Non-metastatic Pancreatic Cancer Research Articles

Neoadjuvant chemotherapy may be the best neoadjuvant therapy modality for non-metastatic pancreatic cancer: a population based study.

Currently, there are no studies showing which neoadjuvant therapy modality can provide better prognosis for patients after pancreatic cancer surgery. This study explores the optimal neoadjuvant therapy model by comparing the survival differences between patients with non-metastatic pancreatic cancer (cT1-4N0-1M0) who received neoadjuvant chemotherapy (NACT) and neoadjuvant chemoradiotherapy (NARCT). We retrospectively analyzed the clinical data of 723 patients with cT1-4N0-1M0 pancreatic cancer who received neoadjuvant therapy before surgery from the Surveillance, Epidemiology, and End Results (SEER) database. After propensity score matching (PSM), we compared the effects of NACT and NARCT on overall survival (OS) and cancer-specific survival (CSS) in patients with non-metastatic pancreatic cancer, and then performed subgroup analyze. Finally, we used univariate and multivariate Cox regression analysis to explore potential risk factors for OS and CSS in patients with non-metastatic pancreatic cancer treated with preoperative neoadjuvant therapy. Before PSM, mOS (30.0 months VS 26.0 months, P=0.122) and mCSS (30.0 months VS 26.0 months, P=0.117) were better in patients with non-metastatic pancreatic cancer treated with NACT compared with NARCT, but this was not statistically significant (P>0.05). After PSM, mOS (30.0 months VS 25.0 months, P=0.032) and mCSS (33.0 months VS 26.0 months, P=0.028) were better in patients with non-metastatic pancreatic cancer treated with NACT compared with NARCT, and this difference was statistically significant (P<0.05). Multivariate Cox regression analysis results showed that age, lymph node positivity, and NARCT were independent adverse prognostic factors for OS and CSS in patients with non-metastatic pancreatic cancer. The study results show that compared with NARCT, NACT is the best preoperative neoadjuvant therapy mode for patients with non-metastatic pancreatic cancer. This result still needs to be confirmed by more prospective randomized controlled trials.

Abstract 455: Identification of hsa-miR-6794-3p as a key regulatory factor in human pancreatic cancer metastasis

Abstract Metastasis is a major factor in treatment failure in patients with pancreatic cancer, but the underlying mechanisms remain unclear, and new, effective treatment strategies are needed. Here, we sought to identify novel microRNAs (miRNAs) with a key role in pancreatic cancer metastasis. Using a microarray analysis to evaluate miRNA expression in metastatic and non-metastatic pancreatic cancer, we found that expression of the miRNA, hsa-miR-6794-3p, was significantly lower in metastatic pancreatic cancer tissues than in non-metastatic pancreatic cancer tissues. Methylation-specific polymerase chain reaction analyses revealed that hsa-miR-6794-3p expression was downregulated in metastatic pancreatic cancer cells by hypermethylation of CpG islands within the hsa-miR-6794-3p promoter. Gain- and loss-of-function approaches using the human pancreatic cancer cell lines, MIA-PaCa-2 and HPAF-II, expressing low and high levels of hsa-miR-6794-3p, respectively, suggested a role for hsa-miR-6794-3p in decreasing cell invasion, migration, and epithelial-mesenchymal transition (EMT) signaling. Notably, we found that hsa-miR-6794-3p exerts its effects by inhibiting expression of the chromatin remodeling factor, RBBP4, through direct binding to the 3’-untranslated region of its mRNA. The resulting suppression of RBBP4 expression increases levels of the transcription factor GRHL2, which is involved in regulating invasion, migration, and EMT signaling in metastatic pancreatic cancer cells. Thus, lower levels of hsa-miR-6794-3p disrupt GRHL2-mediated regulation of these pathways by disinhibiting expression of the GRHL2 negative regulator, RBBP4. Consistent with these findings, an investigation of the relationship between hsa-miR-6794-3p and clinicopathological features in pancreatic cancer patients using publicly available datasets and immunohistochemistry showed that low levels of hsa-miR-6794-3p are correlated with a poorer prognosis in pancreatic cancer patients. Additional preclinical experiments in nude mice clearly demonstrated that hsa-miR-6794-3p is capable of suppressing pancreatic cancer cell metastasis. Taken together, these results suggest that hsa-miR-6794-3p suppresses tumor metastasis and thus represents a promising prognostic biomarker and therapeutic target in pancreatic cancer. Citation Format: Ha Gyeong Kim, Eun-Taex Oh, Yunmi Cho, Heon Joo Park. Identification of hsa-miR-6794-3p as a key regulatory factor in human pancreatic cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 455.

Understanding Surgical Attrition for “Resectable” Pancreatic Cancer

ObjectivesWe used a novel combined analysis to evaluate various factors associated with failure to undergo surgery in non-metastatic pancreatic cancer. MethodsWe identified rates of surgery and reasons for surgical attrition from clinical trials, which studied neoadjuvant therapy in resectable pancreatic cancer. Next, we queried the National Cancer Database (NCDB) for Stage I-III, T1-3 pancreatic adenocarcinoma patients. We investigated the rates and factors associated with the receipt of surgery. Finally, we evaluated variable importance predicting the receipt of surgery. ResultsIn clinical trials, 25-30% of patients did not undergo surgery, mostly due to disease progression. In the NCDB, the overall surgical rate was only 49%, but increased to 67% in a curated cohort meant to mirror clinical trial patients. Patients treated at and low-volume institutions (OR=0.64, 95% CI: 0.61-0.67) and who were uninsured (OR=0.56, 95% CI: 0.52-0.62) and Medicaid-insured (OR=0.67, 95% CI: 0.64-0.71) were less likely to receive potentially curative surgery. ConclusionWe have identified a realistic target surgery rate of 70%-75% in potentially-resectable pancreatic cancer. While attrition to pancreatic cancer surgery is mostly due to tumor biology, our study identified the most important non-medical barriers, such as facility volume and insurance, affecting pancreatic cancer surgery.

Long-Term Outcomes and Risk of Pancreatic Cancer in Intraductal Papillary Mucinous Neoplasms

Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic cysts that can give rise to pancreatic cancer (PC). Limited population data exist on their prevalence, natural history, or risk of malignant transformation (IPMN-PC). To fill knowledge gaps in epidemiology of IPMNs and associated PC risk by estimating population prevalence of IPMNs, associated PC risk, and proportion of IPMN-PC. : This retrospective cohort study was conducted in Olmsted County, Minnesota. Using the Rochester Epidemiology Project (REP), patients aged 50 years and older with abdominal computed tomography (CT) scans between 2000 and 2015 were randomly selected (CT cohort). All patients from the REP with PC between 2000 and 2019 were also selected (PC cohort). Data were analyzed from November 2021 through August 2023. CIs for PC incidence estimates were calculated using exact methods with the Poisson distribution. Cox models were used to estimate age, sex, and stage-adjusted hazard ratios for time-to-event end points. The CT cohort included 2114 patients (1140 females [53.9%]; mean [SD] age, 68.6 [12.1] years). IPMNs were identified in 231 patients (10.9%; 95% CI, 9.7%-12.3%), most of which were branch duct (210 branch-duct [90.9%], 16 main-duct [6.9%], and 5 mixed [2.2%] IPMNs). There were 5 Fukuoka high-risk (F-HR) IPMNs (2.2%), 39 worrisome (F-W) IPMNs (16.9%), and 187 negative (F-N) IPMNs (81.0%). After a median (IQR) follow-up of 12.0 (8.1-15.3) years, 4 patients developed PC (2 patients in F-HR and 2 patients in F-N groups). The PC incidence rate per 100 person years for F-HR IPMNs was 34.06 incidents (95% CI, 4.12-123.02 incidents) and not significantly different for patients with F-N IPMNs compared with patients without IPMNs (0.16 patients; 95% CI, 0.02-0.57 patients vs 0.11 patients; 95% CI, 0.06-0.17 patients; P = .62). The PC cohort included 320 patients (155 females [48.4%]; mean [SD] age, 72.0 [12.3] years), and 9.8% (95% CI, 7.0%-13.7%) had IPMN-PC. Compared with 284 patients with non-IPMN PC, 31 patients with IPMN-PC were older (mean [SD] age, 76.9 [9.2] vs 71.3 [12.5] years; P = .02) and more likely to undergo surgical resection (14 patients [45.2%] vs 60 patients [21.1%]; P = .003) and more-frequently had nonmetastatic PC at diagnosis (20 patients [64.5%] vs 130 patients [46.8%]; P = .047). Patients with IPMN-PC had better survival (adjusted hazard ratio, 0.62; 95% CI, 0.40-0.94; P = .03) than patients with non-IPMN PC. In this study, CTs identified IPMNs in approximately 10% of patients aged 50 years or older. PC risk in patients with F-N IPMNs was low and not different compared with patients without IPMNs; approximately 10% of patients with PC had IPMN-PC, and they had better survival compared with patients with non-IPMN PC.

Pancreatic Adenocarcinoma: Real World Evidence of Care Delivery in AccessHope Data.

Pancreatic adenocarcinoma is an aggressive disease and the delivery of comprehensive care to individuals with this cancer is critical to achieve appropriate outcomes. The identification of gaps in care delivery facilitates the design of interventions to optimize care delivery and improve outcomes in this population. AccessHope™ is a growing organization that connects oncology subspecialists with treating providers through contracts with self-insured employers. Data from 94 pancreatic adenocarcinoma cases (August 2019-December 2022) in the AccessHope dataset were used to describe gaps in care delivery. In all but 6% of cases, the subspecialist provided guideline-concordant recommendations anticipated to improve outcomes. Gaps in care were more pronounced in patients with non-metastatic pancreatic cancer. There was a significant deficiency in germline testing regardless of the stage, with only 59% of cases having completed testing. Only 20% of cases were receiving palliative care or other allied support services. There was no difference in observed care gaps between patients receiving care in the community setting vs. those receiving care in the academic setting. There are significant gaps in the care delivered to patients with pancreatic adenocarcinoma. A concurrent subspecialist review has the opportunity to identify and address these gaps in a timely manner.

Association between Rural Residence and Processes of Care in Pancreatic Cancer Treatment

BackgroundPancreatic adenocarcinoma (PDAC) is an aggressive malignancy associated with poor outcomes. Surgical resection and receipt of multimodal therapy have been shown to improve outcomes in patients with potentially resectable PDAC; however treatment and outcome disparities persist on many fronts. The aim of this study was to analyze the relationship between rural residence and receipt of quality cancer care in patients diagnosed with non-metastatic PDAC. MethodsUsing the National Cancer Database, patients with non-metastatic pancreatic cancer were identified from 2006–2016. Patients were classified as living in metropolitan, urban, or rural areas. Multivariable logistic regression was used to identify predictors of cancer treatment and survival. ResultsA total of 41,786 patients were identified: 81.6% metropolitan, 16.2% urban, and 2.2% rural. Rural residing patients were less likely to receive curative-intent surgery (p = 0.037) and multimodal therapy (p < 0.001) compared to their metropolitan and urban counterparts. On logistic regression analysis, rural residence was independently associated with decreased surgical resection [OR 0.82; CI 95% 0.69–0.99; p = 0.039] and multimodal therapy [OR 0.70; CI 95% 0.38–0.97; p = 0.047]. Rural residence independently predicted decreased overall survival [OR 1.64; CI 95% 1.45–1.93; p < 0.001] for all patients that were analyzed. In the cohort of patients who underwent surgical resection, rural residence did not independently predict overall survival [OR 0.97; CI 95% 0.85–1.11; p = 0.652]. ConclusionsRural residence impacts receipt of optimal cancer care in patients with non-metastatic PDAC but does not predict overall survival in patients who receive curative-intent treatment.

A Machine Learning Approach to Predict Postoperative Pancreatic Fistula After Pancreaticoduodenectomy Using Only Preoperatively Known Data.

Clinically-relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD) is a major postoperative complication and the primary determinant of surgical outcomes. However, the majority of current risk calculators utilize intraoperative and postoperative variables, limiting their utility in the preoperative setting. Therefore, we aimed to develop a user-friendly risk calculator to predict CR-POPF following PD using state-of-the-art machine learning (ML) algorithms and only preoperatively known variables. Adult patients undergoing elective PD for non-metastatic pancreatic cancer were identified from the ACS-NSQIP targeted pancreatectomy dataset (2014-2019). The primary endpoint was development of CR-POPF (grade B or C). Secondary endpoints included discharge to facility, 30-day mortality, and a composite of overall and significant complications. Four models (logistic regression, neural network, random forest, and XGBoost) were trained, validated and a user-friendly risk calculator was then developed. Of the 8666 patients who underwent elective PD, 13% (n = 1160) developed CR-POPF. XGBoost was the best performing model (AUC = 0.72), and the top five preoperative variables associated with CR-POPF were non-adenocarcinoma histology, lack of neoadjuvant chemotherapy, pancreatic duct size less than 3 mm, higher BMI, and higher preoperative serum creatinine. Model performance for 30-day mortality, discharge to a facility, and overall and significant complications ranged from AUC 0.62-0.78. In this study, we developed and validated an ML model using only preoperatively known variables to predict CR-POPF following PD. The risk calculator can be used in the preoperative setting to inform clinical decision-making and patient counseling.

Role of neoadjuvant therapy for nonmetastatic pancreatic cancer: Current evidence and future perspectives

Role of neoadjuvant therapy for nonmetastatic pancreatic cancer: Current evidence and future perspectives

PD-0893 Utility of neoadjuvant CT with/without SBRT to improve outcomes of non-metastatic pancreatic cancer

PD-0893 Utility of neoadjuvant CT with/without SBRT to improve outcomes of non-metastatic pancreatic cancer

Survival Outcomes and Failure Patterns in Patients with Inoperable Non-Metastatic Pancreatic Cancer Treated with Definitive Radiotherapy

This study investigated the long-term results, failure patterns, and prognostic factors of patients with initially inoperable non-metastatic pancreatic cancer (PC) receiving definitive radiotherapy (RT). Between January 2016 and December 2020, a total of 168 non-metastatic PC patients, who were surgically unresectable or medically inoperable, were enrolled to receive definitive RT, with or without chemotherapy. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method with a log-rank test. The cumulative incidence of locoregional and distant progression was estimated using the competing risks model. The Cox proportional-hazards model was used to determine the influence of prognostic variables on OS. With a median follow-up of 20.2 months, the median OS (mOS) and median PFS (mPFS) from diagnosis were 18.0 months [95% confidence interval (CI), 16.5-21.7 months] and 12.3 months (95% CI, 10.2-14.3 months), respectively. The mOS and mPFS from RT were 14.3 months (95% CI, 12.7-18.3 months) and 7.7 months (95% CI, 5.5-12.0 months), respectively. The corresponding 1-year, 2-year, and 3-year OS from diagnosis and RT were 72.1%, 36.6%, and 21.5% as well as 59.0%, 28.8%, and 19.0%, respectively. In a multivariate analysis, stage I-II (p = 0.032), pre-RT CA19-9 ≤ 130 U/mL (p = 0.011), receiving chemotherapy (p = 0.003), and a biologically effective dose (BED10) > 80 Gy (p = 0.014) showed a significant favorable influence on OS. Among the 59 available patients with definite progression sites, the recurrences of local, regional, and distant progression were 33.9% (20/59), 18.6% (11/59), and 59.3% (35/59), respectively. The 1-year and 2-year cumulative incidences of locoregional progression after RT were 19.5% (95% CI, 11.5-27.5%) and 32.8% (95% CI, 20.8-44.8%), respectively. Definitive RT was associated with long-term primary tumor control, resulting in superior survival in patients with inoperable non-metastatic PC. Further prospective randomized trials are warranted to validate our results in these patients.

Neoadjuvant chemotherapy associated with isotoxic high-dose stereotactic body radiotherapy does not increase postoperative complications after pancreaticoduodenectomy for nonmetastatic pancreatic cancer.

The role of radiotherapy in the therapeutic sequence of nonmetastatic pancreatic cancer (PC) is controversial, including isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT). This study aimed to compare postoperative outcome of patients with nonmetastatic PC undergoing neoadjuvant treatment (NAT) including iHD-SBRT versus upfront pancreaticoduodenectomy (PD). All patients undergoing PD for PC from 2017 to 2021 were retrospectively analyzed, identifying patients receiving NAT with iHD-SBRT. Toxicity of treatments and postoperative outcome were assessed and analyzed in a propensity score-matched population. Eighty-nine patients underwent upfront surgery (surgery group) and 22 after NAT and iHD-SBRT (SBRT group). No major side effects SBRT-related were identified preoperatively. Postoperative morbidity was similar between groups. There was no postoperative death in SBRT group, and six in surgery group (p = 0.597). No difference was observed in the rates of complications related to pancreatic surgery. The postoperative hospital stay was shorter in SBRT versus surgery groups (p = 0.016). After propensity score matching, no significant difference in the postoperative morbidity was observed between groups. Incorporation of iHD-SBRT in the NAT sequence before PD for PC did not increase postoperative morbidity compared with upfront surgery. These results confirm the feasibility and safety of iHD-SBRT for the upcoming STEREOPAC trial.

Technical options in surgery for artery-involving pancreatic cancer: Invasion depth matters

BackgroundThe artery involvement explains the majority of primary unresectability of non-metastatic pancreatic cancer patients and both arterial resection and artery-sparing dissection techniques are utilized in curative-intent pancreatectomies for artery-involving pancreatic cancer (ai-PC) patients. MethodsThis narrative review summarized the history of resectability evaluation for ai-PC and attempted to interpret its current pitfalls that led to the divergence of resectability prediction and surgical exploration, with a focus on the rationale and the surgical outcomes of the sub-adventitial divestment technique. ResultsThe circumferential involvement of artery by tumor currently defined the resectability of ai-PC but insufficient to preclude laparotomy with curative intent. The reasons behind could be: 1. The radiographic involvement of tumor to arterial circumference was not necessarily resulted in histopathological artery wall invasion; 2. the developed surgical techniques facilitated radical resection, better perioperative safety as well as oncological benefit. The feasibility of periadventitial dissection, sub-adventitial divestment and other artery-sparing techniques for ai-PC depended on the tumor invasion depth to the artery, i.e., whether the external elastic lamina (EEL) was invaded demonstrating a hallmark plane for sub-adventitial dissections. These techniques were reported to be complicated with preferable surgical outcomes comparing to arterial resection combined pancreatectomies, while the arterial resection combined pancreatectomies were considered performed in patients with more advanced disease. ConclusionsAdequate preoperative imaging modalities with which to evaluate the tumor invasion depth to the artery are to be developed. Survival benefits after these techniques remain to be proven, with more and higher-level clinical evidence needed. Key messageThe current resectability evaluation criteria, which were based on radiographic circumferential involvement of the artery by tumor, was insufficient to preclude curative-intent pancreatectomies for artery-involving pancreatic cancer patients. With oncological benefit to be further proven, periarterial dissection and arterial resection have different but overlapping indications, and predicting the tumor invasion depth in major arteries was critical for surgical planning.

Greco-2: A randomized, phase 2 study of stereotactic body radiation therapy (SBRT) in combination with rucosopasem (GC4711) in the treatment of locally advanced or borderline resectable nonmetastatic pancreatic cancer.

TPS766 Background: While treatment of pancreatic cancer has advanced, survival rates remain low. Stereotactic body radiotherapy (SBRT; high dose per fraction radiation) may exhibit improved clinical outcomes in locally advanced pancreatic cancer but carries potential gastrointestinal toxicity risks. Rucosopasem (GC4711) is one of a class of investigational selective dismutase mimetics that rapidly and specifically converts superoxide to hydrogen peroxide. Studies have shown that normal cells tolerate hydrogen peroxide fluxes better than cancer cells. As radiation response modifiers, dismutase mimetics have the potential to increase tumor control of SBRT without compromising radiation safety. In a pilot phase 1/2 trial in patients with pancreatic cancer, avasopasem, a dismutase mimetic related to rucosopasem, nearly doubled median overall survival in patients receiving SBRT vs placebo plus SBRT. Improvements versus placebo were also observed in local tumor control, time to metastases, and progression-free survival. Altogether, these data support the hypothesis that rucosopasem may improve survival and the benefit-risk ratio of SBRT by improving efficacy without increasing gastrointestinal toxicity. Methods: GRECO-2 is a phase 2, multicenter, randomized, double-blind, placebo-controlled study (NCT04698915) to determine the effect of adding rucosopasem to SBRT on overall survival in patients with borderline resectable or locally advanced, unresectable nonmetastatic pancreatic cancer following initial chemotherapy with a FOLFIRINOX-based regimen or a gemcitabine doublet. Approximately 160 patients will be randomized (approximately 35 sites) to receive rucosopasem 100 mg or placebo via IV infusion over 15 minutes, prior to each SBRT fraction (5 x 10 Gy). Patients judged to be resectable will undergo surgical exploration within 8 weeks after SBRT. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, locoregional control, time to metastasis, surgical resection rate, RO resection rate, best overall response, in-field local response, and safety (acute and late toxicities). Exploratory endpoints include PRO-CTCAE and CA19-9 normalization. This trial (NCT04698915) is now enrolling. Clinical trial information: NCT04698915 .

Neoadjuvant Chemotherapy with Isotoxic High-dose SBRT Does Not Increase Postoperative Complications after Pancreatoduodenectomy for Non-metastatic Pancreatic Cancer

Neoadjuvant Chemotherapy with Isotoxic High-dose SBRT Does Not Increase Postoperative Complications after Pancreatoduodenectomy for Non-metastatic Pancreatic Cancer

1302P Gender differences in tumor characteristics, treatment allocation and survival in patients in a real-world non-metastatic pancreatic cancer cohort

Differences in biological sex and gender may have impact on treatment allocation and survival in patients with localized and locally advanced pancreatic cancer. The aim of the present study is to systematically analyse patient- and tumour characteristics, treatment allocation and overall survival in patients with stage I-III pancreatic cancer in the Netherlands.

GRECO-2: A randomized, phase 2 study of stereotactic body radiation therapy (SBRT) in combination with rucosopasem (GC4711) in the treatment of locally advanced or borderline resectable nonmetastatic pancreatic cancer.

TPS4184 Background: While treatment of pancreatic cancer has advanced, survival rates remain low. Stereotactic body radiotherapy (SBRT; high dose per fraction radiation) may exhibit improved clinical outcomes in locally advanced pancreatic cancer but carries potential gastrointestinal toxicity risks (Zhong 2017). Rucosopasem (GC4711) is one of a class of investigational selective dismutase mimetics that rapidly and specifically converts superoxide to hydrogen peroxide (Riley 2006). Studies have shown that normal cells tolerate hydrogen peroxide fluxes better than cancer cells (Doskey 2016). As radiation response modifiers, dismutase mimetics have the potential to increase tumor control of SBRT without compromising radiation safety (El-Mahdy 2020, Sishc 2021). In a pilot phase 1/2 trial in patients with pancreatic cancer, avasopasem, a dismutase mimetic related to rucosopasem, nearly doubled median overall survival in patients receiving SBRT vs placebo plus SBRT. Improvements versus placebo were also observed in local tumor control, time to metastases, and progression-free survival. Altogether, these data support the hypothesis that rucosopasem may improve survival and the benefit-risk ratio of SBRT by improving efficacy without increasing gastrointestinal toxicity. Materials/Methods: GRECO-2 is a phase 2, multicenter, randomized, double-blind, placebo-controlled study (NCT04698915) to determine the effect of adding rucosopasem to SBRT on overall survival in patients with borderline resectable or locally advanced, unresectable nonmetastatic pancreatic cancer following initial chemotherapy with a FOLFIRINOX-based regimen or a gemcitabine doublet. Approximately 160 patients will be randomized (approximately 35 sites) to receive rucosopasem 100 mg or placebo via IV infusion over 15 minutes, prior to each SBRT fraction (5 x 10 Gy). Patients judged to be resectable will undergo surgical exploration within 8 weeks after SBRT. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, locoregional control, time to metastasis, surgical resection rate, RO resection rate, best overall response, in-field local response, and safety (acute and late toxicities). Exploratory endpoints include PRO-CTCAE and CA19-9 normalization. This trial is now enrolling. Clinical trial information: NCT04698915.

Retrospective Evaluation of Treatment Response in Patients with Nonmetastatic Pancreatic Cancer Using CT and CA 19-9.

Background Imaging studies have limitations in evaluating pancreatic ductal adenocarcinoma (PDAC) treatment response. Purpose To investigate the effectiveness of combined CT and carbohydrate antigen 19-9 (CA 19-9) evaluation at 8 weeks after first-line treatment to predict overall survival (OS) of patients with nonmetastatic PDAC. Materials and Methods Patients with nonmetastatic PDAC who received first-line treatment with either chemotherapy or concurrent chemoradiation in a single-center PDAC cohort registry were retrospectively enrolled in the study between January 2013 and December 2016. Follow-up CT images obtained 8 weeks after treatment were evaluated according to Response Evaluation Criteria in Solid Tumors. Patients with partial response (PR) or stable disease (SD) were defined as CT responders, and those with progressive disease (PD) were defined as CT nonresponders. Patients with a normalized CA 19-9 level at 8-week follow-up were defined as CA 19-9 responders, and those with a nonnormalized or nonelevated CA 19-9 level were defined as CA 19-9 nonresponders. OS was compared using the Kaplan-Meier method with Breslow analysis. Results A total of 197 patients (mean age ± standard deviation, 65 years ± 10; 107 men) were evaluated. Patients with PD (n = 17) showed shorter OS than those with SD (n = 147; P < .001) or PR (n = 33; P = .003). OS did not differ between the patients with PR and those with SD (P = .60). When the CT and CA 19-9 responses were integrated, OS was longest in CT and CA 19-9 responders (group 1, n = 27; median OS, 26.6 months [95% CI: 9.0, 44.1]), followed by CT responders but CA 19-9 nonresponders (group 2, n = 153; median OS, 15.9 months [95% CI: 13.3, 18.5]; P = .007 vs group 1) and CT and CA 19-9 nonresponders (group 3, n = 17; median OS, 6.5 months [95% CI: 0.8, 12.2]; P < .001 vs group 2). Conclusion Integrated evaluation with CT and carbohydrate antigen 19-9 response allowed more accurate stratification of survival in patients with pancreatic ductal adenocarcinoma in the early treatment period than did evaluation according to Response Evaluation Criteria in Solid Tumors. © RSNA, 2022 Online supplemental material is available for this article.

Prognostic Effect of Aberrant Right Hepatic Artery with Pancreaticoduodenectomy: Focus on Hepatic Recurrence

Metastatic progression occurs along the locoregional vasculature, and a common anatomic variant is an aberrant right hepatic artery (aRHA). This study evaluated the effect of an aRHA following pancreaticoduodenectomy, with a focus on hepatic metastases. This was a single-institution retrospective review of non-metastatic pancreatic cancer cases between 2012 and 2020. aRHA cases were compared with patients with conventional anatomy. The primary outcome was hepatic recurrence rates, while secondary analysis survival outcomes were measured by overall survival (OS) and disease-free survival (DFS). Subgroup analysis was stratified by tumor resectability and utilization of systemic therapy. Overall, 207 cases were reviewed, with 17.4% having aRHA anatomy. On multivariate analysis, aRHA increased hepatic recurrence for all-comers (odds ratio [OR] 4.76, 95% confidence interval [CI] 2.18-10.38; p<0.001). aRHA was significant for resectable tumors (OR 2.58, 95% CI 1.89-6.66; p=0.045) and borderline resectable tumors (OR 28.88, 95% CI 5.52-151.18; p<0.0001) in regard to hepatic recurrence on univariate analysis. Increased hepatic recurrence correlated with decreased 3-year OS and DFS rates of 30.6% versus 50.3% (OR 0.44, 95% CI 0.20-0.94; p=0.032) and 13.6% versus 36.9% (OR 0.27, 95% CI 0.08-0.97; p=0.035). Systemic therapy limited the effects of aRHA. aRHA was associated with inferior survival outcomes due to the significantly increased risk of hepatic metastatic disease with aberrant anatomy. This study provides important prognostic information for a commonly encountered anatomic variant.

The Impact of Treatment at Minority-serving Hospitals on Outcomes for Pancreatic Cancer

Introduction: Healthcare for racial minorities is densely concentrated within a small subset of hospitals in the United States. Understanding outcomes at these minority-serving hospitals (MSH) is highly relevant to the study of racial disparities in cancer care. Our aim was to identify the impact of receiving treatment at an MSH on overall survival (OS) and on receipt of definitive treatment for minority patients with pancreatic cancer. Methods: Using the National Cancer Database, we identified all patients diagnosed with non-metastatic biopsy-proven pancreatic adenocarcinoma between 2004-2014. MSH were defined as institutions in the top decile of proportion of Black and Hispanic patients within the cohort. Univariate and multivariate analyses were performed to assess the influence of patient- and hospital-level factors on OS and receipt of definitive treatment for pancreatic cancer. Results: 21,452 Black and Hispanic patients were included. 4,103(19.1%) were treated at MSH. There was no difference in the proportion of patients undergoing resection(p=0.353). On adjusted analysis, there was no difference in OS for patients treated at MSH versus those treated at non-MSH (Hazard Ratio[HR]=0.99, 95%Confidence Interval[CI]:0.95–1.04;p=0.79). Significant factors associated with a decreased likelihood of death were receipt of surgery (HR 0.44, 95%CI:0.42-0.45), administration of systemic chemotherapy (HR 0.90, 95%CI:0.86-0.94), and high income (HR 0.86, 95%CI:0.80-0.92). Conclusions: For Black and Hispanic patients with non-metastatic pancreatic cancer, there was no difference in OS associated with receipt of treatment at MSH, despite differences in patient demographics and hospital characteristics. Further study is required to identify sources and impact of disparities in cancer care.

Novel biochemical markers for non-invasive detection of pancreatic cancer.

To identify non-invasive biomarkers of non-metastatic pancreatic cancer (PC), the blood from 186 patients (PC n=28; DM-diabetes mellitus n=60; ChP-chronic pancreatitis n=47; healthy controls n=51) was analyzed for 58 candidate biomarkers. Their effectiveness to identify PC was compared with CA19-9. Panel defined by Random-forest (RF) analysis (CA19-9, AAT, IGFBP2, albumin, ALP, Reg3A, HSP27) outperforms CA19-9 in discrimination of PC from DM (AUC 0.92 vs. 0.82). Panel (S100A11, CA72-4, AAT, CA19-9, CB, MMP-7, S100P-s, Reg3A) is better in discrimination PC from ChP than CA19-9 (AUC 0.90 vs. 0.75). Panel (MMP-7, Reg3A, sICAM1, OPG, CB, ferritin) is better in discrimination PC from healthy controls than CA19-9 (AUC 0.89 vs. 0.78). Panel (CA19-9, S100P-pl, AAT, albumin, adiponectin, IGF-1, MMP7, S100A11) identifies PC among other groups better than CA19-9 (AUC 0.91 vs. 0.80). Panel defined by logistic regression analysis (prealbumin, IGFBP-2, DJ-1, MIC-1, CA72-4) discriminates PC from DM worse than CA19-9 (AUC 0.80 vs. 0.82). Panel (IGF-1, S100A11, Reg1alfa) outperforms CA19-9 in discrimination PC from ChP (AUC 0.76 vs. 0.75). Panel (IGF-2, S100A11, Reg3A) outperforms CA19-9 in discrimination PC from healthy controls (AUC 0.95 vs. 0.78). Panel (albumin, AAT, S100P-serum, CRP, CA19-9, TFF1, MMP-7) outperforms CA19-9 in identification PC among other groups (AUC 0.89 vs. 0.8). The combination of biomarkers identifies PC better than CA19-9 in most cases. S100A11, Reg3A, DJ-1 were to our knowledge identified for the first time as possible serum biomarkers of PC.