Real time ex vivo chemosensitivity assay for pancreatic adenocarcinoma.

BACKGROUND: Patient-derived organoids (PDOs) and xenografts (PDXs) have been extensively studied for drug-screening. However, their usage is limited due to lengthy establishment time, high engraftment failure rates and different tumor microenvironment from original tumors. To overcome the limitations, we developed real time-live tissue sensitivity assay (RT-LTSA) using fresh tumor samples. METHODS: Tissue slices from resected pancreatic cancer samples were placed in 96-well plates, and the slices were treated with chemotherapeutic agents. The correlation between the chemo-sensitivity of tissue slices and each patient's clinical outcome was analyzed. RESULTS: The viability and tumor microenvironment of the tissue slices are well-preserved over 5 days. The drug sensitivity assay results are available within 5 days after tissue collection. While all 4 patients who received RT-LTSA sensitive adjuvant regimens did not develop recurrence, 7 of 8 patients who received resistant adjuvant regimens developed recurrence. We observed significantly improved disease-free survival in the patients who received RT-LTSA sensitive adjuvant regimens (median: not reached versus 10.6 months, P = 0.02) compared with the patient who received resistant regimens. A significant negative correlation between RT-LTSA value and relapse-free survival was observed (Somer's D: -0.58; P = 0.016). CONCLUSIONS: RT-LTSA which maintains the tumor microenvironment and architecture as found in patients may reflect clinical outcome and could be used as a personalized strategy for pancreatic adenocarcinoma. Further, studies are warranted to verify the findings.

Neoadjuvant chemotherapy and stereotactic body radiation therapy for borderline resectable pancreas adenocarcinoma: influence of vascular margin status and type of chemotherapy.

BACKGROUND: The influence of chemotherapy type and vascular margin status after sequential chemotherapy and stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic cancer (BRPC) is unknown. METHODS: A retrospective review was performed on BRPC patients treated with chemotherapy and 5-fraction SBRT from 2009 to 2021. Surgical outcomes and SBRT-related toxicity were reported. Clinical outcomes were estimated by Kaplan-Meier with log rank comparisons. RESULTS: A total of 303 patients received neoadjuvant chemotherapy and SBRT to a median dose of 40 Gy prescribed to the tumor-vessel interface and median dose of 32.4 Gyto 95% of the gross tumor volume. One hundred and sixty-nine patients (56%) were resected and benefited from improved median OS (41.1 vs 15.5 months, P < 0.001). Close/positive vascular margins were not associated with worse OS or FFLRF. Type of neoadjuvant chemotherapy did not influence OS for resected patients, but FOLFIRINOX was associated with improved median OS in unresected patients (18.2 vs 13.1 months, P = 0.001). CONCLUSION: For BRPC, the effect of a positive or close vascular margin may be mitigated by neoadjuvant therapy. Shorter duration neoadjuvant chemotherapy as well as the optimal biological effective dose of radiotherapy should be prospectively explored.

The impact of age and comorbidity on localized pancreatic cancer outcomes: A US retrospective cohort analysis with implications for surgical centralization.

Introduction: Age and comorbidity are independently associated with worse outcomes for pancreatic adenocarcinoma (PDAC). However, the effect of combined age and comorbidity on PDAC outcomes has rarely been studied. This study assessed the impact of age and comorbidity (CACI) and surgical center volume on PDAC 90-day and overall survival (OS). Methods: This retrospective cohort study used the National Cancer Database from 2004 to 2016 to evaluate resected stage I/II PDAC patients. The predictor variable, CACI, combined the Charlson/Deyo comorbidity score with additional points for each decade lived ≥50 years. The outcomes were 90-day mortality and OS. Results: The cohort included 29,571 patients. Ninety-day mortality ranged from 2 % for CACI 0 to 13 % for CACI 6+ patients. There was a negligible difference (1 %) in 90-day mortality between high- and low-volume hospitals for CACI 0-2 patients; however, there was greater difference for CACI 3-5 (5 % vs. 9 %) and CACI 6+ (8 % vs. 15 %). The overall survival for CACI 0-2, 3-5, and 6+ cohorts was 24.1, 19.8, and 16.2 months, respectively. Adjusted overall survival showed a 2.7 and 3.1 month survival benefit for care at high-volume vs. low-volume hospitals for CACI 0-2 and 3-5, respectively. However, there was no OS volume benefit for CACI 6+ patients. Conclusions: Combined age and comorbidity are associated with short- and long-term survival for resected PDAC patients. A protective effect of higher-volume care was more impactful for 90-day mortality for patients with a CACI above 3. A centralization policy based on volume may have greater benefit for older, sicker patients. Key message: Combined comorbidity and age are strongly associated with 90-day mortality and overall survival for resected pancreatic cancer patients. When assessing the impact of age and comorbidity on resected pancreatic adenocarcinoma outcomes, 90-day mortality was 7 % higher (8 % vs. 15 %) for older, sicker patients treated at high-volume vs. low-volume centers but only 1 % (3 % vs. 4 %) for younger, healthier patients.

Hospital Surgical Volume Is Poorly Correlated With Delivery of Multimodal Treatment for Localized Pancreatic Cancer: A National Retrospective Cohort Study.

Using Donabedian's quality of care model, this study assessed process (hospital multimodal treatment) and structure (hospital surgical case volume) measures to evaluate localized pancreatic cancer outcomes. Background: Treatment at high surgical volume hospitals has been shown to improve short-term outcomes. However, multimodal treatment-surgery and chemotherapy-is the standard of care yet only received by 35% of US patients and has not been examined at the hospital level. Methods: The National Cancer Database was used to identify a cohort of clinical stage I pancreatic cancer patients eligible for multimodal treatment from 2004 to 2016. Hospital multimodal treatment was defined as the number of patients receiving surgery and chemotherapy by the number of eligible patients per hospital. Descriptive statistics and survival analyses were conducted. Results: A total of 16,771 patients met inclusion criteria, of whom 68.0% received curative-intent surgery and 35.8% received multimodal treatment. There was poor correlation between hospital surgical volume and delivery of multimodal treatment (Spearman correlation 0.214; P < 0.001). Of patients cared for at the highest surgical volume hospitals, 18.8% and 52.1% were treated at hospitals with low (0%-25%) and moderate (>25%-50%) multimodal treatment delivery, respectively. Higher hospital multimodal treatment delivery was associated with improved overall survival. Discussion: Although the volume-outcome relationship for pancreatic cancer has demonstrated improved outcomes, this work identified poor correlation between hospital surgical volume and delivery of multimodal treatment. The role of care coordination in the delivery of multimodal treatment warrants further investigation as it is associated with improved survival for patients with localized pancreatic cancer.

Patient-caregiver dyads in pancreatic cancer: identification of patient and caregiver factors associated with caregiver well-being.

We aimed to examine the psychosocial well-being in the pancreas cancer patient-caregiver dyad, and determine patient and caregiver characteristics that predict caregiver distress. This was a cross-sectional, observational study. Demographics and caregiving characteristics were gathered from patients and caregivers. Caregivers completed validated instruments investigating anxiety, depression, perceived stress and caregiver burden. Over a period of eleven months, 128 patient-caregiver dyads were enrolled. Patient and caregiver distress scores were not associated with patient clinical disease burden. Patient distress was a significant predictor of concurrent caregiver distress, anxiety, depression, and perceived burden. Younger caregivers were also associated with higher caregiver anxiety and perceived burden. Additionally, number of caregiving activities and caregiver overall health status were predictors of concurrent caregiver depression and perceived stress. Certain pancreatic cancer patient and caregiver variables may negatively impact the well-being of caregivers. Future efforts should focus on development and implementation of comprehensive caregiver support programs for those at risk for psychosocial distress.

Pilot trial of remote monitoring to prevent malnutrition after hepatopancreatobiliary surgery.

BACKGROUND: Patients undergoing hepatopancreatobiliary (HPB) surgery, such patients with pancreatic, periampullary, and liver cancer, are at high risk for malnutrition. Malnutrition increases surgical complications and reduces overall survival. Despite its severity, there are limited interventions addressing malnutrition after HPB surgery. The aim of this pilot trial was to examine feasibility, acceptability, usability, and preliminary efficacy of a remote nutrition monitoring intervention after HPB surgery. METHODS: Participants received tailored nutritional counseling before and after surgery at 2 and 4 weeks after hospital discharge. Participants also recorded nutritional intake daily for 30 days, and these data were reviewed remotely by registered dietitians before nutritional counseling visits. Descriptive statistics were used to describe study outcomes. RESULTS: All 26 patients approached to participate consented to the trial before HPB surgery. Seven were excluded after consent for failing to meet eligibility criteria (e.g., did not receive surgery). Nineteen participants (52.6% female, median age = 65 years) remained eligible for remote monitoring post-surgery. Nineteen used the mobile app food diary, 79% of participants recorded food intake for greater than 80% of study days, 95% met with the dietitian for all visits, and 89% were highly satisfied with the intervention. Among participants with complete data, the average percent caloric goal obtained was 82.4% (IQR: 21.7). CONCLUSIONS: This intervention was feasible and acceptable to patients undergoing HPB surgery. Preliminary efficacy data showed most participants were able to meet calorie intake goals. Future studies should examine intervention efficacy in a larger, randomized controlled trial. TRIAL REGISTRATION: Clinicaltrials.gov. Registered 16 September 2019, https://clinicaltrials.gov/ct2/show/NCT04091165 .

The Florida Pancreas Collaborative Next-Generation Biobank: Infrastructure to Reduce Disparities and Improve Survival for a Diverse Cohort of Patients with Pancreatic Cancer.

Background: Well-annotated, high-quality biorepositories provide a valuable platform to support translational research. However, most biorepositories have poor representation of minority groups, limiting the ability to address health disparities. Methods: We describe the establishment of the Florida Pancreas Collaborative (FPC), the first state-wide prospective cohort study and biorepository designed to address the higher burden of pancreatic cancer (PaCa) in African Americans (AA) compared to Non-Hispanic Whites (NHW) and Hispanic/Latinx (H/L). We provide an overview of stakeholders; study eligibility and design; recruitment strategies; standard operating procedures to collect, process, store, and transfer biospecimens, medical images, and data; our cloud-based data management platform; and progress regarding recruitment and biobanking. Results: The FPC consists of multidisciplinary teams from fifteen Florida medical institutions. From March 2019 through August 2020, 350 patients were assessed for eligibility, 323 met inclusion/exclusion criteria, and 305 (94%) enrolled, including 228 NHW, 30 AA, and 47 H/L, with 94%, 100%, and 94% participation rates, respectively. A high percentage of participants have donated blood (87%), pancreatic tumor tissue (41%), computed tomography scans (76%), and questionnaires (62%). Conclusions: This biorepository addresses a critical gap in PaCa research and has potential to advance translational studies intended to minimize disparities and reduce PaCa-related morbidity and mortality.

The Impact of Socioeconomic Deprivation on Clinical Outcomes for Pancreatic Adenocarcinoma at a High-volume Cancer Center: A Retrospective Cohort Analysis.

OBJECTIVE: To assess the impact of a granular measure of SED on pancreatic surgical and cancer-related outcomes at a high-volume cancer center that employs a standardized clinic pathway. SUMMARY OF BACKGROUND DATA: Prior research has shown that low socioeconomic status leads to less treatment and worse outcomes for PDAC. However, these studies employed inconsistent definitions and categorizations of socioeconomic status, aggregated individual socioeconomic data using large geographic areas, and lacked detailed clinicopathologic variables. METHODS: We conducted a retrospective cohort study of 1552 PDAC patients between 2008 and 2015. Patients were stratified using the area deprivation index, a validated dataset that ranks census block groups based on SED. Multivariable models were used in the curative surgery cohort to predict the impact of SED on (1) grade 3/4 Clavien-Dindo complications, (2) initiation of adjuvant therapy, (3) completion of adjuvant therapy, and (4) overall survival. RESULTS: Patients from high SED neighborhoods constituted 29.9% of the cohort. Median overall survival was 28 months. The rate of Clavien-Dindo grade 3/4 complications was 14.2% and completion of adjuvant therapy was 65.6%. There was no evidence that SED impacted surgical evaluation, receipt of curative-intent surgery, postoperative complications, receipt of adjuvant therapy or overall survival. CONCLUSIONS: Although nearly one-quarter of curative-intent surgery patients were from high SED neighborhoods, this factor was not associated with measures of treatment quality or survival. These observations suggest that treatment at a high-volume cancer center employing a standardized clinical pathway may in part address socioeconomic disparities in pancreatic cancer.

Neutrophil to lymphocyte ratio, not platelet to lymphocyte or lymphocyte to monocyte ratio, is predictive of patient survival after resection of early-stage pancreatic ductal adenocarcinoma.

BACKGROUND: NLR, PLR, and LMR have been associated with pancreatic ductal adenocarcinoma (PDAC) survival. Prognostic value and optimal cutpoints were evaluated to identify underlying significance in surgical PDAC patients. METHODS: NLR, PLR, and LMR preoperative values were available for 277 PDAC patients who underwent resection between 2007 and 2015. OS, RFS, and survival probability estimates were calculated by univariate, multivariable, and Kaplan-Meier analyses. Continuous and dichotomized ratio analysis determined best-fit cutpoints and assessed ratio components to determine primary drivers. RESULTS: Elevated NLR and PLR and decreased LMR represented 14%, 50%, and 50% of the cohort, respectively. OS (P = .002) and RFS (P = .003) were significantly decreased in resected PDAC patients with NLR ≥5 compared to those with NLR < 5. Optimal prognostic OS and RFS cutpoints for NLR, PLR, and LMR were 4.8, 192.6, and 1.7, respectively. Lymphocytes alone were the primary prognostic driver of NLR, demonstrating identical survival to NLR. CONCLUSIONS: NLR is a significant predictor of OS and RFS, with lymphocytes alone as its primary driver; we identified optimal cutpoints that may direct future investigation of their prognostic value. This study contributes to the growing evidence of immune system influence on outcomes in early-stage pancreatic cancer.

Cancer outcomes are independent of preoperative CA 19-9 in anatomically resectable pancreatic ductal adenocarcinoma: A retrospective cohort analysis.

BACKGROUND AND OBJECTIVES: Current guidelines recommend neoadjuvant therapy for pancreatic ductal adenocarcinoma (PDAC) patients with anatomically resectable tumors but elevated CA 19-9. However, this recommendation is based on data from anatomically resectable and borderline resectable PDAC patients. Therefore, we analyzed the association of preoperative CA 19-9 with oncologic outcomes in a cohort of anatomically resectable PDAC patients. METHODS: A single-institution PDAC database from 2007 to 2015 included patients who underwent guideline-based staging and were anatomically resectable. Patients with bilirubin above 1.5 after decompression, nonsecretors of CA 19-9, and borderline resectable patients were excluded. Statistical analysis included frequency testing and regression modeling for recurrence and survival. RESULTS: One hundred forty-four PDAC patients were identified; 16 (11.1%) had elevated preoperative CA 19-9 ≥ 1000. A CA 19-9 level ≥1000 was not associated with demographic, clinical, or pathological factors. After adjustment for potential confounders, CA 19-9 levels (continuous, median, 500 U/mL, or 1000 U/mL cut-offs) were not associated with recurrence or overall survival (OS). CONCLUSIONS: Although guidelines recommend CA 19-9 to determine the management of anatomically resectable PDAC patients, CA 19-9 was not associated with recurrence or OS in this cohort. Our findings do not suggest that CA 19-9 alone should determine the PDAC treatment strategy.

Outcomes of Gastric Resection in the Establishment of a Comprehensive Oncologic Robotic Program.

BACKGROUND: Robotic-assisted gastrectomy is increasingly utilized for the treatment of gastric malignancies. However, the benefits of robotic surgery have been questioned. This study describes short-term outcomes in the establishment of a comprehensive robotic program for gastric malignancies. MATERIALS AND METHODS: Patients who underwent robotic-assisted gastric resections between 2013 and 2018 were studied. Preoperative measures and surgical outcomes were analyzed. Finally we studied and analyzed robotic and open gastrectomy for the management of gastric adenocarcinoma (GC) at the same institution between 2000 and 2018 for quality benchmarking. RESULTS: Forty six patients (pts.) underwent robotic-assisted gastric resections. 26 (56.5%) were male, with a median age of 62 y (range: 29-87). Pathology included GC, gastrointestinal stromal tumors, neuroendocrine tumors, metastatic lesions, and benign processes. 19 pts. underwent total gastrectomy, 16 distal gastrectomy, four subtotal gastrectomy, and seven wedge resection. Pts. undergoing distal gastrectomy and wedge resection experienced shorter operative times and length of stay than total gastrectomy (P < 0.01; P < 0.01). Four operations (8.8%) were converted to open and 13 pts (28.3%) had postoperative complications, including an 8.7% readmission rate. Median lymph nodes retrieved during total, subtotal, and distal gastrectomy were 20 (13-46), 12.5 (0-26), and 16.5 (0-34), respectively. All pts. underwent margin negative resection. Median follow-up for GC was 21 mo, and 60% of pts. received adjuvant therapy at a median of 59d (range: 23-106). CONCLUSIONS: Robotic gastrectomy is a feasible alternative to open gastrectomy. Our results will help establish benchmarks to improve perioperative outcomes, especially length of stay and time to initiation of therapy.

Comparison of imaging modalities for measuring the diameter of intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are pre-malignant pancreatic cysts detected by imaging. Cyst size is one of many features evaluated on computed tomography (CT), magnetic resonance imaging (MRI), or endoscopic ultrasonography (EUS) to help guide IPMN management. Our objective was to determine which imaging modality best predicts pathological cyst size. METHODS: We analyzed records for 57 IPMN cases surgically treated at Moffitt Cancer Center from 2008 to 2016 for whom pre-operative CT, MRI, and EUS IPMN cyst size and post-operative pathological cyst size values were available. Long axis cyst diameter measurements were compared to each other and corresponding pathological cyst measurements using within-subjects ANOVA, Bland-Altman analysis, and linear regression. Consensus measurements were also performed on CT and MRI images. RESULTS: Cyst size measured via CT and MRI overestimated pathological size by 0.33 cm and 0.27 cm, respectively, whereas EUS underestimated pathological size by 0.05 cm and had the narrowest 95% limit of agreement (LOA). Among pathologically-confirmed cysts <3 cm, MRI overestimated pathological size by 0.30 cm (P = 0.049) and had the widest LOA, followed by EUS and CT. Among cysts ≥3 cm, EUS underestimated pathological size by 0.35 cm (P = 0.059) and MRI and CT overestimated pathological size by 0.23 cm and 0.51 cm, respectively. CONCLUSIONS: In this small retrospective study, EUS cyst size measurements correlated best with pathologic specimens compared to CT and MRI, especially for cysts < 3 cm. Larger prospective studies are needed to determine which imaging modalities are best to risk-stratify IPMNs and guide surgical versus. Non-surgical management.

Completion of adjuvant therapy in patients with resected pancreatic cancer.

BACKGROUND: Adjuvant chemotherapy is the standard of care for resected pancreatic ductal adenocarcinoma (PDAC). It is estimated that only 40-80% eligible patients initiate intended adjuvant chemotherapy. Completion rates are largely unknown. METHODS: A retrospective analysis of outcomes of patients with resected PDAC over an 8-year period at H. Lee Moffitt Cancer Center (MCC) was performed. RESULTS: From a total of 309 patients, 299 were included for further analysis. 242 (81%) initiated adjuvant therapy (AT) and 195 (65%) completed the intended course. The median time-to-initiation of AT was 53 days (7.6 weeks). The most common reasons for early discontinuation of AT (n = 47) were toxicity (n = 29), disease recurrence (n = 9), patient decision (n = 4), unrelated comorbidities (n = 3), and death (n = 1). Completion of AT was an independent predictor of overall survival (OS) and recurrence-free survival (RFS) on multivariable analysis (OS: HR 0.41, CI 0.27-0.61, p < 0.001; RFS: HR 0.52, CI 0.36-0.76, p < 0.001). Factors associated with early termination of AT were vascular resection (OR 0.29, CI 0.13-0.67, p = 0.004) and administration of AT with local oncologist as opposed to MCC (OR 0.41, CI 0.21-0.82, p = 0.010). CONCLUSION: Completion of AT is associated with improved survival in patients with resected PDAC. Factors associated with an inability to complete AT include vascular resection and administration of AT with local care team in the patient's community.

Racial and ethnic disparities in a state-wide registry of patients with pancreatic cancer and an exploratory investigation of cancer cachexia as a contributor to observed inequities.

Pancreatic cancer (PC) is characterized by racial/ethnic disparities and the debilitating muscle-wasting condition, cancer cachexia. Florida ranks second in the number of PC deaths and has a large and understudied minority population. We examined the primary hypothesis that PC incidence and mortality rates may be highest among Black Floridians and the secondary hypothesis that biological correlates of cancer cachexia may underlie disparities. PC incidence and mortality rates were estimated by race/ethnicity, gender, and county using publicly available state-wide cancer registry data that included approximately 2700 Black, 25 200 Non-Hispanic White (NHW), and 3300 Hispanic/Latino (H/L) Floridians diagnosed between 2004 and 2014. Blacks within Florida experienced a significantly (P < 0.05) higher incidence (12.5/100 000) and mortality (10.97/100 000) compared to NHW (incidence = 11.2/100 000; mortality = 10.3/100 000) and H/L (incidence = 9.6/100 000; mortality = 8.7/100 000), especially in rural counties. To investigate radiologic and blood-based correlates of cachexia, we leveraged data from a subset of patients evaluated at two geographically distinct Florida Cancer Centers. In Blacks compared to NHW matched on stage, markers of PC-induced cachexia were more frequent and included greater decreases in core musculature compared to corresponding healthy control patients (25.0% vs 10.1% lower), greater decreases in psoas musculature over time (10.5% vs 4.8% loss), lower baseline serum albumin levels (3.8 vs 4.0 gm/dL), and higher platelet counts (332.8 vs 268.7 k/UL). Together, these findings suggest for the first time that PC and cachexia may affect Blacks disproportionately. Given its nearly universal contribution to illness and PC-related deaths, the early diagnosis and treatment of cachexia may represent an avenue to improve health equity, quality of life, and survival.

Identification of nonalcoholic fatty liver disease following pancreatectomy for noninvasive intraductal papillary mucinous neoplasm.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) following pancreatectomy is a potential cause of long term morbidity in patients undergoing pancreatic resection with curative intent. Prior studies have reported an incidence of NAFLD up to 30% following pancreatectomy but the investigated cohorts were typically a mix of benign and malignant disease. Here we examined the incidence of NAFLD in a homogenous cohort of patients following pancreatectomy for benign intraductal papillary mucinous neoplasm (IPMN). METHODS: A retrospective review of patients who underwent pancreatic resection for IPMN from 2000 to 2016 was performed. Post pancreatectomy CT/MRI scans were obtained as standard surveillance. We investigated changes in the liver parenchymal density on post surgical imaging to estimate the frequency with which NAFLD occurred. Radiographic criteria for NAFLD included Hounsfield units less than 40 on CT or liver:spleen ratio <0.9 on CT or MRI. Fischer's exact test, Kruskal-Wallis test, and logistic regression were performed. RESULTS: Our study cohort included 109 patients who underwent pancreatectomy for nonmalignant intraductal papillary mucinous neoplasm with no evidence of NAFLD preoperatively and at least 6 months follow-up. Mean follow-up was 52 months (range 8-130/months). The incidence of postoperative NAFLD was 17/109 (15.6%). Most cases occurred within 12 months of pancreatectomy. On multivariate analysis, proximal pancreatectomy (pancreaticoduodenectomy) and development of atrophy of the pancreas remnant were significant risk factors for development of hepatic steatosis (p < 0.05). CONCLUSION: Patients undergoing pancreatectomy for benign disease have a significant risk of developing NAFLD but the frequency is lower than previously reported in cohorts that included individuals with malignant disease. Highest risk was observed in individuals who underwent pancreaticoduodenectomy or developed pancreatic atrophy. Further investigations to define the mechanisms that promote steatosis and interventions to prevent subsequent morbidity from NAFLD are warranted.

Adjuvant radiation provides survival benefit for resected pancreatic adenocarcinomas of the tail.

BACKGROUND: The appropriate adjuvant treatment for resected pancreatic cancer remains a controversy. We sought to determine the effect of adjuvant treatment on overall survival (OS) in patients with pancreatic tail adenocarcinoma. METHODS: Retrospective review of patients with upfront surgically resected pancreatic tail cancer treated at our institution between 2000-2012 was performed to determine outcomes of patients treated with and without adjuvant radiation therapy (RT). Survival curves were calculated according to the Kaplan-Meier method. Univariate analysis (UVA) and multivariate analysis (MVA) were performed using the Cox proportional hazards model. RESULTS: Thirty-four patients met inclusion criteria. 79% received adjuvant chemotherapy, either concurrent with RT or alone. The groups were well matched, with the only significant difference being patient sex. On both UVA and MVA there was significantly worse survival in patients with a post-op CA19-9 >90 [hazard ratio (HR) 5.55; 95% confidence interval (CI): 1.20-25.7, P=0.03] and improved survival in patients treated with adjuvant RT (HR 0.15; 95% CI: 0.04-0.58, P=0.006). The median and 2-year OS were 21.6 months and 47% for patients treated with adjuvant RT compared with 11.3 months and 21% for those treated without RT. CONCLUSIONS: Although few in patient numbers, this data suggests integration of adjuvant RT in resected pancreatic tail adenocarcinoma may improve OS.

Impact of sarcopenia in borderline resectable and locally advanced pancreatic cancer patients receiving stereotactic body radiation therapy.

BACKGROUND: Total psoas area (TPA), a marker of sarcopenia, has been used as an independent predictor of clinical outcomes in gastrointestinal (GI) cancers as a proxy for frailty and nutritional status. Our study aimed to evaluate whether TPA, in contrast to traditional measurements of nutrition like body mass index (BMI) and body surface area (BSA), was predictive of outcomes in borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) patients receiving stereotactic body radiation therapy (SBRT). METHODS: Retrospective analysis of an institutional review board approved database of 222 BRPC and LAPC treated with SBRT from 2009-2016 yielded 183 patients that met our selection criteria of pre-SBRT computed tomography (CT) imaging with an identifiable L4 vertebra. Once the L4 vertebral level was identified, the bilateral psoas muscles were manually contoured. This area was normalized by patient height, with units described in mm2/m2. Receiver operating characteristic (ROC) curves were generated for TPA, BMI, and BSA to elicit clinically relevant cutoffs. Regression and Kaplan-Meier analyses were used to correlate toxicity with survival functions. RESULTS: Low TPA (OR =1.903, P=0.036) was predictive of acute toxicities, and only TPA was predictive of Grade 3 or higher acute toxicities (OR =10.24, P=0.007). Both findings were independent of tumor resectability. Pain (P=0.003), fatigue (P=0.040), and nausea (P=0.039) were significantly associated with low TPA. No association was identified between any measurement of nutritional status and the development of late toxicities, overall survival, local progression or local recurrence. However, BRPC patients survived longer (median =21.98 months) than their LAPC (median =16.2 months) counterparts (P=0.002), independent of nutritional status. CONCLUSIONS: TPA measurement is readily available and more specific than BMI or BSA as a predictor of acute radiotoxic complications following SBRT in BRPC/LAPC patients. A TPA of <500 mm2/m2 is a clinically relevant cutoff that can direct physicians to address expected complications of pain, fatigue, and nausea. However, tumor resectability remains as the only predictor of overall survival in this cohort.

Patterns of recurrence and long-term outcomes in patients who underwent pancreatectomy for intraductal papillary mucinous neoplasms with high grade dysplasia: implications for surveillance and future management guidelines.

BACKGROUND: While intraductal papillary mucinous neoplasms (IPMNs) with high-grade dysplasia (HGD) are thought to represent non-invasive, high-risk lesions, its natural history following resection is unknown. METHODS: A retrospective review of HGD-IPMN patients (1999-2015) was performed. Recurrence patterns and clinical outcomes following pancreatectomy were analyzed and the indications for surgery were explored based on current guidelines. RESULTS: HGD was diagnosed in 100 of 314 patients (32%) following pancreatectomy for IPMN. IPMNs were classified as main duct, branch duct, or mixed in 15, 58 and 27 patients, respectively. Following resection, 25 patients had low-risk residual disease in the remnant pancreas. With a median follow-up of 35 months (range 1-129), 9 patients developed progressive or recurrent disease, 4 of whom underwent additional pancreatectomy. Three patients developed invasive adenocarcinoma. Median time to recurrence was 15 months (range 7-72). Based on the management algorithm from the international consensus guidelines, resection was indicated in 76 patients (76%). Other indications for surgery included mixed-duct IPMN(13), increased cyst size(7) and other(4). CONCLUSION: The prognosis of HGD-IPMN following resection is good; however, HGD may be a marker for developing IPMN recurrence or adenocarcinoma. Current guidelines regarding surgical indications for IPMN can miss a significant number of patients with HGD.