Risk of increased mortality in underweight survivors: A brief report from the Childhood Cancer Survivor Study.

BACKGROUND: Approximately 1 in 10 adult survivors of childhood cancer is underweight. Although the consequences of being overweight or obese have been well described, outcomes among childhood cancer survivors who are underweight are unknown. OBJECTIVE: To determine whether underweight status increases the risk of mortality. PROCEDURE: Cohort study: Marginal models with generalized estimating equations to evaluate the associations between body mass index (BMI), serious or life-threatening chronic conditions, and death in the setting of long-term follow-up questionnaires and National Death Index search. PARTICIPANTS: Childhood cancer five-year survivors diagnosed during 1970-1986 in the Childhood Cancer Survivor Study Exposure: Underweight status, defined as body mass index (BMI) < 18.5 kg/m2 compared with ideal body weight. Based on available literature on body weight and mortality from the general population, ideal body weight was defined as BMI 22.0-24.9 kg/m2. MAIN OUTCOMES: Overall mortality and cancer-specific mortality. RESULTS: Of 9454 survivors (median age 35 years old (range, 17-58), an average of 17.5 years from diagnosis), 627 (6.6%) participants were underweight at baseline or follow-up questionnaire. Of 184 deaths, 29 were among underweight survivors. Underweight status was more common among females (9.1% vs. 4.5%, p < .01) and participants with younger age at diagnosis (8.2% for < 5 years vs. 6.1% for ≥5 years, p < .01), lower household income (8.9% for < $20,000 vs. 6.0% for ≥ $20,000, p < .01), or a history of serious chronic condition (p = .05). After adjustment for these factors, in addition to prior smoking and a history of radiation therapy, the risk of all-cause mortality within two years of BMI report was increased (OR 2.85; 95% CI: 1.63-4.97; p < .01) for underweight survivors, compared with ideal-weight survivors. CONCLUSIONS: Childhood cancer survivors who are underweight are at increased risk for late mortality that appears unrelated to smoking status, recognized chronic disease, or subsequent malignancy. Whether targeted nutritional interventions would ameliorate this risk is unknown.

Developing national cancer survivorship standards to inform quality of care in the United States using a consensus approach.

PURPOSE: To develop United States (US) standards for survivorship care that informs (1) essential health system policy and process components and (2) evaluation of the quality of survivorship care. METHODS: The National Cancer Institute and the Department of Veterans Affairs led a review to identify indicators of quality cancer survivorship care in the domains of health system policy, process, and evaluation/assessment. A series of three virtual consensus meetings with survivorship care and research experts and advocates was conducted to rate the importance of the indicators and refine the top indicators. The final set of standards was developed, including ten indicators in each domain. RESULTS: Prioritized items were survivor-focused, including processes to both assess and manage physical, psychological, and social issues, and evaluation of patient outcomes and experiences. Specific indicators focused on developing a business model for sustaining survivorship care and collecting relevant business metrics (e.g., healthcare utilization, downstream revenue) to show value of survivorship care to health systems. CONCLUSIONS: The National Standards for Cancer Survivorship Care can be used by health systems to guide development of new survivorship care programs or services or to assess alignment and enhance services in existing survivorship programs. Given the variety of settings providing care to survivors, it is necessary for health systems to adapt these standards based on factors including age-specific needs, cancer types, treatments received, and health system resources. IMPLICATIONS FOR CANCER SURVIVORS: With over 18 million cancer survivors in the United States, many of whom experience varied symptoms and unmet needs, it is essential for health systems to have a comprehensive strategy to provide ongoing care. The US National Standards for Survivorship Care should serve as a blueprint for what survivors and their families can anticipate after a cancer diagnosis to address their needs.

Survivorship in Advanced Lung Cancer: Understanding a New Landscape and Opportunities.

People with advanced lung cancer represent a distinct group whose needs remain understudied, especially compared with people diagnosed with limited-stage disease. Fortunately, novel treatments such as tyrosine kinase inhibitors and immune checkpoint inhibitors are leading to significant advances in prognosis and survival, even among those with advanced disease at the time of diagnosis. However, there are known gaps in symptom management, psychosocial and nutritional support, complex care coordination, health behavior coaching, and health care delivery efforts among patients living with advanced lung cancer. Many of these patients would benefit from survivorship and palliative care approaches. In particular, survivorship care may include health care maintenance, treatment of immune-related adverse events and late- or long-term effects, frailty assessment and rehabilitation, and care coordination. Palliative care may be best suited to discuss ongoing symptom management, advanced care planning, and end-of-life considerations, as well as psychosocial well-being. To this end, we share a review of the current status of the palliative and survivorship care infrastructure for patients with advanced lung cancer and provide suggestions across the care continuum for this diverse group of patients and families.

Primary care for cancer survivors: a review of national institutes of health-funded grants 2017-2022.

PURPOSE: To describe the characteristics of National Institutes of Health (NIH) grants on primary care cancer research in cancer survivorship funded over the past 5 years. METHODS: Research project grants (RPG) funded during Fiscal Year (FY) 2017 to 2022 focused on cancer survivorship were identified using a text mining algorithm of words from the NIH Research, Condition, and Disease Categorization (RCDC) thesaurus with survivorship-relevant terms. Grants were then reviewed and double-coded to identify those that were carried out in a primary care setting, targeted primary care providers, or had primary care providers in the study team. RESULTS: A total of 24 grants were identified; 23 were funded by the National Cancer Institute and one was funded by the National Institute on Minority Health and Health Disparities. The majority were funded under the R01 mechanism (70.8%) and led by established investigators. Most were interventional design (91.7%), including both survivors and providers (79.2%), and focused care coordination or healthcare utilization (91.7%). CONCLUSIONS: Grants focused on primary care cancer survivorship are uncommon in the NIH portfolio. IMPLICATIONS FOR SURVIVORS: For the over 18 million cancer survivors in the USA, being cared for in a primary care setting is common. Yet, NIH-funded research on primary care cancer survivorship is sparse.

Exercise and QUality diet After Leukemia (EQUAL): A randomized weight loss trial among adult survivors of childhood leukemia in the Childhood Cancer Survivor Study.

BACKGROUND: Obesity is prevalent in childhood cancer survivors and interacts with cancer treatments to potentiate risk for cardiovascular (CV) death. We tested a remote weight-loss intervention that was effective among adults with CV risk factors in a cohort of adult survivors of childhood acute lymphoblastic leukemia (ALL) with overweight/obesity. METHODS: In this phase 3 efficacy trial, survivors of ALL enrolled in the Childhood Cancer Survivor Study with body mass index (BMI)≥25 kg/m2 were randomized to a remotely-delivered weight-loss intervention versus self-directed weight loss, stratified by history of cranial radiotherapy (CRT). The primary endpoint was the difference in weight loss at 24-months in an intent-to-treat analysis. Analyses were performed using linear mixed effects models. RESULTS: Among 358 survivors (59% female, median attained age: 37 years, IQR: 33-43), baseline mean (SD) weight was 98.6 kg (24.0) for the intervention group (n=181) and 94.9 kg (20.3) for controls (n=177). Adherence to the intervention was poor; 15% of individuals in the intervention completed 24/30 planned coaching calls. Weight at 24-months was available for 274 (77%) participants. After controlling for CRT, sex, race/ethnicity, and age, the mean (SE) change in weight from baseline to 24-months was -0.4 kg (0.8) for intervention and 0.2 kg (0.6) for control participants (p=0.59). CONCLUSIONS: A remote weight-loss intervention that was successful among adults with CV conditions did not result in significant weight loss among adult survivors of childhood ALL. IMPACT: Future interventions in this population must be tailored to the unique needs of survivors to encourage engagement and adherence.

Survivorship concerns among individuals diagnosed with metastatic cancer: Findings from the Cancer Experience Registry.

INTRODUCTION: Individuals with metastatic cancer experience many medical, physical, and emotional challenges due to changing medical regimens, oscillating disease states, and side effects. The purpose of this study was to describe the type and prevalence of survivorship concerns reported by individuals with metastatic cancer, and their associations with cancer diagnosis, treatment, and socio-demographic variables. METHODS: This study utilized data from the Cancer Support Community's Cancer Experience Registry. Individuals were included if they self-reported a solid tumor metastatic cancer and completed CancerSupportSource, which evaluates five domains of concerns (emotional well-being, symptom burden, body image/healthy lifestyle, healthcare team communication, and relationships/intimacy). Multivariable linear regression examined associations between independent predictors of each survivorship concern domain. RESULTS: Of the 403 included participants, individuals reported a metastatic diagnosis of breast (43%), colorectal (20%), prostate (7%), lung (7%), gynecologic cancer (6%) and other. Nearly all (96%) reported at least one survivorship concern, with the most prevalent concern about cancer progression or recurrence. Survivorship concerns were higher across multiple domains for individuals unemployed due to disability. Individuals who were less than five years since diagnosis reported higher concerns related to emotional well-being, symptom burden, and healthcare communication compared to those more than five years since diagnosis. CONCLUSION: Individuals with metastatic cancer experience a variety of moderate-to-severe survivorship concerns that warrant additional investigation. IMPLICATIONS FOR CANCER SURVIVORS: As the population of individuals with metastatic cancer lives longer, future research must investigate solutions to address modifiable factors associated with survivorship concerns, such as unemployment due to disability.

Impact of risk-based therapy on late morbidity and mortality in neuroblastoma survivors: a report from the Childhood Cancer Survivor Study.

BACKGROUND: Early efforts at risk-adapted therapy for neuroblastoma are predicted to result in differential late effects; the magnitude of these differences has not been well described. METHODS: Late mortality, subsequent malignant neoplasms (SMNs), and severe/life-threatening chronic health conditions (CHCs), graded according to CTCAE v4.03, were assessed among 5-year Childhood Cancer Survivor Study (CCSS) survivors of neuroblastoma diagnosed 1987-1999. Using age, stage at diagnosis, and treatment, survivors were classified into risk groups (low [n = 425]; intermediate [n = 252]; high [n = 245]). Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) of SMNs were compared with matched population controls. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals for CHC compared with 1029 CCSS siblings. RESULTS: Among survivors (49.8% male; median age = 21 years, range = 7-42; median follow-up = 19.3 years, range = 5-29.9), 80% with low-risk disease were treated with surgery alone, whereas 79.1% with high-risk disease received surgery, radiation, chemotherapy ± autologous stem cell transplant (ASCT). All-cause mortality was elevated across risk groups (SMRhigh = 27.7 [21.4-35.8]; SMRintermediate = 3.3 [1.7-6.5]; SMRlow = 2.8 [1.7-4.8]). SMN risk was increased among high- and intermediate-risk survivors (SIRhigh = 28.0 [18.5-42.3]; SIRintermediate = 3.7 [1.2-11.3]) but did not differ from the US population for survivors of low-risk disease. Compared with siblings, survivors had an increased risk of grade 3-5 CHCs, particularly among those with high-risk disease (HRhigh = 16.1 [11.2-23.2]; HRintermediate = 6.3 [3.8-10.5]; HRlow = 1.8 [1.1-3.1]). CONCLUSION: Survivors of high-risk disease treated in the early days of risk stratification carry a markedly elevated burden of late recurrence, SMN, and organ-related multimorbidity, whereas survivors of low/intermediate-risk disease have a modest risk of late adverse outcomes.

Associations of seven measures of biological age acceleration with frailty and all-cause mortality among adult survivors of childhood cancer in the St. Jude Lifetime Cohort.

Survivors of childhood cancer may experience accelerated biological aging, resulting in premature frailty and death. We used seven measures of biological age in the St. Jude Lifetime (SJLIFE) Cohort to compare biological age acceleration between the SJLIFE Cohort and the third United States National Health and Nutrition Examination Survey controls, explore trajectories of biological age according to cancer treatment and type, and test associations of biological age acceleration with frailty and death (mean follow-up of 26.5 years) among survivors. Survivors of cancer aged 5% faster per year and measured, on average, 0.6-6.44 years biologically older compared to controls and 5-16 years biologically older compared to age-matched individuals at the population level. Survivors treated with hematopoietic cell transplant and vinca alkaloid chemotherapy evidenced the fastest trajectories of biological aging. Biologically, older and faster-aging survivors consistently and robustly had a higher risk of frailty and died earlier than those with slower biological aging, suggesting a potential opportunity to intervene on excess aging.

Advancing health equity in cancer survivorship research: National institutes of health 2017-2022 portfolio review.

BACKGROUND: Communities and researchers have called for a paradigm shift from describing health disparities to a health equity research agenda that addresses structural drivers. Therefore, we examined whether the cancer survivorship research portfolio has made this shift. METHODS: We identified grants focused on populations experiencing health disparities from the National Institutes of Health (NIH) Cancer Survivorship Research Portfolio (N = 724), Fiscal Years 2017-2022. Grant characteristics were abstracted, drivers of health disparities were mapped onto the levels and domains of influence, and opportunities for future research were identified. RESULTS: A total of 147 survivorship grants focused on health disparities were identified, of which 73.5% of grants focused on survivors from racial and ethnic minoritized groups, 25.9% living in rural areas, 24.5% socioeconomically disadvantaged, and 2.7% sexual and gender minority groups. Study designs were 51.0% observational. 82.3% of grants measured or intervened on at least one individual-level of influence, compared to higher levels of influence (32.7% interpersonal, 41.5% institutional/community, and 12.2% societal). Behavioral and healthcare system domains of influence were commonly represented, especially at the individual level (47.6% and 36.1%, respectively). Less frequently represented was the physical/built environment (12.2%). CONCLUSIONS: NIH-funded cancer survivorship research on health disparities is still focused on individual-level of influence. However, the proportion of grants examining structural and social drivers as well as the mechanisms that drive disparities in healthcare and health outcomes among cancer survivors have increased over time. Gaps in funded research on specific populations, cancer types, and focus areas of survivorship science were identified and warrant priority.

Financial toxicity among people with metastatic cancer: findings from the Cancer Experience Registry.

PURPOSE: This study describes financial toxicity (FT) reported by people with metastatic cancer, characteristics associated with FT, and associations between FT and compensatory strategies to offset costs. METHODS: Cancer Support Community's Cancer Experience Registry data was used to identify respondents with a solid tumor metastatic cancer who completed the Functional Assessment of Chronic Illness Therapy COmprehensive Score for Financial Toxicity (FACIT-COST) measure. Multivariable logistic regression analyses examined associations between respondent characteristics and FT, and FT and postponing medical visits, nonadherence to medications, and postponing supportive and/or psychosocial care. RESULTS: 484 individuals were included in the analysis; the most common cancers included metastatic breast (31%), lung (13%), gynecologic (10%), and colorectal (9%). Approximately half of participants (50.2%) reported some degree of FT. Those who were non-Hispanic White, Hispanic, or multiple races (compared to non-Hispanic Black), and who reported lower income, less education, and being less than one year since their cancer diagnosis had greater odds of reporting FT. Individuals with any level of FT were also more likely to report postponing medical visits (Adjusted Odds Ratio [OR] 2.58; 95% Confidence Interval [CI] 1.45-4.58), suboptimal medication adherence (Adjusted OR 5.05; 95% CI 2.77-9.20) and postponing supportive care and/or psychosocial support services (Adjusted OR 4.16; 95% CI 2.53-6.85) compared to those without FT. CONCLUSIONS: With increases in the number of people living longer with metastatic cancer and the rising costs of therapy, there will continue to be a need to systematically screen and intervene to prevent and mitigate FT for these survivors.

Palliative Intent Treatment and Palliative Care Delivery for Individuals With Advanced Nonsmall Cell Lung Cancer and Melanoma: A Patterns of Care Study.

Introduction: This study aimed to describe the patterns of palliative intent treatment and/or palliative care (PC) delivery among a population-based sample of individuals diagnosed with advanced nonsmall cell lung cancer (NSCLC) or advanced melanoma. Methods: Data from 655 advanced-stage melanoma patients and 2688 advanced-stage NSCLC patients included in the National Cancer Institute's 2017/2018 Patterns of Care study were analyzed. Bivariate and multivariate logistic regression analyses examined factors associated with (1) receipt of PC (including palliative surgery, radiation, and/or systemic therapy after cancer diagnosis, and PC consultations); and (2) timing from diagnosis to receipt of PC. Proportional hazards models also examined factors associated with timing of receipt of PC after diagnosis. Results: A total of 23.5% of those with melanoma and 52.6% of those with NSCLC received some type of PC. For melanoma, stage 4 (vs. stage 3) was associated with higher receipt of PC and receipt within three months of diagnosis. For NSCLC, stage 4 (vs. stage 3) and a diagnosis of depression or psychosocial distress within three months of diagnosis were significantly associated with receipt of PC and receipt within three months of diagnosis. Conclusion: Study findings indicate that those with advanced-stage cancer or who report distress are more likely to receive palliative intent treatment and/or PC. Given that individuals with advanced cancers are living longer and often experience long-lasting symptoms, it is critical to identify and overcome barriers for broadly delivering comprehensive palliative and supportive care.

Primary Care Utilization and Cardiovascular Screening in Adult Survivors of Childhood Cancer.

Importance: Cardiovascular disease is the leading noncancer cause of premature death among survivors of childhood cancer. Adult survivors of childhood cancer are largely managed by primary care practitioners (PCPs), and health care utilization patterns related to cardiovascular screening are not well described. Objective: To examine screening and health care utilization among survivors of childhood cancer at high risk for cardiovascular complications. Design, Setting, and Participants: This multicenter cross-sectional study included participants enrolled in a randomized clinical trial from 2017 to 2021. Abstracted documentation of participants' cancer history, cardiotoxic treatment exposures, and survivorship care plans were obtained from participants' PCPs spanning 2 years preceding trial enrollment. Participants were members of the Childhood Cancer Survivor Study cohort at elevated risk for ischemic heart disease or heart failure, enrolled in a randomized trial focused on improving cardiovascular risk factor control. Data were analyzed from November 2022 to July 2023. Main Outcomes and Measures: Outcomes of interest were numbers of PCP and specialist visits, cardiovascular risk factors (hypertension, dyslipidemia, and diabetes), risk factor screening, and cardiac testing. Multivariable logistic regression assessed characteristics associated with up-to-date cardiac testing at enrollment. Results: Of 347 enrolled participants, 293 (84.4%) had evaluable medical records (median [range] age, 39.9 [21.5-65.0] years; 149 [50.9%] male) and were included in analyses. At baseline, 238 participants (81.2%) had a documented PCP encounter; 241 participants (82.3%) had undergone blood pressure screening, 179 participants (61.1%) had undergone lipid testing, and 193 participants (65.9%) had undergone diabetes screening. A total of 63 participants (21.5%) had echocardiography completed or planned. Only 198 participants (67.6%) had records referencing a cancer history. PCP documentation of prior cardiotoxic exposures was low compared with known exposures, including radiation therapy (103 participants [35.2%] vs 203 participants [69.3%]; P < .001) and anthracycline chemotherapy (27 participants [9.2%] vs 222 participants [75.8%]; P = .008). Few records referenced a need for cancer-related late effects surveillance (95 records [32.4%]). Independent factors associated with cardiac screening included documentation of increased cardiovascular disease risk (odds ratio [OR], 11.94; 95% CI, 3.37-42.31), a late-effects surveillance plan (OR, 3.92; 95% CI, 1.69-9.11), and existing cardiovascular risk factors (OR per each additional factor, 2.09; 95% CI, 1.32-3.31). Conclusions and Relevance: This cross-sectional study of adult survivors of childhood cancer at increased risk of cardiovascular disease found low adherence to recommended cardiac testing and documentation of risk for these individuals. Improving accuracy of reporting of survivors' exposures and risks within the medical record may improve screening.

Risk factors for overweight and obesity after childhood acute lymphoblastic leukemia in North America and Switzerland: A comparison of two cohort studies.

BACKGROUND: After childhood acute lymphoblastic leukemia (ALL), sequelae include overweight and obesity, yet with conflicting evidence. We compared the prevalence of overweight and obesity between ≥5-year ALL survivors from the North American Childhood Cancer Survivor Study (CCSS) and the Swiss Childhood Cancer Survivor Study (SCCSS) and described risk factors. METHODS: We included adult childhood ALL survivors diagnosed between 1976 and 1999. We matched CCSS participants (3:1) to SCCSS participants by sex and attained age. We calculated body mass index (BMI) from self-reported height and weight for 1287 CCSS and 429 SCCSS participants; we then compared those with siblings (2034) in North America and Switzerland (678) siblings. We assessed risk factors for overweight (BMI 25-29.9 kg/m2 ) and obesity (≥30 kg/m2 ) using multinomial regression. RESULTS: We found overweight and obesity significantly more common among survivors in North America when compared with survivors in Switzerland [overweight: 30%, 95% confidence interval (CI): 27-32 vs. 24%, 21-29; obesity: 29%, 27-32 vs. 7%, 5-10] and siblings (overweight: 30%, 27-32 vs. 25%, 22-29; obesity: 24%, 22-26 vs. 6%, 4-8). Survivors in North America [odds ratio (OR) = 1.24, 1.01-1.53] and Switzerland (1.27, 0.74-2.21) were slightly more often obese than siblings. Among survivors, risk factors for obesity included residency in North America (5.8, 3.7-9.0); male (1.7, 1.3-2.3); attained age (≥45 years: 5.1, 2.4-10.8); Non-Hispanic Black (3.4, 1.6-7.0); low household income (2.3, 1.4-3.5); young age at diagnosis (1.6, 1.1-2.2). Cranial radiotherapy ≥18 Gray was only a risk factor for overweight (1.4, 1.0-1.8); steroids were not associated with overweight or obesity. Interaction tests found no evidence of difference in risk factors between cohorts. CONCLUSIONS: Although treatment-related risk for overweight and obesity were similar between regions, higher prevalence among survivors in North America identifies important sociodemographic drivers for informing health policy and targeted intervention trials.

Ototoxicity associated with high-dose carboplatin for patients with previously treated germ cell tumors.

BACKGROUND: High-dose carboplatin is an essential part of curative high-dose chemotherapy (HDCT) for patients with previously treated germ cell tumors (GCTs). Although hearing loss (HL) is a known side effect of HDCT, data on its severity and characteristics are limited. METHODS: Eligible patients received HDCT for GCTs from 1993 to 2017 and had audiograms before and after HDCT. HL severity was classified by American Speech-Language-Hearing Association criteria, and mean change in hearing threshold at each frequency (0.25-8 kHz) was estimated from pre- to post-HDCT and between HDCT cycles. RESULTS: Of 115 patients (median age, 32 years), 102 (89%) received three cycles of HDCT. Of 106 patients with normal hearing to mild HL in the speech frequencies (0.5-4 kHz) before HDCT, 70 (66%) developed moderate to profound HL in the speech frequencies after HDCT. Twenty-five patients (22%) were recommended for hearing aids after HDCT. Patients with moderate to profound HL isolated to the higher frequencies (6-8 kHz) before HDCT were more likely to develop moderate to profound HL in the speech frequencies after HDCT (94% vs. 61%; p = .01) and to be recommended for hearing aids (39% vs. 18%; p = .05). CONCLUSIONS: HL was frequent after HDCT for GCTs, with most patients developing at least moderate HL in the speech frequencies and approximately one in five recommended for hearing aids. Moderate to profound HL isolated to high frequencies at baseline was predictive of more clinically significant hearing impairment after HDCT. PLAIN LANGUAGE SUMMARY: Some patients with germ cell tumors, the most common malignancy in adolescent and young adult men, are not cured with standard-dose chemotherapy and require high-dose chemotherapy (HDCT). Using detailed hearing assessments of patients receiving HDCT, we found that most patients developed significant hearing loss and that one in five needed hearing aids. Thus, strategies to reduce this side effect are urgently needed, and all patients receiving HDCT should have a hearing test after therapy.

Clinical Care for People Who Survive Childhood Cancer: A Review.

Importance: An estimated 15 000 children and adolescents aged 0 to 19 years are diagnosed with cancer each year in the US, and more than 85% survive for at least 5 years. By 45 years of age, approximately 95% of people who survive childhood cancer will develop a significant health problem related to the childhood cancer diagnosis or its treatment. Observations: Approximately 500 000 people currently alive in the US have survived childhood cancer. The most common severe or life-threatening chronic health problems related to childhood cancer or its treatment are endocrine disorders such as hypothyroidism or growth hormone deficiency (44%), subsequent neoplasms such as breast cancer or thyroid cancer (7%), and cardiovascular disease such as cardiomyopathy or congestive heart failure, coronary artery disease, and cerebrovascular disease (5.3%). Medical conditions related to a cancer diagnosis during childhood or adolescence are most commonly caused by the radiation therapy and the chemotherapies used to treat cancer and may develop at varying lengths of time after exposure to these treatments. Individuals at highest risk for developing treatment-related health problems include patients with brain cancer treated with cranial irradiation (approximately 70% develop severe or life-threatening health problems) and allogeneic hematopoietic stem cell transplant recipients (approximately 60% develop severe or life-threatening health problems). Individuals at the lowest risk for developing treatment-related health problems include those who survived solid tumors (such as Wilms tumor) treated with surgical resection alone or with minimal chemotherapy, for whom the prevalence of subsequent health problems is similar to people who did not have cancer during childhood or adolescence. People diagnosed with childhood cancer in the 1990s who survived for at least 5 years after the cancer diagnosis have a shorter lifespan (by about 9 years) vs children who were not diagnosed with cancer in the 1990s. Conclusions and Relevance: Approximately 500 000 individuals currently alive in the US have survived childhood cancer. The most common adverse effects in individuals who survived childhood cancer are endocrine disorders, subsequent neoplasms, and cardiovascular disease. There is a need for clinicians and patients to have heightened awareness of these complications.