Publications by authors named "Smita Bhatia"

330 Publications

SARS-CoV-2 in Childhood Cancer in 2020: A Disease of Disparities.

J Clin Oncol 2021 Oct 25:JCO2100702. Epub 2021 Oct 25.

Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL.

Purpose: The Pediatric Oncology COVID-19 Case Report registry supplies pediatric oncologists with data surrounding the clinical course and outcomes in children with cancer and SARS-CoV-2.

Methods: This observational study captured clinical and sociodemographic characteristics for children (≤ 21 years) receiving cancer therapy and infected with SARS-CoV-2 from the pandemic onset through February 19, 2021. The demographic and clinical characteristics of the cohort were compared with population-level pediatric oncology data (SEER). Multivariable binomial regression models evaluated patient characteristics associated with hospitalization, intensive care unit (ICU) admission, and changes in cancer therapy.

Results: Ninety-four institutions contributed details on 917 children with cancer and SARS-CoV-2. Median age at SARS-CoV-2 infection was 11 years (range, 0-21 years). Compared with SEER, there was an over-representation of Hispanics (43.6% 29.7%, < .01), publicly insured (59.3% 33.5%, < .01), and patients with hematologic malignancies (65.8% 38.3%, < .01) in our cohort. The majority (64.1%) were symptomatic; 31.2% were hospitalized, 10.9% required respiratory support, 9.2% were admitted to the ICU, and 1.6% died because of SARS-CoV-2. Cancer therapy was modified in 44.9%. Hispanic ethnicity was associated with changes in cancer-directed therapy (adjusted risk ratio [aRR] = 1.3; 95% CI, 1.1 to 1.6]). Presence of comorbidities was associated with hospitalization (aRR = 1.3; 95% CI, 1.1 to 1.6) and ICU admission (aRR = 2.3; 95% CI, 1.5 to 3.6). Hematologic malignancies were associated with hospitalization (aRR = 1.6; 95% CI, 1.3 to 2.1).

Conclusion: These findings provide critical information for decision making among pediatric oncologists, including inpatient versus outpatient management, cancer therapy modifications, consideration of monoclonal antibody therapy, and counseling families on infection risks in the setting of the SARS-CoV-2 pandemic. The over-representation of Hispanic and publicly insured patients in this national cohort suggests disparities that require attention.
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http://dx.doi.org/10.1200/JCO.21.00702DOI Listing
October 2021

Late health outcomes after dexrazoxane treatment: A report from the Children's Oncology Group.

Cancer 2021 Oct 13. Epub 2021 Oct 13.

Oishei Children's Hospital, Roswell Park Comprehensive Center, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York.

Background: The objective of this study was to examine long-term outcomes among children newly diagnosed with cancer who were treated in dexrazoxane-containing clinical trials.

Methods: P9404 (acute lymphoblastic leukemia/lymphoma [ALL]), P9425 and P9426 (Hodgkin lymphoma), P9754 (osteosarcoma), and Dana-Farber Cancer Institute 95-01 (ALL) enrolled 1308 patients between 1996 and 2001: 1066 were randomized (1:1) to doxorubicin with or without dexrazoxane, and 242 (from P9754) were nonrandomly assigned to receive dexrazoxane. Trial data were linked with the National Death Index, the Organ Procurement and Transplantation Network, the Pediatric Health Information System (PHIS), and Medicaid. Osteosarcoma survivors from the Childhood Cancer Survivor Study (CCSS; n = 495; no dexrazoxane) served as comparators in subanalyses. Follow-up events were assessed with cumulative incidence, Cox regression, and Fine-Gray methods.

Results: In randomized trials (cumulative prescribed doxorubicin dose, 100-360 mg/m ; median follow-up, 18.6 years), dexrazoxane was not associated with relapse (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63-1.13), second cancers (HR, 1.19; 95% CI, 0.62-2.30), all-cause mortality (HR, 1.07; 95% CI, 0.78-1.47), or cardiovascular mortality (HR, 1.45; 95% CI, 0.41-5.16). Among P9754 patients (all exposed to dexrazoxane; cumulative doxorubicin, 450-600 mg/m ; median follow-up, 16.6-18.4 years), no cardiovascular deaths or heart transplantation occurred. The 20-year heart transplantation rate among CCSS osteosarcoma survivors (mean doxorubicin, 377 ± 145 mg/m ) was 1.6% (vs 0% in P9754; P = .13). Among randomized patients, serious cardiovascular outcomes (cardiomyopathy, ischemic heart disease, and stroke) ascertained by PHIS/Medicaid occurred less commonly with dexrazoxane (5.6%) than without it (17.6%; P = .02), although cardiomyopathy rates alone did not differ (4.4% vs 8.1%; P = .35).

Conclusions: Dexrazoxane did not appear to adversely affect long-term mortality, event-free survival, or second cancer risk.
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http://dx.doi.org/10.1002/cncr.33974DOI Listing
October 2021

Early palliative care is associated with less intense care in children dying with cancer in Alabama: A retrospective, single-site study.

Cancer 2021 Oct 6. Epub 2021 Oct 6.

Institute for Cancer Outcomes and Survivorship, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

Background: Regional studies show that children with cancer receive medically intense end-of-life (EOL) care, but EOL care patterns, including palliative care utilization in Alabama, remain unknown.

Methods: This was a retrospective study of 233 children (0-19 years) who received cancer-directed therapy at Children's of Alabama and died from 2010 through 2019. Rates and disparities in palliative care utilization and the association between palliative care and intense EOL care, death location, and hospice were examined.

Results: The median death age was 11 years; 62% were non-Hispanic White. Forty-one percent had a non-central nervous system (CNS) solid tumor. Fifty-eight percent received palliative care, and 36% received early palliative care (≥30 days before death). Children without relapsed/refractory disease were less likely to receive palliative care than those who had relapsed/refractory disease (adjusted odds ratio [aOR], 0.2; 95% confidence interval [CI], 0.1-0.7). Children with CNS tumors and hematologic malignancies were less likely to have early palliative care (aOR for CNS tumors, 0.4; 95% CI, 0.2-0.7; aOR for hematologic malignancies, 0.3; 95% CI, 0.2-0.7) than children with non-CNS solid tumors. Late palliative care (vs none) was associated with more medically intense care (aOR, 3.3; 95% CI, 1.4-7.8) and hospital death (aOR, 4.8; 95% CI, 1.9-11.6). Early palliative care (vs none) was associated with more hospice enrollment (aOR, 3.4; 95% CI, 1.5-7.6) but not medically intense care (aOR, 1.3; 95% CI, 0.6-2.9) or hospital death (aOR, 1.8; 95% CI, 0.8-3.7).

Conclusions: Fifty-eight percent of children dying of cancer in Alabama receive palliative care, but EOL care varies with the receipt and timing (early vs late) of palliative care. Whether this variation reflects differences in child and family preferences or systemic factors (eg, hospice access) remains unknown.
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http://dx.doi.org/10.1002/cncr.33935DOI Listing
October 2021

Functional Outcomes and Social Attainment in Asian/Pacific Islander Childhood Cancer Survivors in the United States: A Report from the Childhood Cancer Survivor Study.

Cancer Epidemiol Biomarkers Prev 2021 Oct 4. Epub 2021 Oct 4.

School of Pharmacy, Faculty of Medicine, Chinese University of Hong Kong

Background: Given the relatively small population of Asians or Pacific Islanders (API) in the United States, studies describing long-term outcomes in API survivors of childhood cancer are limited. This study compared functional outcomes between API versus non-Hispanic White (NHW) survivors.

Methods: This study included 203 API five-year survivors (age at follow-up: 29.2 [SD=6.3] years) and 12,186 NHW survivors (age at follow-up 31.5[SD=7.3] years) from the Childhood Cancer Survivor Study. Self-reported functional outcomes of neurocognitive function, emotional distress, quality of life, and social attainment were compared between the two groups using multivariable regression, adjusted for sex, age at diagnosis and evaluation, cancer diagnosis, and neurotoxic treatment.

Results: No statistically significant race/ethnicity-based differences were identified in neurocognitive and emotional measures. API survivors reported, on average, less bodily pain than NHW survivors (mean 54.11 [SD=8.98] vs. 51.32 [SD=10.12]; P<.001). NHW survivors were less likely to have attained at least a college degree than API survivors (odds ratio[OR]=0.50; 95% confidence interval[CI]=0.34, 0.73). API survivors were more likely than NHW survivors to be never-married (OR=2.83, 95% CI=1.93, 4.13) and to live dependently (OR=3.10; 95% CI=2.02, 4.74). Older age (>45 years), brain tumor diagnosis, and higher cranial radiation dose were associated with poorer functional outcomes in API survivors (all, P's<0.05).

Conclusion: We observed differences in social attainment between API and NHW survivors, though statistically significant differences in neurocognitive and emotional outcomes were not identified.

Impact: Future studies should evaluate whether racial/ethnic differences in environmental and sociocultural factors may have differential effects on health and functional outcomes.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0628DOI Listing
October 2021

Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma.

Nat Commun 2021 09 20;12(1):5531. Epub 2021 Sep 20.

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Radiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. We performed DNA methylation profiling, RNA-seq, and DNA sequencing on 32 RIG tumors and an in vitro drug screen in two RIG cell lines. We report that based on DNA methylation, RIGs cluster primarily with the pediatric receptor tyrosine kinase I high-grade glioma subtype. Common copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, and Ch. 13q and Ch. 14q loss; focal alterations include PDGFRA and CDK4 gain and CDKN2A and BCOR loss. Transcriptomically, RIGs comprise a stem-like subgroup with lesser mutation burden and Ch. 1p loss and a pro-inflammatory subgroup with greater mutation burden and depleted DNA repair gene expression. Chromothripsis in several RIG samples is associated with extrachromosomal circular DNA-mediated amplification of PDGFRA and CDK4. Drug screening suggests microtubule inhibitors/stabilizers, DNA-damaging agents, MEK inhibition, and, in the inflammatory subgroup, proteasome inhibitors, as potentially effective therapies.
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http://dx.doi.org/10.1038/s41467-021-25709-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452624PMC
September 2021

Impact of telehealth visits on hydroxyurea response in sickle cell anemia.

Pediatr Blood Cancer 2021 Dec 17;68(12):e29354. Epub 2021 Sep 17.

Division of Pediatric Hematology and Oncology, University of Alabama at Birmingham, Birmingham, Alabama.

Background: It is important to ensure access to hydroxyurea (HU) for patients with sickle cell anemia (SCA) living in rural areas. The University of Alabama at Birmingham (UAB) Pediatric Sickle Cell program's satellite clinics reduce the barrier of transportation to the university-based clinic. However, as compared with the university clinic, these satellite clinics do not offer immediate access to HU dosing laboratory results and a nurse clinician calls families with HU dose adjustments after the clinic visit. This study evaluated the impact of telehealth dosing adjustments on HU laboratory and clinical response as compared with university-based patients.

Methods: A one-year retrospective chart review was performed to evaluate HU laboratory and clinical response based on clinic location and socioeconomic status for patients with SCA. We identified the number of clinic and acute care visits for one year and calculated the mean complete blood count and fetal hemoglobin (HbF) values for each patient.

Results: We identified 107 academic center participants with SCA-prescribed HU and 65 satellite clinic participants. The mean age of participants was 11 ± 5 years. We identified no difference in HbF (13.3 ± 0.7 vs 11.7 ± 0.8, P = 0.13), Hb (8.46 ± 1.1 vs 8.55 ± 1.1, P = 0.59), mean corpuscular volume (91.0 ± 10.6 vs 91.7 ± 9.5, P = 0.67), or absolute neutrophil count (4.85 ± 2.3 vs 4.87 ± 2.3, P = 0.95) when comparing Birmingham versus satellite clinics. We also identified no difference in hospital admissions (0.99 ± 0.1 versus 0.85 ± 0.2, P = 0.49), based on clinic location.

Conclusions: The use of telehealth did not negatively impact laboratory response to HU. Future studies should identify novel approaches to improve access to HU among patients with SCA living in rural areas.
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http://dx.doi.org/10.1002/pbc.29354DOI Listing
December 2021

Peripheral Blood Cytopenia and Risk of Cardiovascular Disease and Mortality.

J Am Heart Assoc 2021 Sep 13;10(18):e020809. Epub 2021 Sep 13.

Division of Biomedical Informatics and Personalized Medicine Department of Medicine, Anschutz Medical Campus, University of Colorado Aurora CO.

Background Individual blood cell count abnormalities have been associated with cardiovascular disease and increased mortality. In this study, we defined a "cytopenia phenotype," reflecting bone marrow hypoproliferation, to determine if peripheral blood cytopenia is associated with increased cardiovascular disease and mortality risk. Methods and Results Study participants were derived from a biracial observational cohort study, REGARDS (Reasons for Geographic and Racial Differences in Stroke), that enrolled 30 239 Black and White participants aged ≥45 years between 2003 and 2007. Median follow up was ≈9 years. The current study included 19 864 participants from REGARDS study (37.9% men, 40% Black participants) who have complete blood count available at study enrollment. We defined a cytopenia phenotype based on age-, sex-, and race-adjusted lowest fifth percentile of blood counts. Multivariable Cox proportional hazards models estimated the hazard ratios (HR) and 95% CI of cytopenia for mortality and incident cardiovascular disease in adjusted models. Mean age of the study participants was 64 years (SD:9.7). The prevalence of cytopenia was 1.9% (n=378). Cytopenia was associated with increased risk of all-cause mortality (HR, 1.73; 95% CI, 1.34-2.22) and cardiovascular disease mortality (HR, 1.56; 95% CI, 1.11-2.29). Cytopenia was associated with stroke risk in Black but not White participants (HR, 1.96 versus 0.86; -interaction for race=0.08) and was not associated with coronary heart disease risk. Conclusions We defined a cytopenia phenotype with clinical implications for mortality and stroke risk in a large biracial and geographically diverse population. Whether generated through somatic mutations or decreased organ function, cytopenia was associated with mortality risk and was a race-specific risk factor for stroke.
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http://dx.doi.org/10.1161/JAHA.121.020809DOI Listing
September 2021

Trends in Late Mortality and Life Expectancy After Allogeneic Blood or Marrow Transplantation Over 4 Decades: A Blood or Marrow Transplant Survivor Study Report.

JAMA Oncol 2021 Sep 9. Epub 2021 Sep 9.

Population Sciences, City of Hope, Duarte, California.

Importance: The past 4 decades have seen substantial changes in allogeneic blood or marrow transplantation (BMT) practice, with the overarching goal of expanding the eligible patient pool while optimizing disease-free survival.

Objective: To determine trends in life expectancy and cause-specific late mortality after allogeneic BMT performed over a 40-year period.

Design, Setting, And Participants: A retrospective cohort study of 4741 individuals who lived 2 or more years after allogeneic BMT performed between January 1, 1974, and December 31, 2014, was conducted at City of Hope, University of Minnesota, or University of Alabama at Birmingham. The end of follow-up was March 23, 2020.

Exposures: Allogeneic BMT performed in 3 eras: 1974-1989, 1990-2004, and 2005-2014.

Main Outcomes And Measures: All-cause, recurrence-related, and nonrecurrence-related mortality and projected reduction in life expectancy. Information regarding vital status and cause of death was obtained from the National Death Index Plus and Accurint databases.

Results: Of the 4741 individuals included in the study, 2735 (57.7%) were male; median age at BMT was 33 years (range, 0-75 years). The cumulative incidence of recurrence-related mortality plateaued at 10 years, reaching 12.2% (95% CI, 11.0%-13.4%) at 30 years from BMT. In contrast, the incidence of nonrecurrence-related mortality continued to increase and was 22.3% (95% CI, 20.4%-24.3%) at 30 years. Leading causes of nonrecurrence-related mortality included infection (30-year cumulative incidence, 10.7%; standardized mortality ratio [SMR], 52.0), subsequent malignant neoplasms (30-year cumulative incidence, 7.0%; SMR, 4.8), cardiovascular disease (30-year cumulative incidence, 4.6%; SMR, 4.1), and pulmonary disease (30-year cumulative incidence, 2.7%; SMR, 13.9). Compared with the general population, the relative mortality remained higher at 30 or more years after BMT (SMR, 5.4; 95% CI, 4.0-7.1). The cohort experienced a 20.8% reduction in life expectancy (8.7 years of life lost). Compared with 1974-1989 (reference), the adjusted 10-year hazard ratio (HR) of all-cause mortality declined over the 3 eras (1990-2004: HR, 0.67; 95% CI, 0.53-0.85; 2005-2014: HR, 0.52; 95% CI, 0.39-0.69; P < .001 for trend), as did years of life lost (1974-1989: 9.9 years [reference]; 1990-2004: 6.5 years; and 2005-2014: 4.2 years). The reduction in late mortality was most pronounced among individuals who underwent transplantation at ages younger than 18 years (1990-2004: HR, 0.62; 95% CI, 0.40-0.96; 2005-2014: HR, 0.30; 95% CI, 0.16-0.54; reference: 1974-1989; P < .001 for trend) and those who received bone marrow (1990-2004: HR, 0.70; 95% CI, 0.54-0.90; 2005-2014: HR, 0.45; 95% CI, 0.29-0.69; reference: 1974-1989; P < .001 for trend).

Conclusions And Relevance: This cohort study noted that late mortality among recipients of allogeneic BMT has decreased over the past 40 years; however, life expectancy was not restored to expected rates compared with the general US population. Furthermore, the reduction in risk of late mortality appeared to be confined to those who underwent transplantation at a younger age or those who received bone marrow. Further efforts to mitigate disease recurrence, infections, subsequent neoplasms, cardiovascular disease, and pulmonary disease may be useful in this population.
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http://dx.doi.org/10.1001/jamaoncol.2021.3676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430905PMC
September 2021

Polygenic Risk Score Improves Risk Stratification and Prediction of Subsequent Thyroid Cancer after Childhood Cancer.

Cancer Epidemiol Biomarkers Prev 2021 Aug 31. Epub 2021 Aug 31.

St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: Subsequent thyroid cancer (STC) is one of the most common malignancies in childhood cancer survivors. We aimed to evaluate the polygenic contributions to STC risk and potential utility in improving risk prediction.

Methods: A polygenic risk score (PRS) was calculated from 12 independent SNPs associated with thyroid cancer risk in the general population. Associations between PRS and STC risk were evaluated among survivors from St. Jude Lifetime Cohort (SJLIFE) and were replicated in survivors from Childhood Cancer Survivor Study (CCSS). A risk prediction model integrating the PRS and clinical factors, initially developed in SJLIFE, and its performance were validated in CCSS.

Results: Among 2,370 SJLIFE survivors with a median follow-up of 28.8 [interquartile range (IQR) = 21.9-36.1] years, 65 (2.7%) developed STC. Among them, the standardized PRS was associated with an increased rate of STC [relative rate (RR) = 1.57; 95% confidence interval (CI) = 1.24-1.98; < 0.001]. Similar associations were replicated in 6,416 CCSS survivors, among whom 121 (1.9%) developed STC during median follow-up of 28.9 (IQR = 22.6-34.6) years (RR = 1.52; 95% CI = 1.25-1.83; < 0.001). A risk prediction model integrating the PRS with clinical factors showed better performance than the model considering only clinical factors in SJLIFE ( = 0.004, AUC = 83.2% vs. 82.1%, at age 40), which was further validated in CCSS ( = 0.010, AUC = 72.9% vs. 70.6%).

Conclusions: Integration of the PRS with clinical factors provided a statistically significant improvement in risk prediction of STC, although the magnitude of improvement was modest.

Impact: PRS improves risk stratification and prediction of STC, suggesting its potential utility for optimizing screening strategies in survivorship care.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0448DOI Listing
August 2021

Long-term Follow-up Care for Childhood, Adolescent, and Young Adult Cancer Survivors.

Pediatrics 2021 09;148(3)

Department of Pediatrics, University of California, Los Angeles, Los Angeles, California.

Progress in therapy has made survival into adulthood a reality for most children, adolescents, and young adults with a cancer diagnosis today. Notably, this growing population remains vulnerable to a variety of long-term therapy-related sequelae. Systematic ongoing follow-up of these patients is, therefore, important to provide for early detection of and intervention for potentially serious late-onset complications. In addition, health counseling and promotion of healthy lifestyles are important aspects of long-term follow-up care to promote risk reduction for physical and emotional health problems that commonly present during adulthood. Both general and subspecialty health care providers are playing an increasingly important role in the ongoing care of childhood cancer survivors, beyond the routine preventive care, health supervision, and anticipatory guidance provided to all patients. This report is based on the guidelines that have been developed by the Children's Oncology Group to facilitate comprehensive long-term follow-up of childhood, adolescent, and young adult cancer survivors (www.survivorshipguidelines.org).
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http://dx.doi.org/10.1542/peds.2021-053127DOI Listing
September 2021

Late-occurring venous thromboembolism in allogeneic blood or marrow transplant survivors: a BMTSS-HiGHS2 risk model.

Blood Adv 2021 Oct;5(20):4102-4111

Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL.

Allogeneic blood or marrow transplant (BMT) recipients are at risk for venous thromboembolism (VTE) because of high-intensity therapeutic exposures, comorbidities, and a proinflammatory state due to chronic graft-versus-host disease (GVHD). The long-term risk of VTE in allogeneic BMT survivors remains unstudied. Participants were drawn from the Blood or Marrow Transplant Survivor Study (BMTSS), a retrospective cohort study that included patients who underwent transplantation between 1974 and 2014 and survived ≥2 years after BMT. We analyzed the risk of VTE in 1554 2-year survivors of allogeneic BMT compared with 907 siblings. Using backward variable selection guided by minimizing Akaike information criterion, we created a prediction model for risk of late-occurring VTE. Allogeneic BMT survivors had a 7.3-fold higher risk of VTE compared with siblings (95% CI, 4.69-11.46; P < .0001). After a median follow-up of 11 years, conditional on surviving the first 2 years after BMT, the cumulative incidence of late-occurring VTE was 2.4% at 5 years, 4.9% at 10 years, and 7.1% at 20 years after BMT. The final model for VTE risk at 2 years post-BMT included History of stroke, chronic GVHD, Hypertension, Sex (male vs female) and Stem cell source (peripheral blood stem cells vs other) ("HiGHS2") (corrected C-statistics: 0.73; 95% CI = 0.67-0.79). This model was able to classify patients at high and low VTE risk (10-year cumulative incidence, 9.3% vs 2.4% respectively; P < .0001). The BMTSS HiGHS2 risk model when applied at 2 years post-BMT can be used to inform targeted prevention strategies for patients at high risk for late-occurring VTE.
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http://dx.doi.org/10.1182/bloodadvances.2021004341DOI Listing
October 2021

Comprehensive characterization of pharmacogenetic variants in TPMT and NUDT15 in children with acute lymphoblastic leukemia.

Pharmacogenet Genomics 2021 Aug 18. Epub 2021 Aug 18.

Department of Pharmaceutical Sciences Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee Institute for Cancer Outcomes and Survivorship and Division of Pediatric Hematology-Oncology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Thiopurines [e.g. 6-mercaptopurine (6MP)] are essential for the cure of acute lymphoblastic leukemia (ALL) but can cause dose-limiting hematopoietic toxicity. Germline variants in drug-metabolizing enzyme genes TPMT and NUDT15 have been linked to the risk of thiopurine toxicity. However, the full spectrum of genetic polymorphism in these genes and their impact on the pharmacological effects of thiopurines remain unclear. Herein, we comprehensively sequenced the TPMT and NUDT15 genes in 685 children with ALL from the Children's Oncology Group AALL03N1 trial and evaluated their association with 6MP dose intensity. We identified 6 and 5 coding variants in TPMT and NUDT15 respectively, confirming the association at known pharmacogenetic variants. Importantly, we discovered a novel gain-of-function noncoding variants in TPMT associated with increased 6MP tolerance (rs12199316), with independent validation in 380 patients from the St. Jude Total Therapy XV protocol. Located adjacent to a regulatory DNA element, this intergenic variant was strongly associated TPMT transcription, with the variant allele linked to higher expression (P = 2.6 × 10-9). For NUDT15, one noncoding common variant, rs73189762, was identified as potentially related to 6MP intolerance. Collectively, we described pharmacogenetic variants in TPMT and NUDT15 associated with thiopurine sensitivity, providing further insights for implementing pharmacogenetics-based thiopurine individualization.
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http://dx.doi.org/10.1097/FPC.0000000000000453DOI Listing
August 2021

Frequency of Pathogenic Germline Variants in Cancer-Susceptibility Genes in the Childhood Cancer Survivor Study.

JNCI Cancer Spectr 2021 Apr 23;5(2):pkab007. Epub 2021 Jan 23.

Basic Research Subdirection, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.

Background: Pediatric cancers are the leading cause of death by disease in children despite improved survival rates overall. The contribution of germline genetic susceptibility to pediatric cancer survivors has not been extensively characterized. We assessed the frequency of pathogenic or likely pathogenic (P/LP) variants in 5451 long-term pediatric cancer survivors from the Childhood Cancer Survivor Study.

Methods: Exome sequencing was conducted on germline DNA from 5451 pediatric cancer survivors (cases who survived ≥5 years from diagnosis; n = 5105 European) and 597 European cancer-free adults (controls). Analyses focused on comparing the frequency of rare P/LP variants in 237 cancer-susceptibility genes and a subset of 60 autosomal dominant high-to-moderate penetrance genes, for both case-case and case-control comparisons.

Results: Of European cases, 4.1% harbored a P/LP variant in high-to-moderate penetrance autosomal dominant genes compared with 1.3% in controls (2-sided  = 3 × 10). The highest frequency of P/LP variants was in genes typically associated with adult onset rather than pediatric cancers, including , , , , and . A statistically significant excess of P/LP variants, after correction for multiple tests, was detected in patients with central nervous system cancers (, , , ), Wilms tumor (, ), non-Hodgkin lymphoma (), and soft tissue sarcomas (, , , , ) compared with other pediatric cancers.

Conclusion: In long-term pediatric cancer survivors, we identified P/LP variants in cancer-susceptibility genes not previously associated with pediatric cancer as well as confirmed known associations. Further characterization of variants in these genes in pediatric cancer will be important to provide optimal genetic counseling for patients and their families.
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http://dx.doi.org/10.1093/jncics/pkab007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023430PMC
April 2021

Clinical and genetic risk factors for radiation-associated ototoxicity: A report from the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort.

Cancer 2021 Nov 19;127(21):4091-4102. Epub 2021 Jul 19.

Department of Medicine, University of Chicago, Chicago, Illinois.

Background: Cranial radiation therapy (CRT) is associated with ototoxicity, which manifests as hearing loss and tinnitus. The authors sought to identify clinical determinants and genetic risk factors for ototoxicity among adult survivors of pediatric cancer treated with CRT.

Methods: Logistic regression evaluated associations of tinnitus (n = 1991) and hearing loss (n = 2198) with nongenetic risk factors and comorbidities among CRT-treated survivors in the Childhood Cancer Survivor Study. Genome-wide association studies (GWASs) of CRT-related tinnitus and hearing loss were also performed.

Results: Males were more likely to report CRT-related tinnitus (9.4% vs 5.4%; P = 5.1 × 10 ) and hearing loss (14.0% vs 10.7%; P = .02) than females. Survivors with tinnitus or hearing loss were more likely to experience persistent dizziness or vertigo (tinnitus: P < 2 × 10 ; hearing loss: P = 6.4 × 10 ), take antidepressants (tinnitus: P = .02; hearing loss: P = .01), and report poorer overall health (tinnitus: P = 1.5 × 10 ; hearing loss: P = 1.7 × 10 ) in comparison with controls. GWAS of CRT-related tinnitus revealed a genome-wide significant signal in chromosome 1 led by rs203248 (P = 1.5 × 10 ), whereas GWAS of CRT-related hearing loss identified rs332013 (P = 5.8 × 10 ) in chromosome 8 and rs67522722 (P = 7.8 × 10 ) in chromosome 6 as nearly genome-wide significant. A replication analysis identified rs67522722, intronic to ATXN1, as being significantly associated with CRT-related hearing loss (P = .03) and de novo hearing loss (P = 3.6 × 10 ).

Conclusions: CRT-associated ototoxicity was associated with sex, several neuro-otological symptoms, increased antidepressant use, and poorer self-reported health. GWAS of CRT-related hearing loss identified rs67522722, which was supported in an independent cohort of survivors.

Lay Summary: Hearing loss and subjective tinnitus (the perception of noise or ringing in the ear) are long-term side effects of cancer treatment and are common in children treated with radiation to the brain. These toxicities can affect childhood development and potentially contribute to serious learning and behavioral difficulties. This study's data indicate that males are at greater risk for hearing loss and tinnitus than females after radiation therapy to the brain. Those who develop these toxicities are more likely to use antidepressants and report poorer overall health. Health care providers can improve the management of survivors by informing patients and/or their parents of these risks.
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http://dx.doi.org/10.1002/cncr.33775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516694PMC
November 2021

PediCARE: Development of a poverty-targeted intervention for pediatric cancer.

Pediatr Blood Cancer 2021 Oct 30;68(10):e29195. Epub 2021 Jun 30.

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Background: Poverty is associated with inferior psychosocial outcomes, higher rates of relapse, and decreased overall survival in children with cancer. Despite this, there are few evidence-based, poverty-targeted interventions and none specific to pediatric oncology. To address this gap, we developed and refined the Pediatric Cancer Resource Equity (PediCARE) intervention, a household material hardship (HMH) targeted intervention providing transportation and groceries to pediatric oncology families.

Methods: This was a single-arm pilot study conducted at a single, large, tertiary pediatric cancer center. Newly diagnosed patients with HMH-exposure were directly assigned to receive PediCARE for a total of three months. Quantitative and qualitative approaches were used to evaluate its acceptability and to rapidly refine the intervention.

Results: Nine families (100% of those approached) consented to enrollment with no attrition over the three-month study period. Families were highly satisfied with the intervention and recommended participation to others. All of the families utilized the grocery delivery component of PediCARE, and seven utilized the transportation component. Qualitative participant feedback was used to rapidly refine the intervention including logistics of intervention delivery, and dose of intervention components.

Conclusion: PediCARE, a poverty-targeted intervention, was highly acceptable to pediatric oncology families. The intervention was refined in real-time utilizing quantitative and qualitative feedback. Next steps include intervention evaluation in a randomized, controlled feasibility study.
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http://dx.doi.org/10.1002/pbc.29195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384686PMC
October 2021

Healthcare utilization and spending among older patients diagnosed with Non-Hodgkin lymphoma.

J Geriatr Oncol 2021 Jun 24. Epub 2021 Jun 24.

Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, USA; Division of Pediatric Oncology, University of Alabama at Birmingham, USA.

Background: Developing appropriate care models for patients diagnosed with non-Hodgkin lymphoma (NHL) >65y require examination of current healthcare utilization patterns and cost, but non-malignant condition-specific utilization and Medicare spending among older patients has not been characterized.

Methods: Using SEER-Medicare, 14,533 patients diagnosed with NHL at age > 65 between 2008 and 2015 and a comparable non-cancer cohort (n = 14,533) were identified. Hospitalizations and outpatient visits for 109 non-malignant conditions were grouped into ten categories, allowing condition-specific utilization and spending calculation from diagnosis to 5y, censoring at blood or marrow transplantation, 6mo prior to death or end (12/31/2016). Using the 90th percentile as a cut-off, factors associated with high-hospitalization rates and high-spending were evaluated.

Results: Patients with NHL were 1.5-fold more likely to be hospitalized and 1.8-fold more likely to experience outpatient visits when compared with the non-cancer cohort. Patients with NHL had greater aging-related, cardiovascular, and gastrointestinal hospitalizations than controls (p < 0.001). Average Medicare spending/visit was higher for patients with NHL (hospitalization: $16,950 vs. $13,474, p < 0.001; outpatient: $1176 vs. $392, p < 0.001). Factors associated with high-utilization and high-spending included diffuse large B cell lymphoma subtype, non-white race, and residence in low-education area.

Conclusions: Older patients with NHL experienced higher utilization and higher spending per-utilization compared to a non-cancer cohort over five years from cancer diagnosis. Clinical and demographic sub-groups demonstrated increased risk for the highest spending and utilization. The substantial utilization and spending for non-malignant conditions among older patients with NHL provides quantifiable evidence for survivor-adapted healthcare management policies.
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http://dx.doi.org/10.1016/j.jgo.2021.06.006DOI Listing
June 2021

Individual prediction of nonadherence to oral mercaptopurine in children with acute lymphoblastic leukemia: Results from COG AALL03N1.

Cancer 2021 Oct 23;127(20):3832-3839. Epub 2021 Jun 23.

Institute for Cancer Outcomes and Survivorship, Division of Pediatric Hematology and Oncology, University of Alabama at Birmingham, Birmingham, Alabama.

Background: Poor mercaptopurine (6MP) adherence (mean adherence rate < 90%) increases the relapse risk among children with acute lymphoblastic leukemia (ALL). 6MP adherence remains difficult to measure in real time. Easily measured patient-level factors could identify patients at risk for poor adherence.

Methods: The authors measured 6MP adherence via electronic monitoring for 6 months per patient. Using data from month 3, they created a risk prediction model for 6MP nonadherence in 407 children with ALL (mean age, 7.7 ± 4.4 years); they used receiver operating characteristic analyses in the training set (n = 250) and replicated this in the test set (n = 157).

Results: Age, race/ethnicity, 6MP dose intensity, absolute neutrophil count, 6MP ingestion patterns, and household structure were retained in the prediction model. The model yielded areas under the receiver operating characteristic curve (AUCs) of 0.79 (95% confidence interval [CI], 0.71-0.85) and 0.74 (95% CI, 0.63-0.85) in the training and test sets, respectively. The model performed better for those who were ≥12 years old (AUC, 0.79; 95% CI, 0.59-0.99) than those <12 years old (AUC, 0.70; 95% CI, 0.58-0.81). Using the predicted probability of nonadherence based on receiver operating characteristic analysis, the authors developed a binary risk classifier to classify patients with a high or low probability of nonadherence. The sensitivity and specificity of the binary risk classifier were 71% and 76%, respectively. Adjusted for clinical prognosticators, the risk of relapse was 2.2-fold higher (95% CI, 0.94-5.1; P = .07) among patients with a high probability of nonadherence in comparison with those with a low probability, as identified by the risk prediction model.

Conclusions: The risk prediction model identified patients with a high probability of nonadherence and could be used in real time to personalize recommendations and interventions in the clinic.

Lay Summary: The vast majority of children with acute lymphoblastic leukemia, the most common childhood cancer, are cured. The treatment of acute lymphoblastic leukemia includes taking an oral chemotherapy medicine (mercaptopurine) for approximately 2 years. Children who miss doses of this medicine (specifically children who take the medicine less than 90% of the time that it is prescribed) are more likely to suffer leukemia relapse. The authors of this article have measured mercaptopurine adherence with electronic bottle caps to determine characteristics of patients that predict nonadherence, and they have created a prediction tool that could allow physicians to identify and intervene with patients at high risk of nonadherence.
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http://dx.doi.org/10.1002/cncr.33760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478829PMC
October 2021

Reduction in Late Mortality Among Patients With Multiple Myeloma Treated With Autologous Peripheral Blood Stem Cell Transplantation-A Blood or Marrow Transplant Survivor Study Report.

Transplant Cell Ther 2021 10 19;27(10):840.e1-840.e7. Epub 2021 Jun 19.

Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, Alabama; Division of Hematology-Oncology, Department of Pediatrics, University of Alabama at Birmingham, Alabama. Electronic address:

Therapeutic practices for multiple myeloma (MM) have evolved, such that novel-agent-based therapy and autologous peripheral blood stem cell transplantation (aPBSCT) is the current standard. Whether cause-specific mortality has changed with time remains unclear. We examined late cause-specific mortality among patients with MM receiving aPBSCT from 1989 to 2014. We conducted a prospective cohort study using participants enrolled in the enrolled in the Blood or Marrow Transplant Survivor Study. We created 3 eras to reflect changing MM therapy: <2000 (pre-thalidomide); 2000-2005 (thalidomide); 2006-2014 (lenalidomide). We used Kaplan-Meier techniques and Cox regression for examining all-cause mortality, and subdistribution hazards models for cause-specific mortality. In total, 1906 patients were followed up for a median of 9.2 years. Conditional on surviving 2 years, the 10-year overall survival was 45%. The 10-year cumulative incidence of myeloma- and non-myeloma-related mortality was 33% and 13%, respectively. Multivariable analysis showed declining MM-specific mortality (subdistribution hazard ratio [SHR] = 0.80, 95% confidence interval [CI], 0.60-1.07; SHR = 0.46, 95% CI, 0.34-0.62; referent group: <2000), infection-related mortality (SHR = 0.50, 95% CI, 0.29-0.85; SHR = 0.35, 95%CI 0.21-0.60; referent group: <2000) and cardiovascular disease-related mortality (SHR = 0.45, 95% CI 0.20-0.99; SHR = 0.41, 95% CI 0.18-0.93; referent group: <2000). Although primary disease remains the major cause of late mortality, we observed a significant temporal decline in myeloma-, infection-, and cardiac-related late mortality over the past 25 years.
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http://dx.doi.org/10.1016/j.jtct.2021.06.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478837PMC
October 2021

Association Between Chronologic Age and Geriatric Assessment-Identified Impairments: Findings From the CARE Registry.

J Natl Compr Canc Netw 2021 06 11:1-6. Epub 2021 Jun 11.

Institute for Cancer Outcomes and Survivorship.

Background: The NCCN Guidelines for Older Adult Oncology recommend that, when possible, older adults with cancer undergo a geriatric assessment (GA) to provide a comprehensive health appraisal to guide interventions and appropriate treatment selection. However, the association of age with GA-identified impairments (GA impairments) remains understudied and the appropriate age cutoff for using the GA remains unknown.

Patients And Methods: We designed a cross-sectional study using the Cancer and Aging Resilience Evaluation (CARE) registry of older adults with cancer. We included adults aged ≥60 years diagnosed with gastrointestinal malignancy who underwent a patient-reported GA prior to their initial consultation at the gastrointestinal oncology clinic. We noted the presence of GA impairments and frailty using Rockwood's deficit accumulation approach. We studied the relation between chronologic age and GA impairments/frailty using Spearman rank correlation and chi-square tests of trend.

Results: We identified 455 eligible older adults aged ≥60 years with gastrointestinal malignancies; the median age was 68 years (range, 64-74 years) and colorectal (33%) and pancreatic (24%) cancers were the most common cancer type. The correlation between chronologic age and number of geriatric impairments was weak and did not reach statistical significance (Spearman ρ, 0.07; P=.16). Furthermore, the prevalence of domain-specific impairments or frailty was comparable across the 3 age groups (60-64 years, 65-74 years, ≥75 years) with the exception of comorbidity burden. Notably, 61% of patients aged 60 to 64 years had ≥2 GA impairments and 35% had evidence of frailty, which was comparable to patients aged 65 to 74 years (66% and 36%, respectively) and ≥75 years (70% and 40%, respectively).

Conclusions: Using chronologic age alone to identify which patients may benefit from GA is problematic. Future studies should identify screening tools that may identify patients at high risk of frailty and GA impairments.
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http://dx.doi.org/10.6004/jnccn.2020.7679DOI Listing
June 2021

High incidence of thromboembolism in patients with chronic GVHD: association with severity of GVHD and donor-recipient ABO blood group.

Blood Cancer J 2021 05 18;11(5):96. Epub 2021 May 18.

Blood and Marrow Transplant Program, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.

Chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (HCT) is associated with systemic inflammation and endothelial dysfunction, increasing risk for thromboembolic events (TEE). In 145 adult recipients who developed cGVHD after a matched sibling or umbilical cord blood donor HCT from 2010 to 2018, 32(22%) developed at least 1 TEE event, and 14(10%) developed 2 TEE events. The 5-year cumulative incidence of TEE was 22% (95% CI, 15-29%) with a median time from cGVHD to TEE of 234 days (range, 12-2050). Median time to the development of LE DVT or PE was 107 (range, 12-1925) compared to 450 days (range, 158-1300) for UE DVT. Cumulative incidence of TEE was 9% (95% CI, 0-20%), 17% (95% CI, 9-25%), and 38% (95% CI, 22-55%) in those with mild, moderate, and severe GVHD, respectively. Higher risk for TEE was associated with cGVHD severity (hazard ratio [HR] 4.9, [95% CI, 1.1-22.0]; p = 0.03), non-O-donor to recipient ABO match compared to O-donor to O-recipient match (HR 2.7, [95% CI, 1.0-7.5]; p = 0.053), and personal history of coronary artery disease (HR 2.4, [95% CI, 1.1-5.3]; p = 0.03). TEE was not associated with 2-year non-relapse mortality or 5-year overall survival.
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http://dx.doi.org/10.1038/s41408-021-00488-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131386PMC
May 2021

Fatigue is independently associated with functional status limitations in older adults with gastrointestinal malignancies-results from the CARE registry.

Support Care Cancer 2021 Nov 15;29(11):6793-6800. Epub 2021 May 15.

Institute for Cancer Outcomes & Survivorship, University of Alabama At Birmingham, Birmingham, AL, USA.

Purpose: Fatigue is a component of frailty and may undermine functional well-being and independent living. The prevalence of fatigue and its impact on functional limitations among older adults with cancer remains understudied.

Methods: Using participants enrolled in the Cancer and Aging Resilience Evaluation (CARE), a prospective registry of patients (≥ 60 years) with cancer, who underwent a geriatric assessment (GA) at the first visit with oncology, we examined the presence of fatigue based on self-report of moderate to severe fatigue on PROMIS global health 10-item instrument at the time of GA. We examined the association of fatigue with impairments in instrumental activities of daily living (IADL) and activities of daily living (ADL) adjusting for age, sex, race/ethnicity, education, cancer type and stage, pain, comorbidities, and time from cancer.

Results: We included 374 older adults with cancer with a median age of 70 years; 56% were male and 23% black. Diagnoses included colorectal (33%) and pancreatic cancers (25%), with most patients with advanced stage disease (71% stage III/IV). Overall, 210 (58%) patients reported significant fatigue. Patients reporting significant fatigue had an increased odds of IADL (adjusted odds ratio, aOR 1.9; 95% CI 1.1-3.2) or ADL impairment (aOR 3.6; 95% CI 1.4-9.3), as compared to those without, after adjusting for aforementioned confounders.

Conclusions: Over half of older adults with cancer reported moderate to severe fatigue that was independently associated with functional status limitations. Further understanding of the multifaceted aspects of fatigue and development of interventions combating fatigue in this population is urgently needed.
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http://dx.doi.org/10.1007/s00520-021-06273-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464529PMC
November 2021

Contribution of Polygenic Risk to Hypertension Among Long-Term Survivors of Childhood Cancer.

JACC CardioOncol 2021 Mar 16;3(1):76-84. Epub 2021 Mar 16.

Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA.

Background: Childhood cancer survivors experience significantly higher rates of hypertension which potentiates cardiovascular disease, but the contribution and relationship of genetic and treatment factors to hypertension risk are unknown.

Objectives: To determine the contribution of a blood pressure polygenic risk score (PRS) from the general population and its interplay with cancer therapies to hypertension in childhood cancer survivors.

Methods: Using 895 established blood pressure loci from the general population, we calculated a PRS for 3572 childhood cancer survivors of European ancestry from Childhood Cancer Survivor Study (CCSS) original cohort, 1889 from CCSS expansion cohort, and 2534 from the St. Jude Lifetime Cohort (SJLIFE). Hypertension was assessed using National Cancer Institute criteria based on self-report of a physician diagnosis in CCSS and by blood pressure measurement in SJLIFE.

Results: In the combined sample of 7995 survivors, those in the top decile of the PRS had an odds ratio (OR) of 2.66 (95% CI=2.03-3.48) for hypertension compared to survivors in the bottom decile. The PRS-hypertension association was modified by being overweight/obese (per SD interaction OR=1.13; 95% CI=1.01-1.27) and exposure to hypothalamic-pituitary axis radiation (per SD interaction OR=1.18; 95% CI=1.05-1.33). Attributable fractions for hypertension to the PRS and cancer therapies were 21.0% and 15.7%, respectively, they jointly accounted for 40.2% of hypertension among survivors.

Conclusions: A blood pressure PRS from the general population is significantly associated with hypertension among childhood cancer survivors and contributes to approximately one quarter of hypertension risk among survivors. These findings highlight the importance of screening for hypertension in all childhood cancer survivors, and identify higher risk subgroups.
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http://dx.doi.org/10.1016/j.jaccao.2021.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026142PMC
March 2021

Measuring Financial Distress and Quality of Life Over Time in Patients With Gynecologic Cancer-Making the Case to Screen Early in the Treatment Course.

JCO Oncol Pract 2021 Oct 17;17(10):e1576-e1583. Epub 2021 Feb 17.

Division of Preventive Medicine, Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, AL.

Purpose: Our objective was to measure the trajectory of financial distress and to determine its relationship with quality of life (QOL) among patients with cancer.

Materials And Methods: We conducted a longitudinal survey of patients with gynecologic cancer starting a new line of systemic therapy at baseline, 3 months, and 6 months. Financial distress was measured using a Comprehensive Score for Financial Toxicity (COST) < 26, and QOL was measured using Functional Assessment of Cancer Therapy-General (FACT-G) with lower scores indicating worse responses. One-way repeated analysis of variances, generalized estimating equation models, and correlation coefficients were used to evaluate financial distress and QOL over time.

Results: There were 90 of 121 (74%) baseline participants with a 6-month follow-up. The average age was 60 years, 29% were African-American, 57% had an annual income < $40,000 in US dollars, and 6% were uninsured. At baseline, 54% of patients screened positive for financial distress, which was unchanged at 3 months (50%, = .27) but decreased at 6 months (46%, = .04) compared with baseline. There was no change in average COST (23.6, 25.1, 25.6; = .33) or FACT-G (70.8, 71.0, 72.8; = .68) over time. Less financial distress was moderately correlated with better QOL (r = 0.63, 0.61, 0.60) at each time point. The presence of financial distress was associated with a 16-point decrease in FACT-G QOL score over time.

Conclusion: Upfront screening with COST identified 90% of patients who experienced financial distress, and COST did not change significantly over time. More severe financial distress was moderately correlated with worse QOL, and its presence was associated with a clinically meaningful 16-point decrease in QOL.
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http://dx.doi.org/10.1200/OP.20.00907DOI Listing
October 2021

Sexual behaviors and human papillomavirus vaccine non-initiation among young adult cancer survivors.

J Cancer Surviv 2021 Dec 6;15(6):942-950. Epub 2021 Feb 6.

University of Alabama at Birmingham School of Nursing, Birmingham, AL, USA.

Background: Young adult cancer survivors are at risk for subsequent human papillomavirus (HPV)-related malignancies. High-risk sexual behavior increases risk for HPV acquisition; HPV vaccination protects against infection. We aimed to determine the prevalence of sexual behaviors, factors related to high-risk sexual behaviors, and the relationship between sexual behaviors and HPV vaccine non-initiation among survivors.

Methods: Survivors at comprehensive cancer centers, aged 18-26 years and 1-5 years post-treatment, reported sexual behaviors and HPV vaccine initiation (i.e., ≥ 1 dose). Multivariable logistic regression was performed to calculate odds ratios (OR) and 95% confidence intervals (95%CI) for factors associated with high-risk sexual behaviors (age at first intercourse < 16 years, ≥ 3 lifetime sexual partners, or condom use ≤ 50% of the time) and to explore the relationship between sexual behaviors and vaccine non-initiation.

Results: Of the 312 participants (48.1% female, median age at cancer diagnosis 17.2 years and at survey 20.9 years), sexual intercourse was reported by 63.1%. Of those reporting intercourse, 74.6% reported high-risk sexual behavior. Factors related to high-risk sexual behavior included currently dating/partnered (OR = 4.39, 95%CI 2.5-7.7, P < 0.001) and perceived susceptibility to HPV (OR = 1.76, 95%CI 1.3-2.5, P < 0.001). Most survivors (75.3%) reported HPV vaccine non-initiation; sexual behaviors were not associated with vaccine non-initiation (P = 0.4).

Conclusions: Many survivors participate in high-risk sexual behaviors, yet HPV vaccine initiation rates are low. Factors related to high-risk sexual behaviors can inform interventions to reduce risk for HPV acquisition among survivors.

Implications For Cancer Survivors: Cancer survivors participate in sexual behaviors that increase risk for HPV acquisition and would benefit from vaccination.
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http://dx.doi.org/10.1007/s11764-021-01000-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342627PMC
December 2021

Venous-thromboembolism in elderly patients with acute myeloid leukemia.

Thromb Res 2021 04 18;200:9-11. Epub 2021 Jan 18.

Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL, USA.

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http://dx.doi.org/10.1016/j.thromres.2020.12.032DOI Listing
April 2021

Expenditures among young adults with acute lymphoblastic leukemia by site of care.

Cancer 2021 Jun 19;127(11):1901-1911. Epub 2021 Jan 19.

Division of Pediatric Hematology-Oncology, Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, Alabama.

Background: Individuals diagnosed with acute lymphoblastic leukemia (ALL) between the ages of 22 and 39 years experience worse outcomes than those diagnosed when they are 21 years old or younger. Treatment at National Cancer Institute-designated Comprehensive Cancer Centers (CCC) mitigates these disparities but may be associated with higher expenditures.

Methods: Using deidentified administrative claims data (OptumLabs Data Warehouse), the cancer-related expenditures were examined among patients with ALL diagnosed between 2001 and 2014. Multivariable generalized linear model with log-link modeled average monthly health-plan-paid (HPP) expenditures and amount owed by the patient (out-of-pocket [OOP]). Cost ratios were used to calculate excess expenditures (CCC vs non-CCC). Incidence rate ratios (IRRs) compared CCC and non-CCC monthly visit rates. Models adjusted for sociodemographics, comorbidities, adverse events, and months enrolled.

Results: Clinical and sociodemographic characteristics were comparable between CCC (n = 160) and non-CCC (n = 139) patients. Higher monthly outpatient expenditures in CCC patients ($15,792 vs $6404; P < .001) were driven by outpatient hospital HPP expenditures. Monthly visit rates and per visit expenditures for nonchemotherapy visits (IRR = 1.6; P = .001; CCC = $8247, non-CCC = $1191) drove higher outpatient hospital expenditures among CCCs. Monthly OOP expenditures were higher at CCCs for outpatient care (P = .02). Inpatient HPP expenditures were significantly higher at CCCs ($25,918 vs $13,881; ꞵ = 0.9; P < .001) before accounting for adverse events but were no longer significant after adjusting for adverse events (ꞵ = 0.4; P = .1). Hospitalizations and length of stay were comparable.

Conclusions: Young adults with ALL at CCCs have higher expenditures, likely reflecting differences in facility structure, billing practices, and comprehensive patient care. It would be reasonable to consider CCCs comparable to the oncology care model and incentivize the framework to achieve superior outcomes and long-term cost savings.

Lay Summary: Health care expenditures in young adults (aged 22-39 years) with acute lymphoblastic leukemia (ALL) are higher among patients at National Cancer Institute-designated Comprehensive Cancer Centers (CCC) than those at non-CCCs. The CCC/non-CCC differences are significant among outpatient expenditures, which are driven by higher rates of outpatient hospital visits and outpatient hospital expenditures per visit at CCCs. Higher expenditures and visit rates of outpatient hospital visits among CCCs may also reflect how facility structure and billing patterns influence spending or comprehensive care. Young adults at CCCs face higher inpatient HPP expenditures; these are driven by serious adverse events.
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http://dx.doi.org/10.1002/cncr.33413DOI Listing
June 2021

Impact of access to care on 1-year mortality following allogeneic blood or marrow transplantation.

Bone Marrow Transplant 2021 06 8;56(6):1364-1372. Epub 2021 Jan 8.

Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL, USA.

Mortality is highest in the first year following an allogeneic hematopoietic stem cell transplant. With recent advancements, we have expanded the pool of patients to whom we are able to offer transplant as a treatment option. In this context, we analyzed socioeconomic, patient, disease and transplant-related variables that predicted for 1-year all-cause, relapse-related (RRM) and non-relapse related mortality (NRM) in 304 patients at the University of Alabama at Birmingham. The 1-year overall survival, RRM and NRM rates were 60.5%, 13.5% and 22.7% respectively. A KPS score < 80, pre-transplant infection and hypertension and non-complete remission disease status adversely effected all-cause mortality. For NRM, increasing age, pre-transplant infection and diabetes, and poor access to care were associated with higher mortality whereas haploidentical donor type was associated with improved survival. For RRM, a KPS score <80, high/very high disease risk index and the presence of comorbidities were risk factors for higher mortality. Poor access to care, in addition to individual comorbidities, performance status and high-risk disease characteristics, is associated with adverse outcomes following transplant. We propose the incorporation of socioeconomic variables with patient, disease, and transplant-related variables to predict 1-year NRM.
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http://dx.doi.org/10.1038/s41409-020-01184-8DOI Listing
June 2021

Preventive health service use among survivors of adolescent and young adult cancer.

Prev Med Rep 2020 Dec 1;20:101278. Epub 2020 Dec 1.

Kaiser Permanente Southern California, Department of Research & Evaluation, 100 S Los Robles Ave, Pasadena, CA 91101, USA.

Preventive health screenings are essential for survivors of adolescent and young adult (AYA) cancer survivors, who are at greater risk for non-cancer related death compared to individuals without a history of cancer. However, little research exists examining their use of screening services. In order to identify potential areas for targeted improvements in AYA survivorship care, we examined adherence to United States Preventive Services Task Force (USPSTF) screening recommendations among members of Kaiser Permanente Southern California. The study population included individuals diagnosed with cancer between ages 15-39 from 2000 to 2012 who survived at least two years post-diagnosis (n = 6779) and a matched cohort of non-cancer comparisons (n = 25640). To assess adherence to screening services, we calculated a Prevention Index (PI, proportion of person-time covered by receipt of recommended clinical preventive services relative to the time eligible) for every individual and the distributions for each service. We also evaluated predictors for adherence using logistic regression. Adherence was significantly (p-value < 0.05) higher among survivors than non-cancer subjects for screenings for dyslipidemia (71.16% and 65.94, respectively), hypertension (97.43% and 89.11%), cervical cancer (87.36% and 84.45%), colorectal cancer (83.23% and 58.27%), and influenza vaccination (36.79% and 33.21%). The logistic regression showed that survivors were significantly more likely to adhere to guidelines compared to non-cancer peers for all screenings except breast cancer, with the greatest difference found for colorectal cancer (odds ratio: 5.04, p-value: <0.01). While AYA survivors appear to use preventive screenings more than comparisons, there is room for improvement for certain services, most notably for influenza vaccination.
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http://dx.doi.org/10.1016/j.pmedr.2020.101278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770961PMC
December 2020

SARC-F for screening of sarcopenia among older adults with cancer.

Cancer 2021 May 28;127(9):1469-1475. Epub 2020 Dec 28.

Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, Alabama.

Background: Sarcopenia is associated with adverse outcomes among older adults with cancer; however, no easily applied sarcopenia measure exists for use in clinical practice. The use of SARC-F, a 5-item self-reported sarcopenia screening questionnaire, among older adults with cancer remains to be investigated.

Methods: Older adults (aged ≥60 years) with cancer enrolled in the University of Alabama Cancer and Aging Resilience Evaluation Registry were identified. Patients completed the SARC-F questionnaire (with scores ≥4 considered positive for sarcopenia). The authors assessed for differences in geriatric assessment domain impairments, health-related quality of life, and health care utilization between those with and without sarcopenia using multivariate regression, then assessed the association of sarcopenia with survival using Kaplan-Meier methods and a Cox regression model, adjusting for covariates.

Results: In total, 256 older adults were identified. The median age was 69 years, 59% of participants were men, and 75% were White. The median SARC-F score was 2 (interquartile range, 0-4), and 33% of participants screened positive. Those with sarcopenia had higher odds of having multiple impairments, including impaired instrumental activities of daily living (adjusted odds ratio [aOR], 18.1; 95% CI, 7.5-43.8) and frailty (aOR, 43.5; 95% CI, 17.7-106.8) as well as reduced physical and mental health-related quality of life (β coefficient, -13.6 and -11.5, respectively) and increased emergency room visits (aOR, 2.4; 95% CI, 1.3-4.7). Furthermore, sarcopenia was independently associated with inferior overall survival (adjusted hazard ratio, 2.98; 95% CI, 1.1-8.3; P = .04).

Conclusions: One-third of older adults with cancer in this cohort screened positive for sarcopenia using the SARC-F screening questionnaire, and these positive scores are associated with geriatric assessment domain impairments, reduced health-related quality of life, increased emergency room visits, and inferior overall survival.
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http://dx.doi.org/10.1002/cncr.33395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085056PMC
May 2021

Genetics of Anthracycline Cardiomyopathy in Cancer Survivors: State-of-the-Art Review.

Authors:
Smita Bhatia

JACC CardioOncol 2020 Nov 22;2(4):539-552. Epub 2020 Dec 22.

Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Anthracyclines are an integral part of chemotherapy regimens used to treat a variety of childhood-onset and adult-onset cancers. However, the development of cardiac dysfunction and heart failure often compromises the clinical utility of anthracyclines. The risk of cardiac dysfunction increases with anthracycline dose. This anthracycline-cardiac dysfunction association is modified by several demographic and clinical factors, such as age at anthracycline exposure (<4 years and ≥65 years); female sex; chest radiation; presence of cardiovascular risk factors (diabetes, hypertension); and concurrent use of cyclophosphamide, paclitaxel, and trastuzumab. However, the clinical variables alone yield modest predictive power in detecting cardiac dysfunction. Recently, attention has focused on the molecular basis of anthracycline-related cardiac dysfunction, providing an initial understanding of the mechanism of anthracycline-related cardiomyopathy. This review describes the current state of knowledge with respect to the pathogenesis of anthracycline-related cardiomyopathy and identifies the critical next steps to mitigate this problem.
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http://dx.doi.org/10.1016/j.jaccao.2020.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757557PMC
November 2020
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