Πέμπτη 1 Ιουνίου 2017

Geographic epidemiology of hepatocellular carcinoma, viral hepatitis, and socioeconomic position in New York City

Abstract

Purpose

Liver cancer (hepatocellular carcinoma (HCC)) incidence and mortality rates are increasing in the United States. New York City (NYC) has a high burden of liver cancer risk factors, including hepatitis C (HCV) and hepatitis B (HBV) infection, which disproportionately affect persons of low socioeconomic position. Identifying neighborhoods with HCC disparities is essential to effectively define targeted cancer control strategies.

Methods

New York State Cancer Registry data from 1 January 2001 through 31 December 2012 were matched with NYC HCV and HBV surveillance data. HCC data were aggregated to NYC Zip Code Tabulation Areas (ZCTAs). Moran's I cluster analysis, Poisson regression, and geographically weighted Poisson regression were used to identify hotspots in HCC incidence and to examine the spatial associations with viral hepatitis rates, poverty, and uninsured status.

Results

Among NYC residents, 8,827 HCC cases were diagnosed during 2001–2012. Significant clustering was detected in the HCC rates (Moran's I = 0.25) with the strongest clustering found in HCC patients with comorbid HCV infection (Moran's I = 0.47). Poverty and uninsured status were associated (p < 0.05) with increased rates of HCC patients with HBV or HCV infection. Neighborhoods with high rates of HCC without viral hepatitis infection had lower rates of poverty and uninsured status.

Conclusions

The geographic variation in HCC highlights the need for neighborhood-targeted interventions to address risk factors and barriers to care. The clusters of HCC by viral hepatitis status may serve as a basis for healthcare policymakers and practitioners to prioritize neighborhoods for cancer screening and control efforts.



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Dexrazoxane added to doxorubicin-based adjuvant chemotherapy of breast cancer: a retrospective cohort study with a comparative analysis of toxicity and survival.

Dexrazoxane is indicated as a cardioprotective agent for patients receiving doxorubicin who are at increased risk for cardiotoxicity. Concerns have been raised on the use of dexrazoxane, particularly in adjuvant therapy, because of the risk of interference with the antitumor effect of doxorubicin. Two meta-analyses in metastatic breast cancer have rejected this hypothesis, but have shown an apparent increase in the severity of myelosuppression when dexrazoxane is used. Here, we analyzed retrospectively a cohort of our institute database to assess whether the addition of dexrazoxane causes more bone marrow suppression in breast cancer patients receiving doxorubicin-based adjuvant therapy. The secondary objectives were assessment of the incidence of febrile neutropenia, dose-schedule modifications, recorded cardiac events or cardiac test abnormalities, and overall survival. Eight hundred and twenty-two female patients who received adjuvant (or neoadjuvant) doxorubicin and cyclophosphamide for breast cancer between 2001 and 2013 were included. One hundred and four of these patients also received dexrazoxane concurrently with the adjuvant treatment. Hospital records and, when accessible, community clinic records were reviewed. The median follow-up duration was 7 years for patients receiving dexrazoxane and 7.5 years for patients not receiving dexrazoxane. 85.6% of patients were alive at data lock. Compared with the nondexrazoxane group, patients who received dexrazoxane were older (median age at diagnosis 59 vs. 52 years) and more likely to receive dose-dense AC therapy (73 vs. 59%) and adjuvant trastuzumab treatment (29 vs. 15%). Compared with the nondexrazoxane group, dexrazoxane treatment was associated with a higher rate of hematological side effects: leukopenia (48 vs. 39%), neutropenia (45 vs. 31%, P=0.003), anemia (86 vs. 73%, P=0.005), and thrombocytopenia (37 vs. 22%, P=0.001). There were more febrile neutropenia hospitalizations (20 vs. 10%, P=0.001) and dose reductions (22 vs. 8%, P

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Pharmacokinetics of venetoclax in patients with 17p deletion chronic lymphocytic leukemia.

Venetoclax is a first-in-class orally available, B-cell lymphoma (BCL)-2 inhibitor indicated for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) harboring the 17p deletion. We used a novel approach for evaluating venetoclax pharmacokinetics using only sparse sampling in 155 patients enrolled in a phase 2, multicenter, open-label study in CLL patients with the 17p deletion. Patients received venetoclax doses within 30 min after the completion of breakfast or the first meal of the day, with no specific recommendations for the fat content in the meal. Blood samples for venetoclax assay were collected during the ramp-up period and on day 1 of weeks 8, 12, 16, 24, and every 12 weeks thereafter. The mean postdose (8 h) plasma venetoclax concentrations increased with increasing weekly venetoclax dose during the ramp-up period to reach 1.89 [micro]g/ml on week 5 day 1 at the 400 mg dose. The mean predose concentration at the 400 mg dose ranged between 0.69 and 0.99 [micro]g/ml across visits between weeks 8 and 120. Repeated-measures analysis detected no statistical significance (P>=0.05) for the mean predose concentrations at any of the times tested from weeks 8 to 24. The study shows that the pharmacokinetic profile of venetoclax in CLL patients with the 17p deletion is comparable to the overall CLL as well as non-Hodgkin's lymphoma patient populations. Furthermore, no specific recommendation in terms of fat content in the meal is needed for the intake of venetoclax in patients with CLL. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Geographic epidemiology of hepatocellular carcinoma, viral hepatitis, and socioeconomic position in New York City

Abstract

Purpose

Liver cancer (hepatocellular carcinoma (HCC)) incidence and mortality rates are increasing in the United States. New York City (NYC) has a high burden of liver cancer risk factors, including hepatitis C (HCV) and hepatitis B (HBV) infection, which disproportionately affect persons of low socioeconomic position. Identifying neighborhoods with HCC disparities is essential to effectively define targeted cancer control strategies.

Methods

New York State Cancer Registry data from 1 January 2001 through 31 December 2012 were matched with NYC HCV and HBV surveillance data. HCC data were aggregated to NYC Zip Code Tabulation Areas (ZCTAs). Moran's I cluster analysis, Poisson regression, and geographically weighted Poisson regression were used to identify hotspots in HCC incidence and to examine the spatial associations with viral hepatitis rates, poverty, and uninsured status.

Results

Among NYC residents, 8,827 HCC cases were diagnosed during 2001–2012. Significant clustering was detected in the HCC rates (Moran's I = 0.25) with the strongest clustering found in HCC patients with comorbid HCV infection (Moran's I = 0.47). Poverty and uninsured status were associated (p < 0.05) with increased rates of HCC patients with HBV or HCV infection. Neighborhoods with high rates of HCC without viral hepatitis infection had lower rates of poverty and uninsured status.

Conclusions

The geographic variation in HCC highlights the need for neighborhood-targeted interventions to address risk factors and barriers to care. The clusters of HCC by viral hepatitis status may serve as a basis for healthcare policymakers and practitioners to prioritize neighborhoods for cancer screening and control efforts.



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Dexrazoxane added to doxorubicin-based adjuvant chemotherapy of breast cancer: a retrospective cohort study with a comparative analysis of toxicity and survival.

Dexrazoxane is indicated as a cardioprotective agent for patients receiving doxorubicin who are at increased risk for cardiotoxicity. Concerns have been raised on the use of dexrazoxane, particularly in adjuvant therapy, because of the risk of interference with the antitumor effect of doxorubicin. Two meta-analyses in metastatic breast cancer have rejected this hypothesis, but have shown an apparent increase in the severity of myelosuppression when dexrazoxane is used. Here, we analyzed retrospectively a cohort of our institute database to assess whether the addition of dexrazoxane causes more bone marrow suppression in breast cancer patients receiving doxorubicin-based adjuvant therapy. The secondary objectives were assessment of the incidence of febrile neutropenia, dose-schedule modifications, recorded cardiac events or cardiac test abnormalities, and overall survival. Eight hundred and twenty-two female patients who received adjuvant (or neoadjuvant) doxorubicin and cyclophosphamide for breast cancer between 2001 and 2013 were included. One hundred and four of these patients also received dexrazoxane concurrently with the adjuvant treatment. Hospital records and, when accessible, community clinic records were reviewed. The median follow-up duration was 7 years for patients receiving dexrazoxane and 7.5 years for patients not receiving dexrazoxane. 85.6% of patients were alive at data lock. Compared with the nondexrazoxane group, patients who received dexrazoxane were older (median age at diagnosis 59 vs. 52 years) and more likely to receive dose-dense AC therapy (73 vs. 59%) and adjuvant trastuzumab treatment (29 vs. 15%). Compared with the nondexrazoxane group, dexrazoxane treatment was associated with a higher rate of hematological side effects: leukopenia (48 vs. 39%), neutropenia (45 vs. 31%, P=0.003), anemia (86 vs. 73%, P=0.005), and thrombocytopenia (37 vs. 22%, P=0.001). There were more febrile neutropenia hospitalizations (20 vs. 10%, P=0.001) and dose reductions (22 vs. 8%, P

from Cancer via ola Kala on Inoreader http://ift.tt/2qBP0iE
via IFTTT

Pharmacokinetics of venetoclax in patients with 17p deletion chronic lymphocytic leukemia.

Venetoclax is a first-in-class orally available, B-cell lymphoma (BCL)-2 inhibitor indicated for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) harboring the 17p deletion. We used a novel approach for evaluating venetoclax pharmacokinetics using only sparse sampling in 155 patients enrolled in a phase 2, multicenter, open-label study in CLL patients with the 17p deletion. Patients received venetoclax doses within 30 min after the completion of breakfast or the first meal of the day, with no specific recommendations for the fat content in the meal. Blood samples for venetoclax assay were collected during the ramp-up period and on day 1 of weeks 8, 12, 16, 24, and every 12 weeks thereafter. The mean postdose (8 h) plasma venetoclax concentrations increased with increasing weekly venetoclax dose during the ramp-up period to reach 1.89 [micro]g/ml on week 5 day 1 at the 400 mg dose. The mean predose concentration at the 400 mg dose ranged between 0.69 and 0.99 [micro]g/ml across visits between weeks 8 and 120. Repeated-measures analysis detected no statistical significance (P>=0.05) for the mean predose concentrations at any of the times tested from weeks 8 to 24. The study shows that the pharmacokinetic profile of venetoclax in CLL patients with the 17p deletion is comparable to the overall CLL as well as non-Hodgkin's lymphoma patient populations. Furthermore, no specific recommendation in terms of fat content in the meal is needed for the intake of venetoclax in patients with CLL. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/2rlJuhj
via IFTTT