Publications by authors named "Saro H Armenian"

114 Publications

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

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

Integration of Pediatric Hodgkin Lymphoma Treatment and Late Effects Guidelines: Seeing the Forest Beyond the Trees.

J Natl Compr Canc Netw 2021 06 30;19(6):755-764. Epub 2021 Jun 30.

1Department of Oncology, and.

The successful integration of clinical trials into pediatric oncology has led to steady improvement in the 5-year survival rate for children diagnosed with Hodgkin lymphoma (HL). It is estimated that >95% of children newly diagnosed with HL will become long-term survivors. Despite these successes, survival can come at a cost. Historically, long-term survivors of HL have a high risk of late-occurring adverse health effects and increased risk of nonrelapse mortality compared with the general population. The recognition of late-occurring events paired with the decades of life remaining for children cured of HL have made paramount the need to develop effective treatments that minimize the risk of late toxicity. Toward this goal, multiple, dose-intense, risk- and response-based regimens that use lower cumulative doses of chemotherapy and radiation have been developed. Appropriate frontline treatment selection requires a level of familiarity with the efficacy, acute toxicity, convenience, and late effects of treatments that may be impractical for providers who infrequently treat children with HL. There is an increasing need for guideline developers to begin to merge considerations from both frontline treatment and survivorship guidelines into practical documents that integrate potential long-term health risks. Herein, we take the first steps toward doing so by aligning cumulative treatment exposures, anticipated risks of late toxicity, and suggested surveillance recommendations for NCCN-endorsed Pediatric HL Guidelines. Future studies that integrate simulation modeling will strengthen this integrated approach and allow for opportunities to incorporate regimen-specific risks, health-related quality of life, and cost-effectiveness into decision tools to optimize HL therapy.
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http://dx.doi.org/10.6004/jnccn.2021.7042DOI Listing
June 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

Late-occurring infections in a contemporary cohort of hematopoietic cell transplantation survivors.

Cancer Med 2021 05 9;10(9):2956-2966. Epub 2021 Apr 9.

Department of Population Sciences, City of Hope, Duarte, CA, USA.

Background: There is a paucity of studies describing the incidence and risk factors for late-occurring (≥1 year) infectious complications in contemporary survivors of hematopoietic cell transplantation (HCT).

Methods: This was a retrospective cohort study of 641 1-year survivors of HCT, transplanted between 2010 and 2013 as adults, and in remission from their primary disease. Standardized definitions were used to characterize viral, fungal, and bacterial infections. Cumulative incidence of infections was calculated, with relapse/progression considered as a competing risk event. Fine-Gray subdistribution hazard ratio estimates and 95% confidence intervals (CI) were obtained, adjusted for relevant covariates.

Results: Median age at HCT was 55.2 years (range 18.1-78.1 years); 54.0% were survivors of allogeneic HCT. The 5-year cumulative incidence of a late-occurring infection for the entire cohort was 31.6%; the incidence of polymicrobial (≥2) infections was 10.1%. In survivors who developed at least one infection, the 5-year incidence of a subsequent infection was 45.3%. Among allogeneic HCT survivors, patients with acute lymphoblastic (HR = 1.82 95% CI [1.12-2.96]) or myeloid (HR = 1.50 95% CI [1.02-2.20]) leukemia, and those with an elevated HCT-Comorbidity index score (HR = 1.09 95% CI [1.01-1.17]) were more likely to develop late-occurring infections; there was an incremental risk associated with severity of graft versus host disease (GVHD) at 1-year post-HCT (mild: HR = 2.17, 95% CI [1.09-4.33]; moderate/severe: HR = 3.78, 95% CI [1.90-7.53]; reference: no GVHD).

Conclusions: The burden of late-occurring infections in HCT survivors is substantial, and there are important patient- and HCT-related modifiers of risk over time. These findings may help guide personalized screening and prevention strategies to improve outcomes after HCT.
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http://dx.doi.org/10.1002/cam4.3896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086032PMC
May 2021

Prevalence and risk factors for vitamin D deficiency in long-term childhood cancer survivors.

Pediatr Blood Cancer 2021 Jul 6;68(7):e29048. Epub 2021 Apr 6.

Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, California, USA.

Background: Childhood cancer survivors (CCS) have increased risk of developing chronic health conditions, including musculoskeletal disorders. Little is known regarding vitamin D deficiency (VDD, <20 ng/ml) and its association with bone mineral density (BMD) in long-term CCS. We evaluated the prevalence and risk factors for VDD in a large, diverse population of long-term CCS, and examined the association between VDD and BMD in patients who underwent guideline-recommended dual-energy X-ray absorptiometry (DXA) screening.

Methods: This cross-sectional study included 446 consecutive CCS seen from March 2018 to September 2020. Univariate analyses examined associations between CCS demographics, socioeconomic status, and treatment exposures and VDD. Multivariable logistic regressions identified factors associated with odds of VDD and reduced BMD.

Results: Median age at evaluation was 27.5 years (range 7-67 years); median time from completing therapy was 14.2 years (range 2-65 years). Fifty percent were female, and 45% were Hispanic. Twenty-four percent had VDD. In multivariable analysis, overweight and obese BMI were associated with VDD (overweight: OR 1.78, 95% CI 1.03-3.07, p = 0.04; obese: OR 2.40, 95% CI 1.39-4.13, p < 0.01; reference: normal/underweight), as was Hispanic or black race/ethnicity (OR 2.40, 95% CI 1.41-4.09, p < 0.01; reference: non-Hispanic white). In the 118 CCS with DXA results, VDD was independently associated with reduced BMD (OR 3.58, 95%CI 1.33-9.59, p = 0.01).

Conclusions: CCS have a high prevalence of VDD. High BMI and Hispanic or black race/ethnicity were associated with VDD. Survivors with VDD had a greater than threefold risk of reduced BMD. Risk-based screening may facilitate timely interventions to mitigate VDD and improve BMD in CCS.
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http://dx.doi.org/10.1002/pbc.29048DOI Listing
July 2021

Challenges associated with retrospective analysis of left ventricular function using clinical echocardiograms from a multicenter research study.

Echocardiography 2021 02 24;38(2):296-303. Epub 2021 Jan 24.

The Hospital for Sick Children, University of Toronto, Toronto, ON, USA.

Background: Retrospective multicenter research using echocardiograms obtained for routine clinical care can be hampered by issues of individual center quality. We sought to evaluate imaging and patient characteristics associated with poorer quality of archived echocardiograms from a cohort of childhood cancer survivors.

Methods: A single blinded reviewer at a central core laboratory graded quality of clinical echocardiograms from five centers focusing on images to derive 2D and M-mode fractional shortening (FS), biplane Simpson's ejection fraction (EF), myocardial performance index (MPI), tissue Doppler imaging (TDI)-derived velocities, and global longitudinal strain (GLS).

Results: Of 535 studies analyzed in 102 subjects from 2004 to 2017, all measures of cardiac function could be assessed in only 7%. While FS by 2D or M-mode, MPI, and septal E/E' could be measured in >80% studies, mitral E/E' was less consistent (69%), but better than EF (52%) and GLS (10%). 66% of studies had ≥1 issue, with technical issues (eg, lung artifact, poor endocardial definition) being the most common (33%). Lack of 2- and 3-chamber views was associated with the performing center. Patient age <5 years had a higher chance of apex cutoff in 4-chamber views compared with 16-35 years old. Overall, for any quality issue, earlier era of echo and center were the only significant risk factors.

Conclusion: Assessment of cardiac function using pooled multicenter archived echocardiograms was significantly limited. Efforts to standardize clinical echocardiographic protocols to include apical 2- and 3-chamber views and TDI will improve the ability to quantitate LV function.
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http://dx.doi.org/10.1111/echo.14983DOI Listing
February 2021

Atrial Fibrillation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation.

J Clin Oncol 2021 03 8;39(8):902-910. Epub 2021 Jan 8.

Department of Population Sciences, City of Hope; Duarte, CA.

Purpose: To examine the incidence and risk factors for de novo atrial fibrillation (AF) after allogeneic hematopoietic cell transplantation (HCT) and to describe the impact of AF on HCT-related outcomes.

Methods: A retrospective cohort study design was used to examine AF and associated outcomes in 487 patients who underwent allogeneic HCT from 2014 to 2016 and to characterize patient- and HCT-related risk factors. A nested case-control study design was used to describe the association between pre-HCT echocardiographic measures and future AF events.

Results: The median age at HCT was 52.4 years (18.1-78.6); the median time to AF was 117.5 days (4.0-1,405.0). The 5-year cumulative incidence of AF was 10.6%. Older (≥ 50 years) age (hazard ratio [HR], 2.76; 95% CI, 1.37 to 5.58), HLA-unrelated donor (HR, 2.20; 95% CI, 1.18 to 4.12), dyslipidemia (HR, 2.40; 95% CI, 1.23 to 4.68), and pre-HCT prolonged QTc interval (HR, 2.55; 95% CI, 1.38 to 4.72) were independent risk factors for AF. Despite having comparable left ventricular systolic function, patients who developed AF were significantly more likely to have lower left atrial ejection fraction, left atrial reservoir function, and elevated tricuspid regurgitant jet velocity prior to HCT, compared with patients who did not. The incidence rate of stroke after AF was 143 per 1,000 person-years. In adjusted analyses, AF was associated with a 12.8-fold (HR, 12.76; 95% CI, 8.76 to 18.57) risk of all-cause mortality and 15.8-fold (HR, 15.78; 95% CI, 8.70 to 28.62) risk of nonrelapse mortality.

Conclusion: The burden of AF after allogeneic HCT population is substantial, and the development of AF is associated with poor survival. We identified important associations between patient demographics, pre-HCT cardiac parameters, HCT-related exposures, and risk of AF, setting the stage for targeted prevention strategies during and after HCT.
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http://dx.doi.org/10.1200/JCO.20.02401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078261PMC
March 2021

Cardiovascular Health during and after Cancer Therapy.

Cancers (Basel) 2020 Dec 11;12(12). Epub 2020 Dec 11.

Department of Cardiovascular Disease, Mayo Clinic, Rochester, MN 55905, USA.

Certain cancer treatments have been linked to specific cardiovascular toxicities, including (but not limited to) cardiomyopathy, atrial fibrillation, arterial hypertension, and myocarditis. Radiation, anthracyclines, human epidermal growth factor receptor 2 (Her2)-directed therapies, fluoropyrimidines, platinums, tyrosine kinase inhibitors and proteasome inhibitors, immune checkpoint inhibitors, and chimeric antigen-presenting (CAR)-T cell therapy can all cause cardiovascular side effects. Management of cardiovascular dysfunction that occurs during cancer therapy often requires temporary or permanent cessation of the risk-potentiating anti-neoplastic drug as well as optimization of medical management from a cardiovascular standpoint. Stem cell or bone marrow transplant recipients face unique cardiovascular challenges, as do patients at extremes of age.
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http://dx.doi.org/10.3390/cancers12123737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763346PMC
December 2020

A Randomized Phase IIb Study of Low-dose Tamoxifen in Chest-irradiated Cancer Survivors at Risk for Breast Cancer.

Clin Cancer Res 2021 02 3;27(4):967-974. Epub 2020 Dec 3.

Dana Farber Cancer Institute, Boston, Massachusetts.

Purpose: Low-dose tamoxifen reduces breast cancer risk, but remains untested in chest-irradiated cancer survivors-a population with breast cancer risk comparable with mutation carriers. We hypothesized that low-dose tamoxifen would be safe and efficacious in reducing radiation-related breast cancer risk.

Patients And Methods: We conducted an investigator-initiated, randomized, phase IIb, double-blinded, placebo-controlled trial (FDA IND107367) between 2010 and 2016 at 15 U.S. sites. Eligibility included ≥12 Gy of chest radiation by age 40 years and age at enrollment ≥25 years. Patients were randomized 1:1 to low-dose tamoxifen (5 mg/day) or identical placebo tablets for 2 years. The primary endpoint was mammographic dense area at baseline, 1 and 2 years. IGF-1 plays a role in breast carcinogenesis; circulating IGF-1 and IGF-BP3 levels at baseline, 1 and 2 years served as secondary endpoints.

Results: Seventy-two participants (low-dose tamoxifen: = 34, placebo: = 38) enrolled at a median age of 43.8 years (35-49) were evaluable. They had received chest radiation at a median dose of 30.3 Gy. Compared with the placebo arm, the low-dose tamoxifen arm participants had significantly lower mammographic dense area ( = 0.02) and IGF1 levels ( < 0.0001), and higher IGFBP-3 levels ( = 0.02). There was no difference in toxicity biomarkers (serum bone-specific alkaline phosphatase, lipids, and antithrombin III; urine N-telopeptide cross-links) between the treatment arms. We did not identify any grade 3-4 adverse events related to low-dose tamoxifen.

Conclusions: In this randomized trial in chest-irradiated cancer survivors, we find that low-dose tamoxifen is effective in reducing established biomarkers of breast cancer risk and could serve as a risk-reduction strategy.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887034PMC
February 2021

Longitudinal trajectory of frailty in blood or marrow transplant survivors: Report from the Blood or Marrow Transplant Survivor Study.

Cancer 2021 03 18;127(5):794-800. Epub 2020 Nov 18.

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

Background: Blood or bone marrow transplantation (BMT) survivors with frailty are at a higher risk of subsequent mortality. Longitudinal trends in the frailty state are not known and could help identify vulnerable subpopulations at risk of subsequent adverse events.

Methods: This study included a cohort of 470 autologous and allogeneic BMT recipients who had survived ≥2 years after BMT and completed a baseline questionnaire (t1) at a median of 7.3 years after BMT and a follow-up questionnaire (t2) 13.2 years after t1. The main outcome was change in frailty state between t1 and t2. Frailty phenotype was defined as exhibiting ≥3 of the following characteristics: clinically underweight, exhaustion, low energy expenditure, slow walking speed, and muscle weakness. The following categories of change in frailty state were evaluated: worsened, improved, and stable.

Results: Of the 470 participants, 36.4% were aged ≥60 years at t1, and 50.6% were men. The prevalence of frailty increased from 4.8% at t1 to 9.6% at t2. Worsening was observed in 18.8% of patients, and improvement was reported in 9.7%. Pre-BMT exposure to vincristine (odds ratio [OR], 2.1; 95% CI, 1.3-3.39) was associated with worsening. Female sex (OR, 1.5; 95% CI, 0.93-2.4) was associated with a trend toward worsening. Pre-BMT exposure to vincristine (OR, 2.79; 95% CI, 1.44-5.43), a history of chronic graft-versus-host disease (OR, 2.58; 95% CI, 1.2-5.5), and grade 3 and 4 chronic health conditions at t1 (OR, 2.1; 95% CI, 1.08-4.33) were associated with frailty at t2.

Conclusions: In a cohort of BMT survivors who were followed longitudinally for a median of 20.6 years from BMT, the frailty status worsened for approximately20% over a 13-year timespan. BMT survivors who are at risk for worsening frailty could benefit from targeted interventions.
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http://dx.doi.org/10.1002/cncr.33313DOI Listing
March 2021

Primer on Biomarker Discovery in Cardio-Oncology: Application of Omics Technologies.

JACC CardioOncol 2020 Sep 15;2(3):379-384. Epub 2020 Sep 15.

Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.

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http://dx.doi.org/10.1016/j.jaccao.2020.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560982PMC
September 2020

Feasibility of a behavioral intervention using mobile health applications to reduce cardiovascular risk factors in cancer survivors: a pilot randomized controlled trial.

J Cancer Surviv 2021 Aug 10;15(4):554-563. Epub 2020 Oct 10.

Fred Hutchinson Cancer Research Center, PO Box 19024, Mailstop M4-C308, Seattle, WA, 98109, USA.

Purpose: Determine the feasibility of a remotely delivered mobile health (mHealth)-supported intervention to improve diet and physical activity in hematologic malignancy survivors.

Methods: Pilot randomized controlled trial of a 16-week intervention for improving diet and physical activity: individualized goal-setting (daily steps, sodium, saturated fat, added sugar intake) per feedback from mHealth trackers (Fitbit for activity; Healthwatch360 for diet), supplemented by a Facebook peer support group. Controls accessed the trackers without goal-setting or peer support. Everyone received standardized survivorship counseling with tailored advice from a clinician. Actigraphy and food frequency questionnaires assessed activity and diet at baseline and follow-up.

Results: Forty-one participants (51.2% male; median age 45.1 years; 7.0 years from treatment) were randomized (24 intervention; 17 control). Fitbit and Healthwatch360 use were more common among intervention versus control participants (75.0% versus 70.6% and 50.0% versus 17.7% of eligible days, respectively). Most intervention participants (66.7%) engaged with Facebook; overall, 91.7% interacted with the study's mHealth applications. While no comparisons in activity or dietary outcomes between intervention versus control group met statistical significance, the intervention was associated with greater reductions in the targeted dietary factors and improvements in Healthy Eating Index-2015 score, moderate-vigorous physical activity time, and daily steps. Participant retention at 6 months was 90.2%.

Conclusions: An intervention for cardiovascular risk reduction based on individualized goal-setting enhanced by mHealth and social media peer support was feasible and acceptable among cancer survivors.

Implications For Cancer Survivors: Effective and easily disseminated strategies that improve diet and physical activity in this population are needed.

Trial Registration: Registered in ClinicalTrials.gov (NCT03574012) on June 29, 2018.
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http://dx.doi.org/10.1007/s11764-020-00949-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035343PMC
August 2021

Feasibility of geriatric assessment before transplant conditioning regimen in older HCT recipients.

Bone Marrow Transplant 2021 03 29;56(3):726-729. Epub 2020 Sep 29.

Department of Population Sciences, Beckman Research Institute at City of Hope, Duarte, CA, USA.

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http://dx.doi.org/10.1038/s41409-020-01064-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256689PMC
March 2021

Guidance regarding COVID-19 for survivors of childhood, adolescent, and young adult cancer: A statement from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Pediatr Blood Cancer 2020 12 23;67(12):e28702. Epub 2020 Sep 23.

Department of Malignant Haematology, Great Ormond Street Hospital for Children NHS Trust, London, UK.

Childhood, adolescent, and young adult (CAYA) cancer survivors may be at risk for a severe course of COVID-19. Little is known about the clinical course of COVID-19 in CAYA cancer survivors, or if additional preventive measures are warranted. We established a working group within the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) to summarize existing evidence and worldwide recommendations regarding evidence about factors/conditions associated with risk for a severe course of COVID-19 in CAYA cancer survivors, and to develop a consensus statement to provide guidance for healthcare practitioners and CAYA cancer survivors regarding COVID-19.
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http://dx.doi.org/10.1002/pbc.28702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537044PMC
December 2020

Cost-Effectiveness of the International Late Effects of Childhood Cancer Guideline Harmonization Group Screening Guidelines to Prevent Heart Failure in Survivors of Childhood Cancer.

J Clin Oncol 2020 11 14;38(33):3851-3862. Epub 2020 Aug 14.

Division of General Pediatrics, Boston Children's Hospital, Boston, MA.

Purpose: Survivors of childhood cancer treated with anthracyclines and/or chest-directed radiation are at increased risk for heart failure (HF). The International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) recommends risk-based screening echocardiograms, but evidence supporting its frequency and cost-effectiveness is limited.

Patients And Methods: Using the Childhood Cancer Survivor Study and St Jude Lifetime Cohort, we developed a microsimulation model of the clinical course of HF. We estimated long-term health outcomes and economic impact of screening according to IGHG-defined risk groups (low [doxorubicin-equivalent anthracycline dose of 1-99 mg/m and/or radiotherapy < 15 Gy], moderate [100 to < 250 mg/m or 15 to < 35 Gy], or high [≥ 250 mg/m or ≥ 35 Gy or both ≥ 100 mg/m and ≥ 15 Gy]). We compared 1-, 2-, 5-, and 10-year interval-based screening with no screening. Screening performance and treatment effectiveness were estimated based on published studies. Costs and quality-of-life weights were based on national averages and published reports. Outcomes included lifetime HF risk, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Strategies with ICERs < $100,000 per QALY gained were considered cost-effective.

Results: Among the IGHG risk groups, cumulative lifetime risks of HF without screening were 36.7% (high risk), 24.7% (moderate risk), and 16.9% (low risk). Routine screening reduced this risk by 4% to 11%, depending on frequency. Screening every 2, 5, and 10 years was cost-effective for high-risk survivors, and every 5 and 10 years for moderate-risk survivors. In contrast, ICERs were > $175,000 per QALY gained for all strategies for low-risk survivors, representing approximately 40% of those for whom screening is currently recommended.

Conclusion: Our findings suggest that refinement of recommended screening strategies for IGHG high- and low-risk survivors is needed, including careful reconsideration of discontinuing asymptomatic left ventricular dysfunction and HF screening in low-risk survivors.
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http://dx.doi.org/10.1200/JCO.20.00418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676889PMC
November 2020

Technology-enabled activation of skin cancer screening for hematopoietic cell transplantation survivors and their primary care providers (TEACH).

BMC Cancer 2020 Aug 3;20(1):721. Epub 2020 Aug 3.

Department of Social and Behavioral Sciences, Harvard TH Chan School of Public Health, Boston, MA, USA.

Background: Hematopoietic cell transplantation (HCT) is a curative option for a growing number of patients with hematologic diseases and malignancies. However, HCT-related factors, such as total body irradiation used for conditioning, graft-versus-host disease, and prolonged exposure to immunosuppressive therapy, result in very high risk for melanoma and non-melanoma skin cancer (NMSC). In fact, skin cancer is the most common subsequent neoplasm in HCT survivors, tending to develop at a time when survivors' follow-up care has largely transitioned to the primary care setting. The goal of this study is to increase skin cancer screening rates among HCT survivors through patient-directed activation alone or in combination with physician-directed activation. The proposed intervention will identify facilitators of and barriers to risk-based screening in this population and help reduce the burden of cancer-related morbidity after HCT.

Methods/design: 720 HCT survivors will be enrolled in this 12-month randomized controlled trial. This study uses a comparative effectiveness design comparing (1) patient activation and education (PAE, N = 360) including text messaging and print materials to encourage and motivate skin examinations; (2) PAE plus primary care physician activation (PAE + Phys, N = 360) adding print materials for the physician on the HCT survivors' increased risk of skin cancer and importance of conducting a full-body skin exam. Patients on the PAE + Phys arm will be further randomized 1:1 to the teledermoscopy (PAE + Phys+TD) adding physician receipt of a portable dermatoscope to upload images of suspect lesions for review by the study dermatologist and an online course with descriptions of dermoscopic images for skin cancers.

Discussion: When completed, this study will provide much-needed information regarding strategies to improve skin cancer detection in other high-risk (e.g. radiation-exposed) cancer survivor populations, and to facilitate screening and management of other late effects (e.g. cardiovascular, endocrine) in HCT survivors.

Trial Registration: ClinicalTrials.gov, NCT04358276 . Registered 24 April 2020.
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http://dx.doi.org/10.1186/s12885-020-07232-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397711PMC
August 2020

Longitudinal Changes in Echocardiographic Parameters of Cardiac Function in Pediatric Cancer Survivors.

JACC CardioOncol 2020 Mar 17;2(1):26-37. Epub 2020 Mar 17.

Clinical Research and Public Health Sciences Divisions, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Background: Childhood cancer survivors undergo serial echocardiograms to screen for cardiotoxicity. It is not clear whether small longitudinal changes in functional or structural parameters over time have clinical significance.

Objectives: To assess the timing of changes in serial echocardiographic parameters in pediatric age childhood cancer survivors and to evaluate their associations with cardiomyopathy development.

Methods: We performed a multi-center retrospective case-control study of ≥1-year survivors following the end of cancer therapy. Cardiomyopathy cases (fractional shortening (FS) ≤28% or ejection fraction (EF) ≤50% on ≥2 occasions) were matched to controls (FS ≥30%, EF ≥55%, not on cardiac medications) by cumulative anthracycline and chest radiation dose, follow-up duration, and age at diagnosis. Digitally archived clinical surveillance echocardiograms were quantified in a central core lab, blinded to patient characteristics. Using mixed models with interaction terms between time and case status, we estimated the least square mean differences of 2D, M-mode, pulsed wave Doppler and tissue Doppler imaging derived parameters across time between cases and controls.

Results: We identified 50 matched case-control pairs from 5 centers. Analysis of 412 echocardiograms (cases, n=181; controls, n=231) determined that indices of LV systolic function (FS, biplane EF), diastolic function (mitral E/A ratio), and LV size (end diastolic dimension z-scores) were significantly different between cases and controls, even four years prior to the development of cardiomyopathy.

Conclusions: Longitudinal changes in cardiac functional parameters can occur relatively early in pediatric age childhood cancer survivors and are associated with the development of cardiomyopathy.
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http://dx.doi.org/10.1016/j.jaccao.2020.02.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384713PMC
March 2020

Total Body Irradiation and Risk of Breast Cancer After Blood or Marrow Transplantation: A Blood or Marrow Transplantation Survivor Study Report.

J Clin Oncol 2020 09 16;38(25):2872-2882. Epub 2020 Jul 16.

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

Purpose: To examine the association between total body irradiation (TBI) and subsequent breast cancer in women treated with blood or marrow transplantation (BMT) for hematologic malignancies.

Patients And Methods: Participants were drawn from the BMT Survivor Study (BMTSS), a retrospective cohort study that included patients who underwent transplantation between 1974 and 2014 and survived for ≥ 2 years after BMT. Patients with pre-BMT chest radiation or a history of breast cancer were excluded. Participants completed the BMTSS survey, which included details regarding breast cancer diagnosis. Subsequent breast cancer was confirmed by pathology report review or physician notes. Cox proportional hazards models assessed the association between TBI and subsequent breast cancer. Standardized incidence ratios were calculated to determine the excess risk of subsequent breast cancer compared with that in the general population.

Results: A total of 1,464 female BMT survivors (allogeneic: n = 788; autologous: n = 676) participated, with a median follow-up of 9.3 years from BMT. TBI was used in 660 patients (46%). Thirty-seven women developed subsequent breast cancer (allogeneic: n = 19; autologous: n = 18). Multivariable analysis revealed that exposure to TBI was associated with an increased risk of subsequent breast cancer among allogeneic BMT survivors (hazard ratio [HR], 3.7 [95% CI, 1.2 to 11.8]; = .03) and autologous BMT survivors (HR, 2.6 [95% CI, 1.0 to 6.8]; = .048). Pre-BMT exposure to alkylating agents was associated with an increased risk of subsequent breast cancer among autologous BMT survivors (HR, 3.3 [95% CI, 1.0 to 9.0]; = .05). Compared with that in the general population, exposure to TBI at age < 30 years was associated with a 4.4-fold higher risk of subsequent breast cancer in allogeneic BMT survivors and a 4.6-fold higher risk in autologous BMT survivors.

Conclusion: The association between TBI and subsequent breast cancer, especially among those exposed at a young age, as well as pre-BMT exposure to alkylating agents, should inform breast cancer screening for early detection.
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http://dx.doi.org/10.1200/JCO.20.00231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460149PMC
September 2020

Chronic Comorbidities Among Survivors of Adolescent and Young Adult Cancer.

J Clin Oncol 2020 09 16;38(27):3161-3174. Epub 2020 Jul 16.

Department of Population Sciences, City of Hope, Duarte, CA.

Purpose: To describe the incidence, relative risk, and risk factors for chronic comorbidities in survivors of adolescent and young adult (AYA) cancer.

Methods: This retrospective cohort study included 2-year survivors of AYA cancer diagnosed between age 15 and 39 years at Kaiser Permanente Southern California from 2000 to 2012. A comparison cohort without cancer was individually matched (13:1) to survivors of cancer on age, sex, and calendar year. Using electronic medical records, all participants were followed through December 31, 2014, for chronic comorbidity diagnoses. Poisson regression was used to evaluate the association between cancer survivor status and risk of developing each comorbidity. The associations between cumulative exposure to chemotherapy and radiation therapy and selected comorbidities were examined for survivors of cancer.

Results: The cohort included 6,778 survivors of AYA cancer and 87,737 persons without a history of cancer. The incidence rate ratio (IRR) for survivors of cancer was significantly increased for nearly all comorbidities examined. IRR ranged from 1.3 (95% CI, 1.2 to 1.4) for dyslipidemia to 8.3 (95% CI, 4.6 to 14.9) for avascular necrosis. Survivors of AYA cancer had a 2- to 3-fold increased risk for cardiomyopathy, stroke, premature ovarian failure, chronic liver disease, and renal failure. Among survivors of cancer, significant associations between chemotherapy and radiation therapy exposures and late effects of cardiomyopathy, hearing loss, stroke, thyroid disorders, and diabetes were observed from the multivariable analyses. Forty percent of survivors of AYA cancer had multiple (≥ 2) comorbidities at 10 years after index date, compared with 20% of those without cancer.

Conclusion: Risk of developing comorbidities is increased in survivors of AYA cancer compared with the general population. Specific cancer treatment exposures were associated with risk of developing different comorbidities. These findings have important implications for survivorship care planning and patient education.
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http://dx.doi.org/10.1200/JCO.20.00722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499612PMC
September 2020

Counseling and surveillance of obstetrical risks for female childhood, adolescent, and young adult cancer survivors: recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Am J Obstet Gynecol 2021 01 2;224(1):3-15. Epub 2020 Jun 2.

Conroe Regional Medical Center, Shenandoah, TX.

Female childhood, adolescent, and young adult cancer survivors have an increased risk of adverse pregnancy outcomes related to their cancer- or treatment-associated sequelae. Optimal care for childhood, adolescent, and young adult cancer survivors can be facilitated by clinical practice guidelines that identify specific adverse pregnancy outcomes and the clinical characteristics of at-risk subgroups. However, national guidelines are scarce and vary in content. Here, the International Late Effects of Childhood Cancer Guideline Harmonization Group offers recommendations for the counseling and surveillance of obstetrical risks of childhood, adolescent, and young adult survivors. A systematic literature search in MEDLINE database (through PubMed) to identify all available evidence published between January 1990 and December 2018. Published articles on pregnancy and perinatal or congenital risks in female cancer survivors were screened for eligibility. Study designs with a sample size larger than 40 pregnancies in childhood, adolescent, and young adult cancer survivors (diagnosed before the age of 25 years, not pregnant at that time) were eligible. This guideline from the International Late Effects of Childhood Cancer Guideline Harmonization Group systematically appraised the quality of available evidence for adverse obstetrical outcomes in childhood, adolescent, and young adult cancer survivors using Grading of Recommendations Assessment, Development, and Evaluation methodology and formulated recommendations to enhance evidence-based obstetrical care and preconception counseling of female childhood, adolescent, and young adult cancer survivors. Healthcare providers should discuss the risk of adverse obstetrical outcomes based on cancer treatment exposures with all female childhood, adolescent, and young adult cancer survivors of reproductive age, before conception. Healthcare providers should be aware that there is no evidence to support an increased risk of giving birth to a child with congenital anomalies (high-quality evidence). Survivors treated with radiotherapy to volumes exposing the uterus and their healthcare providers should be aware of the risk of adverse obstetrical outcomes such as miscarriage (moderate-quality evidence), premature birth (high-quality evidence), and low birthweight (high-quality evidence); therefore, high-risk obstetrical surveillance is recommended. Cardiomyopathy surveillance is reasonable before pregnancy or in the first trimester for all female survivors treated with anthracyclines and chest radiation. Female cancer survivors have increased risks of premature delivery and low birthweight associated with radiotherapy targeting the lower body and thereby exposing the uterus, which warrant high-risk pregnancy surveillance.
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http://dx.doi.org/10.1016/j.ajog.2020.05.058DOI Listing
January 2021

Morbidity burden in survivors of multiple myeloma who underwent autologous transplantation: A Bone Marrow Transplantation Survivor Study.

Cancer 2020 07 15;126(14):3322-3329. Epub 2020 May 15.

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

Background: Autologous blood or bone marrow transplantation (aBMT) is considered the standard of care for patients with multiple myeloma (MM). Significantly improved survival necessitates an understanding of the morbidity burden borne by the growing survivor population.

Methods: The authors evaluated severe and/or life-threatening chronic health conditions (CHCs) and subsequent neoplasms (SNs) in patients with MM who were treated with aBMT using the Bone Marrow Transplant Survivor Study. A total of 630 study participants had undergone aBMT for MM at 1 of 3 BMT centers, had survived ≥2 years after aBMT, and were aged ≥18 years at the time of survey completion. Survivors of aBMT identified 289 nearest-age siblings to constitute an unaffected comparison group. Scoring of CHCs was based on version 5 of the National Cancer Institute Common Terminology Criteria for Adverse Events to determine severity (with grade 3 indicating serious and grade 4 indicating life-threatening).

Results: The 10-year cumulative incidence of any grade 3 to 4 CHC among survivors of aBMT was 57.6 ± 3.2%. Survivors of MM were found to be at 40% higher odds of developing grade 3 to 4 CHCs when compared with siblings (95% confidence interval [95% CI], 1.0-1.9). Among SNs, 96% were solid tumors, yielding a 10-year cumulative incidence of 13.6% ± 2.5%. Pre-aBMT exposure to cyclophosphamide (hazard ratio [HR], 3.5; 95% CI, 1.5-8.1) and immunomodulatory drugs (HR, 3.9; 95% CI, 1.5-10.1) were associated with an increased risk of solid tumors. Melanoma (10-year cumulative incidence: 3.3% ± 1.2%) and squamous cell carcinoma (10-year cumulative incidence: 5.1% ± 1.8%), were the most common SNs. Pre-aBMT exposure to cyclophosphamide (HR, 6.02; 95% CI, 1.4-26.1) and immunomodulatory drugs (HR, 7.9; 95% CI, 0.9-68.5) was associated with an increased risk of melanoma.

Conclusions: The 10-year cumulative incidence of severe and/or life-threatening CHCs was found to approach 60% in long-term survivors of MM, with solid SNs constituting a large morbidity burden. The current study has provided evidence supporting the close monitoring of survivors to manage morbidity.
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http://dx.doi.org/10.1002/cncr.32941DOI Listing
July 2020

Abnormal body composition is a predictor of adverse outcomes after autologous haematopoietic cell transplantation.

J Cachexia Sarcopenia Muscle 2020 08 25;11(4):962-972. Epub 2020 Mar 25.

Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA.

Background: The number of patients undergoing autologous haematopoietic cell transplant (HCT) is growing, but little is known about the factors that predict adverse outcomes. Low muscle mass and obesity are associated with disability and premature mortality in individuals with non-malignant diseases and may predict outcomes after autologous HCT.

Methods: This was a retrospective cohort study of 320 patients who underwent autologous HCT for Hodgkin or non-Hodgkin lymphoma between 2009 and 2014. Sarcopenia {skeletal muscle index male: <43 cm/m [body mass index (BMI) < 25 kg/m ] or < 53 cm/m [BMI ≥ 25 kg/m ] and female: <41 cm/m [regardless of BMI]) and obesity [total abdominal adiposity ≥450.0 cm (male), ≥396.4 cm (female)] were assessed from single-slice abdominal pre-HCT computed tomography images. Length of hospital stay, first unplanned intensive care unit admission, and 30-day unplanned readmission were evaluated based on body composition using multivariable regression analysis, and mortality was evaluated with Kaplan-Meier analysis and Gray's test.

Results: Median age at HCT was 53.3 years (range, 18.5 to 78.1 years); 26.3% were sarcopenic and an additional 7.8% were sarcopenic obese pre-HCT. Sarcopenic obesity was associated with increased risk of prolonged hospitalization [odds ratio (OR) = 3.6, 95% confidence interval (CI) 1.3-9.8], intensive care unit admission (OR = 4.7, 95% CI 1.5-16.1), and unplanned readmission after HCT (OR = 13.6, 95% CI 2.5-62.8). Patients who were sarcopenic obese also had the highest mortality risk at 1 year [hazard ratio (HR): 3.9, 95% CI 1.1-11.0] and 5 years (HR: 2.5, 95% CI 1.1-5.5), compared with patients with normal body composition. Sarcopenia alone, but not obesity alone, was associated with an increased risk of these outcomes, albeit with a lower magnitude of risk than in patients who were sarcopenic obese.

Conclusions: Sarcopenic obesity was an important predictor of outcomes in patients undergoing autologous HCT. These findings could inform targeted prevention strategies in patients at highest risk of complications after HCT.
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http://dx.doi.org/10.1002/jcsm.12570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432567PMC
August 2020

Feasibility and Acceptability of Using a Telehealth Platform to Monitor Cardiovascular Risk Factors in Hematopoietic Cell Transplantation Survivors at Risk for Cardiovascular Disease.

Biol Blood Marrow Transplant 2020 06 16;26(6):1233-1237. Epub 2020 Apr 16.

Department of Population Sciences, City of Hope, Duarte, California. Electronic address:

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in hematopoietic cell transplantation (HCT) survivors. In these patients, such risk factors as hypertension, diabetes, obesity, and physical inactivity are important modifiers of CVD risk. However, the period when HCT survivors are at greatest risk of developing these risk factors, and in turn CVD, coincides with a drop in engagement in survivorship care. We examined the feasibility and acceptability of a 4-week remote risk-based monitoring (blood pressure monitor, weight scale, pulse oximeter, glucometer) and management program in 18 (11 allogeneic and 7 autologous) HCT survivors at intermediate-high risk of CVD. The median patient age was 66 years (range, 53 to 74 years), 67% had hypertension, 22% had diabetes, 11% were obese (body mass index ≥30 kg/m), 56% were at intermediate risk of CVD, and 44% were at high risk of CVD. Weekly compliance with the remote monitoring schedule (≥3 readings/week using all devices) ranged from 72% in week 1 to 83% in weeks 2 to 4. Fifteen participants (83%) generated 86 alerts that were outside the predetermined range of normal; 63 of these readings (73%) normalized without intervention, and 23 (27%) necessitated triage by the study research nurse. Nearly all participants reported that the study kept them motivated and involved in their healthcare, and >85% agreed that the study supported their healthcare goals, helped them learn and manage their health conditions, and increased their access to healthcare. These findings may set the foundation for innovative risk-based and remote interventions to reduce the burden of CVD in this growing population of patients.
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http://dx.doi.org/10.1016/j.bbmt.2020.02.027DOI Listing
June 2020

Cause-specific mortality in survivors of adolescent and young adult cancer.

Cancer 2020 05 4;126(10):2305-2316. Epub 2020 Mar 4.

Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California.

Background: Few studies have adequately addressed long-term survival (>20 years from diagnosis) among survivors of adolescent and young adult (AYA) cancers.

Methods: In this retrospective, population-based cohort study in a US integrated health care system, the authors examined cause-specific mortality in 2-year survivors of AYA cancers (patients aged 15-39 years who were diagnosed between 1990 and 2012; N = 10,574) matched (by age, sex, and calendar year) to individuals without cancer (N = 136,683) to determine whether mortality rates changed over time. Incidence rate ratios (IRRs) for mortality were estimated using multivariable Poisson regression. A multivariable Cox model was used to examine predictors of cause-specific mortality among AYA cancer survivors.

Results: Through December 31, 2014, 1352 deaths were observed among AYA cancer survivors, yielding an overall survival rate of 78.5% at 25 years after diagnosis. Overall, AYA cancer survivors were at 10.4-fold increased risk for death (95% CI, 9.7-fold to 11.2-fold increased risk for death) compared with the matched noncancer cohort, and this risk remained elevated at >20 years after diagnosis (IRR, 2.9; 95% CI, 2.0-4.3). The absolute excess risk for death from any cause was 12.7 per 1000 person-years (95% CI, 11.9-13.4 per 1000 person-years). Starting at 15 years after diagnosis, the incidence of second cancer-related mortality exceeded the rate of recurrence-related mortality, and similar trends were observed for deaths from other health-related conditions. The 8-year cumulative incidence of mortality declined over time (before 2000, 12.6%; 2000-2006, 10.1%; after 2006, 7.3%; P < .001), largely because of declines in recurrence-related mortality. Age, sex, race/ethnicity, cancer stage at diagnosis, and cancer treatment predicted cause-specific mortality.

Conclusions: The current data highlight the need for specialized, long-term follow-up care for AYA cancer survivors.
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http://dx.doi.org/10.1002/cncr.32775DOI Listing
May 2020

Conditional Survival, Cause-Specific Mortality, and Risk Factors of Late Mortality After Allogeneic Hematopoietic Cell Transplantation.

J Natl Cancer Inst 2020 11;112(11):1153-1161

Department of Population Sciences, City of Hope, Duarte, CA, USA.

Background: Long-term mortality after hematopoietic cell transplantation (HCT) is conventionally calculated from the time of HCT, ignoring temporal changes in survivors' mortality risks. Conditional survival rates, accounting for time already survived, are relevant for optimal delivery of survivorship care but have not been widely quantified. We estimated conditional survival by elapsed survival time in allogeneic HCT patients and examined cause-specific mortality.

Methods: We calculated conditional survival rates and standardized mortality ratio for overall and cause-specific mortality in 4485 patients who underwent HCT for malignant hematologic diseases at a large transplant center during 1976-2014. Statistical tests were two-sided.

Results: The 5-year survival rate from HCT was 48.6%. After surviving 1, 2, 5, 10, and 15 years, the subsequent 5-year survival rates were 71.2%, 78.7%, 87.4%, 93.5%, and 86.2%, respectively. The standardized mortality ratio was 30.3 (95% confidence interval [CI] = 29.2 to 35.5). Although the standardized mortality ratio declined in longer surviving patients, it was still elevated by 3.6-fold in survivors of 15 years or more (95% CI = 3.0 to 4.1). Primary disease accounted for 50% of deaths in the overall cohort and only 10% in 15-year survivors; the leading causes of nondisease-related mortality were subsequent malignancy (26.1%) and cardiopulmonary diseases (20.2%). We also identified the risk factors for nondisease-related mortality in 1- and 5-year survivors.

Conclusion: Survival probability improves the longer patients survive after HCT. However, HCT recipients surviving 15 years or more remain at elevated mortality risk, largely because of health conditions other than their primary disease. Our study findings help inform preventive and interventional strategies to improve long-term outcomes after allogeneic HCT.
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http://dx.doi.org/10.1093/jnci/djaa022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669225PMC
November 2020

Changes in Cardiovascular Biomarkers With Breast Cancer Therapy and Associations With Cardiac Dysfunction.

J Am Heart Assoc 2020 01 21;9(2):e014708. Epub 2020 Jan 21.

Department of Medicine Division of Cardiology Perelman School of Medicine at the University of Pennsylvania Philadelphia PA.

Background We examined the longitudinal associations between changes in cardiovascular biomarkers and cancer therapy-related cardiac dysfunction (CTRCD) in patients with breast cancer treated with cardotoxic cancer therapy. Methods and Results Repeated measures of high-sensitivity cardiac troponin T (hs-cTnT), NT-proBNP (N-terminal pro-B-type natriuretic peptide), myeloperoxidase, placental growth factor, and growth differentiation factor 15 were assessed longitudinally in a prospective cohort of 323 patients treated with anthracyclines and/or trastuzumab followed over a maximum of 3.7 years with serial echocardiograms. CTRCD was defined as a ≥10% decline in left ventricular ejection fraction to a value <50%. Associations between changes in biomarkers and left ventricular ejection fraction were evaluated in repeated-measures linear regression models. Cox regression models assessed the associations between biomarkers and CTRCD. Early increases in all biomarkers occurred with anthracycline-based regimens. hs-cTnT levels >14 ng/L at anthracycline completion were associated with a 2-fold increased CTRCD risk (hazard ratio, 2.01; 95% CI, 1.00-4.06). There was a modest association between changes in NT-proBNP and left ventricular ejection fraction in the overall cohort; this was most pronounced with sequential anthracycline and trastuzumab (1.1% left ventricular ejection fraction decline [95% CI, -1.8 to -0.4] with each NT-proBNP doubling). Increases in NT-proBNP were also associated with CTRCD (hazard ratio per doubling, 1.56; 95% CI, 1.32-1.84). Increases in myeloperoxidase were associated with CTRCD in patients who received sequential anthracycline and trastuzumab (hazard ratio per doubling, 1.28; 95% CI, 1.04-1.58). Conclusions Cardiovascular biomarkers may play an important role in CTRCD risk prediction in patients with breast cancer who receive cardiotoxic cancer therapy, particularly in those treated with sequential anthracycline and trastuzumab therapy. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01173341.
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http://dx.doi.org/10.1161/JAHA.119.014708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033834PMC
January 2020

Cardiovascular events in cancer survivors.

Semin Oncol 2019 12 19;46(6):426-432. Epub 2019 Nov 19.

Department of Medicine, Campus Bio-Medico University, Rome, Italy. Electronic address:

Malignant disease and its treatment carry huge burdens for patients. Some are immediate, in that the disease itself presents as a life threatening event, or the treatment may result in immediate and devastating toxicity. More often the treatment of cancer is associated with more subtle or late events, yet these may impact the quality of life for cancer survivors in a variety of ways. In addition to the physical sequelae of cancer or its treatment, cancer survivors often experience consequences in the form of social or mental incapacity. Session III of this Colloquium on Cardio-Oncology focuses on some of these concerns, both from the perspective of health care providers who strive to minimize the burdens, but also from the viewpoint of the patient him or herself who must deal with the price that must often be paid for increased survival or cure.
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http://dx.doi.org/10.1053/j.seminoncol.2019.01.007DOI Listing
December 2019

Helping the cardio-oncologist: from real life to guidelines.

Semin Oncol 2019 12 20;46(6):433-436. Epub 2019 Nov 20.

MD Anderson Cancer Center and University of Texas, Houston, TX.

Guidelines for the diagnosis, management, and surveillance of cancer patients have evolved with the single goal of improving patient care based on established data when available, or in the absence of firm data, on the standard practices of those with broad experience in actual hands-on patient care. Two initiatives intended to disseminate information to cardio-oncologists, were discussed in this session: the first, from the American Society of Clinical Oncology was focused on available data and the confidence level of that data; the second, from The European Society of Cardiology was a position paper. Interestingly, notwithstanding the somewhat different focus, there is considerable agreement between these two initiatives. Nevertheless, guidelines my not be applicable to all afflicted patients, and may raise questions as to when deviations from published standards should be considered. Such deviations may result in allegations of failure to meet standards of care or legal liability.
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http://dx.doi.org/10.1053/j.seminoncol.2019.01.005DOI Listing
December 2019
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