Resectable Pancreatic Adenocarcinoma Research Articles

Prognostic significance of preoperative lymphocytes, albumin, and neutrophils (LANR) index in resectable pancreatic ductal adenocarcinoma

PurposeThe index composed of preoperative lymphocytes, albumin, and neutrophils (LANR), a new composite score based on inflammatory response and nutritional status, has been reported to be associated with the prognosis of multiple types of cancer, but the role of LANR in the prognosis of resectable pancreatic ductal adenocarcinoma (PDAC) has not yet been elucidated.Patients and methodsThe data of 142 patients with PDAC who underwent radical resection in the Affiliated Hospital of Jiangnan University from January 2015 to December 2018 were retrospectively analyzed. Receiver Operating Characteristic (ROC) curves were generated to determine the optimal cut-off values for these parameters, as well as the sensitivity and specificity of LANR in predicting survival. The Kaplan–Meier method was used to draw the survival curves. Log rank test was used for univariate analysis, and Cox proportional hazards regression model was used for multivariate analysis. ResultsThe optimal cut-off value of LANR was 18.145, and a low preoperative LANR was significantly correlated with the location of the tumor (p = 0.047). Multivariate analysis showed that tumor differentiation degree (HR:2.357, 95%CI:1.388–4.003,p = 0.002), lymph node metastasis (HR:1.755, 95%CI: 1.115–2.763, p = 0.015), TNM stage (HR:4.686, 95%CI: 2.958–7.425, p < 0.001), preoperative cancer antigen 19 − 9 levels (HR:1.001, 95%CI: 1.000-1.001, p < 0.001) and preoperative LANR (HR:0.221, 95%CI: 0.111–0.441, p < 0.001) were independent risk factors for a poor prognosis in patients undergoing radical resection of PDAC.ConclusionThis study found that preoperative LANR can be used to assess the prognosis of radical resection in patients with PDAC; those with low preoperative LANR had a worse outcome.

Perineural Invasion is an Important Prognostic Factor in Patients With Radically Resected (R0) and Node-negative (pN0) Pancreatic Cancer.

To investigate the association between perineural invasion (PNI) and overall survival (OS) in a nationwide cohort of patients with resected pancreatic ductal adenocarcinoma (PDAC), stratified for margin negative (R0) or positive (R1) resection and absence or presence of lymph node metastasis (pN0 or pN1-N2, respectively). Patients with R0 and pN0 resected PDAC have a relatively favorable prognosis. As PNI is associated with worse OS, this might be a useful factor to provide further prognostic information for patients counselling. A nationwide observational cohort study was performed including all patients who underwent PDAC resection in the Netherlands (2014-2019) with complete information on relevant pathological features (PNI, R status, and N status). OS was assessed using Kaplan-Meier curves, and Cox-proportional hazard analyses were performed to calculate hazard ratio's (HR) with corresponding 95% confidence intervals (CI). In total, 1630 patients were included with a median follow-up of 43 (interquartile range 33-58) months. PNI was independently associated with worse OS in both R0 patients (HR 1.49 [95%CI 1.18-1.88]; P<0.001) and R1 patients (HR 1.39 [95% CI 1.06-1.83]; P=0.02), as well as in pN0 patients (HR 1.75 [95%CI 1.27-2.41]; P<0.001) and pN1-N2 patients (HR 1.35 [95% CI 1.10-1.67]; P<0.01). In 315 patients with R0N0, multivariable analysis showed that PNI was the strongest predictor of OS (HR 2.24 [95% CI 1.52-3.30]; P<0.001). PNI is strongly associated with worse survival in patients with resected PDAC, in particular in patients with relatively favorable pathological features. These findings may aid patient stratification and counselling and help guide treatment strategies.

ENDOSCOPIC ULTRASOUND-GUIDED RADIOFREQUENCY ABLATION FOR PANCREATIC ADENOCARCINOMA

Emerging data suggest neoadjuvant chemotherapy (NAC) for resectable pancreatic ductal adenocarcinoma (PDAC) is associated with improved survival. However, less than 40% demonstrate a meaningful radiographic response to NAC. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as a new modality to treat PDAC. We hypothesize that NAC plus EUS-RFA can be used in the management of resectable PDAC. Prospective review of PDAC patients meeting criteria of resectable tumor anatomy that underwent NAC chemotherapy plus EUS-RFA followed by pancreatic resection. Radiographic imaging, perioperative and short-term outcomes were recorded. Surgical pathology specimens were analyzed for treatment response. Three eligible patients with resectable PDAC received 4 months of NAC plus EUS-RFA. One month after NAC and EUS-RFA completion, all 3 patients underwent standard pancreaticoduodenectomy without complications. After a 6-week recovery, all patients completed 2 months of post-op adjuvant chemotherapy. In our institutional experience, this treatment protocol appears safe as patients tolerated the combination of chemotherapy and ablation. Patients underwent pancreatic resection with uneventful recovery. This novel neoadjuvant approach may provide a more effective alternative to chemotherapy alone.

Safety and Effectiveness of Perioperative Hyperthermic Intraperitoneal Chemotherapy with Gemcitabine in Patients with Resected Pancreatic Ductal Adenocarcinoma: Clinical Trial EudraCT 2016-004298-41.

Despite the improvement in therapies, pancreatic cancer represents one of the most cancer-related deaths. In our hypothesis, we propose that Hyperthermic Intraperitoneal Chemotherapy with gemcitabine after pancreatic cytoreductive surgery could reduce tumor progression by reducing residual neoplastic volume and residual pancreatic cancer stem cells. A randomized trial involving 42 patients. All patients were diagnosed with pancreatic ductal adenocarcinoma. Group I: R0 resection. Group II. R0 resection and HIPEC with gemcitabine (120 mg/m2 for 30 min). Effectiveness was measured with analysis of overall survival, disease-free survival, distant recurrence, locoregional recurrence, and measuring of pancreatic cancer stem cells (EpCAM+CXCR4+CD133+). From 2017 to 2023, 63 patients were recruited for our clinical trial; 21 patients were included in each group, and 21 were excluded. Locoregional recurrence, p-value: 0.022, was lower in the experimental group. There were no significant differences between the two groups in hospital mortality, perioperative complications, or hospital costs. We found a significant decrease in pancreatic cancer stem cells in patients in the experimental group after treatment, p -value of 0.018. The use of HIPEC with gemcitabine after surgery in patients with resectable pancreatic ductal adenocarcinoma reduces locoregional recurrence and may be associated with a significant decrease in pancreatic cancer stem cells.

Neoadjuvant Chemotherapy and Radiation Improves Recurrence-free and Overall Survival in Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma.

The objective of this study is to analyze the outcomes of patients with resectable/borderline resectable PDAC who receive total neoadjuvant therapy vs upfront surgery. Patients who were treated at a single institution from 2006 to 2021 were included. The primary outcome was overall survival (OS). Secondary outcomes included disease free survival (DFS), rates of lymph node positivity, and R0 resection. All survival analyses were performed with intention-to-treat. 26 patients received neoadjuvant chemotherapy and radiation (TNT), 28 received neoadjuvant chemotherapy only (NAC), and 168 received upfront surgery. Demographics were comparable across all three groups. Patients who received TNT or NAC had longer OS and DFS compared to the surgery first patients (P < .01). Patients who received TNT had a lymph node positivity rate of 0% at time of surgery compared to 5.3% and 13.3% in the NAC and surgery-first groups, respectively (P < .01). The rate of R0 resection did not differ between groups (P = .17). Patients with resectable/borderline resectable PDAC who receive neoadjuvant therapy have longer OS and RFS relative to those who receive upfront surgery.

The Oncological Stress Test of Neoadjuvant Therapy: A Systematic Review in Outcomes of Neoadjuvant Therapy Compared to Upfront Resection Approach for Borderline Resectable Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma, increasingly diagnosed in the United States, has a disheartening initial resection rate of 15%. Neoadjuvant therapy, particularly FOLFIRINOX and gemcitabine-based regimens, is gaining favor for its potential to improve resectability rates and achieving microscopically negative margins (R0) in borderline resectable cases, marked by intricate arterial or venous involvement. Despite surgery being the sole curative approach, actual benefit of neoadjuvant therapy remains debatable. This study scrutinizes current literature on oncological outcomes post-resection of borderline resectable pancreatic cancer. A MEDLINE/PubMed search was conducted to systematically compare oncological outcomes of patients treated with either neoadjuvant therapy with intent of curative resection or an "upfront resection" approach. A total of 1293 studies were initially screened and 30 were included (n = 1714) in this analysis. All studies included data on outcomes of patients with borderline resectable pancreatic adenocarcinoma being treated with neoadjuvant therapy (n = 1387) or a resection-first approach (n = 356). Patients treated with neoadjuvant therapy underwent resection 52% of the time, achieving negative margins of 43% (n = 601). Approximately 77% of patients who received an upfront resection underwent a successful resection, with 39% achieving negative margins. Neoadjuvant therapy remains marginally efficacious in treatment of borderline resectable pancreatic adenocarcinoma, as patients undergo an operation and successful resection less often when treated with neoadjuvant therapy. Rates of curative resection are comparable, despite neoadjuvant therapy being a primary recommendation in borderline resectable cases and employed more often than upfront resection. Upfront resection may offer improved resection rates by intention-to-treat, which can provide more patients with paths to curative resection.

Adjuvant chemotherapy for adenocarcinoma arising from intraductal papillary mucinous neoplasia: multicentre ADENO-IPMN study.

The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival. This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching. Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes. Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.

Treatment strategies for borderline resectable pancreatic neuroendocrine tumors: a narrative review.

Well-differentiated pancreatic neuroendocrine tumors (pNETs) are a group of rare, heterogeneous tumors that originate in the endocrine tissue of the pancreas and account for 1-2% of all pancreatic neoplasms. The majority of pNETs are non-functional and typically follow a more indolent course. Especially at early stages, the primary management of pNETs is surgical resection which is associated with relatively low rates of recurrence and excellent long-term prognosis. On the other hand, some patients will present with locally advanced primary tumors or low volume metastatic disease in which complete surgical resection may be more difficult to achieve and recurrence rates are significant. Unlike treatment of borderline resectable (BR) pancreatic adenocarcinoma, in which neoadjuvant treatment strategies are becoming standardized, borderline resectability is not a currently established terminology for pNETs and the optimal multidisciplinary treatment approach is poorly understood. We performed a literature search on PubMed, Google Scholar, and ClinicalTrials.gov using keywords, including 'pancreatic neuroendocrine tumor' and 'borderline resectable'. All studies and review articles in English with full text were considered. Each publication was independently reviewed. We introduce the concept of BR-pNETs, focusing on important criteria that should be included in their definition by balancing the feasibility of resection and the clinical utility of surgery. We suggest that extended resection, involving vascular reconstruction, adjacent organ resection, and/or liver metastasis, should be considered at experienced, high volume centers. Furthermore, we outline multidisciplinary treatment strategies, including systemic and locoregional treatment options, for optimizing outcomes for this growing patient population. Formalizing the definition of resectability in pNETs through multidisciplinary collaborative research will be important for standardizing the indications for multimodality treatment and aggressive surgical approaches for patients.

Comparison of prognosis and postoperative morbidities between standard pancreaticoduodenectomy and the TRIANGLE technique for resectable pancreatic ductal adenocarcinoma.

Radical surgery combined with systemic chemotherapy offers the possibility of long-term survival or even cure for patients with pancreatic ductal adenocarcinoma (PDAC), although tumor recurrence, especially locally, still inhibits the treatment efficacy. The TRIANGLE technique was introduced as an extended dissection procedure to improve the R0 resection rate of borderline resectable or locally advanced PDAC. However, there was a lack of studies concerning postoperative complications and long-term outcomes of this procedure on patients with resectable PDAC. To compare the prognosis and postoperative morbidities between standard pancreaticoduodenectomy (PD) and the TRIANGLE technique for resectable PDAC. Patients with resectable PDAC eligible for PD from our hospital between June 2018 and December 2021 were enrolled in this retrospective cohort study. All the patients were divided into PDstandard and PDTRIANGLE groups according to the surgical procedure. Baseline characteristics, surgical data, and postoperative morbidities were recorded. All of the patients were followed up, and the date and location of tumor recurrence, and death were recorded. The Kaplan-Meier method and log-rank test were used for the survival analysis. There were 93 patients included in the study and 37 underwent the TRIANGLE technique. Duration of operation was longer in the PDTRIANGLE group compared with the PDstandard group [440 (410-480) min vs 320 (265-427) min] (P = 0.001). Intraoperative blood loss [700 (500-1200) mL vs 500 (300-800) mL] (P = 0.009) and blood transfusion [975 (0-1250) mL vs 400 (0-800) mL] (P = 0.009) were higher in the PDTRIANGLE group. There was a higher incidence of surgical site infection (43.2% vs 12.5%) (P = 0.001) and postoperative diarrhea (54.1% vs 12.5%) (P = 0.001) in the PDTRIANGLE group. The rates of R0 resection and local recurrence, overall survival, and disease-free survival did not differ significantly between the two groups. The TRIANGLE technique is safe, with acceptable postoperative morbidities compared with standardized PD, but it does not improve prognosis for patients with resectable PDAC.

Abstract 3181: Immune modulatory activity of radio-sensitizing gold nanoparticle

Abstract Radiation therapy (RT) is frequently used in the neoadjuvant setting in borderline resectable and some resectable pancreatic ductal adenocarcinoma (PDAC) and in the definitive setting in locally advanced PDACs which is third leading cause of cancer associated death. Higher doses of RT improve overall treatment outcomes but increasing the dose significantly above 50Gy in standard 2Gy fractions risks profound gastrointestinal (GI) toxicity. Additionally, genotoxic stress such as RT, can induce CXCL12 secretion by cancer associated fibroblast (CAFs) and overexpression of CXC motif chemokine receptor 4 (CXCR4) in cancer cells. CXCL12-CXCR4 downstream signaling results in immune suppression and consequent enhanced tumor growth and metastasis and poor prognosis in PDAC. To overcome these clinical challenges, we have developed multimodal gold nanoparticle constructs (GNPs) by functionalizing the CXCR4 antagonists to (i) bind to CXCR4 and mediate GNP internalization, (ii) abolish the feedback immune inhibitory signals mediated by CXCR4 overexpression, and (iii) enhance therapeutic benefit of radiation. To achieve these multimodal activities, we have covalently attached the CXCR4 antagonist, AMD070, to thiol-terminated polyethylene glycol (PEG) to synthesize AMD-PEG which was then conjugated with GNPs to produce AMD-PEG-GNP. In our experiment AMD-PEG-GNP has successfully inhibited CXCL12-CXCR4 downstream signalling such as reduction of ERK phosphorylation in PDAC cells. To analyze the radiosensitization role of GNP nanoconjugates, PDAC cells were incubated with AMD-PEG, PEG-GNP and AMD-PEG-GNPs for 4 hours and then treated with increasing doses of radiated, from 1-4Gy. AMD-PEG-GNP demonstrated a systematic enhancement on reactive oxygen species (ROS) production and downregulation of a colony formation. Collectively, the results from in vitro study with PDAC cells confirm that the nanoconjugate with AMD070 enhances radio-cytotoxicity and impair CXCL12-CXCR4 downstream signaling. Hence AMD-PEG-GNP has strong merit to enhance radiation dose locally and simultaneously restrict RT induced immunosuppression in PDAC. Citation Format: Tanmay Kulkarni, Shamit Dutta, Hazel Parent, Karington Perry, Yuri Mackeyev, Santanu Bhattacharya. Immune modulatory activity of radio-sensitizing gold nanoparticle [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 3181.

O79: Adjuvant chemotherapy following surgery for adenocarcinoma arising from intraductal papillary mucinous neoplasia and impact on recurrence and survival: ADENO-IPMN study

Abstract Background The clinical impact of giving adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia (IPMN) is unclear. The present study aims to identify factors related to receipt of adjuvant chemotherapy, the type and its impact on recurrence, site specific recurrence and survival in a large international cohort of patients. Method Patients undergoing pancreatic resection for adenocarcinoma arising from IPMN between 2010-2020 at 18 pancreatic centres were identified. Propensity score matching (PSM) and survival analyses were performed to identify the impact of adjuvant chemotherapy on recurrence and survival. Results A total of 459 patients underwent pancreatic resection and 275 patients (59.9%) received adjuvant chemotherapy (Gemcitabine,51.3%; Gemcitabine-capecitabine,21.8%; Folfirinox,8.0%; and other,18.9%). In multivariate analysis, poor differentiation (30.2%vs.19.0%; p=0.007) was associated with adjuvant chemotherapy use. Adjuvant chemotherapy was not associated with all, locoregional, systemic or site-specific recurrence compared to no adjuvant chemotherapy on Kaplan-Meier analysis (median time to recurrence 26 versus 50 months; p=0.14), multivariate analysis (HR 0.79, p=0.175), and on propensity score matching (HR 0.76, p=0.111). No particular subgroup had lower rates of recurrence with adjuvant chemotherapy. No particular chemotherapy regime resulted in lower recurrence rates or longer survival. The overall or disease-free survival rates were not significantly different in multivariate analysis. Conclusion Based on the contemporary data, adjuvant chemotherapy after pancreatic resection for adenocarcinoma arising from IPMN does not appear to impact on recurrence rates, recurrence patterns and long term survival. However, data on the most potent chemotherapy (Folfirinox) is limited and warrants further studies

Limited Role of the Apparent Diffusion Coefficient (ADC) for Tumor Grade and Overall Survival in Resectable Pancreatic Ductal Adenocarcinoma.

This study evaluated the relationship between apparent diffusion coefficient (ADC) values in pancreatic ductal adenocarcinoma (PDAC) and tumor grades based on WHO, Adsay, and Kalimuthu classifications, using whole-mount pancreatectomy specimens. If glandular formation plays a key role in the degree of diffusion restriction, diffusion-weighted imaging could facilitate non-invasive grading of PDAC. A freehand region of interest (ROI) was drawn along tumor borders on the preoperative ADC map in each tumor-containing slice. Resection specimens were retrospectively graded according to WHO, Adsay, and Kalimuthu classifications and correlated with overall survival and the 10th percentile of whole-volume ADC values. Findings from 40 patients (23 male, median age 67) showed no correlation between ADC p10 values and WHO differentiation (p = 0.050), Adsay grade (p = 0.955), or Kalimuthu patterns (p = 0.117). There was no association between ADC p10 and overall survival (p = 0.082) and other clinicopathological variables. Survival was significantly lower for poor tumor differentiation (p = 0.046) and non-glandular Kalimuthu patterns (p = 0.016) and there was a trend towards inferior survival for Adsay G3 (p = 0.090) after correction for age, tumor location, and stage. Preoperative ADC measurements for determining PDAC aggressiveness had limited clinical utility, as there was no correlation with histological parameters or overall survival in resectable PDAC.

Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial

Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial

Radiation Therapy Quality Assurance Analysis of Alliance A021501: Preoperative mFOLFIRINOX or mFOLFIRINOX Plus Hypofractionated Radiation Therapy for Borderline Resectable Adenocarcinoma of the Pancreas

BackgroundAlliance A021501 is the first randomized trial to evaluate stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemotherapy. In this post hoc study, we reviewed the quality of radiation therapy (RT) delivered. MethodsSBRT (6.6 Gy x 5) was intended, although hypofractionated RT (5 Gy x 5) (HIGRT) was permitted if SBRT specifications could not be met. Institutional credentialing through the National Cancer Institute-funded Imaging and Radiation Oncology Core (IROC) was required. Rigorous RT quality assurance (RT QA) was mandated, including pretreatment review by a radiation oncologist. Revisions were required for unacceptable deviations. Additionally, we performed a post hoc RT QA analysis in which contours and plans were reviewed by 3 radiation oncologists and assigned a score (1, 2, 3) based on adequacy. A score of 1 indicated no deviation, a 2 indicated minor deviation, and a 3 indicated a major deviation that could be clinically significant. Clinical outcomes were compared by treatment modality and by case score. ResultsForty patients were registered to receive RT (1 planned but not treated) at 27 centers (18 academic, 9 community). Twenty-three centers were appropriately credentialed for moving lung/liver targets, while 4 were approved for static head and neck only. Thirty-two of 39 patients (82.1%) were treated with SBRT, and 7 (17.9%) with HIGRT. Five cases (13%) required revision prior to treatment. On post hoc review, 23 patients (59.0%) were noted to have suboptimal contours or plan coverage, 12 (30.8%) were scored a 2 and 11 cases (28.2%) were scored a 3. There were no apparent differences in failure patterns or surgical outcomes based on treatment technique or post hoc case score. Details related to on-treatment imaging were not recorded. ConclusionDespite rigorous QA, we encountered variability in simulation, contouring, plan coverage, and dose on trial. While clinical outcomes did not appear to be impacted, findings from this analysis serve to inform subsequent PDAC SBRT trial designs and QA requirements.

Examining neoadjuvant treatment candidates in resectable pancreatic cancer based on tumor-vessel interactions and CA 19-9 levels: a retrospective cohort study.

The applicability of neoadjuvant treatment (NAT) for resectable pancreatic ductal adenocarcinoma (PDAC) has arisen, however, high-level evidence is lacking. This study aimed to explore patient subgroups with high-risk resectable PDAC for selecting candidates who may benefit from NAT. The 1132 patients with resectable or borderline resectable PDAC who underwent surgery between 2007 and 2021 were retrospectively reviewed. Patients with resectable PDAC without contact of major vessels (R-no contact) ( n =651), with contact of portal vein or superior mesenteric vein (PV/SMV) ≤180° (R-contact) ( n =306), and borderline resectable PDAC without arterial involvement (BR-V) ( n =175) were analyzed. The mean age was 64.3±9.8 years, and 647 patients (57.2%) were male. The median follow-up was 26 months in the entire cohort. Patients with resectable PDAC without vascular contact had the most improved overall survival (OS) (median; 31.5 months). OS did not significantly differ between NAT and upfront surgery in the entire resectable PDAC cohort. However, in R-contact group, NAT showed significantly improved OS compared to upfront surgery (33 vs. 23 months). Neoadjuvant FOLFIRINOX was showed a better OS than gemcitabine-based regimens in patients who underwent NAT (34 vs. 24 months). NAT was associated with a better survival in the patients with CA 19-9 level ≥150U/ml, only when the tumor has PV/SMV contact in resectable disease (40 vs. 19 months, P =0.001). NAT can be considered as an effective treatment in patients with resectable PDAC, particularly when the tumor is in contact with PV/SMV and CA 19-9 ≥150U/ml.

Tumor location, clinicopathological features, and perioperative and prognostic outcomes in patients who underwent pancreatic resection following neoadjuvant chemoradiotherapy for resectable pancreatic cancer: A retrospective study

Background/Objective: Preoperative treatment of resectable pancreatic ductal adenocarcinoma (PDAC) is gaining popularity worldwide. However, the characteristics of tumors located in the pancreatic head (Ph), or those in the body or tail (Pbt), after surgery following neoadjuvant chemoradiotherapy (NACRT) remain unclear. This study aimed to evaluate and compare the clinicopathological features, perioperative outcomes, and prognosis of patients with resectable PDAC who underwent NACRT followed by curative pancreatic resection, focusing on distinguishing between Ph and Pbt PDACs. MethodsWe included 107 patients with resectable PDAC who underwent curative resection following NACRT between 2009 and 2023. Clinicopathological features, perioperative and prognostic outcomes, recurrence patterns, and prognoses were compared between Ph and Pbt PDAC groups. ResultsTumors were found in the Ph and Pbt in 64 and 43 patients, respectively. Albumin levels and lymphocyte-to-monocyte ratios after NACRT were significantly lower in the Ph group than in the Pbt group. The Pbt group showed significantly higher rates of positive peritoneal lavage cytology and serosal, arterial, and portal vein invasion than the Ph group did. Overall and recurrence-free survival were similar between the two groups. The most common site of initial postoperative recurrence was the lung only in both groups; however, the rate of peritoneal dissemination only was significantly higher in the Pbt group than in the Ph group. ConclusionsThe prognoses based on tumor locations in the Ph and Pbt after surgery following NACRT are similar. Following the resection of resectable Pbt PDAC, the possibility of peritoneal dissemination recurrence should be considered.

Prolonged length of stay and omission of adjuvant therapy are associated with early mortality after pancreatic adenocarcinoma resection

BackgroundSurgical resection is the preferred treatment for non-metastatic pancreatic adenocarcinoma, but post-resection survival is highly variable. We use the National Cancer Database Participant Use Files to investigate risk factors associated with early mortality (survival less than one year) after pancreatic adenocarcinoma resection. Methods51,345 cases of pancreatic adenocarcinoma were identified. 16,234 had survival between three months and one year (early mortality), and 35,111 had survival greater than one year. Descriptive analyses and multivariate Cox regression models were performed to identify demographic, perioperative, and tumor biology factors associated with early mortality. A sub-analysis subsequently explored the relationship between the length of stay and chemotherapy utilization. ResultsOf the 51,345 cases of pancreatic adenocarcinoma, 16,234 had early mortality. In multivariate models adjusted for demographic, socioeconomic, facility type, tumor characteristics, and hospital risk factors, patients with early mortality also had longer lengths of stay, more unplanned readmissions. They were more likely to receive treatment at non-academic centers. Adjuvant chemotherapy utilization was lower in patients with early mortality, particularly in those with longer lengths of stay. ConclusionReducing the length of stay, decreasing variability across different forms of health insurance, and increasing access to treatment at academic centers may reduce early mortality. Adjuvant chemotherapy is associated with a reduced risk of early mortality but is highly underutilized, especially in patients with prolonged hospital stays. Given that delays in receiving adjuvant chemotherapy were associated with an increased risk of early mortality, interventions to decrease perioperative complications to ensure timely access to adjuvant chemotherapy may improve survival.

The Molecular Twin artificial-intelligence platform integrates multi-omic data to predict outcomes for pancreatic adenocarcinoma patients.

Contemporary analyses focused on a limited number of clinical and molecular biomarkers have been unable to accurately predict clinical outcomes in pancreatic ductal adenocarcinoma. Here we describe a precision medicine platform known as the Molecular Twin consisting of advanced machine-learning models and use it to analyze a dataset of 6,363 clinical and multi-omic molecular features from patients with resected pancreatic ductal adenocarcinoma to accurately predict disease survival (DS). We show that a full multi-omic model predicts DS with the highest accuracy and that plasma protein is the top single-omic predictor of DS. A parsimonious model learning only 589 multi-omic features demonstrated similar predictive performance as the full multi-omic model. Our platform enables discovery of parsimonious biomarker panels and performance assessment of outcome prediction models learning from resource-intensive panels. This approach has considerable potential to impact clinical care and democratize precision cancer medicine worldwide.

FOLFIRINOX plus high intensity focused ultrasound for locally advanced/borderline resectable pancreatic ductal adenocarcinoma: A prospective single arm phase II trial.

670 Background: FOLFIRINOX has been the standard regimen for locally advanced pancreatic cancer (LAPC) for palliation and borderline resectable pancreatic cancer (BRPC) for neoadjuvant treatment. According to the results of animal studies, concurrent use of high intensity focused ultrasound (HIFU) and chemotherapy can enhance the drug delivery to the target tissue. In this phase II trial, we aimed to evaluate the safety and therapeutic efficacy of FOLFIRINOX plus HIFU for patients with LAPC or BRPC. Methods: This study was designed as a prospective single center phase II trial (Study identifier: NCT05262452). We prospectively enrolled 60 patients (M:F=35:25; median age, 67.0 years old) with LAPC (n=23) or BRPC (n=37). The median tumor size was 4.0 cm (Interquartile range, 2.7-4.6). All patients were treated by FOLFIRINOX (oxaliplatin, 85mg/m2 of body-surface area; irinotecan, 180mg/m2; leucovorin, 400 mg/m2; and fluorouracil, 400 mg/m2 given as a bolus followed by 2400 mg/m2 given as a 46-hour continuous infusion) every 2 weeks until disease progression. HIFU was combined in the first 4 cycles of chemotherapy with following parameters: intensity of 2.0 kw/cm2, duty cycle of 1%, exposure time of 3 seconds and PRF of 10Hz. Follow-up contrast enhanced CT was taken every 4 cycles for the response evaluation using response evaluation criteria for solid tumor 1.1. Overall survival (OS) and progression-free survival were estimated using Kaplan-Meier method. All analyses were intention-to-treat. Results: Two patients withdrew the consent, and two patients could not complete planned 4 cycles of FOLFIRINOX plus HIFU treatment owing to sepsis from severe neutropenia related to chemotherapy. Among 56 patients who completed the 4 cycle of FOLFIRINOX plus HIFU and continued chemotherapy, partial response was achieved in 36 patients (60.0%, 36/60), and stable disease in 20 patients. Regarding the adverse effect (AE), 32 of 60 patients experienced grade 3 (n=22) or grade 4 (n=10) AE, all of them were related to FOLFIRINOX chemotherapy. No AE related to HIFU was observed. The estimated OS was 94.8%, 75.9% and 67.6% at 6-, 12- and 18 months, respectively. Regarding the PFS, the 6-, 12- and 18-month PFS was 91.9%, 70.3% and 56.2%, respectively. Conclusions: FOLFIRINOX plus HIFU was safe and effective treatment for LAPC/BRPC, providing 60.0% of partial response rate without any additional AE to chemotherapy. Clinical trial information: NCT05262452 .

Postoperative complications following neoadjuvant therapy and surgery in a phase 2 borderline resectable pancreatic cancer clinical trial (Alliance A021501).

664 Background: Postoperative complications in patients with borderline resectable pancreatic cancer treated with neoadjuvant therapy and pancreatectomy in the national cooperative group setting have not been previously characterized. Further, the impact of preoperative hypofractionated radiotherapy on postoperative outcomes is largely unknown. We sought to quantify perioperative morbidity among patients with pancreatic cancer who received neoadjuvant modified FOLFIRINOX chemotherapy with or without hypofractionated radiotherapy on a multicenter clinical trial. Methods: The A021501 phase 2 trial randomized patients with borderline resectable pancreatic ductal adenocarcinoma to 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX then hypofractionated radiotherapy (Arm 2), followed by pancreatectomy (Dec 31, 2016-Jan 1, 2019). Patients underwent resection according to defined operative standards at enrolling centers without specific requirements for either surgeon or hospital volume. Surgical complications and adverse events were assessed and captured at a single time point of 90 days after surgery and compared between treatment arms. Results: Of 126 enrolled patients, 51 (40%) underwent pancreatectomy (n=32, Arm 1; n=19, Arm 2) at 28 institutions. Vascular resection was performed in 19 patients (37%). One patient in Arm 2 died within 90 days after surgery. Rates of any surgical complication were 19% (n=6) in Arm 1 and 42% (n=8) in Arm 2 (p=0.07). Median length of stay was 7 days (range 5-38 days). Five (10%) patients required reoperation within 90 days. Readmission rates were higher in Arm 2 than Arm 1 (16% vs. 42%, p=0.04) but there were no differences in rates of reoperation, pancreatic fistula or abscess requiring drainage, or wound infection between study arms. 54% of patients (n=26/48) experienced a grade 3 or higher adverse event, with no difference between treatment arms (47% versus 67%, p=0.7). Rates of initiation of adjuvant therapy did not differ between treatment arms (66% vs. 68%, p=0.4). Pancreatic fistula and abscess were associated with adjuvant therapy (p&lt;0.01). No difference in overall survival was observed based on occurrence of surgical complications (HR 1.1; 95% CI 0.5-2.6). Conclusions: In this national cooperative group study of patients with borderline resectable pancreatic cancer,postoperative complications following neoadjuvant chemotherapy, radiation, and surgical resection were consistent with rates previously reported by high-volume institutions and using large datasets. Multimodality trials of preoperative therapy for locoregionally advanced pancreatic cancer may be safely performed in the cooperative group setting. Clinical trial information: NCT02839343 .