Cancer Registries: Can We Improve the Quality of Thyroid Cancer Data?

BACKGROUND: Cancer registries are used to report cancer care trends and outcomes. Information from these data sets is utilized to craft practice guidelines and management recommendations. Limited knowledge is available regarding the quality of the data contained within registries. We sought to determine the accuracy of a single variable, 'surgery of the primary site', in the Tennessee Cancer Registry (TCR). METHODS: A retrospective review of the TCR thyroid database was performed. Hospital facilities were classified as either Commission on Cancer (CoC) or non-CoC accredited. Certified Tumor Registrars at the TCR reviewed the abstracted text and/or telephoned the reporting facility staff to confirm the definitive thyroid procedure. RESULTS: A total of 921 thyroid cancer cases, diagnosed/treated at TN facilities during 2004-2011, were coded with thyroid lobectomy (TL). Overall, 369 (40 %) were incorrectly coded, of which 247(67 %) were changed to total thyroidectomy. The majority of cases (80 %) were reported by CoC facilities. When compared by facility type, 42 % of records submitted from CoC facilities contained incorrect codes for the variable 'surgery of the primary site' TL compared with 34 % of records submitted by non-CoC facilities (p = 0.047). CONCLUSION: In this study of the TCR, 40 % of records contained inaccurate coding of the variable 'surgery of the primary site'. Upon validation, 27 % of all records were changed from TL to total thyroidectomy. The rate of incorrect coding was higher in CoC reporting facilities than in non-CoC facilities. Using text-to-code re-abstraction audits and facility contact these discrepancies can be validated and corrected to improve data quality.

The effect of health insurance status on the treatment and outcomes of patients with colorectal cancer.

BACKGROUND AND OBJECTIVES: Uninsured and underinsured cancer patients often have delayed diagnosis and inferior outcomes. As healthcare reform proceeds in the US, this disparity may gain increasing importance. Our objective was to investigate the impact of health insurance status on the presentation, treatment, and survival among colorectal cancer (CRC) patients. METHODS: A total of 10,692 patients diagnosed with CRC between 2004 and 2008 identified from the Tennessee Cancer Registry were stratified into five groups: Private, Medicare, Military, Medicaid, and uninsured. Multivariable regression models were constructed to test the association of insurance with receipt of recommended adjuvant therapy and overall survival (OS). RESULTS: Uninsured and Medicaid patients were more often African American (AA) and presented with higher stage tumors (P < 0.001). Medicare patients were less likely to receive recommended adjuvant therapy (OR 0.54). Lack of insurance, Medicaid, and failure to receive recommended adjuvant therapy were independently associated with worse OS. CONCLUSIONS: Although uninsured and Medicaid patients receive recommended adjuvant therapy comparable to other patients, they present with later stage disease and have a worse OS. Future studies are needed to better explain these disparities especially in the light of changing healthcare climate in the US.

Health insurance status affects staging and influences treatment strategies in patients with hepatocellular carcinoma.

BACKGROUND: Lack of health insurance is associated with poorer outcomes for patients with cancers amenable to early detection. The effect of insurance status on hepatocellular carcinoma (HCC) presentation stage and treatment outcomes has not been examined. We examined the effect of health insurance status on stage of presentation, treatment strategies, and survival in patients with HCC. METHODS: The Tennessee Cancer Registry was queried for patients treated for HCC between January 2004 and December 2006. Patients were stratified by insurance status: (1) private insurance; (2) government insurance (non-Medicaid); (3) Medicaid; (4) uninsured. Logistic, Kaplan-Meier, and Cox models tested the effects of demographic and clinical covariates on the likelihood of having surgical or chemotherapeutic treatments and survival. RESULTS: We identified 680 patients (208 private, 356 government, 75 Medicaid, 41 uninsured). Uninsured patients were more likely to be men, African American, and reside in an urban area (all P < 0.05). The uninsured were more likely to present with stage IV disease (P = 0.005). After adjusting for demographics and tumor stage, Medicaid and uninsured patients were less likely to receive surgical treatment (both P < 0.01) but were just as likely to be treated with chemotherapy (P ≥ 0.243). Survival was significantly better in privately insured patients and in those treated with surgery or chemotherapy (all P < 0.01). Demographic adjusted risk of death was doubled in the uninsured (P = 0.005). CONCLUSIONS: Uninsured patients with HCC are more likely to present with late-stage disease. Although insurance status did not affect chemotherapy utilization, Medicaid and uninsured patients were less likely to receive surgical treatment.

Extracellular matrix and HIF-1 signaling: the role of prolidase.

Hypoxia-inducible factor-1 (HIF-1) plays an important role in stress-responsive gene expression. Although primarily sensitive to hypoxia, HIF-1 signaling can be regulated by a number of stress factors including metabolic stress, growth factors and molecules present in the extracellular matrix (ECM). Degradation of ECM by metalloproteinases (MMP) is important for tumor progression, invasion and metastasis. ECM is predominantly collagen, and the imino acids (Pro and HyPro) comprise 25% of collagen residues. The final step in collagen degradation is catalyzed by prolidase, the obligate peptidase for imidodipeptides with Pro and HyPro in the carboxyl terminus. Defective wound healing in patients with inherited prolidase deficiency is associated with histologic features of angiopathy suggesting that prolidase may play a role in angiogenesis. Because HIF-1 alpha is central to angiogenesis, we considered that prolidase may modulate this pathway. To test this hypothesis, we made expression constructs of human prolidase and obtained stable transfectants in colorectal cancer cells (RKO). Overexpression of prolidase resulted in increased nuclear hypoxia inducible factor (HIF-1 alpha) levels and elevated expression of HIF-1-dependent gene products, vascular endothelial growth factor (VEGF) and glucose transporter-1 (Glut-1). The activation of HIF-1-dependent transcription was shown by prolidase-dependent activation of hypoxia response element (HRE)-luciferase expression. We used an oxygen-dependent degradation domain (ODD)-luciferase reporter construct as a surrogate for HIF-1 alpha as an in situ prolyl-hydroxylase assay. Since this reporter is degraded by VHL-dependent mechanisms, the increased levels of luciferase observed with prolidase expression reflected the decreased HIF-1 alpha prolyl hydroxylase activity. Additionally, the differential expression of prolidase in 2 breast cancer cell lines showed prolidase-dependent differences in HIF-1 alpha levels. These findings show that metabolism of imidodipeptides by prolidase plays a previously unrecognized role in angiogenic signaling.

A novel time-course cDNA microarray analysis method identifies genes associated with the development of cisplatin resistance.

In recent years, most cDNA microarray studies of chemotherapeutic drug resistance have not considered the temporal pattern of gene expression. The objective of this study was to examine systematically changes in gene expression of NCI-H226 and NCI-H2170 lung cancer cells treated weekly with IC10 doses of cisplatin. NCI-H226 lung cancer cells were treated weekly with an IC10 dose of cisplatin. Candidate genes with a fold change of 2.0 or more were identified from this study. A second experiment was conducted by exposing NCI-H2170 cells to cisplatin doses that were increased in week 4 and decreased in week 5. Overall, 44 genes were differentially expressed in both the NCI-H226 and NCI-H2170 cell lines. In the NCI-H2170 cell line, 24 genes had a twofold gene expression change from weeks 3 to 4. Real-time PCR found a significant correlation of the gene expression changes for seven genes of interest. This small time-ordered series identified novel genes associated with cisplatin resistance. This kind of analysis should be viewed as a first step towards building gene-regulatory networks.

Micronutrients and cancer therapy.

The effect of micronutrient supplementation on the effectiveness of cancer chemotherapeutic agents is reviewed, and the efficacy of antioxidants, folic acid, and other vitamins and minerals is discussed. Although some micronutrients show promise in enhancing the cytotoxicity of anticancer agents in vitro, caution should be exercised in recommending micronutrient supplementation for cancer patients receiving chemotherapeutic drugs. To date, few well-controlled clinical trials have been conducted to evaluate the efficacy of micronutrients in promoting the sensitivity of tumors to chemotherapeutic agents.

Human papillomavirus and molecular considerations for cancer risk.

Human papillomaviruses (HPVs) are a major cause of cancer globally, including cervical cancer. The HPV 'early' proteins, E6 and E7, are the chief oncoproteins involved in cancer progression. These oncoproteins are more highly expressed in high-grade dysplasias and invasive cancer coincident with reduced viral DNA replication and reduced production of infective progeny virions. The E6 and E7 oncoproteins interact with several cellular proteins-classically TP53 and RB1, respectively-leading to the degradation of several of these proteins, although all interactions do not necessarily result in the degradation of a cellular protein. HPV infection is also associated with viral and host DNA methylation changes, many of which also occur in cancer types not associated with HPV infection. The E6 and E7 interactions with cellular proteins and DNA methylation changes are associated with changes in the integrity of key cellular pathways that regulate genomic integrity, cell adhesion, the immune response, apoptosis, and cell cycle control. The alterations in key cellular pathways may provide useful biomarkers to improve the sensitivity of current cancer screening methods, such as the Papanicolaou test. This review provides a detailed summary of the interactions of E6 and E7 with cellular proteins and alterations in cellular DNA methylation associated with HPV infection. The importance of molecular biomarkers to the clinical setting, underserved populations, and general public health is discussed.

Intrinsic cisplatin resistance in lung and ovarian cancer cells propagating in medium acutely depleted of folate.

Many tumors develop intrinsic and/or acquired resistance to cisplatin. The purpose of the present study was to examine the influence of acute extracellular folate depletion prior to cisplatin treatment on the development of intrinsic cisplatin resistance. Lung and ovarian cancer cells were propagated in medium acutely depleted of folate and subsequently treated with cisplatin. The IC50 level for cisplatin, cell viability, cell proliferation, and global DNA methylation were determined. Gene expression profiling was performed using the Atlas Cancer 1.2 Array. Acute extracellular folate depletion resulted in the development of intrinsic cisplatin resistance. Cells propagating in medium acutely depleted of folate had a survival advantage compared to control cells when exposed to cisplatin, and thymidine supplementation did not reverse the intrinsic cisplatin resistance. cDNA microarray analysis revealed some novel genes associated with the development of intrinsic cisplatin resistance. Our report is the first to demonstrate that acute extracellular folate depletion results in intrinsic cisplatin resistance. If these results are confirmed by in vivo human studies, it would suggest that the folate status of the recipient of cisplatin might have an impact on response to that chemotherapeutic agent.