The Evolving Diagnostic and Treatment Landscape of NTRK -Fusion-Driven Pediatric Cancers
AbstractThe neurotrophin receptor tyrosine kinase (NTRK1-3) genes have been identified as key fusion partners in a range of pediatric cancers. In childhood cancers,ETV6-NTRK3 fusions are found in the majority of infantile fibrosarcomas and congenital mesoblastic nephromas.NTRK fusions are also found in mammary analog secretory carcinomas (MASC), secretory breast carcinomas, and with modest frequency in high-grade gliomas in very young children. While there are a range of multi-receptor tyrosine kinase inhibitors that show efficacy against TRK kinases, there are now multiple highly selective TRK inhibitors in clinical evaluation. Entrectinib and larotrectinib have been evaluated in early-phase clinical trials for children and demonstrated high response rates with good durability of response. Both agents are now approved in the United States in an age and histology agnostic manner for children (age > 12 years for entrectinib; all ages for larotrectinib) for the treatment of solid tumors harboringNTRK fusions without an option for complete surgical resection, with relapsed disease, or without a viable alternative systemic option. More recently, two second-generation TRK inhibitors, selitrectinib and repotrectinib, have been developed and are currently being evaluated in pediatric early phase trials. The Children ’s Oncology Group has also launched a phase II trial of larotrectinib as a neoadjuvant agent for patients with newly diagnosed infantile fi...
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CONCLUSION: Survival across the two time periods remained stable for oral SCC but showed a significant increase for oropharyngeal SCC, possibly because of improvements in the patients ’ response to radiotherapy, such as intensity-modulated radiation therapy, and the use of more accurate diagnostic imaging approaches.
ABSTRACT Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in S ão Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration o...
Goals: The main purpose of this study was to assess the recent trends in mortality and health care utilization of hepatocellular carcinoma (HCC) among Medicare population in the United States. Background: The incidence of HCC is increasing in the United States. Materials and Methods: Data were obtained for a sample of Medicare beneficiary from 2005 to 2014. Diagnosis of HCC and etiology of liver disease were based on ICD-9 codes. Temporal trends in HCC rates, clinical, demographical and utilization parameters were analyzed by joinpoint regression model. Results: Study cohort included 13,648 Medicare recipients w...
Conclusions: Prediagnosis use of metformin dose ≤1500 mg/d is associated with longer overall survival of elderly diabetic HCC patients.