Agreement Between Self-Reported and Confirmed Cancer Diagnoses in New York City Firefighters and EMS Workers, 2001-2011.

OBJECTIVES: Because of the delay in availability of cancer diagnoses from state cancer registries, self-reported diagnoses may be valuable in assessing the current cancer burden in many populations. We evaluated agreement between self-reported cancer diagnoses and state cancer registry-confirmed diagnoses among 21,437 firefighters and emergency medical service workers from the Fire Department of the City of New York. We also investigated the association between World Trade Center (WTC) exposure and other characteristics in relation to accurate reporting of cancer diagnoses. METHODS: Participants self-reported cancer status in questionnaires from October 2, 2001, to December 31, 2011. We obtained data on confirmed cancer diagnoses from nine state cancer registries, which we used as our gold standard. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), comparing self-reported cancer diagnoses with confirmed cancer diagnoses. We used multivariable logistic regression models to assess the association between WTC exposure and correct self-report of cancer status, false-positive cancer reports, and false-negative cancer reports. RESULTS: Sensitivity and specificity for all cancers combined were 90.3% and 98.7%, respectively. Specificities and NPVs remained high in different cancer types, while sensitivities and PPVs varied considerably. WTC exposure was not associated with accurate reporting. CONCLUSION: We found high specificities, NPVs, and general concordance between self-reported cancer diagnoses and registry-confirmed diagnoses. Given the low population prevalence of cancer, self-reported cancer diagnoses may be useful for determining non-cancer cases. Because of the low sensitivities and PPVs for some individual cancers, however, case confirmation with state cancer registries or medical records remains critically important.

World Trade Center-related physical and mental health burden among New York City Fire Department emergency medical service workers.

OBJECTIVES: To describe the health burden among Fire Department of the City of New York (FDNY) emergency medical service (EMS) workers and examine its association with work at the World Trade Center (WTC) disaster site. METHODS: In this observational cohort study, we used FDNY physician diagnoses to estimate the cumulative incidence of physical health conditions including rhinosinusitis, gastroesophageal reflux disease (GERD), obstructive airways disease (OAD) and cancer among EMS workers and demographically similar firefighters who were active on 11 September 2001 (9/11). Validated screening instruments were used to estimate the prevalence of probable post-traumatic stress disorder (PTSD), probable depression and probable harmful alcohol use. We also analysed the association between health conditions and WTC-exposure. RESULTS: Among 2281 EMS workers, the 12-year post-9/11 cumulative incidence (11 September 2001 to 31 December 2013) of rhinosinusitis was 10.6%; GERD 12.1%; OAD 11.8%; cancer 3.1%. The prevalence of probable PTSD up to 12 years after exposure was 7%; probable depression 16.7%; and probable harmful alcohol use 3%. Compared with unexposed, EMS workers who arrived earliest at the site had higher adjusted relative risks (aRR) for most conditions, including rhinosinusitis (aRR=3.7; 95% CI 2.2 to 6.0); GERD (aRR=3.8; 95% CI 2.4 to 6.1); OAD (aRR=2.4: 95% CI 1.7 to 3.6); probable PTSD (aRR=7.0; 95% CI 3.6 to 13.5); and, probable depression (aRR=2.3; 95% CI 1.6 to 3.1). CONCLUSIONS: In this 12-year study, we documented a high burden of health conditions associated with WTC-exposure among FDNY EMS workers. These findings underscore the importance of continued monitoring and treatment of this workforce.

Detection of cerebrospinal fluid tumor cells and its clinical relevance in leptomeningeal metastasis of breast cancer.

Circulating tumor cells are commonly observed in the peripheral blood of advanced breast cancer patients. We tested the feasibility of tumor cell detection in the cerebrospinal fluid (CSF) and studied its clinical relevance in leptomeningeal metastasis (LM) of breast cancer. CSF samples were collected from 38 metastatic breast cancer patients known or suspected to have LM. Control CSF samples were collected from 14 individuals without solid tumor malignancy. We used a modified CellSearch™ assay and an alternative EPCAM-based method involving immunomagnetic enrichment followed by flow cytometry (IE/FC) to enumerate CSF tumor cells (CSFTCs). CSFTCs were assayed at time of LM diagnosis and over the course of LM-directed therapy. We analyzed a total of 102 CSF samples with modified CellSearch™. The CSFTC counts were strongly correlated with the corresponding IE/FC results (Pearson's r = 0.94). Twenty-eight out of 30 samples in which malignant cells were identified by CSF cytology were CSFTC-positive by modified CellSearch™. Baseline CSFTC levels from 21 patients eventually diagnosed with LM were significantly higher than the controls (p = 0.0202), whereas 13 patients deemed not to have LM showed CSFTC results indistinguishable from the controls. In patients with serial samples, it was possible to monitor CSFTC levels as a potential biomarker of treatment response. CSFTC detection using a modified CellSearch™ assay demonstrated high sensitivity in detecting malignant cells in CSF and may be a promising method for diagnosing LM and monitoring LM during treatment.

Genome-wide copy number analysis of cerebrospinal fluid tumor cells and their corresponding archival primary tumors.

A debilitating complication of breast cancer is the metastatic spread of tumor cells to the leptomeninges or cerebrospinal fluid (CSF). Patients diagnosed with this aggressive clinical syndrome, known as leptomeningeal carcinomatosis, have very poor prognosis. Despite improvements in detecting cerebrospinal fluid tumor cells (CSFTCs), information regarding their molecular biology is extremely limited. In our recent work, we utilized a protocol previously used for circulating tumor cell isolation to purify tumor cells from the CSF. We then performed genomic characterization of CSFTCs as well as archival tumors from the same patient. Here, we describe the microarray data and quality controls associated with our study published in the Cancer Research journal in 2013 [1]. We also provide an R script containing code for quality control of microarray data and assessment of copy number calls. The microarray data has been deposited into Gene Expression Omnibus under accession # GSE46068.

Molecular profiling of tumor cells in cerebrospinal fluid and matched primary tumors from metastatic breast cancer patients with leptomeningeal carcinomatosis.

Although leptomeningeal carcinomatosis is a well-established clinical syndrome, virtually nothing is known about the tumor cells responsible for this particularly aggressive metastatic process. To isolate cerebrospinal fluid-derived tumor cells (CSFTC) from 15 patients with metastatic breast cancer diagnosed with leptomeningeal carcinomatosis, CSF samples were subjected to a two-step method involving immunomagnetic enrichment and fluorescence-activated cell sorting (IE/FACS), a technique previously used for isolating circulating tumor cells (CTC) from blood. CSFTCs were subjected to genome-wide copy number analysis by array comparative genomic hybridization. Genomic profiling was successfully performed for 13 of 15 patients (87%). Copy number analysis in CSFTCs revealed genomic alterations commonly observed in primary breast cancer and CTCs, indicating their malignant origin. Interestingly, 12 (92%) harbored high-level gains on the 8q24 locus, which includes the MYC oncogene. Comparison of CSFTCs against corresponding archival primary tumors in six patients revealed clonal relationships with some divergence. Good concordance among serial samples attested to the reproducibility of the assay. Our approach for isolation and molecular analysis of CSFTCs yielded new insights into the molecular nature of these cells. Further genomic and functional analyses may help elucidate mechanisms by which tumor cells metastasize to the central nervous system.