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Toxicities Associated with Cisplatin-Based Chemotherapy and Radiotherapy in Long-Term Testicular Cancer Survivors.

ABSTRACT: Testicular cancer has become the paradigm of adult-onset cancer survivorship, due to the young age at diagnosis and 10-year relative survival of 95%. This clinical review presents the current status of various treatment-related complications experienced by long-term testicular cancer survivors (TCS) free of disease for 5 or more years after primary treatment. Cardiovascular disease and second malignant neoplasms represent the most common potentially life-threatening late effects. Other long-term adverse outcomes include neuro- and ototoxicity, pulmonary complications, nephrotoxicity, hypogonadism, infertility, and avascular necrosis. Future research efforts should focus on delineation of the genetic underpinning of these long-term toxicities to understand their biologic basis and etiopathogenetic pathways, with the goal of developing targeted prevention and intervention strategies to optimize risk-based care and minimize chronic morbidities. In the interim, health care providers should advise TCS to adhere to national guidelines for the management of cardiovascular disease risk factors, as well as to adopt behaviors consistent with a healthy lifestyle, including smoking cessation, a balanced diet, and a moderate to vigorous intensity exercise program. TCS should also follow national guidelines for cancer screening as currently applied to the general population.

SUBMITTER: Fung C

PROVIDER: S-EPMC5835297 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Toxicities Associated with Cisplatin-Based Chemotherapy and Radiotherapy in Long-Term Testicular Cancer Survivors.

Fung Chunkit C Dinh Paul P Ardeshir-Rouhani-Fard Shirin S Schaffer Kerry K Fossa Sophie D SD Travis Lois B LB

Advances in urology 20180218

Testicular cancer has become the paradigm of adult-onset cancer survivorship, due to the young age at diagnosis and 10-year relative survival of 95%. This clinical review presents the current status of various treatment-related complications experienced by long-term testicular cancer survivors (TCS) free of disease for 5 or more years after primary treatment. Cardiovascular disease and second malignant neoplasms represent the most common potentially life-threatening late effects. Other long-term ...[more]

PMID: 29670654

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Project description:BackgroundIt is unknown how body fat distribution modulates the cardiometabolic risk of testicular cancer survivors after cisplatin-based chemotherapy.MethodsFor 455 patients enrolled in the Platinum Study at Memorial Sloan Kettering Cancer Center, visceral (VAT) and subcutaneous (SAT) adipose tissue was quantified on prechemotherapy computed tomography. The VAT-to-SAT ratio was calculated as a quantitative measure of central adiposity. Endpoints were incidence of new posthemotherapy cardiometabolic disease (new antihypertensive, lipid-lowering, or diabetes medication), and postchemotherapy Framingham risk scores. Cox models and linear regression with interaction terms were applied. Postchemotherapy body fat distribution was analyzed in 108 patients. All statistical tests were 2-sided.ResultsThe baseline median age was 31 years (interquartile range [IQR] = 26-39 years), body mass index (BMI) was 26 kg/m2 (IQR = 24-29 kg/m2), and the VAT-to-SAT ratio was 0.49 (IQR = 0.31-0.75). The median follow-up was 26 months (IQR = 16-59 months). Higher prechemotherapy VAT-to-SAT ratios inferred a higher likelihood of new cardiometabolic disease among patients with a BMI of 30 kg/m2 or greater (age-adjusted hazard ratio = 3.14, 95% confidence interval = 1.02 to 9.71, P = .047), but not other BMI groups. The prechemotherapy VAT-to-SAT ratio was associated with postchemotherapy Framingham risk scores in univariate regression analysis (exp(β)-estimate: 2.10, 95% confidence interval = 1.84 to 2.39, P < .001); in a multivariable model, this association was stronger in younger vs older individuals. BMI increased in most patients after chemotherapy and correlated with increases in the VAT-to-SAT ratio (Spearman r = 0.39, P < .001).ConclusionsIn testicular cancer survivors, central adiposity is associated with increased cardiometabolic risk after cisplatin-based chemotherapy, particularly in obese or young men. Weight gain after chemotherapy occurs preferentially in the visceral compartment, providing insight into the pathogenesis of cardiovascular disease in this population.

Project description:BACKGROUND:Treatment for cancer may lead to development of cognitive difficulties in cancer survivors. This study aimed to evaluate long-term cognitive functioning (CogF) in germ-cell tumor (GCT) survivors. SUBJECTS, MATERIALS, AND METHODS:GCT survivors (n = 155) from the National Cancer Institute of Slovakia completed the Functional Assessment of Cancer Therapy Cognitive Function at a median of 10 years of follow-up (range: 5-32). The study group consisted of survivors receiving a cisplatin-based chemotherapy, radiotherapy to the retroperitoneal lymph nodes, or both, whereas the control group included survivors treated with orchiectomy only. RESULTS:Of the total survivors, 138 received treatment beyond orchiectomy and 17 controls had orchiectomy alone. Any treatment resulted in significantly greater cognitive difficulties on the overall cognitive function score. Treatment with radiotherapy was associated with cognitive declines in overall cognitive functioning and in subscales for perceived cognitive impairment and cognitive impairment perceived by others (both p < .05). The burden of chemotherapy plus radiotherapy or radiotherapy versus controls resulted in the impairment in all cognitive functioning domains (all p < .05). Overall long-term cognitive impairment was independent of age in the multivariable analysis. CONCLUSION:This prospective study shows that GCT survivors suffer from a long-term CogF impairment. These results may help guide clinicians' decisions in treatment and follow-up of GCTs. IMPLICATIONS FOR PRACTICE:In this study, long-term survivors of germ-cell tumors have reported cognitive impairment after curative treatment with radiotherapy and chemotherapy compared with controls who had treatment with orchiectomy only. These data provide an argument against the use of adjuvant radiotherapy for stage I seminoma. Unnecessary overtreatment with chemotherapy and additional radiotherapy after chemotherapy should be avoided.

Project description:ContextTesticular germ-cell tumors (GCT) are highly curable. A multidisciplinary approach, including cisplatin-based chemotherapy has resulted in cure in the majority of patients with GCT. Thus, the life expectancy of survivors will extend to many decades post-diagnosis. Late treatment toxicities associated with cisplatin-based chemotherapy may impact their future health.ObjectiveTo systematically evaluate evidence regarding the long-term toxicity of cisplatin in GCT survivors.Evidence acquisitionWe carried out a critical review of PubMed/Medline in February 2017 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Identified reports were reviewed according to the Consolidated Standards of Reporting Trials (CONSORT) criteria. Eighty-three publications were selected for inclusion in this analysis.Evidence synthesisIncluded reports evaluated long-term toxicities of cisplatin-based chemotherapy in GCT survivors. Studies reporting neuro- and ototoxicity, secondary malignancies, cardiovascular, renal and pulmonary toxicities, hypogonadism and infertility were found. Seven studies (8%) reported genetic underpinnings of long-term toxicities and 3 (4%) and 14 (19%) studies correlated long-term toxicities with circulating platinum levels and cumulative dose of cisplatin, respectively. Significant risks for long-term toxicities associated with cisplatin and platinum-based regimens were reported. The cumulative dose of cisplatin and circulating platinum were reported as risk factors. Several single-nucleotide polymorphisms identified patients susceptible to cisplatin compared with wild-type individuals.ConclusionsGCT survivors cured with cisplatin-based chemotherapy are at risk for long-term side-effects. Detection of single-nucleotide polymorphisms could be a valuable tool for predicting long-term toxicities.Patient summaryHerein, this article summarizes the available evidence of long-term toxicity of cisplatin-based chemotherapy in GCT survivors and provide insights from Indiana University.

Project description:PurposesPhysical activity (PA) may mitigate late cardiometabolic toxicity of cisplatin-based chemotherapy in testicular germ cell tumor (TGCT) long-term survivors. In this cross-sectional study, we evaluated the effects of habitual PA on metabolic syndrome (MetS) prevalence, and on the markers of cardiometabolic health and chronic inflammation in a population of long-term TGCT survivors.MethodsMetS prevalence was evaluated, and habitual PA was assessed using Baecke's habitual PA questionnaire in TGCT survivors (n=195, age=41.1±8.1years, 11.7±5.2years post-therapy) and healthy male controls (n=41, age=38.2±8.8years). Participants were stratified into low- and high-PA groups based on median values. Differences were examined between low- and high-PA groups (in the entire sample, TGCT survivor sub-samples differing in disease stage, and healthy controls), and between TGCT survivors and controls. Next, TGCT survivors were stratified into age- and BMI-matched sub-groups based on post-treatment time (5-15/15/30years) and number of chemotherapy cycles (≤3/>3), allowing us to detect age- and BMI-independent effects of habitual PA on cardiometabolic health in the given TGCT survivor sub-populations. A correlation matrix of habitual PA and sport activity with cardiometabolic and pro-inflammatory markers was generated.ResultsTGCT survivors had higher MetS prevalence than controls. Patients with high habitual PA had lower waist circumference and Systemic Inflammation Index. Habitual PA scores correlated positively with HDL-cholesterol and negatively with waist circumference and atherogenic risk. Furthermore, cardiometabolic benefits of habitual PA were more pronounced in patients with disease stages 1 and 2. Effects of habitual PA on patients sub-populations stratified by chemotherapy dose and post-treatment time clearly showed that higher levels of habitual PA were associated with lower numbers of MetS components, except for patients who received more than 3 chemotherapy cycles and were examined more than15 years post-therapy.ConclusionsHigher levels of habitual PA effectively mitigated cardiometabolic toxicity in TGCT survivors. Patients with higher cumulative doses of chemotherapy may need structured exercise interventions involving higher-intensity physical activity to achieve significant improvements in cardiometabolic health.

Dataset Information

Toxicities Associated with Cisplatin-Based Chemotherapy and Radiotherapy in Long-Term Testicular Cancer Survivors.

Publications

Toxicities Associated with Cisplatin-Based Chemotherapy and Radiotherapy in Long-Term Testicular Cancer Survivors.

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