Effects Of Childhood Cancer Therapy Research Articles

Genetic and epigenetic bases of long-term adverse effects of childhood cancer therapy.

Over the past decade, genome-scale molecular profiling of large childhood cancer survivorship cohorts has led to unprecedented advances in our understanding of the genetic and epigenetic bases of therapy-related adverse health outcomes in this vulnerable population. To facilitate the integration of knowledge generated from these studies into formulating next-generation precision care for survivors of childhood cancer, we summarize key findings of genetic and epigenetic association studies of long-term therapy-related adverse effects including subsequent neoplasms and cardiomyopathies among others. We also discuss therapy-related genotoxicities including clonal haematopoiesis and DNA methylation, which may underlie accelerated molecular ageing. Finally, we highlight enhanced risk prediction models for survivors of childhood cancer that incorporate both genetic factors and treatment exposures, aiming to achieve enhanced accuracy in predicting risks for this population. These new insights will hopefully inspire future studies that harness both expanding omics resources and evolving data science methodology to accelerate the translation of precision medicine for survivors of childhood cancer.

A PhD completed. Long-term effects of childhood cancer therapy on oral health

In recent years, the five-year survival rate for childhood cancer has increased to about 80%. However, childhood cancer therapy can have serious long-term adverse effects on general health later in life. Of survivors, 75% experience 1 or more late effects. This PhD research aimed to gain more insight into the long-term effects on oral health of childhood cancer therapy, 15 years or more after diagnosis. This study, which is part of the Dutch Childhood Cancer Survivor Study Late Effects 2 (DCCSS LATER 2 Study), showed that oral complications such as dental developmental disorders and hyposalivation occur frequently. Most important risk factors were head and neck radiotherapy of the salivary glands, (alkylating) cytostatic agents, and age at the time of the cancer diagnosis. Dentists should be aware of childhood cancer in the medical history of their patient and of the type of therapy received. Regular dental visits are an essential part of long-term follow-up care of childhood cancer survivors.

Secondary Effects of Childhood Cancer Therapy

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Chemotherapy as a risk factor for caries and gingivitis in children with acute lymphoblastic leukemia: A retrospective cohort study.

Dental and oral anomalies are among the most common long-term side effects of childhood cancer therapy. To evaluate chemotherapy as a risk factor for caries lesions and gingivitis in children with acute lymphoblastic leukemia (ALL) treated with the ALL IC-BFM 2009 chemotherapy protocol. A retrospective cohort study was designed. Clinical records of 23 paediatric patients with ALL exposed to chemotherapy in the Regional Hospital in Valdivia, Chile, and 46 unexposed patients assessed every 3months for 24months were analyzed. The data on gender, age, index of the number of decayed, missing, or filled teeth, and the presence of gingivitis were recorded (Mann-Whitney U test and logistic regression analysis, p≤.05). A significantly greater frequency of gingivitis (69.57%; p<.002) and a mean of new caries lesions were observed in children treated with chemotherapy than in the unexposed children (p<.01). The chemotherapy protocol presented a relative risk of 2.15 (95% CI=1.22 - 2.66; p=.01) for new caries lesions and 2.29 (95% CI=1.76 - 3.82; p=.002) for gingivitis. The ALL IC-BFM 2009 chemotherapy protocol in patients with ALL is a risk factor for new caries lesions and gingivitis.

Neurotoxic Effects of Childhood Cancer Therapy and Its Potential Neurocognitive Impact.

Neurotoxic Effects of Childhood Cancer Therapy and Its Potential Neurocognitive Impact.

Dental late effects of antineoplastic treatment on childhood cancer survivors: Radiographic findings.

Dental anomalies are common late side effects of childhood cancer therapy and may lead to anatomical, functional, and aesthetic sequelae. The study aimed to record dental late effects of antineoplastic treatment and associate them with disease and treatment characteristics in order to identify possible risk factors. Orthopantomograms of 70 survivors aged 4-21years, who were treated at ages 0-10years for any type of malignancy and completed antineoplastic treatment at least one year before, were examined. Incidence of developmental disturbances was recorded. Their severity was calculated, and odds ratios for the development of severe defects were estimated. Root defects presented in 62% of the participants, with impaired root growth being the most common (58%). Increased incidence was associated with combination treatment protocols, irradiation to the head and neck region, and administration of antimetabolites, steroids, and vincristine. Mean DeI value was 17.46 with risk factors for the development of severe root defects being diagnosis of acute lymphoblastic leukemia, combination treatment protocols, administration of cyclophosphamide and steroids, and hemopoietic stem cell transplantation. Root defects are common among childhood cancer survivors, with their incidence and severity being affected by multiple disease and treatment characteristics.

The Experience of Chemotherapy-Induced Peripheral Neuropathy Among Childhood Cancer Survivors

As the number of childhood cancer survivors (CCS) is increasing, it is imperative to understand the late effects of childhood cancer therapy to optimize their health and quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is an unpleasant effect of chemotherapy that affects the peripheral nervous system. This qualitative study uses narrative analysis with a phenomenological influence to understand the lived experience of CIPN among five CCS utilizing photo-elicitation. The lived experience of CIPN is characterized by "a condition of disconnection" with three subthemes: (1) disconnection between mind and body, (2) disconnection between anticipated potential and reality, and (3) disconnection between survivors and support. The condition of disconnection leads to a variety of negative physical and emotional performance outcomes. These findings support the need for refined clinical strategies for identifying this underappreciated condition and further development of interventions to "rebuild the connections" that CCS are lacking.

Evidence for Genetic Risk Contributing to Long-Term Adverse Treatment Effects in Childhood Cancer Survivors.

Survivors of childhood cancer are at increased risk for therapy-related morbidities and mortality. Although the demographic and clinical factors predicting the risk for long-term effects of cancer therapy are well known, the impact of genetic risk for specific late effects is less clearly defined. Here, we review the extant literature and recent research describing genetic modifiers to risk for the more common late effects of childhood cancer therapy. Results of this research support the need for clinical trials that attempt to further refine risk prediction by incorporating genetic testing into existing algorithms that are primarily based on clinical and demographic factors. Confirmation of genetic predisposition, as defined by reproducibility and prospective validation, would permit therapeutic modification and discussion of individualized survivor care plans even at initial cancer diagnosis.

Cardiac Diseases Following Childhood Cancer Treatment: Cohort Study.

Cardiac disease (CD) is one of the major side effects of childhood cancer therapy, but until now little has been known about the relationship between the heart radiation dose (HRD) received during childhood and the risk of CD. The cohort comprised 3162 5-year survivors of childhood cancer. Chemotherapy information was collected and HRD was estimated. There were 347 CDs in 234 patients, 156 of them were rated grade ≥3. Cox and Poisson regression models were used. The cumulative incidence of any type of CD at 40 years of age was 11.0% (95% confidence interval [CI], 9.5-12.7) and 7·4% (95% CI, 6.2-8.9) when only the CDs of grade ≥3 were considered. In comparison with patients who received no anthracycline and either no radiotherapy or an HRD<0·1Gy, the risk was multiplied by 18·4 (95% CI, 7.1-48.0) in patients who had received anthracycline and no radiotherapy or a HRD <0.1Gy, by 60.4 (95% CI, 22.4-163.0) in those who had received no anthracycline and an HRD≥30Gy, and 61.5 (95% CI, 19.6-192.8) in those who had received both anthracycline and an HRD≥30Gy. Survivors of childhood cancers treated with radiotherapy and anthracycline run a high dose-dependent risk of developing CD. CDs develop earlier in patients treated with anthracycline than in those treated without it.

The effect of childhood cancer therapy on ovarian reserve and pubertal development

The effects of childhood cancer therapy on ovarian reserve tests and on pubertal development within 5 years were compared with a control group. The study group was composed of 41 patients who underwent chemotherapy during pre-menarche (subgroup A; n = 15) and after menarche (subgroup B; n = 26); the control group was composed of 44 patients admitted with non-cancer related diseases (in total n = 85). Mean total ovarian volume and total antral follicle counts on ultrasound examination were significantly lower in the study group compared with the control group (3.5 ± 2.3 versus 5.2 ± 2.4 ml; P = 0.001; and 3.4 ± 3.3 versus 8.6 ± 3.5; P < 0.001, respectively). Mean FSH level was significantly higher in the study group (13.5 ± 16.2 versus 7.3 ± 2.7 mIU/ml; P = 0.017). Anti-Müllerian hormone levels in subgroup A were significantly higher than in subgroup B (1.8 ± 0.1 versus 1.5 ± 0.08 pg/dl; P = 0.034). In conclusion ovarian volume, antral follicle count and FSH can be used for evaluating the harmful effect of cancer chemotherapy on ovarian follicles. Post-menarche, Anti-Müllerian values reveal that ovarian follicles are more sensitive to the devastating effects of cytotoxic treatment.

Thyroid abnormalities in survivors of childhood cancer.

Ob­jec­ti­ve: To investigate the late side effects of childhood cancer therapy on the thyroid gland and to determine the risk factors for development of thyroid disorder among childhood cancer survivors.Methods: One hundred and twenty relapse-free survivors of childhood cancer (aged 6-30 years) were included in this study. The diagnoses of patients were lymphoma, leukemia, brain tumor, rhabdomyosarcoma and nasopharyngeal carcinoma (NPC). The patients were divided into two groups depending on the treatment: group 1-chemotherapy (ChT) only (n=52) and group 2-combination therapy of ChT + radiotherapy (RT) (head/neck/thorax) (n=68). Thyroid function tests, urinary iodine levels, and thyroid gland ultrasound examinations were evaluated in both groups.Results: Incidence of thyroid disease was 66% (n=79) in the survivors. The thyroid abnormalities were: hypothyroidism (HT) (n=32, 27%), thyroid nodules (n=27, 22%), thyroid parenchymal heterogeneity (n=40, 33%), autoimmune thyroiditis (n=36, 30%), and thyroid malignancy (n=3, 2%). While the incidence of HT and thyroid nodules in group 2 was significantly higher than in group 1, the incidence of thyroid parenchymal heterogeneity and autoimmune thyroiditis was similar in the two patient groups. HT and thyroid malignancy were seen only in group 2. In multivariate logistic regression analysis, a history of Hodgkin lymphoma (HL), brain tumor and NPC, as well as cervical irradiation and 5000-5999 cGy doses of radiation were found to constitute risk factors for HT. History of HL and 4000-5999 cGy doses of radiation were risk factors for thyroid nodules. Head/neck irradiation and treatment with platinum derivatives were risk factors for autoimmune thyroiditis. In univariate analysis, a history of NPC, cervical + nasopharyngeal irradiation, and treatment with platinum derivatives were risk factors for thyroid parenchymal heterogeneity.Conclusion: Our results indicate that there is especially an increased risk of HT and thyroid nodules in patients treated with combination therapy of ChT with head/neck/thorax RT. Although chemotherapeutic agents per se do not seem to cause HT, longer follow-up is needed to assess whether or not there is an increased risk for autoimmune thyroiditis and thyroid parenchymal heterogeneity after antineoplastic therapy.

Primary thyroid cancer as late effects of childhood cancer therapy: a case series of five patients

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Auditory late effects of childhood cancer therapy: a report from the Children's Oncology Group.

Children treated for malignancies may be at risk for early- or delayed-onset hearing loss that can affect learning, communication, school performance, social interaction, and overall quality of life. Survivors at particular risk include those treated with platinum compounds (cisplatin and/or carboplatin) for neuroblastoma, hepatoblastoma, osteosarcoma, or germ-cell tumors and/or those treated with radiation that affects the ear at doses of >30 Gy for pediatric head and neck tumors. The aims of the Auditory/Hearing Late Effects Task Force of the Children's Oncology Group in this report were to (1) review ototoxicity resulting from childhood cancer therapy including platinum compounds (cisplatin and carboplatin) and radiation, (2) describe briefly cochlear pathophysiology and genetics of cisplatin-related hearing loss, (3) explain the impact of hearing loss resulting from chemotherapy and radiation, and (4) offer recommendations regarding evaluation and management of pediatric patients who are at risk for treatment-related hearing loss. A questionnaire is included as a tool to assist pediatricians in assessment.

The Late Effects of Childhood Cancer Therapy

In this article the difficulties that face survivors of childhood cancer therapy are presented, and the late effects of such therapy, separated into nonmalignant and malignant late effects, are discussed according to organ system. Recommendations for monitoring the late effects are set forth. A table listing radiation-therapy site and chemotherapeutic agents and selected late effects that result from their use is provided. Finally, a brief recommendation regarding the establishment of a late-effects clinic is also presented.

Endocrine late effects of childhood cancer therapy

In the past decades, new cancer treatment approaches for children and adolescents have led to a decrease in recurrence rates and an increase in long-term survival. Recent studies have focused on the evaluation of the late effects on bone of pediatric cancer-related treatments, such as chemotherapy, radiation and surgery. Treatment of childhood cancer can impair the attainment of peak bone mass, predisposing to premature onset of low bone mineral density, or causing other bone side-effects, such as bone quality impairment or avascular necrosis of bone. Lower bone mineral density and microarchitectural deterioration can persist during adulthood, thereby increasing fracture risk. Overall, long-term follow-up of childhood cancer survivors is essential to define specific groups at higher risk of long-term bone complications, identify unrecognized long-term adverse effects, and improve patient care. Children and adolescents with a cancer history should be carefully monitored, and patients should be informed of possible late complications of their previous medical treatment. The International Osteoporosis Foundation convened a working group to review the bone complications of pediatric cancer survivors, outlining recommendations for the management of bone health, in order to prevent and treat these complications.

Late effects of childhood cancer therapy

One in every 900 young adults is a survivor of childhood cancer. Survivors may experience a wide variety of late effects stemming from the treatment they received. It is estimated that a significant portion of adult survivors of childhood cancer are not followed regularly in a center familiar with the late effects of their specific therapy. Therefore it is important for health care professionals in any setting to have an understanding of these possible late effects and encourage the survivor to seek appropriate follow-up. This article will provide a general overview of the potential late effects of childhood cancer therapy. Copyright 2003, Elsevier Inc. All rights reserved.

Late effects of childhood cancer therapy

Late effects of childhood cancer therapy