Karynsa Cetin

Hospitalisation for venous thromboembolism in cancer patients and the general population: a population-based cohort study in Denmark, 1997-2006.

Background:Venous thromboembolism (VTE) frequently complicates cancer. Data on tumour-specific VTE predictors are limited, but may inform strategies to prevent thrombosis.Methods:We computed incidence rates (IRs) with 95% confidence intervals (CIs) for VTE hospitalisation in a cohort of cancer patients (n=57 591) and in a comparison general-population cohort (n=287 476) in Denmark. The subjects entered the study in 1997–2005, and the follow-up continued through 2006. Using Cox proportional-hazards regression, we estimated relative risks (RRs) for VTE predictors, while adjusting for comorbidity.Results:Throughout the follow-up, VTE IR was higher among the cancer patients (IR=8.0, 95% CI=7.6–8.5) than the general population (IR=4.7, 95% CI=4.3–5.1), particularly in the first year after cancer diagnosis (IR=15.0, 95% CI=13.8–16.2, vs IR=8.6, 95% CI=7.6–9.9). Incidence rates of VTE were highest in patients with pancreas (IR=40.9, 95% CI=29.5–56.7), brain (IR=17.7, 95% CI=11.3–27.8) or liver (IR=20.4, 95% CI=9.2–45.3) tumours, multiple myeloma (IR=22.6, 95% CI=15.4–33.2) and among patients with advanced-stage cancers (IR=27.7, 95% CI=24.0–32.0) or those who received chemotherapy or no/symptomatic treatment. The adjusted RR (aRR) for VTE was highest among patients with pancreas (aRR=16.3, 95% CI=8.1–32.6) or brain cancer (aRR=19.8 95% CI=7.1–55.2), multiple myeloma (aRR=46.1, 95% CI=13.1–162.0) and among patients receiving chemotherapy, either alone (aRR=18.5, 95% CI=11.9–28.7) or in combination treatments (aRR=16.2, 95% CI=12.0–21.7).Conclusions:Risk of VTE is higher among cancer patients than in the general population. Predictors of VTE include recency of cancer diagnosis, cancer site, stage and the type of cancer-directed treatment.

Survival by histologic subtype in stage IV nonsmall cell lung cancer based on data from the Surveillance, Epidemiology and End Results Program

Background: The role of histology in the targeted management of nonsmall cell lung cancer (NSCLC) has garnered renewed attention in recent years. We provide contemporary population-based estimates of survival and an assessment of important prognostic factors in stage IV NSCLC by major histologic subtype. Methods: Using data from the Surveillance, Epidemiology and End Results (SEER) Program, we stratified 51,749 incident stage IV NSCLC patients (1988–2003 with follow-up through 2006) by major histologic subtype. We used Kaplan–Meier and Cox proportional hazards methods to describe overall survival and the prognostic influence of select patient, tumor, and treatment characteristics for each histologic subgroup. Results: Survival was highest in patients with bronchioloalveolar adenocarcinoma (1-year survival: 29.1%) and lowest in those with large cell tumors (1-year survival: 12.8%). Diagnosis in later years, female gender, younger age, either Asian/Pacific Islander or Hispanic race/ethnicity, lower tumor grade, and surgery or beam radiation as part of first-line treatment were generally independently associated with a decreased risk of death, but the prognostic significance of some of these factors (age, ethnicity, tumor grade) varied according to histologic subtype. Conclusion: Findings demonstrate a poor prognosis across histologic subtypes in stage IV NSCLC patients but highlight differences in both absolute survival and the relative importance of select prognostic factors by histologic subclassification. More research using other sources of population-based data could help clarify the role of histology in the presentation, management, and prognosis of late-stage NSCLC.

Estimated number of prevalent cases of metastatic bone disease in the US adult population.

Background The prevalence of metastatic bone disease in the US population is not well understood. We sought to estimate the current number of US adults with metastatic bone disease using two large administrative data sets. Methods Prevalence was estimated from a commercially insured cohort (ages 18–64 years, MarketScan database) and from a fee-for-service Medicare cohort (ages ≥65 years, Medicare 5% database) with coverage on December 31, 2008, representing approximately two-thirds of the US population in each age group. We searched for claims-based evidence of metastatic bone disease from January 1, 2004, using a combination of relevant diagnosis and treatment codes. The number of cases in the US adult population was extrapolated from age- and sex-specific prevalence estimated in these cohorts. Results are presented for all cancers combined and separately for primary breast, prostate, and lung cancer. Results In the commercially insured cohort (mean age = 42.3 years [SD = 13.1]), we identified 9505 patients (0.052%) with metastatic bone disease. Breast cancer was the most common primary tumor type (n = 4041). In the Medicare cohort (mean age = 75.6 years [SD = 7.8]), we identified 6427 (0.495%) patients with metastatic bone disease. Breast (n = 1798) and prostate (n = 1862) cancers were the most common primary tumor types. We estimate that 279,679 (95% confidence interval: 274,579–284,780) US adults alive on December 31, 2008, had evidence of metastatic bone disease in the previous 5 years. Breast, prostate, and lung cancers accounted for 68% of these cases. Conclusion Our findings suggest that approximately 280,000 US adults were living with metastatic bone disease on December 31, 2008. This likely underestimates the true frequency; not all cases of metastatic bone disease are diagnosed, and some diagnosed cases might lack documentation in claims data.

Recent Time Trends in the Epidemiology of Stage IV Prostate Cancer in the United States: Analysis of Data From the Surveillance, Epidemiology, and End Results Program*

OBJECTIVES To describe recent epidemiologic trends in stage IV prostate cancer. Although advances in screening and diagnostic techniques have led to earlier detection of prostate cancer, a portion of patients still present with late-stage disease. METHODS Population-based cancer registry data from the Surveillance, Epidemiology, and End Results Program (cases from 1988 to 2003, follow-up through 2005) were used to calculate annual age-adjusted incidence rates of stage IV prostate cancer (overall and for the subset presenting with distant metastases) and to assess time trends in patient, tumor, and treatment characteristics and survival. RESULTS From 1988 to 2003, the age-adjusted incidence of stage IV prostate cancer significantly declined by 6.4% each year. The proportion of men diagnosed at younger ages, with poorly differentiated tumors, or who underwent a radical prostatectomy significantly increased over time. Five-year relative survival improved across the study period (from 41.6% to 62.3%), particularly in those diagnosed at younger ages or with moderately to well-differentiated tumors. Later years of diagnosis were independently associated with a decreased risk of death (from all causes and from prostate cancer specifically) after controlling for important patient, tumor, and treatment characteristics. Tumor grade and receipt of radical prostatectomy appeared to be the strongest independent prognostic indicators. Temporal trends were similar in the subset presenting with distant metastases, except that no significant improvement in survival was observed. CONCLUSIONS As younger men may expect to live longer with advanced prostate cancer, there remains a need to widen the range of therapeutic and supportive care options.

Bone metastasis, skeletal-related events, and mortality in lung cancer patients: a Danish population-based cohort study.

OBJECTIVES To estimate the incidence rate of bone metastasis and subsequent skeletal-related events (SREs) (radiation to bone, spinal cord compression, fracture, and surgery to bone) in lung cancer patients and to quantify their impact on mortality. MATERIALS AND METHODS We conducted a nationwide cohort study of patients diagnosed with lung cancer between 1999 and 2010 in Denmark. We computed the cumulative incidence (%) of bone metastasis and subsequent SREs (treating death as a competing risk) and corresponding incidence rates (per 1000 person-years). Survival was evaluated using the Kaplan-Meier method for three dynamic lung cancer patient cohorts-no bone metastasis; bone metastasis without SREs; and bone metastasis with SREs. Based on a Cox proportional hazards model, we computed mortality rate ratios (MRRs) comparing mortality rates between these patient cohorts, adjusting for age, comorbidity, stage, and histology. Analyses were conducted for the lung cancer patient cohort overall and by histologic subtype. RESULTS We identified 29,720 patients with incident lung cancer (median follow-up: 7.3 months). The 1-year cumulative incidence of bone metastasis was 5.9%, and the 1-year cumulative incidence of subsequent SREs was 55.0%. The incidence of bone metastasis and SREs was higher in patients with non-small cell lung cancer (NSCLC) versus SCLC. One-year survival was 37.4% in patients with no bone metastasis; 12.1% in patients with bone metastasis without SREs; and 5.1% in patients with both bone metastasis and SREs. When mortality rates between patients with bone metastasis with and without an SRE were compared, 2-month mortality rates were similar, but the >2-month adjusted MRR was 2.0 (95% confidence interval: 1.7-2.2). CONCLUSION Bone metastases predict a poor prognosis in lung cancer patients. The majority of lung cancer patients with bone metastasis will also experience an SRE, which may further increase the rate of mortality.

Timing of androgen deprivation therapy use and fracture risk among elderly men with prostate cancer in the United States.

Fractures are a recognized consequence of androgen deprivation therapy (ADT); however, less is known about the incidence of fracture in relation to the timing of ADT use or the impact of fracture on mortality in men with prostate cancer.

The epidemiology of malignant giant cell tumors of bone: an analysis of data from the Surveillance, Epidemiology and End Results Program (1975–2004)

Malignant giant cell tumor (GCT) of bone is a rare tumor with debilitating consequences. Patients with GCT of bone typically present with mechanical difficulty and pain as a result of bone destruction and are at an increased risk for fracture. Because of its unusual occurrence, little is known about the epidemiology of malignant GCT of bone. This report offers the first reliable population-based estimates of incidence, patient demographics, treatment course and survival for malignancy in GCT of bone in the United States. Using data from the National Cancer Institutes Surveillance, Epidemiology and End Results (SEER) program, we estimated the overall incidence and determinants of survival among patients diagnosed with malignant GCT of bone from 1975–2004. Cox proportional hazards regression was used to evaluate demographic and clinical determinants of survival among malignant GCT cases. Based on analyses of 117 malignant GCT cases, the estimated annual incidence in the United States was 1.6 per 10,000,000 persons per year. Incidence was highest among adults aged 20 to 44 years (2.4 per 10,000,000 per year) and most patients were diagnosed with localized (31.6%) or regional (29.9%) disease compared to distant disease (16.2%). Approximately 85% of patients survived at least 5 years, with survival poorest among older patients and those with evidence of distant metastases at time of diagnosis. The current study represents the largest systematic investigation examining the occurrence and distribution of malignancy in GCT of bone in the general U.S. population. We confirm its rare occurrence and suggest that age and stage at diagnosis are strongly associated with long-term survival.

Risk of arterial thrombotic and venous thromboembolic events in patients with primary chronic immune thrombocytopenia: a Scandinavian population-based cohort study

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Survival in patients with breast cancer with bone metastasis: a Danish population-based cohort study on the prognostic impact of initial stage of disease at breast cancer diagnosis and length of the bone metastasis-free interval

Objectives Since population-based data on prognostic factors affecting survival in patients with breast cancer with bone metastasis (BM) are currently limited, we conducted this nationwide retrospective cohort study to examine the prognostic role of disease stage at breast cancer diagnosis and length of BM-free interval (BMFI). Setting Denmark. Participants 2427 women with a breast cancer diagnosis between 1997 and 2011 in the Danish Cancer Registry and a concurrent or subsequent BM diagnosis in the Danish National Registry of Patients. Primary and secondary outcome measures Survival (crude) based on Kaplan-Meier method and mortality risk (crude and adjusted for age, year of diagnosis, estrogen receptor status and comorbidity) based on Cox proportional hazards regression analyses by stage of disease at breast cancer diagnosis and by length of BMFI (time from breast cancer to BM diagnosis), following patients from BM diagnosis until death, emigration or until 31 December 2012, whichever came first. Results Survival decreased with more advanced stage of disease at the time of breast cancer diagnosis; risk of mortality during the first year following a BM diagnosis was over two times higher for those presenting with metastatic versus localised disease (adjusted HR=2.12 (95% CI 1.71 to 2.62)). With respect to length of BMFI, survival was highest in women with a BMFI <1 year (ie, in those who presented with BM at the time of breast cancer diagnosis or were diagnosed within 1 year). However, among patients with a BMFI ≥1 year, survival increased with longer BMFI (1-year survival: 39.9% (95% CI 36.3% to 43.6%) for BMFI 1 to <3 years and 52.6% (95% CI 47.4% to 57.6%) for BMFI ≥5 years). This pattern was also observed in multivariate analyses. Conclusions Stage of disease at breast cancer diagnosis and length of BMFI appear to be important prognostic factors for survival following BM.

Androgen deprivation therapy and cataract incidence among elderly prostate cancer patients in the United States.

PURPOSE The side-effects associated with androgen deprivation therapy (ADT) include weight gain, dyslipidemia, and insulin resistance. As cataracts have been linked to these metabolic abnormalities, an increased risk of cataract may be another adverse consequence of ADT use. METHODS Using data from the Surveillance, Epidemiology and End Results-Medicare database, we estimated risk of cataract associated with ADT among 65,852 prostate-cancer patients. ADT treatment was defined as at least one dose of a gonadotropin-releasing hormone agonist or orchiectomy within 6 months after prostate cancer diagnosis. The outcome measure was a first claim of cataract diagnosis identified in Medicare claim files. Cox regression was used to estimate hazard ratios (HR) for the effects of ADT treatment, controlling for confounders. RESULTS Gonadotropin-releasing hormone agonist use was associated with a modest increase in cataract incidence (HR 1.09, 95% confidence interval 1.06-1.12). Orchiectomy was also associated with an increased risk of cataract among men with no history of cataract prior to prostate cancer diagnosis (HR 1.26, 95% confidence interval 1.07-1.47). CONCLUSIONS In the first systematic investigation of the association between ADT and cataract, our results suggest an elevation in the incidence of cataract among ADT users. Further study, preferably prospective in design, is needed to provide additional evidence to support or refute these findings.