Subsequent primary neoplasms after childhood cancer therapy - design and description of the German nested case-control study STATT-SCAR.

BACKGROUND: Subsequent primary neoplasms (SPN) are among the most severe late effects and the second most frequent cause of death in childhood cancer patients. In this paper we introduce method and properties of the STATT-SCAR study (Second Tumor After Tumor Therapy, Second Cancer After Radiotherapy), which is a joint nested matched case-control study to evaluate the impact of chemotherapy (STATT) as well as radiotherapy (SCAR) on the risk of developing a SPN. METHODS: Based on the cohort of the German childhood cancer registry (GCCR), we selected patients diagnosed with a first neoplasm before age 15 or younger between 1980 and 2014. We selected those with a SPN at least half a year after the first neoplasm, and matched up to four controls to each case. Therapy data were acquired from various sources, including clinical study centers and treating hospitals. To analyze the impact of radiotherapy, organ doses were estimated by using reconstructed treatment plans. The effect of chemotherapy was analyzed using substance groups summarized after isotoxic dose conversion. RESULTS: 1244 cases with a SPN were identified and matched with 4976 controls. Treatment data were acquired for 83% of all match groups (one case and at least one control). Based on preliminary analyses, 98% of all patients received chemotherapy and 54% of all patients were treated with radiotherapy. CONCLUSIONS: Based on our data, detailed analyses of dose response relationships and treatment element combinations are possible, leading to a deeper insight into SPN risks after cancer treatments. TRIAL REGISTRATION: The study is registered at the German clinical trial register (DRKS) under number DRKS00017847 [45].

Health status, health-related quality of life, and socioeconomic outcome in childhood brain tumor survivors: a German cohort study.

BACKGROUND: With rising numbers of childhood cancer survivors, somatic and socioeconomic outcome as well as health-related quality of life (QoL) gain increasing relevance. Based on the first nationwide German Survey on Life Situation, State of Health, and Quality of Life of Childhood Cancer Survivors, the VIVE survey, we report the outcome of survivors of childhood brain tumors localized in the posterior fossa. METHODS: Two hundred seventy participants with a median follow-up period of 21.9 years completed a questionnaire on socioeconomic and somatic late effects as well as a standardized QoL questionnaire (European Organisation for Research and Treatment of Cancer QLQ-C30). Comparisons were performed between World Health Organization (WHO) grades I-II, WHO grades III-IV brain tumor survivors (BTS), and the general population adjusting for potential confounders. RESULTS: The socioeconomic and QoL results of WHO grades I-II BTS were largely comparable to the general population, while grades III-IV BTS were at higher risk for significantly worse outcomes. Of WHO grades III-IV BTS, 36.8% were still living with their parents or in assisted living facilities compared with 16.1% of grades I-II BTS and 7.8% of the age-adjusted general population. Of grades III-IV BTS, 60.8% achieved at least an intermediate school degree in comparison to 80.5% of grades I-II BTS and 75.6% of the general population. Grades III-IV BTS developed up to 2 times more somatic late effects than survivors of grades I-II tumors. CONCLUSION: Derived from a large and homogeneous cohort, these results stress the importance of an appropriate follow-up period focusing not only on physical aspects but encompassing the entire living situation to allow patient-tailored support.

Pharmacokinetics and pharmacodynamics of isothiocyanates.

Isothiocyanates from Brassica vegetables are of great interest for use in the cure of bacterial infections, as is their potential application in the prevention and treatment of cancer. Although much information is available on their mode of action within the cell, when it comes to the question of whether the necessary pharmacologic concentration has been reached at the target organ, detailed knowledge is still lacking. However, a basic prerequisite for clinical application to humans is knowledge of isothiocyanate pharmacokinetic and dynamic behavior in the human body (e.g., to define intake intervals or to ascertain constant levels of the active compound). In this context, we, therefore, reviewed the available literature on in vitro studies, as well as animal and human intervention trials conducted with isothiocyanate and isothiocyanate-containing food preparations.

The association between insomnia and cardiovascular diseases.

Insomnia, the most common sleep complaint in the general population, is defined by difficulty initiating or maintaining sleep, or nonrestorative sleep, accompanied by some form of daytime impairment. In the current review, we present an overview of recent studies on the association between insomnia and cardiovascular disease. It can be concluded that there is growing evidence for the hypothesis that insomnia is associated with an increased risk for cardiovascular disease independently of classic coronary risk factors. Furthermore, insomnia is likely to be associated with hypertension and elevated resting heart rate, both known to lead to cardiovascular disease. However, the existing evidence is not totally consistent and most findings have not been replicated unequivocally. The major limitations of the cited studies include the failure to use state-of-the-art criteria for insomnia diagnosis, the failure to control for depression, and the use of hypnotic medication and sleep apnea as potential confounders. However, the results suggest that insomnia is associated with an increased risk for cardiovascular disease mediated by hypertension or elevated resting heart rate. Consequently, more effort should be dedicated to cope with the high prevalence of insomnia in the general population.