tumor grade and histology. Kaplan–Meier survival curves showed similar results. Preoperative serum fibrinogen is a novel independent prognostic biomarker in operable NSCLC.     

Definitive radiotherapy for stage I nonsmall cell lung cancer

BACKGROUND:

The current study characterizes the overall survival (OS) and cause‐specific survival (CSS) of patients with stage I nonsmall cell lung cancer (NSCLC) who were treated with radiotherapy alone, and analyzes the variables potentially affecting survival outcomes.

METHODS:

A total of 8524 patients with stage I NSCLC (according to the sixth edition of the American Joint Committee on Cancer staging manual) who were diagnosed between 1988 and 2008 were retrospectively analyzed using the population‐based Surveillance, Epidemiology, and End Results database. Cox regression analysis was used to calculate hazard ratios (HR) from multivariate analyses.

RESULTS:

The 1‐year, 2‐year, and 5‐year OS rates were 62%, 37%, and 11%, respectively; the corresponding lung cancer CSS survival rates were 68%, 45%, and 20%, respectively. Approximately 77% of deaths were from lung cancer (5292 of 6891 total deaths). Cardiac (n = 477 deaths) and pulmonary (other than lung cancer deaths; n = 475 deaths) deaths accounted for 14% of deaths. From Cox proportional hazards analyses, male sex (HR, 1.2) and squamous cell carcinoma histology (HR, > 1.1) were found to be significantly (P < .0001) adverse prognostic factors for both OS and lung cancer CSS. A more recent calendar year of diagnosis was associated with significantly (P < .0001) improved OS (HR, 0.84 per decade) and lung cancer CSS. This trend was also significant (P < 0.0001) when restricting analyses to those patients with tumors measuring ≤ 5 cm (n = 5402 patients). T1 classification (vs T2 or T unknown) and smaller tumor size were found to be significantly (P < .0001) favorable factors.

CONCLUSIONS:

From a population‐based registry analysis of patients with stage I NSCLC, significant (albeit modest) improvements in survival in more recent years were appreciated, which likely reflect technologic advances in the diagnosis of, staging of, and radiotherapy for NSCLC. Cancer 2012. © 2012 American Cancer Society.