Pancreatic cancer cachexia: a review of mechanisms and therapeutics.

Over the last decade, we have gained new insight into the pathophysiology of cachexia associated with pancreatic cancer. Unfortunately, its treatment is complex and remains a challenge. Pancreatic cancer cachexia is a multifactorial syndrome characterized by uncompensated adipose tissue and skeletal muscle loss in the setting of anorexia that leads to progressive functional impairment. This paper will review the current concepts of pancreatic cancer cachexia, its assessment and pathophysiology as well as current and future treatments. The successful management of pancreatic cancer cachexia will likely require a multimodal approach that includes nutritional support and combination pharmaceutical interventions

Randomised phase III trial of trabectedin versus doxorubicin-based chemotherapy as first-line therapy in translocation-related sarcomas

Abstract Aim This randomised phase III trial evaluated first-line trabectedin versus doxorubicin-based chemotherapy (DXCT) in patients with advanced/metastatic translocation-related sarcomas (TRS). Methods Patients were randomly assigned (1:1) to receive trabectedin 1.5mg/m 2 24-h intravenous (i.v.) infusion every 3weeks (q3wk) ( Arm A ), or doxorubicin 75mg/m 2 i.v. q3wk, or doxorubicin 60mg/m 2 i.v. plus ifosfamide (range, 6–9g/m 2 ) i.v. q3wk ( Arm B ). Progression-free survival (PFS) by independent review was the primary efficacy end-point. Results One hundred and twenty-one patients were randomised; 88 of them had TRS confirmed by central pathology review (efficacy population). Twenty-nine PFS events were assessed by independent review (16 with trabectedin; 13 with DXCT). PFS showed non-significant difference between arms (stratified log rank test, p =0.9573; hazard ratio=0.86, p =0.6992). At the time of this analysis, 63.9% and 58.3% of patients were alive in trabectedin and DXCT arms, respectively. There was no statistically significant difference in survival curves. Response rate according to Response Evaluation Criteria in Solid Tumours (RECIST) v.1.0 was significantly higher in DXCT arm (27.0% versus 5.9%), but response according to Choi criteria showed fewer differences between treatment arms (45.9% versus 37.3%). Safety profile was as expected for both arms, with higher incidence of severe neutropenia, alopecia and mucositis in the DXCT arm. Conclusion Neither trabectedin nor doxorubicin-based chemotherapy showed significant superiority in the first-line treatment of patients with advanced translocation-related sarcoma

Targeting mTOR in Pancreatic Ductal Adenocarcinoma.

Treatment options for advanced pancreatic ductal adenocarcinoma (PDAC) are limited; however, new therapies targeting specific tumor-related molecular characteristics may help certain patient cohorts. Emerging preclinical data have shown that inhibition of mammalian target of rapamycin (mTOR) in specific KRAS-dependent PDAC subtypes leads to inhibition of tumorigenesis in vitro and in vivo. Early phase II studies of mono-mTOR inhibition have not shown promise. However, studies have shown that combined inhibition of multiple steps along the mTOR signaling pathway may lead to sustained responses by targeting mechanisms of tumor resistance. Coordinated inhibition of mTOR along with specific KRAS-dependent mutations in molecularly defined PDAC subpopulations may offer a viable alternative for treatment in the future

Socioeconomic disparities and outcomes in midgut neuroendocrine tumors

Abstract only 613 Background: Demographic and socioeconomic disparities have been shown to effect cancer specific outcomes in numerous malignancies but the effect in midgut neuroendocrine tumors (mNETs) is unknown. We sought to investigate whether these factors are associated with survival in mNETs. Methods: The NCDB was queried to identify patients with mNETs between 2004 and 2015. Only patients treated at a single hospital with complete data were included. Overall Survival (OS) was compared based on demographic data, socioeconomic factors, insurance status and place of living. Results: A total of 14,083 patients were identified with a mean age of 72 years (range 18-90). The majority of patients were Caucasian (83.9%) and male (50.9%). Most patients had private insurance (50.5%) or medicare (41.3%). Patients typically lived in larger metropolitan areas (51.5%) and 60.7% lived in zip codes with median household incomes > $48,000. Only 14.7$63,000],p 20% no HSD] vs 80.7% [ 20% no HSD) (HR 1.14, 95% CI 1.02-1.26), no insurance (HR 1.66, 95% CI 1.33-2.06) and not living in proximity to a metro area (HR 1.27, 95% CI 1.10-1.47). Conclusions: Socioeconomic factors shown to have worse OS in patients with mNETs were lower median income, lower education, treatment at a community cancer center and not living in proximity to a metro area. Patient demographic and socioeconomic factors play an important role in OS for patients with mNETs and access to care must be considered in this subpopulation of cancer patients

Targeting mTOR in Pancreatic Ductal Adenocarcinoma

Treatment options for advanced pancreatic ductal adenocarcinoma (PDAC) are limited, however, new therapies targeting specific tumor-related molecular characteristics may help certain patient cohorts. Emerging preclinical data has shown that inhibition of mechanistic target of rapamycin (mTOR) in specific KRAS-dependent PDAC subtypes leads to inhibition of tumorigenesis in vitro as well as in vivo. Early phase II studies of mono-mTOR inhibition have not shown promise. However, studies have shown that combined inhibition of multiple steps along the mTOR signaling pathway may lead to sustained responses by targeting mechanisms of tumor resistance. Coordinated inhibition of mTOR along with specific KRAS-dependent mutations in molecularly defined PDAC subpopulations may offer a viable alternative for treatment in the future