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Pancreatic neuroendocrine tumors (p-NETs) entail a vast array of tumors, which can vary from benign neoplastic growths to rapidly aggressive malignancies. Such is the case with ectopic adrenocorticotropic hormone (ACTH)-producing p-NETs. These tumors have been found to be quite aggressive and a challenge to treat, especially due to the occurrence of metastatic disease even after resection of the primary tumor. We discuss the case of a 44-year-old female who initially presented with vague, non-specific symptoms, in which a malignant p-NET was found to be the cause of her clinical presentation. Although resection of the pancreatic mass was performed, the patient presented again with metastatic disease to the liver.

Pancreatic cancer, as the 4th leading cause of cancer death in the U.S., remains a challenging disease for all oncologists. Less than 20% of all cases could be potentially cured by surgical resection, while the majority of cases are deemed either unresectable or metastatic upon diagnosis. In this year's American Society of Clinical Oncology (ASCO) Annual Meeting, several studies were presented with novel approaches towards treating locally advanced pancreatic cancer. The LAP-07 study, a large phase III study with two separate randomizations, updated their accrual status, but with no interim data yet reported (Abstract #e14619). A single institutional review study reported its promising results on the incorporation of interferon to chemoradiation, but the toxicities could be concerning (Abstract #e14648). Abstract #e14607 demonstrated promising survival data from a tri-modality approach incorporating local and systemic chemotherapy concurrent with external beam radiation as well as radiofrequency ablation. The tolerability of sorafenib in locally advanced pancreatic cancer was shown in a small phase I study (Abstract #e14525). CyberKnife® stereotactic body radiation therapy was investigated as a modality for local palliation (Abstract #e14506). More effective therapeutic agents and approaches are still needed in this difficult disease. This highlight article will focus on the management of locally advanced pancreatic cancer.

Gemcitabine monotherapy and gemcitabine-based regimens are the current standard of care for locally advanced or metastatic pancreatic adenocarcinoma. However, there is still great controversy over the role of salvage chemotherapy after failure of gemcitabine. This review is an update on the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting regarding the most important developments in the treatment of refractory pancreatic cancer, as they were reported in Abstracts #e14542 and #e14588.

GemOx (gemcitabine 1000 mg/m(2)100 min on day 1 and oxaliplatin 100 mg/m(2) on day 2 every 2 weeks) achieved a response rate of 26.8%, improved progression-free survival (PFS) but failed to demonstrate a benefit in overall survival (OS) compared with gemcitabine in pancreatic cancer. This regimen has regained attention after recent pooled- and meta-analysis suggested a survival benefit of gemcitabine-platinum doublets over gemcitabine. However, GemOx is associated with inconvenience to patients, early cumulative dose developing neuropathy and thrombocytopenia. In addition, fixed dose rate of gemcitabine showed no benefit30 min infusion schedule in the ECOG6201 study. Pharmacokinetic profiles of both drugs did not show statistically significant difference regardless of the order of administration.In order to create a more convenient and equally effective regimen, we conducted a retrospective study to evaluate the efficacy and safety of single-day modified GemOx (S-GemOx, gemcitabine 1000 mg/m(2)30 min and oxaliplatin 85 mg/m(2)2 h on day 1 every 2 weeks) in patients with pancreatic and biliary cancers.In all, 34 patients (median age 60 years, male/female: 17/17) received S-GemOx including locally advanced or metastatic pancreatic cancer (26) and biliary duct carcinoma (8). Median treatment was six cycles with duration of 12 weeks (range (r): 2 - 56). Median cumulative dose of oxaliplatin was 517.5 mg/m(2) (r: 85 - 2380). A total of 27 of 34 patients were evaluated for efficacy after initial staging: 1 (3.7%) complete response (CR), 4 (14.8%) partial response (PR), 18 (66.7%) stable disease and 4 (14.8%) progression of disease. Overall response rate (CR + PR) was 18.5%. Median PFS and OS were 7 and 11.6 months, respectively. All patients were assessed for toxicities. Grade 3/4 hematological toxicities include anemia (8%), neutropenia (11%), thrombocytopenia (5%), nausea/vomiting (3%), diarrhea (3%), hypersensitivity reaction (14%) and neuropathy (3%). No deaths occurred due to therapy.S-GemOx regimen provides convenient schedule, toxicities appear to be comparable with GemOx. The incidence of neuropathy (3 vs 19.1%) and thrombocytopenia (5 vs 14%) are substantially lower compared with GemOx. Prospective studies of S-GemOx in a large patient population are warranted.

Pancreatic cancer is a devastating disease with few effective treatment modalities. Stereotactic body radiation therapy is a novel technique that takes advantage of the technologic advancements in image guidance and radiation dose delivery to direct ablative doses to tumors with acceptable toxicity that was not previously achievable with conventional techniques. Recent literature contains reports of stereotactic body radiation therapy in patients with locally advanced pancreatic tumors. This paper presents a summary of the current data and highlights the limitations and the promise. Further clinical study in the form of multi-institutional trials is warranted to establish the role of stereotactic body radiation therapy as a comparable noninvasive alternative to surgery.