Localized Pancreatic Cancer Research Articles

Surgical patterns of care of pancreatic cancer. A French population-based study

IntroductionSurgical resection is the standard recommended treatment in localized pancreatic cancer. The benefit of neoadjuvant chemotherapy is still debated. The aim of this population-based study was to describe the pancreatic cancer surgical management. Material and methodsAn observational real-world study from the French Network of Cancer Registries sampled 638 pancreatic adenocarcinomas diagnosed in 2019. Characteristics of patients, tumours and recommended and administered treatments were collected. Operability of the patients and resectability of the tumours were described. A multivariate logistic regression was used to identify factors associated with the probability of having surgical resection. ResultsAmong the 263 (41 %) patients with M0 pancreatic adenocarcinomas, 202 patients (77 %) were considered operable and 157 (60 %) also had a tumour considered resectable. Upfront resection was recommended for 68 % and resection after neoadjuvant chemotherapy for 32 % of these patients. Among operable patients with resectable tumour, 36 % underwent upfront R0 resection, and 15 % achieved R0 resection following neoadjuvant chemotherapy. Eventually, among M0 pancreatic adenocarcinomas, age over 80 years (OR≥80 years vs < 65 years: 0.16 [0.06–0.39], p < 0.001) and WHO performance status over 0 (OR1-2 vs 0: 0.43 [0.24–0.79], p = 0.013) decreased the odds of having resection. R0 surgical resection was achieved in 61 % of patients selected for upfront surgical recommendation, and 29 % of those selected for a prior neoadjuvant chemotherapy. ConclusionIn a non-selected population, one-third of patients with localized pancreatic cancer had a complete R0 surgical resection. Neoadjuvant chemotherapy did not achieve a resection rate similar to that of patients selected for upfront surgical indication.

Chemotherapy switch for localized pancreatic cancer: a systematic review and meta-analysis.

Patients with localized (that is non-metastatic) pancreatic ductal adenocarcinoma with an inadequate response or toxicity to first-line chemotherapy may benefit from chemotherapy switch. The aim was to explore the available data on the use and effect of chemotherapy switch, as reported in the literature. A systematic search was conducted in Embase, MEDLINE (Ovid), the Web of Science, Cochrane, and Google Scholar on 1 December 2023. The main outcomes were the proportion of patients who underwent chemotherapy switch and the carbohydrate antigen 19-9 response and resection, R0 resection, and ypN0 resection rates after chemotherapy switch. Data were pooled using a random-effects model. A total of five retrospective studies, representing 863 patients with localized pancreatic ductal adenocarcinoma, were included and 226 of the 863 patients underwent chemotherapy switch. In four studies, first-line chemotherapy consisted of 5-fluorouracil/leucovorin/irinotecan with oxaliplatin ('FOLFIRINOX') and patients were switched to gemcitabine with nab-paclitaxel. Reasons for chemotherapy switch included an inadequate biochemical, clinical, or radiological response, or toxicity. Three studies compared patients who underwent chemotherapy switch with patients who only received first-line chemotherapy and found that the proportion of patients who underwent chemotherapy switch was 20.5% (95% c.i. 10.5% to 36.3%). The pooled resection rate after chemotherapy switch was 42.0% (95% c.i. 16.6% to 72.5%). Two studies compared the chance of resection after chemotherapy switch versus first-line chemotherapy alone and found a risk ratio of 0.88 (95% c.i. 0.65 to 1.18). Two studies, with a combined total of 576 patients, found similar postoperative survival for patients who underwent chemotherapy switch and patients who only received first-line chemotherapy. One in five patients with localized pancreatic ductal adenocarcinoma underwent chemotherapy switch after an inadequate response or toxicity to first-line chemotherapy. The pooled resection rate after chemotherapy switch was 42% and similar in overall survival compared with first-line chemotherapy only. Three ongoing trials are investigating chemotherapy switch in patients with an inadequate radiological or carbohydrate antigen 19-9 response.

Abstract A019: Black race and CA 19-9 nonproduction is associated with limited pathologic response to neoadjuvant chemotherapy in patients with localized pancreatic cancer

Abstract Introduction: Black patients with pancreatic ductal adenocarcinoma (PDAC) are less likely to have major pathologic response (MPR) following induction chemotherapy. Our previous study suggested a lower baseline CA 19-9 among Black patients. We aimed to determine if CA 19-9 nonproduction contributes to racial differences in neoadjuvant chemotherapy (NAC) response. We then investigated the biological mechanisms underlying reduced response in CAnonprod with multi-omic analysis. Methods: Black and White patients with PDAC receiving ≥ 2 cycles of NAC followed by pancreatectomy at 7 high-volume centers were reviewed. Patients were categorized as CAproducers (CAprod, CA 19-9 &amp;gt; 5 U/mL) or CAnonprod (CA 19-9 ≤ 5 U/mL). Uni- and multi-variable models evaluated differences in rates of CAnonprod by race, and the association of CAnonprod with MPR (CAP 0/1). The Pancreatic Cancer Action Network SPARK platform was queried for patients with CA 19-9 and genomic data. Fisher’s exact test was used to compare differentially mutated genes between CAnonprod and CAprod. Differential gene expression (DEG) analysis identified significantly differentially expressed genes using an absolute fold change of ≥ 2 and p-adj &amp;lt; 0.05 as a cutoff. quanTIseq computational pipeline was used for immune cell deconvolution analysis of the two groups. Results: Our cohort included 385 CAprod and 30 CAnonprod. CAnonprod had a significantly higher rate of Black patients (50% vs 13%, p&amp;lt;0.01). Compared with CAprod, CAnonprod received similar rates of FOLFIRINOX (60% vs. 57%, p=0.27) and duration of NAC (4 vs 5 cycles, p=0.83). Rate of MPR was higher among CAprod compared to CAnonprod (26% vs 8%, p=0.03). No CAnonprod patient had a complete pathologic response vs 28 (7%) of CAprod (p=0.12). CAnonprod was independently associated with decreased odds of MPR (OR 0.21, CI [0.04-0.99]). Black race was independently associated with increased odds of CAnonprod (OR 8.66, CI [3.81 – 19.7]). When CA 19-9 production status was matched by race, there was no difference between rate of MPR between White and Black CAnonprod; both experienced low rates of MPR (12% and 9%, respectively, (p=0.68)). CAnonprod had higher rates of SWI/SNF alterations (50% CAnonprod vs 33% CAprod, p&amp;lt; 0.01; P-adj=ns), and ARID1B was the most frequently mutated gene in CAnonprod (28% vs 11%, p&amp;lt; 0.01; P-adj=ns). DEG analysis showed the LIPF gene was significantly downregulated in CAnonprod compared to CAprod. There was no difference in immune cell distribution between CAprod and CAnonprod. Conclusion: CA 19-9 non-production is more prevalent in Black patients and potentially mediates the lower rates of MPR following NAC. CA 19-9 non-production is associated with higher rates of SWI/SNF alterations and a downregulation of the LIPF gene encoding gastric lipase, unveiling a potential biologic or metabolomic difference in response to chemotherapy between races. Citation Format: Mary P. Martos, Erin M. Dickey, Kawther Abdilleh, Syed A. Ahmad, Shishir K. Maithel, Chet W. Hammill, Hong Jin Kim, Daniel E. Abbott, David A. Kooby, Alexander A. Parikh, Peter J. Hosein, Nipun B. Merchant, Jashodeep Datta, Caitlin A. Hester. Black race and CA 19-9 nonproduction is associated with limited pathologic response to neoadjuvant chemotherapy in patients with localized pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A019.

Abstract A022: Neoadjuvant ablative radiation downstages high-risk features and alters immune response in pancreatic cancer

Abstract Purpose: Increasing evidence shows neoadjuvant (NA) therapy benefits surgical selection and survival in localized pancreatic cancer. However, the optimal NA therapy for resectable, borderline resectable (BRPC), and locally advanced pancreatic cancer (LAPC) remains unclear. We hypothesize that NA stereotactic ablative radiotherapy (SAbR) benefits patients with BRPC and LAPC who do not progress on chemotherapy (CTH), especially with arterial involvement. To evaluate this, we retrospectively reviewed outcomes and molecular features of patients treated with NA CTH and NA CTH followed by SAbR to understand the contribution of radiation. Methods: We retrospectively reviewed clinical data for 133 patients treated with NA CTH and 48 with NA CTH + SAbR. Bulk RNA sequencing was performed on fresh surgical tissue from 29 CTH-treated and 14 CTH + SABR-treated patients. We conducted gene set enrichment analysis (GSEA), CIBERSORTx cellular deconvolution, and Single-Cell Identification of Subpopulations with Bulk Sample Phenotype Correlation (Scissor) analysis to correlate clinical outcomes with transcriptomic features. Results: Molecular subtyping of PDAC transcriptomic signatures from post-treatment tissues revealed similar subtype proportions after both treatments. However, at baseline and before surgery, patients receiving SABR had more advanced clinical T staging, NCCN resectability, and arterial involvement. Despite this, the NA CTH + SAbR cohort showed similar overall survival, local-regional progression-free survival (LRPFS), and distant metastasis progression-free survival (DPFS) compared to NA CTH only. NA CTH + SABR-treated patients had significantly improved post-treatment T and N staging, tumor size, and treatment effect. These improvements correlated with better survival, LRPFS, and DPFS. RNAseq analysis indicated that patients with nodal involvement had significantly increased GSEA of MYC targets and worse DPFS. Tumor-arterial involvement at diagnosis significantly reduced local-regional control for NA CTH only. In contrast, patients with arterial involvement receiving NA CTH + SAbR had significantly improved local control. CIBERSORTx cell fraction deconvolution revealed no significant differences in tumor and immune cell subsets between treatments, but GSEA indicated substantial changes in immune-related gene sets, particularly those related to myeloid and T cell activation, suggesting functional changes correlating with treatment response and local control. Scissor identified gene signatures from activated CD8 T cells correlating with improved local control, while signatures from Treg and naïve T cells negatively impacted LRPFS. Conclusions: Molecular analysis and clinical features showed that patients treated with NA CTH + SAbR experienced downstaging and had similar outcomes, with indications of a differential immune response. Given these findings, the role of SAbR in the NA setting should be further evaluated, especially in the context of improved chemotherapy and novel combination therapies that leverage biological responses. Citation Format: Peter Q. Leung, Eslam A. Elghonaimy, Ahmed M. Elamir, Megan Wachsmann, Song Zhang, Neha Barrows, Rachel von Ebers, Cassandra Hamilton, Grace Josephson, Salwan Al Mutar, Patricio M. Polanco, Nina N. Sanford, Syed M. Ali Kazmi, Matthew R. Porembka, David Hsieh, Adam C. Yopp, Muhammad S. Beg, Herbert J. Zeh, Todd A. Aguilera. Neoadjuvant ablative radiation downstages high-risk features and alters immune response in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A022.

Incidence of Pancreatic Leakage in Isolated Biliary Limb Roux-en-Y Reconstruction in Whipple Procedure

Abstract Background Whipple is currently the procedure of choice in the treatment of localized pancreatic cancer. Isolated Roux-en-Y loop pancreaticojejunostomy was proposed as a method of reconstruction following pancreaticoduodenectomy. The idea is to isolate the bile from pancreatic secretions to minimize pancreatic enzyme activation and ultimately pancreatic fistula formation. It was also proposed that if a pancreatic fistula develops, it will be a pure fistula and thereby more benign as opposed to a mixed pancreatic fistula containing bile. Objective To estimate the incidence of pancreatic fistula in patients undergoing isolated Roux-en- Y hepaticojejunostomy reconstruction following pancreaticoduodenectomy. Patients and Methods In this prospective observational study, our aim is to calculate the incidence of post-operative pancreatic fistula in 20 patients that underwent Roux-en-Y isolated biliary limb reconstruction following pancreaticoduodenectomy for the treatment of pancreatic cancer. The study includes patients that underwent this procedure at Ain Shams University Hospitals in the period between January 2021 and July 2022 with a post-operative follow up period of 3 weeks. Patients were diagnosed with pancreatic cancer using MRI or CT scans with some of them also undergoing endoscopic US with biopsy. They were then admitted to one of the two main Ain Shams University Hospitals for pre-operative preparation. Results Our study did no estimate post-operative complications such as delayed gastric emptying and wound infection. Pancreaticoduodenectomy is a major surgery that carries a significant burden in terms of morbidity and mortality. Post-operative pancreatic fistula can be fatal as it can lead to vascular pseudoaneurysms that may fatally rupture. The idea behind using isolated biliary limb roux-en-y reconstruction is to alleviate the morbidity caused by post-operative pancreatic fistula. Conclusion Further comparative studies with a higher number of patients are recommended to assess and compare the value of isolated biliary limb reconstruction when compared to conventional reconstruction.

EUS-guided hydrogel injection to separate pancreatic head carcinoma from duodenum for enhanced radiotherapy: Multi-site feasibility study.

Background and study aims The proximity of a pancreas head tumor to the duodenum often limits delivery of an ablative dose of radiation therapy. This study evaluated the feasibility and safety of using an injectable polyethylene glycol (PEG) hydrogel between the head of the pancreas and duodenum. Patients and methods In a multi-site feasibility cohort study of patients with localized pancreatic cancer, PEG hydrogel was injected under endoscopic ultrasound guidance to temporarily position the duodenum away from the pancreas. Procedure characteristics were recorded, including hydrogel volume and space created. Patients were monitored for adverse events (AEs) and radiotherapy toxicity. Results In all six intent-to-treat patients (four with borderline resectable, two with locally advanced disease), the ability to place and visualize PEG hydrogel and create space between the duodenum and the head of the pancreas was successful. There were no procedure-related AEs resulting in radiotherapy delay. There were no device-related AEs and no reports of pancreatitis. Conclusions PEG hydrogel was successfully placed, created space between the duodenum and the head of the pancreas, and was not associated with major toxicity. Enhancing radiotherapy for pancreatic cancer by using PEG hydrogel to create peri-duodenal space could have beneficial implications for treatment and warrants more exploration.

Intraoperative strategies and techniques to achieve surgical radicality in pancreatic cancer

SummaryThe treatment of pancreatic cancer presents a challenging task in surgical oncology, demanding innovative approaches to achieve radical resection and improve patient outcomes. This article provides an overview of state-of-the-art surgical principles and techniques for achieving surgical radicality in localized pancreatic cancer, with a particular emphasis on artery-first approaches, the triangle operation, arterial and venous dissection techniques, including arterial divestment, and the significance of R0 resections with complete lymphadenectomy. By applying these techniques and principles of surgical radicality, surgeons are able to enhance resectability, minimize complications, and potentially extend patient survival in the rapidly evolving field of multimodal pancreatic cancer management.

Intratumoral Injection of Large Surface Area Microparticle Taxanes in Carcinomas Increases Immune Effector Cell Concentrations, Checkpoint Expression, and Synergy with Checkpoint Inhibitors: A Review of Preclinical and Clinical Studies.

This review summarizes development of large surface area microparticle paclitaxel (LSAM-PTX) and docetaxel (LSAM-DTX) for local treatment of primary carcinomas with emphasis on immunomodulation. Intratumoral (IT) delivery of LSAM-PTX and LSAM-DTX provides continuous, therapeutic drug levels for several weeks. Preclinical studies and clinical trials reported a reduction in tumor volume (TV) and immunomodulation in primary tumor and peripheral blood with increases in innate and adaptive immune cells and decreases in suppressor cells. Increased levels of checkpoint expression of immune cells occurred in clinical trials of high-risk non-muscle-invasive bladder cancer (LSAM-DTX) and unresectable localized pancreatic cancer (LSAM-PTX). TV reduction and increases in immune effector cells occurred following IT LSAM-DTX and IT LSAM-PTX together with anti-mCTLA-4 and anti-mPD-1, respectively. Synergistic benefits from combinatorial therapy in a 4T1-Luc breast cancer model included reduction of metastasis with IT LSAM-DTX + anti-mCTLA-4. IT LSAM-PTX and LSAM-DTX are tumoricidal, immune enhancing, and may improve solid tumor response to immune checkpoint inhibitors without additional systemic toxicity.

Association of race and CA 19-9 nonproduction with limited pathologic response to neoadjuvant chemotherapy in patients with localized pancreatic cancer.

609 Background: Black patients with pancreatic ductal adenocarcinoma (PDAC) are less likely to have major pathologic response (MPR) following induction chemotherapy compared to non-Black patients. Rare reports have suggested that Black patients are more likely to be CA 19-9 non-producers. We aimed to determine if disproportionate rates of CA 19-9 nonproduction underlie racial differences in neoadjuvant chemotherapy response in patients with localized PDAC. We also explored differences in somatic mutations between CA 19-9 producers (CAprod) and non-producers (CAnonprod). Methods: Black and White patients with localized PDAC receiving ≥ 2 cycles of neoadjuvant chemotherapy followed by pancreatectomy (2010-2019) at 7 high-volume centers were reviewed. Patients were categorized as CAprod (CA 19-9 &gt; 5 U/mL) or CAnonprod (CA 19-9 ≤ 5 U/mL). Uni- and multi-variable models evaluated differences in rates of CAnonprod by race, and the association of CAnonprod with MPR (CAP 0/1). The Pancreatic Cancer Action Network (PanCAN)’s SPARK health data platform which contains clinical and multi-omic data from the PanCAN Know Your Tumor program was queried to identify patients with CA 19-9 and genomic data. Fisher’s exact test was used to compare differentially mutated genes between CAprod and CAnonprod patients. Results: Our cohort included 385 (93.3%) CAprod and 30 (6.7%) CAnonprod. CAnonprod patients were more likely to be Black than CAprod (50.0% vs 12.5%, p&lt;0.01). There were no other differences in demographic or clinical features between CAnonprod and CAprod. Most patients received FOLFIRINOX vs Gemcitabine based chemotherapy (60.3% CAprod vs. 56.7% CAnonprod, p=0.27) with a median number of 4.0 vs 5.0 cycles (p=0.83), respectively. Rate of MPR was significantly higher in patients with CAprod compared with CAnonprod patients (26.3% vs 7.7%, p=0.03). No CAnonprod patient had a complete pathologic response vs 28 (7.3%) of CAprod (p=0.12). CAnonprod was independently associated with decreased odds of MPR (OR 0.21, CI [0.04-0.99]). Black race was independently associated with increased odds of CAnonprod (OR 8.66, CI [3.81 – 19.7]). When stratified by production of CA 19-9, there was no significant difference between rate of MPR between Black and White patients. In the PanCAN KYT analysis, CAnonproduc had higher rates of SWI/SNF alterations (50.0% of CAnonprod vs 30.1% of CAprod, P&lt;0.01;P-adj=ns; ARID1B was the most frequently mutated SWI/SNF gene in CAnonprod (31.0% vs 9.0% CApos, p&lt;0.01; P-adj=ns). Conclusions: CAnonprod were more likely to be Black and have significantly worse rates of MPR following neoadjuvant chemotherapy in patients with localized PDAC. Moreover, CAnonprod was associated with higher rates of SWI/SNF alterations, noting a potential biologic basis for racial differences in chemotherapy response to curative-intent treatment for PDAC.

Factors associated with the receipt of surgery in acinar cell carcinoma of the pancreas.

668 Background: Acinar cell carcinoma of the pancreas (PACC) accounts for 1-2% of adult pancreatic tumors. Clinically, this malignancy presents as a hypersecretory syndrome as lipase is released into circulation. Median overall survival is 18 to 47 months. Aggressive surgical resection is associated with long-term survival in PACC patients. This appears to be the treatment of choice for most localized pancreatic cancers, however, there are no clear treatment guidelines or standardized protocols for PACC due to its rarity. Further, no significant study has analyzed the factors correlated with receiving this surgery. This study aims to uncover the possible factors associated with the receipt of tumor resection in patients with PACC. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with PACC from 2004 to 2019 using the histology code 8550 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Multilevel Logistic Regression were performed, and data were analyzed using SPSS version 29. Statistical significance was set at α = 0.05. Results: 1430 patients with PACC were queried. 600 (41.95%) patients received surgical resection. Surgical patients experienced longer overall survival than non-surgical patients (87.5 months vs. 25.3 months, P &lt; 0.01). Of the surgical patients, wider surgical margins and complete tumor resection were associated with improved survival (P&lt;0.001). Stage I and II disease, well and moderately differentiated disease, and receiving treatment at an academic/research facility were associated with an increased likelihood of receiving surgery (P&lt;0.001). Metastasis at the time of diagnosis was associated with a decreased likelihood of receiving surgery (P&lt;0.001). Income status, race, insurance status, and age did not appear to be significant predicting factors of surgery. Of the initial sample, 219 (15.31%) patients received adjuvant chemotherapy, 8 (0.55%) patients received adjuvant radiation, and 4 (0.28%) patients received both adjuvant chemotherapy and radiation. Adjuvant therapies did not appear to impact the overall survival of PACC patients. Conclusions: This study confirms that tumor resection is associated with increased survival in patients with PACC. Improved survival with surgery is correlated to wider surgical margins and complete tumor resection. It appears that patients with well or moderately differentiated disease, stage I or II disease, and treatment at an academic/research facility are more likely to receive surgery. PACC patients with metastasis to distant sites are less likely to receive surgery. The efficacy of adjuvant therapy remains unclear. Further studies are needed to better understand the factors involved in receiving surgery and other treatment modalities as part of PACC treatment.

Abstract C071: Radiomics of pre-operative CT scans capture biologic processes within the liver in patients undergoing pancreatectomy

Abstract Introduction: Pancreatic cancer (PC) is a highly lethal malignancy, largely due to its propensity for early dissemination and protracted subclinical course until it reaches advanced stages. Available diagnostic modalities are often unable to diagnose early events in the metastatic process, including pre-metastatic niches, micrometastases, or small macrometastases. We have previously shown that quantitative image features (QIFs) of the liver in pre-operative contrast-enhanced CT (CECT) scans can identify PC patients at risk of impending liver metastasis (PMID 35366706). Further, we found that perioperative liver biopsy in patients with untreated localized PC can capture cellular and molecular features of evolving pre-metastatic niches, which can predict timing and patterns of PC recurrence (doi.org/10.1158/1538-7445.PANCA22-PR012). In the present study, we sought to examine whether liver QIFs can capture specific biologic processes at the cellular level, which could in turn inform non-invasively on the status of the liver milieu that determine metastatic risk and potentially reveal opportunities for therapeutic intervention. Methods: Intraoperative liver biopsies were obtained from patients undergoing pancreatectomy for resectable PC (n=29) or non-cancerous pancreatic lesions (n=7) and were analyzed histologically for fibrosis, steatosis, portal and lobular inflammation. Immunostaining for immune cell populations and extracellular matrix proteins were performed. Liver biopsy histopathological features were then compared to 255 QIFs. Univariate analysis (UVA) was performed with logistic/linear regression, after stratification for biliary obstruction and presence of PC. For continuous variables, multivariate analysis (MVA) was performed using generalized linear model. For categorical variables, MVA was performed with Naïve-bayes classifier and ‘Leave-one image out’ method of cross validation after selecting the features with MRMR algorithm. Results: On UVA, multiple features correlated significantly with liver fibrosis, steatosis, and portal inflammation, as well fibronectin and collagen IV immunostaining. Further, significant correlations were found with CD11b+ cell density (cells/mm2), IBA1+ area, CD8+ staining intensity, CD3+ and CD8+ lobular infiltration, and total Ki67+ cell density. No significant associations were found with lobular inflammation, CD3+ intensity, or CD68+ cell density. On MVA, several QIFs remained significant predictors of the aforementioned 11 histopathologic variables. The best prediction was achieved for liver fibrosis (QIFs: RLM9, LBP56, LBP118, LBP3, LBP9, and LBP102; AUC 0.78) and steatosis (FD1_47; AUC 0.79). Conclusion: CECT liver texture analysis may predict biological processes affecting differential contrast perfusion, tissue distribution and parenchymal retention, enabling determination of liver histopathology non-invasively. Therefore, this approach may hold promise in identifying pre-metastatic niches or micrometastatic disease in evolution and risk-stratifying PC patients in a non-invasive fashion. Citation Format: Constantinos P. Zambririnis, Linda Bojmar, Jonathan Hernandez, Gokce Askan, Jian Zheng, Ahmad B. Barekzai, Natally Horvat, Vinod P. Balachandran, Jeffrey A. Drebin, Peter Kingham, Michael I. D’Angelica, Olca Basturk, Mithat Gönen, Alice Wei, Robert Schwartz, David C. Lyden, William R. Jarnagin, Jayasree Chakraborty. Radiomics of pre-operative CT scans capture biologic processes within the liver in patients undergoing pancreatectomy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C071.

Second-line chemotherapy in localized pancreatic cancer: a systematic review and meta-analysis

Second-line chemotherapy in localized pancreatic cancer: a systematic review and meta-analysis

Gastrointestinal Malignancies: Pancreatic Cancer Clinical Trials in Neoadjuvant Chemotherapy.

Surgical resection is the only known treatment associated with long-term survival in pancreatic adenocarcinoma. While adjuvant therapy has shown a clear survival benefit, neoadjuvant chemotherapy has gained interest due to its ability to prioritize the treatment of micrometastatic disease prior to resection and improve chemotherapy tolerance prior to a major operation. Investigations have focused on evaluating the survival benefit of neoadjuvant therapy using single and combination chemotherapy as well as radiation therapy. Landmark trials in localized pancreatic cancer have paved the way for the standard use of neoadjuvant therapy for pancreatic adenocarcinoma.

Variation in outcomes and practice patterns among patients with localized pancreatic cancer: the impact of the pancreatic cancer multidisciplinary clinic.

Patients with localized pancreatic adenocarcinoma (PDAC) benefit from multi-modality therapy. Whether care patterns and oncologic outcomes vary if a patient was seen through a pancreatic multi-disciplinary clinic (PMDC) versus only individual specialty clinics is unclear. Using institutional Pancreatic Cancer Registry, we identified patients with localized PDAC from 2019- 2022 who eventually underwent resection. It was our standard practice for borderline resectable (BRPC) patients to undergo ≤4 months of neoadjuvant chemotherapy, ± radiation, followed by exploration, while locally advanced (LAPC) patients were treated with 4-6 months of chemotherapy, followed by radiation and potential exploration. Descriptive and multivariable analyses (MVA) were performed to examine the association between clinic type (PMDC vs individual specialty clinics i.e. surgical oncology, medical oncology, or radiation oncology) and study outcomes. A total of 416 patients met inclusion criteria. Of these, 267 (64.2%) had PMDC visits. PMDC group received radiation therapy more commonly (53.9% versus 27.5%, p=0.001), as compared to individual specialty clinic group. Completion of neoadjuvant treatment (NAT) was far more frequent in patients seen through PMDC compared to patients seen through individual specialty clinics (69.3% vs 48.9%). On MVA, PMDC group was significantly associated with receipt of NAT per institutional standards (adjusted OR 2.23, 95% CI 1.46-7.07, p=0.006). Moreover, the average treatment effect of PMDC on progression-free survival (PFS) was 4.45 (95CI: 0.87-8.03) months. No significant association between overall survival (OS) and clinic type was observed. Provision of care through PMDC was associated with significantly higher odds of completing NAT per institutional standards as compared to individual specialty clinics, which possibly translated into improved PFS. The development of multidisciplinary clinics for management of pancreatic cancer should be incentivized, and any barriers to such development should be addressed.

Circulating tumor DNA (CtDNA) as clinical applicable biomarker for neoadjuvant chemotherapy vs. surgery in localized pancreatic cancer

Circulating tumor DNA (CtDNA) as clinical applicable biomarker for neoadjuvant chemotherapy vs. surgery in localized pancreatic cancer

Second-line chemotherapy in localized pancreatic cancer: a systematic review and meta-analysis

Second-line chemotherapy in localized pancreatic cancer: a systematic review and meta-analysis

Incidence of gastrointestinal bleeding following neoadjuvant chemotherapy and chemoradiation for localized pancreatic cancer

Incidence of gastrointestinal bleeding following neoadjuvant chemotherapy and chemoradiation for localized pancreatic cancer

Preoperative chemotherapy, radiotherapy and surgical decision-making in patients with borderline resectable and locally advanced pancreatic cancer.

Surgical resection combined with systemic chemotherapy is the cornerstone of treatment for patients with localized pancreatic cancer. Upfront surgery is considered suboptimal in cases with extensive vascular involvement, which can be classified as either borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In these patients, FOLFIRINOX or gemcitabine plus nab-paclitaxel chemotherapy is currently used as preoperative chemotherapy and is eventually combined with radiotherapy. Thus, more patients might reach 5-year overall survival. Patient selection for chemotherapy, radiotherapy and subsequent surgery is based on anatomical, biological and conditional parameters. Current guidelines and clinical practices vary considerably regarding preoperative chemotherapy and radiotherapy, response evaluation, and indications for surgery. In this Review, we provide an overview of the clinical evidence regarding disease staging, preoperative therapy, response evaluation and surgery in patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In addition, a clinical work-up is proposed based on the available evidence and guidelines. We identify knowledge gaps and outline a proposed research agenda.

Personalized treatment in localized pancreatic cancer

SummaryThe treatment elements used for pancreatic ductal adenocarcinoma (PDAC) include surgical resection, systemic cytotoxic agents, and targeted drugs. For second- and third-line therapies in PDAC, approximately 15% of patients have actionable mutations although only 2.5% receive matched targeted treatment but with a significant improvement in survival of around 16 months. For the majority of PDAC patients the current most effective strategy is surgical resection of the primary tumor and systemic combination chemotherapy. The chemotherapy regimens and the order of delivery relative to the resection reference point have been based to a large extent on randomized trials using a newly developed empirical staging (Em) system. Although the reductionist TNM based AJCC and UICC systems work well for pathology staging, they are less accurate and less manageable for treatment decision-making. This Em system defines locally resectable (EmR), borderline resectable (EmBR), and unresectable (EmUR) stages, plus the emerging entity of oligometastatic disease (EmOm). For EmR patients, 6 months of adjuvant chemotherapy achieves 5‑year survival rates of 30–50%. In EmBR short-course (2 months) neoadjuvant plus 6‑month adjuvant chemotherapy increases 12-month survival rates to around 77%, compared to 40% for upfront surgery, despite resection rates of 64–85% and 75%, respectively. Longer-course (4 months) neoadjuvant chemotherapy has also been shown to achieve an 18-month overall survival of 67%. In EmUR, induction therapy (3–6 months) may result in resections rates of 20–60% with significantly improved survival rates compared to no resection. For all stages including the polymetastatic (EmPm) setting, patients with good performance status receive combination chemotherapies based on either oxaliplatin (FOLFIRINOX or NALIRIFOX) or gemcitabine (GEM-CAP, or Gem-NabP). Molecular subtypes (Moffitt, Collisson, Bailey, and Cheng-Sen-Yue) are shown to be associated with treatment responses. Transcriptomic signatures have also been developed as classifiers for determining either oxaliplatin- or gemcitabine-based therapies (PurIST, Tiriac, GemPred+, and ESPAC) and are being evaluated in various studies. Most notably the ESPAC transcriptomic signature is being used as the treatment classifier in the experimental arms of the randomized ESPAC6 adjuvant trial in EmR patients and the ESPAC7 induction therapy trial in EmUR patients. Genomic and transcriptomic profiling at baseline and over time is an integral part of ESPAC6/7 to deepen our understanding of tumor plasticity during the course of therapy, identifying the intrinsic (persister cell) and acquired (genetic) tumor plasticity evolving over time and in reaction to different therapies in order to enable a scientific approach to overcoming clonal-resistance clades.

Fragmented care in localized pancreatic cancer: Is commission on cancer accreditation associated with improved overall survival?

BackgroundPrior studies of fragmentation of care in pancreatic cancer have not adjusted for indicators of hospital quality such as Commission on Cancer accreditation. The effect of fragmentation of care has not been well defined. MethodsWe queried the National Cancer Database to identify patients undergoing pancreaticoduodenectomy and distal pancreatectomy with perioperative systemic therapy for clinical stages I–III pancreatic cancer between 2006 and 2019. Patients who received systemic therapy at a center different than the center performing surgery were categorized as having fragmentation of care. Patients having fragmentation of care were further categorized on the basis of whether (fragmentation of care Commission on Cancer) or not (fragmentation of care non-Commission on Cancer) systemic therapy was administered at a facility accredited by the Commission on Cancer. ResultsA total of 11,732 patients met inclusion criteria; 5,668 (48.3%) underwent fragmentation of care, and 3,426 (29.2%) fragmentation of care non-Commission on Cancer. Patients undergoing fragmentation of care non-Commission on Cancer were less likely to receive neoadjuvant systemic therapy than those undergoing fragmentation of care Commission on Cancer or non-fragmented care (27.7% vs 40.1% vs 36.8%, P < .001). On Cox analysis, advanced age, comorbid disease, node-positive disease, and facility type were associated with risk of overall survival. Fragmentation of care was not (adjusted hazard ratio = 0.99, 95% confidence interval [0.94–1.06], P = .8). On Kaplan-Meier analysis, there were no significant differences in 5-year overall survival between treatment cohorts. ConclusionIn patients undergoing fragmentation of care for localized pancreatic cancer, those treated with systemic therapy in Commission on Cancer accredited facilities are more likely to be given neoadjuvant therapy but demonstrate no significant improvement in survival relative to those undergoing non-fragmented care or those undergoing fragmentation of care but receiving systemic therapy in nonaccredited facilities.