Phase 1 trial of navitoclax and sorafenib in patients with relapsed or refractory solid tumors with hepatocellular carcinoma expansion cohort.

Navitoclax (ABT-263) is an oral BCL2 homology-3 mimetic that binds with high affinity to pro-survival BCL2 proteins, resulting in apoptosis. Sorafenib, an oral multi kinase inhibitor also promotes apoptosis and inhibits tumor angiogenesis. The efficacy of either agent alone is limited; however, preclinical studies demonstrate synergy with the combination of navitoclax and sorafenib.

Second-line treatment for metastatic pancreatic cancer.

Pancreatic cancer is the fourth-leading cause of cancer-related death. It is commonly diagnosed at an advanced stage, when no curative options exist. Over the last decade, combination chemotherapy has shown a survival benefit compared with single-agent gemcitabine and has become established as first-line therapy in metastatic pancreatic cancer.

Gastroesophageal Junction Adenocarcinoma: Is There an Optimal Management?

The incidence of gastroesophageal junction (GEJ) adenocarcinomas has been rising over the past few decades, creating a need for effective therapeutic strategies. Treatment of locally advanced GEJ tumors, in particular, present a unique challenge because these tumors have generally been approached as either esophageal or gastric cancers, and thus optimal preoperative management remains uncertain. Both neoadjuvant chemoradiation and perioperative chemotherapy have been widely adopted in standard practice; however, it is unclear which approach offers the optimal outcome for the fit patient capable of receiving any planned strategy.

A Routine Laboratory Data-Based Model for Predicting Recurrence After Curative Resection of Stage II Colorectal Cancer.

Use of chemotherapy in stage II colorectal cancer (CRC) is controversial because it improves survival only in some patients. We aimed to develop a statistical model using routine and readily available blood tests to predict the prognosis of patients with stage II CRC and to identify which patients are likely to benefit from chemotherapy. We divided 422 patients with stage II CRC into a training and a testing set.

Pancreatic cancer survivors' preferences, barriers, and facilitators related to physical activity and diet interventions.

Purpose: To conduct a telephone survey establishing pancreatic cancer survivors' level of interest in, preferences for, and perceived barriers and facilitators to participating in exercise and diet intervention programming. These data will inform the development of such interventions for newly-diagnosed patients.

Methods: Seventy-one survivors treated for resectable pancreatic adenocarcinoma from October 2011 to August 2014 were identified through an institutional cancer registry and contacted via telephone.

RNA sequencing of pancreatic adenocarcinoma tumors yields novel expression patterns associated with long-term survival and reveals a role for ANGPTL4.

Background: Pancreatic adenocarcinoma patients have low survival rates due to late-stage diagnosis and high rates of cancer recurrence even after surgical resection. It is important to understand the molecular characteristics associated with survival differences in pancreatic adenocarcinoma tumors that may inform patient care.

Results: RNA sequencing was performed for 51 patient tumor tissues extracted from patients undergoing surgical resection, and expression was associated with overall survival time from diagnosis.

Patterns of Failure for Lymph Node-Positive Resected Pancreatic Adenocarcinoma After Adjuvant Radiotherapy or Gemcitabine-based Chemotherapy Alone.

Purpose: The purpose of this study was to investigate the effect of radiotherapy on local control and mordibity for patients with resected lymph node-positive pancreatic cancer as compared to gemcitabine-based chemotherapy alone.

Materials And Methods: Sixty-nine patients received adjuvant therapy for pancreatic adenocarcinoma with lymph node involvement after surgical resection and met the inclusion criteria for this analysis. Forty (58 %) patients received postoperative radiotherapy (PORT) to a median dose of 50.

Esophageal and esophagogastric junction cancers, version 1.2015.

Esophageal cancer is the sixth most common cause of cancer deaths worldwide. Adenocarcinoma is more common in North America and Western European countries, originating mostly in the lower third of the esophagus, which often involves the esophagogastric junction (EGJ). Recent randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival in patients with resectable cancer.

Quantitative perfusion- and diffusion-weighted magnetic resonance imaging of gastrointestinal cancers treated with multikinase inhibitors: a pilot study.

Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) are often used to detect the early response of solid tumors to an effective therapy. The early changes in intratumoral physiological parameters measured by DCE-MRI/DWI have been evaluated as surrogate biomarkers allowing a tailored treatment for the individual patient.

Methods: Patients with newly diagnosed, biopsy-proven, treatment-naïve gastrointestinal stromal tumor (GIST) or hepatocellular carcinoma (HCC) were enrolled prospectively after institutional review board (IRB)-approved informed consent (5 patients per tumor type).

Hepatobiliary cancers, version 2.2014.

Hepatobiliary cancers include a spectrum of invasive carcinomas arising in the liver (hepatocellular carcinoma), gall bladder, and bile ducts (cholangiocarcinomas). Gallbladder cancer and cholangiocarcinomas are collectively known as biliary tract cancers. Gallbladder cancer is the most common and aggressive type of all the biliary tract cancers.

Pancreatic adenocarcinoma: a pilot study of quantitative perfusion and diffusion-weighted breath-hold magnetic resonance imaging.

Purpose: To confirm the feasibility of breath-hold DCE-MRI and DWI at 3T to obtain the intra-abdominal quantitative physiologic parameters, K(trans), k ep, and ADC, in patients with untreated pancreatic ductal adenocarcinomas.

Methods: Diffusion-weighted single-shot echo-planar imaging (DW-SS-EPI) and dynamic contrast-enhanced (DCE) MRI were used for 16 patients with newly diagnosed biopsy-proven pancreatic ductal adenocarcinomas. K(trans), k ep, and apparent diffusion coefficient (ADC) values of pancreatic tumors, non-tumor adjacent pancreatic parenchyma (NAP), liver metastases, and normal liver tissues were quantitated and statistically compared.

The effects of liver impairment on the pharmacokinetics of brivanib, a dual inhibitor of fibroblast growth factor receptor and vascular endothelial growth factor receptor tyrosine kinases.

Purpose: Hepatic impairment may impede tyrosine kinase inhibitor metabolism. This phase I study compared the pharmacokinetics of brivanib in patients with hepatocellular carcinoma (HCC) and varying levels of hepatic impairment with those with non-HCC malignancies and normal liver function.

Methods: Patients were assigned to the following groups: Groups A, B, and C (HCC plus mild, moderate, or severe hepatic impairment, respectively) and Group D (non-HCC malignancy and normal hepatic function).

Gastric cancer, version 2.2013: featured updates to the NCCN Guidelines.

The NCCN Clinical Practice Guidelines in Oncology for Gastric Cancer provide evidence- and consensus-based recommendations for a multidisciplinary approach for the management of patients with gastric cancer. For patients with resectable locoregional cancer, the guidelines recommend gastrectomy with a D1+ or a modified D2 lymph node dissection (performed by experienced surgeons in high-volume centers). Postoperative chemoradiation is the preferred option after complete gastric resection for patients with T3-T4 tumors and node-positive T1-T2 tumors.

Resectability of pancreatic adenocarcinoma in patients with locally advanced disease downstaged by preoperative therapy: a challenge for MDCT.

Objective: The purpose of this study was to determine whether preoperative neoadjuvant therapy in patients with locally advanced pancreatic cancer affects the ability of multiphasic MDCT to predict successful surgical resection.

Materials And Methods: From 2000 to 2006, there were 12 patients with prior neoadjuvant therapy successfully downstaged by CT and 31 age-matched pancreatic cancer patients without preoperative therapy who underwent pancreatic MDCT followed by attempted pancreaticoduodenectomy. Three readers blinded to surgical findings independently analyzed immediate preoperative MDCT scans of 43 patients comprising the retrospective data set in random order for vascular involvement (degree of contact and narrowing) and distant metastases.

Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial.

PURPOSE No established treatment exists for pancreatic neuroendocrine tumor (NET) progression after failure of chemotherapy. Everolimus (RAD001), an oral inhibitor of mammalian target of rapamycin, in combination with octreotide has demonstrated encouraging antitumor activity in patients with NETs. PATIENTS AND METHODS This open-label, phase II study assessed the clinical activity of everolimus in patients with metastatic pancreatic NETs who experienced progression on or after chemotherapy.

Multidetector computed tomography during combined therapy for pancreatic adenocarcinoma.

By using experimental combined adjuvant and neoadjuvant therapies in pancreatic ductal adenocarcinoma patients, progress has been made in survival, clinical benefit response, and even downstaging of tumors to allow surgical resection. The use of combined modality approaches in pancreatic ductal adenocarcinoma is associated with increased gastrointestinal toxicity, which may manifest as bowel wall abnormalities and peripancreatic inflammatory changes on multiphasic multidetector computed tomography and affect assessment of the pancreatic tumor. During preoperative neoadjuvant therapy, occult metastatic disease may be given the opportunity to manifest, thus preventing the morbidity of attempted resection or laparotomy.