Pancreatic Cancer Frequently Infiltrates the TRIANGLE Compartment: A Surgical Option to Prevent Local Recurrence

Therapeutic Advances in Pancreatic Cancer

Mapping Patterns of Local Failure Following Pancreaticoduodenectomy for Pancreatic Cancer: A New Approach to Adjuvant Radiation Fields

Locoregional treatment outcomes for patients with ipsilateral supraclavicular metastases at diagnosis of breast cancer

The US Cancer Moonshot initiative

This prospective multicenter study aimed to evaluate the diagnostic performance of 80-kVp thin-section pancreatic CT in determining pancreatic ductal adenocarcinoma (PDAC) resectability according to the recent National Comprehensive Cancer Network (NCCN) guidelines. We prospectively enrolled surgical resection candidates for PDAC from six tertiary referral hospitals (study identifier: NCT03895177). All participants underwent pancreatic CT using 80 kVp tube voltage with 1-mm reconstruction interval. The local resectability was prospectively evaluated using NCCN guidelines at each center and classified into three categories: resectable, borderline resectable, and unresectable. A total of 138 patients were enrolled; among them, 60 patients underwent neoadjuvant therapy. R0 resection was achieved in 103 patients (74.6%). The R0 resection rates were 88.7% (47/53), 52.4% (11/21), and 0.0% (0/4) for resectable, borderline resectable, and unresectable disease, respectively, in 78 patients who underwent upfront surgery. Meanwhile, the rates were 90.9% (20/22), 76.7% (23/30), and 25.0% (2/8) for resectable, borderline resectable, and unresectable PDAC, respectively, in patients who received neoadjuvant therapy. The area under curve of high-resolution CT in predicting R0 resection was 0.784, with sensitivity, specificity, and accuracy of 87.4% (90/103), 48.6% (17/35), and 77.5% (107/138), respectively. Tumor response was significantly associated with the R0 resection after neoadjuvant therapy (odds ratio [OR] = 38.99, p = 0.016). An 80-kVp thin-section pancreatic CT has excellent diagnostic performance in assessing PDAC resectability, enabling R0 resection rates of 88.7% and 90.9% for patients with resectable PDAC who underwent upfront surgery and patients with resectable PDAC after neoadjuvant therapy, respectively. • The margin-negative (R0) resection rates were 88.7% (47/53), 52.4% (11/21), and 0.0% (0/4) for resectable, borderline resectable, and unresectable pancreatic ductal adenocarcinoma (PDAC), respectively, on 80-kVp thin-section pancreatic CT in the 78 patients who underwent upfront surgery. • Among the 60 patients who underwent neoadjuvant therapy, the R0 rates were 90.9% (20/22), 76.7% (23/30), and 25.0% (2/8) for resectable, borderline resectable, and unresectable PDAC, respectively. • Tumor response, along with the resectability status on pancreatic CT, was significantly associated with the R0 resection rate after neoadjuvant therapy.

Neoadjuvant Chemotherapy in Pancreatic Cancer: An Appraisal of the Current High-Level Evidence

Recommendations for a More Organized and Effective Approach to the Early Detection of Pancreatic Cancer From the PRECEDE (Pancreatic Cancer Early Detection) Consortium

This video manuscript by Ikoma and colleagues demonstrates their approach to the superior mesenteric artery and hepatic artery periadventitial dissection. The quality of superior mesenteric artery and hepatic artery dissections should be maintained in robotic pancreatoduodenectomy when performed for pancreatic cancer, to provide the best possible oncological outcomes.

Neoadjuvant therapy (NAT) is a growing strategy for patients with resectable pancreatic ductal adenocarcinoma (PDAC). Elderly patients are at increased risk of treatment withdrawal due to functional decline, and the benefit of NAT in this cohort remains to be studied. The objective of this study was to compare outcomes of elderly patients with resectable head PDAC who underwent NAT or a surgery-first (SF) approach. All patients 75 years of age and older with radiographically resectable (National Comprehensive Cancer Network criteria) PDAC who underwent pancreaticoduodenectomy at a single institution from 2008 to 2017 were analyzed. Baseline characteristics and perioperative outcomes were compared between the SF and NAT cohorts. Recurrence-free survival and overall survival (OS) were analyzed by treatment strategy. Overall, 158 patients were identified: SF cohort=90 (57%) and NAT cohort=68 (43%). Patients in the SF cohort were older (80 vs. 78 years; p=0.01) but there were no differences in preoperative comorbidities or frailty indices. SF patients had a trend toward higher rates of major complications (38% vs. 24%; p=0.06) with higher Comprehensive Complication Index totals (20.9 vs. 20; p=0.03). There were similar rates of adjuvant therapy. NAT was associated with significantly longer OS (24.6 vs. 17.6 months; p=0.01) in both the intent-to-treat and resected cohorts. On multivariable analysis (MVA), NAT remained an independent predictor of OS (hazard ratio 0.60; p=0.02). NAT is safe and effective for elderly patients with PDAC. This study suggests NAT is associated with fewer complications after surgery, equal rates of adjuvant therapy receipt, and increased OS over a surgery-first approach.

Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial

Complete circumferential lymphadenectomy around the superior mesenteric artery with preservation of nerve plexus reduces locoregional recurrence after pancreatoduodenectomy for resectable pancreatic ductal adenocarcinoma

4131 Background: Sarcopenia and sarcopenic obesity have been associated with overall survival (OS) in patients (pts) with borderline resectable and advanced pancreatic ductal adenocarcinoma (PDA), but little is known about the effect of body composition on OS in pts with resectable PDA. We examined the relationship between skeletal muscle and adipose tissue measurements on baseline computed tomography (CT) and OS of pts with resectable PDA in a secondary analysis of SWOG S1505 (NCT02562716). Methods: SWOG S1505 enrolled pts with resectable PDA who were randomized to receive neoadjuvant FOLFIRINOX or gemcitabine-nab paclitaxel, followed by surgical resection. Baseline axial CT images at the L3 level were analyzed with externally validated software and measurements were recorded for skeletal muscle area (SMA), density (SMD) and index (SMI); visceral adipose tissue area (VATA) and density (VATD); and subcutaneous adipose tissue area (SATA) and density (SATD). Sarcopenia was defined as SMI < 52 cm2/m2 for men and < 39 cm2/m2 for women; sarcopenic obesity was defined as sarcopenia and a body mass index (BMI) >30 kg/m2. The relationships between CT metrics and OS were analyzed using Cox regression models, with 95% CI. Statistical significance was defined as p < 0.05. Results: Of 98 pts with available baseline abdominal CT, 8 were excluded for scan quality, resulting in 90 evaluable cases: 51 men (57%), 39 women (43%); mean age, 63.2 years, SD 8.5; mean BMI, 29.3 kg/m2, SD 6.4; 80 (89%) White, 6 (7%) Black, and 4 (4%) unknown. Sarcopenia was present in 32 (36%) and sarcopenic obesity in 10 (11%) patients. Univariable analyses for the variables of interest indicated VATA (HR 1.24; 0.97-1.60; p = 0.09) and SMD (HR 0.75; 0.57-0.98; p = 0.04) were associated with OS. Analyses adjusted for sex, race, age, BMI, performance score, contrast use, sarcopenia, and sarcopenic obesity showed VATA was associated with OS (HR 1.58; 1.0-2.51; p = 0.05). No significant difference in median OS was observed between pts with vs. without sarcopenia (OS 23.6 [19.3-NA] vs. 27.9 months [18.6-NA], respectively). Pts with vs. without sarcopenic obesity had lower median OS: 18.6 (14.7-NA) vs. 25.1 (10.5-46.0) months, respectively, but this difference was not statistically significant (HR 1.90, 95%CI 0.81-4.47, p = 0.14). Conclusions: This is one of the first studies to systematically evaluate body composition parameters in a prospective trial of patients with resectable PDA who received neoadjuvant chemotherapy. We found that visceral fat (VATA) is a prognostic marker in this population, but that sarcopenia may not be predictive in early PDA. Further studies to define the impact of longitudinal changes in body composition on individual outcomes may provide greater precision in predicting OS for subsets of pts with pancreatic cancer. Clinical trial information: NCT02562716.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the United States. Previous studies have indicated that microsatellite instability and deficient mismatch repair (MMR) may be associated with improved survival in patients with pancreatic cancer. Here, we aim to investigate the impact of deficient MMR (dMMR) status on oncologic outcomes in patients after resection of PDAC and periampullary adenocarcinoma. Methods: This is a single-institution, retrospective study based on a prospectively maintained database. Pancreatic ductal adenocarcinoma (N = 342) and periampullary adenocarcinoma patients (N = 76) who underwent pancreatic resection surgery between 2016 and 2021 were included. Immunohistochemistry staining results of MMR proteins and next-generation sequencing data were recorded. Cancer-type dependent Cox regression analyses were performed to assess overall and disease-free survival, which was complemented with a 1:2 propensity-score matching for each of the cancer types in order to compare oncologic outcomes. Results: A total of 418 pancreatic cancer patients were included in the analysis. Fifteen patients (3.5%) were diagnosed as dMMR (PDAC N = 7 and periampullary adenocarcinoma N = 8). Cox regression modeling of dMMR status interaction with TNM staging and cancer type revealed that dMMR status strongly improves overall survival (p < 0.05). After propensity-score matching, Cox regression identified dMMR status as a significant marker of improved overall survival (HR = 0.27, 95%CI 0.09-0.88, p = 0.029). Conclusions: Overall, our findings suggest that dMMR status is associated with markedly improved survival outcomes in patients after resection of pancreatic and periampullary cancer. Future large-scale studies are needed to further validate this finding.

Pancreatic cancer patients with para-aortic lymph node metastasis have a poor prognosis and patients living longer than 3 years are rare. We had a patient with pancreatic cancer who survived for more than 10 years after removal of the para-aortic lymph node metastasis. A 57-year-old woman was diagnosed with pancreatic head cancer and underwent a pancreaticoduodenectomy with subtotal gastric resection following Whipple reconstruction in 2000. Para-aortic lymph node metastasis was detected during the operation by intraoperative pathological diagnosis and an extended lymphadenectomy was performed with vascular skeletonization of the celiac and superior mesenteric arteries. In 2004, a low-density area was detected around the superior mesenteric artery (SMA) 5 cm from its root and she was treated with gemcitabine, and the area was undetectable after 3 years of treatment. In 2010, computed tomography showed a low-density area around the same lesion with an increased carcinoembryonic antigen level. After 4 months of gemcitabine treatment, we resected the tumor en bloc with the associated superior mesenteric vein and perineural tissue. Histopathological examination of the resected specimen revealed a well-differentiated tubular adenocarcinoma that closely resembled the original primary pancreatic cancer, indicating perineural recurrence 10 years after the initial resection. She had no recurrence around the SMA for more than one year. Although a meta-analysis has not proved the efficacy of preventive radical dissection, this case indicates that a patient with well-differentiated, chemotherapy-responsive pancreatic cancer with para-aortic lymph node metastasis could have a long survival time through extended dissection of the lymph nodes.

Decision letter: Neutrophil-mediated fibroblast-tumor cell il-6/stat-3 signaling underlies the association between neutrophil-to-lymphocyte ratio dynamics and chemotherapy response in localized pancreatic cancer: A hybrid clinical-preclinical study