Nonmetastatic Pancreatic Adenocarcinoma Research Articles

In search of lost time: Delays in adjuvant therapy for pancreatic adenocarcinoma among under-resourced patient populations

BackgroundThe initiation of adjuvant chemotherapy for pancreatic adenocarcinoma within 12 weeks after surgery is recommended by the National Comprehensive Cancer Network. This study seeks to identify factors associated with delayed adjuvant chemotherapy and whether delays impact survival in under-resourced populations. MethodsPatients with nonmetastatic pancreatic adenocarcinoma who received a definitive resection followed by adjuvant chemotherapy between 2006 and 2017 were queried from the National Cancer Database. Multivariate logistic regression models were constructed to determine the relationship between socioeconomic/clinical variables and delayed adjuvant chemotherapy. Kaplan Meier curves compared survival between under-resourced patients receiving delayed versus timely adjuvant chemotherapy. ResultsAmong 25,008 patients, timely adjuvant chemotherapy varied by stage (stage 1: 67.9% vs stage 2: 75.8% vs stage 3: 89.2%; P < .001). Older age (odds ratio 1.02, 95% confidence interval 1.02–1.03; P < .001), Non-Hispanic Black race (odds ratio 1.25, 95% confidence interval 1.11–1.41; P < .001), increasing comorbidity score (odds ratio 1.18, 95% confidence interval 1.12–1.23; P < .001), 30-day readmission (odds ratio 1.45, 95% confidence interval 1.28–1.63; P < .001), and undergoing a Whipple (odds ratio 1.30, 95% confidence interval 1.16–1.44; P < .001) were associated with delayed adjuvant chemotherapy. Conversely, the highest neighborhood median income quartile (odds ratio 0.84, 95% confidence interval 0.73–0.97; P = .021), private insurance (odds ratio 0.59, 95% confidence interval 0.46–0.76; P < .001), Medicare (odds ratio 0.68, 95% confidence interval 0.52–0.88; P = .003), and receipt of neoadjuvant therapy (odds ratio 0.05, 95% confidence interval 0.04–0.06; P < .001) were associated with timely adjuvant chemotherapy. Non-Hispanic Black patients and patients with the lowest neighborhood education had worse overall survival when receiving delayed versus timely adjuvant chemotherapy. ConclusionTimely adjuvant chemotherapy for pancreatic adenocarcinoma was only achieved in 73.3% of patients. Age, race, comorbidities, median income, and insurance were identified as barriers. Delayed adjuvant chemotherapy was associated with worse survival among under-resourced populations.

Multi-Phase, Contrast-Enhanced Computed Tomography-Based Radiomic Prognostic Marker of Non-Metastatic Pancreatic Ductal Adenocarcinoma.

Simple SummaryPatients with PDA lesions with high attenuation values had longer OS in the RPC and BRPC/LAPC groups and were more likely to undergo a surgical resection after neoadjuvant chemotherapy. These results indicate that intra-tumoral contrast enhancement on CT is an independent prognostic factor in patients with non-metastatic PDA.Background/Aim: This study investigated the predictive ability of intra-tumor enhancement on computed tomography (CT) for the outcomes of patients with pancreatic ductal adenocarcinoma (PDA). Methods: Multi-phase, contrast-enhanced CT (including unenhanced, pancreatic parenchymal phase (PPP) and portal venous phase (PVP)) images of patients diagnosed with non-metastatic PDA were analyzed to investigate prognostic factors. Results: Two hundred ninety-eight patients with PDA (159 with resectable pancreatic cancer (RPC) and 139 with borderline resectable pancreatic cancer (BRPC)/locally advanced pancreatic cancer (LAPC)) were included. The attenuation values of PDA during the PPP (94.5 vs. 60.7 HU; p <0.001) and PVP (101.5 vs. 75.5 HU; p <0.001) were higher in patients with RPC than in those with BRPC/LAPC. Well-enhanced PDA during the PPP was associated with longer overall survival in the RPC group (27.9 vs. 15.4 months; p <0.001) and the BRPC/LAPC group (22.7 vs. 13.6 months; p = 0.024). Patients with BRPC/LAPC who underwent neoadjuvant treatment and had well-enhanced PDA during the PPP were more likely to undergo resection. Although tumor size was also an independent prognostic factor, it was not correlated with intra-tumoral enhancement during the PPP. Conclusions: Intra-tumoral contrast enhancement on CT is an independent prognostic factor in patients with non-metastatic PDA.

Impact of Multicenter Treatment in Pancreatic Cancer Patients on Time-to-Treatment, Completion of Adjuvant Chemotherapy and Survival

Introduction: Pancreatic surgery is centralized to improve postoperative outcomes. Consequently, patients with pancreatic cancer may undergo pancreatic surgery in an expert center and adjuvant chemotherapy in a local hospital. We aimed to assess whether multicenter treatment (MCT) is associated with a delayed time-to-chemotherapy and failure to complete adjuvant chemotherapy. Methods: This retrospective study included patients with non-metastatic pancreatic ductal adenocarcinoma (PDAC) registered in the Netherlands Cancer Registry between 2015-2018. MCT was defined as pancreatic surgery in an expert center and adjuvant chemotherapy in a non-expert center. A delayed care process was defined as >6 weeks between first hospital visit and start tumor treatment. Time-to-chemotherapy was defined as time between resection and chemotherapy initiation. We performed χ2tests and multivariable logistic regression analyses. Results: In total, 4662 patients were included. 1449 patients underwent resection, 868 (60%) received adjuvant chemotherapy. MCT was observed in 377 patients (43%). Time-to-chemotherapy was 53 days (IQR 43-66) in MCT patients compared to 55 days (IQR 43-67) in patients with monocenter treatment (P=0.92). MCT was significantly associated with failure to complete adjuvant chemotherapy in univariate analysis (OR=1.35; 95% CI 1.02-1.77) but not in multivariable analysis. In multivariable analysis, diagnosis in a local hospital and subsequent treatment in an expert center was associated a delayed care process (OR=1.64; 95% CI 1.47-1.87, P<0.004). Conclusion: These preliminary results suggest MCT is not associated with a delayed time-to-treatment or failure to complete adjuvant chemotherapy. However, a delayed care process was observed for patients with a first visit in a local hospital. Note: These are preliminary results, we will analyse the associations for neoadjuvant therapy, survival and multilevel analyses.

Impact of Multicenter Diagnostic Workup on Time-to-Diagnosis and Time-to-Treatment in Patients with Pancreatic Ductal Adenocarcinoma: A Nationwide Analysis

Background: Due to centralization of pancreatic surgery, patients with suspected pancreatic cancer may undergo multicenter diagnostic workup, i.e. in both a local hospital and a pancreatic expert center. The aim of this study was to assess whether this multicenter diagnostic workup is associated with repetition of diagnostics, a prolonged diagnostic phase, and treatment delay. Materials and methods: This retrospective study included all patients diagnosed with non-metastatic pancreatic ductal adenocarcinoma (PDAC) in 2015, registered in the Netherlands Cancer Registry. Multicenter diagnostic workup was defined as diagnostic investigations in both a local hospital and a pancreatic expert center. A prolonged diagnostic phase was defined as ≥3 weeks from initial hospital visit to final diagnosis. A delayed time-to-treatment was defined as ≥6 weeks from the first hospital visit to start of tumor treatment. Multivariable logistic regression analyses were performed. Results: In total, 951 patients were included. Nineteen percent (n=181) underwent multicenter diagnostic workup. Significantly more patients with a multicenter workup had a prolonged diagnostic phase (70% vs 56%, P<0.01) and a delayed time-to-treatment (76% vs 64%, P<0.01) when compared with patients with monocenter workup. In multivariate analysis, multicenter diagnostic workup was a strong risk factor for a delayed diagnostic phase (OR=2.4; 95%CI 1.64–3.52, P<0.001). Conclusion: Multicenter diagnostic workup for patients suspected of PDAC is associated with a delayed time-to-diagnosis and delayed time-to-treatment compared to patients with monocenter diagnostic workup. These preliminary results suggest that pancreatic expert centers and local hospitals may need to improve their collaborative pancreatic care network. Note: These are preliminary results, we will analyse associations between multicenter diagnostics and the repetition of diagnostic investigations, delayed time-to-treatment (adjusted for covariates) and survival. Multilevel analysis will be performed, which will reveal how much variation in the outcome can be attributed to the different pancreatic cancer networks (expert hospital+ non-expert hospitals).

The Impact of Care Fragmentation on Pancreatic Cancer Care: More Complex Than It Seems

Introduction: Fragmentation of care (FC)—care at >1 facility—has been associated with increased cost, delayed treatment, and worse survival for gastrointestinal cancers. We assessed the impact of FC on pancreatic cancer care in California. Methods: Using the California Cancer Registry, linked with ambulatory surgery, emergency visits and discharge records from the Office of Statewide Health Planning Database, patients diagnosed with non-metastatic pancreatic ductal adenocarcinoma (PDAC) from 2007-2017 were identified. FC was determined by the number of unique facilities where patients received cancer care over the initial 12 months. We evaluated the association between FC and all-cause mortality using multivariable-adjusted Cox regression. Results: Among 9,464 PDAC patients, 4,545 patients received care at 1 facility (48.0%), 3,571 (37.7%) at 2, and 1,348 (14.2%) at >3. After adjusting for patient, tumor and hospital characteristics, female sex (HR=0.93 [0.89-0.97], p=0.001), high socioeconomic status (highest vs lowest quintile: HR=0.75 [0.70-0.82], p=<0.001) and cancer-hospital designations (all HR<1, p<0.001; see table) were associated with lower mortality. Mortality was lower for patients treated at 2 facilities compared to those treated at 1 facility (HR=0.95 [0.90-0.99], p=0.02), but was similar for patients treated at >3 vs 1 facility (HR=1.01 [0.94-1.07], p=0.87). Conclusions: Although prior data suggested that FC at >1 facility compromised cancer outcomes, in this large population-based cohort, PDAC patients treated at 2 facilities had better survival. FC is more complex than previously hypothesized. Our ongoing research is directed at better understanding “positive fragmentation” (e.g., seeking higher level of care) versus disjointed care (previously ascribed to fragmentation).

Alterations in Driver Genes Are Associated with Response to Neoadjuvant Folfirinox in Patients with Nonmetastatic Pancreatic Ductal Adenocarcinoma

Ecker, Brett L. MD; Janssen, Quisette MD; Tao, Alice BA; Tansey, Wesley PhD; D'Angelica, Michael MD; Drebin, Jeffrey A. MD, PhD, FACS; Jarnagin, William R. MD, FACS; Kingham, Peter T. MD, FACS; Soares, Kevin MD; Wei, Alice C. MD, FACS Author Information

β6-Integrin Serves as a Potential Serum Marker for Diagnosis and Prognosis of Pancreatic Adenocarcinoma.

INTRODUCTION:Despite enormous efforts during the past decades, pancreatic adenocarcinoma (PAC) remains one of the most deleterious cancer entities. A useful biomarker for early detection or prognosis of PAC does not yet exist. The goal of our study was the characterization of β6-integrin (ITGB6) as a novel serum tumor marker for refined diagnosis and prognosis of PAC. Serum ITGB6 levels were analyzed in 3 independent PAC cohorts consisting of retrospectively and prospectively collected serum and/or (metastatic) PAC tissue specimens.METHODS:Using 2 independent cohorts, we measured serum ITGB6 concentrations in 10 chronic pancreatitis patients, 10 controls, as well as in 27 (cohort 1) and 24 (cohort 2) patients with PAC, respectively. In these patients, we investigated whether ITGB6 serum levels correlate with known clinical and prognostic markers for PAC and whether they might differ between patients with PAC or benign inflammatory diseases of the pancreas.RESULTS:We found that elevated serum ITGB6 levels (≥0.100 ng/mL) in patients suffering from metastasizing PAC presented an unfavorable prognostic outcome. By correlating the ITGB6 tissue expression in primary and metastatic PAC with clinical parameters, we found that positive ITGB6 expression in the tumor tissue is linked to increased serum ITGB6 levels in nonmetastatic PAC and correlates with carbohydrate antigen 19-9 and clinical outcome.DISCUSSION:Our findings suggest that ITGB6 might serve as a novel serum biomarker for early diagnosis and prognosis of PAC. Given the limited specificity and sensitivity of currently used carbohydrate antigen 19-9–based assays, ITGB6 may have the potential to improve the diagnostic accuracy for PAC.

Predicting Adverse Pathologic Features and Clinical Outcomes of Resectable Pancreas Cancer With Preoperative CA 19-9.

BackgroundWe evaluated preoperative CA 19-9 levels in patients with resected pancreatic cancer to analyze whether they were predictive of clinical outcomes and could help select patients for additional therapy. We hypothesized that elevated CA 19-9 would be associated with worse pathologic findings and oncologic outcomes.MethodsThis study assessed 509 patients with non-metastatic pancreatic adenocarcinoma who underwent resection at our institution from 1995-2011 and had preoperative CA 19-9 recorded. No patients received neoadjuvant therapy. CA 19-9 level was analyzed as a continuous and a dichotomized (> vs. ≤ 55 U/mL) variable using logistic and Cox models.ResultsMedian follow-up was 7.8 years, and the median age was 66 years (33-90). 64% of patients had elevated preoperative CA 19-9 (median: 141 U/mL), that did not correlate with bilirubin level or tumor size. Most patients had ≥ T3 tumors (72%) and positive lymph nodes (62%). The rate of incomplete (R1 or R2) resection was 19%. Increasing preoperative CA 19-9 was associated with extra-pancreatic extension (p=0.0005), lymphovascular space invasion (p=0.0072), incomplete resection [HR (95% CI) 2.0 (1.2-3.5)], and lower OS [HR = 1.6 (1.3-2.0)]. Each doubling in preoperative CA 19-9 value was associated with an 8.3% increased risk of death [HR = 1.08 (1.02-1.15)] and a 10.0% increased risk of distant recurrence [HR = 1.10 (1.02-1.19)]. Patients classified as non-secretors had comparable outcomes to patients with normal CA 19-9.ConclusionsElevated preoperative CA 19-9 level was associated with adverse pathologic features, incomplete resection, and inferior clinical outcomes. Neither tumor size nor bilirubin confound an elevated CA 19-9 level. Preoperative CA 19-9 level may help select patients for additional therapy.

A nomogram predicting overall survival in patients with non-metastatic pancreatic head adenocarcinoma after surgery: a population-based study

BackgroundPancreatic head adenocarcinoma (PHAC), a malignant tumour, has a very poor prognosis, and the existing prognostic tools lack good predictive power. This study aimed to develop a better nomogram to predict overall survival after resection of non-metastatic PHAC.MethodsPatients with non-metastatic PHAC were collected from the Surveillance, Epidemiology, and End Results (SEER) database and divided randomly into training and validation cohorts at a ratio of 7:3. Cox regression analysis was used to screen prognostic factors and construct the nomogram. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated to evaluate the performance of the model. The predictive accuracy and clinical benefits of the nomogram were validated using the area under the curve (AUC), calibration curves, and decision curve analysis (DCA).ResultsFrom 2010 to 2016, 6419 patients with non-metastatic PHAC who underwent surgery were collected from the SEER database. A model including T stage, N stage, grade, radiotherapy, and chemotherapy was constructed. The concordance index of the nomogram was 0.676, and the AUCs of the model assessing survival at multiple timepoints within 60 months were significantly higher than those of the American Joint Committee on Cancer (AJCC) 8th staging system in the training cohort. Calibration curves showed that the nomogram had ability to predict the actual survival. The NRI, IDI, and DCA curves also indicated that our nomogram had higher predictive capability and clinical utility than the AJCC staging system.ConclusionsOur nomogram has an ability to predict overall survival after resection of non-metastatic PHAC and includes prognostic factors that are easy to obtain in clinical practice. It would help assist clinicians to conduct personalized medicine.

Real-world patterns of adjuvant chemotherapy treatment for patients with resected pancreatic adenocarcinoma.

The aim of the study was to analyze the real-world treatment patterns of adjuvant chemotherapy administration among patients with resected pancreatic adenocarcinoma. Cases with non-metastatic pancreatic adenocarcinoma, diagnosed 2007-2018, treated with upfront surgical resection, and recorded within Alberta Cancer registry were accessed. Multivariable logistic regression analysis was conducted to evaluate factors predicting use of adjuvant chemotherapy. Kaplan-Meier survival estimates and multivariable Cox regression analysis were used to compare overall survival among patients treated with adjuvant gemcitabine versus those treated with adjuvant gemcitabine + capecitabine. A total of 695 patients who have undergone upfront surgical treatment of pancreatic adenocarcinoma, including 445 patients (64%) who received adjuvant chemotherapy and 250 patients (36%) who did not receive adjuvant chemotherapy. The following factors were associated with lower probability to receive adjuvant chemotherapy: older age (OR 0.94; 95% CI 0.93-0.96), node negativity (OR 0.47; 95% CI 0.33-0.67), higher Charlson comorbidity index (OR 0.86; 95% CI 0.74-0.99), and living within the Northern zone of the province (OR for Calgary zone versus North zone: 2.24; 95% CI 1.29-3.90). Within patients who received adjuvant gemcitabine ± capecitabine, factors associated with worse overall survival included higher Charlson comorbidity index (HR 1.18; 95% CI 1.00-1.40), and node-positive disease (HR for node-negative versus node-positive disease: 0.51; 95% CI 0.33-0.78). Type of chemotherapy was not predictive of overall survival (HR for gemcitabine versus gemcitabine plus capecitabine: 1.40; 95% CI 0.98-2.00). P value for interaction between type of chemotherapy and nodal status was 0.038. In this real-world study, the added benefit of adjuvant gemcitabine + capecitabine (compared to adjuvant gemcitabine) seems to be limited to patients with node-positive disease.

Does Major Pancreatic Surgery Have Utility in Nonagenarians with Pancreas Cancer?

This study aims to define the role of surgery and assess different therapies for nonagenarians with localized, nonmetastatic pancreatic adenocarcinoma (PDAC). The National Cancer Database (NCDB) was queried for patients ≥ 90 years of age with nonmetastatic, localized PDAC from 2004-2016. Postoperative mortality was assessed at 30 and 90 days in patients receiving pancreatoduodenectomy or total pancreatectomy. Overall survival (OS) was compared between three treatment groups: surgery alone, chemotherapy alone, and chemoradiation (chemoRT) alone. Of 380,524 patients with PDAC, 98 patients ≥ 90 years of age underwent curative-intent resection; 55% were female and 75% had a Charlson-Deyo comorbidity score of 0. A total of 17% received postoperative chemotherapy, 51.1% had poorly differentiated tumors with a median tumor size of 3 cm, 55.1% had positive lymph nodes, and 19.4% had positive resection margins. Postoperative median length of stay was 11 days. Postoperative 30- and 90-day mortality was 10.0% and 18.9%, respectively. Median OS for the surgery alone group was 11.6 months compared with 20.4 months in those receiving adjuvant therapy (p = 0.01). Among nonoperative PDAC patients, median OS in patients receiving chemotherapy only (n = 207) was 7.2 months, while chemoRT only (n = 100) was similar to surgery only (11 versus 11.6 months, p = 0.97). Even in well-selected nonagenarians, pancreatoduodenectomy or total pancreatectomy carries a high mortality rate. While adjuvant therapy after resection provides the best survival, it is seldom achieved, and chemoRT alone affords identical survival statistics as surgery alone. These data suggest it is reasonable to consider chemoRT as initial therapy, then reassess candidacy for resection if performance status allows.

Evaluation of response using FDG-PET/CT and diffusion weighted MRI after radiochemotherapy of pancreatic cancer: a\xa0non-randomized, monocentric phase\xa0II clinical trial\u2014PaCa-DD-041 (Eudra-CT 2009-011968-11)

BackgroundPancreatic cancer is a devastating disease with a 5-year survival rate of 20–25%. As approximately only 20% of patients diagnosed with pancreatic cancer are initially staged as resectable, it is necessary to evaluate new therapeutic approaches. Hence, neoadjuvant (radio)chemotherapy is a promising therapeutic option, especially in patients with a borderline resectable tumor. The aim of this non-randomized, monocentric, prospective, phase II clinical study was to assess the prognostic value of functional imaging techniques, i.e., [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) and diffusion weighted magnetic resonance imaging (DW-MRI), prior to and during neoadjuvant radiochemotherapy.MethodsPatients with histologically proven resectable, borderline resectable or unresectable non-metastatic pancreatic adenocarcinoma received induction chemotherapy followed by neoadjuvant radiochemotherapy. Patients underwent FDG-PET/CT and DW-MRI including T1- and T2-weighted sequences prior to and after neoadjuvant chemotherapy as well as following induction radiochemotherapy. The primary endpoint was the evaluation of the response as quantified by the standardized uptake value (SUV) measured with FDG-PET. Response to treatment was evaluated by FDG-PET and DW-MRI during and after the neoadjuvant course. Morphologic staging was performed using contrast-enhanced CT and contrast-enhanced MRI to decide inclusion of patients and resectability after neoadjuvant therapy. In those patients undergoing subsequent surgery, imaging findings were correlated with those of the pathologic resection specimen.ResultsA total of 25 patients were enrolled in the study. The response rate measured by FDG-PET was 85% with a statistically significant decrease of the maximal SUV (SUVmax) during therapy (p < 0.001). Using the mean apparent diffusion coefficient (ADC), response was not detectable with DW-MRI. After neoadjuvant treatment 16 patients underwent surgery. In 12 (48%) patients tumor resection could be performed. The median overall survival of all patients was 25 months (range: 7–38 months).ConclusionBased on these limited patient numbers, it was possible to show that this trial design is feasible and that the neoadjuvant therapy regime was well tolerated. FDG-PET/CT may be a reliable method to evaluate response to the combined therapy. In contrast, when evaluating the response using mean ADC, DW-MRI did not show conclusive results.

Ablative Five-Fraction Stereotactic Body Radiation Therapy for Inoperable Pancreatic Cancer Using Online MR-Guided Adaptation

PurposePatients with inoperable pancreatic adenocarcinoma have limited options, with traditional chemoradiation providing modest clinical benefit and an otherwise poor prognosis. Stereotactic body radiation therapy for pancreatic cancer is limited by proximity to organs-at-risk (OAR). However, stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) has shown promise in delivering ablative doses safely. We sought to demonstrate the benefits of SMART using a 5-fraction approach with daily on-table adaptation. Methods and MaterialsPatients with locally advanced, nonmetastatic pancreatic adenocarcinoma were treated with 50 Gy in 5 fractions (biologically effective dose10 100 Gy) with a prescribed goal of 95% planning target volume coverage by 95% of prescription, prioritizing hard OAR constraints. Daily online adaptation was performed using magnetic resonance-guidance and on-table reoptimization. Patient outcomes, treatment factors, and daily adaptation were evaluated. ResultsForty-four patients were treated with SMART at our institution from 2014 to 2019. Median follow-up from date of diagnosis was 16 months (range, 6.7-51.6). Late toxicity was limited to 2 (4.6%) grade 3 (gastrointestinal ulcers) and 3 (6.8%) grade 2 toxicities (duodenal perforation, antral ulcer, and gastric bleed). Tumor abutted OARs in 35 patients (79.5%) and tumor invaded OARs in 5 patients (11.1%). Reoptimization was performed for 93% of all fractions. Median overall survival was 15.7 months (95% confidence interval, 10.2-21.2), while 1-year and 2-year overall survival rates were 68.2% and 37.9%, respectively. One-year local control was 84.3%. ConclusionsThis is the first reported experience using 50 Gy in 5 fractions for inoperable pancreatic cancer. SMART allows this ablative dose with promising outcomes while minimizing toxicity. Additional prospective trials evaluating efficacy and safety are warranted.

Abstract B110: Racial disparities in pancreatic adenocarcinoma survival. Do they exist for patients who already survived their first year?

Abstract Purpose: Population-based studies indicated that prognosis of pancreatic adenocarcinoma (PAC) is worse in black patients compared to other races. Nonetheless, survival probabilities can change over time based on number of years (yr.) already survived by patients; a concept called conditional survival. This study explored the dynamic changes in risk according to patient characteristics, particularly race, on survival of PAC patients using cancer-specific survival (CSS) estimates. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried for data on adult patients with non-metastatic PAC, diagnosed between 1988 and 2010. Patient characteristics, such as age, race, tumor grade, and stage were collected at the time of diagnosis. CSS probabilities, as well as Cox proportional hazard ratios (HRs), were computed at the time of diagnosis (Actuarial CSS and baseline HR), and after already surviving 1 to 6 yr. after diagnosis (Conditional CSS and HR). Harrell’s concordance index (C-index) was used to measure the cross-validation accuracy of the Cox models. Results: Our search retrieved data on 20,491 patients, with a mean age at diagnosis of 67.2 yr. Most of the patients were White (81.6%), followed by Black (12%) and Asians/Pacific Islander (6.4%). The stage was T1-2N0M0 in 15.9%, T3-4N0M0 in 41.8%, and T1-4N1M0 in 42.3% of patients. The 3-yr actuarial CSS calculated from time of diagnosis was significantly different across racial groups, at 11%, 10%, and 13% for Whites, Blacks, and Asians, respectively (P &amp;lt; 0.01). Conversely, for patients who already survived 1 yr. after diagnosis, the probability of surviving an additional 2 yr. was similar across races, at 26.2%, 27.1%, and 29.9%, for Whites, Blacks, and Asians, respectively (P = 0.218). As patients survived for longer periods of time following diagnosis, conditional CSS estimates increased similarly across different races; for White, Black, and Asian patients who already survived 3 yr. after diagnosis, the probability of surviving an additional 2 yr. was 62.6%, 60.5%, and 62.1%, respectively (P = 0.532). In multivariate cox models, the prognostic effect of race lost significance if patients already survived ≥1 yr. after diagnosis (Baseline HR = 1.114, 95%CI [1.045- 1.187], mean C-index = 67%; conditional HR at 1 yr = 1.015, 95%CI [0.919- 1.12], mean C-index = 60%). The prognostic effect of tumor grade, site, and age lost significance if patients already survived ≥2, ≥4, and ≥6 yr. after diagnosis, respectively. Tumor stage maintained its prognostic significance over time (conditional HR at 6 yr = 1.522, 95%CI [1.049- 2.208], mean C-index = 59%). Conclusion: Racial disparities in survival outcomes exist at the time of diagnosis for PAC patients. However, the survival impact of these disparities does not seem to persist over time. Other variables, such as age, tumor grade, stage, and treatment received should be taken into account when predicting future prognosis of PAC patients who have already survived ≥ 1 yr. after diagnosis. Citation Format: Anas M Saad, Maha AT Elsebaie, Mohamed Amgad, Muneer J Al-Husseini, Kyrillus S Shohdy, Omar Abdel-Rahman. Racial disparities in pancreatic adenocarcinoma survival. Do they exist for patients who already survived their first year? [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B110.

Radiographic portal or superior mesenteric vein invasion is an independent prognostic factor in non-metastatic pancreatic ductal adenocarcinoma: A missing block of clinical T staging?

BackgroundVenous invasion is not included in the pancreatic ductal adenocarcinoma (PDAC) staging, and its correlation with prognosis remains unclear. We evaluated the prognostic impact of radiographic portal/superior mesenteric vein (PV/SMV) invasion, and its possibility of complementing T staging. MethodsWe identified patients with non-metastatic PDAC using our institutional cohort, and divided them according to PV/SMV invasion at imaging, defined as >180-degree tumor-vessel interface or contour deformity. We conducted Cox proportional hazard regression, and compared survival in the original and 1:1 propensity score matched datasets. ResultsWe identified 454 patients [PV/SMV(+): 172; PV/SMV(−): 282]. In the multivariate analysis, PV/SMV invasion, age (≥70 years), performance status, tumor size (2–4, >4 cm), lymph nodes >4, and arterial invasion was correlated with prognosis. The PV/SMV(+) group had a shorter overall survival (OS) than the PV/SMV(−) group in the original (14.4 vs. 20.9 months; P < 0.001) and matched datasets (14.3 vs. 17.2 months; P = 0.009). Among patients without arterial invasion (cT1–cT3), the PV/SMV(+) group had a shorter OS (15.9 vs. 21.2 months; P = 0.002). Moreover, their OS did not differ from that of patients with arterial invasion (cT4) (15.9 vs. 14.4 months; P = 0.907). Patients with vessel (artery/vein) invasion had a shorter OS than those without vessel invasion (14.5 vs. 21.2 months; P < 0.001). ConclusionsRadiographic PV/SMV invasion in non-metastatic PDAC was correlated with a poor prognosis. It could identify a group with shorter OS among patients without arterial invasion (cT1–cT3). It is suggested that inclusion of PV/SMV invasion in clinical T4 criteria should be considered.

Predictive value of 0.35T magnetic resonance imaging radiomic features in stereotactic ablative body radiotherapy of pancreatic cancer: A pilot study.

The aim of this study was to evaluate the potential and feasibility of radiomic features extracted from low field strength (0.35T) magnetic resonance images (MRIs) in predicting treatment response for patients with pancreatic cancer undergoing stereotactic body radiotherapy (SBRT). Twenty patients with unresected, non-metastatic pancreatic ductal adenocarcinoma (PDAC) were enrolled, all of whom received neoadjuvant chemotherapy followed by five-fraction MR-guided SBRT with a radiation dose range of 33-50Gy. For each patient, five daily setup scans were acquired from a hybrid 0.35T MRI/radiotherapy unit. Tumor heterogeneity quantified with radiomic features extracted from the gross tumor volume (GTV) was averaged over the course of treatment. Random forest (RF) and adaptive least absolute shrinkage and selection operator (LASSO) classification models were constructed to identify radiomics features predictive of treatment response. Predictive capability of the top-performing features was then evaluated using the receiver operating characteristic area under curve (AUC) obtained using leave-one-out cross-validation. Half of the 20 patients showed response to treatment, defined by tumor regression on histopathology or tumor response on follow-up dynamic contrast-enhanced computed tomography (CT). The most predictive features selected by the RF method were GLCM energy and GLSZM gray-level variance. The RF-based model achieved an AUC=0.81 with a 95% confidence interval of [0.594 to 1] The LASSO algorithm selected GLCM energy as the only predictive feature, achieving an AUC=0.81 with 95% confidence interval of [0.596 to 1]. The findings of this study suggest that radiomic features extracted during MR-guided SBRT may contain predictive information about response of PDAC patients to treatment. Using the images acquired during treatment of PDAC patients supports continued expansion of radiomic analysis based on low field strength MR images and may hold the potential for providing timely indications of response to treatment.

The Main Bottleneck for Non-Metastatic Pancreatic Adenocarcinoma in Past Decades: A Population-Based Analysis.

BackgroundDespite recent advancements in surgical techniques, chemotherapy, and radiotherapy, the 5-year survival rate of patients with pancreatic ductal adenocarcinoma (PDAC) remains an unsatisfactory ~8%.Material/MethodsData were extracted to identify patients with non-metastatic pancreatic adenocarcinoma diagnosed in the periods 1988–1996 and 2010–2014 in the Surveillance, Epidemiology, and End Results (SEER) database. The statistical analyses were performed with the log-rank test, Pearson’s chi-square test, propensity score matching, and Cox regression model.ResultsThe hazard ratio (HR) of surgery was reduced from 0.454 to 0.302 in Cox regression modeling, and there was no overlapping about the 95% confidence intervals (CI) of surgery between the 2 periods. The HR values of radiotherapy, which were new prognostic factor for resectable PDAC in 2010–2014, were reduced in both the resectable and unresectable groups. The upgraded chemotherapy regimen reduced the HR values from 0.738 to 0.689 in all PADC patients, and from 0.656 to 0.588 in unresectable PDAC. The log-rank test results showed that advances in surgery significantly improved the median survival from 13 months to 32 months. Radiotherapeutic and chemotherapeutic advancements extended median survival by 12 months and 11 months, respectively, in resectable PDAC. The median survivals were extended by 3 months for both of radiotherapy and chemotherapy in unresectable PDAC.ConclusionsThe development of chemotherapy and radiotherapy has been slow, especially for unresectable PDAC. Although advances in surgery contributed significantly to improved survival for resectable PDAC, lack of early diagnostic tools, which lead to low resection rates, remain a barrier for all PDAC patients.

Abstract B26: Targeted and sustained drug delivery therapy for localized pancreatic cancer: In vivo validation in porcine models

Abstract As systemic therapy improves, local control of nonmetastatic pancreatic adenocarcinoma (PDAC) remains a major challenge. Up to 40% of patients present with locally advanced and borderline resectable anatomy, for whom enhanced local downsizing of disease could improve resection rates and thus overall survival (OS). Additionally, for the 20% of PDAC patients who undergo resection, improved postoperative local control may translate into improved local disease-free intervals. Targeted therapies with reduced systemic toxicity are needed for the treatment of PDAC since current therapies have not provided meaningful advances. PanTher is developing a novel locally targeted drug delivery product (PTM-101) to treat localized PDAC by directly delivering chemotherapeutic agents to the primary tumor. PTM-101 is a bioresorbable polymeric patch containing paclitaxel surgically placed onto the tumor. The ingredients biodegrade over time, resulting in sustained release of drug, thereby providing localized treatment. In murine orthotopic patient-derived xenograft models, we showed that PTM-101 is 12 times more effective in controlling tumor progression compared to the same agent given via systemic route, without the toxicity of systemic therapy. In addition, increase in OS and inhibition of metastasis have been achieved after single treatment. Here we describe testing the implantation of clinically sized product in large animal models in preparation of our first-in-man study. To understand feasibility and safety of implant of PTM-101, two pilot studies were conducted in porcine models. In the first study, PTM-101 was sterilely implanted onto the peritoneum laparoscopically. In the second, it was placed in an open technique directly onto the ventral surface of a healthy porcine pancreas. In both cases, PTM-101 was designed to deliver drug locally over a 30-day period. Study parameters included body weights, hematology, urinalyses, drug levels in the blood and at the implantation site, and histomorphologic evaluation of major organs. In these models, we demonstrated that surgical implantation of PTM-101 can be achieved without complication and our approach ensures localized delivery of a large amount of encapsulated drug, resulting in higher drug concentration and retention in the area underneath the implant. More importantly, no detectable levels of the drug were present in the blood at any point during the 30-day treatment, validating once more the ability of PTM-101 to direct delivery only at the intended site. By changing the route of administration to target just the area of interest, PTM-101 is designed to increase the amount of drug reaching the tumor with the aim to enhance therapeutic efficacy. This could open the door to clinically relevant applications in patients with localized PDAC: (i) preoperatively as neoadjuvant treatment to control progression and downsize locally advanced and borderline anatomy to improve resectability, or (ii) post-resection to reduce the rate of local recurrence. Citation Format: Margaret Lashof-Sullivan, Amanda L. McSweeney, David T. Ting, Michael P. Kim, Ching-Wei D. Tzeng, Laura Indolfi. Targeted and sustained drug delivery therapy for localized pancreatic cancer: In vivo validation in porcine models [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B26.

Sociodemographic Disparities in the Receipt of Adjuvant Chemotherapy Among Patients With Resected Stage I-III Pancreatic Adenocarcinoma.

Adjuvant therapy for resected pancreatic adenocarcinoma was given a category 1 NCCN recommendation in 2000, yet many patients do not receive chemotherapy after definitive surgery. Whether sociodemographic disparities exist for receipt of adjuvant chemotherapy is poorly understood. The National Cancer Database was used to identify patients diagnosed with nonmetastatic pancreatic adenocarcinoma who underwent definitive surgery from 2004 through 2015. Multivariable logistic regression defined the adjusted odds ratio (aOR) and associated 95% CI of receipt of adjuvant chemotherapy. Among patients receiving chemotherapy, multivariable logistic regression assessed the odds of treatment with multiagent chemotherapy. Among 18,463 patients, 11,288 (61.1%) received any adjuvant chemotherapy. Sociodemographic factors inversely associated with receipt of any adjuvant chemotherapy included uninsured status (aOR, 0.61; 95% CI, 0.50-0.74), Medicaid insurance (aOR, 0.66; 95% CI, 0.57-0.77), and lower income (P<.001 for all income levels compared with ≥$46,000). Black race (aOR, 0.72; 95% CI, 0.57-0.90) and female sex (aOR, 0.75; 95% CI, 0.65-0.86) were associated with lower odds of receiving multiagent chemotherapy. There was a statistically significant interaction term between black race and age/comorbidity status (P=.03), such that 26.4% of black versus 35.8% of nonblack young (aged ≤65 years) and healthy (Charlson-Deyo comorbidity score 0) patients received multiagent adjuvant chemotherapy (P=.006), whereas multiagent adjuvant chemotherapy rates were similar among patients who were not young and healthy (P=.15). In this nationally representative study, receipt of adjuvant chemotherapy appeared to be associated with sociodemographic characteristics, independent of clinical factors. Sociodemographic differences in receipt of adjuvant chemotherapy may represent a missed opportunity for improving outcomes and a driver of oncologic disparities.

Neoadjuvant Therapy for Resectable Pancreatic Cancer: An Evolving Paradigm Shift

Non-metastatic pancreatic adenocarcinoma (PDAC) is associated with a high rate of recurrence and lethality. In addition, less than half of all patients are able to complete systemic therapy after curative-intent pancreatectomy. With its well-known potential benefits, this report highlights the current prospective data relevant to the use of neoadjuvant systemic therapy in resectable PDAC. Recently, there have been numerous reports, many of which consist of long-awaited multi-intuitional trial data evaluating the use of neoadjuvant systemic chemotherapy in non-metastatic PDAC as well as the use of combination chemotherapy regimens in the adjuvant setting. Currently, recommended guidelines for neoadjuvant systemic therapy only exist for borderline-resectable and locally-advanced disease. Given the plethora of new data, there has been a shift in the paradigm of how resectable pancreatic cancer is treated at certain centers across the world. This review highlights the relevant available data from recent sentinel prospective trials and how they relate to the systemic treatment of resectable PDAC in the neoadjuvant setting.