Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer

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Predicting Survival for Chimeric Antigen Receptor T-Cell Therapy: A Validation of Survival Models Using Follow-Up Data From ZUMA-1

ObjectivesSurvival extrapolation for chimeric antigen receptor T-cell therapies is challenging, owing to their unique mechanistic properties that translate to complex hazard functions. Axicabtagene ciloleucel is indicated for the treatment of relapse or refractory diffuse large B-cell lymphoma after 2 or more lines of therapy based on the ZUMA-1 trial. Four data snapshots are available, with minimum follow-up of 12, 24, 36, and 48 months. This analysis explores how survival extrapolations for axicabtagene ciloleucel using ZUMA-1 data can be validated and compared.MethodsThree different parametric modeling approaches were applied: standard parametric, spline-based, and cure-based models. Models were compared using a range of metrics, across the 4 data snapshot, including visual fit, plausibility of long-term estimates, statistical goodness of fit, inspection of hazard plots, point-estimate accuracy, and conditional survival estimates.ResultsStandard and spline-based parametric extrapolations were generally incapable of fitting the ZUMA-1 data well. Cure-based models provided the best fit based on the earliest data snapshot, with extrapolations remaining consistent as data matured. At 48 months, the maximum survival overestimate was 8.3% (Gompertz mixture-cure model) versus the maximum underestimate of 33.5% (Weibull standard parametric model).ConclusionsWhere a plateau in the survival curve is clinically plausible, cure-based models may be helpful in making accurate predictions based on immature data. The ability to reliably extrapolate from maturing data may reduce delays in patient access to potentially lifesaving treatments. Additional research is required to understand how models compare in broader contexts, including different treatments and therapeutic areas.     

Immunotherapy: A new standard in the treatment of metastatic clear cell renal cell carcinoma

Renal cell cancer (RCC) represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney (90%). In the mid-nineties of the last century, the standard of treatment for patients with metastatic RCC was cytokines. Sunititib and pazopanib were registered in 2007 and 2009, respectively, and have since been the standard first-line treatment for metastatic clear cell RCC (mccRCC). Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells (NK) and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy. With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved [immunotherapy and immunotherapy/tyrosine kinase inhibitors (TKI)] for the first-line treatment of mccRCC. Nivolumab/ipilimumab is approved for the treatment of patients with intermediate and poor prognoses. Several checkpoint inhibitors (pembrolizumab, nivolumab, avelumab) in combination with TKI (axitinib, lenvatinib, cabozantinib) are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression. There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.     

Exploring the potential of exosomes in diagnosis and drug delivery for pancreatic ductal adenocarcinoma

Pancreatic cancer (PC) is a cancer of the digestive system, and pancreatic ductal adenocarcinoma (PDAC) accounts for approximately 90% of all PC cases. Exosomes derived from PDAC (PDAC-exosomes) promote PDAC development and metastasis. Exosomes are nanoscale vesicles secreted by most cells, which can carry biologically active molecules and mediate communication and cargo transportation among cells. Recent studies have focused on transforming exosomes into good drug delivery systems (DDSs) to improve the clinical treatment of PDAC. This review considers PDAC as the main research object to introduce the role of PDAC-exosomes in PDAC development and metastasis. This review focuses on the following two themes: (a) the great potential of PDAC-exosomes as new diagnostic markers for PDAC, and (b) the transformation of exosomes into potential DDSs.     

The effect of granulocyte colony-stimulating factors on survival parameters in pediatric patients with acute lymphoblastic leukemia: a retrospective study

ObjectiveThere is a paucity of data concerning the use of granulocyte colony-stimulating factors (G-CSFs) in pediatric patients with acute lymphoblastic leukemia (ALL). The aim of the present study was to evaluate the effect of G-CSF use on relapse-free and overall survival in 358 consecutive, newly diagnosed pediatric ALL patients uniformly treated at the same institution between April 2012 and April 2020.Materials and MethodsPatients were evaluated in two separate periods, based on the G-CSF treatment approach. All patients who underwent ALL treatment between April 2012 and December 2016 received G-CSF (G-CSF⁺ arm; n: 245) in the course of the protocol for reducing the risk of febrile neutropenia and/or inducing neutrophil recovery to prevent any treatment delay. No patients after December 2016 received G-CSF, even if they belonged to the high-risk group, and these were included in the G-CSF^? arm (n: 113).ResultsEstimated mean relapse-free (106.5 months; 95 % CI 102?110.8 vs 82 months 95 % CI 75.2?88.9; p: 0.794) and overall survival (111.4 months; 95 % CI 108?114.8 vs 85 months 95 % CI 80.4?89.8; p: 0.431) rates were similar between the G-CSF⁺ and G-CSF^? groups.ConclusionsOur findings indicate that G-CSF use during ALL treatment had no effect on relapse rates or overall survival.