Dataset Information

Long-term exposure to circulating platinum is associated with late effects of treatment in testicular cancer survivors.

ABSTRACT:

Background

The success of cisplatin-based (Platinol, Bristol-Myers Squibb Company, New York, NY, USA) chemotherapy for testicular cancer comes at the price of long-term and late effects related to healthy tissue damage. We assessed and modelled serum platinum (Pt) decay after chemotherapy and determined relationships between long-term circulating Pt levels and known late effects.

Patients and methods

In 99 testicular cancer survivors, treated with cisplatin-based chemotherapy, serum and 24-h urine samples were collected during follow-up (1-13 years after treatment). To build a population pharmacokinetic model, measured Pt data were simultaneously analysed, together with cisplatin dose, age, weight and height using the NONMEM software. Based on this model, area under the curve between 1 and 3 years after treatment (Pt AUC1-3 years) was calculated for each patient. Predicted long-term Pt exposure was related to renal function and to late effects of treatment assessed median 9 (3-15) years after chemotherapy.

Results

Decay of Pt was best described by a two-compartment model. Mean terminal T1/2 was 3.7 (range 2.5-5.2) years. Pt AUC1-3 years correlated with cumulative cisplatin dose, and creatinine clearance before and 1 year after treatment. Patients with paraesthesia had higher Pt AUC1-3 years (30.9 versus 27.0 µg/l month) compared with those without paraesthesia (P = 0.021). Patients with hypogonadism, elevated LDL-cholesterol levels or hypertension also had higher Pt AUC1-3 years.

Conclusions

Renal function before and after cisplatin treatment is an important determinant of long-term Pt exposure. Known long-term effects of testicular cancer treatment, such as paraesthesia, hypogonadism, hypercholesterolaemia and hypertension, are associated with long-term circulating Pt exposure.

SUBMITTER: Boer H

PROVIDER: S-EPMC4621032 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Long-term exposure to circulating platinum is associated with late effects of treatment in testicular cancer survivors.

Boer H H Proost J H JH Nuver J J Bunskoek S S Gietema J Q JQ Geubels B M BM Altena R R Zwart N N Oosting S F SF Vonk J M JM Lefrandt J D JD Uges D R A DR Meijer C C de Vries E G E EG Gietema J A JA

Annals of oncology : official journal of the European Society for Medical Oncology 20150907 11

<h4>Background</h4>The success of cisplatin-based (Platinol, Bristol-Myers Squibb Company, New York, NY, USA) chemotherapy for testicular cancer comes at the price of long-term and late effects related to healthy tissue damage. We assessed and modelled serum platinum (Pt) decay after chemotherapy and determined relationships between long-term circulating Pt levels and known late effects.<h4>Patients and methods</h4>In 99 testicular cancer survivors, treated with cisplatin-based chemotherapy, ser ...[more]

PMID: 26347114

Similar Datasets

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: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.

Project description:BackgroundPlastic pollution is greatly serious in the ocean and soil. Microplastics (MPs) degraded from plastic has threatened animals and humans health. The accumulation of MPs in the tissues and blood in animals and humans has been found. There is therefore a need to assess the toxicological effects of MPs on the reproductive system.ResultsIn this study, we explored the effect of polystyrene microplastics (PS-MPs) on premature testicular aging in vitro and in vivo. In vitro, we found that testicular sertoli cells (TM4 cells) was prematurely senescent following PS-MPs treatment by the evaluation of a range of aging marker molecules (such as Sa-β-gal, p16 and 21). TM4 cells were then employed for in vitro model to study the potential molecular mechanism by which PS-MPs induce the premature senescence of TM4 cells. NF-κB is identified as a key molecule for PS-MPs-induced TM4 cellular senescence. Furthermore, through eliminating reactive oxygen species (ROS), the activation of nuclear factor kappa B (NF-κB) was blocked in PS-MPs-induced senescent TM4 cells, indicating that ROS triggers NF-κB activation. Next, we analyzed the causes of mitochondrial ROS (mtROS) accumulation induced by PS-MPs, and results showed that Ca2+ overload induced the accumulation of mtROS. Further, PS-MPs exposure inhibits mitophagy, leading to the continuous accumulation of senescent cells. In vivo, 8-week-old C57 mice were used as models to assess the effect of PS-MPs on premature testicular aging. The results illustrated that PS-MPs exposure causes premature aging of testicular tissue by testing aging markers. Additionally, PS-MPs led to oxidative stress and inflammatory response in the testicular tissue.ConclusionIn short, our experimental results revealed that PS-MPs-caused testicular premature aging is dependent on Ca2+/ROS/NF-κB signaling axis. The current study lays the foundation for further exploration of the effects of microplastics on testicular toxicology.

Project description:Parents of children with cancer desire information regarding the late effects of treatment. In the current study, the authors assessed parents' preparedness for late effects at least 5 years after their child's diagnosis.A cross-sectional survey was conducted of all eligible parents of children with cancer between April 2004 and September 2005 at Dana-Farber/Boston Children's Cancer and Blood Disorders Center within 1 year of diagnosis, and a follow-up questionnaire was administered at least 5 years later.Approximately 66% of parents of children who were still living, and who were able to be contacted, completed the follow-up questionnaire (91 of 138 parents). Approximately 77% of respondents (70 of 91 respondents) were parents of disease-free survivors and 23% (21 of 91 respondents) were parents of children with recurrent disease. The majority of parents believed they were well prepared for their child's oncology treatment (87%), but fewer felt prepared for future limitations experienced by their children (70%; P = .003 using the McNemar test) or for life after cancer (62%; P<.001). On bivariable analysis among parents of disease-free survivors, parents were more likely to believe themselves to be prepared for future limitations when they also reported that communication with the oncologist helped to address worries regarding the future (odds ratio, 4.50; P = .01). At the time of diagnosis, both parents and physicians underestimated a child's risk of future limitations; 45% of parents and 39% of clinicians predicted future limitations in physical abilities, intelligence, or quality of life, but at the time of the follow-up questionnaire >5 years later, 72% of children experienced limitations in at least 1 domain.Parents believe themselves to be less prepared for survivorship than for treatment. High-quality communication may help parents to feel more prepared for life after cancer therapy. Cancer 2016;122:2587-94. © 2016 American Cancer Society.

Project description:Simple Summary Due to previous cancer and its treatments, long-term childhood cancer survivors (CCS) are at risk of developing medical comorbidities, as well as socioeconomic vulnerability. Above all, work placement, financial independence, and job satisfaction can represent burdensome areas for some CCS. Regarding this topic, it is important to consider the variety of country-specific educational and vocational systems. The aim of this study is to provide a description of the occupational status of CCS in the Italian socio-economic scenery and to evaluate the association between late effects and unemployment and late effects and job satisfaction. Our data contribute to the description of the different country scenery of work placement for CCS in Europe and agree with previous literature on the impact of severe late effects on occupation. Future research in this field can be focused on interventions to improve CCS in obtaining jobs suitable for their health. Abstract Late effects of cancer and its treatments during childhood or adolescence can impact work placement and increase the risk of unemployment. The aim of this study is to describe the work placement and the perceived job and economic satisfaction of long-term childhood cancer survivors (CCS). Jobs have been categorized according to the International Standard Classification of Occupations version 08 (ISCO-08), and satisfaction has been evaluated through the Satisfaction Profile (SAT-P). Out of 240 CCS (female = 98) included: 53 were students, 46 were unemployed and 141 were employed. Within unemployed survivors, 89.13% were affected by late effects (n = 41). The presence of at least one severe late effect was significantly associated with the probability of unemployment (OR 3.21; 95% CI 1.13–9.12, p < 0.050), and having any late effect was inversely related to the level of satisfaction of the financial situation of unemployed CCS (b −35.47; 95% CI −59.19, −11.74, p = 0.004). Our results showed that being a survivor with severe comorbidities has a significantly negative impact on occupation and worsens the perception of satisfaction of economic situations. Routinary follow-up care of CCS should include the surveillance of socioeconomic development and provide interventions, helping them to reach jobs suitable for their health.

Dataset Information

Long-term exposure to circulating platinum is associated with late effects of treatment in testicular cancer survivors.

Background

Patients and methods

Results

Conclusions

Publications

Long-term exposure to circulating platinum is associated with late effects of treatment in testicular cancer survivors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets