G. T. Armstrong

Testicular Cancer Survivorship: Research Strategies and Recommendations

Testicular cancer represents the most curable solid tumor, with a 10-year survival rate of more than 95%. Given the young average age at diagnosis, it is estimated that effective treatment approaches, in particular, platinum-based chemotherapy, have resulted in an average gain of several decades of life. This success, however, is offset by the emergence of considerable long-term morbidity, including second malignant neoplasms, cardiovascular disease, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, decreased fertility, and psychosocial problems. Data on underlying genetic or molecular factors that might identify those patients at highest risk for late sequelae are sparse. Genome-wide association studies and other translational molecular approaches now provide opportunities to identify testicular cancer survivors at greatest risk for therapy-related complications to develop evidence-based long-term follow-up guidelines and interventional strategies. We review research priorities identified during an international workshop devoted to testicular cancer survivors. Recommendations include 1) institution of lifelong follow-up of testicular cancer survivors within a large cohort setting to ascertain risks of emerging toxicities and the evolution of known late sequelae, 2) development of comprehensive risk prediction models that include treatment factors and genetic modifiers of late sequelae, 3) elucidation of the effect(s) of decades-long exposure to low serum levels of platinum, 4) assessment of the overall burden of medical and psychosocial morbidity, and 5) the eventual formulation of evidence-based long-term follow-up guidelines and interventions. Just as testicular cancer once served as the paradigm of a curable malignancy, comprehensive follow-up studies of testicular cancer survivors can pioneer new methodologies in survivorship research for all adult-onset cancer.

Twenty years of follow-up among survivors of childhood and young adult acute myeloid leukemia: A report from the Childhood Cancer Survivor Study

Limited data exist on the comprehensive assessment of late medical and social effects experienced by survivors of childhood and young adult acute myeloid leukemia (AML).

Twenty-five year follow-up of childhood Wilms tumor: A report from the Childhood Cancer Survivor Study†‡

Treatment cures over 90% of children with Wilms tumor (WT) who subsequently risk late morbidity and mortality. This study describes the 25‐year outcomes of 5‐year WT survivors in the Childhood Cancer Survivor Study (CCSS).

Secondary Gastrointestinal Cancer in Childhood Cancer Survivors: A Cohort Study

BACKGROUND Childhood cancer survivors develop gastrointestinal cancer more frequently and at a younger age than the general population, but the risk factors have not been well-characterized. OBJECTIVE To determine the risk and associated risk factors for gastrointestinal subsequent malignant neoplasms (SMNs) in childhood cancer survivors. DESIGN Retrospective cohort study. SETTING The Childhood Cancer Survivor Study, a multicenter study of childhood cancer survivors diagnosed between 1970 and 1986. PATIENTS 14 358 survivors of cancer diagnosed when they were younger than 21 years of age who survived for 5 or more years after the initial diagnosis. MEASUREMENTS Standardized incidence ratios (SIRs) for gastrointestinal SMNs were calculated by using age-specific population data. Multivariate Cox regression models identified associations between risk factors and gastrointestinal SMN development. RESULTS At median follow-up of 22.8 years (range, 5.5 to 30.2 years), 45 cases of gastrointestinal cancer were identified. The risk for gastrointestinal SMNs was 4.6-fold higher in childhood cancer survivors than in the general population (95% CI, 3.4 to 6.1). The SIR for colorectal cancer was 4.2 (CI, 2.8 to 6.3). The highest risk for gastrointestinal SMNs was associated with abdominal radiation (SIR, 11.2 [CI, 7.6 to 16.4]). However, survivors not exposed to radiation had a significantly increased risk (SIR, 2.4 [CI, 1.4 to 3.9]). In addition to abdominal radiation, high-dose procarbazine (relative risk, 3.2 [CI, 1.1 to 9.4]) and platinum drugs (relative risk, 7.6 [CI, 2.3 to 25.5]) independently increased the risk for gastrointestinal SMNs. LIMITATION This cohort has not yet attained an age at which risk for gastrointestinal cancer is greatest. CONCLUSION Childhood cancer survivors, particularly those exposed to abdominal radiation, are at increased risk for gastrointestinal SMNs. These findings suggest that surveillance of at-risk childhood cancer survivors should begin at a younger age than that recommended for the general population. PRIMARY FUNDING SOURCE National Cancer Institute.

Melanoma as a subsequent neoplasm in adult survivors of childhood cancer: A report from the childhood cancer survivor study

Childhood cancer survivors have a sixfold increased risk of developing subsequent neoplasms when compared to the general population. We sought to describe the occurrence of melanoma as a subsequent neoplasm among adult survivors of childhood cancer.

Employer-sponsored health insurance coverage limitations: results from the Childhood Cancer Survivor Study

PurposeThe Affordable Care Act (ACA) will expand health insurance options for cancer survivors in the USA. It is unclear how this legislation will affect their access to employer-sponsored health insurance (ESI). We describe the health insurance experiences for survivors of childhood cancer with and without ESI.MethodsWe conducted a series of qualitative interviews with 32 adult survivors from the Childhood Cancer Survivor Study to assess their employment-related concerns and decisions regarding health insurance coverage. Interviews were performed from August to December 2009 and were recorded, transcribed, and content analyzed using NVivo 8.ResultsUninsured survivors described ongoing employment limitations, such as being employed at part-time capacity, which affected their access to ESI coverage. These survivors acknowledged they could not afford insurance without employer support. Survivors on ESI had previously been denied health insurance due to their preexisting health conditions until they obtained coverage through an employer. Survivors feared losing their ESI coverage, which created a disincentive to making career transitions. Others reported worries about insurance rescission if their cancer history was discovered. Survivors on ESI reported financial barriers in their ability to pay for health care.ConclusionsChildhood cancer survivors face barriers to obtaining ESI. While ACA provisions may mitigate insurance barriers for cancer survivors, many will still face cost barriers to affording health care without employer support.

Recurrent stroke in childhood cancer survivors

Objective: To estimate the rates and predictors of recurrent stroke among survivors of pediatric cancer who have had a first stroke. Methods: The Childhood Cancer Survivor Study is a retrospective cohort study with longitudinal follow-up that enrolled 14,358 survivors (<21 years old at diagnosis; diagnosed 1970–1986; survived ≥5 years after cancer diagnosis) and followed them prospectively since 1994. We surveyed 443 survivors who reported a first stroke to identify recurrent stroke, and estimated recurrent stroke rates ≥5 years after cancer diagnosis. Results: Among 329 respondents (74% response rate), 271 confirmed a first stroke at a median age of 19 years (range 0–53), and 70 reported a second stroke at a median age of 32 years (range 1–56). In a multivariable Cox proportional hazards model, independent predictors of recurrent stroke included cranial radiation therapy (CRT) dose of ≥50 Gy (vs none, hazard ratio [HR] 4.4; 95% confidence interval [CI] 1.4–13.7), hypertension (HR 1.9; 95% CI 1.0–3.5), and older age at first stroke (HR 6.4; 95% CI 1.8–23; for age ≥40 vs age 0–17 years). The 10-year cumulative incidence of late recurrent stroke was 21% (95% CI 16%–27%) overall, and 33% (95% CI 21%–44%) for those treated with ≥50 Gy of CRT. Conclusion: Survivors of childhood cancer, particularly those previously treated with high-dose cranial radiation, have a high risk of recurrent stroke for decades after a first stroke. Although these strokes are mostly occurring in young adulthood, hypertension, an established atherosclerotic risk factor, independently predicts recurrent stroke in this population.

Cancer Prevention and Screening Practices of Siblings of Childhood Cancer Survivors: A Report from the Childhood Cancer Survivor Study

Background: To compare the skin and breast/cervical cancer prevention/screening practices of adult siblings of childhood cancer survivors with controls and to identify modifying factors for these practices. Methods: Cross-sectional, self-report data from 2,588 adult siblings of 5+ year survivors of childhood cancer were analyzed to assess cancer prevention/screening practices. Two age, sex, and race/ethnicity-matched samples (N = 5,915 and N = 37,789) of the Behavioral Risk Factor Surveillance System participants served as the comparison populations. Sociodemographic and cancer-related data were explored as modifying factors for sibling cancer prevention/screening practices through multivariable logistic regression. Results: Compared with controls, siblings were more likely to practice skin cancer prevention behaviors: use of protective clothing [OR, 2.85; 95% confidence interval (CI), 2.39–3.39], use of shade (OR, 2.11; 95% CI, 1.88–2.36), use of sunscreen (OR, 1.27; 95% CI, 1.14–1.40), and wearing a hat (OR, 1.77; 95% CI, 1.58–1.98). No differences were noted for breast/cervical cancer screening including mammography and Pap testing. Having less than a high school education and lack of health insurance were associated with diminished cancer prevention/screening behaviors. Survivor diagnosis, treatment intensity, adverse health, chronic health conditions, and second cancers were not associated with sibling cancer prevention/screening behaviors. Conclusions: Siblings of cancer survivors report greater skin cancer prevention practices when compared with controls; however, no differences were noted for breast/cervical cancer screening practices. Access to care and lack of education may be associated with decreased cancer prevention/screening behaviors. Interventions are needed to address these barriers. Impact: Research should be directed at understanding the impact of the cancer experience on sibling health behaviors. Cancer Epidemiol Biomarkers Prev; 21(7); 1078–88. ©2012 AACR.

SECONDARY GASTROINTESTINAL MALIGNANCIES IN CHILDHOOD CANCER SURVIVORS: A COHORT STUDY

Background Childhood cancer survivors develop gastrointestinal malignancies more frequently and at a younger age than the general population, but risk factors for their development have not been well characterized.

Predictors of Colorectal Cancer Surveillance among Radiation-treated Survivors of Childhood Cancer

Purpose: To identify predictors of adherence to colorectal cancer (CRC) surveillance guidelines among survivors of childhood cancer who received ≥30 Gy radiotherapy to the abdomen, pelvis, or spine, and were 36 years or older at the time of last contact. Methods: We sought to identify predictors of self-reported CRC surveillance participation among 5-year survivors who completed the Childhood Cancer Survivor Study (CCSS) 2007 Follow-Up Questionnaire and met the criteria above. Univariate and multivariable generalized linear models with a log link and Poisson distribution were used to calculate relative risks (RR) with 95% confidence intervals (95% CI) for adherence to CRC surveillance guidelines (i.e., home stool blood testing and/or colonoscopy/sigmoidoscopy). Results: The mean age of 711 childhood cancer survivors eligible for the study was 44 years (SD = 5.2 years). Among them, 231 (32.5%) reported ever performing home stool blood testing and 276 (38.8%) reported ever having colonoscopy or sigmoidoscopy. Of the 711 participants, 60 (8.4%) reported home stool blood testing in the past year (meeting screening guidelines for the general adult population) and 207 (29.1%) reported having a colonoscopy or sigmoidoscopy in the past 5 years (meeting surveillance recommendations for survivors of childhood cancer treated with radiation). In the multivariable analyses, factors associated with CRC surveillance were age 50 years or older (RR = 2.4, 95% CI = 1.9–2.9); having routine cancer follow-up visit within one year prior to questionnaire completion (RR = 1.7, 95% CI = 1.2–2.5); having a physical impairment requiring the assistance of others for routine activities of daily living (RR = 1.7, 95% CI = 1.2–2.2); and having discussed future cancer risk with a physician at their most recent follow-up visit (RR = 1.3, 95% CI = 1.1–1.6). Conclusions: More than 70% of survivors at risk for CRC were not screened as recommended. Indeed, unless a physician discussed their future cancer risk, most survivors were not screened until they reached age 50, the time at which CRC screening is recommended for individuals at average CRC risk. These findings underscore the need for education of survivors and their physicians regarding the heightened CRC risk following radiation.Purpose: To identify predictors of adherence to colorectal cancer (CRC) surveillance guidelines among survivors of childhood cancer who received ≥30 Gy radiotherapy to the abdomen, pelvis, or spine, and were 36 years or older at the time of last contact. Methods: We sought to identify predictors of self-reported CRC surveillance participation among 5-year survivors who completed the Childhood Cancer Survivor Study (CCSS) 2007 Follow-Up Questionnaire and met the criteria above. Univariate and multivariable generalized linear models with a log link and Poisson distribution were used to calculate relative risks (RR) with 95% confidence intervals (95% CI) for adherence to CRC surveillance guidelines (i.e., home stool blood testing and/or colonoscopy/sigmoidoscopy). Results: The mean age of 711 childhood cancer survivors eligible for the study was 44 years (SD = 5.2 years). Among them, 231 (32.5%) reported ever performing home stool blood testing and 276 (38.8%) reported ever having colonoscopy or sigmoidoscopy. Of the 711 participants, 60 (8.4%) reported home stool blood testing in the past year (meeting screening guidelines for the general adult population) and 207 (29.1%) reported having a colonoscopy or sigmoidoscopy in the past 5 years (meeting surveillance recommendations for survivors of childhood cancer treated with radiation). In the multivariable analyses, factors associated with CRC surveillance were age 50 years or older (RR = 2.4, 95% CI = 1.9–2.9); having routine cancer follow-up visit within one year prior to questionnaire completion (RR = 1.7, 95% CI = 1.2–2.5); having a physical impairment requiring the assistance of others for routine activities of daily living (RR = 1.7, 95% CI = 1.2–2.2); and having discussed future cancer risk with a physician at their most recent follow-up visit (RR = 1.3, 95% CI = 1.1–1.6). Conclusions: More than 70% of survivors at risk for CRC were not screened as recommended. Indeed, unless a physician discussed their future cancer risk, most survivors were not screened until they reached age 50, the time at which CRC screening is recommended for individuals at average CRC risk. These findings underscore the need for education of survivors and their physicians regarding the heightened CRC risk following radiation. The following are the 18 highest scoring abstracts of those submitted for presentation at the 37th Annual ASPO meeting held March 10–12, 2013, in Memphis, TN.