Scott Stryker

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.

Regional Variation and Challenges in Estimating the Incidence of Giant Cell Tumor of Bone

BACKGROUND Estimating the incidence of giant cell tumor of bone is challenging because few population-based cancer registries record benign bone tumors. We compared two approaches, the indirect (relative index) estimation approach used in The Burden of Musculoskeletal Diseases in the United States (BMUS) and a direct incidence rate approach (from registries that record giant cell tumor), to estimate giant cell tumor incidence in France, Germany, Italy, Spain, the U.K., Sweden, Australia, Canada, Japan, and the U.S. METHODS Giant cell tumor of bone incidence was calculated with use of the BMUS relative index of giant cell tumor to osteosarcoma in three scenarios (low, base case, and high) from case series. We compared the BMUS approach with the latest data from tumor registries in Australia (1972 to 1996), Japan (2006 to 2008), and Sweden (1993 to 2011) that record giant cell tumors. United Nations population estimates were used to project results to 2013. RESULTS The low scenario in the BMUS approach reflects data from Unni and Inwards; the incidence of giant cell tumor of bone is 0.34 relative to osteosarcoma. As the incidence of osteosarcoma is 31.4% of the total incidence of bone and joint cancers, the incidence of giant cell tumor is 0.11 times that of all bone and joint cancers. The base scenario reflects the series by Mirra et al., with a giant cell tumor incidence of 0.47 relative to osteosarcoma (0.15 to all bone and joint cancers). The high scenario reflects the series by Ward, with an incidence of 0.84 relative to osteosarcoma (0.26 to all bone and joint cancers). Differences among the three series reflect referral to a national center of excellence compared with referral to a local oncology practice. Registry data indicated a giant cell tumor incidence rate per million per year of 1.33 in Australia, 1.03 in Japan, and 1.11 in Sweden in 2013. The estimated incidence rate per million in the ten countries in 2013 ranged from 1.03 (Japan) to 1.17 (Canada) with use of the registry-based approach and from 0.73 (Japan) for the low scenario) to 2.20 (Germany) for the base case with use of the BMUS approach. CONCLUSIONS Giant cell tumor of bone affects approximately one person per million per year in the ten countries studied. Estimates derived with use of age-specific incidences from tumor registries were typically within the range of the low and base case BMUS scenarios. We recommend the registry-derived method for estimating the incidence of giant cell tumor.

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

Akhtari, M. & Waller, E.K. (2009) Howell-Jolly bodylike inclusions in neutrophils. Blood, 114, 2860. Andre, E., Chevalier, C. & Scheiff, J.M. (2011) Howell-Jolly-like bodies in leucocytes: first description in leucocytes other than neutrophils. European Journal of Haematology, 86, 182–183. Ghosh, K., Muirhead, D., Christie, B. & Hiwase, D. (1999) Ultrastructural changes in peripheral blood neutrophils in a patient receiving ganciclovir for CMV pneumonitis following allogenic bone marrow transplantation. Bone Marrow Transplantation, 24, 429–431. Kennedy, G.A., Kay, T.D., Johnson, D.W., Hawley, C.M., Campbell, S.B., Isbel, N.M., Marlton, P., Cobcroft, R., Gill, D. & Cull, G. (2002) Neutrophil dysplasia characterised by a pseudo-Pelger-Huet anomaly occurring with the use of mycophenolate mofetil and ganciclovir following renal transplantation: a report of five cases. Pathology, 34, 263–266. Morales-Indiano, C., Arenillas Rocha, L., Mas Bosch, V. & Florensa Brichs, L. (2014) HowellJolly body-like inclusions in immunocompromised patients with antiviral treatment. Annals of Hematology, 93, 2091–2092. Ong, M.C., Veillon, D.M., Nordberg, M.L. & Cotelingam, J.D. (2010) Karyopyknotic cytoplasmic inclusions in neutrophils. The Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society, 162, 228– 230.

Population-based study of giant cell tumor of bone in Sweden (1983–2011)

INTRODUCTION Giant-cell tumor of bone (GCTB) is a locally aggressive histologically benign neoplasm with a less common malignant counterpart. Longitudinal data sources on GCTB are sparse, limited to single institution case series or surgical outcomes studies. The Swedish Cancer Registry is one of the few national population-based databases recording GCTB, representing a unique source to study GCTB epidemiology. We estimated incidence rate (IR) and overall mortality rates based on registry data. MATERIALS AND METHODS We identified patients with a GCTB diagnosis in the Swedish Cancer Registry from 1983 to 2011: benign (ICD-7 196.0-196.9; PAD 741) and malignant (PAD 746). Results were stratified by age at diagnosis, gender, and anatomical lesion location. RESULTS The cohort included 337 GCTB cases (IR of 1.3 per million persons per year). The majority (n=310) had primary benign GCTB (IR of 1.2 per million per year). Median age at diagnosis was 34 years (range 10-88) with 54% (n=183) females. Malignant to benign ratio for women was 0.095 (16/167) and for men 0.077 (11/143). Incidence was highest in the 20-39 years age group (IR of 2.1 per million per year). The most common lesion sites were distal femur and proximal tibia. Mortality at 20 years from diagnosis was 14% (n=48) and was slightly higher for axial (17%; n=6) and pelvic (17%; n=4) lesions. Recurrence occurred in 39% of primary benign cases and 75% of primary malignant cases. CONCLUSIONS In our modern population-based series primary malignant cases were uncommon (8%), peak incidence 20-39 years with slight predominance in women. Recurrence rates remain significant with overall 39% occurring in benign GCTB, and 75% in malignant form. The linkage between databases allowed the first population based estimates of the proportion of patients who received surgery at initial GCTB diagnosis, and those who also received subsequent surgeries.

Appropriateness of granulocyte colony-stimulating factor use in patients receiving chemotherapy by febrile neutropenia risk level

Objective Inappropriate granulocyte colony-stimulating factor use with myelosuppressive chemotherapy has been reported. Using the Oncology Services Comprehensive Electronic Records electronic medical record database, prophylactic granulocyte colony-stimulating factor (pegfilgrastim/filgrastim) use in cancer patients was assessed by febrile neutropenia risk level. Methods Patients with nonmetastatic or metastatic breast, head/neck, colorectal, ovarian/gynecologic, lung cancer, or non-Hodgkin’s lymphoma who received myelosuppressive chemotherapy from June 2013 to May 2014 were included. Prophylactic granulocyte colony-stimulating factor use with high-risk, intermediate-risk, and low-risk chemotherapy and distribution of National Comprehensive Cancer Network risk factors with intermediate-risk regimens were assessed. Results Overall, 86,189 patients received ∼4.2 million chemotherapy cycles (high risk, 9%; intermediate risk, 48%; low risk, 43%). Prophylactic granulocyte colony-stimulating factor was given in 24% of cycles (high risk, 59%; intermediate risk, 29%; low risk, 11%). For nonmetastatic solid tumors, granulocyte colony-stimulating factor was given in 78% (high risk), 31% (intermediate risk), and 6% (low risk) of cycles. For metastatic solid tumors or non-Hodgkin’s lymphoma, granulocyte colony-stimulating factor was given in 50% (high risk), 27% (intermediate risk), and 11% (low risk) of cycles. Among patients receiving intermediate-risk regimens with granulocyte colony-stimulating factor, febrile neutropenia risk factors were identified in 56% (95% confidence interval, 51.1–60.9%) of patients with nonmetastatic solid tumors (n = 400) and in 70% (64.5–73.5%) of patients with metastatic solid tumors or non-Hodgkin’s lymphoma (n = 400). Conclusion Prophylactic granulocyte colony-stimulating factor use was appropriately highest for high-risk regimens and lowest for low-risk regimens yet still potentially underused in high risk regimens, overused in low-risk regimens, and not appropriately targeted in intermediate-risk regimens, indicating a need for further education on febrile neutropenia risk evaluation and appropriate granulocyte colony-stimulating factor use.

1460PPOPULATION-BASED STUDY OF GIANT CELL TUMOUR OF THE BONE IN SWEDEN

ABSTRACT Aim: Giant-cell tumour of the bone (GCTB) is a locally aggressive and histologically benign neoplasm with a less common malignant counterpart. Sources of data on GCTB are sparse, and most published data are from individual case reports or case series. The Swedish Cancer Registry is one of the few national population-based databases that routinely records GCTB; representing a unique source to study the epidemiology of GCTB. The primary goal was to estimate the incidence rate (IR) and mortality rates of GCTB as recorded in the registry. Methods: We identified patients with a GCTB diagnosis in the Swedish Cancer Registry from 1983-2011: benign (ICD-7 196.0-196.9; PAD 741) and malignant (PAD 746). Results were stratified by age at diagnosis, gender, and anatomical lesion location. Mortality was described for patients diagnosed 1997-2011. Results: The cohort included 337 GCTB cases, corresponding to an IR of 1.3 per million persons per year. The majority (n=310) were primary benign (b)GCTB with population IR of 1.2 per million per year. Median age was 34 years (range 10–88) with 54% (n=183) female. Malignant to benign ratio was higher among women 0.095 (16/167) than men 0.077(11/143). Incidence was highest in the 20–29 years age group with an IR of 2.5 per million per year. The most common lesion site for both bGCTB and malignant (m)GCTB was the lower extremity (Table). Overall mortality at 14 years since diagnosis was 9% (n=14) and was higher for pelvic lesions (n=2; 15%). bGCTB mGCTB N Incidence * N Incidence * Age 0–19 43 0.67 2 0.03 20–39 133 1.86 15 0.21 40–59 90 1.31 5 0.07 60+ 44 0.74 5 0.08 Location Axial 33 0.13 2 0.01 Pelvic 19 0.07 4 0.02 Upper extremity 81 0.32 4 0.02 Lower extremity 143 0.56 13 0.05 Non-spec 34 0.13 4 0.02 * per million, per year Conclusions: This population-based, retrospective cohort study confirmed that GCTB is a rare disease in Sweden. Consistent with the published literature, malignant cases were uncommon (8%), peak incidence between 20–39 years, slight predominance in women, and most common lesion location was lower extremity. Further work is ongoing to elucidate risk factors associated with outcomes of patients with GCTB. Disclosure: J. Amelio: JA is employed by and owns stock in Amgen; J. Sandberg: JS is employed at IMS and are consultants for Amgen; R. Hernandez: RH is employed by and own stocks in Amgen; P. Sobocki: PS is employed at IMS and are consultants for Amgen; S. Stryker: SS is employed by and owns stock in Amgen; J. Engellau: JE is a board member of Genovis Inc. He has participated advisory board meetings for Amgen and lectured for Amgen on the topic GCTB; B. Bach: BB is employed by and owns stock in Amgen; A. Liede: AL is employed by and owns stock in Amgen

Renal impairment, hemoglobinuria, and hemoglobinemia among patients with idiopathic thrombocytopenic purpura

Renal impairment (RI) and events potentially leading to RI were reported in idiopathic thrombocytopenic purpura (ITP) patients with specific medications. This study was conducted to estimate the incidence rate (IR) of RI, hemoglobinuria and hemoglobinemia (HE) and characterize baseline risk factors in ITP and ITP‐free patients. Incident ITP and matched non‐ITP patients were identified from an electronic medical record database from 1990 to 2002. ITP patients were classified by the treatment first received (initiators) or ever received (users). All cohorts were followed for study outcomes. IRs were calculated and standardized by age and gender. A total of 881 ITP and 4,496 ITP‐free patients yielded 3,044 and 16,006 person‐years, respectively. The ITP cohort had a slightly higher prevalence of autoimmune diseases and infections than the ITP‐free cohort. The IR (/10,000 person‐years) for RI, hemoglobinuria and HE was 14.2, 35.7, and 7.1 in the ITP cohort; 10.0, 48.8, and 0 in the ITP‐free cohort; and 18.3, 37.1, and 6.1 in untreated ITP patients, respectively. The risk of RI, HE or hemoglobinuria was not found to differ substantially between ITP and non‐ITP patients or across ITP treatments. Am. J. Hematol., 2011.