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Sorafenib-treated patients display a substantial variation in the incidence of toxicity. We aimed to investigate the association of genetic polymorphisms with observed toxicity on sorafenib. We genotyped 114 patients that were treated with sorafenib at the Erasmus MC Cancer Institute, the Netherlands, for SLCO1B1, SLCO1B3, ABCC2, ABCG2, UGT1A1 and UGT1A9. The UGT1A1 (rs8175347) polymorphism was associated with hyperbilirubinemia and treatment interruption. Polymorphisms in SLCO1B1 (rs2306283, rs4149056) were associated with diarrhea and thrombocytopenia, respectively. None of the investigated polymorphisms was associated with overall or progression-free survival in hepatocellular cancer patients. Polymorphisms in SLCO1B1 and UGT1A1 are associated with several different sorafenib side effects.

Sorafenib-treated patients display a substantial variation in the incidence of toxicity. We aimed to investigate the association of genetic polymorphisms with observed toxicity on sorafenib. We genotyped 114 patients that were treated with sorafenib at the Erasmus MC Cancer Institute, the Netherlands, for and . The (rs8175347) polymorphism was associated with hyperbilirubinemia and treatment interruption. Polymorphisms in (rs2306283, rs4149056) were associated with diarrhea and thrombocytopenia, respectively. None of the investigated polymorphisms was associated with overall or progression-free survival in hepatocellular cancer patients. Polymorphisms in and are associated with several different sorafenib side effects.

Samenvatting Er is onvoldoende bekend over de middellangetermijnoverleving van niet-gemetastaseerd spierinvasieve blaaskanker (SIBC) na open (ORC) versus robotgeassisteerde (RARC) cystectomie, met of zonder neoadjuvante chemotherapie (NAC). Om de vijfjaarsoverleving na beide interventies en de invloed van NAC te onderzoeken, is een retrospectieve studie verricht in 19 Nederlandse ziekenhuizen tussen 2012 en 2015. Van de totaal 1.534 cT1-4N0-1-patiënten ondergingen 1.086 patiënten een ORC en 389 een RARC. De vijfjaarsoverleving was 51% na ORC (95%-BI 47–53) versus 58% na RARC (95%-BI 52–63); de hazard ratio na multivariabele correctie was 1,00 (95%-BI 0,84–1,20). 226 van de 965 cT2-4aN0-patiënten werden behandeld met NAC. Na case-control matching bleek (y)pT0 vaker voor te komen na NAC dan zonder NAC (31 vs. 15%; p  < 0,01). De beste vijfjaarsoverleving trad op bij patiënten met ypT0 na NAC, namelijk 89% (95%-BI 81–97). Concluderend laat deze deze studie bij patiënten met SIBC vergelijkbare vijfjaarsoverleving zien na ORC of na RARC. De beste overleving was bij patiënten die waren behandeld met NAC voorafgaand aan cystectomie.

High-grade gliomas (HGG) are serious primary brain tumors that may prevent the patient from functioning normally in social, emotional and cognitive respect. Often the partner’s role will convert to that of informal caregiver. Consequently, they may experience significant stress and reductions in caregiver mastery, negatively affecting their health-related quality of life (HRQOL). We aimed at (1) determining factors that impact HRQOL and mastery of caregivers of HGG patients, and (2) investigate if a structured intervention consisting of psychoeducation and cognitive behavioral therapy leads to improvements in the mental component of HRQOL and mastery of caregivers. Fifty-six patient-caregiver dyads were randomly assigned to the intervention group or the care as usual group. The intervention program consisted of six one-hour sessions with a psychologist. Participants completed questionnaires concerning their perceptions of the patients’ HRQOL (SF-36), neurological functioning (BN20), and cognitive functioning (MOS), and concerning their own HRQOL (SF-36) and feelings of caregiver mastery (CMS) both at baseline (i.e. before randomization) and every 2 months thereafter until 8 months later, five times in total. Patients’ HRQOL and neurological functioning were found to be related to HRQOL and feelings of mastery of the informal caregiver at baseline. The intervention helped caregivers in maintaining a stable level of HRQOL and improved feelings of mastery over an 8 month period. Our findings suggest that informal caregivers can benefit from a psychological intervention as it is a helpful tool in maintaining a stable level of mental functioning and caregiver mastery.

Many biology-based precision drugs are available that neutralize aberrant molecular pathways in cancer. Molecular heterogeneity and the lack of reliable companion diagnostic biomarkers for many drugs makes targeted treatment of cancer inaccurate for many individuals. Identifying actionable hyperactive biological pathways in individual cancers may improve this situation. To achieve this we applied a novel targeted RNA next generation sequencing (t/RNA-NGS) technique to surgically obtained glioma tissues. The test combines mutation detection with analysis of biological pathway activities that are involved in tumour behavior in many cancer types (e.g. tyrosine kinase signaling, angiogenesis signaling, immune response, metabolism), via quantitative measurement of transcript levels and splice variants of hundreds of genes. We here present proof of concept that the technique, which uses molecular inversion probes, generates a histology-independent molecular diagnosis and identifies classifiers that are strongly associated with conventional histopathology diagnoses and even with patient prognosis. The test not only confirmed known glioma-associated molecular aberrations but also identified aberrant expression levels of actionable genes and mutations that have so far been considered not to be associated with glioma, opening up the possibility of drug repurposing for individual patients. Its cost-effectiveness makes t/RNA-NGS to an attractive instrument to aid oncologists in therapy decision making.

Hundreds of biology-based precision drugs are available that neutralize aberrant molecular pathways in cancer. Molecular heterogeneity and the lack of reliable companion diagnostic biomarkers for many drugs makes targeted treatment of cancer inaccurate for many individuals, leading to futile overtreatment. To acquire a comprehensive insight in aberrant actionable biological pathways in individual cancers we applied a cost-effective targeted RNA next generation sequencing (NGS) technique. The test allows NGS-based measurement of transcript levels and splice variants of hundreds of genes with established roles in the biological behavior in many cancer types. We here present proof of concept that the technique generates a correct molecular diagnosis and a prognosis for glioma patients. The test not only confirmed known brain cancer-associated molecular aberrations but also identified aberrant expression levels of actionable genes and mutations that are associated with other cancer types. Targeted RNA-NGS is therefore a highly attractive method to guide precision therapy for the individual patient based on pathway analysis.