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Background: Childhood cancer survivors treated with anthracyclines are at high risk for asymptomatic left ventricular dysfunction (ALVD), subsequent heart failure, and death. The consensus-based Children's Oncology Group (COG) Long-Term Follow-up Guidelines recommend lifetime echocardiographic screening for ALVD. Objective: To evaluate the efficacy and cost-effectiveness of the COG guidelines and to identify more cost-effective screening strategies. Design: Simulation of life histories using Markov health states. Data Sources: Childhood Cancer Survivor Study; published literature. Target Population: Childhood cancer survivors. Time Horizon: Lifetime. Perspective: Societal. Intervention: Echocardiographic screening followed by angiotensin-converting enzyme (ACE) inhibitor and β-blocker therapies after ALVD diagnosis. Outcome Measures: Quality-adjusted life-years (QALYs), costs, incremental cost-effectiveness ratios (ICERs) in dollars per QALY, and cumulative incidence of heart failure. Results of Base-Case Analysis: The COG guidelines versus no screening have an ICER of $61 500, extend life expectancy by 6 months and QALYs by 1.6 months, and reduce the cumulative incidence of heart failure by 18% at 30 years after cancer diagnosis. However, less frequent screenings are more cost-effective than the guidelines and maintain 80% of the health benefits. Results of Sensitivity Analysis: The ICER was most sensitive to the magnitude of ALVD treatment efficacy; higher treatment efficacy resulted in lower ICER. Limitation: Lifetime non-heart failure mortality and the cumulative incidence of heart failure more than 20 years after diagnosis were extrapolated; the efficacy of ACE inhibitor and β-blocker therapy in childhood cancer survivors with ALVD is undetermined (or unknown). Conclusion: The COG guidelines could reduce the risk for heart failure in survivors at less than $100 000/QALY. Less frequent screening achieves most of the benefits and would be more cost-effective than the COG guidelines. [ABSTRACT FROM AUTHOR]

Background. Substantial evidence supports the use of adjuvant trastuzumab with chemotherapy for patients with human epidermal growth factor receptor (HER)-2+ breast cancer; however, a lesser amount of data is available to guide use of this therapy in older patients and in those with significant medical comorbidities. The goal of the current study was to understand how patient age and health status impact oncologists' decisions to recommend adjuvant therapy in older women with HER-2+ breast cancer. Methods. Medical oncologists (n=151) participated in an online survey regarding treatment recommendations for a hypothetical patient of varying age and health status with tumor stage 2, nodal stage 2, estrogen receptor-negative, HER-2+ breast cancer. Survey respondents recommended either chemotherapy plus trastuzumab, chemotherapy alone, trastuzumab alone, or no therapy. The effect of age and health status on therapeutic recommendations was assessed. Findings. As the hypothetical patient's age increased or health status deteriorated, oncologists were less likely to recommend a combination of chemotherapy plus trastuzumab. In contrast, oncologists were more likely to recommend either trastuzumab alone or no therapy for patients with advanced age and deteriorating health status. Chemotherapy alone was recommended by only 7.5% of respondents, on average. Interpretation. With limited evidence-based data for the treatment of older women with early-stage HER-2α breast cancer, medical oncologists recommend a diverse array of therapeutic approaches. With increasing age and declining health status they were less likely to recommend chemotherapy plus trastuzumab and more likely to recommend single-agent trastuzumab or no therapy. The Oncologist 2009;14:883-890 [ABSTRACT FROM AUTHOR]

Background: Although an association between benign digestive diseases and smoking or drinking habits was reported, consistent results have not been obtained either in European, American or Japanese populations. Methods: Smoking and alcohol habits as risk factors for the incidence of gastric ulcer, duodenal ulcer, chronic liver disease and cirrhosis as well as cholelithiasis were examined using the longitudinal data of the Adult Health Study collected biennially between 1958 and 1998. During 1958-1998, 1,093 gastric ulcers, 437 duodenal ulcers, 2,054 chronic liver diseases and cirrhoses, and 1,136 cholelithiasis cases were newly detected based on medical history, fluoroscopy or endoscopy and ultrasonography. Smoking and drinking histories were obtained from five and three questionnaires, respectively, administered during different periods. The relative risks (RRs) for ever smoked to never smoked and that for ever drank to never drank were estimated after adjustment for city, sex, age, birth cohort, calendar time and radiation dose. Results: The analysis showed a positive association of smoking with gastric ulcer (RR: 2.03, 95% CI: 1.71-2.41), duodenal ulcer (RR: 1.31, 95% CI: 0.99-1.72), chronic liver disease and cirrhosis (RR: 1.23, 95% CI: 1.08-1.39) and cholelithiasis (RR: 1.19, 95% CI: 1.02-1.40), and a positive association of drinking with chronic liver disease and cirrhosis (RR: 1.10, 95% CI: 0.99-1.23). Conclusions: Thepeptic ulcer, chronic liver disease and cholelithiasis incidence increased significantly with smoking, and the chronic liver disease incidence increased significantly with drinking simultaneously in a prospective study of a Japanese population. [ABSTRACT FROM AUTHOR]

The Adult Health Study (AHS) is a longitudinal study that has included biennial blood pressure measurements since 1958. In the present study, we applied the mixed effects model for serially measured data on the AHS population to (1) examine age-related changes in blood pressure and (2) detect possible radiation effects. The estimated longitudinal model of systolic blood pressure (SBP) depicted a linear increase from 30 to 80 years of age for both sexes. The diastolic blood pressure (DBP) rose linearly to about 65 years of age and then leveled off. There were marked differences in the longitudinal trends of DBP among birth cohorts, particularly for men, with higher DBP levels in the younger cohort. The present analysis demonstrated a small but statistically significant effect of ionizing radiation on the longitudinal trends of both SBP and DBP. This phenomenon is compatible with the degenerative effect of ionizing radiation on blood vessels. [Copyright &y& Elsevier]

The authors examined risk factors for benign thyroid nodules and their influence on radiation effects among 544 subjects who were exposed to childhood radiation treatment for benign head and neck conditions at a Chicago, Illinois hospital during 1939-1962. In follow-up through 1991, benign thyroid nodules were diagnosed in 131 patients. The risk of benign nodules was elevated in women (relative risk (RR) = 2.2, 95% confidence interval (CI) 1.6-3.2), Jews (RR = 1.7, 95% CI 1.1-2.5), college graduates (RR = 1.8, 95% CI 1.2-2.8), and subjects whose mother had cancer (RR = 1.7, 95% CI 1.2-2.5). There were increasing trends for risk with increasing body mass index in women and decreasing height in men. Risk was increased for women who never married (RR = 3.7, 95% CI 1.6-7.3) or who never had a full-term pregnancy (RR = 2.0, 95% CI 1.1-3.3). A significant radiation dose-response relationship was observed that was not modified by sex, education, Jewish religion, or reproductive factors. The data suggest that there are genetic, life-style (including ascertainment), and hormonal factors associated with the development of benign thyroid nodules. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing autologous hematopoietic cell transplantation (HCT) have a >2‐fold risk of developing cardiovascular disease (CVD; heart failure, myocardial infarction, and stroke), compared to the general population. Coronary artery calcium (CAC) is predictive of CVD in nononcology patients but is not as well studied in patients who underwent HCT and survivors of HCT.The objective of this study was to examine the association between CAC and CVD risk and outcomes after HCT in patients with lymphoma. Methods: This was a retrospective cohort study of 243 consecutive patients who underwent a first autologous HCT for lymphoma between 2009 and 2014. CAC (Agatston score) was determined from chest computed tomography obtained <60 days from HCT. Multivariable Cox regression analysis was used to calculate hazard ratio (HR) estimates and 95% confidence intervals (CIs), adjusted for covariates (age, conventional risk factors [e.g., hypertension and dyslipidemia], and cancer treatment). Results: The median age at HCT was 55.7 years (range, 18.5–75.1 years), 59% were male, and 60% were non‐Hispanic White. The prevalence of CAC was 37%. The 5‐year CVD incidence for the cohort was 12%, and there was an incremental increase in the incidence according to CAC score: 0 (6%), 1–100 (20%), and >100 (32%) (p =.001). CAC was significantly associated with CVD risk (HR, 3.0; 95% CI, 1.2–7.5) and worse 5‐year survival (77% vs. 50%; p <.001; HR, 2.0; 95% CI, 1.1–3.4), compared to those without CAC. Conclusions: CAC is independently associated with CVD and survival after HCT. This highlights the importance of integrating readily available imaging information in risk stratification and decision‐making in patients undergoing HCT, which sets the stage for strategies to optimize outcomes after HCT. Hematopoietic cell transplantation (HCT) survivors have an increased risk of cardiovascular disease (CVD) compared to the general population, and therefore thorough assessment of cardiovascular risk before HCT is essential. This study showed that the coronary artery calcium (CAC) score, obtained from routine pretransplant imaging, is significantly associated with CVD posttransplant and is a useful addition to traditional cardiovascular risk factors. Further prospective studies are needed to understand how CAC screening should be formally incorporated into pretransplant workup, cardiovascular risk assessment, and clinical decision‐making and its effect on posttransplant outcomes. [ABSTRACT FROM AUTHOR]

Background: Blood or marrow transplantation (BMT) survivors carry a high burden of morbidity, yet health care utilization by this vulnerable population remains understudied. Patterns and predictors of various domains of health care utilization in long‐term BMT survivors were evaluated. Methods: Study participants were drawn from the Bone Marrow Transplant Survivor Study (BMTSS). Patients transplanted between 1974 and 2014 at one of three transplant centers who had survived ≥2 years after BMT and were aged ≥18 years at the time of the study were included. A BMTSS survey served as the source of data for health care utilization, sociodemographics, and chronic health conditions. Domains of health care utilization in the 2 years preceding study participation included routine checkups, BMT‐related visits, transplant/cancer center visits, emergency room (ER) visits, hospitalizations, and high health care utilization (≥7 physician visits during the 2 years before the study). Clinical characteristics and therapeutic exposures were abstracted from medical records. Results: In this cohort of 3342 BMT survivors (52% allogeneic), the prevalence of health care utilization declined over time since BMT for both allogeneic and autologous BMT survivors, such that among those who had survived ≥20 years, only 49%–53% had undergone routine checkups, 37%–38% reported BMT‐related visits, and 28%–29% reported transplant/cancer center visits. The presence of severe/life‐threatening conditions and chronic graft‐vs‐host disease increased the odds of health care utilization across all domains. Lower education, lack of insurance, and Hispanic ethnicity were associated with a lower prevalence of routine checkups and/or transplant/cancer center visits. Lower income increased the odds of ER visits but reduced the odds of hospitalizations or high health care utilization. Conclusions: This study identified vulnerable populations of long‐term BMT survivors who would benefit from specialized risk‐based anticipatory care to reduce high health care utilization, ER visits, and hospitalizations. Health care utilization (including routine medical checkups) declines with increasing time since blood or marrow transplantation, except among survivors with severe/life‐threatening chronic health conditions as well as those with chronic graft‐vs‐host disease. Lower education and lack of insurance are associated with lower health care utilization. [ABSTRACT FROM AUTHOR]

Carvedilol improves cardiac function in patients with heart failure but remains untested as cardioprotective therapy in long-term childhood cancer survivors (ie, those who have completed treatment for childhood cancer and are in remission) at risk for heart failure due to high-dose anthracycline exposure. We aimed to evaluate the activity and safety of low-dose carvedilol for heart failure risk reduction in childhood cancer survivors at highest risk for heart failure. PREVENT-HF was a randomised, double-blind, phase 2b trial done at 30 hospitals in the USA and Canada. Patients were eligible if they had any cancer diagnosis that resulted in at least 250 mg/m2 cumulative exposure to anthracycline by age 21 years; completed their cancer treatment at least 2 years previously; an ejection fraction of at least 50% or fractional shortening of at least 25%, or both; and bodyweight of at least 40 kg. Patients were randomly assigned (1:1) with automated computer-generated permuted block randomisation (block size of 4), stratified by age at diagnosis, time since diagnosis, and history of chest-directed radiotherapy, to carvedilol (up-titrated from 3·125 g per day to 12·5 mg per day) or placebo orally for 2 years. Participants, staff, and investigators were masked to study group allocation. The primary endpoint was to establish the effect of carvedilol on standardised left ventricular wall thickness–dimension ratio Z score (LVWT/Dz). Treatment effects were analysed with a linear mixed-effects model for normally distributed data with a linear time effect and testing the significance of treatment*time interaction in the modified intention-to-treat (mITT) cohort (ie, all randomly assigned participants who had a baseline and at least one subsequent echocardiogram measurement). Safety was assessed in the ITT population (ie, all randomly assigned participants). This trial was registered with ClinicalTrials.gov , NCT027175073 , and enrolment and follow-up are complete. Between July 3, 2012, and June 22, 2020, 196 participants were enrolled, of whom 182 (93%) were eligible and randomly assigned to either carvedilol (n=89) or placebo (n=93; ITT population). Median age was 24·7 years (IQR 19·6–36·6), 91 (50%) participants were female, 91 (50%) were male, and 119 (65%) were non-Hispanic White. As of data cutoff (June 10, 2022), median follow-up was 725 days (IQR 378–730). 151 (n=75 in the carvedilol group and n=76 in the placebo group) of 182 participants were included in the mITT population, among whom LVWT/Dz was similar between the two groups (−0·14 [95% CI −0·43 to 0·16] in the carvedilol group vs −0·45 [−0·77 to −0·13] in the placebo group; difference 0·31 [95% CI –0·10 to 0·73]; p=0·14). Two (2%) of 89 patients in the carvedilol group two adverse events of grade 2 or higher (n=1 shortness of breath and n=1 arthralgia) and none in the placebo group. There were no adverse events of grade 3 or higher and no deaths. Low-dose carvedilol appears to be safe in long-term childhood cancer survivors at risk for heart failure, but did not result in significant improvement of LVWT/Dz compared with placebo. These results do not support the use of carvedilol for secondary heart failure prevention in anthracycline-exposed childhood cancer survivors. National Cancer Institute, Leukemia & Lymphoma Society, St Baldrick's Foundation, Altschul Foundation, Rally Foundation, American Lebanese Syrian Associated Charities. [ABSTRACT FROM AUTHOR]

Purpose: Data regarding changes in functional status and health-related quality of life (HRQOL) before and after surgery are lacking. We identified colorectal cancer patients from the SEER-Medicare Health Outcomes Survey (MHOS) linked database to evaluate the association between HRQOL and survival.Methods: HRQOL survey data captured physical/mental health, activities of daily living (ADLs), and medical comorbidities. Patients who underwent surgery with HRQOL surveys prior to cancer diagnosis and ≥ 1 year after diagnosis were selected. Patient, disease, and HRQOL measures were analyzed in regard to overall survival (OS), disease-specific survival (DSS), and non-DSS.Results: Of 590 patients included, 55% were female, 75% were Caucasian, and 83% had colonic primary. Disease extent was localized for 52%, regional for 41%, and distant for 7%. Median OS was 83 months. Decreased OS was independently associated with age ≥ 75 (HR 1.7, p < 0.0001), male sex (HR 1.4, p = 0.011), advanced disease (regional-HR 2.0, p < 0.0001; distant-HR 7.0, p < 0.0001), and decreased mental HRQOL (HR 1.4, p = 0.005). Decreased DSS was independently associated with advanced disease (regional-HR 4.1, p < 0.0001; distant-HR 16.5, p < 0.0001) and rectal primary (HR 1.6, p = 0.047). Decreased non-DSS was independently associated with age ≥ 75 (HR 2.2, p < 0.0001), male sex (HR 1.4, p = 0.03), decreased mental HRQOL (HR 1.4, p = 0.02), and increased comorbidities (HR 1.4, p = 0.04).Conclusions: The potential overall survival benefit of oncologic surgery is diminished by declines in physical and mental health. Early identification of older surgical patients at risk for functional and HRQOL declines may improve survival following colorectal cancer surgery. [ABSTRACT FROM AUTHOR]

Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC). Emerging data suggest that these agents can result in clinically significant cardiotoxicity, compromising the care. We conducted a prospective longitudinal study to evaluate the incidence of de novo cardiac dysfunction as assessed by echocardiography and blood biomarkers in mRCC patients receiving TKI with or without ICI followed at baseline, 3-month and 6-month. We recruited consecutive newly diagnosed mRCC patients treated at our institution between 2015 and 2018 as well as patients with localized RCC not treated with systemic therapies and healthy control (HC) subjects for comparison. Twenty-eight patients were enrolled in the mRCC group (a mean age of 65.2 ± 7.5 years), 29 patients in the localized RCC group (63.6 ± 8.9 years), and 20 volunteers in the HC group (52.9 ± 9.6 years). At baseline, patients from all three groups had normal cardiac function as measured by left ventricular ejection fraction (LVEF), although patients with mRCC or localized RCC had significantly lower mean LVEF compared to HC (61.9%, 62.4%, and 68.1% respectively). Otherwise, there were no statistically significant changes in echocardiographic parameters or incidence of clinical heart failure from baseline to 6-months in patients with mRCC. Cardiac blood biomarkers including troponin I, brain natriuretic peptide, and galectin-3 remained stable over time. Our findings suggest that contemporary treatment strategies of mRCC at this single institution are well tolerated without clinically meaningful overt declines in cardiac function over time. Further studies are warranted to include a larger number of patients to better assess the overall cardiovascular safety associated with contemporary treatments of mRCC. • Contemporary treatments of metastatic renal cell carcinoma (mRCC) include tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) but their cardiovascular safety has not been well documented. • We conducted a prospective longitudinal study to evaluate the incidence of de novo cardiac dysfunction in mRCC patients receiving TKI with or without ICI. • Our findings suggest that contemporary treatment strategies of mRCC at this single institution are well tolerated without clinically meaningful overt cardiac dysfunction. • Further studies are warranted to include a larger number of patients to better assess the overall cardiovascular safety associated with contemporary treatments of mRCC. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing hematopoietic cell transplantation (HCT) are at high risk of chronic health complications, including frailty and physical dysfunction. Conventional exercise programs have been shown to improve frailty in other cancer populations, but these have largely been based out of rehabilitation facilities that may act as geographic and logistical barriers. There is a paucity of information on the feasibility of implementing telehealth exercise interventions in long-term HCT survivors. Methods: We conducted a pilot randomized trial to assess the feasibility of an 8-week telehealth exercise intervention in 20 pre-frail or frail HCT survivors. Participants were randomized to either a telehealth exercise (N = 10) or delayed control (N = 10). We administered a remote physical function assessment at baseline, followed by an 8-week telehealth exercise intervention (30-60 min/session, 3 sessions/week), and post-intervention. The primary endpoint was feasibility as determined by 1) > 70% of participants completing all remote physical functional assessments, and 2) > 70% of participants in the exercise group completing > 70% (17/24) of the prescribed exercise sessions. Exploratory outcomes included changes in gait speed, handgrip strength, and short physical performance battery. Results: The mean [standard deviation] age at study enrollment was 64.7 [9.1] years old. Twelve had undergone allogenic and 8 had undergone autologous HCT at an average of 17 years from study enrollment. Both feasibility criteria were achieved. Nineteen patients (95%) completed all remote study outcome assessments at baseline and post-intervention, and nine participants in the exercise group completed > 70% of prescribed exercise sessions. Overall, no significant group x time interaction was observed on handgrip strength, fatigue, body mass index, and short physical performance battery test (P < 0.05). However, there were significant within-group improvements in four-meter gait speed (+ 13.9%; P = 0.004) and 5-minute gait speed (+ 25.4%; P = 0.04) in the exercise group whereas non-significant changes in four-meter gait speed (-3.8%) and 5-minute gait speed (-5.8%) were observed after 8 weeks. Conclusion: Implementing an 8-week telehealth exercise intervention for long-term HCT survivors was feasible. Our findings set the stage for innovative delivery of supervised exercise intervention that reduces the burden of frailty in HCT survivors as well as other at-risk cancer survivors. Trial registration: The protocol and informed consent were approved by the institutional IRB (IRB#20731) and registered (ClinicalTrials.gov NCT04968119; date of registration: 20/07/2021). [ABSTRACT FROM AUTHOR]

Background: A comprehensive assessment of morbidity after allogeneic bone marrow transplantation (BMT) performed in childhood remains understudied. Methods: Seven hundred eighty‐nine allogeneic BMT recipients who had survived ≥2 years after BMT performed between 1974 and 2014 at age <22 years and 690 siblings completed a 255‐item survey self‐reporting sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life‐threatening], or 5 [fatal]) was assigned to the conditions using Common Terminology Criteria for Adverse Events, version 5.0. For the BMT cohort, the cumulative incidence of chronic health conditions was calculated as a function of time from BMT. Proportional subdistribution hazards models were used to determine predictors of grade 3–5 conditions. Logistic regression was used to estimate the risk of grade 3–4 conditions in BMT recipients who were alive at the time of this study compared with siblings. Results: The median age at transplantation was 11.3 years (range, 0.4–22.0 years), and the median length of follow‐up was 11.7 years (range, 2.0–45.3 years). The most prevalent primary diagnoses were acute lymphoblastic leukemia (30.7%), and acute myeloid leukemia/myelodysplastic syndrome (26.9%). At age 35 years, the cumulative incidence of a grade 3–4 condition was 53.8% (95% CI, 46.7%–60.3%). The adjusted odds ratio of a grade 3–4 condition was 15.1 in survivors (95% CI, 9.5–24.0) compared with siblings. The risk of a grade 3–5 condition increased with age at BMT (hazard ratio [HR], 1.03; 95% CI, 1.01–1.05) and was higher among females (HR, 1.27; 95% CI, 1.02–1.59), patients who received total body irradiation (HR, 1.71; 95% CI, 1.27–2.31), and those reporting chronic graft‐versus‐host disease (HR, 1.38; 95% CI, 1.09–1.74). Conclusions: Two‐year survivors of allogeneic BMT in childhood have an increased risk of grade 3–4 chronic health conditions compared with siblings, suggesting the need for long‐term follow‐up. Two‐year survivors of allogeneic bone marrow transplantation in childhood have a substantially increased risk of chronic health conditions compared with siblings. By age 35 years, more than one half of bone marrow transplantation recipients had a severe or life‐threatening chronic health condition. [ABSTRACT FROM AUTHOR]

Background: Blood or marrow transplantation (BMT) is increasingly offered to older individuals with hematologic malignancies. The high prevalence of chronic health conditions in such individuals necessitates use of multiple medications. Beers Criteria represent a list of potentially inappropriate medications (PIMs) shown to increase the risk of health problems in the elderly. We sought to determine the prevalence and predictors of PIM use in older BMT survivors and identify associations with health problems. Methods: Study participants were drawn from the BMT Survivor Study, a cohort study of patients transplanted at three US transplant centers between 1974 and 2014 and surviving ≥2 years. For this report, the survivors were aged ≥65 years. Siblings served as a comparison group. Participants self‐reported sociodemographics, chronic health conditions, and medication use. Logistic regression analyses identified predictors of PIM use and associations with health problems. Results: Overall, PIM use was comparable between BMT survivors (49.4%) and siblings (49.3%) (odds ratio [OR] = 0.9; 95% CI, 0.7–1.2); however, BMT survivors were more likely to use >1 PIM (17.4% vs. 12.4%; OR = 1.5; 95% CI, 1.01–2.4) and central nervous system–related PIMs (8.3% vs. 4.3%; OR = 2.18; 95% CI, 1.17–4.09). Predictors of PIM use included presence of severe/life‐threatening chronic health conditions (OR = 1.5; 95% CI, 1.1–2.0), and chronic graft versus host disease (OR = 1.7; 95% CI, 1.1–2.7). Survivors taking >1 PIM reported more issues with vertigo (OR = 2.3; 95% CI, 1.1–4.7), balance (OR = 2.6; 95% CI, 1.7–4.1), faintness/dizziness (OR = 2.8; 95% CI, 1.8–4.6), and personal care (OR = 4.5; 95% CI, 1.4–14.8). Conclusions: This study shows the health problems associated with PIM use and identifies vulnerable populations at higher risk for PIM use, providing evidence for caution in using PIMs in high‐risk populations. Older blood or marrow transplantation survivors were more likely to use multiple potentially inappropriate medications than a sibling comparison group. Survivors with multimorbidity and/or chronic graft versus host disease were more likely to use these medications; survivors taking multiple potentially inappropriate medications reported several health problems. [ABSTRACT FROM AUTHOR]