Late endocrine diseases in survivors of adolescent and young adult cancer in California: a population-based study.

BACKGROUND: Cancer survivors have increased risk of endocrine complications, but there is a lack of information on the occurrence of specific endocrinopathies at the population-level. METHODS: We used data from the California Cancer Registry (2006-2018) linked to statewide hospitalisation, emergency department, and ambulatory surgery databases. We estimated the cumulative incidence of and factors associated with endocrinopathies among adolescents and young adults (AYA, 15-39 years) who survived ≥2 years after diagnosis. RESULTS: Among 59,343 AYAs, 10-year cumulative incidence was highest for diabetes (4.7%), hypothyroidism (4.6%), other thyroid (2.2%) and parathyroid disorders (1.6%). Hypothyroidism was most common in Hodgkin lymphoma, leukaemia, breast, and cervical cancer survivors, while diabetes was highest among survivors of leukaemias, non-Hodgkin lymphoma, colorectal, cervical, and breast cancer. In multivariable models, factors associated with increased hazard of endocrinopathies were treatment, advanced stage, public insurance, residence in low/middle socioeconomic neighbourhoods, older age, and non-Hispanic Black or Hispanic race/ethnicity. Haematopoietic cell transplant was associated with most endocrinopathies, while chemotherapy was associated with a higher hazard of ovarian dysfunction and hypothyroidism. CONCLUSIONS: We observed a high burden of endocrinopathies among AYA cancer survivors, which varied by treatment and social factors. Evidence-based survivorship guidelines are needed for surveillance of these diseases.

Late venous thromboembolism in survivors of adolescent and young adult cancer: A population-based study in California.

INTRODUCTION: Venous thromboembolism (VTE), a common complication in cancer patients, occurs more often during the initial phase of treatment. However, information on VTE beyond the first two years after diagnosis ('late VTE') is scarce, particularly in young survivors. METHODS: We examined the risk of, and factors associated with, late VTE among adolescents and young adults (AYA, 15-39 years) diagnosed with cancer (2006-2018) who survived ≥2 years. Data were obtained from the California Cancer Registry linked to hospitalization, emergency department and ambulatory surgery data. We used non-parametric models and Cox proportional hazard regression for analyses. RESULTS: Among 59,343 survivors, the 10-year cumulative incidence of VTE was 1.93 % (CI 1.80-2.07). The hazard of VTE was higher among those who had active cancer, including progression from lower stages to metastatic disease (Hazard Ratio (HR) = 10.41, 95 % confidence interval (CI): 8.86-12.22), second primary cancer (HR = 2.58, CI:2.01-3.31), or metastatic disease at diagnosis (HR = 2.38, CI:1.84-3.09). The hazard of late VTE was increased among survivors who underwent hematopoietic cell transplantation, those who received radiotherapy, had a VTE history, public insurance (vs private) or non-Hispanic Black/African American race/ethnicity (vs non-Hispanic White). Patients with leukemias, lymphomas, sarcoma, melanoma, colorectal, breast, and cervical cancers had a higher VTE risk than those with thyroid cancer. CONCLUSIONS: VTE risk remained elevated ≥2 years following cancer diagnosis in AYA survivors. Active cancer is a significant risk factor for VTE. Future studies might determine if late VTE should prompt evaluation for recurrence or second malignancy, if not already known.

Utilization of Autologous Hematopoietic Cell Transplantation Over Time in Multiple Myeloma: A Population-Based Study.

PURPOSE: Autologous hematopoietic cell transplantation (autoHCT) is associated with survival benefits in multiple myeloma (MM), but utilization remains low and differs by sociodemographic factors. Prior population-based studies have not fully captured autoHCT utilization or examined relationships between sociodemographic factors and autoHCT trends over time. PATIENTS AND METHODS: We used a novel data linkage between the California Cancer Registry, Center for International Blood and Marrow Transplant Research, and hospitalizations to capture autoHCT in a population-based MM cohort (n = 29, 109; 1991-2016). Due to interactions by treatment era, stratified multivariable Cox proportional hazards regression models determined factors associated with autoHCT. RESULTS: The frequency of MM patients who received autoHCT increased from 5.7% (1991-1995) to 27.4% (2011-2016). In models by treatment era, patients with public/no (vs. private) health insurance were less likely to receive autoHCT (2011-2016 Medicare hazard ratio (HR) 0.70, 95% confidence interval (CI): 0.63-0.78; Medicaid HR 0.81, CI: 0.72-0.91; no insurance HR 0.56, CI: 0.32-0.99). In each treatment era, Black/African American (vs. non-Hispanic White) patients were less likely to receive autoHCT (2011-2016 HR 0.83, CI: 0.72-0.95). Hispanic patients were less likely to undergo autoHCT, most prominently in the earliest treatment era (1991-1995 HR 0.58, 95% CI: 0.37-0.90; 2011-2016 HR 1.07, CI: 0.96-1.19). Patients in lower socioeconomic status neighborhoods were less likely to utilize autoHCT, but differences decreased over time. CONCLUSIONS: Despite increases in autoHCT utilization, sociodemographic disparities remain. Identifying and mitigating barriers to autoHCT is essential to ensuring more equitable access to this highly effective therapy.

Comparison of Vital Status, Cause of Death, and Follow-Up after Hematopoietic Cell Transplantation in Linked Center for International Blood and Marrow Transplant Research and California Cancer Registry Data, 1991 to 2018.

Assessing outcomes following hematopoietic cell transplantation (HCT) poses challenges due to the necessity for systematic and often prolonged patient follow-up. Linking the HCT database of the Center for International Blood and Marrow Transplant Research (CIBMTR) with cancer registry data may improve long-term outcome ascertainment, but the reliability of mortality data in death certificates from cancer registries among HCT recipients remains unknown. We compared the classification of vital status and primary cause of death (COD), as well as the length of follow-up between the CIBMTR and California Cancer Registry (CCR) to assess the possibility of supplementing the CIBMTR with cancer registry data. This retrospective study leveraged a linked CIBMTR-CCR dataset. We included patients who were California residents at the time of HCT and received a first allogeneic (allo) or autologous (auto) HCT for a hematologic malignancy diagnosed during 1991-2016. Follow-up was through 2018. We analyzed 18,450 patients (alloHCT, n = 8232; autoHCT, n = 10,218). The Vital status agreement was 97.7% for alloHCT and 97.2% for autoHCT. Unknown COD was higher in CIBMTR (12.9%) than in CCR (1.6%). After excluding patients with unknown COD information, the overall agreement of primary COD (cancer versus noncancer) was 53.7% for alloHCT and 83.2% for autoHCT. This agreement was lower within the first 100 days post-HCT (alloHCT, 31.0%; autoHCT, 54.6%). Compared with CIBMTR, deaths due to cancer were higher in CCR (alloHCT, 90.0%; autoHCT, 90.1% versus alloHCT, 47.3%; autoHCT, 82.5% in CIBMTR). CIBMTR reports more frequently noncancer-related deaths, including graft-versus-host disease and infections. The cumulative incidence of cancer-specific mortality at 20 years differed, particularly for alloHCT (CCR, 53.7%; CIBMTR, 27.6%). The median follow-up among alive patients was longer in CCR (alloHCT, 6.0 years; autoHCT, 4.7 years) than in CIBMTR (alloHCT, 5.0 years; autoHCT, 3.8 years). Our findings highlight the completeness of vital status data in CIBMTR but reveal substantial disagreement in primary COD. Consequently, caution is required when interpreting HCT studies that use only death certificates to estimate cause-specific mortality outcomes. Improving the accuracy of COD registration and follow-up completeness by developing communication pathways between cancer registries and hospital-based cohorts may enhance our understanding of late effects and long-term outcomes among HCT survivors.

Impact of Specialized Treatment Setting on Survival in Adolescent and Young Adult ALL.

PURPOSE: Unlike children with ALL who receive cancer care primarily at specialized cancer centers (SCCs; National Cancer Institute and/or Children's Oncology Group centers), adolescents and young adults (AYAs; 15-39 years) receive care in a variety of settings. Using population-based data, we describe where AYAs with ALL receive treatment and determine associations with overall survival (OS). METHODS: Data from the 2004 to 2018 California (CA, n = 2,283), New York (NY, n = 795), and Texas (TX, n = 955) state cancer registries were used to identify treatment setting of AYAs with newly diagnosed ALL. Multivariable Cox proportional hazards regression models evaluated associations with OS. RESULTS: Seventy percent were older than 18 years, and 65% were male. A majority in CA (63%) and TX (64%) were Hispanic while most in NY were non-Hispanic White (50%). Treatment at an SCC occurred in 48.2% (CA), 44.4% (NY), and 19.5% (TX). Across states, AYAs who were older or uninsured were less likely to receive treatment at an SCC. Treatment at an SCC was associated with superior OS in CA (hazard ratio [HR], 0.73; 95% CI, 0.63 to 0.85) and TX (HR, 0.61; 95% CI, 0.45 to 0.83); a nonsignificant association was seen in NY (HR, 0.83; 95% CI, 0.64 to 1.08). CONCLUSION: Only 20%-50% of AYA patients with ALL received frontline treatment at SCCs. Treatment of ALL at an SCC was associated with superior survival, highlighting the importance of policy efforts to improve access and reduce inequities in AYA ALL care.

Pregnancy outcomes in women with sickle cell disease in California.

Adverse pregnancy outcomes occur frequently in women with sickle cell disease (SCD) across the globe. In the United States, Black women experience disproportionately worse maternal health outcomes than all other racial groups. To better understand how social determinants of health impact SCD maternal morbidity, we used California's Department of Health Care Access and Information data (1991-2019) to estimate the cumulative incidence of pregnancy outcomes in Black women with and without SCD-adjusted for age, insurance status, and Distressed Community Index (DCI) scores. Black pregnant women with SCD were more likely to deliver at a younger age, use government insurance, and live in at-risk or distressed neighborhoods, compared to those without SCD. They also experienced higher stillbirths (26.8, 95% confidence interval [CI]: 17.5-36.1 vs. 12.4 [CI: 12.1-12.7], per 1000 births) and inpatient maternal mortality (344.5 [CI: 337.6-682.2] vs. 6.1 [CI: 2.3-8.4], per 100 000 live births). Multivariate logistic regression models showed Black pregnant women with SCD had significantly higher odds ratios (OR) for sepsis (OR 14.89, CI: 10.81, 20.52), venous thromboembolism (OR 13.60, CI: 9.16, 20.20), and postpartum hemorrhage (OR 2.25, CI 1.79-2.82), with peak onset in the second trimester, third trimester, and six weeks postpartum, respectively. Despite adjusting for sociodemographic factors, Black women with SCD still experienced significantly worse pregnancy outcomes than those without SCD. We need additional studies to determine if early introduction to reproductive health education, continuation of SCD-modifying therapies during pregnancy, and increasing access to multidisciplinary perinatal care can reduce morbidity in pregnant women with SCD.

Linking the Center for International Blood and Marrow Transplant Research Registry to the California Cancer Registry and California Hospital Patient Discharge Data.

Advances in hematopoietic cell transplantation (HCT) have substantially improved patient survival, increasing the importance of studying outcomes and long-term adverse effects in the rapidly growing population of HCT survivors. Large-scale registry data from the Center for International Blood and Marrow Transplant Research (CIBMTR) are a valuable resource for studying mortality and late effects after HCT, providing detailed data reported by HCT centers on transplantation-related factors and key outcomes. This study was conducted to evaluate the robustness of CIBMTR outcome data and assess health-related outcomes and healthcare utilization among HCT recipients. We linked data from the CIBMTR for California residents with data from the population-based California Cancer Registry (CCR) and hospitalization information from the California Patient Discharge Database (PDD). In this retrospective cohort study, probabilistic and deterministic record linkage used key patient identifiers, such as Social Security number, ZIP code, sex, birth date, hematologic malignancy type and diagnosis date, and HCT type and date. Among 22,733 patients registered with the CIBMTR who underwent autologous or allogeneic HCT for hematologic malignancy between 1991 and 2016, 89.0% were matched to the CCR and/or PDD (n = 17,707 [77.9%] for both, n = 1179 [5.2%] for the CCR only, and n = 1342 [5.9%] for the PDD only). Unmatched patients were slightly more likely to have undergone a first autologous HCT than an allogeneic HCT (12.6% versus 9.0%), to have a larger number of missing linkage identifiers, and to have undergone HCT prior to 2010. Among the patients reported to the CIBMTR who matched to the CCR, 85.7% demonstrated concordance of both hematologic malignancy type and diagnosis date across data sources. This linkage presents unparalleled opportunities to advance our understanding of HCT practices and patient outcomes.

Racial disparities in cancer-associated thrombosis.

Race and ethnicity are associated with risk of venous thromboembolism in population-based studies. Blacks/African Americans have a higher incidence, whereas Asians/Pacific Islanders and Hispanics have a lower incidence of venous thromboembolism compared with non-Hispanic Whites. The impact of race/ethnicity on the incidence of cancer-associated thrombosis (CAT), a common complication in patients with malignancy, has not been well defined. Using the California Cancer Registry linked to the California Patient Discharge Dataset and Emergency Department Utilization database, we studied a large, diverse cohort of patients (n = 942 109) from 2005 to 2017 with the 13 most common, first primary malignancies to determine the association between race/ethnicity and incidence of incident and recurrent CAT. Multivariable Cox proportional hazards regression models were performed to determine the effect of race/ethnicity on the risk of overall CAT, specific CAT by location, and recurrent CAT. Blacks/African Americans had a higher incidence of CAT for all tumor types except myeloma, whereas Asians/Pacific Islanders had a consistently lower incidence of CAT compared with non-Hispanic Whites, after adjusting for potential confounders. The main driver for the racial/ethnic differences was incidence of pulmonary embolism. We speculate the association of race/ethnicity with incidence of CAT may be partially because of underlying thrombotic predisposition that varies by ancestry, but we also must consider the impact of social determinants of health on our results.

Second primary malignancy risk after Hodgkin lymphoma treatment among HIV-uninfected and HIV-infected survivors.

We compared secondary primary malignancy risk (SPM) in HIV-uninfected and HIV-infected Hodgkin lymphoma (HL) survivors. We used data from the California Cancer Registry on patients diagnosed with HL from 1990 to 2015 (all ages included), and standardized incidence ratios (SIRs) and multivariable competing risk models for analyses. Of 19,667 survivors, 735 were HIV-infected. Compared with the general population, the risk of SPM was increased by 2.66-fold in HIV-infected and 1.92-fold in HIV-uninfected survivors. Among HIV-infected survivors, median time to development of SPM was shorter (5.4 years) than in HIV-uninfected patients (8.1 years). Additionally, the highest risk of SPM was observed <2 years after diagnosis in HIV-infected survivors (SIR = 4.47), whereas risk was highest ≥20 years after diagnosis (SIR = 2.39) in HIV-uninfected survivors. The risk of SPMs persisted for decades and was higher among HIV-infected survivors, suggesting that these patients should benefit from long-term surveillance and cancer prevention practices.

Incidence and Outcomes Associated with 6,841 Isolated Distal Deep Vein Thromboses in Patients with 13 Common Cancers.

INTRODUCTION: The epidemiology of isolated distal deep venous thrombosis (iDDVT) among cancer patients is not well described, particularly the incidence of recurrent venous thromboembolism (rVTE) and effect on mortality by cancer type. METHODS: The cumulative incidence (CI) of iDDVT was determined for patients with 13 common cancers between 2005 and 2017 using the California Cancer Registry linked to the California Patient Discharge and Emergency Department Utilization datasets. The CI of rVTE was calculated and association of incident cancer-associated thrombosis (CT) location with rVTE was determined using Cox proportional hazards regression models. The association of incident CT location with overall and cancer-specific mortality was determined using Cox models, stratified by cancer site, and adjusted for individual characteristics. RESULTS: Among 942,109 cancer patients, CT occurred in 62,003 (6.6%): of these, 6,841 (11.0%) were iDDVT. Compared with more proximal sites of CT, iDDVT was associated with similar risk for rVTE. IDDVT was associated with increased mortality across all cancer types when compared with patients without CT (hazard ratio: 1.56-4.60). The effect of iDDVT on mortality was similar to that of proximal DVT (pDVT) for most cancers except lung, colorectal, bladder, uterine, brain, and myeloma, where iDDVT was associated with a lesser association with mortality. CONCLUSION: iDDVT represented 11% of CT. The risk of rVTE after iDDVT was similar to other sites of CT and rVTE occurred in more proximal locations after an incident iDDVT. IDDVT was associated with increased mortality and this effect was similar to that of pulmonary embolism or pDVT for most cancer types.

The incidence of cancer-associated thrombosis is increasing over time.

Cancer-associated thrombosis (CAT) is an important cause of morbidity and mortality for patients with malignancy and varies by primary cancer type, stage, and therapy. We aimed to characterize the incidence, risk factors, temporal trends, and the effect on mortality of CAT. The California Cancer Registry was linked to the statewide hospitalization database to identify individuals with the 13 most common malignancies diagnosed between 2005 and 2017 and determine the 6- and 12-month cumulative incidence of CAT by venous thromboembolism (VTE) location, tumor type, and stage after adjusting for competing risk of death. Cox proportional hazard regression models were used to determine risk factors associated with CAT and the effect of CAT on all-cause mortality. 942 019 patients with cancer were identified; 62 003 (6.6%) had an incident diagnosis of CAT. Patients with pancreatic, brain, ovarian, and lung cancer had the highest, and patients with breast and prostate cancer had the lowest 12-month cumulative incidence of CAT. For most malignancies, men, those with metastatic disease and more comorbidities, and African Americans (vs non-Hispanic Whites) were at highest risk for CAT. Patients diagnosed with cancer between 2014 and 2017 had a higher risk of CAT compared with those diagnosed between 2005 and 2007. CAT was associated with increased overall mortality for all malignancies (HR ranges 1.89 to 4.79). The incidence of CAT increased over time and was driven by an increase in pulmonary embolism±deep vein thrombosis (PE±DVT). CAT incidence varies based on tumor type and stage and on individual risk factors including gender, race/ethnicity, and comorbidities. For all tumor types, CAT is associated with an increased mortality.

Treatment at Specialized Cancer Centers Is Associated with Improved Survival in Adolescent and Young Adults with Soft Tissue Sarcoma.

Background: Soft tissue sarcomas (STS) are a heterogeneous group of tumors whose management benefits from a multidisciplinary therapeutic approach. Published data suggest that cancer treatment at a specialized cancer center (SCC) can improve survival in other cancers. Therefore, we examined the impact of the location of treatment on survival in children and adolescents and young adults (AYAs) with STS. Methods: We performed a population-based analysis of children and AYAs hospitalized within 1 year of diagnosis with first primary STS (2000-2014) using the California Cancer Registry linked with hospitalization data. Patients were categorized based on receiving all inpatient treatments at a SCC versus part/none. Multivariable Cox proportional hazards regression identified factors associated with overall and STS-specific survival by age group. Results are presented as adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Of the 1,674 patients with STS, 142 were children (0-14) and 1,532 were AYAs (15-39) and 89.4% and 40.4% received all inpatient treatments at a SCC, respectively. Overall, the 5-year survival was improved for patients who received all inpatient care at a SCC (59.8% vs. those who received part/none, 50.7%). Multivariable regression analysis found that having all treatments at a SCC was associated with better overall survival (HR, 0.79, CI: 0.65-0.95) in AYAs, but not in children. Conclusions: Our findings demonstrate that treatment for STS at a SCC is associated with better survival in AYAs. Eliminating barriers to treatment of AYAs with STS at SCCs could improve survival in this population.

Long-term Follow-up and Correlative Analysis of Two Phase II Trials of Rituximab and Lenalidomide Followed by Continuous Lenalidomide in Untreated and Relapsed/Refractory Indolent Lymphoma.

PURPOSE: Rituximab and lenalidomide are effective for previously untreated and relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). However, long-term survival and predictive biomarkers are not well described. PATIENTS AND METHODS: We conducted two phase II open-label trials involving 60 patients with previously untreated and R/R advanced-stage iNHL. Patients received lenalidomide and rituximab induction followed by continuous lenalidomide until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Correlative studies included plasma cytokine monitoring, flow cytometry of peripheral blood mononuclear cells (PBMC; days 0, 15, 30, and 60), and RNA sequencing (RNA-seq) of pretreatment tumor biopsies. RESULTS: At a median follow-up of 63 months for previously untreated and 100 months for R/R, ORR was 82% for both. The 11 R/R patients who achieved complete remission remained in continuous remission for 16 to 141 months, thereafter. Median overall survival (OS) was not reached in the previously untreated and was 140 months (95% confidence interval, 53.4-140) in the R/R group. A mixed-effects linear regression model identified significant associations between Granzyme B+ (GranB+) CD8+ T cells and long-term complete response (LTCR; P = 5.3e-4). Furthermore, prior to start of therapy, treatment response could be predicted by B-cell and GranB+ CD8+ T-cell levels (% total lymphocytes). CONCLUSIONS: Rituximab plus lenalidomide followed by continuous lenalidomide is effective with manageable toxicity in patients with previously untreated and R/R iNHL. This regimen produces durable remissions, even in heavily pretreated patients, with some lasting greater than 10 years. GranB+ CD8+ T cells, B cells, and plasma IFNγ allowed prediction of LTCR but need validation in larger trials.

Incidence of Upper Extremity Deep Vein Thrombosis in Acute Leukemia and Effect on Mortality.

The cumulative incidence, risk factors, rate of subsequent venous thromboembolism (VTE) and bleeding and impact on mortality of isolated upper extremity deep vein thrombosis (UE DVT) in acute leukemia are not well-described. The California Cancer Registry, used to identify treated patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) diagnosed between 2009 and 2014, was linked with the statewide hospitalization database to determine cumulative incidences of UE DVT and subsequent VTE and bleeding after UE DVT diagnosis. Cox proportional hazards regression models were used to assess the association of UE DVT on the risk of subsequent pulmonary embolism (PE) or lower extremity deep vein thrombosis (LE DVT) and subsequent bleeding, and the impact of UE DVT on mortality. There were 5,072 patients identified: 3,252 had AML and 1,820 had ALL. Three- and 12-month cumulative incidences of UE DVT were 4.8% (95% confidence interval [CI]: 4.1-5.6) and 6.6% (95% CI: 5.8-7.5) for AML and 4.1% (95% CI: 3.2-5.1) and 5.9% (95% CI: 4.9-7.1) for ALL, respectively. Twelve-month cumulative incidences of subsequent VTE after an incident UE DVT diagnosis were 5.3% for AML and 12.2% for ALL. Twelve-month cumulative incidences of subsequent bleeding after an incident UE DVT diagnosis were 15.4% for AML and 21.1% for ALL. UE DVT was associated with an increased risk of subsequent bleeding for both AML (hazard ratio [HR]: 2.07; 95% CI: 1.60-2.68) and ALL (HR: 1.62; 95% CI: 1.02-2.57) but was not an independent risk factor for subsequent PE or LE DVT for either leukemia subtype. Isolated incident UE DVT was associated with increased leukemia-specific mortality for AML (HR: 1.42; 95% CI: 1.16-1.73) and ALL (HR: 1.80; 95% CI: 1.31-2.47). UE DVT is a relatively common complication among patients with AML and ALL and has a significant impact on bleeding and mortality. Further research is needed to determine appropriate therapy for this high-risk population.

Impact of insurance type and timing of Medicaid enrollment on survival among adolescents and young adults with cancer.

BACKGROUND: Adolescents and young adults (AYAs) with public or no insurance experience later stage at diagnosis and worse overall survival compared with those with private insurance. However, prior studies have not distinguished the survival impact of continuous Medicaid coverage prior to diagnosis compared with gaining Medicaid coverage at diagnosis. METHODS: We linked a cohort of AYAs aged 15-39 who were diagnosed with 13 common cancers from 2005 to 2014 in the California Cancer Registry with California Medicaid enrollment files to ascertain Medicaid enrollment, with other insurance determined from registry data. We used Cox proportional hazards regression to evaluate the impact of insurance on survival, adjusting for clinical and demographic characteristics. RESULTS: Among 62 218 AYAs, over 65% had private/military insurance, 10% received Medicaid at diagnosis, 13.2% had continuous Medicaid, 4.1% had discontinuous Medicaid, 1.7% had other public insurance, 3% were uninsured, and 2.6% had unknown insurance. Compared with those with private/military insurance, individuals with Medicaid insurance had significantly worse survival regardless of when coverage began (received Medicaid at diagnosis: hazard ratio [95% confidence interval]: 1.51 [1.42-1.61]; continuously Medicaid insured: 1.42 [1.33-1.52]; discontinuous Medicaid: 1.64 [1.49, 1.80]). Analyses of those with Medicaid insurance only demonstrated slightly worse cancer-specific survival among those with discontinuous Medicaid or enrollment at diagnosis compared with those with continuous enrollment, but results were not significant stratified by cancer site. CONCLUSIONS AND RELEVANCE: AYAs with Medicaid insurance experience worse cancer-specific survival compared with those with private/military insurance, yet continuous enrollment demonstrates slight survival improvements, providing potential opportunities for future policy intervention.

High incidence of venous thromboembolism and major bleeding in patients with primary CNS lymphoma.

Venous thromboembolism (VTE) and major bleeding in primary central nervous system lymphoma (PCNSL) patients are not well described. We identified 992 PCNSL patients using the California Cancer Registry (2005-2014). The cumulative incidence of VTE and major bleeding was determined using California hospitalization data. The 12-month cumulative incidence of VTE was 13.6% (95% confidence interval (CI) 11.5-15.8%); chemotherapy and radiation therapy were associated with increased risk of VTE (hazard ratio (HR) 2.41, CI 1.31-4.46 and HR 1.56, CI 1.08-2.25, respectively). The 12-month cumulative incidence of major bleeding was 12.4% (CI 10.1-14.6%). Pulmonary embolism (PE) and proximal deep vein thrombosis were associated with increased risk of major bleeding, likely due to anticoagulation. PE (HR 1.61, CI 1.11-2.33, p=.011) and major bleeding (HR 2.36, CI 1.82-3.06, p<.0001) were associated with increased mortality. This study highlights the high incidence of both VTE and major bleeding and the significant impact on survival for PCNSL patients.

Treatment Complications and Survival Among Children and Young Adults With Acute Lymphoblastic Leukemia.

PURPOSE: We previously demonstrated lower early mortality for young adults (YAs) with acute lymphoblastic leukemia (ALL) who received induction treatment at specialized cancer centers (SCCs) versus community hospitals. The aim of this study is to determine the impact of inpatient location of treatment throughout therapy on long-term survival, complications, and cost-associations that have not yet been evaluated at the population level. METHODS: Using the California Cancer Registry linked to a hospitalization database, we identified patients, 0-39 years of age, diagnosed with first primary ALL who received inpatient treatment between 1991 and 2014. Patients were classified as receiving all or part or none of their inpatient treatment at an SCC within 3 years of diagnosis. Inverse probability-weighted, multivariable Cox regression models estimated the associations between location of treatment and sociodemographic and clinical factors with survival. We compared 3-year inpatient costs overall and per day by age group and location of care. RESULTS: Eighty-four percent (0-18 years; n = 4,549) of children and 36% of YAs (19-39 years; n = 683) received all treatment at SCCs. Receiving all treatment at an SCC was associated with superior leukemia-specific (hazard ratio [HR], 0.76; 95% CI, 0.67 to 0.88) and overall survival (HR, 0.87; 95% CI, 0.77 to 0.97) in children and in YAs (HR, 0.71; 95% CI, 0.61 to 0.83; HR, 0.70; 95% CI, 0.62 to 0.80) even after controlling for complications. The cost of inpatient care during the full course of therapy was higher in patients receiving all of their care at SCCs. CONCLUSION: Our results demonstrate that inpatient treatment at an SCC throughout therapy is associated with superior survival; therefore, strong consideration should be given to referring these patients to SCCs.

Bleeding in patients with sickle cell disease: a population-based study.

Bleeding is a known complication of sickle cell disease (SCD) and includes hemorrhagic stroke, hematuria, and vitreous hemorrhage. However, the incidence of bleeding events in patients with SCD has not been well described. We present a retrospective, population-based study examining the cumulative incidence of bleeding in 6423 patients with SCD from 1991 to 2014. We also studied risk factors associated with bleeding and the effects of bleeding on mortality, using Cox proportional hazards regression models. We used California emergency department and hospitalization databases to identify patients with SCD with intracranial hemorrhage, gastrointestinal (GI) bleeding, hemophthalmos, gross hematuria, epistaxis, menorrhagia, and other bleeding events. The cumulative incidence of any first bleeding event at age 40 years was 21% (95% confidence interval [CI], 19.8%-22.3%), increasing with age to 41% by age 60 years (95% CI, 38.8%-43.1%). The majority of bleeding events were GI (41.6%), particularly from the upper GI tract. A higher bleeding risk was associated with increased frequency of hospitalization (hazard ratio [HR], 2.16; 95% CI, 1.93-2.42), venous thromboembolism 180 days before bleeding event (HR, 4.24; 95% CI, 2.86-6.28), osteonecrosis of the femoral head (HR, 1.25; 95% CI, 1.08-1.46), and ischemic stroke (HR, 1.65; 95% CI, 1.20-2.26). Bleeding was also associated with a twofold increased risk for death (HR, 2.09; 95% CI, 1.82-2.41) adjusted for other SCD-related complications. Our novel finding of a high incidence of bleeding in patients with SCD, particularly from the upper GI tract, suggests that patients with SCD may be predisposed to bleeding, with possible etiologies including increased use of nonsteroidal anti-inflammatory drugs, mucosal infarction from vascular occlusion by sickled red blood cells, and increased stress ulceration from frequent hospitalization.

Impaired Immune Health in Survivors of Diffuse Large B-Cell Lymphoma.

PURPOSE: Therapeutic advances for diffuse large B-cell lymphoma (DLBCL) have led to an increasing number of survivors. Both DLBCL and its treatments perturb the immune system, yet little is known about immune health during extended survivorship. METHODS: In this retrospective cohort study, we compared 21,690 survivors of DLBCL from the California Cancer Registry (CCR) to survivors of breast, prostate, head and neck, and melanoma cancers. We linked their CCR records to a statewide database documenting hospital, emergency room, and ambulatory surgery visits and investigated the incidence of autoimmune conditions, immune deficiencies, and infections 1-10 years after cancer diagnosis. RESULTS: We found elevated incidence rate ratios (IRRs) for many immune-related conditions in survivors of DLBCL compared with other cancer survivors, including significantly and consistently elevated IRRs for viral and fungal pneumonias (up to 10.8-fold), meningitis (up to 5.3-fold), as well as humoral deficiency (up to 17.6-fold) and autoimmune cytopenias (up to 12-fold). IRRs for most conditions remained high even in the late survivorship period (5-10 years after cancer diagnosis). The elevated risks could not be explained by exposure to chemotherapy, stem-cell transplantation, or rituximab, except for IRRs for humoral deficiency, which were consistently higher after the incorporation of rituximab into DLBCL treatments. CONCLUSION: To our knowledge, this is the largest cohort study with extended follow-up to demonstrate impaired immune health in survivors of DLBCL. The observed persistent, elevated risks for autoimmune diseases, immune deficiencies, and infectious conditions may reflect persistent immune dysregulation caused by lymphoma or treatment and may lead to excess morbidity and mortality during survivorship. Improved understanding of these risks could meaningfully improve long-term care of patients with DLBCL.

Bariatric surgery to aLleviate OCcurrence of Atrial Fibrillation Hospitalization-BLOC-AF.

BACKGROUND: Obesity is associated with a higher incidence of atrial fibrillation (AF). Weight reduction improves outcomes in patients known to have AF. OBJECTIVE: The purpose of this study was to compare the incidence of heart failure (HF) or first-time AF hospitalization in obese patients undergoing bariatric surgery (BAS) vs other abdominal surgeries. METHODS: A retrospective cohort study was conducted using linked hospital discharge records from 1994-2014. Obese patients without known AF or atrial flutter (AFL) who had undergone abdominal hernia or laparoscopic cholecystectomy surgery were identified for each case that underwent BAS (2:1). Clinical outcomes were HF, first-time hospitalization for AF, AFL, gastrointestinal bleeding (GIB), and ischemic or hemorrhagic stroke. Outcomes were analyzed using conditional proportional hazard modeling accounting for the competing risk of death, adjusting for demographics and comorbidities. RESULTS: There were 1581 BAS cases and 3162 controls (48% age <50 years; 60% white; 79% female; mean CHA2DS2VASc score 1.6 ± 1.2) with follow-up of 66 months. Compared to controls, BAS cases had a significantly lower risk of new-onset AF (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.54-0.93) or HF (HR 0.74; 95% CI 0.60-0.91) but a higher risk of GIB (HR 2.1; 95% CI 1.5-3.0), with no differences in AFL, ischemic stroke, or hemorrhagic stroke. Reduction in AF improved as follow-up increased beyond 60 months. CONCLUSION: In patients undergoing BAS, the risk of either HF or AF was reduced by ∼29% but with greater risk of GIB. The findings support the hypothesis that weight loss reduces the long-term risk of HF or incident AF hospitalization.