Cancer-Related Worry as a Predictor of 5-yr Physical Activity Level in Childhood Cancer Survivors.

PURPOSE: Cancer-related worry (CRW; concerns related to cancer and its late effects) is prevalent among childhood cancer survivors. Elevated CRW has been associated with self-reported suboptimal physical activity. The aim of this investigation was to describe associations between CRW and objectively assessed physical activity in childhood cancer survivors. METHODS: CRW was assessed at a baseline evaluation using six survey items. Weekly minutes of moderate and vigorous physical activity were captured by actigraphy 5.25 (3.8-8.0) yr later. Factor analysis was used to identify types of worry; multiple regression determined independent associations between CRW and moderate and vigorous physical activity adjusting for sex, race, diagnosis, age at baseline, anxiety level at baseline, self-reported physical activity at baseline, and pain interference at baseline. RESULTS: Participants ( n = 1223) were an average of 30.9 (SD, 6.9) yr at baseline and 36.1 (SD, 7.1) yr at follow-up. Thirty-seven percent were survivors of leukemia, 26% of non-CNS solid tumors, 19% of lymphoma, 11% of CNS tumors, and 6% of other malignancies. Two types of CRW were identified: "body-focused" and "general fear." Body-focused CRW ( ß = -19.6, P = 0.012), endorsing pain interference ( ß = -27.7, P = 0.002) at baseline, and having a diagnosis of CNS tumor ( ß = -41.3, P = 0.0003) or non-CNS solid tumor ( ß = -19.4, P = 0.02) were negatively associated with physical activity at follow-up. CONCLUSIONS: CRW related to bodily function and appearance is associated with decreased physical activity. Clinicians should consider the potential negative impact of CRW on physical activity levels and provide behavioral counseling.

Progression of Frailty in Survivors of Childhood Cancer: A St. Jude Lifetime Cohort Report.

BACKGROUND: Some adult survivors of childhood cancers develop frailty at higher rates than expected based on their chronological age. This study examined the incidence of frailty among survivors at 10 or more years after diagnosis, frailty prevalence 5 years later, and risk factors for becoming frail. METHODS: Frailty was measured at study entry and 5 years later. Logistic regression tested the associations of several factors with having frailty at 5 years for all participants and separately by sex and by study entry frailty status. Cox models evaluated the hazard of death associated with entry frailty considering covariates. RESULTS: Cancer survivors (range = 0-22 years at diagnosis, median = 7 years) were ages 18-45 years (median = 30 years) at study entry. Frailty prevalence increased from 6.2% (95% confidence interval [CI] = 5.0% to 7.5%) to 13.6% (95% CI = 11.9% to 15.4%) at 5 years. Risk factors for frailty at follow-up among all survivors included chest radiation 20 Gy or higher (odds ratio [OR] = 1.98, 95% CI = 1.29 to 3.05), cardiac (OR = 1.58, 95% CI = 1.02 to 2.46), and neurological (OR = 2.58, 95% CI = 1.69 to 3.92) conditions; lack of strength training (OR = 1.74, 95% CI = 1.14 to 2.66); sedentary lifestyle (OR = 1.75, 95% CI = 1.18 to 2.59); and frailty at study entry (OR = 11.12, 95% CI = 6.64 to 18.61). The strongest risk factor for death during follow-up was prior frailty (OR = 3.52, 95% CI = 1.95 to 6.32). CONCLUSIONS: Prevalent frailty more than doubled at 5 years after study entry among adult childhood cancer survivors. Frailty at entry was the strongest risk factor for death. Because treatment exposures cannot be changed, mitigation of other risk factors for frailty, including lack of strength training and sedentary lifestyle, may decrease risk of adverse health events and improve longevity in survivors.

Kidney Function after Treatment for Childhood Cancer: A Report from the St. Jude Lifetime Cohort Study.

BACKGROUND: Survivors of childhood cancer may be at increased risk for treatment-related kidney dysfunction. Although associations with acute kidney toxicity are well described, evidence informing late kidney sequelae is less robust. METHODS: To define the prevalence of and risk factors for impaired kidney function among adult survivors of childhood cancer who had been diagnosed ≥10 years earlier, we evaluated kidney function (eGFR and proteinuria). We abstracted information from medical records about exposure to chemotherapeutic agents, surgery, and radiation treatment and evaluated the latter as the percentage of the total kidney volume treated with ≥5 Gy (V5), ≥10 Gy (V10), ≥15 Gy (V15), and ≥20 Gy (V20). We also used multivariable logistic regression models to assess demographic and clinical factors associated with impaired kidney function and Elastic Net to perform model selection for outcomes of kidney function. RESULTS: Of the 2753 survivors, 51.3% were men, and 82.5% were non-Hispanic White. Median age at diagnosis was 7.3 years (interquartile range [IQR], 3.3-13.2), and mean age was 31.4 years (IQR, 25.8-37.8) at evaluation. Time from diagnosis was 23.2 years (IQR, 17.6-29.7). Approximately 2.1% had stages 3-5 CKD. Older age at evaluation; grade ≥2 hypertension; increasing cumulative dose of ifosfamide, cisplatin, or carboplatin; treatment ever with a calcineurin inhibitor; and volume of kidney irradiated to ≥5 or ≥10 Gy increased the odds for stages 3-5 CKD. Nephrectomy was significantly associated with stages 3-5 CKD in models for V15 or V20. CONCLUSIONS: We found that 2.1% of our cohort of childhood cancer survivors had stages 3-5 CKD. These data may inform screening guidelines and new protocol development.

Long-term renal function after treatment for unilateral, nonsyndromic Wilms tumor. A report from the St. Jude Lifetime Cohort Study.

BACKGROUND: The impact of specific treatment modalities on long-term renal function and blood pressure among adult survivors of Wilms tumor (WT) has not been well documented. METHODS: Among 40 WT survivors and 35 noncancer controls, we estimated the glomerular filtration rate (eGFR) using the Chronic Kidney Disease-Epidemiology (CKD-EPI) equations with and without cystatin C, obtained 24-hour ambulatory blood pressure readings, and, among survivors only, measured 99m Tc diethylenetriamine pentaacetic acid (DTPA) plasma clearance. Survivors were treated with unilateral nephrectomy and nonnephrotoxic chemotherapy. Twenty received whole abdomen radiation therapy (WART) [median -16.5 Gray (Gy)], and 20 received no radiation therapy. Pairwise comparisons between survivors treated with and without WART, and each group to controls were performed using two-sample t tests. RESULTS: Twenty-six (65%) WT survivors were female, and 33 (83%) were non-Hispanic white. GFR estimated with creatinine or creatinine + cystatin C was decreased among irradiated survivors compared with controls. No irradiated or unirradiated participant had an eGFR (creatinine + cystatin C) < 60 mL/min/1.73 m2 . The prevalence of hypertension was significantly increased among unirradiated (25%) and irradiated survivors (35%) compared with controls (0%). Of the 24-hour ambulatory blood pressure monitoring parameters evaluated, only mean sleep period diastolic blood pressure load of those who received WART was significantly different from that of controls. CONCLUSIONS: Chronic kidney disease was infrequent in long-term survivors of unilateral nonsyndromic WT, whether treated with WART or no radiation. The prevalence of hypertension was increased in both groups compared with controls, emphasizing the need for ongoing monitoring of renal and cardiovascular health.

Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study.

BACKGROUND: Few data define the dose-specific relation between alkylating agent exposure and semen variables in adult survivors of childhood cancer. We undertook this study to test the hypothesis that increased exposure to alkylating agents would be associated with decreased sperm concentration in a cohort of adult male survivors of childhood cancer who were not exposed to radiation therapy for their childhood cancer. METHODS: We did semen analysis on 214 adult male survivors of childhood cancer (median age 7·7 years [range 0·01-20·3] at diagnosis, 29·0 years [18·4-56·1] at assessment, and a median of 21·0 years [10·5-41·6] since diagnosis) who had received alkylating agent chemotherapy but no radiation therapy. Alkylating agent exposure was estimated using the cyclophosphamide equivalent dose (CED). Odds ratios (ORs) and 95% CIs for oligospermia (sperm concentration >0 and <15 million per mL) and azoospermia were calculated with logistic regression modelling. FINDINGS: Azoospermia was noted in 53 (25%) of 214 participants, oligospermia in 59 (28%), and normospermia (sperm concentration ≥15 million per mL) in 102 (48%) participants. 31 (89%) of 35 participants who received CED less than 4000 mg/m(2) were normospermic. CED was negatively correlated with sperm concentration (correlation coefficient=-0·37, p<0·0001). Mean CED was 10 830 mg/m(2) (SD 7274) in patients with azoospermia, 8480 mg/m(2) (4264) in patients with oligospermia, and 6626 mg/m(2) (3576) in patients with normospermia. In multivariable analysis, CED was significantly associated with an increased risk per 1000 mg/m(2) CED for azoospermia (OR 1·22, 95% CI 1·11-1·34), and for oligospermia (1·14, 1·04-1·25), but age at diagnosis and age at assessment were not. INTERPRETATION: Impaired spermatogenesis was unlikely when the CED was less than 4000 mg/m(2). Although sperm concentration decreases with increasing CED, there was substantial overlap of CED associated with normospermia, oligospermia, and azoospermia. These data can inform pretreatment patient counselling and use of fertility preservation services. FUNDING: US National Cancer Institute, American Lebanese Syrian Associated Charities.