Pulmonary tuberculosis increases the risk of lung cancer: a population-based cohort study

BACKGROUND:

The possible effect of pulmonary tuberculosis (TB) on subsequent lung cancer development has been suspected, but the evidence remains inconsistent. The purpose of this study was to perform a nationwide population‐based cohort study to investigate the risk of lung cancer after pulmonary TB infection.

METHODS:

This nationwide population‐based cohort study was based on data obtained from the Taiwan National Health Insurance Database. In total, 5657 TB patients and 23,984 controls matched for age and sex were recruited for the study from 1997 to 2008.

RESULTS:

The incidence rate of lung cancer (269 of 100,000 person‐years) was significantly higher in the pulmonary TB patients than that in controls (153 of 100,000 person‐years) (incidence rate ratio [IRR], 1.76; 95% confidence interval [CI], 1.33‐2.32; P < .001). Compared with the controls, the IRRs of lung cancer in the TB cohort were 1.98 at 2 to 4 years, 1.42 at 5 to 7 years, and 1.59 at 8 to 12 years after TB infections. The multivariate Cox proportional hazards model revealed pulmonary TB infections (hazard ratio [HR], 1.64; 95% CI, 1.24‐2.15; P < .001) and chronic obstructive pulmonary disease (HR, 1.09; 95% CI, 1.03‐1.14; P = .002) to be independent risk factors for lung cancer.

CONCLUSIONS:

Pulmonary infection with TB is associated with an increased risk of lung cancer. Cancer 2011. © 2010 American Cancer Society.     

The human CYP2E1 gene and lung cancer: DraI and RsaI restriction fragment length polymorphisms in a Finish study population

We investigated point mutational DraI and RsaI restriction fragmentlength polymorphisms (RFLPs) in the CYP2E1 gene in 101 lungcancer patients, 40 patients with other pulmonary diseases and121 healthy control subjects. In the DraI RFLP analysis of the121 healthy control subjects, 96 had the DD genotype, 24 theCD genotype and one the CC genotype. Genotypic distributionin the patients with other pulmonary disease showed a similartrend (P = 0.50), though the group was considerably smaller.The distribution of Dral genotypes in the lung cancer patientswas not significantly different from that of the healthy controls(P = 0.44). We were not able to reproduce the results of a Japanesereport describing a statistically significant association betweenthe rare DraI RFLP genotype CC and predisposition to lung cancer.Furthermore, this genotype was much less frequent in our studypopulations than In the Japanese study. The other point mutationstudied, which results in RsaI restriction site polymorphismin the 5'-flanking region of the CYP2E1 gene, was almost absentin our study groups. These findings on our Finnish lung cancerpopulation suggest that the CYP2E1 gene polymorphisms studieddo not have an important role in susceptibility to lung cancer.     

Patients With Lung Cancer With Metachronous or Synchronous Gastric Cancer

BackgroundThere are few reports of treatment and outcome for patients with metachronous or synchronous lung and gastric cancers. To evaluate them, we conducted a retrospective study.Patients and MethodsThe medical records of patients with lung cancer who previously or simultaneously had gastric cancer seen in our division between January 1979 and July 2008 were reviewed.ResultsForty-five (3.2%) of 1391 patients had previous or simultaneous gastric cancer. The proportion of men was higher among patients with lung cancer with gastric cancer than those without (P = .0006). There was a significant difference in age at the time of diagnosis of lung cancer between the 45 patients with gastric cancer and the 1346 patients without it (P = .0344). The proportion of smokers was higher among lung cancer patients with gastric cancer than those without (P = .0015). Twenty-seven of 45 patients had smoking-related cell types of lung cancer: squamous cell carcinoma and small-cell lung cancer. The proportion of these 2 cell types was higher in patients with lung cancer with gastric cancer than those without (P = .02). The diagnosis of gastric cancer preceded the diagnosis of lung cancer in 33 patients, and the median duration from the diagnosis of gastric cancer to that of the lung cancer was 6 years.ConclusionFor patients with gastric cancer, smoking cessation, a chest radiograph at least yearly for several years, and swift evaluation of signs or symptoms that are suggestive of lung cancer should be recommended, especially in elderly men with gastric cancer and smoking habit.     

Association of diffuse, random pulmonary metastases, including miliary metastases, with epidermal growth factor receptor mutations in lung adenocarcinoma

BACKGROUND:

Although the association of multiple pulmonary metastases, and particularly miliary metastases, with response to gefitinib treatment in patients with nonsmall cell lung cancer has been reported, the association of miliary pulmonary metastases with epidermal growth factor receptor gene (EGFR) mutations remains unclear.

METHODS:

The authors retrospectively investigated the association of diffuse, random pulmonary metastases in patients with lung adenocarcinoma. The study included 163 Japanese patients who had unresectable, advanced lung adenocarcinoma diagnosed between April 2003 and March 2010. Computed tomography scans that were obtained at the time of diagnosis were analyzed by 2 investigators. For the purposes of this study, diffuse, random pulmonary metastases were defined as multiple nodules (n = 50; ≤3 cm in greatest dimension) distributed diffusely and randomly throughout the lungs.

RESULTS:

Of 163 patients, 55 had pulmonary metastases, and EGFR mutations were detected in 22 of those 55 patients. The mutations were identified preferentially among women (P = .15) and were identified significantly among patients who had a smoking history of <10 pack‐years (P = .0057). Diffuse, random pulmonary metastases were identified in 11 of 22 patients who had EGFR mutations and in 4 of 33 patients who had the wild‐type EGFR (P = .0043). On the basis of multivariate analyses, EGFR mutations were associated independently with a smoking history of <10 pack‐years (P = .026) and with diffuse, random pulmonary metastases (P = .012).

CONCLUSIONS:

When patients with lung adenocarcinomas who had EGFR mutations developed pulmonary metastases, they tended to be diffuse and random, including military metastases. However, such metastases were much less common in patients who had lung adenocarcinomas with wild‐type EGFR. Cancer 2011. © 2010 American Cancer Society.     

Combined effect of CYP1A1 inducibility and GSTM1 polymorphism on histological type of lung cancer

The combinations of the CYP1A1 inducibility and GSTM1 polymorphismhave been investigated in relation to the histological typeand peripheral or bronchial location of lung cancer in 54 surgicallytreated, current smoker lung cancer patients. The induced CYP1A1was detected in 46 patients (85%) and the homozygous GSTM1 nullgenotype in 32 patients (59%). The role of CYP1A1 inducibilitywas found to be more important than that of GSTM1 polymorphism,because the non-inducible CYP1A1 was associated solely withbronchial tumours (P=0.001), mainly squamous cell carcinomas.In patients with inducible CYP1A1, the expressing GSTM1 geneappeared to have a protective effect against contracting bronchiallung cancer, since 88% (14/16) of the lung tumours in this patientgroup were peripheral, whereas almost equal numbers of peripheraland bronchial tumours were observed In those patients lackingthe gene (P= 0.037).     

Metformin decreases lung cancer risk in diabetic patients in a dose-dependent manner

Objectives

Higher risk of lung cancer has been noted in patients with type 2 diabetes mellitus (DM). Some observational studies have shown a reduced risk of lung cancer in DM patients taking metformin, but a dose–response relationship has never been reported. The aim of this study is to exam the association between the dose of metformin and the incidence of lung cancer in a Chinese population.

Materials and methods

The dataset used for this nationwide population-based study is a cohort of 1 million subjects randomly sampled from individuals enrolled in the Taiwan National Health Insurance system. We enrolled all subjects with newly diagnosed type 2 DM between 1997 and 2007. Subjects with a diagnosis of neoplasm before DM diagnosis, those using metformin before DM diagnosis, those with polycystic ovary syndrome, and those with a DM diagnosis before their 15 years of age were excluded. The demographic data and duration, cumulative dose and intensity of metformin use were compared between patients developing lung cancer and those without lung cancer.

Results

Totally, 47,356 subjects were identified. After adjusting for age, gender, and modified Charlson Comorbidity Index score, the utilization of metformin was an independent protecting factor, and the risk of developing lung cancer decreased progressively with either the higher cumulative dose or the higher intensity of metformin use.

Conclusions

This study revealed that the use of metformin decreased the risk of lung cancer in a dose-dependent manner in patients with type 2 DM. The chemo-preventive effect of metformin deserves further study.     

Impact of Tumor Extent and Location on Treatment Outcome in Patients with Stage III Non-small Cell Lung Cancer Treated with Radiation Therapy

The results of treatment of 141 patients with stage III non-smallcell lung cancer (NSCLQ who received definitive radiation therapyat Gunma University Hospital between 1976 and 1989 were retrospectivelyanalyzed. Radiation was given with standard fractionation fora planned prophylactic dose of 40 Gy over 4 weeks and a definitivedose of 60 Gy over 6 weeks or more. The two- and five-year survivalrates were 27% and 12% for stage IIIA, and 18% and 8% for stageIIIB, respectively (P = 0.052). By univariate analysis, a primarytumor less than 5 cm in diameter was also an important predictorof survival (P = 0.008). As for tumor location, the patientswith primary tumors in the upper lobes or the superior segmentof the lower lobes of the lung lived longer than those withprimary tumors at any other site (P = 0.032). Patients withepidermoid carcinoma had a higher survival rate at 5 years thanthose with other histologic types (14% vs 3%, P = 0.074). Multivariateanalysis showed that among tumor characteristics, the site ofthe primary tumor, the pattern of tumor spread and N stage weresignificantly associated with overall survival. Among the patientswith stage III NSCLC, those with stage IIIA epidermoid carcinomain the upper lobe or the superior segment of the lower lobeof the lung were considered to be the most favorable candidatesfor definitive radiation therapy.     

The relationship between chronic obstructive pulmonary disease and lung cancer in African American patients

RationaleAirflow obstruction and/or emphysema have been associated with lung cancer risk; however, this relationship and the joint occurrence of these conditions are not well studied in the African American populationObjectiveTo describe the prevalence of airflow obstruction and/or emphysema in African Americans with lung cancer and to evaluate their impact on the management and outcome of lung cancer.MethodsMedical records of 114 African Americans who had participated in population-based case-control studies of lung cancer and who sought medical care at the Karmanos Cancer Center in Detroit, Michigan, were reviewed. The medical records of these patients were reviewed for demographics, type and stage of lung cancer, spirometry, treatment, and outcome. Computed tomographies (CT) of the chest about the time of the diagnosis of lung cancer were reviewed by a radiologist for evidence of emphysema. COPD was diagnosed when there were changes consistent with emphysema on CTs and/or airflow obstruction by spirometry.ResultsThere were no differences by sex for age at lung cancer diagnosis (P = .78) and tumor histology (P = .43). The men were more likely to present at a later stage of lung cancer diagnosis compared with the women (P = .04), and the women were more likely to have surgery than the men (P = .03). Overall, 94% of the men and 78% of the women in this population had spirometry and/or CT evidence of COPD. The men were somewhat more likely to have COPD diagnosed by either CT or spirometry than were the women (P = .06), but the Global Obstructive Lung Disease Classification scores did not differ by sex among those with spirometry-diagnosed COPD (P = .34). Seventy-eight percent of individuals who did not report a previous diagnosis of COPD had clinical evidence of COPD, whereas 94% of individuals who reported a previous diagnosis of COPD also had clinical evidence of COPD (P = .03). Among individuals who had both spirometry and CT data available, 29% had CT evidence of emphysema but normal spirometry. No differences in COPD diagnosis (P = .82) or emphysema diagnosis (P = .51) were noted by tumor histology. Stage at diagnosis also did not differ by COPD or emphysema diagnosis (P = .30 and P = .06, respectively), nor did treatment modality (P = .54 and P = .10, respectively). Patients with lung cancer and with COPD, diagnosed either via spirometry or CT, did not show an increased risk of death compared with patients with lung cancer and without COPD after adjusting for age at diagnosis, sex, and stage (hazard ratio, 1.31 [95% CI, 0.68-2.53]).ConclusionThere is a high incidence of COPD, emphysema in particular, in a selected group of African American patients with lung cancer. A significant number of these patients were not aware that they had COPD. There was no significant difference in the outcome of lung cancer in relation to the presence or absence of COPD.     

Interhospital Differences in Cancer Survivals in Japan

The present study was an investigation of variations in cancersurvival rates among hospitals in Japan, focusing in particularon the number of hospital beds as an institutional characteristic.Using data from 11 population-based cancer registries, the three-yearsurvival rates for stomach cancer (n 1665), colorectal cancer(n 1090) and lung cancer (n 895) patients diagnosed in 1985were calculated according to three different hospital categories(100–299, 300–499, 500+ beds). Cox's proportionalhazards model was conducted, with adjustments for sex, age,clinical stage at diagnosis and treatment status, excludingpatients who had been detected by screening (asymptomatic cases).The stomach and lung cancer patients treated in small hospitals(100–299 beds) were at a significantly higher risk ofdeath than those treated in large hospitals (500+ beds) (hazardratio (HR)=1.36, 95% confidence interval (CI)= 1.11–1.65;HR=1.41, 95% CI = 1.13–1.77, respectively). Similar findingswere observed among colorectal cancer patients although theywere not statistically significant. The findings can providesome information useful for the development of future publichealth policies aimed at controlling cancer mortality ratesin our country.     

肺腺癌患者中EGFR突变与肺结核的相关性研究

  目的  研究肺腺癌患者中表皮生长因子受体（epidermal growth factor receptor,EGFR）基因突变与肺结核在肺腺癌中的相关性。  方法  采用PCR扩增及基因测序方法检测506例肺腺癌患者EGFR基因突变情况,分析其与肺结核之间的关系,进一步使用Kaplan-Meier法进行生存分析并行Log-rank检验。  结果  506例肺腺癌患者中有218例患者存在EGFR突变,其中25例患者有感染肺结核病史。在肺腺癌患者中,有肺结核病史的患者EGFR基因突变率,尤其是外显子21缺失显著高于单纯肺腺癌者（P= 0.047,P=0.002）。肺腺癌与结核灶在同一肺叶或同侧肺的患者EGFR基因突变率明显高于二者在不同侧肺,尤其是外显子21突变（P=0.020,P=0.030）。有肺结核病史患者的2年生存率明显高于单纯肺腺癌患者（P=0.039）,且在未经EGFR-TKIs治疗的具有肺结核史的患者中,EGFR突变组与野生型组相比,2年生存率无统计学差异（P=0.948）,经过EGFR-TKIs治疗的患者2年生存率亦差异无统计学意义（P=0.425）。  结论  肺腺癌患者中,有肺结核病史的患者EGFR基因突变发生率明显增高,且EGFR基因突变与其预后无关。      

Human immunodeficiency virus-associated lung cancer in the era of highly active antiretroviral therapy

BACKGROUND:

Lung cancer is the leading cause of death among non‐acquired immunodeficiency syndrome (AIDS)‐defining malignancies. Because highly active antiretroviral therapy (HAART) has improved the survival of patients with human immunodeficiency virus (HIV), the authors evaluated lung cancer outcomes in the HAART era.

METHODS:

HIV‐positive patients who were diagnosed with lung cancer at the authors' institution during the HAART era (1995‐2008) were analyzed. Patient charts were reviewed for clinical and laboratory data. The CD4 count at diagnosis was treated as a continuous variable and subcategorized into distinct variables with 3 cutoff points (50 cells/mL, 200 cells/mL, and 500 cells/mL). Pearson correlation coefficients were estimated for each covariate studied. Survival was determined by using the Kaplan‐Meier method.

RESULTS:

Of 80 patients, 73 had nonsmall cell lung cancer. Baseline characteristics were as follows: median patient age, 52 years; male, 80%; African Americans, 84%; injection drug users, 25%; smokers, 100%; and previous exposure to antiretroviral agents, 55%. At the time of cancer diagnosis, the mean CD4 count was 304 cells/mL, and the mean viral load was 82,420 copies/mL. The latency between HIV diagnosis and lung cancer diagnosis was significantly shorter among women (4.1 years vs 7.7 years; P = .02), and 71% of patients received anticancer therapy. The 1‐year and 3‐year survival rates for stage IIIB/IV were 25% and 0%, respectively. Grade 3/4 toxicities occurred in 60% of patients who received chemoradiation versus 36% of patients who received chemotherapy. Cancer‐related survival was better for patients with CD4 counts >200 cells/mL (P = .0298) and >500 cells/mL (P = .0076).

CONCLUSIONS:

The latency from diagnosis of HIV to lung cancer was significantly shorter for women. Although outcomes for patients with lung cancer who have HIV remain poor, a high CD4 count was associated with improved lung cancer‐related survival. Cancer 2012;. © 2011 American Cancer Society.     

Clinical characteristics of 45 patients with invasive pulmonary aspergillosis

BACKGROUND:

Invasive aspergillosis (IA) is a common complication in patients with hematologic malignancies. Patients with solid tumors also are at risk for IA because they may develop neutropenia as a result of chemotherapy and radiotherapy. However, studies of IA in patients with solid tumors are rare. In this study, the risk factors and clinical characteristics of pulmonary infection and death mediated by invasive pulmonary aspergillosis (IPA) as complications in patients with lung cancer were determined.

METHODS:

The authors conducted a retrospective analysis of the clinical notes from 45 patients who had IPA.

RESULTS:

Among 1711 patients with lung cancer, 45 patients contracted pulmonary aspergillosis (2.63%). There were 10 cases of proven disease and 35 cases of probable disease. In univariate analysis, the main predisposing factors were clinical stage IV disease (P = .018), chemotherapy during the month preceding infection (P = .033), and corticosteroid use (≥3 days; P = .038). In multivariate analysis, only clinical stage IV disease (P = .018) was associated with IPA. Furthermore, the mortality rate among lung cancer patients who had pulmonary aspergillosis was 51.1% (23 of 45 patients). Of the patients who died, corticosteroid therapy (P = .001) and grade 3/4 neutropenia (P = .013) were correlated statistically with pulmonary aspergillosis in patients with lung cancer.

CONCLUSIONS:

In univariate analysis, the risk factors for IPA in lung cancer included chemotherapy and corticosteroid use in the month preceding infection and clinical stage IV disease. However, in multivariate analysis, only clinical stage IV disease was identified as a risk factor for IPA. Cancer 2009. © 2009 American Cancer Society.     

Differential Diagnoses of Solitary Pulmonary Nodules in Patients with an Extrcrlhoracic Malignant Tumor：CT and Pathologic Correlations

Objective To determine the possibility of definitive diagnosis for solitary pulmonary nodules in patients with a primary extrathoracic malignant neoplasm (ETM-SPN), and to further evaluate the value of CT for differential diagnosis in ETM-SPN by a multivariate retrospective study. Methods Eighty-three patients with pathologically and clinically proven ETM-SPN with a diameter smaller than 3 cm were included in this study. The pathological characteristics of the SPN were correlated with those of the extrathoracic neoplasm, with the patient’s age, gender, smoking history, disease -free time interval between the diagnosis of the extrathoracic malignancy and that of the lung lesion. In all 83 cases, CT scans were reviewed to confirm the solitary nature, size, and nodular morphology of the lung lesion. Results Of all 83 cases, the mean age was (57.43±15.34) years. There were 51 males and 32 females, with the ratio of 1.59:1. The lesions included solitary metastasis in 43 cases, pulmonary malignant lesions in 33, and benign lesions in seven. Between the primary lung cancers and solitary metastasis groups, there was no significant difference in the gender ratio (1.20:1 vs 2.31:1, x²=0.0209,P>0.05), but there was a significant difference between the mean age (62.48 ±11.96 years vs 54.10±16.49 years,t =3.34,P<0.05). In the primary lung cancer and metastasis patient group, the percentage of patients who had a smoking history were 39.3 %(11/17) and 35.9 %(14/39), respectively. Patients with a primary lung cancer had no significant higher frequency of smoking history than did those with a metastatic lesion (x²=0.640,P>0.05). Of 81 cases who were followed-up, the mean time of the disease-free interval between extrapulmonary malignancy diagnosis and pulmonary lesion differentiation was 39.73 ±6.29 months (range 0∼300 months, median 20.00 months), whereas those in the primary lung cancer group and metastatic group were 65.62 ±13.45 months and 22.83 ±4.19 months respectively. This difference was significant between the two groups (Wilcoxon rank sum test,U=2.796,P<0.01). Of all 83 cases, there were ten extrapulmonary squamous carcinomas and 58 adenocarcinomas with ratio of primary lung cancer and solitary metastasis of the tumors were 7: 3 and 24:34, respectively (Ξ² =1.781, P >0.05), without showing a statistically significant relevance between the pathologic patterns of extrapulmonary malignancy and characteristics of the lung nodules. Of all the 83 cases, the mean diameters were (2.77 ±.25) cm, whereas the diameters of 33 cases of primary lung cancer and 43 cases of a solitary metastatic lesion were (2.86±1.18) cm and (2.62±1.31) cm, respectively. There was no association between the two groups (t=1.29,P>0.05). There was a statistically significant association between primary lung cancer and the metastatic group with spiculate and smooth edges of the lung lesion (Ξ²=8.562,P<0.01; Ξ²=15.220,P<0.001). The study showed that a lung nodule with a spiculated margin correlated with a primary lung carcinoma, whereas those nodules with a smooth edge may more frequently show as a metastastic pulmonary lesion. CTpathologic correlative analyses of hilar and mediastinal adenopathy were reviewed in 37 patients who underwent lobectomy and thoracotomy. There was no statistical significant difference between the primary lung cancer group and the metastatic group (Ξ²=2.801,P>0.05). Conclusion The likelihood of a primary lung cancer versus a metastasis of ETM-SPN smaller than 3 cm mainly depends on the patient’s age, free interval between the two tumors and CT morphological characteristics of the lung lesion. This study showed there was no significant relevancy to factors such as gender, smoking history, pathological patterns of the extrapulmonary neoplasm or whether there has hilar or mediastinal adenopathy.     

The impact of pregnancy on breast cancer outcomes in women ≤35 years

BACKGROUND:

Some evidence suggests that women with pregnancy‐associated breast cancers (PABC) have a worse outcome compared with historical controls. However, young age is a worse prognostic factor independently, and women with PABC tend to be young. The purpose of the current study was to compare locoregional recurrence (LRR), distant metastases (DM), and overall survival (OS) in young patients with PABC and non‐PABC.

METHODS:

Data for 668 breast cancers in 652 patients aged ≤35 years were retrospectively reviewed. One hundred four breast cancers (15.6%) were pregnancy‐associated; 51 cancers developed during pregnancy and 53 within 1 year after pregnancy.

RESULTS:

The median follow‐up for all living patients was 114 months. Patients who developed PABC had more advanced T classification, N classification, and stage group (all P < .04) compared with patients with non‐PABC. Patients with PABC had no statistically significant differences in 10‐year rates of LRR (23.4% vs 19.2%; P = .47), DM (45.1% vs 38.9%; P = .40), or OS (64.6% vs 64.8%; P = .60) compared with patients with non‐PABC. For those patients who developed breast cancer during pregnancy, any treatment intervention during pregnancy provided a trend toward improved OS compared with delaying evaluation and treatment until after delivery (78.7% vs 44.7%; P = .068).

CONCLUSIONS:

Young patients with PABC had no statistically significant differences in LRR, DM, or OS compared with those with non‐PABC; however, pregnancy contributed to a delay in breast cancer diagnosis, evaluation, and treatment. Primary care and reproductive physicians should be aggressive in the workup of breast symptoms in the pregnant population to expedite diagnosis and allow multidisciplinary treatment. Cancer 2009. © 2009 American Cancer Society.     

Multiple primary malignancies involving lung cancer-clinical characteristics and prognosis.

The incidence of multiple primary malignancies has increased in recent decades. The present study attempts to determine the clinical characteristics, the smoking factor, prognosis and temporal relationship of lung cancer to other cancers in patients with multiple primary malignancies. A total of 193 patients with multiple primary cancers involving lung cancer were found among 22,405 cancer cases diagnosed in Taipei Veterans General Hospital, between 1993 and 1997. Patients' clinical characteristics, smoking habit, tumor location, lung cancer histology, staging and survival were recorded and analyzed. The results showed that smoking is a significant risk factor for the development of multiple primary malignancies involving lung cancer (P<0.001). Of the 193 patients in this study, 51 had lung cancer diagnosed before the occurrence of other primary cancers (lung cancer first group, LCF group) and the remaining 142 patients had another cancer site develop ahead of the lung cancer (other cancer first group, OCF group). There was a significant difference between the time of the diagnosis of the first primary cancer to that of the second primary cancer in the LCF group and in the OCF group (median 10 vs. 46 months, P<0.001). For lung cancer staging, 53.3% of LCF patients suffered from stage I-II lung cancer, while 24.5% of OCF patients suffered from stage I-II lung cancer. Upper aerodigestive tract tumors were the most frequent tumors accompanying lung cancer, followed by colorectal and cervical cancer. Patients with cervical cancer were at a higher risk of developing lung cancer. Median survival was 65 months in the LCF patients and 81 months in the OCF patients, when calculated from the diagnosis of the first cancer (P=0.558). Median survival was 36 and 14 months, respectively, when calculated from the diagnosis of the second cancer (P=0.081). Median survival (37 vs. 14 months, P=0.085) and 3-year survival (62.5 vs. 25.4%, P=0.002), calculated from the diagnosis of the second primary lung cancer, was better in those LCF patients who developed another primary lung cancer than in the OCF patients who developed a second primary lung cancer. In conclusion, smoking is a risk factor for the development of multiple primary cancers. Upper aerodigestive tract cancer, colorectal cancer and cervical cancer were the tumors most frequently accompanying lung cancer. The staging status and median survival of patients who had a second primary lung cancer were better than in the general lung cancer population. Careful follow-up and intensive treatment is suggested for these patients.     

P53 polymorphisms and haplotypes in lung cancer

An association between the BstU I 1–1 (Pro—Pro)genotype of the p53 codon 72 polymorphism and lung cancer haspreviously been reported by Kawajiri et al. A reanalysis ofthe data by Kawajiri et al. revealed no significant differencebetween patients and controls with respect to allele frequencies,and the increased frequency of BstU 11–1 homozygotes wasmostly ascribable to a deviation from the Hardy—Weinbergequilibrium. In an attempt to replicate the results by Kawajiriet al. we have studied three p53 polymorphisms (BstU I and MspI RFLPs in exon 4 and intron 6 respectively and a 16 bp duplicationin intron 3) and their haplotypes in Swedish lung cancer patientsand controls. The results concerning the codon 72 polymorphismwere largely negative. Thus there was no significant associationbetween lung cancer and the BstU I 1–1 type, and onlya marginal difference (P=0.044) with respect to the BstU I allelefrequency when lung cancer patients were compared with patientswith chronic obstructive pulmonary disease (COPD). However,when the analysis was based on haplotype frequencies largerdifferences appeared and it was found that only BstU I 1 (pro)alleles linked to 16 bp 1 alleles were associated with lungcancer. Pro alleles linked to the 16 bp duplication appearedinstead to confer some protection against cancer. Thus the codon72 alleles need not be functionally involved in lung cancer,but may rather be markers in linkage disequilibrium with othercancer susceptibility sites on p53.     

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.     

An analysis of cytokine status in the serum and effusions of patients with tuberculous and lung cancer

The present study was designed to ascertain whether or not the pleural effusion and serum cytokine levels (granulocyte-macrophage colony-stimulating factor [GM-CSF], interleukin-10 [IL-10], and interferon-gamma [IFN gamma]) in lung cancer patients differ from tuberculous (TB) pleural effusion, in which a strong cellular immune reaction is found; and, whether cytokine levels are a prognostic factor in lung cancer patients with malignant effusion. A total of 202 lung cancer patients with malignant pleural effusion and 26 patients with TB pleural effusion were studied consecutively between 1995 and 1998. Serum and effusion cytokine levels were analyzed with ELISA assays. The results showed that pleural effusion GM-CSF and IL-10 levels were significantly higher than serum levels in both cancer and TB patients. Pleural effusion IFN gamma levels were significantly higher than serum levels in TB patients. IFN gamma levels in both pleural effusion and serum were significantly higher in TB patients than in those with cancer. No significant difference was found, between TB and cancer patients, in the serum or pleural effusion levels of either IL-10 or GM-CSF. The ratio of pleural effusion IFN gamma to serum IFN gamma, effusion IFN gamma to effusion IL-10, and effusion IL-10 to serum IL-10, were all significantly higher in TB than in cancer patients, suggesting a higher cellular activity and T-helper 1 (Th1) reaction in TB pleural effusion than in malignant effusions, which were predominantly Th2 type. Survival analysis showed no significant difference in lung cancer patients with different levels of these cytokines. It was concluded that lung cancer patients with malignant pleural effusion had poorer immune profiles than those with TB pleurisy, both locally and systemically; and the cytokine profiles were not prognostic factors for lung cancer patients with malignant pleural effusion.     

Antidiabetes drugs correlate with decreased risk of lung cancer: a population-based observation in Taiwan

BackgroundThe risk of some forms of cancer has been found to be higher in patients with diabetes mellitus (DM) than in the general population. The aim of this study was to examine, with sufficient statistical power, the association between DM and lung cancer and the impact of antidiabetes drugs on lung cancer risk in Taiwan.Materials and MethodsFrom a randomly selected data set of 1 million National Health Insurance (NHI) claims in Taiwan from 2000-2005, 19,624 cases (patients ≥ 20 years of age) of newly diagnosed DM were identified. From the same data set, 78,496 enrollees with no record of DM were selected as controls and were matched in sex and age to the first group. The incidence of newly diagnosed lung cancer was compared between patients with DM and controls for a period of 9 years (2000-2008).ResultsThe multivariate Cox model analysis showed a slightly increased hazard ratio (HR) of 1.05 of lung cancer in patients with DM, but the association was not statistically significant. However the use of antidiabetes drugs, such as metformin, thiazolidinediones, or alpha-glucosidase inhibitors, correlates with a decreased lung cancer risk of 39%-45%. A significant association was found between lung cancer risk and male sex (HR, 2.23), pulmonary tuberculosis (HR, 1.60), chronic obstructive pulmonary disease (HR, 1.21), and age (HR, 1.07).ConclusionPatients with DM are not at increased risk for the development of lung cancer, but the use of antidiabetes drugs would considerably decrease the risk. In this cohort, male sex, age, pulmonary tuberculosis, and chronic obstructive pulmonary disease were all associated with an increased risk of lung cancer, consistent with findings in the literature and indicative of the validity of our study.