Interval lung cancers not detected on screening chest X-rays: How are they different?

Background: The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial provides us an opportunity to describe interval lung cancers not detected by screening chest X-ray (CXR) compared to screen-detected cancers.

Methods: Participants were screened for lung cancer with CXR at baseline and annually for two (never smokers) or three (ever smokers) more years. Screen-detected cancers were those with a positive CXR and diagnosed within 12 months.

Diagnostic evaluation following a positive lung screening chest radiograph in the Prostate, Lung, Colorectal, Ovarian (PLCO) Cancer Screening Trial.

Lung cancer is the major cause of cancer mortality. One of the aims of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) was to determine if annual screening chest radiographs reduce lung cancer mortality. We enrolled 154,900 individuals, aged 55-74 years; 77,445 were randomized to the intervention arm and received an annual chest radiograph for 3 or 4 years.

Screening by chest radiograph and lung cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial.

Context: The effect on mortality of screening for lung cancer with modern chest radiographs is unknown.

Objective: To evaluate the effect on mortality of screening for lung cancer using radiographs in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

Design, Setting, And Participants: Randomized controlled trial that involved 154,901 participants aged 55 through 74 years, 77,445 of whom were assigned to annual screenings and 77,456 to usual care at 1 of 10 screening centers across the United States between November 1993 and July 2001.

Lung cancer risk prediction: Prostate, Lung, Colorectal And Ovarian Cancer Screening Trial models and validation.

Introduction: Identification of individuals at high risk for lung cancer should be of value to individuals, patients, clinicians, and researchers. Existing prediction models have only modest capabilities to classify persons at risk accurately.

Methods: Prospective data from 70 962 control subjects in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) were used in models for the general population (model 1) and for a subcohort of ever-smokers (N = 38 254) (model 2).

Dietary factors and risk of chronic lymphocytic leukemia and small lymphocytic lymphoma: a pooled analysis of two prospective studies.

Background: Other than male sex, family history, advanced age, and race, risk factors for chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) are unknown. Very few studies have investigated diet in relation to these leukemias, and no consistent associations are known.

Methods: Using two large prospective population-based studies, we evaluated the relationship between diet and CLL/SLL risk.

Associations between anthropometry, cigarette smoking, alcohol consumption, and non-Hodgkin lymphoma in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Prospective studies of lifestyle and non-Hodgkin lymphoma (NHL) are conflicting, and some are inconsistent with case-control studies. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was used to evaluate risk of NHL and its subtypes in association with anthropometric factors, smoking, and alcohol consumption in a prospective cohort study. Lifestyle was assessed via questionnaire among 142,982 male and female participants aged 55-74 years enrolled in the PLCO Trial during 1993-2001.

Lung cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

Background: The 5-year overall survival rate of lung cancer patients is approximately 15%. Most patients are diagnosed with advanced-stage disease and have shorter survival rates than patients with early-stage disease. Although screening for lung cancer has the potential to increase early diagnosis, it has not been shown to reduce lung cancer mortality rates.

Interaction of CYP1B1, cigarette-smoke carcinogen metabolism, and lung cancer risk.

A previously published case-control study nested in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial found a significant relationship of serum levels of total NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides) to prospective lung cancer risk. The present paper examines this relationship in the context of single-nucleotide polymorphisms (SNPs) in genes important in the metabolism of tobacco smoke carcinogens. DNA was extracted from the subjects' lymphocytes and analyzed for SNPs in 11 locations on four genes related to tobacco carcinogen metabolism.

A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma.

Three genetic loci for lung cancer risk have been identified by genome-wide association studies (GWAS), but inherited susceptibility to specific histologic types of lung cancer is not well established. We conducted a GWAS of lung cancer and its major histologic types, genotyping 515,922 single-nucleotide polymorphisms (SNPs) in 5739 lung cancer cases and 5848 controls from one population-based case-control study and three cohort studies. Results were combined with summary data from ten additional studies, for a total of 13,300 cases and 19,666 controls of European descent.

A prospective study of serum soluble CD30 concentration and risk of non-Hodgkin lymphoma.

Prediagnostic serum concentration of soluble CD30 (sCD30), a marker for chronic B-cell stimulation, has been associated with increased risk of developing AIDS-related non-Hodgkin lymphoma (NHL) in a recent study of HIV(+) patients. To investigate among healthy persons whether serum sCD30 is associated with NHL risk, we carried out a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. There was a strong dose-response relationship between prediagnostic sCD30 concentration and NHL risk among 234 cases and 234 individually matched controls (odds ratio [95% confidence interval] for second, third, and fourth quartiles vs first quartile: 1.

Prediction of true positive lung cancers in individuals with abnormal suspicious chest radiographs: a prostate, lung, colorectal, and ovarian cancer screening trial study.

Introduction: Chest radiographs are routinely employed in clinical practice. Radiographic findings that are abnormal suspicious (AS) for lung cancer occur commonly. The majority of AS radiographic abnormalities are not cancer.

Phase III randomised study of dexamethasone with or without oblimersen sodium for patients with advanced multiple myeloma.

Upregulation of the Bcl-2 antiapoptotic protein is reported to be associated with aggressive clinical course in multiple myeloma. Oblimersen sodium is a bcl-2 antisense oligonucleotide complementary to the first six codons of the open-reading frame of bcl-2 mRNA that can decrease transcription of Bcl-2 protein and increase myeloma cell susceptibility to cytotoxic agents. In this phase III randomised trial, we investigated in patients with relapsed/refractory myeloma whether addition of oblimersen to dexamethasone improved clinical outcomes vs.

Genomic variation in myeloma: design, content, and initial application of the Bank On A Cure SNP Panel to detect associations with progression-free survival.

Background: We have engaged in an international program designated the Bank On A Cure, which has established DNA banks from multiple cooperative and institutional clinical trials, and a platform for examining the association of genetic variations with disease risk and outcomes in multiple myeloma. We describe the development and content of a novel custom SNP panel that contains 3404 SNPs in 983 genes, representing cellular functions and pathways that may influence disease severity at diagnosis, toxicity, progression or other treatment outcomes. A systematic search of national databases was used to identify non-synonymous coding SNPs and SNPs within transcriptional regulatory regions.

Appraisal of immunoglobulin free light chain as a marker of response.

The immunoglobulin free light chain (FLC) assay is an invaluable tool for following patients with oligosecretory plasma cell dyscrasia. Baseline values have also been shown to be prognostic in all plasma cell disorders tested. A looming question, however, is the role it should play in following myeloma patients with disease that is measurable using serum and urine electrophoresis.

Factors associated with human small aggressive non small cell lung cancer.

Background: Some non-small cell lung cancers (NSCLC) progress to distant lymph nodes or metastasize while relatively small. Such small aggressive NSCLCs (SA-NSCLC) are no longer resectable with curative intent, carry a grave prognosis, and may involve unique biological pathways. This is a study of factors associated with SA-NSCLC.

Multiple myeloma: a review of the epidemiologic literature.

Multiple myeloma, a neoplasm of plasma cells, accounts for approximately approximately 15% of lymphatohematopoietic cancers (LHC) and 2% of all cancers in the US. Incidence rates increase with age, particularly after age 40, and are higher in men, particularly African American men. The etiology is unknown with no established lifestyle, occupational or environmental risk factors.

Abnormalities on chest radiograph reported in subjects in a cancer screening trial.

Background: Chest radiographs (CXRs) are commonly performed for diagnostic and other purposes. There is little literature either on the prevalence in the general population of various abnormalities seen on CXRs or on the risks associated with these abnormalities.

Methods: We followed up > 70,000 men and women who were enrolled in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Tumor suppressor p16 methylation in multiple myeloma: biological and clinical implications.

The biological and clinical implications of p16 gene methylation in multiple myeloma (MM) are still unclear despite previous studies. In this comprehensive study, using methylation-specific PCR (MS-PCR), we show that p16 methylation is relatively common and occurs in monoclonal gammopathy of undetermined significance (MGUS; n=17), smoldering multiple myeloma (SMM; n=40), and MM (n=522) at a prevalence of 24%, 28%, and 34%, respectively. However, p16 methylation does not appear to affect gene expression level.

Complete response in multiple myeloma: clinical trial E9486, an Eastern Cooperative Oncology Group study not involving stem cell transplantation.

Background: The importance of obtaining a complete response (CR) in multiple myeloma (MM) treated with chemotherapy is unclear.

Methods: The Eastern Cooperative Oncology Group evaluated 653 previously untreated patients with active MM randomized to vincristine, carmustine (BCNU), melphalan, cyclophosphamide, and prednisone (VBMCP), to VBMCP and recombinant interferon alfa-2 (INFalpha-2), or to VBMCP and high-dose cyclophosphamide.

Results: Objective response was achieved in 420 (67%) of the 628 eligible patients, and 85 (14%) achieved a CR.

Baseline chest radiograph for lung cancer detection in the randomized Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Background: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was initiated in 1992 to examine cause-specific mortality reduction from screening for these four cancers in men and women. We report lung cancer detection results of the baseline screening round.

Methods: Of the 154,942 participants enrolled, who were aged 55-74 years with no history of PLCO cancers, 77,465 were randomly assigned to the intervention arm.

Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer.

The Lung Screening Study (LSS) was a pilot study designed to assess the feasibility of conducting a large scale randomized controlled trial (RCT) of low radiation dose spiral computed tomography (LDCT) versus chest X-ray (CXR) for lung cancer screening. Baseline results of LSS have been previously reported. Here, we report on the findings at the year one screen and on the final results of the LSS study.

Pentostatin, chlorambucil and prednisone therapy for B-chronic lymphocytic leukemia: a phase I/II study by the Eastern Cooperative Oncology Group study E1488.

Pentostatin is a purine nucleoside analog with demonstrated activity in low-grade lymphoid malignancies. The purpose of this study was to determine the dose of pentostatin (dCF) that could be combined with chlorambucil and prednisone to treat chronic lymphocytic leukemia (CLL), evaluate the toxicity of the resulting regimen and to estimate its efficacy. This was a multi-institutional Eastern Cooperative Oncology Group (ECOG) phase I-II study.