Low-risk Survivors Research Articles

Demand for oncology visits among low-risk breast cancer survivors.

490 Background: The number of breast cancer (BC) survivors in the United States is large and rapidly growing. An unsustainable number of survivors receive care from oncology providers indefinitely, with a disproportionate number of those being white, high socioeconomic women, potentially contributing to disparities in care. Demand for oncology visits among low-risk BC survivors may decrease access to care for more complex, vulnerable survivors and new cancer patients and increase costs without improving quality of care, but has not been quantified. Our study's objective was to quantify demand for oncology visits among low-risk survivors. Methods: We utilized Atrium Health Wake Forest Baptist Comprehensive Cancer Center cancer registry data and electronic medical record data to identify BC survivors with scheduled appointments with an oncology physician from 7/1/2023 to 7/1/2024, excluding patients with Stage IV disease. We defined low-risk BC survivors as those with ductal carcinoma in situ (DCIS) or Stage I BC >5 years from diagnosis, or any survivor >10 years from diagnosis without evidence of recurrence. We used descriptive statistics to quantify demand for oncology visits among low-risk survivors. Results: We identified 877 BC survivors with a scheduled oncology appointment. Of those, 128 (14.5%), were classified as low-risk and possibly transition-eligible, including 50 with DCIS and 66 with Stage I BC >5 years from diagnosis and 57 who were >10 years post-diagnosis. Conclusions: We developed an efficient method to identify low-risk BC survivors actively receiving oncology physician care. While there are limitations, such as incomplete data and lack of analytic support at smaller institutions, this is an adoptable approach to identify survivors eligible for transition of care to an oncology advanced practice provider or primary care provider. Interventions to improve transitions, and thus increase access and quality of oncologic care, must be prioritized in the face of growing numbers of survivors, rapid therapeutic advances, and oncology physician burnout.[Table: see text]

Predicting therapy-induced cardiomyopathy in long-term survivors of childhood cancer: A report from the St. Jude Lifetime Cohort (SJLIFE) and the Childhood Cancer Survivor Study (CCSS).

12018 Background: Cancer-therapy-induced cardiomyopathy (CCM) is the leading noncancer cause of mortality among long-term survivors of childhood cancer, the prevalence of which increases with age. Early identification of survivors at risk provides opportunities for targeted prevention strategies. Here, we developed and validated a clinically applicable CCM prediction model based on survivor characteristics, treatment exposures and inherited genetic variation among long-term survivors of childhood cancer. Methods: Long-term survivors from SJLIFE (training cohort; n = 3,350; median age 34 years, range 8-72 years) and CCSS (validation cohort; n = 7,008; median age 36 years, range 11-64 years) were assessed by the five different general population polygenic risk scores (multiPRS) for dilated cardiomyopathy, hypertrophic cardiomyopathy, heart failure, ejection fraction and left ventricular end systolic volume. Multivariable logistic regression was used to predict 15-year risk of the CCM (defined as CTCAE grade ≥3 cardiomyopathy requiring heart failure medications or heart transplantation or leading to death). Model performance was assessed by the area under the receiver operating characteristic curve (AUC). Results: CCM was clinically identified in 150 (4.5%) SJLIFE and self-reported in 156 (2.1%) CCSS survivors, respectively. AUC of clinical models with attained age, sex, age at primary cancer diagnosis, cumulative anthracycline dose, mean heart radiation dose (heart RT), and genetic ancestry was 0.81 (95% CI, 0.78-0.85) in SJLIFE and 0.78 (95% CI, 0.74-0.81) in CCSS. Inclusion of cardiovascular risk factors (hypertension, dyslipidemia, and diabetes) significantly increased AUC to 0.83 (95% CI, 0.80-0.87; P= 0.011; SJLIFE) and 0.84 (95% CI, 0.80-0.87; P< 0.001; CCSS). The addition of the multiPRS further provided significant but modest increases in AUC in SJLIFE (0.84; 95% CI, 0.81-0.87; P= 0.022) and CCSS (0.85; 95% CI, 0.81-0.88; P= 0.031). In low-risk survivors (exposed to < 100 mg/m2 anthracyclines and < 15 Gray heart RT), we observed a possibly larger magnitude AUC increase after adding multiPRS, 0.73 (95% CI, 0.65-0.82) to 0.76 (95% CI, 0.68-0.83; P= 0.11) in SJLIFE and 0.77 (95% CI, 0.65-0.90) to 0.82 (95% CI, 0.69-0.94; P= 0.073) in CCSS. Conclusions: Inherited polygenic factors contributed significantly to improve CCM prediction over available clinical risk factors and may be of benefit to low-risk survivors for whom routine cardiac surveillance is not currently recommended.

Real-world risk-stratified cancer survivorship pathways.

36 Background: Risk-stratified survivorship care pathways are critical for meeting needs of cancer survivors and the oncology workforce. To support a clinical trial evaluating a survivorship model that transitions low-risk survivors to a primary care physician (PCP)-led survivorship clinic within an integrated healthcare system, we captured data on real-time clinical risk stratification of low-risk patients potentially eligible between 6 and 36 months after treatment cessation. Methods: After oncology stakeholder input, we developed a screening algorithm to identify low-risk breast and colorectal cancer (CRC) survivors from the electronic medical record based on data from pathology, treatment, and utilization records. The algorithm identified patients meeting study eligibility criteria: adult stage 0-IIb breast cancer or stage I-II CRC patients diagnosed with first primary cancer, excluding those with treatments indicative of high-risk or metastatic disease, ongoing ovarian suppression or trastuzumab treatment (breast), neoadjuvant chemotherapy (breast), or enrollment in other cancer clinical trials. Next, the treating oncologist was asked to confirm or deny patient eligibility based on low-risk criteria; if denied, ineligibility reason was requested. Characteristics and proportions of low-risk patients confirmed/denied eligibility and reasons for ineligibility are summarized. Results: 530 patients were identified and evaluated: 488 breast and 42 CRC. Mean age was 61 years (SD: 11.6, range 23-95); 96% female; 22% had stage 0 disease (breast only), 51% stage I, and 28% stage II. By cancer type, 390 breast patients were deemed eligible (80%); 31 CRC patients were eligible (74%). A greater proportion of Asian and Black patients were categorized eligible vs. ineligible (13% vs. 9%, and 25% vs.14%, respectively), and a smaller proportion of Hispanic and White were categorized eligible (26% vs. 33%, and 31% vs. 42%, respectively). Reasons for ineligibility included: suspicious for recurrence (6%), new primary disease (3%), complex case/condition (36%), patient preference (34%), and other/none (22%). “Complex case/condition” included reasons such as intolerance of chemotherapy, patient declined chemotherapy and/or endocrine treatment (breast), co-occurring hematology disorder; “other/none” included reasons such as current pregnancy Lynch syndrome, and no reason. Conclusions: Oncologists confirmed eligibility for 80% of algorithm-identified low-risk patients for referral to the PCP-led survivorship clinic. Of those ineligible, patient preference and complex case/condition were the most common reasons reported for ineligibility. Consensus-based risk algorithms supported by clinician review can quickly and effectively perform case identification of low-risk patients who may be appropriately transitioned to other settings for survivorship care.

Treatment exposure-based risk-stratification for care of survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.

10056 Background: Treatment exposure-based risk-stratification oflong-term cancer survivors is needed to allocate tailored health care in survivorship clinics. Investigators from the United Kingdom (UK) developed a treatment exposure-based algorithm that stratifies survivors into low, medium, and high risk groups. Because this algorithm has not been validated, we sought to use the large, diverse population of the Childhood Cancer Survivor Study (CCSS) to validate risk for poor outcomes. Methods: Five-year survivors of childhood cancer (diagnosed between 1970-1999 at < 21 years of age) were categorized into low, medium, and high risk groups based on treatment exposures and diagnoses (Table). Primary endpoints included cumulative health-related (i.e., non-recurrence, non-external) late mortality and cumulative incidence of grade 3-5 chronic conditions (CTCAEv4.03) conditional on reaching age 20 without the outcome. Siblings were a comparison group for chronic conditions. Cox proportional hazards models among survivors estimated hazard ratios (HRs) and 95% confidence intervals (CI) adjusted for sex and race. Results: A total of 21,504 survivors were analyzed with a median follow-up of 22 years. Application of the risk stratification algorithm resulted in 3,152 low risk, 6,443 medium risk, and 11,909 high risk survivors. Among those who survived to age 20 without any grade 3-5 conditions, the risk of developing one by age 35 was 12.2% (95% CI 1.0-14.7%), 14.2% (12.8-15.7%) and 25.4% (24.2-26.6%) for low, medium, and high-risk patients, respectively, and 6.9% (6.1-7.9%) for siblings. HRs of grade 3-5 conditions for medium (HR 1.8, 95% CI 1.6-2.1) and high (HR 3.9, 95% CI 3.5-4.4) risk relative to low risk survivors, respectively, were elevated. Cumulative health-related mortality was similarly associated with risk categories; conditional on being alive at age 20, survivors within low, medium, and high risk groups had cumulative incidences of 2.3% (95% CI 1.7-3.1%), 3.3% (2.8-3.9%) and 6.1% (5.6-6.6%), respectively, by age 35. Conclusions: Risk categorizations based on treatment exposures were effective at providing generalized risk stratification within the CCSS with respect to risk of grade 3-5 conditions and health related mortality, particularly for identifying high risk survivors. These risk groups may be useful to physicians in determining follow-up intervals and guiding management and long-term surveillance of these survivors. [Table: see text]

Associations between global longitudinal strain (GLS), N-terminal-prohormone brain natriuretic peptide (NT-proBNP) and subsequent cardiomyopathy (CM) in a clinically assessed cohort of childhood cancer survivors exposed to cardiotoxic therapy.

10052 Background: Among survivors exposed to anthracycline or chest radiation (RT) who have an ejection fraction (EF) of ≥50%, the utility of GLS and NT-proBNP to identify survivors who are at highest risk for future CM is unknown. Methods: Survivors participating in the St. Jude Lifetime Cohort, ≥5 years from cancer diagnosis and at risk for CM per the International Guideline Harmonization Group (IGHG), underwent baseline surveillance echocardiography. A baseline GLS and NT-proBNP was also performed for survivors with an EF ≥50%. Multivariable Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of CM (graded per modified Common Terminology Criteria for Adverse Events v4.0) based on abnormal baseline GLS (≥ -18) and/or NT-proBNP (>age-sex-specific 97.5th percentiles) adjusted for age at baseline assessment, age at diagnosis, sex, race, hypertension, diabetes, obesity, and IGHG risk group (Table footnote). Results: Among 1598 at-risk survivors (median age 35.1, range 9.4-68.8 years), all had GLS and 1110 NT-proBNP at baseline. 165 (10.3%) developed CM ≥ grade 2 at a median follow-up of 5.2 (0.7-10.0) years. IGHG moderate- and high-risk survivors exposed to anthracyclines were at increased risk of CM at follow-up if both baseline GLS and NT-proBNP were abnormal (HR=3.4, 95% CI: 1.9-5.8; Table) or GLS was abnormal and NT-proBNP not assessed (HR=3.8, 95% CI: 2.0-7.2), or when GLS was normal and NT-proBNP was abnormal (HR=1.9, 95% CI: 1.1-3.4). Abnormal GLS and/or NT-proBNP were not associated with increased risk of CM in IGHG low-risk survivors or in those defined as moderate- to high-risk due to chest RT only. Conclusions: Among long-term survivors of childhood cancer exposed to >100 mg/m2 anthracycline, abnormal GLS and NT-proBNP identified those survivors at increased risk of future CM despite an EF ≥50% on surveillance echocardiography. Conditional surveillance strategies utilizing GLS and NT-proBNP may benefit moderate- to high-risk survivors. [Table: see text]

Feasibility and preliminary effectiveness of a cancer survivorship care delivery intervention.

19 Background: A large and rapidly increasing number of US cancer survivors who have completed active treatment continue to seek oncology care. Low-risk survivors who continue to seek oncology care incur greater costs but experience worse care quality and outcomes than those who seek primary care. In this study, we assessed the feasibility and preliminary effectiveness of START (Supporting Transitions AfteR Treatment), a theory-driven, stakeholder-engaged intervention intended to improve the transition of low-risk survivors to primary care. Methods: To pilot START, beginning in August 2020, we engaged oncology providers (n = 5) and staff (n = 4) at a small community affiliate of our academic comprehensive cancer center. We worked with a nurse navigator, office manager, and physician champion to refine START’s content and delivery to accommodate the needs of a busy community cancer center. We queried electronic health records (EHRs) to assess the feasibility of identifying low-risk survivors and measuring key outcomes (i.e., receipt of recommended health maintenance services). In a formal meeting, we introduced providers to START and helped them to identify survivors whom they agreed should be transitioned to primary care. Front desk staff flagged these survivors to remind providers to transition them in upcoming appointments. Beginning in July 2021, we will conduct in-depth, semi-structured interviews with oncology providers and staff and survivors regarding their perspectives on START’s acceptability, appropriateness, and feasibility. Results: We successfully identified survivors using EHRs and engaged the nurse navigator and providers in identifying the subset of survivors whom they deemed eligible for transitioning to primary care. Preliminary results indicate that START helped providers to transition eligible survivors to primary care. We have successfully engaged cancer center data managers in measuring relevant outcomes using EHRs. Informal provider and staff feedback suggests that START is an acceptable, appropriate, and feasible approach to transitioning survivors. Conclusions: At the conference, we will report on oncology provider and staff and survivor perceptions of START’s acceptability, appropriateness, and feasibility for improving survivorship care delivery and preliminary findings regarding START’s effectiveness in increasing survivors’ receipt of recommended health maintenance services. Findings will be used to refine START and form the basis of a clinical trial to evaluate its effectiveness in improving survivorship outcomes.

Refining the 10-Year Prediction of Left Ventricular Systolic Dysfunction in Long-Term Survivors of Childhood Cancer

BackgroundIn childhood cancer survivors (CCS) at risk for heart failure, echocardiographic surveillance recommendations are currently based on anthracyclines and chest-directed radiotherapy dose. Whether the ejection fraction (EF) measured at an initial surveillance echocardiogram can refine these recommendations is unknown. ObjectivesThe purpose of this study was to assess the added predictive value of EF at >5 years after cancer diagnosis to anthracyclines and chest-directed radiotherapy dose in CCS, for the development of left ventricular dysfunction with an ejection fraction <40% (LVD40). MethodsEchocardiographic surveillance was performed in 299 CCS from the Emma Children’s Hospital in the Netherlands. Cox regression models were built including cardiotoxic cancer treatment exposures with and without EF to estimate the probability of LVD40 at 10-year follow-up. Calibration, discrimination, and reclassification were assessed. Results were externally validated in 218 CCS. ResultsCumulative incidences of LVD40 at 10-year follow-up were 3.7% and 3.6% in the derivation and validation cohort, respectively. The addition of EF resulted in an integrated area under the curve increase from 0.74 to 0.87 in the derivation cohort and from 0.72 to 0.86 in the validation cohort (likelihood ratio p < 0.001). Reclassification of CCS without LVD40 improved significantly (noncase continuous net reclassification improvement 0.50; 95% confidence interval [CI]: 0.40 to 0.60). A predicted LVD40 probability ≤3%, representing 75% of the CCS, had a negative predictive value of 99% (95% CI: 98% to 100%) for LVD40 within 10 years. However, patients with midrange EF (40% to 49%) at initial screening had an incidence of LVD40 of 11% and a 7.81-fold (95% CI: 2.07- to 29.50-fold) increased risk of LV40 at follow-up. ConclusionsIn CCS, an initial surveillance EF, in addition to anthracyclines and chest-directed radiotherapy dose, improves the 10-year prediction for LVD40. Through this strategy, both the identification of low-risk survivors in whom the surveillance frequency may be reduced and a group of survivors at increased risk of LVD40 could be identified.

Echocardiography for the 10-year prediction of cardiomyopathy in long-term survivors of childhood cancer

Abstract Background Childhood cancer survivors (CCS) treated with anthracyclines and/or chest-directed radiotherapy receive life-long echocardiographic surveillance to detect cardiomyopathy early. Current risk stratification and surveillance frequency recommendations are based on anthracycline- and chest-directed radiotherapy dose. We assessed the added prognostic value of an initial left ventricular ejection fraction (EF) measurement at &amp;gt;5 years after cancer diagnosis. Patients and methods Echocardiographic follow-up was performed in asymptomatic CCS from the Emma Children's Hospital (derivation; n=299; median time after diagnosis, 16.7 years [inter quartile range (IQR) 11.8–23.15]) and from the Radboud University Medical Center (validation; n=218, median time after diagnosis, 17.0 years [IQR 13.0–21.7]) in the Netherlands. CCS with cardiomyopathy at baseline were excluded (n=16). The endpoint was cardiomyopathy, defined as a clinically significant decreased EF (EF&amp;lt;40%). The predictive value of the initial EF at &amp;gt;5 years after cancer diagnosis was analyzed with multivariable Cox regression models in the derivation cohort and the model was validated in the validation cohort. Results The median follow-up after the initial EF was 10.9 years and 8.9 years in the derivation and validation cohort, respectively, with cardiomyopathy developing in 11/299 (3.7%) and 7/218 (3.2%), respectively. Addition of the initial EF on top of anthracycline and chest radiotherapy dose increased the C-index from 0.75 to 0.85 in the derivation cohort and from 0.71 to 0.92 in the validation cohort (p&amp;lt;0.01). The model was well calibrated at 10-year predicted probabilities up to 5%. An initial EF between 40–49% was associated with a hazard ratio of 6.8 (95% CI 1.8–25) for development of cardiomyopathy during follow-up. For those with a predicted 10-year cardiomyopathy probability &amp;lt;3% (76.9% of the derivation cohort and 74.3% of validation cohort) the negative predictive value was &amp;gt;99% in both cohorts. Conclusion The addition of the initial EF &amp;gt;5 years after cancer diagnosis to anthracycline- and chest-directed radiotherapy dose improves the 10-year cardiomyopathy prediction in CCS. Our validated prediction model identifies low-risk survivors in whom the surveillance frequency may be reduced to every 10 years. Calibration in both cohorts Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Dutch Heart Foundation

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

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. 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/m2 and/or radiotherapy < 15 Gy], moderate [100 to < 250 mg/m2 or 15 to < 35 Gy], or high [≥ 250 mg/m2 or ≥ 35 Gy or both ≥ 100 mg/m2 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. 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. 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.

Cost-effectiveness of screening guidelines to prevent heart failure in childhood cancer survivors: A report from the Childhood Cancer Survivor Study (CCSS).

10052 Background: Childhood cancer survivors treated with anthracyclines or chest radiation therapy (RT) are at risk for left ventricular dysfunction (LVD) and subsequent heart failure (HF). The International Guideline Harmonization Group (IGHG) recommends risk-based screening echocardiograms for LVD, but evidence supporting its frequency and cost-effectiveness is limited. Methods: Using data from the CCSS, we developed a microsimulation model of the clinical course of LVD and HF to estimate long-term health and economic outcomes associated with screening for IGHG-defined risk groups (low [anthracycline 1-99 mg/m2 and/or RT &lt; 15 Gy], moderate [100 to &lt; 250 mg/m2 or 15 to &lt; 35 Gy], high [≥ 250 mg/m2 or ≥ 35 Gy or (≥ 100 mg/m2 and ≥ 15 Gy)]). We compared 1, 2, and 5-year interval-based screening to no screening. Screening performance and pharmacological treatment effectiveness were based on published studies. Costs and quality of life weights were based on US averages and published studies. Outcomes included lifetime HF risk, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Strategies with ICERs &lt; $100,000/QALY gained were considered cost-effective. Results: Among the IGHG risk groups, the lifetime HF risk in the absence of screening was 37% (high), 25% (moderate) and 17% (low). Screening every 2 or 5 years was cost-effective for the high-risk group, and every 5 years for the moderate-risk group. In contrast, routine screening may not be cost-effective for the low risk group, representing ~40% of those for whom screening is currently recommended. Conclusions: Our findings can inform screening guidelines and suggest that LVD/HF surveillance for low-risk survivors warrants careful consideration. [Table: see text]

Oncologist or primary care for low-risk cancer survivors?

Oncologist or primary care for low-risk cancer survivors?

The occurrence of adverse events in low-risk non-survivors in pediatric intensive care patients: an exploratory study

We studied the occurrence of adverse events (AEs) in low-risk non-survivors (LNs), compared to low-risk survivors (LSs), high-risk non-survivors (HNs), and high-risk survivors (HSs) in two pediatric intensive care units (PICUs). The study was performed as a retrospective patient record review study, using a PICU-trigger tool. A random sample of 48 PICU patients (0–18 years) was chosen, stratified into four subgroups of 12 patients: LNs, LSs, HNs, and HSs. Primary outcome was the occurrence of AEs. The severity, preventability, and nature of the indentified AEs were determined. In total, 45 AEs were found in 20 patients. The occurrence of AEs in the LN group was significantly higher compared to that in the LS group and HN group (AE occurrence: LN 10/12 patients, LS 1/12 patients; HN 2/12 patients; HS 7/12 patients; LN-LS difference, p < 0.001; LN-HN difference, p < 0.01). The AE rate in the LN group was significantly higher compared to that in the LS and HN groups (median [IQR]: LN 0.12 [0.07–0.29], LS 0 [0–0], HN 0 [0–0], and HS 0.03 [0.0–0.17] AE/PICU day; LN-LS difference, p < 0.001; LN-HN difference, p < 0.01). The distribution of the AEs among the four groups was as follows: 25 AEs (LN), 2 AEs (LS), 8 AEs (HN), and 10 AEs (HS). Fifteen of forty-five AEs were preventable. In 2/12 LN patients, death occurred after a preventable AE.Conclusion: The occurrence of AEs in LNs was higher compared to that in LSs and HNs. Some AEs were severe and preventable and contributed to mortality.What is Known:• 59–76% of all PICU patients encounter at least one adverse event during their PICU stay.• It is unknown if adverse events play a role in death of low-risk PICU patients.What is New:• In low-risk PICU non-survivors, occurrence of adverse events is higher compared to low-risk PICU survivors and to high-risk PICU non-survivors.• Severe and preventable adverse events occur in low-risk PICU non-survivors, some contributing to mortality.

Prediction of Ischemic Heart Disease and Stroke in Survivors of Childhood Cancer.

Purpose We aimed to predict individual risk of ischemic heart disease and stroke in 5-year survivors of childhood cancer. Patients and Methods Participants in the Childhood Cancer Survivor Study (CCSS; n = 13,060) were observed through age 50 years for the development of ischemic heart disease and stroke. Siblings (n = 4,023) established the baseline population risk. Piecewise exponential models with backward selection estimated the relationships between potential predictors and each outcome. The St Jude Lifetime Cohort Study (n = 1,842) and the Emma Children's Hospital cohort (n = 1,362) were used to validate the CCSS models. Results Ischemic heart disease and stroke occurred in 265 and 295 CCSS participants, respectively. Risk scores based on a standard prediction model that included sex, chemotherapy, and radiotherapy (cranial, neck, and chest) exposures achieved an area under the curve and concordance statistic of 0.70 and 0.70 for ischemic heart disease and 0.63 and 0.66 for stroke, respectively. Validation cohort area under the curve and concordance statistics ranged from 0.66 to 0.67 for ischemic heart disease and 0.68 to 0.72 for stroke. Risk scores were collapsed to form statistically distinct low-, moderate-, and high-risk groups. The cumulative incidences at age 50 years among CCSS low-risk groups were < 5%, compared with approximately 20% for high-risk groups ( P < .001); cumulative incidence was only 1% for siblings ( P < .001 v low-risk survivors). Conclusion Information available to clinicians soon after completion of childhood cancer therapy can predict individual risk for subsequent ischemic heart disease and stroke with reasonable accuracy and discrimination through age 50 years. These models provide a framework on which to base future screening strategies and interventions.

Identification and Characteristics of Low-Risk Survivors of an Acute Myocardial Infarction

There are limited contemporary data available describing the characteristics of patients who neither died nor were readmitted to the hospital during the first year after hospital discharge for an acute myocardial infarction (AMI) in comparison with those who died and/or were readmitted to the hospital during this high-risk period. Residents of the Worcester, Massachusetts, metropolitan area discharged after an AMI from 3 central Massachusetts hospitals on a biennial basis from 2001 to 2011 comprised the study population. The average age of this population (n= 4,268) was 69years, 62% were men, and 92% were white. From 2001 to 2011, 43.5% of patients were classified as low-risk survivors of an AMI, 12.3% died, and 44.2% did not die but had at least 1 rehospitalization during the subsequent year. The proportion of low-risk survivors increased from 42.6% to 46.4%, whereas the proportion of those who died within a year after hospital discharge decreased from 14.3% to 10.5%, respectively, during the years under study. After adjusting for several patient characteristics, younger (≤65years) persons, men, those who were married, those who did not present with multimorbidities, and patients who did not develop in-hospital clinical complications were more likely to be classified as a low-risk AMI survivor. Identifying low-risk survivors of an AMI may help health care providers to focus more intensive efforts and interventions on those at higher risk for dying and/or being readmitted to the hospital during the postdischarge transition period after an AMI.

Contrast Enhanced Cardiac CT Detects Coronary Artery Disease In 44% Of Asymptomatic Long-Term Adult Allogeneic Stem Cell Transplant Survivors

Long term allogeneic stem cell transplantation (allo-SCT) survivors face a 2.3 fold increase risk of premature cardiovascular (CV) related death compared to the general population. A reliable screening strategy to identify allo-SCT survivors at risk for CV-related disease is therefore warranted to minimize future events. Cardiac CT is an emerging non-invasive imaging technology with high sensitivity for detecting coronary artery disease (CAD) and high negative predictive value to exclude the presence of CAD. We conducted the first prospective non-randomized single institution study to evaluate Agatston coronary calcium scoring by CT with concomitant coronary CT angiograms as a tool to identify the survivors at risk for CV disease. Sixteen asymptomatic post allo-SCT survivors (11 males; 5 females) with median age of 45 years (range 22-66) at transplant underwent coronary calcium scoring and contrast enhanced coronary CT angiograms at a median follow up of 5 years post transplant. 10-year Framingham cardiovascular risk scores (incorporating age, sex, total cholesterol, HDL cholesterol, systolic BP, HTN, smoking status) were also calculated at time of screening. Two were classified as high risk, 1 intermediate and 13 as low risk. Iodinated IV contrast was administered for coronary artery visualization and IV hydration given to patients with decreased creatinine clearance. Non-obstructive CAD was detected in seven (44%) patients. Additionally, four (25%) of these subjects had aortic root calcification. Lesion distributions by arterial territory were: left main 5.8%, left anterior descending 35.3%, left circumflex 29.4% and right coronary artery 29.4%. Characteristics of coronary plaques were: 47% calcified, 47% mixed calcified / non-calcified, and 6% non-calcified. In those with CAD, the median coronary calcium score was 55 (range: 0-992) (p<0.001), corresponding to the 75th percentile (range: 33rd to 97th percentile) (p < 0.001) adjusted for age, gender, and ethnicity. In comparison, those without any CAD had a median coronary calcium score of 0, < 1 percentile. There was one patient with <1% Framingham cardiovascular risk score who had a zero coronary calcium score with non-obstructive CAD on the CT angiogram. The radiation exposure during the procedure was acceptable, at a median of 0.60 mSv (range 0.18 to 3.12 mSv) for the coronary calcium score and 0.85 mSv (range 0.34 to 8.01) for the coronary CT angiogram. There were no complications related to the procedure. Current (2010 AHA/ACC) guidelines suggest a role for coronary calcium scoring for screening asymptomatic non-transplant individuals with intermediate Framingham risk. However, we detected CAD in 4 of 13 (30.8%) low risk transplant survivors. Coronary calcium scoring alone (sensitivity of 85.7% and specificity of 100%) may be adequate for screening and avoids the use of IV contrast. In conclusion, coronary calcium score with or without CT angiogram is a safe, feasible, highly sensitive study in transplant survivors; even asymptomatic, low-risk survivors may benefit from screening.Table 1Coronary Calcium Scoring in Subjects With and Without CAD by AngiographyPresent CAD by CT angiographyAbsent CAD by CT angiographyp-valueAgatston coronary calcium scoreMedian 55 (range 0 to 992)0 (range 0 to 0)< 0.001Coronary Calcium score percentileMedian 75th % ile (range 0 to 97)< 1st % ile (range 0 to 0 )<0.001 Disclosures:No relevant conflicts of interest to declare.

Gene expression profiling and cardiac allograft rejection monitoring: Is IMAGE just a mirage?

The search for an effective non-invasive monitoring technique for cardiac allograft rejection eluded us until the discovery and validation of a commercially available gene-based peripheral blood bio-signature signal. The Invasive Monitoring Attenuation through Gene Expression (IMAGE) trial tested the hypothesis of cardiac biopsy minimization using this gene-based panel in stable, low-risk survivors, late after cardiac transplantation and demonstrated non-inferiority of this strategy. We present a clinician's critical perspective on this important effort and outline the key caveats and highlights for the potential way forward in using these results. Furthermore, we contend that it may not be necessary to replace an invasive cardiac biopsy strategy with anything other than better standardized clinical and functional allograft vigilance in low-risk survivors.

Conditional Survival After Surgical Treatment of Melanoma: An Analysis of the Surveillance, Epidemiology, and End Results Database

Survival curves following surgical treatment of cutaneous melanoma are heavily influenced by early deaths. Therefore, survival estimates may be misleading for long-term cancer survivors. We examined whether conditional survival (CS) is more accurate in predicting long-term melanoma survival. We used the Surveillance, Epidemiology, and End Results database (1992-2005) to identify patients who underwent surgical treatment for melanoma. We included patients with T2-T4 disease and with known nodal status. Patients were stratified into low-risk (T2-3N0M0) and high-risk (T4N0M0 or T2-4N1-3M0) categories. We defined CS as time-specific estimates conditioned on living to a certain point in follow-up, and calculated 10-year cancer-specific survival curves conditioned on annual survival. We adjusted for potential confounders using a Cox proportional hazards regression model (alpha = 0.05). A total of 8647 patients met inclusion criteria (low-risk, 5987 [69.2%]; high-risk, 2660 [30.8%]). At diagnosis, low-risk patients had a significantly better 10-year survival rate (low-risk, 79.6%; high-risk, 41.2%; P < 0.001). On CS analysis, survival differences remained until 8 years after treatment, after which 10-year cancer-specific survival rates were no longer significantly different (P = 0.51) for low-risk (95.4%) and high-risk (91.7%) groups. Multivariate analysis demonstrated that age, gender, location, and ulceration (initial predictors of survival) were no longer predictive after 8 years of survival. For patients who survive 8 years after surgical treatment of melanoma, CS data become discordant with traditionally used estimates. Our findings have important implications for patient counseling, as high-risk melanoma survivors may require no more intensive surveillance than low-risk survivors 8 years after treatment.

Quantitative adenosine 201Tl single-photon emission computed tomography for the early assessment of patients surviving acute myocardial infarction.

We prospectively investigated whether adenosine 201Tl tomography (SPECT) could determine the extent of coronary artery disease, the presence of jeopardized myocardium, and the risk for in-hospital cardiac events in 120 clinically stable patients early (5 +/- 3 days) after myocardial infarction. All patients had coronary angiography and SPECT in close proximity. Adenosine SPECT identified 99% of infarct-related arteries and 82% of severely stenosed (> or = 70%) noninfarct arteries. Multivessel disease was accurately predicted in 69% of patients. Sixty-five percent of stenosed noninfarct arteries had matching thallium perfusion defects, and 92% of these were reversible. The specificity of adenosine SPECT was > 90%. Thallium redistribution occurred often within infarct (59%) and noninfarct (92%) zones. The patency status of the arteries, however, did not predict the presence or extent of jeopardized myocardium. The perfusion defect size was larger (p = 0.0001) in patients with (45 +/- 18%) than in those without (22 +/- 15%) in-hospital cardiac events. Furthermore, 90% of patients with events had a > or = 20% perfusion defect compared with only 38% of those without events (p = 0.0001). The positive-predictive accuracy for developing a cardiac event was 70% when the perfusion defect size was > 30%. The ischemic defect also was larger in patients with (19 +/- 14%) than in those without (10 +/- 10%) events (p = 0.001). The positive- and negative-predictive values for developing early postinfarction angina were 43% and 91%, respectively, when the ischemic defect was > 12%. In selected low-risk survivors of myocardial infarction, early quantitative adenosine SPECT is safe and accurate in detecting and localizing coronary stenoses, assessing the extent of jeopardized myocardium, and determining subsequent risk for in-hospital cardiac events.

Routine exercise testing or thallium-201 scintigraphy for prediction of cardiac events post-myocardial infarction?

The efficacy of 12 lead exercise testing and rest/exercise 201Tl scintigraphy as indicators of coronary anatomy and prognosis was compared in 46 low risk survivors of acute myocardial infarction. The non invasive procedures were performed at discharge, and cardiac catheterization was performed six weeks post discharge. On exercise testing, ST depression in leads remote from the site of infarction was considered to indicate multivessel disease and reversible ischaemia. On 201Tl scintigraphy, a perfusion defect remote from the site of infarction indicated multivessel disease, while a defect which reperfused at rest indicated reversible ischaemia. During the mean follow-up of 13 +/- 3 months, 14(30%) patients experienced cardiac events. Thallium scintigraphy was a more sensitive, but less specific, indicator of multivessel disease than exercise testing. Both exercise testing and 201Tl scintigraphy had a similar sensitivity (79% vs 79%), specificity (78% vs 88%) and predictive accuracy (78% vs 85%) for predicting subsequent cardiac events. Thus, in our patient population, 201Tl scintigraphy could not be demonstrated to be superior to routine exercise testing in low risk patients post myocardial infarction.

Medically directed at-home rehabilitation soon after clinically uncomplicated acute myocardial infarction: A new model for patient care

Medically directed at-home rehabilitation was compared with group rehabilitation which began 3 weeks after clinically uncomplicated acute myocardial infarction (AMI) in 127 men, mean age 53 ± 7 years. Between 3 and 26 weeks after AMI, adherence to individually prescribed exercise was equally high (at least 71%), the increase in functional capacity equally large (1.8 ± 1.0 METs) and nonfatal reinfarction and dropout rates equally low (both 3% or less) in the 66 men randomized to home training and the 61 men randomized to group training. No training-related complications occurred in either group. The low rate of reinfarction and death (5% and 1%, respectively) in the study as a whole, which included 34 patients with no training and 37 control patients, reflected a stepwise process of clinical evaluation, exercise testing at 3 weeks and frequent telephone surveillance of patients who underwent exercise training. Medically directed at-home rehabilitation has the potential to increase the availability and to decrease the cost of rehabilitating low-risk survivors of AMI.