The Innate Immune Landscape of dMMR/MSI Cancers Predicts the Outcome of Nivolumab Treatment: Results from the Drug Rediscovery Protocol.

Purpose: The treatment efficacy of nivolumab was evaluated in patients with advanced, treatment-refractory solid mismatch repair deficiency/microsatellite-instable (dMMR/MSI) tumors, and in-depth biomarker analyses were performed to inform precision immunotherapy approaches.

Patients And Methods: Patients with dMMR/MSI tumors who exhausted standard-of-care treatment options were enrolled in the Drug Rediscovery Protocol, a pan-cancer clinical trial that treats patients with cancer based on their tumor molecular profile with off-label anticancer drugs (NCT02925234). Patients received nivolumab (four cycles of 240 mg every 2 weeks, thereafter 480 mg every 4 weeks).

Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer.

Background: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported.

First-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CAIRO5): an open-label, multicentre, randomised, controlled, phase 3 study from the Dutch Colorectal Cancer Group.

Background: Patients with initially unresectable colorectal cancer liver metastases might qualify for local treatment with curative intent after reducing the tumour size by induction systemic treatment. We aimed to compare the currently most active induction regimens.

Methods: In this open-label, multicentre, randomised, phase 3 study (CAIRO5), patients aged 18 years or older with histologically confirmed colorectal cancer, known RAS/BRAF mutation status, WHO performance status of 0-1, and initially unresectable colorectal cancer liver metastases were enrolled at 46 Dutch and one Belgian secondary and tertiary centres.

Platelet Transfusion before CVC Placement in Patients with Thrombocytopenia.

Background: Transfusion guidelines regarding platelet-count thresholds before the placement of a central venous catheter (CVC) offer conflicting recommendations because of a lack of good-quality evidence. The routine use of ultrasound guidance has decreased CVC-related bleeding complications.

Methods: In a multicenter, randomized, controlled, noninferiority trial, we randomly assigned patients with severe thrombocytopenia (platelet count, 10,000 to 50,000 per cubic millimeter) who were being treated on the hematology ward or in the intensive care unit to receive either one unit of prophylactic platelet transfusion or no platelet transfusion before ultrasound-guided CVC placement.

Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial.

Purpose: The benefit of neoadjuvant chemoradiotherapy in resectable and borderline resectable pancreatic cancer remains controversial. Initial results of the PREOPANC trial failed to demonstrate a statistically significant overall survival (OS) benefit. The long-term results are reported.

Patients with Rare Cancers in the Drug Rediscovery Protocol (DRUP) Benefit from Genomics-Guided Treatment.

Purpose: Patients with rare cancers (incidence less than 6 cases per 100,000 persons per year) commonly have less treatment opportunities and are understudied at the level of genomic targets. We hypothesized that patients with rare cancer benefit from approved anticancer drugs outside their label similar to common cancers.

Experimental Design: In the Drug Rediscovery Protocol (DRUP), patients with therapy-refractory metastatic cancers harboring an actionable molecular profile are matched to FDA/European Medicines Agency-approved targeted therapy or immunotherapy.

Radiofrequency ablation and chemotherapy versus chemotherapy alone for locally advanced pancreatic cancer (PELICAN): study protocol for a randomized controlled trial.

Background: Approximately 80% of patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy, of whom approximately 10% undergo a resection. Cohort studies investigating local tumor ablation with radiofrequency ablation (RFA) have reported a promising overall survival of 26-34 months when given in a multimodal setting. However, randomized controlled trials (RCTs) investigating the effect of RFA in combination with chemotherapy in patients with LAPC are lacking.

The treatment and survival of elderly patients with locally advanced pancreatic cancer: A post-hoc analysis of a multicenter registry.

Background: The treatment options for patients with locally advanced pancreatic cancer (LAPC) have improved in recent years and consequently survival has increased. It is unknown, however, if elderly patients benefit from these improvements in therapy. With the ongoing aging of the patient population and an increasing incidence of pancreatic cancer, this patient group becomes more relevant.

Treatment strategies and clinical outcomes in consecutive patients with locally advanced pancreatic cancer: A multicenter prospective cohort.

Introduction: Since current studies on locally advanced pancreatic cancer (LAPC) mainly report from single, high-volume centers, it is unclear if outcomes can be translated to daily clinical practice. This study provides treatment strategies and clinical outcomes within a multicenter cohort of unselected patients with LAPC.

Materials And Methods: Consecutive patients with LAPC according to Dutch Pancreatic Cancer Group criteria, were prospectively included in 14 centers from April 2015 until December 2017.

Survival of patients with deficient mismatch repair metastatic colorectal cancer in the pre-immunotherapy era.

Background: Metastatic colorectal cancer patients with deficient mismatch repair (dMMR mCRC) benefit from immunotherapy. Interpretation of the single-arm immunotherapy trials is complicated by insignificant survival data during systemic non-immunotherapy. We present survival data on a large, comprehensive cohort of dMMR mCRC patients, treated with or without systemic non-immunotherapy.

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): a multicenter stepped-wedge cluster randomized controlled trial.

Background: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life.

Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial.

Purpose: Preoperative chemoradiotherapy may improve the radical resection rate for resectable or borderline resectable pancreatic cancer, but the overall benefit is unproven.

Patients And Methods: In this randomized phase III trial in 16 centers, patients with resectable or borderline resectable pancreatic cancer were randomly assigned to receive preoperative chemoradiotherapy, which consisted of 3 courses of gemcitabine, the second combined with 15 × 2.4 Gy radiotherapy, followed by surgery and 4 courses of adjuvant gemcitabine or to immediate surgery and 6 courses of adjuvant gemcitabine.

mutations identify a molecular subgroup of diffuse large B-cell lymphoma with an unfavorable prognosis.

The 2016 World Health Organization classification defines diffuse large B-cell lymphoma (DLBCL) subtypes based on Epstein-Barr virus (EBV) infection and oncogenic rearrangements of as drivers of lymphomagenesis. A subset of DLBCL, however, is characterized by activating mutations in We investigated whether mutations could improve the classification and prognostication of DLBCL. In 250 primary DLBCL, mutations were identified by allele-specific polymerase chain reaction or next-generation-sequencing, rearrangements were analyzed by fluorescence hybridization, and EBV was studied by EBV-encoded RNA hybridization.

Outcome effects of antiretroviral drug combinations in HIV-positive patients with chemotherapy for lymphoma: a retrospective analysis.

Background The combination of combined active antiretroviral therapy (cART) with chemotherapy in the treatment of lymphoma in human immunodeficiency virus (HIV)-positive patients has improved the overall survival of these patients. However, drug-drug interactions between antineoplastic agents and the antiretroviral agents non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) can occur by influencing the activity of the CYP3A4 enzyme. So far, little is known about the clinical relevance of this interaction: the effect on the efficacy and toxicity of the chemotherapy.

Enzalutamide as a Fourth- or Fifth-Line Treatment Option for Metastatic Castration-Resistant Prostate Cancer.

Objective: To evaluate the efficacy of enzalutamide (Enz) as fourth- or fifth-line treatment in men with metastasized castration-resistant prostate cancer (mCRPC), by analyzing a retrospective cohort of heavily pretreated patients.

Methods: We evaluated toxicity, overall survival (OS), progression-free survival (PFS) and time to prostate-specific antigen (PSA) progression data from 47 CRPC patients treated with fourth- or fifth-line Enz.

Results: All patients were treated with docetaxel and abiraterone acetate and 42 patients (89%) with cabazitaxel.

Prognostic parameters for response to enzalutamide after docetaxel and abiraterone treatment in metastatic castration-resistant prostate cancer patients; a possible time relation.

Background: Abiraterone Acetate (AA) and Enzalutamide (Enz) are effective hormonal treatments in mCRPC patients. Retrospective studies suggested clinical cross-resistance between Enz and AA. However, 12.

Clinical activity and tolerability of enzalutamide (MDV3100) in patients with metastatic, castration-resistant prostate cancer who progress after docetaxel and abiraterone treatment.

Background: Enzalutamide (Enz) and abiraterone acetate (AA) are hormone treatments that have a proven survival advantage in patients with metastatic, castration-resistant prostate cancer who previously received docetaxel (Doc). Recently, limited activity of AA after Enz and of Enz after AA was demonstrated in small cohort studies. Here, the authors present the activity and tolerability of Enz in patients who previously received AA and Doc in the largest cohort to date.

In situ detection of spontaneous superoxide anion and singlet oxygen production by mitochondria in rat liver and small intestine.

In the present study, the endogenous formation of reactive oxygen species was localized in rat liver and small intestine. The 3,3'-diaminobenzidine (DAB)-Mn2+ technique in which cobalt ions were included in the incubation medium was applied to unfixed cryostat sections of intact tissues. Addition of manganese ions to the DAB-Co(2+)-containing medium greatly increased the amounts of final reaction product formed compared with incubations with only DAB and cobalt ions.