scholarly journals Exercise and Childhood Cancer—A Historical Review

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 82
Author(s):  
Javier S. Morales ◽  
Pedro L. Valenzuela ◽  
Daniel Velázquez-Díaz ◽  
Adrián Castillo-García ◽  
David Jiménez-Pavón ◽  
...  

Childhood cancer survivors are at risk of developing important adverse effects, many of which persist for years after the end of treatment. The implementation of interventions aiming at attenuating tumor/treatment-associated adverse effects is therefore a major issue in pediatric oncology, and there is growing evidence that physical exercise could help in this regard. The present review aims to summarize the main milestones achieved in pediatric exercise oncology. For this purpose, we conducted a systematic review of relevant studies written in English in the electronic database PubMed (from inception to 14 August 2021). This review traces the field of pediatric exercise oncology throughout recent history based on three fundamental pillars: (i) exercise during childhood cancer treatment; (ii) exercise during/after hematopoietic stem cell transplantation; and (iii) exercise after childhood cancer treatment. Accumulating evidence––although still preliminary in many cases––supports the safety and potential benefits of regular exercise (with no major contraindications in general) in the childhood cancer continuum, even during the most aggressive phases of treatment. Exercise can indeed represent an effective coadjuvant therapy for attenuating cancer-related adverse effects.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10014-10014
Author(s):  
Melissa A. Richard ◽  
Sogol Mostoufi-Moab ◽  
Nisha Rathore ◽  
Austin L. Brown ◽  
Stephen J. Chanock ◽  
...  

10014 Background: Childhood cancer survivors face increased risk for DM, a polygenic trait also attributable to cancer treatment exposures, particularly abdominal radiation. We aimed to characterize the role of genetic and treatment risk factors for DM among two large cohorts of childhood cancer survivors. Methods: We performed a nested case-control genome-wide association study for DM managed with oral medications in the original CCSS cohort (diagnosed 1970-1986). Logistic regression was conducted in the total sample (N = 5083) and stratified by 1) European ancestry (EA) and 2) abdominal radiation. Replication of suggestive variants (P < 1×10-7) using Fisher’s exact test was performed in independent cohorts: i) CCSS expansion diagnosed 1987-1999 (N = 2588) and ii) SJLIFE diagnosed 1962-2012 (N = 2182). To evaluate the effect of cancer treatment on the background genetic predisposition to DM, we estimated standardized effect sizes (Z’) among EA survivors in each abdominal radiation group for 398 index variants from the largest population-based EA DM study. Radiation group Z’ estimates were compared using linear regression. Results: In the original CCSS cohort we identified nine variants associated with DM and provide further support for four linked variants in the ERCC6L2 locus. Among all survivors, the rs55849673-A allele was associated with increased odds for DM among survivors in the original CCSS cohort (minor allele frequency [MAF]-cases = 0.055; MAF-controls = 0.024; adjusted odds ratio [aOR] = 2.9, 95% CI: 2.0-4.2, P = 3.7×10-8). Allele frequencies were consistent in the CCSS expansion (MAF-cases = 0.075; MAF-controls = 0.028; P = 0.07) and SJLIFE (MAF-cases = 0.036; MAF-controls = 0.027; P = 0.5). Additionally, rs55849673-A estimates were consistent among EA survivors and stronger among survivors not treated with abdominal radiation (MAF-cases = 0.052; MAF-controls = 0.021; aOR = 3.6, P = 1.6×10-6). Notably, in the CCSS expansion all rs55849673-A EA carriers who developed DM did not receive abdominal radiation (MAF-cases = 0.1; MAF-controls = 0.026; P = 0.04). More broadly, the Z’ of population-based DM index variants were 78% lower in survivors treated with abdominal radiation than survivors not treated with abdominal radiation (beta = 0.22; P = 0.01), indicating the background genetic risk for DM may be altered by treatment. Conclusions: We provide evidence for a novel locus of DM in childhood cancer survivors. This locus is a regulatory region associated with expression of ERCC6L2, a gene implicated in an East Asian population-based DM study. Taken together, our findings support the overwhelming effect of abdominal radiation on DM risk in childhood cancer survivors, relative to other risk factors, and provide insight on a genetic locus that may be useful for DM risk prediction in the context of cancer treatment.


Author(s):  
F. Daniel Armstrong ◽  
Maria L. Goldman

Childhood cancer is a rare disease, accounting for only 1% of all malignancies in humans of all ages. In 2007, approximately 10,400 new cases of cancer were diagnosed in children 14 years of age and younger (American Cancer Society 2007). Significant advances in diagnostic techniques and tailored treatments during the past three decades have increased the 5-year survival rate for all cancers to over 80% (Twombly 2007). For acute lymphoblastic leukemia (ALL), the most common form of childhood cancer, the current survival rate is approaching 90% (Pui and Howard 2008). Better survival has led to increased awareness and focus on the consequences of cancer treatment, called late effects. The Children’s Oncology Group has developed and published guidelines for monitoring childhood cancer survivors for late effects in nearly every organ system (Landier et al. 2004), with a recent growing interest in those affecting cognitive, academic, social, and behavioral function (Nathan et al. 2007), which are the focus of this chapter. It was long assumed that a cancer diagnosis and the severe toxicity associated with treatment was such a traumatic event that significant adverse psychological consequences were inevitable. Recent, large reports from the Childhood Cancer Survivorship Study and reviews of smaller studies suggest that this is not the case for the majority of children and adolescents treated for and surviving cancer (Eiser, Hill, and Vance 2000; Zebrack et al. 2002; Zeltzer et al. 2009). With the exception of children who experience central nervous system (CNS) cancer or cancer treatment (Zebrack et al. 2004), most childhood cancer survivors are not significantly different from the general population on measures of depression (Phipps and Srivastava 1999), selfesteem (Noll et al. 1999), hopefulness (Ritchie 2001), or posttraumatic stress disorder (PTSD). Some children experience symptoms of posttraumatic stress during acute treatment, but these symptoms diminish over time (Phipps et al. 2006). For children with CNS cancer or who receive treatment that affects the CNS, the picture is somewhat different, with poorer emotional and social functioning, neurocognitive function, and overall health-related quality of life (HRQL) reported in this subpopulation (Calaminus et al. 2000; Vannatta et al. 2007).


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22525-e22525
Author(s):  
Daniel M. Green ◽  
Mingjuan Wang ◽  
Matthew J. Krasin ◽  
Deokumar Srivastava ◽  
Mary V. Relling ◽  
...  

e22525 Background: Many childhood cancer survivors have been exposed to hepatotoxic agents. We assessed longitudinal hepatic injury, using alanine aminotransferase (ALT) elevation, and associated factors in a large cohort of long-term survivors. Methods: We evaluated SJLIFE participants ( > 10 years post-diagnosis, age ≥18 years) who had two or more determinations of ALT (T1 baseline, T2 last evaluation). Elevated ALT was defined as ALT > Upper Limit of Normal (ULN, 30 IU/mL for males and 19 IU/mL for females). Elastic net was used to perform model selection for elevated ALT at T2. Modified Poisson regression was used to identify risk factors for elevated ALT at T2. Results: Serial ALT assessments were available for 1941 survivors (49.6% female, 82.2% non-Hispanic white [NHW]). Their median age at diagnosis and T1 were 7.6 years (interquartile range [IQR] = 3.4-13.5) and 31.7 years (IQR = 26.1-38.1), respectively. Elapsed time from diagnosis to T1, and T1 to T2, were 23.3 years (IQR = 17.8-29.6) and 5.2 years (IQR = 4.4-5.7). ALT was normal at T1 and T2 in 45.7%, and persistently (25.9%) or newly (11.7%) abnormal in 37.6%. Compared to those with normal ALT at T1, those with elevated ALT at T2 were more likely to have NHW race/ethnicity, treatment with busulfan, increasing volume of the liver exposed to 10 Gray (Gy) or more (V10), body mass index (BMI) > 25 kg/m2, hepatitis C, metabolic syndrome, or treatment with atorvastatin, rosuvastatin or simvastatin at T2. History of hematopoietic stem cell transplantation (HSCT), but not busulfan, were additional risk factors included in the models for V15 and V20 (Table). Conclusions: Demographic, treatment, lifestyle, and non-oncologic interventions increase the risk for ALT elevation in survivors. These results may guide future treatment designs and lifestyle interventions. [Table: see text]


2019 ◽  
Vol 29 (06) ◽  
pp. 808-812 ◽  
Author(s):  
Kirsten Rose-Felker ◽  
Karen Effinger ◽  
Michael S Kelleman ◽  
Ritu Sachdeva ◽  
Lillian R. Meacham ◽  
...  

AbstractBackground:Cardiovascular disease is a leading cause of morbidity and mortality in childhood cancer survivors. Cardiologists must be aware of risk factors and long-term follow-up guidelines, which have historically been the purview of oncologists. Little is known about paediatric cardiologists’ knowledge regarding the cardiotoxicity of cancer treatment and how to improve this knowledge.Methods:A total of 58 paediatric cardiologists anonymously completed a 21-question, web-based survey focused on four cardio-oncology themes: cancer treatment-related risk factors (n = 6), patient-related risk factors (n = 6), recommended surveillance (n = 3), and cardiac-specific considerations (n = 6). Following the baseline survey, a multi-disciplinary team of paediatric cardiologists and cancer survivor providers developed an in-person and web-based educational intervention. A post-intervention survey was conducted 5 months later.Results:The response rate was 41/58 (70.7%) pre-intervention and 30/58 (51.7%) post-intervention. On the baseline survey, the percentage of correct answers was 68.8 ± 10.3%, which improved to 79.2 ± 16.2% after the intervention (p = 0.009). The theme with the most profound knowledge deficit was surveillance; however, it also had the greatest improvement after the intervention (49.6 ± 26.7 versus 66.7 ± 27.7% correct, p = 0.025). Individual questions with the largest per cent improvement pertained to risk of cardiac dysfunction with time since treatment (52.4 versus 93.1%, p = 0.002) and the role of dexrazoxane (48.8 versus 82.8%, p = 0.020).Conclusion:Specific knowledge deficits about the care of paediatric cancer survivors were identified amongst cardiologists using a web-based survey. Knowledge of surveillance was initially lowest but improved the most after an educational intervention. This highlights the need for cardio-oncology-based educational initiatives among paediatric cardiologists.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 12073-12073
Author(s):  
Wendy Bottinor ◽  
Cindy Im ◽  
Saro Armenian ◽  
Borah Hong ◽  
Rebecca M. Howell ◽  
...  

12073 Background: The direct impact of a major cardiovascular (CV) event on mortality among childhood cancer survivors is not well described. We hypothesized that mortality following a major CV event would be higher among survivors compared with siblings and that mortality would be influenced by primary cancer treatment. Methods: The CCSS cohort has conducted longitudinal follow-up of 25,658 survivors of childhood cancer and 5,051 siblings. All-cause and CV-cause specific mortality after a first event of heart failure (HF), coronary artery disease (CAD), or stroke occurring at least 5 years after cancer diagnosis, was estimated using the Kaplan-Meier method. The relative hazards (HR) and 95% confidence intervals (CI) between survivors and siblings as well as the influence of demographic (sex, age, race/ethnicity) and cancer treatment factors were estimated via Cox regression. Results: In total, 1780 survivors and 91 siblings experienced a serious CV event. Total deaths included 706 survivors (271 cardiac causes, 381 non-cardiac causes, 54 unknown causes) and 14 siblings. Survivors were a median age of 31.5 years (range 6.5-61.5) and 20.0 years (range 5.0-44.6) since cancer diagnosis at time of CV event. After a CV event, estimated 10- and 20-y all-cause mortality was significantly higher among survivors than siblings (Table). The HR for all-cause mortality was significantly higher among survivors than siblings after HF (HR 5.2, CI 2.1-13.0), CAD (HR 4.2, CI 2.0-9.0), and stroke (HR 4.6, CI 1.5-14.6). HF and stroke-specific mortality were not significantly increased among survivors versus siblings, in contrast to CAD-specific mortality (HR 3.5, CI 1.1-11.0). Among survivors, heart dose from radiotherapy (per 10 Gy) was associated with increased all-cause and cause-specific mortality after HF (HR 1.2, CI 1.0-1.3; HR 1.3, CI 1.0-1.7), all-cause mortality after CAD (HR 1.2, CI 1.0-1.3), and cause-specific mortality after stroke (HR 2.5, CI 1.2-4.9). Brain dose from radiotherapy was associated with increased all-cause mortality (HR 1.1, CI, 1.0-1.2, per 10 Gy) after stroke. Anthracycline dose was not associated with increased overall or cause-specific mortality risk after a CV event. Conclusions: After a CV event, mortality is higher among survivors than siblings. In survivors, mortality is primarily driven by non-cardiac causes. CAD and prior radiotherapy exposure to the heart and brain also influenced mortality.[Table: see text]


2019 ◽  
Vol 8 (12) ◽  
pp. 2204 ◽  
Author(s):  
Ylenia Duca ◽  
Andrea Di Cataldo ◽  
Giovanna Russo ◽  
Emanuela Cannata ◽  
Giovanni Burgio ◽  
...  

Background: A multi-disciplinary approach has led to an improvement in prognosis of childhood cancers. However, in parallel with the increase in survival rate, there is a greater occurrence of long-term toxicity related to antineoplastic treatment. Hypogonadism and infertility are among the most frequent endocrinological sequelae in young adult childhood cancer survivors. The aim of this study was to identify which category of patients, grouped according to diagnosis, therapy, and age at treatment, shows the worst reproductive function in adulthood. Methods: We evaluated morpho-volumetric development of the testis, endocrine function of the hypothalamic–pituitary–gonadal axis, and sperm parameters in 102 young adult childhood cancer survivors. Results: Overall, about one-third of patients showed low total testicular volume, total testosterone (TT) <3.5 ng/mL, and altered sperm count. Hodgkin’s disease, hematopoietic stem cell transplantation, and non-cranial irradiation associated to chemotherapy were risk factors for poor gonadal function. Patients treated in pubertal age showed lower total testicular volume; however, the difference was due to more gonadotoxic treatment performed in older age. Testicular volume was more predictive of spermatogenesis than follicle-stimulating hormone (FSH), while anti-Müllerian hormone (AMH) was not useful in the evaluation of testicular function of male childhood cancer survivors. Conclusions: Pre-pubertal subjects at high risk of future infertility should be candidates for testicular tissue cryopreservation.


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