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.     

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.     

Low socioeconomic status is a poor prognostic factor for survival in stage I nonsmall cell lung cancer and is independent of surgical treatment, race, and marital status

BACKGROUND: Racial minorities exhibit poor survival with nonsmall cell lung cancer (NSCLC) that generally is attributed to low socioeconomic status (SES). In this study, the authors investigated the role of SES in this survival disparity among patients with stage I NSCLC. METHODS: A case-only analysis was performed on California Cancer Registry (CCR) data (1989-2003). Univariate survival analyses were performed using the Kaplan-Meier method. Multivariate survival analyses were performed using Cox proportional hazards ratios. RESULTS: In total, 19,702 incident cases of stage I NSCLC were analyzed. Low SES was identified more commonly in African-American and Hispanic patients and was associated significantly with men, unmarried status, stage IB disease, squamous cell histology, poorly differentiated tumors, fewer surgical resections performed, and less overall treatment received. Reasons for no surgery were associated strongly with low SES and unmarried status but not with race. In multivariate analysis, each incremental improvement in SES quintile was associated with statistically significant decreases in the hazard ratios (HRs) for death (second SES quintile [SES2] vs SES1: HR, 0.91; 95% confidence interval [95% CI], 0.85-0.98; SES3 vs SES1: HR, 0.90; 95% CI, 0.84-0.97; SES4 vs SES1: HR, 0.83; 95% CI, 0.77-0.89; SES5 vs SES1: HR, 0.78; 95% CI, 0.72-0.84; P(trend) < .0001). African-American or Hispanic race was not an independent poor prognostic factor for survival after adjustment for surgery, SES, and marital status. CONCLUSIONS: Low SES was an independent poor prognostic factor for survival in patients with stage I NSCLC and was independent of surgery, race, and marital status.     

Extent of lymphadenectomy and outcome for patients with stage I nonsmall cell lung cancer

BACKGROUND:

It is uncertain whether lymphadenectomy (LA) affects overall survival (OS) or disease‐free survival (DFS) rates for patients with stage I nonsmall cell lung cancer (NSCLC), as is the optimal number of lymph nodes that should be recovered.

METHODS:

There were 24,273 patients with stage I NSCLC diagnosed from 1992 to 2002 who were included in the Surveillance, Epidemiology, and End Results database and who underwent a definitive surgical procedure. Median follow‐up was 35 months.

RESULTS:

For the entire population, having LA was associated with an increase in the 5‐year OS rate from 41.6% to 58.4% (P<.0001) and in DFS from 58.0% to 73.09%, compared with not having LA. Outcome improved with increasing number of recovered lymph nodes, with a plateau at 11 or more lymph nodes. For patients diagnosed from 1998 to 2002 undergoing only N1 or only N2 dissections, LA was also associated with statistically significant improvements in OS in both groups and a significant difference and trend for improved DFS in the 2 groups, respectively. The maximum differences in both OS and DFS between those with no LA and those with LA occurred when 11 to 16 lymph nodes were removed for the former group or 7 to 10 lymph nodes for the latter group, respectively.

CONCLUSIONS:

LA was associated with increased rates of OS and DFS, compared with no LA. Our results also suggest the minimum number of recovered lymph nodes needed to see the maximum staging accuracy conferred by LA. Cancer 2009. © 2009 American Cancer Society.     

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.     

High‐dose proton therapy and carbon‐ion therapy for stage I nonsmall cell lung cancer

BACKGROUND:

A study was undertaken to evaluate the clinical outcome of particle therapy for stage I nonsmall cell lung cancer (NSCLC).

METHODS:

From April 2003 to April 2007, 80 patients with stage I NSCLC were treated with proton therapy or carbon‐ion therapy (57 with proton therapy and 23 with carbon‐ion therapy) using 3 treatment protocols. In the first protocol, 80 gray equivalents (GyE) of proton therapy was given in 20 fractions, and the second proton therapy protocol used 60 GyE in 10 fractions. For carbon‐ion therapy, 52.8 GyE was given in 4 fractions. After achieving promising preliminary results for the first protocol, the authors started to use the second proton therapy protocol to shorten the overall treatment time. Carbon‐ion therapy was started in 2005, and thereafter, both proton and carbon‐ion therapy plans were made for each patient, and the 1 that appeared superior was adopted. Patient age ranged from 48 to 89 years (median, 76 years). Thirty‐seven patients were medically inoperable, and 43 refused surgery. Forty‐two patients had T1 tumors, and 38 had T2 tumors.

RESULTS:

The median follow‐up period for living patients was 35.5 months. For all 80 patients, the 3‐year overall survival, cause‐specific survival, and local control rates were 75% (IA: 74%; IB: 76%), 86% (IA: 84%; IB: 88%), and 82% (IA: 87%; IB: 77%), respectively. There were no significant differences in treatment results among the 3 protocols. Grade 3 pulmonary toxicity was observed in only 1 patient.

CONCLUSIONS:

Proton therapy and carbon‐ion therapy are safe and effective for stage I NSCLC. Further investigation of particle therapy for stage I NSCLC is warranted. Cancer 2010. © 2010 American Cancer Society.     

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.     

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.     

66例广泛期小细胞肺癌患者预后分析

目的:分析广泛期小细胞肺癌的独立预后因素。方法:回顾性分析安阳市肿瘤医院2005年7月至2009年7月治疗的66例广泛期小细胞肺癌的临床资料,所有患者均经组织病理或细胞学确诊。生存分析采用Kaplan-Meier法计算生存率,Log-rank检验进行单因素分析,并对有意义的单因素通过COX风险模型筛选影响预后因素。结果:广泛期患者1、2、3年生存率分别为40.9%、13.6%、6.1%,中位生存时间为10个月。单因素分析显示体重减轻情况、一线化疗疗效、总化疗周期数、治疗方式、低钠血症与患者预后相关,具有统计学差异。多因素分析显示一线化疗疗效、总化疗周期数、低钠血症对患者的总生存时间具有显著影响。结论:一线化疗疗效、总化疗周期数和低钠血症是影响广泛期小细胞肺癌的独立预后因素。     

Predominant infiltration of macrophages and CD8(+) T Cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer

BACKGROUND.: The purpose of this study was to investigate whether tumor-infiltrating immune cells in biopsy specimens can be used to predict the clinical outcome of stage IV nonsmall cell lung cancer (NSCLC) patients. METHOD.: The authors performed an immunohistochemical study to identify and count the number of CD68(+) macrophages, c-kit(+) mast cells, and CD8(+) T cells in both cancer nests and cancer stroma in pretreatment biopsy specimens obtained from 199 patients with stage IV NSCLC treated by chemotherapy, and then analyzed for correlations between the number of immune cells and clinical outcome, including chemotherapy response and prognosis. RESULTS.: There was no correlation between the number of immune cells in either cancer nests or stroma and chemotherapy response. Patients with more tumor-infiltrating macrophages in cancer nests than in cancer stroma (macrophages, nests > stroma) had significantly better survival than nests < stroma cases median survival time (MST 440 days vs 199 days; P < .0001). Patients with more tumor-infiltrating CD8(+) T cells in cancer nests than in cancer stroma (CD8(+) T cells: nests > stroma) showed significantly better survival than in nests < stroma cases (MST 388 days vs 256 days; P = .0070). The proportion of tumor-infiltrating macrophages or CD8(+) T cells between cancer nests and stroma became independent prognostic factors in the multivariate analysis. Neither the number of mast cells in nests nor in stroma correlated with the clinical outcome. CONCLUSIONS.: Evaluation of the numbers of macrophages and CD8(+) T cells in cancer nests and stroma are useful biomarkers for predicting the prognosis of stage IV NSCLC patients treated with chemotherapy, but could fail to predict chemotherapy response. Cancer 2008. (c) 2008 American Cancer Society.     

Prognostic value of symptom burden for overall survival in patients receiving chemotherapy for advanced nonsmall cell lung cancer

BACKGROUND:

Patient–reported outcomes have shown independent prognostic value for patients with nonsmall cell lung cancer (NSCLC). However, translating patient‐reported outcomes into useful prognostic information for individual patients has been problematic.

METHODS:

A total of 94 patients with advanced NSCLC and an Eastern Cooperative Oncology Group performance status (PS) of 0 to 2 who qualified for chemotherapy rated symptom severity using the M. D. Anderson Symptom Inventory before and after their first chemotherapy cycle. Prognostic values of baseline symptoms and changes in symptom severity were examined by Cox proportional hazards models.

RESULTS:

In multivariate analysis, controlled for demographic and other factors, baseline coughing rated ≥4 independently predicted significantly higher risk for shorter survival (hazards ratio [HR], 8.69; P < .0001). Patients with coughing ≥4 and a PS of 2 were more likely to have shorter survival (HR, 20.6; P < .0001) than patients with coughing <4 and a PS of 0 to 1. A 1–point or greater increase in severity of fatigue (P < .05), shortness of breath, or poor appetite (P < .01) from baseline to the end of the first chemotherapy cycle was also found to be independently associated with higher risk for poor survival.

CONCLUSIONS:

An increased risk for shorter survival was indicated by moderate to severe coughing at baseline or by increased fatigue or shortness of breath during the first chemotherapy cycle in patients with advanced NSCLC. Although cross–validation is needed, these data suggest that an individual patient's symptom severity scores, quickly obtainable in the clinic, might contribute clinically useful information for treatment planning for that patient. Cancer 2010. © 2010 American Cancer Society.     

老年广泛期小细胞肺癌患者的预后分析

目的:分析老年广泛期小细胞肺癌患者的独立预后因素。方法:回顾性研究2010年6月至2015年6月在安阳市肿瘤医院治疗的60例老年广泛期小细胞肺癌患者的临床资料,所有患者均经细胞学或组织病理明确诊断。采用Kaplan-Meier法计算生存时间和生存率,采用Log-rank检验单因素分析,对有统计学意义的单因素采用Cox风险模型进行多因素分析。结果:60例老年广泛期小细胞肺癌患者1年、2年、3年生存率分别为38.3%、8.3%、3.3%,中位生存时间为10.0个月。单因素分析显示年龄、ECOG评分、一线化疗疗效、化疗周期数、肝转移情况和合并慢性疾病情况是影响患者预后的因素,P值小于0.05,具有统计学差异。Cox风险模型分析显示,年龄、ECOG评分、一线化疗疗效、化疗周期数和肝转移情况对患者的总生存时间具有显著影响。结论:患者年龄、ECOG评分、一线化疗疗效、化疗周期数和肝转移情况是影响老年广泛期小细胞肺癌的独立预后因素。     

A comparison of survival and disease-specific survival in surgically resected, lymph node-positive bronchioloalveolar carcinoma versus nonsmall cell lung cancer: implications for adjuvant therapy

BACKGROUND: The objective of this study was to assess whether disease-specific survival (DSS) and overall survival (OS) differed among patients who had N1 and N2 bronchioloalveolar carcinoma (BAC) compared with patients who had non-BAC nonsmall cell lung cancer (NSCLC). METHODS: The Surveillance, Epidemiology, and End Results (SEER) Program database from 1992 to 2002 contained 684 patients with BAC and 9809 patients with non-BAC NSCLC who had N1/N2 tumors and who underwent a definitive surgical procedure. OS and DSS rates were compared according to potential prognostic factors, including the use of a matched-pair analysis. RESULTS: The BAC patients with either pathologic N1 or N2 lymph node status were significantly more likely to be women, and nonblack/nonwhite race, but significantly less likely to have poorly differentiated or undifferentiated tumors than patients with non-BAC cancers with comparable lymph node status. The median follow-up of all patients was 29 months. There was a significant difference in DSS between patients with N2 BAC and non-BAC cancers, but not for patients with N1 disease. There was a nonsignificant trend toward longer OS for patients with N2 BAC compared with non-BAC cancers. CONCLUSIONS: Patients with lymph node-positive BAC had distinctly different patient and tumor characteristics than patients with lymph node-positive non-BAC NSCLC. Because DSS appears to be better for patients with N2 BAC, they may not benefit as much from adjuvant therapy as patients with non-BAC NSCLC.     

CD24 is an independent prognostic marker of survival in nonsmall cell lung cancer patients

Originally identified as a B-cell marker, expression of the cell surface molecule CD24 has meanwhile been observed in a variety of human malignancies. It appears to function as a ligand of P-Selectin, an adhesion molecule that is present in activated platelets and endothelial cells. We aimed to determine the rate of CD24 expression in our nonsmall cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters including patients' survival. A total of 89 NSCLC were analysed immunohistochemically using a monoclonal CD24 antibody (clone 24C02) and a standard detection system (LSAB, DAKO) on NSCLC tissue microarrays (TMA). The staining was semiquantitatively scored (0, 1+, 2+, 3+) and grouped into high (2+, 3+)- and low (0, 1+)-level expression for statistical analysis. A high level of CD24 expression was observed in 45% of the cases, preferentially adenocarcinomas. Patients whose tumours had a high CD24 expression showed a significantly shorter median survival time of 23 months vs 38 months (P=0.033, log-rank test). Similarly tumour, grading, nodal status and clinical stage were significant prognostic markers in univariate survival analysis. Importantly, in the Cox regression-based multivariate analysis, CD24 expression (P=0.025) together with tumour stage (P=0.006) and grade (P=0.011) proved to be independent prognostic parameters. We hypothesise that the decreased survival of NSCLC patients with strongly CD24-positive tumours is related to an enhanced propensity of haematogenous metastasis formation, which might be P-Selectin mediated.     

Final survival and safety results from a multicenter, open-label, phase 3b trial of erlotinib in patients with advanced nonsmall cell lung cancer

BACKGROUND: Erlotinib is an orally available, reversible inhibitor of epidermal growth factor receptor (EGFR) with a proven survival advantage for patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) who have failed a prior chemotherapy. This phase 3b, multicenter, open-label trial of erlotinib in patients with advanced NSCLC who had progressed after standard chemotherapy treatment was conducted to examine the efficacy and safety of erlotinib monotherapy in patients with advanced NSCLC who had developed disease progression after previous chemotherapy and to characterize the duration of survival and the response rate of erlotinib-treated patients in subpopulations defined by other patient characteristics before U.S. Food and Drug Administration approval. METHODS: A total of 229 patients were enrolled and treated with the standard dose of erlotinib (150 mg once daily). The coprimary objectives were to characterize the overall response rate (ORR) and overall survival (OS) associated with erlotinib therapy in this group and in patient subsets defined by tobacco history. Secondary objectives were to assess safety, to characterize OS and ORR in patient subpopulations, and to determine duration of time on treatment. Patients could remain on study up to 9 months after approval. RESULTS: The ORR was 8.3% (95% confidence interval [95% CI], 5.2-2.4%). The ORR in never-smokers, previous smokers, and current smokers was 28.6% (95% CI, 13.2-50.6%), 6.0% (95% CI, 3.0-10.4%), and 7.3% (95% CI, 2.0-19.0%), respectively. The median OS for all patients was 6.3 months (95% CI, 4.7-8.0 months). In previous and current smokers, the median survival was 5.2 months (95% CI, 4.2-7.3 months) and 6.3 months (95% CI, 3.6-9.2 months), respectively, and was not reached in never-smokers. The median duration of treatment was 10.6 weeks. One (0.4%) interstitial lung disease-like event was reported. CONCLUSIONS: No new safety signals were noted. The observed ORR and survival data are consistent with results from the pivotal trial BR.21.     

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.     

Stereotactic body radiotherapy using a radiobiology-based regimen for stage I nonsmall cell lung cancer: a multicenter study

BACKGROUND:

The most common regimen of stereotactic body radiotherapy (SBRT) for stage I nonsmall cell lung cancer in Japan is 48 grays (Gy) in 4 fractions over 4 days. Radiobiologically, however, higher doses are necessary to control larger tumors, and interfraction intervals should be >24 hours to take advantage of reoxygenation. In this study, the authors tested the following regimen: For tumors that measured <1.5 cm, 1.5 to 3.0 cm, and >3.0 cm in greatest dimension, radiation doses of 44 Gy, 48 Gy, and 52 Gy, respectively, were given in 4 fractions with interfraction intervals of ≥3 days.

METHODS:

Among 180 patients with histologically proven disease who entered the study, 120 were medically inoperable, and 60 were operable. The median patient age was 77 years (range, 29‐92 years). SBRT was performed with 6‐megavolt photons using 4 noncoplanar beams and 3 coplanar beams. Isocenter doses of 44 Gy, 48 Gy, and 52 Gy were received by 4 patients, 124 patients, and 52 patients, respectively.

RESULTS:

The overall survival rate for all 180 patients was 69% at 3 years and 52% at 5 years. The 3‐year survival rate was 74% for operable patients and 59% for medically inoperable patients (P = .080). The 3‐year local control rate was 86% for tumors ≤3 cm (44/48 Gy) and 73% for tumors >3 cm (52 Gy; P = .050). Grade ≥2 radiation pneumonitis developed in 13% of patients (10% of the 44‐Gy/48‐Gy group and 21% of the 52‐Gy group; P = .056). All other grade 2 toxicities developed in <4% of patients.

CONCLUSIONS:

The SBRT protocol used in this study yielded reasonable local control and overall survival rates and acceptable toxicity. Dose escalation is being investigated. Cancer 2012;. © 2011 American Cancer Society.     

From conventionally fractionated radiation therapy to hyperfractionated radiation therapy alone and with concurrent chemotherapy in patients with early-stage nonsmall cell lung cancer

BACKGROUND: The authors' single-institution experience in patients with early-stage (I and II) nonsmall cell lung cancer (NSCLC) who were treated between 1980 and 1998 with either conventionally fractionated (CF) radiation therapy (RT), or hyperfractionated (HFX) RT, or HFX RT with concurrent paclitaxel/carboplatin (HFX RT-Pac/C) was reviewed. METHODS: Seventy-eight patients received 60 grays (Gy) in 30 daily fractions (CF), 116 patients received 69.6 Gy (1.2 Gy twice daily), and 56 patients received 67.6 Gy (1.3 Gy twice daily) with concurrent, low-dose, daily C (25 mg/m2) and Pac (10 mg/m2). Biologically equivalent doses for the 3 groups were 72 Gy, 78 Gy, and 76 Gy, respectively, for acute effects (alpha/beta = 10 Gy) and 120 Gy, 111 Gy, and 111 Gy, respectively, for late effects (alpha/beta = 2 Gy). RESULTS: For all 250 patients, the overall median survival was 27 months, the cause-specific survival was 27 months, the local progression-free survival was 32 months, and distant metastasis-free survival was not achieved; and the respective 5-year survival rates were 27%, 32%, 45%, and 68%. CF achieved significantly inferior survival than either HFX RT alone or HFX RT-Pac/C (P = .0332 and P = .0013, respectively), and no difference was observed between the 2 HFX RT regimens (P = .1934). Only acute hematologic high-grade toxicity (grade >or=3) was more frequent with HFX RT-Pac/C than with either RT alone, whereas other toxicities were similar between the 3 treatment groups. CONCLUSIONS: HFX RT with or without concurrent chemotherapy may be better than CF in patients with early-stage NSCLC. The role of chemotherapy deserves further investigation, because the group that received chemotherapy in the current study had a higher incidence of acute high-grade hematologic toxicity.     

Varying recurrence rates and risk factors associated with different definitions of local recurrence in patients with surgically resected,stage I nonsmall cell lung cancer

BACKGROUND:

The objective of this study was to examine the effects of different definitions of local recurrence on the reported patterns of failure and associated risk factors in patients who undergo potentially curative resection for stage I nonsmall cell lung cancer (NSCLC).

METHODS:

The study included 306 consecutive patients who were treated from 2000 to 2005 without radiotherapy. Local recurrence was defined either as “radiation” (r‐LR) (according to previously defined postoperative radiotherapy fields), including the bronchial stump, staple line, ipsilateral hilum, and ipsilateral mediastinum; or as “comprehensive” (c‐LR), including the same sites plus the ipsilateral lung and contralateral mediastinal and hilar lymph nodes. All recurrences that were not classified as “local” were considered to be distal.

RESULTS:

The median follow‐up was 33 months. The proportions of c‐LR and r‐LR at 2 years, 3 years, and 5 years were 14%, 21%, and 29%, respectively, and 7%, 12%, and 16%, respectively. Significant risk factors for c‐LR on multivariate analysis were diabetes, lymphatic vascular invasion, and tumor size; and significant factors for r‐LR were resection of less than a lobe and lymphatic vascular invasion. The proportions of distant (nonlocal) recurrence using these definitions at 2 years, 3 years, and 5 years were 10%, 12%, and 18%, respectively, and 14%, 19%, and 29%, respectively. Significant risk factors for distant failure were histology when using the c‐LR definition and tumor size when using the r‐LR definition.

CONCLUSIONS:

Local recurrence increased nearly 2‐fold when a broad definition was used instead of a narrow definition. The definition also affected which factors were associated significantly with both local and distant failure on multivariate analysis. Comparable definitions must be used when analyzing different series. Cancer 2010. © 2010 American Cancer Society.