Neuroendocrine liver metastasis: The chance to be cured after liver surgery

Background and Objective: Neuroendocrine liver metastasis tumors (NELM) are a heterogeneous group of neoplasms with varied histologic features and a wide range of clinical behaviors. We aimed to identify the fraction of patients cured after liver surgery for NELM. Methods: Cure fraction models were used to analyze 376 patients who underwent hepatectomy with curative intent for NELM. Results: The median and 5-year disease-free survival (DFS) were 4.5 years and 46%, respectively. The probability of being cured from NELM by liver surgery was 44%; the time to cure was 5.1 years. In a multivariable cure model, type of neuroendocrine tumor (NET), grade of tumor differentiation, and rate of liver involvement resulted as independent predictors of cure. The cure fraction for patients with well differentiated NELM from gastrointestinal NET or a functional pancreatic NET, and with <50% of liver-involvement was 95%. Patients who had moderately/poorly differentiated NELM from a non-functional pancreatic NET, and with <50% of liver-involvement was 43%. In the presence of all the three unfavorable prognostic factors (nonfunctional PNET, liver involvement >50%, moderately/poorly differentiation), the cure fraction was 8%. Conclusions: Statistical cure after surgery for NELM is possible, and allow for a more accurate prediction of long-term outcome among patients with NELM undergoing liver resection

Treatment of borderline resectable (BR) and locally advanced (LA) pancreatic cancer in the era of FOLFIRINOX and gemcitabine plus nab-paclitaxel: A multi-institutional study

451 Background: FOLFIRINOX or Gemcitabine+nab-Paclitaxel (Gem/nPac) has superior overall survival (OS) compared with gemcitabine alone in pts with Stage 4 pancreatic cancer (PC). Based on these results, FOLFIRINOX or Gem/nPac has been utilized in neoadjuvant (NA) setting for BR and LA PC. This report describes our multi-institutional experience with NA treatment with FOLFIRINOX or Gem/nPac followed by surgical resection. Methods: Pts with BR and LA PC who received NA FOLFIRINOX or Gem/nPac and underwent surgical resection between 2011 and 2015 at 7 high volume pancreas centers were reviewed. Pre-operative chemoradiation therapy (pCXRT) was administered selectively based on radiographic response (RR). Near-complete (minimal residual disease) or complete pathologic response (PR) was categorized as marked PR. Results: 86 pts received either NA FOLFIRINOX (69%) or Gem/nPac therapy (31%) for BR (67%), LA (32%) PC. pCXRT was administered in 71% of pts. Pts received a median of 4 cycles of FOLFIRINOX (range 1-28) and 3 cycles of Gem/nPac (range 2-13). No grade 4-5 toxicities were noted. The majority of pts underwent pancreaticoduodenectomy (84%) and vascular resection was performed in 53% - 40 with venous resection and 6 with arterial resection. R0 resection rate was 86% with no difference between two treatment groups (p = 0.9). Reduction in CA 19-9 or RR did not correlate with pathological response (p = 0.8). A marked PR was seen in 12 pts – 13.6% vs. 15.4% for FOLFIRINOX and Gem/nPac, respectively (p = 0.8). Adjuvant chemotherapy or CXRT was administered in 44% of pts. With a median follow up of 20 months (mo), OS was 27.4 mo with median OS in marked PR was 53 vs. 25 mo in moderate PR/non-responders (p = 0.04). Recurrence was noted in 45 pts – 49% had distant recurrence, 20% had local recurrence and 31% had both. Conclusions: Neoadjuvant FOLFIRINOX or Gem/nPac therapy in conjunction with aggressive surgical resection in BR and select LA PDAC pts result in significant long-term survival especially in marked pathologic responders. Further, optimization of treatment protocols in the neoadjuvant and adjuvant setting is warranted since recurrence rates are high

A multi-center study of 349 pancreatic mucinous cystic neoplasms: Preoperative risk factors for adenocarcinoma

231 Background: Pancreatic mucinous cystic neoplasms (MCN) are defined by presence of ovarian stroma per WHO 2000 classification. Given their malignant potential, current guidelines recommend resection. However, there are limited data on preoperative risk factors for adenocarcinoma (AC) and high grade dysplasia (HGD) occurring in an MCN. Methods: MCN resections from 2000-2014 at the 8 institutions of the Central Pancreas Consortium were included. Patients with and without AC/HGD were compared. Primary aims were to determine preoperative risk factors for AC/HGD in an MCN and to assess outcomes of MCN-associated AC. Results: Of 1667 resections for pancreatic cystic lesions, 349 pts (21%) had an MCN with 52 (15%) having MCN-associated AC/HGD. Male gender (29 vs 8%; p<0.001), head/neck location (39 vs 13%; p<0.001), increased MCN size (7.2 vs 4.6 cm; p=0.004), radiographic presence of a solid component/mural nodule (54 vs 20%; p<0.001), and duct dilation (43 vs 12%; p<0.001) were associated with AC/HGD compared to benign MCN. All persisted as independent predictors of MCN-associated AC/HGD (Table). AC/HGD was not associated with presence of radiographic septations or preoperative cyst fluid analysis (CEA, amylase, or mucin). Median CA19-9 for patients with AC/HGD was 210 vs 15 U/ml for those without (p=0.001). In the 44 pts with AC, 41 (93%) had lymph nodes harvested with nodal metastases in only 14 (34%). Median FU for pts with AC was 27 mos. AC recurred in 12 pts (27%) with a 3-yr RFS of 59%. OS for pts with MCN-associated AC was 64% at 3 yrs. Conclusions: Adenocarcinoma or high grade dysplasia is present in 15% of resected pancreatic mucinous cystic neoplasms. Pre-operative factors associated with AC/HGD in an MCN include male gender, head/neck location, larger MCN, solid component/mural nodule, and duct dilation on imaging. MCN-associated AC appears to have decreased LN involvement and increased RFS and OS compared to typical pancreatic ductal adenocarcinoma. [Table: see text