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

Favorable perioperative outcomes after resection of borderline resectable pancreatic cancer treated with neoadjuvant stereotactic radiation and chemotherapy compared with upfront pancreatectomy for resectable cancer

Neoadjuvant multi-agent chemotherapy and stereotactic body radiation therapy (SBRT) are utilized to increase margin negative (R0) resection rates in borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) patients. Concerns persist that these neoadjuvant therapies may worsen perioperative morbidities and mortality. Upfront resection patients (n=241) underwent resection without neoadjuvant treatment for resectable disease. They were compared to BRPC or LAPC patients (n=61) who underwent resection after chemotherapy and 5 fraction SBRT. Group comparisons were performed by Mann-Whitney U or Fisher's exact test. Overall Survival (OS) was estimated by Kaplan-Meier and compared by log-rank methods. In the neoadjuvant therapy group, there was significantly higher T classification, N classification, and vascular resection/repair rate. Surgical positive margin rate was lower after neoadjuvant therapy (3.3% vs. 16.2%, P=0.006). Post-operative morbidities (39.3% vs. 31.1%, P=0.226) and 90-day mortality (2% vs. 4%, P=0.693) were similar between the groups. Median OS was 33.5 months in the neoadjuvant therapy group compared to 23.1 months in upfront resection patients who received adjuvant treatment (P=0.057). Patients with BRPC or LAPC and sufficient response to neoadjuvant multi-agent chemotherapy and SBRT have similar or improved peri-operative and long-term survival outcomes compared to upfront resection patients

Adjuvant radiotherapy and lymph node dissection in pancreatic cancer treated with surgery and chemotherapy

The objective of this study was to determine the effects of postoperative radiation therapy (PORT) and lymph node dissection (LND) on survival in patients with pancreatic cancer. The 2004 to 2008 Surveillance, Epidemiology, and End Results (SEER) database was analyzed to identify patients with pancreatic cancer who underwent surgery and received chemotherapy and to evaluate the correlation between overall survival (OS), PORT, and LND. In total, 2966 patients were identified who underwent pancreatic resection (1842 PORT, 1124 no PORT). Median survival, 1-year OS, and 3-year OS were 21 months, 77%, and 28%, respectively, with PORT versus 20 months, 70%, and 25%, respectively, without PORT (P = .02). Subset analysis revealed that the benefit of PORT was limited to lymph node-positive (N1) patients. Median survival, 1-year OS, and 3-year OS for patients with N1 disease were 19 months, 73%, and 25%, respectively, for those who received PORT versus 18 months, 67%, and 20%, respectively, for those who did not receive PORT (P < .01). An increasing lymph node count was associated with increased survival on multivariate analysis in all patients and in patients with N1 disease (both P < .001). Significant cutoff points for OS based on LND in patients with N1 disease were identified for those who had ≥8, ≥10, ≥12, ≥15, and ≥20 lymph nodes resected. Multivariate analysis for OS revealed that increasing age, T3 and T4 tumors, N1 stage, and moderately and poorly differentiated grade were prognostic for increased mortality, while female gender, PORT, and LND were prognostic for decreased mortality. In patients with N1 disease, other than patient age, all of these factors remained significant. In patients with N0 disease, only T1 and T2 tumor classification and having a tumor that was less than high grade were associated with survival benefit. This SEER analysis demonstrated an associated survival benefit of PORT and LND in patients with N1, surgically resected pancreatic cancer who received chemotherapy

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 mm 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 \u3c500 \u3em

Survival benefits of adjuvant radiotherapy and lymph node dissection in pancreatic cancer treated with surgery and chemotherapy

Abstract only 263 Background: Prior SEER analyses of the benefit of radiotherapy in surgically resected pancreatic cancer could not analyze chemotherapy recipients due to limited database information. Recent updates permit us to determine the effects of postoperative radiation therapy (PORT) and lymph node resection (LNR) on overall survival (OS) in pancreatic cancer among patients treated with both surgery and chemotherapy. Methods: An analysis of surgically resected pancreatic cancer patients receiving chemotherapy from the SEER database between 2004-2008 was performed. Survival was calculated by Kaplan-Meier method and log-rank analysis. Multivariate analysis (MVA) was by the Cox proportional hazard model. Results: We identified 2,966 patients who met inclusion criteria. PORT significantly improved OS in pancreatic cancer patients treated with surgery and chemotherapy (p=0.02). Median survival (MS), 1-year OS, and 3-year OS was 21 months, 77%, and 28% with PORT (n=1842) versus 20 months, 70%, and 25% without radiation (n=1124). On subset analysis, the benefit of PORT was limited to node positive patients. In N1 patients (n=2043) MS, 1-year OS, and 3-year OS was 19 months, 73%, and 25% with PORT versus 18 months, 67%, and 20% without PORT (p<0.01). For N0 patients (n=923) MS, 1-year OS, and 3-year OS was 26 months, 85%, and 36% with PORT versus 25 months, 79%, and 38% without PORT (p=0.87). Increasing nodal count on LNR correlated with improved OS on MVA for all and N1 patients (each p<0.001). Significant cut points for OS based on LNR in N1 patients were found for greater than 8, 10, 12, 15, 20, and 30 nodes resected (p<0.05 for all). Prognostic factors on MVA include receipt of radiation, age, female sex, well differentiated grade, N0 status, and disease contained within the pancreas (p < 0.03 for all). In N1 patients (n=2043), these factors remained significant except patient age. In N0 patients (n=923), only pancreas-confined disease and less than high grade tumor were associated with survival benefit. Conclusions: PORT and degree of LNR are both correlated with improved OS in pancreatic cancer patients treated with surgery and chemotherapy. Benefit of PORT and LNR seems limited to node positive patients

Survival benefits of adjuvant radiotherapy and lymph node dissection in pancreatic cancer treated with surgery and chemotherapy.

Abstract only 263 Background: Prior SEER analyses of the benefit of radiotherapy in surgically resected pancreatic cancer could not analyze chemotherapy recipients due to limited database information. Recent updates permit us to determine the effects of postoperative radiation therapy (PORT) and lymph node resection (LNR) on overall survival (OS) in pancreatic cancer among patients treated with both surgery and chemotherapy. Methods: An analysis of surgically resected pancreatic cancer patients receiving chemotherapy from the SEER database between 2004-2008 was performed. Survival was calculated by Kaplan-Meier method and log-rank analysis. Multivariate analysis (MVA) was by the Cox proportional hazard model. Results: We identified 2,966 patients who met inclusion criteria. PORT significantly improved OS in pancreatic cancer patients treated with surgery and chemotherapy (p=0.02). Median survival (MS), 1-year OS, and 3-year OS was 21 months, 77%, and 28% with PORT (n=1842) versus 20 months, 70%, and 25% without radiation (n=1124). On subset analysis, the benefit of PORT was limited to node positive patients. In N1 patients (n=2043) MS, 1-year OS, and 3-year OS was 19 months, 73%, and 25% with PORT versus 18 months, 67%, and 20% without PORT (p<0.01). For N0 patients (n=923) MS, 1-year OS, and 3-year OS was 26 months, 85%, and 36% with PORT versus 25 months, 79%, and 38% without PORT (p=0.87). Increasing nodal count on LNR correlated with improved OS on MVA for all and N1 patients (each p<0.001). Significant cut points for OS based on LNR in N1 patients were found for greater than 8, 10, 12, 15, 20, and 30 nodes resected (p<0.05 for all). Prognostic factors on MVA include receipt of radiation, age, female sex, well differentiated grade, N0 status, and disease contained within the pancreas (p < 0.03 for all). In N1 patients (n=2043), these factors remained significant except patient age. In N0 patients (n=923), only pancreas-confined disease and less than high grade tumor were associated with survival benefit. Conclusions: PORT and degree of LNR are both correlated with improved OS in pancreatic cancer patients treated with surgery and chemotherapy. Benefit of PORT and LNR seems limited to node positive patients

Outcomes of adjuvant radiotherapy and lymph node dissection in elderly patients with pancreatic cancer treated with surgery and chemotherapy.

Abstract only 332 Background: To determine the effects of postoperative radiation therapy (PORT) and lymph node resection (LNR) on survival in patients age ≥ 70 with pancreatic cancer treated with surgery and chemotherapy. Methods: An analysis of patients with surgically resected pancreatic cancer who received chemotherapy from the SEER database from 2004-2008 was performed to determine association of PORT and LNR on survival. Survival curves were calculated according to the Kaplan-Meier method and log-rank analysis. Multivariate analysis (MVA) was performed by the Cox proportional hazard model. Results: We identified 961 patients who met inclusion criteria. The only significant difference between PORT patients and no PORT patients was age, median 75 and 76 years, respectively (p=0.007). Overall survival (OS) in PORT versus no PORT was not statistically different in the whole cohort (p=0.064), N0 (p=0.803) or N1 (p=0.0501). On univariate analysis (UVA) there was increased OS in patients with lower T stage (p<0.001), N0 status (p<0.001), lower AJCC stage (p<0.001) and lower grade (p<0.001). No OS difference was seen based on gender, location, or PORT. There was no difference in OS based on number of lymph nodes removed in all patients (p=0.74), N0 (p=0.59), and N1 (p=0.07). MVA for all patients revealed higher T stage, N1, and high grade were prognostic for worse mortality, while there was a trend for decreased mortality with PORT (p=0.052). In N0 patients, increased T-stage and grade were prognostic for worse survival, while PORT and number of lymph nodes removed were not. In N1 patients, higher T-stage and grade were prognostic for increased mortality, while increasing number of lymph nodes removed was associated with decreased mortality. PORT trended towards improved survival in N1 patients (p=0.06). Age, gender and tumor location were not prognostic for survival. Conclusions: Adjuvant radiation therapy and number of lymph nodes removed in patients age ≥70 does not seem to correlate with increased OS in surgically resected pancreatic cancer treated with chemotherapy. Future clinical trials will need to address age as a stratification factor for pancreatic cancer in the adjuvant setting

Outcomes of adjuvant radiotherapy and lymph node resection in elderly patients with pancreatic cancer treated with surgery and chemotherapy

Background: We sought to determine the effects of post- operative radiation therapy (PORT) and lymph node resection (LNR) on survival in patients >= 70 years with pancreatic cancer treated with surgery and chemotherapy. Methods: An analysis of patients >= 70 years with surgically resected pancreatic cancer who received chemotherapy from the SEER database between 2004- 2008 was performed to determine association of PORT and LNR on survival. Results: We identified 961 patients who met inclusion criteria. There was a trend towards increased survival associated with PORT in all patients (P=0.052) and N1 patients (P=0.060) but no benefit in N0 patients (P=0.161). There was no difference in OS based on number of lymph nodes removed in all (P=0.741), N0 (P=0.588), and N1 (P=0.070) patients. MVA for all patients revealed that higher T stage, N1, and high grade tumors were prognostic for increased mortality, while there was decreased mortality with PORT and mild benefit with increased lymph nodes resected (P=0.084). Conclusions: PORT demonstrated no benefit in survival of pancreatic cancer patients >= 70 who are resected and treated with adjuvant chemotherapy. Future investigation will need to address age as a stratification factor for pancreatic cancer in the adjuvant setting