Faculty Bibliography

BACKGROUND:To improve outcomes for patients with pancreatic ductal adenocarcinoma, a complete resection is crucial. However, evidence regarding the impact of microscopically positive surgical margins (R1) on recurrence is conflicting due to varying definitions and limited populations of patients with borderline-resectable and locally advanced pancreatic cancer. Therefore, we aimed to determine the impact of the resection margin status on recurrence and survival in patients with pancreatic ductal adenocarcinoma stratified by local tumor stage. METHODS:We performed a retrospective cohort study on patients with nonmetastatic pancreatic ductal adenocarcinoma undergoing pancreatectomy at a high-volume academic center (2012-2022). R1 was subclassified into microscopic invasion of the margin (R1 direct) or carcinoma present within 1 mm but not directly involving the margin (R1 <1 mm). Overall survival and time to recurrence were assessed by log-rank test and multivariable Cox regression. RESULTS:Of 472 included patients, 154 (33%) had an R1 resection. Of those 50 (32%) had R1 <1 mm and 104 (68%) R1 direct. The most commonly involved margin was the uncinate (41%) followed by the pancreatic neck (16%) and vascular margins (9%). Overall, a stepwise shortening of time to recurrence and overall survival was observed with an increasing degree of margin involvement (median time to recurrence: R0 39.3 months, R1 <1 mm 16.0 months, and R1 direct 13.4 months, all comparisons P < .05). Multivariable analyses confirmed the independent prognostic value of R1 direct across all surgical stages. CONCLUSION/CONCLUSIONS:The resection margin status portends an independent prognostic value. Moreover, this association persists in patients with borderline-resectable and locally advanced pancreatic cancer. Increasing the R0-resection rate is the most important potentially influenceable prognostic factor for improving surgery-related outcomes.

PURPOSE/OBJECTIVE:Dynamics of carbohydrate antigen 19-9 (CA19-9) often inform treatment decisions during and after neoadjuvant chemotherapy (NAT) of patients with pancreatic ductal adenocarcinoma (PDAC). However, considerable dispute persists regarding the clinical relevance of specific CA19-9 thresholds and dynamics. Therefore, we aimed to define optimal thresholds for CA19-9 values and create a biochemically driven composite score to predict survival in CA19-9-producing patients with PDAC after NAT. METHODS:Patients with PDAC who underwent NAT and surgical resection from 2012 to 2022 were retrospectively identified from three high-volume centers. CA19-9 nonproducers and patients with 90-day mortality, and macroscopically incomplete resections were excluded. A composite score was created on the basis of relative CA19-9 change and newly defined optimal thresholds of pre- and postneoadjuvant values for overall survival (OS) using patients from two centers and validated using data from the third center. RESULTS:< .001). Major serological response (90% decrease of CA19-9) had a positive and negative predictive value of 32% and 88%, respectively. CONCLUSION/CONCLUSIONS:The composite score consisting of CA19-9 levels at diagnosis, after neoadjuvant treatment, and its dynamics demonstrates prognostic discrimination between low and high scores. However, better predictive biomarkers are needed to facilitate treatment decisions during neoadjuvant treatment.

BACKGROUND OBJECTIVES/OBJECTIVE:The aim of this study was to determine the role of site-specific metastatic patterns over time and assess factors associated with extended survival in metastatic PDAC. Half of all patients with pancreatic ductal adenocarcinoma (PDAC) present with metastatic disease. The site of metastasis plays a crucial role in clinical decision making due to its prognostic value. METHODS:We examined 56,757 stage-IV PDAC patients from the National Cancer Database (2016-2019), categorizing them by metastatic site: multiple, liver, lung, brain, bone, carcinomatosis, or other. The site-specific prognostic value was assessed using log-rank tests while time-varying effects were assessed by Aalen's linear hazards model. Factors associated with extended survival (>3years) were assessed with logistic regression. RESULTS:Median overall survival (mOS) in patients with distant lymph node-only metastases (9.0 months) and lung-only metastases (8.1 months) was significantly longer than in patients with liver-only metastases (4.6 months, p < 0.001). However, after six months, the metastatic site lost prognostic value. Logistic regression identified extended survivors (3.6 %) as more likely to be younger, Hispanic, privately insured, Charlson-index <2, having received chemotherapy, or having undergone primary or distant site surgery (all p < 0.001). CONCLUSION/CONCLUSIONS:While synchronous liver metastases are associated with worse outcomes than lung-only and lymph node-only metastases, this predictive value is diminished after six months. Therefore, treatment decisions beyond this time should not primarily depend on the metastatic site. Extended survival is possible in a small subset of patients with favorable tumor biology and good conditional status, who are more likely to undergo aggressive therapies.

OBJECTIVE:To analyze postrecurrence progression in the context of recurrence sites and assess implications for postrecurrence treatment. BACKGROUND:Most patients with resected pancreatic ductal adenocarcinoma (PDAC) recur within 2 years. Different survival outcomes for location-specific patterns of recurrence are reported, highlighting their prognostic value. However, a lack of understanding of postrecurrence progression and survival remains. METHODS:This retrospective analysis included surgically treated patients with PDAC at NYU Langone Health (2010-2021). Sites of recurrence were identified at the time of diagnosis and further follow-up. Kaplan-Meier curves, log-rank test, and Cox regression analyses were applied to assess survival outcomes. RESULTS:Recurrence occurred in 57.3% (196/342) patients with a median time to recurrence of 11.3 months (95% CI: 12.6-16.5). The first site of recurrence was local in 43.9% of patients, liver in 23.5%, peritoneal in 8.7%, lung in 3.6%, whereas 20.4% had multiple sites of recurrence. Progression to secondary sites was observed in 11.7%. Only lung involvement was associated with significantly longer survival after recurrence compared with other sites (16.9 vs 8.49 months, P = 0.003). In local recurrence, 21 (33.3%) patients were alive after 1 year without progression to secondary sites. This was associated with a CA19-9 of <100 U/mL at the time of primary diagnosis ( P = 0.039), nodal negative disease ( P = 0.023), and well-moderate differentiation ( P = 0.042) compared with patients with progression. CONCLUSION/CONCLUSIONS:Except for lung recurrence, postrecurrence survival after PDAC resection is associated with poor survival. A subset of patients with local-only recurrence do not quickly succumb to systemic spread. This is associated with markers for favorable tumor biology, making them candidates for potential curative re-resections when feasible.

BACKGROUND:The appropriate surgical approach for pancreatic ductal adenocarcinoma (PDAC) is determined by the tumor's relation to the porto-mesenteric axis. Although the extent and location of lymphadenectomy is dependent on the type of resection, a pancreatoduodenectomy (PD), distal pancreatectomy (DP), or total pancreatectomy (TP) are considered equivalent oncologic operations for pancreatic neck tumors. Therefore, we aimed to assess differences in histopathological and oncological outcomes for surgical approaches in the treatment of pancreatic neck tumors. METHODS:Patients with resected PDAC located in the pancreatic neck were identified from the National Cancer Database (2004-2020). Patients with metastatic disease were excluded. Furthermore, patients with 90-day mortality and R2-resections were excluded from the multivariable Cox-regression analysis. RESULTS:Among 846 patients, 58% underwent PD, 25% DP, and 17% TP with similar R0-resection rates (p = 0.722). Significant differences were observed in nodal positivity (PD:44%, DP:34%, TP:57%, p < 0.001) and mean-number of examined lymph nodes (PD:17.2 ± 10.4, DP:14.7 ± 10.5, TP:21.2 ± 11.0, p < 0.001). Furthermore, inadequate lymphadenectomy (< 12 nodes) was observed in 30%, 44%, and 19% of patients undergoing PD, DP, and TP, respectively (p < 0.001). Multivariable analysis yielded similar overall survival after DP (HR:0.83, 95%CI:0.63-1.11), while TP was associated with worse survival (HR:1.43, 95%CI:1.08-1.89) compared to PD. CONCLUSION/CONCLUSIONS:While R0-rates are similar amongst all approaches, DP is associated with inadequate lymphadenectomy which may result in understaging disease. However, this had no negative influence on survival. In the premise that an oncological resection of the pancreatic neck tumor is feasible with a partial pancreatectomy, no benefit is observed by performing a TP.

The treatment of borderline resectable (BR) pancreatic cancer is challenging and requires a multidisciplinary approach with chemotherapy, radiation and surgical resection. Despite using chemotherapy and radiotherapy in the neoadjuvant setting, achievement of negative surgical margins remains technically challenging. Positive margins are associated with increased local recurrences and worse overall survival and there are no standard options for treatment. The CivaSheet is an FDA-cleared implantable sheet with a matrix of unidirectional planar low-dose-rate (LDR) Palladium-103 (Pd-103) sources. The sources are shielded on one side with gold to spare radio-sensitive structures such as the bowel. The sheet can easily be customized and implanted at the time of surgery when there is concern for close or positive margins. The CivaSheet provides an interesting solution to target the region of close/positive margins after pancreatectomy. Here we discuss the physical properties, the dosimetry, clinical workflow and early patient outcomes with the CivaSheet in pancreatic cancer.

BACKGROUND:Margin negative resection in pancreatic cancer remains the only curative option but is challenging, especially with the retroperitoneal margin. Intraoperative radiation therapy (IORT) can improve rates of local control but requires specially designed facilities and equipment. This retrospective review describes initial results of a novel implantable mesh of uni-directional low dose rate (LDR) Pd-103 sources (sheet) used to deliver a focal margin-directed high-dose boost in patients with concern for close or positive margins. METHODS:Eleven consecutive patients from a single institution with resectable or borderline resectable pancreatic cancer with concern for positive margins were selected for sheet placement and retrospectively reviewed. Procedural outcomes, including the time to implant the device and complications, and clinical outcomes, including survival and patterns of failure, are reported. A dosimetric comparison of the LDR sheet with hypothetical stereotactic body radiotherapy (SBRT) boost is reported. RESULTS:One patient had a resectable disease, and 10 patients had a borderline resectable disease and underwent neoadjuvant treatment. Sheet placement added 15 min to procedural time with no procedural or sheet-related complications. At a median follow up of 13 months, 64% (n = 7) of patients are alive and 55% (n = 6) are disease-free. Compared to a hypothetical SBRT boost, the LDR sheet delivered a negligible dose to kidneys, liver, and spinal cord with a 50% reduction in max dose to the small bowel. CONCLUSION:This is the first report of the use of an implantable uni-directional LDR brachytherapy sheet in patients with resected pancreatic cancer with concern for margin clearance, with no associated toxicity and favorable clinical outcomes.

Esophageal squamous cell carcinoma and adenocarcinoma account for 95% of all esophageal malignancies. The rates of esophageal adenocarcinoma have increased in Western countries, making it the predominant type of esophageal cancer. Treatment of both types of cancer has transformed to a more minimally invasive approach, with endoscopic methods being used for superficial cancers and more frequent use of video-assisted and laparoscopic modalities for locally advanced tumors. The current National Comprehensive Cancer Network guidelines advocate a trimodal approach to treatment, with neoadjuvant chemoradiation and surgery for locally advanced cancers.

OBJECTIVES/OBJECTIVE:Ivor Lewis and McKeown esophagectomy are common techniques to treat esophageal cancer. In this study, we aim to compare these two approaches. METHOD/METHODS:We used the American College of Surgeons National Surgical Quality Improvement Project database (2005-2017) to compare both techniques using bivariate analysis after propensity matching. RESULTS:We identified 6136 patients with esophagectomy and divided them into 2 groups based on whether they received a McKeown (1676; 27.31%) or an Ivor Lewis (4460; 70.14%) esophagectomy. McKeown esophagectomy was associated with higher rates of superficial surgical site infections (8.02% vs 3.67%, p < 0.001), anastomotic leaks (9.12% vs 7.71%, p = 0.02), prolonged intubation (15.06% vs 10.10%, p < 0.001), re-intubation (15.30% vs 10.34%, p ≤ 0.001), and return to the OR (16.46% vs 11.32%, p < 0.001). The McKeown esophagectomy patients also had longer hospital length of stay (14.5 ± 11.99 vs 13.37 ± 11.8, p = 0.002), higher re-admission rate (21.56% vs 16.87%, p = 0.002), and higher discharges to nursing/rehabilitation institutions (14.06% vs 11.99%, p = 0.004).The mortality rate and positive resection margins were not significantly different. There was a trend toward more utilization of Ivor Lewis esophagectomy over years. CONCLUSION/CONCLUSIONS:When compared to Ivor Lewis esophagectomy, McKeown esophagectomy is associated with more unplanned intubation, increased difficulty weaning from the ventilator, incisional surgical site infections, anastomotic leak, and higher length of stay.