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The majority of PCs present as advanced disease, and treatment goals are for prolongation of life and palliation of the symptoms. Oncologists rely on our radiology colleagues to provide information on the extent of disease and the effectiveness of our treatment. The stakes rise in those patients where the disease has seemingly not spread and who might be treated with a goal of cure. For this subset of patients, medical oncologists and surgeons require as precise a radiologic description as possible in order to most accurately characterize the extent of the disease, in turn informing us as to the likelihood of a successful surgery and potential cure. In this paper, we review the fine points of imaging that distinguish resectable from borderline or unresectable patients, explain the principles of neoadjuvant and adjuvant therapy for pancreatic cancer, highlight some of the novel therapies now being pioneered in pancreatic cancer, and review radiologic features important for palliative care in patients with these tumors.

Background: The impact of preoperative chemoradiation on postoperative morbidity and mortality of patients with pancreatic adenocarcinoma remains controversial., Methods: Consecutive pancreatectomies for adenocarcinoma performed between 2011 and 2015 were prospectively monitored for 90 days by using a previously reported surveillance system to determine the association between preoperative chemoradiation and adverse events, pancreatic fistulae, readmissions, and mortality., Results: Among 209 consecutive patients who underwent pancreatectomy, 159 (76 %) experienced at least one adverse event within 90 postoperative days. Patients who received preoperative chemoradiation (n = 137, 66 %) were more likely to have borderline resectable/locally advanced tumors, to have received induction chemotherapy, and to require vascular resection at pancreatectomy than those who did not receive chemoradiation (all P < 0.05). Nonetheless, there were no significant differences in the rates of severe complications, readmission, or mortality between these groups (all P > 0.05). Among patients who underwent pancreatoduodenectomy, the rate of pancreatic fistula was similar between those who received chemoradiation and those who did not (P = 0.96). In contrast, those who received chemoradiation prior to distal pancreatectomy had a lower rate of pancreatic fistula (P < 0.01)., Conclusion: Preoperative chemoradiation is not associated with an increase in 90-day morbidity or mortality, and it may reduce the rate of pancreatic fistula following distal pancreatectomy.

Background: Little is known about changes in body composition that may occur during neoadjuvant therapy for pancreatic cancer. This study was designed to characterize these changes and their potential relationships with therapeutic outcomes., Methods: The study population consisted of patients with potentially resectable pancreatic cancer treated on a phase II trial of neoadjuvant chemotherapy and chemoradiation. Skeletal muscle and adipose tissue compartments were measured before and after administration of neoadjuvant therapy using SliceOMatic software (TomoVision, 2012) and protocol-mandated CT scans. Sarcopenia was defined using gender-adjusted norms., Results: Among 89 eligible patients, 46 (52 %) patients met anthropometric criteria for sarcopenia prior to the initiation of neoadjuvant therapy. Further depletion of skeletal muscle, visceral adipose tissue, and subcutaneous adipose tissue occurred during neoadjuvant therapy, but these losses did not preclude the performance of potentially curative surgery. Degree of skeletal muscle loss correlated with disease-free survival while visceral adipose loss was associated with overall and progression-free survival. However, completion of all therapy, including pancreatectomy, was the only independently significant predictor of outcome in a multivariate analysis of overall survival., Discussion: These data suggest that body composition analysis of standard CT images may provide clinically relevant information for patients with potentially resectable pancreatic cancer who receive neoadjuvant therapy. Anthropometric changes must be considered in the design of preoperative therapy regimens, and further efforts should focus on maintenance of muscle and visceral adipose tissue in the preoperative setting.

Background: Venous resection may be required to achieve complete resection of pancreatic cancers. We assessed the ability of radiographic criteria to predict the need for superior mesenteric-portal vein (SMV-PV) resection and the presence of histologic vein invasion., Methods: All patients who underwent pancreaticoduodenectomy from 2004 to 2011 at the authors' institution were identified. Preoperative pancreatic protocol CT images were re-reviewed to characterize the extent of tumor-vein circumferential interface (TVI) as demonstrating no interface, ≤ 180° of vessel circumference, >180° of vessel circumference, or occlusion. Findings were correlated with the need for venous resection, histologic venous invasion, and survival., Results: A total of 254 patients underwent pancreaticoduodenectomy and met inclusion criteria; 98 (39.6 %) required SMV-PV resection. In our cohort, 76.4 % of patients received neoadjuvant chemoradiation. The TVI classification system predicted with fair accuracy both the need for SMV-PV resection at the time of surgery and histologic invasion of the vein. In particular, 89.5 % of patients with TVI > 180° or occlusion required SMV-PV resection. Of those, 82.4 % had documented histologic SMV-PV invasion. TVI ≤ 180° was associated with favorable overall survival compared to a greater circumferential interface., Conclusions: A tomographic classification of the tumor-SMV-PV interface can predict the need for venous resection, pathologic venous involvement, and survival. To assist in treatment planning, a standardized assessment of this anatomic relationship should be routinely performed.

Metastatic pancreatic cancer carries a poor prognosis, with median survival on the order of several months. There is evidence that combining gemcitabine with either erlotinib or cisplatin may be superior to single agent gemcitabine in patients with good performance (PS 0-1). We retrospectively compared outcomes of patients treated with either the three drug regimen of gemcitabine, cisplatin, and erlotinib (GCE) or the doublet of gemcitabine and cisplatin (GC) in order to assess the potential benefit of erlotinib. We also evaluated the role of erlotinib among smokers and non-smokers. We retrospectively analyzed 145 patients who presented between 2006 and 2009 with previously untreated metastatic pancreatic cancer initially treated at the M.D. Anderson cancer center with either GC or GCE. Information on tumor characteristics and overall survival time (OS) was collected by medical record review. Kaplan-Meier curves were used to estimate OS. Log rank tests were used to compare OS between groups. The Cox proportional hazards regression model was used to evaluate the ability of patient prognostic variables or treatment group to predict OS. A total of 71 patients were treated with GC, while 74 were treated with GCE. Cox analyses found no significant difference in overall survival (median 5.5 vs. 8.0 months, respectively, p-value=0.1). Small sampling numbers may have contributed to this result. One year survival was 23 % in the GCE group and 13 % in the GC group. Patients with poor performance status (PS=2-3) had worse survival as compared to patients with better performance status (PS=0-1, p=0.001). As in earlier studies, patients treated with more lines of therapy tended to have better survival (p <0.0001), and CA19-9 was found to be a significant predictor for OS (p=0.001). No statistical evidence of a survival difference was found between smokers and non-smokers in both treatment groups (p=0.72). In conclusion, though there was a trend towards improved survival with the addition of erlotinib to gemcitabine and cisplatin, this does not reach statistical significance.

Objectives: To determine the influence of neoadjuvant chemoradiation and standardized dissection of the superior mesenteric artery upon the oncologic outcome of patients with localized pancreatic adenocarcinoma., Methods: One hundred ninety-four patients with pancreatic adenocarcinoma who underwent pancreaticoduodenectomy between 2004 and 2008 were evaluated. The retroperitoneal dissection was performed directly along the superior mesenteric artery in all cases. A standard histopathologic protocol that measured the "superior mesenteric artery (SMA) margin distance" between cancer cells and the superior mesenteric artery was employed., Results: Seventy-six percent of patients received neoadjuvant chemoradiation. The SMA margin was positive in 4% of patients but an additional 22% of patients with a negative margin had a SMA margin distance of ≤1 mm. Preoperative CT images overestimated the SMA margin distance in 73% of cases. Patients who received chemoradiation had longer SMA margin distances than those who did not. Patients who received chemoradiation and had a SMA margin of >1 mm had the lowest recurrence rates. Administration of neoadjuvant chemoradiation and lower estimated blood loss were independently associated with longer progression-free survival on multivariate analysis., Conclusions: Preoperative chemoradiation and meticulous dissection of the superior mesenteric artery maximize the distance between cancer cells and the SMA margin and may influence locoregional control.

Purpose: We conducted a phase II trial to assess the survival duration and quality of life of patients who received adjuvant interferon-based chemoradiation for pancreatic adenocarcinoma after pancreaticoduodenectomy., Methods: Patients with a performance status of 0 or 1 were enrolled to receive interferon-alfa-2b (3 million units MWF), cisplatin (30 mg/m(2), 6 doses) and 5-fluorouracil (5-FU; 175 mg/m(2)/day), concurrent with external-beam radiation (50.4 Gy) and followed by 2 courses of systemic 5-FU. The protocol was modified to include an optional 9 day break in the middle of chemoradiation. Quality of life was assessed by use of validated instruments., Results: Twenty-eight patients were eligible for analysis. The operation of 15 (54%) patients was performed at other institutions. All patients had T3 tumors, 22 (79%) had positive lymph nodes and 4 (14%) had positive (R1) margins. 24 (86%) patients completed therapy. In all, 25 (89%) patients experienced grade 3 toxicity and 3 (11%) patients were hospitalized. The most common grade 3 events were leukopenia (15, 54%) and neutropenia (12, 43%). No grade 4 toxicity occurred. Overall quality of life decreased during chemoradiation but returned to baseline thereafter and was stable throughout surveillance. 19 patients have died; the median follow-up of the 9 survivors is 62 months. The median OS duration of treated patients was 42.3 (95% confidence interval 30.5-54.2) months., Conclusions: Adjuvant interferon-based chemoradiation can be delivered safely and tolerably-though with substantial reversible toxicity-to patients of good performance status at an experienced cancer center. Therapy may be associated with an improvement in overall survival.

Introduction: Actual 5-year survival rates of 10-18% have been reported for patients with resected pancreatic adenocarcinoma (PC), but the use of multimodality therapy was uncommon in these series. We evaluated long-term survival and patterns of recurrence in patients treated for PC with contemporary staging and multimodality therapy., Methods: We analyzed 329 consecutive patients with PC evaluated between 1990 and 2002 who underwent resection. Each received a multidisciplinary evaluation and a standard operative approach. Pre- or postoperative chemotherapy and/or chemoradiation were routine. Surgical specimens of 5-year survivors were re-reviewed. A multivariate model of factors associated with long-term survival was constructed., Results: Patients underwent pancreaticoduodenectomy (n = 302; 92%), distal (n = 20; 6%), or total pancreatectomy (n = 7; 2%). A total of 108 patients (33%) underwent vascular reconstruction, 301 patients (91%) received neoadjuvant or adjuvant therapy, 157 specimens (48%) were node positive, and margins were microscopically positive in 52 patients (16%). Median overall survival and disease-specific survival was 23.9 and 26.5 months. Eighty-eight patients (27%) survived a minimum of 5 years and had a median overall survival of 11 years. Of these, 21 (24%) experienced recurrence, 7 (8%) after 5 years. Late recurrences occurred most frequently in the lungs, the latest at 6.7 years. Multivariate analysis identified disease-negative lymph nodes (P = .02) and no prior attempt at resection (P = 0.01) as associated with 5-year survival., Conclusions: Our 27% actual 5-year survival rate for patients with resected PC is superior to that previously reported, and it is influenced by our emphasis on detailed staging and patient selection, a standardized operative approach, and routine use of multimodality therapy.

This study was designed to determine the safety and optimal dosing of TAS-102, a novel oral combination of alphaalphaalpha-trifluorothymidine (FTD) and an inhibitor of thymidine phoshorylase, in patients with solid tumors. Patients who met the eligibility criteria were treated with one of two different TAS-102 regimens: once per day on either days 1-5 and 8-12 every 4 weeks (schedule A) or days 1-5 every 3 weeks (schedule B). The primary objectives were the determination of the maximum tolerated dose, dose-limiting toxicities (DLTs), and recommended phase II dose. Pharmacokinetic analysis was conducted during courses 1 and 2. Sixty-three patients received a total of 172 courses of therapy with the median number of courses delivered on both schedules being 2. DLTs were observed in three patients on schedule A, 70 mg/m(2)/day (1) and 110 mg/m(2)/day (2); and in five patients on schedule B, 120 mg/m(2)/day (1), 170 mg/m(2)/day (2), 180 mg/m(2)/day (2). Granulocytopenia was the DLT in seven of the eight cases. The most frequent toxicities were nausea, fatigue, granulocytopenia, anemia, diarrhea, and abdominal pain. Twelve patients, 6 on schedule A and 6 on schedule B, were treated at the recommended phase II dose, with good tolerance. No objective responses were seen in this heavily pretreated, 5-FU-refractory population. The pharmacokinetic parameters of FTD are a T (max) of 0.53 to 3.15 h, t (1/2) of 1.46 to 4.20 h, volume of distribution of 0.0526 to 0.483 l/kg, and clearance of 0.0194 to 0.197 1/h/kg. The recommended phase II doses for TAS-102 are 100 mg/m(2)/day on schedule A and 160 mg/m(2)/day on schedule B. Future development of TAS-102 should focus upon multiple daily dosing schedules.