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Purpose Neoadjuvant chemoradiation is an alternative to the surgery-first approach for resectable pancreatic cancer (PDA) and represents the standard of care for borderline resectable (BLR). Materials and methods All patients with resectable and BLR PDA treated with neoadjuvant chemoradiation using IMRT between 1/2009 and 11/2011 were reviewed. Patients were treated to a customized CTV which included the primary mass and regional vessels. Results Neoadjuvant chemoradiation was completed in 69 patients (39 BLR and 30 resectable). Induction chemotherapy was used in 32 (82%) of the 39 patients with BLR disease prior to chemoXRT. All resectable patients were treated with chemoXRT alone. Following neoadjuvant treatment, 48 (70%) of the 69 patients underwent successful pancreatic resection with 47 (98%) being margin negative (RO). In 30 of the BLR patients who had arterial abutment or SMV occlusion, 19 (63%) were surgically resected and all had RO resections. The cumulative incidence of local failure at 1 and 2 years was 2% (95% CI 0–6%) and 9% (95% CI 0.6–17%) respectively. The median overall survival for all patients, patients undergoing resection, and patients without resection were 20, 26 and 11 months respectively. Sixteen (23%) of the 69 patients are alive without disease with a median follow-up of 47 months (36–60). Conclusion Neoadjuvant chemoXRT can facilitate a margin negative resection in patients with localized PCa. [ABSTRACT FROM AUTHOR]

Background: Resection of the superior mesenteric vein (SMV)-portal vein (PV)-splenic vein (SV) confluence during pancreatectomy for pancreatic cancer requires management of the SV. Discussion: Simple SV ligation can result in sinistral portal hypertension if the inferior mesenteric vein (IMV) enters the confluence and is thereby resected, or if the IMV is insufficient to drain the SV. We describe herein three patients whose clinical course confirms the importance of the IMV decompressing the SV to avoid sinistral hypertension. [ABSTRACT FROM AUTHOR]

Background: Among patients with localized pancreatic cancer (PC), the benefit of adjuvant therapy after neoadjuvant therapy and surgery is unknown.Methods: Patients with localized PC who completed all intended neoadjuvant therapy and surgery were categorized based on the receipt of adjuvant therapy and by pathologic lymph node status (LN-/LN+).Results: Data was available from 234 consecutive patients, 121 (52%) with resectable and 113 (48%) with borderline resectable PC. Of the 234 patients, 92 (39%) were LN+ and 142 (61%) were LN-. The median overall survival (OS) for the 234 patients was 39 months, 42.3 months for patients who received any adjuvant therapy and 34.1 months for those who did not (p = 0.29). Of the 92 LN+ patients, the median OS with and without adjuvant therapy was 29.5 and 23.2 months, respectively (p = 0.02). Of the142 LN- patients, the median OS was 45 months with or without adjuvant therapy (p = 0.86). In an adjusted hazard model, additional adjuvant therapy had a significant protective effect among LN+ patients (HR 0.39; 95% CI 0.21-0.70; p = 0.002) but not in LN- patients (HR 0.89; 95% CI 0.53-1.52; p = 0.68).Conclusion: Among patients with localized PC who received neoadjuvant therapy and surgery, the benefit of adjuvant therapy was limited to those with node-positive disease. [ABSTRACT FROM AUTHOR]

Background The prognostic value of CA19-9 in patients with pancreatic cancer ( PC) treated with neoadjuvant therapy has not been well described. Methods Pre-treatment CA19-9 levels (with concomitant normal bilirubin level) in patients with localized PC were categorized as normal (≤35), low (36-200), moderate (201-1000), or high (>1000). Post-treatment CA19-9 was measured after neoadjuvant therapy, prior to surgery. Results Pre-treatment CA19-9 levels were evaluable in 235 patients, levels were normal in 60 (25%) patients, low in 78 (33%) patients, moderate in 69 (29%) and high in 28 (12%). After neoadjuvant therapy, post-treatment CA19-9 normalized (≤ 35) in 40 (51%) of the patients in the low group, 14 (21%) of the moderate and 5 (19%) of the high group ( P < 0.001). Of the 235 patients, 168 (71%) completed all intended therapy including a pancreatectomy; 44 (73%), 62 (79%), 46 (67%) and 16 (57%) of the normal, low, moderate and high groups ( P = 0.10). Among these 168 patients, the median overall survival was 38.4, 43.6, 44.7, 27.2 and 26.4 months for normal, low, moderate and high CA19-9 groups (log rank P = 0.72). Among resected patients, an elevated pre-treatment CA19-9 was of little prognostic value; instead, it was the CA19-9 response to neoadjuvant therapy that was prognostic [hazard ratio (HR): 1.80, P = 0.02]. Conclusions Among patients who completed neoadjuvant therapy and surgery, pre-treatment CA19-9 obtained at the time of diagnosis was not predictive of overall survival, but normalization of post-treatment CA19-9 in response to neoadjuvant therapy was highly prognostic. [ABSTRACT FROM AUTHOR]

The toxicity of pharmacologic ascorbate is mediated by the generation of H2O2 via the oxidation of ascorbate. Because pancreatic cancer cells are sensitive to H2O2 generated by ascorbate, they would also be expected to become sensitized to agents that increase oxidative damage such as ionizing radiation. The current study demonstrates that pharmacologic ascorbate enhances the cytotoxic effects of ionizing radiation as seen by decreased cell viability and clonogenic survival in all pancreatic cancer cell lines examined, but not in nontumorigenic pancreatic ductal epithelial cells. Ascorbate radiosensitization was associated with an increase in oxidative stress--induced DNA damage, which was reversed by catalase. In mice with established heterotopic and orthotopic pancreatic tumor xenografts, pharmacologic ascorbate combined with ionizing radiation decreased tumor growth and increased survival, without damaging the gastrointestinal tract or increasing systemic changes in parameters indicative of oxidative stress. Our results demonstrate the potential clinical utility of pharmacologic ascorbate as a radiosensitizer in the treatment of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Objectives This study was conducted to determine if routine staging chest computed tomography ( CT) or positron emission tomography ( PET) scanning alters the clinical management of patients with newly diagnosed pancreatic adenocarcinoma. Methods All new pancreas cancers seen in medical oncology, radiation oncology and surgery from 1 June 2008 to 20 June 2010 were retrospectively reviewed. Patients with metastatic disease on chest CT or PET, that had been unsuspected on initial imaging, were identified. Results Pancreatic adenocarcinoma was present in 247 consecutive patients. Abdominal CT demonstrated metastases in 108 (44%) and localized disease in 139 (56%) patients. Chest CT and PET were not performed in 15 (11%) of these 139 patients. In the remaining 124 patients, CT imaging suggested resectable disease in 46, borderline resectable disease in 52 and locally advanced disease in 26 patients. Chest CT demonstrated an unsuspected lymphoma in one patient with borderline resectable disease and PET identified extrapancreatic disease in two patients with locally advanced disease. Chest CT and PET added no information in 121 (98%) of the 124 patients. Conclusions The addition of chest CT and PET to high-quality abdominal CT is of little clinical utility; additional sites of metastasis are rarely found. As the quality of abdominal imaging declines, the yield from other imaging modalities will increase. Dedicated pancreas-specific abdominal CT remains the cornerstone of initial staging in suspected or biopsy-proven pancreatic cancer. [ABSTRACT FROM AUTHOR]