Resectable Pancreatic Cancer Research Articles

Single-incision plus one port laparoscopic pancreaticoduodenectomy with major venous resection and reconstruction for pancreatic cancer with video recordings

Laparoscopic pancreaticoduodenectomy (LPD) with superior mesenteric/portal vein (SMV/PV) resection and reconstruction was the most technically challenging procedure and had been rarely reported. However, single-incision plus one-port LPD (SILPD +1) with SMV/PV resection and reconstruction has never been reported. In this study, we will demonstrate the feasibility, safety, key surgical procedure, and long-term outcomes for SILPD +1 with SMV/PV resection and reconstruction using video evidence. Two cases of SILPD +1 with SMV/PV wedge resection were carried out by the authors. There was no tumor recurrence during the one-year follow-up. It is worth noting that skilled laparoscopic technicians are necessary to safely complete the procedure with good short-term and long-term outcomes.

Durvalumab and stereotactic ablative body radiotherapy (SABR) in locally advanced (LA) and borderline resectable (BR) pancreatic cancer (PDAC): Long-term outcomes and correlative insights.

4174 Background: Immune checkpoint blockade (ICB) has limited activity in genomically unselected patients (pts) with PDAC. While anti-tumor activity with combination SABR/ICB has been shown, biomarkers of response are poorly defined. We conducted a phase 1/2 study of PD-L1 inhibitor Durvalumab (D) and SABR after induction chemotherapy in LA and BR PDAC (NCT03245541). We report long-term outcomes and correlative biospecimen analyses. Methods: A multi-institutional, single arm phase 1/2 trial was conducted at Cedars-Sinai and Memorial Sloan Kettering. Initial clinical data reported by Tuli et al, ASCO 2023. Pre-treatment tissue assessed for p40 and GATA3 to determine classical vs basal subtype by immunohistochemistry. Tissue interrogated by immunofluorescence for PD-L1 expression and infiltration of immune cell subsets. Multiparametric immunophenotyping of peripheral blood mononuclear cells (PBMCs) by flow cytometry conducted on baseline and on treatment samples. Wilcoxon rank sum test used to determine difference in biomarkers from each timepoint; p-value <0.05 significant. Results: N= 36 enrolled from 08/2017-05/2022; N=31(86%) LA, N=5 (14%) BR. N= 9 (25%) underwent resection; all R0. At median follow up 36.5 months, 6- and 12-month PFS 69%, 36%. Median PFS 8.7m (95% CI 6.1-14), median OS 16m (95% CI 13-26). N=2 (6%) alive without disease progression. Correlative analyses summarized (table). Key findings; Classical/basal subtyping feasible on N=9 (8 classical, 1 basal). Median PD-L1 score not associated with survival. Peri-tumoral, but not intratumoral CD8+ cells associated with PFS >6 months. Flow cytometry feasible for 70 samples from N=35. Frequency of pre-treatment non-naïve CD4+ FoxP3+ Treg associated with PFS >12. CD103+ CD8+ T Cells significantly expanded on treatment only in patients with PFS>12m (p=0.038) and were significantly enriched relative to PFS<12m on treatment. Conclusions: A proportion of pts with LA PDAC achieve durable control with D and SABR after induction chemotherapy. Baseline peri-tumoral CD8+ cells and peripheral CD103+ CD8 T cells and CD4+ Treg in PBMCs at baseline and on treatment may predict for benefit. Further analyses ongoing and validation in larger cohorts is warranted. Clinical trial information: NCT03245541 . [Table: see text]

Neoadjuvant fractionated versus hypofractionated chemoradiotherapy in resectable and borderline resectable pancreatic cancer.

Neoadjuvant fractionated versus hypofractionated chemoradiotherapy in resectable and borderline resectable pancreatic cancer.

Recurrence patterns and surveillance strategies in long-term survivors of resected pancreatic cancer.

e16361 Background: Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related mortality in the United States. After resection, the 2-year disease-free survival is < 50%. Surveillance guidelines after resection vary significantly between expert groups. The level of evidence is particularly weak for patients who are alive and disease-free after 2 years. Our objective was to report rates and predictors of recurrence in this population. Methods: We reviewed all patients who underwent resection of stage I-III PDA at Columbia University Irving Medical Center from 2011-2022. Eligibility criteria included patients who were alive and disease-free at 2 years after diagnosis. Demographic, surgical, and treatment characteristics were recorded. Imaging studies and tumor markers were reviewed and median time between studies after 2 years of follow up was determined. Recurrence was confirmed histologically or radiologically. Follow up and survival times were calculated using Kaplan Meier statistics. Associations between patient characteristics and recurrence risk were evaluated using a Cox proportional-hazards regression adjusted for demographic and treatment characteristics. Results: We reviewed 743 patients and 225 met eligibility criteria. The median age at diagnosis was 67.5 years. Median interval between surveillance imaging was 59 days and median interval between CA 19-9 draws was 41 days. After a median follow-up of 5.2 years from diagnosis, 84/225 (37%) patients experienced a late recurrence. Of these, 35% (29/84) had local recurrence, and 65% (55/84) had distant recurrence. The most common distant sites were lung (51%) and liver (27%). Lymph node positivity at resection was associated with late recurrence risk (p = 6x10-6), but T-stage (p = 0.5), margins (p = 0.9), age (p = 0.2) and chemotherapy receipt (p = 0.3) were not. Of the 72 patients with CA 19-9-producing tumors (baseline CA 19-9 > 37 U/mL) and complete normalization of CA 19-9 postoperatively, 30 patients had recurrence with CA 19-9 checked in the 9 months preceding recurrence. CA 19-9 re-elevation preceded recurrence in 83% (25/30) of late recurrences. Median time from CA 19-9 elevation to confirmation of recurrence was 5 months. Conclusions: The rate of recurrence for patients with PDA who are disease-free 2 years after diagnosis is lower than that for patients in their first 2 years. The most common sites of late recurrence are local and lung. For long-term PDA survivors with CA 19-9 producing tumors, serial CA 19-9 monitoring may be used to guide imaging. Positive lymph nodes at resection identify patients who are at highest risk for late recurrence.

Tislelizumab combined with gemcitabine and albumin paclitaxel as preoperative therapy for patients with borderline resectable pancreatic cancer: A prospective, single-arm, phase II trial.

4162 Background: Pancreatic cancer is a highly aggressive disease with low resection rate and poor prognosis. Neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC) is increasing in acceptability, but no standard treatment has been established. Herein, we aimed to assess the safety and efficacy of a new mode of preoperative therapy for patients with BRPC. Methods: This is a single arm, exploratory phase II clinical trial. Gemcitabine (1000 mg/m2) and albumin paclitaxel (125 mg/m2; AG) were administered to patients with BRPC on days 1 and 8, along with tislelizumab (200 mg) on day 1 intravenously (IV) every three weeks. Surgical intervention was assessed after two cycles of treatment. Primary endpoint was adverse events (AE) and R0 resection rate. Secondary endpoints were objective response rate (ORR) and progression free survival (PFS) by mRECIST, relapse-free survival (RFS) and overall survival (OS). Results: Between October 2022 and December 2023, 21 patients were enrolled in the study. At the end of the last follow-up (January 27, 2024), 15 patients had a best response of partial response, the ORR was 71.4% according to mRECIST. The disease control rate (DCR) was 85.7%. The 12-months PFS rate, and 12-months OS rate were 68.2% (95% CI: 38.0%–86.0%), and 63.8% (95% CI: 33.2%–88.3%), respectively. After the two cycles of neoadjuvant therapy, 14 patients underwent resection (66.7%,14/21) and the R0 resection rate was 100%. For those patients who did not undergo surgery, 3 of them achieved PR but refused surgery, 3 patients developed disease progression and lost the chance of surgery. 1 patient died of severe pneumonia caused by H1N1 infection. So far the safety of neoadjuvant treatment was satisfied, no grade 4 or above treatment-related-adverse events (TRAEs) were observed. Grade 3 TRAEs were reported in 3(14.29%) patients. Frequently occurring adverse events were grade 1-2, including myelosuppression (90.47%), albuminuria (80.95%), nausea (61.90%), elevated aspartate aminotransferase (47.62%) and elevated alanine aminotransferase (38.10%). Grade 3 or higher adverse events were pneumonia (4.76%), elevated AST (4.76%), elevated ALT (4.76%) and myelosuppression (4.76%). Conclusions: Anti-PD-1 inhibitor tislelizumab plus AG chemotherapy displayed promising antitumor activity and acceptable safety profile for patients with BRPC. Clinical trial information: ChiCTR2200063680.

A phase I/II open-label clinical trial of CPI-613 in combination with modified FOLFIRINOX in patients with locally advanced (LAPC) or borderline resectable pancreatic cancer (BRPC).

4172 Background: Pancreatic ductal adenocarcinoma (PDA) carries a poor prognosis with a 5-year relative survival rate of 13%. Surgical resection is the only curative treatment option, but less than 20% of patients are eligible at diagnosis. A subset of patients with locally advanced disease can become candidates for resection with neoadjuvant (NA) therapy. mFOLFIRINOX is the standard of care in the adjuvant setting, with extrapolated data supporting its use in the NA setting. CPI-613/Devimistat (D) is a small molecule that targets mitochondrial metabolism in tumor cells leading to ROS-mediated apoptosis. A phase III trial of mFOLFIRINOX + D at 500 mg/m2 in metastatic PDA did not meet primary endpoint of overall survival (OS). Here we present the results of the combination’s use at standard and escalated doses in LAPC and BRPC. Methods: In this investigator-initiated, single-center, phase I/II, open-label trial treatment-naïve patients with investigator assessed LAPC or BRPC were treated with mFOLFIRINOX in 14 day cycles + D. In the standard dosing (SD) cohort, patients received D at 500mg/m2 while in the dose escalation (DE) cohort; D at 750 mg/m2 or 1000 mg/m2 was used. Radiographic response was assessed every 8 weeks. Patients who remained unresectable after 12 cycles could receive additional standard treatments, including chemoradiotherapy. The primary endpoint was median overall survival (mOS), with the study powered to show a mOS improvement from the historical standard of 14 months to 28 months with mFOLFIRINOX + D. Secondary endpoints were median progression free survival (mPFS), percent resected, and safety outcomes. NCT03699319 Results: Between Dec 2018 and Mar 2022, 37 patients and 11 patients enrolled in the SD and DE cohorts. Median age 69 years (range 47-78), male/female (27/21), Caucasian (83%), LAPC/BRPC (34/14). One patient (2%) withdrew, 4 patients (8%) discontinued treatment due to toxicity, 9 patients (19%) had progressive disease prior to completion of 12 cycles. In all patients mOS was 16.3 months and mPFS was 10.7 months. By cohort: SD/DE mOS: 16.2/17.6 months (p=0.56). Fourteen patients (29%) had partial response by RECIST 1.1. Twenty patients (41.7%) had resection; mOS 29.7 months. In the SD cohort, 78% and 24% of patients had grade 3 and/or 4 AEs. There were no dose limiting toxicities (DLT) in the DE cohort, and eight patients received the maximum dose of 1000 mg/m2 of D. After the DLT period, 100% patients in DE cohort had grade 3 toxicity and 55% had grade 4 toxicity. For all the most common toxicities (gr3,4) were neutropenia (27%,25%), diarrhea (25%,0), anorexia wt. loss (23%,0), nausea/vomiting (23%,0). Conclusions: The combination of mFOLFIRINOX and D is feasible in the LAPC/BRPC population at increased dose levels of D; however, it did not meet the primary endpoint of doubling OS compared to historical controls. Clinical trial information: NCT03699319 .

PD-1 blockade plus chemotherapy followed by concurrent SBRT with SIB as preoperative therapy for patients with potentially resectable pancreatic cancer: A single-arm phase 2 study.

e16312 Background: Pancreatic cancer has 10% low rate of early diagnosis and resection due to its insidious onset and poor prognosis. We aimed to assess the safety and efficacy of a new mode of preoperative therapy for patients with Potentially Resectable Pancreatic Cancer. Methods: This is a single arm clinical trial (NCT05634564). Gemcitabine (1000 mg/m2) and nabpaclitaxel (125 mg/m2; AG) were administered to patients with LAPC or BRPC on days 1 and 8, along with tislelizumab (200 mg) on day 1 intravenously (IV) every three weeks. Concurrently, the patients underwent stereotactic body radiotherapy (SBRT) with simultaneous integrated boost (SIB)during the third cycle of treatment. Surgical intervention was reassessed after four cycles of treatment. Objective response rate (ORR) was the primary endpoint and Disease control rate (DCR), R0 resection rate, median overall survival (mOS), median progression free survival (mPFS) rate, time to progression (TTP) and safety were analyzed as secondary endpoints. Results: Between May 2020 and April 2023, 62 patients with LAPC or BRPC were enrolled. Until the last follow-up time (January 30, 2024) ,56 of them included in the intention-to-treat (ITT) analysis who completed at least three cycles of tislelizumab plus AG and underwent concurrent radiotherapy. The median age in intention-to-treat analysis was 65 years. 25 patients had a best response of partial response, the ORR was 44.6%, DCR was 100%. Thirty-one patients met the criteria for surgical resection after treatment, 9 of whom refused surgery and continued conservative treatment. 22 patients underwent resection, and the R0 resection rate was 95.45%. Two of the 22 resected patients achieved pathologic complete response (pCR) and five patients achieved major pathological response (MPR). The pathologic complete response rate was 9.10% and significant pathological response rate was 31.82%. The TTP was 19.38 months (95% CI: 12.8%-27.9%), and the mOS was 21.32 months (95% CI:15.9%-NR). The 12-months PFS rate and 12-months OS rate were 59.9% (95% CI:45.2%-71.8%) and 74.4% (95% CI:59.9%-84.3%), respectively. Grade 5 adverse events were not observed. The most common grade 3-4 hematological and non-hematological toxicities were leukopenia (17.9%), neutropenia (16.1%), anemia (8.9%), thrombocytopenia (7.1%), rash: dermatitis (7.1%), Peripheral neuropathy (3.6%). Conclusions: Anti-PD-1 inhibitor tislelizumab plus AG chemotherapy followed by concurrent SBRT with SIB significantly prolonged mPFS rate, as well as R0 resection rate of surgical patients, and also improved the major pathological response rate. Clinical trial information: NCT05634564 .

Prognostic Factors for Early Recurrence After Resection of Pancreatic Cancer: A Systematic Review and Meta-Analysis

More than half of pancreatic ductal adenocarcinomas (PDACs) recur within 12 months after curative-intent resection. This systematic review and meta-analysis was conducted to identify all reported prognostic factors for early recurrence in resected PDACs. After a systematic literature search, a meta-analysis was conducted using a random effects model. Separate analyses were performed for adjusted vs unadjusted effect estimates as well as reported odds ratios (ORs) and hazard ratios (HRs). Risk of bias was assessed using the Quality in Prognostic Studies tool, and evidence was rated according to Grading of Recommendations Assessment, Development and Evaluation recommendations. After 2903 abstracts were screened, 65 studies were included. Of these, 28 studies (43.1%) defined early recurrence as evidence of recurrence within 6 months, whereas 34 (52.3%) defined it as evidence of recurrence within 12 months after surgery. Other definitions were uncommon. Analysis of unadjusted ORs and HRs revealed 41 and 5 prognostic factors for early recurrence within 6 months, respectively. When exclusively considering adjusted data, we identified 25 and 10 prognostic factors based on OR and HR, respectively. Using a 12-month definition, we identified 38 (OR) and 15 (HR) prognostic factors from unadjusted data and 38 (OR) and 30 (HR) prognostic factors from adjusted data, respectively. On the basis of frequency counts of adjusted data, preoperative carbohydrate antigen 19-9, N status, nondelivery of adjuvant therapy, grading, and tumor size based on imaging were identified as key prognostic factors for early recurrence. Reported prognostic factors of early recurrence vary considerably. Identified key prognostic factors could aid in the development of a risk stratification framework for early recurrence. However, prospective validation is necessary.

An Analysis on the Effect of Income Changes in the Resection of Early-Stage Pancreatic Adenocarcinoma.

The impact of socioeconomic inequalities on cancer care and outcomes has been well recognized and the underlying causes are likely multifactorial. Income is regarded as a cornerstone of socioeconomic status and has been assumed to correlate with access to care. We therefore sought to investigate whether income and changes in income would affect the rate of patients undergoing surgical resection for early-stage pancreatic cancer. Inflation-adjusted income data were obtained from the United States Census Bureau from 2010 to 2019. The cancer data were obtained from the SEER database. Counties present in both data sets were included in the analysis. Patients with stage I or II pancreatic cancer who underwent formal resection were deemed to have undergone appropriate surgical management. Patients were grouped into an early (2010-2014) and late (2015-2019) time period. The final analysis included 23968 patients from 173 counties across 11 states. The resection rate was 45.1% for the entire study and rose from 42.8% to 47.4% from the early to late time periods (P < .001). The median change in income between the two time periods was an increase by $2387. The rate of resection was not dependent on income class or income change in our study population. Our surgical care of pancreatic cancer is improving with more patients undergoing resection. In addition, there are now fewer disparities between patients of lower-income and higher-income groups with respect to receiving surgical intervention. This implies that our access to care has improved over the past decade. This is an encouraging finding with regards to reducing health care disparities.

Placental growth factor promotes neural invasion and predicts disease prognosis in resectable pancreatic cancer

BackgroundSurgery represents the only curative treatment option for pancreatic ductal adenocarcinoma (PDAC), but recurrence in more than 85% of patients limits the success of curative-intent tumor resection. Neural invasion (NI), particularly the spread of tumor cells along nerves into extratumoral regions of the pancreas, constitutes a well-recognized risk factor for recurrence. Hence, monitoring and therapeutic targeting of NI offer the potential to stratify recurrence risk and improve recurrence-free survival. Based on the evolutionary conserved dual function of axon and vessel guidance molecules, we hypothesize that the proangiogenic vessel guidance factor placental growth factor (PlGF) fosters NI. To test this hypothesis, we correlated PlGF with NI in PDAC patient samples and functionally assessed its role for the interaction of tumor cells with nerves.MethodsSerum levels of PlGF and its soluble receptor sFlt1, and expression of PlGF mRNA transcripts in tumor tissues were determined by ELISA or qPCR in a retrospective discovery and a prospective validation cohort. Free circulating PlGF was calculated from the ratio PlGF/sFlt1. Incidence and extent of NI were quantified based on histomorphometric measurements and separately assessed for intratumoral and extratumoral nerves. PlGF function on reciprocal chemoattraction and directed neurite outgrowth was evaluated in co-cultures of PDAC cells with primary dorsal-root-ganglia neurons or Schwann cells using blocking anti-PlGF antibodies.ResultsElevated circulating levels of free PlGF correlated with NI and shorter overall survival in patients with PDAC qualifying for curative-intent surgery. Furthermore, high tissue PlGF mRNA transcript levels in patients undergoing curative-intent surgery correlated with a higher incidence and greater extent of NI spreading to tumor-distant extratumoral nerves. In turn, more abundant extratumoral NI predicted shorter disease-free and overall survival. Experimentally, PlGF facilitated directional and dynamic changes in neurite outgrowth of primary dorsal-root-ganglia neurons upon exposure to PDAC derived guidance and growth factors and supported mutual chemoattraction of tumor cells with neurons and Schwann cells.ConclusionOur translational results highlight PlGF as an axon guidance factor, which fosters neurite outgrowth and attracts tumor cells towards nerves. Hence, PlGF represents a promising circulating biomarker of NI and potential therapeutic target to improve the clinical outcome for patients with resectable PDAC.Graphical

Comparison of the different versions of NCCN guidelines for predicting margin-negative resection of pancreatic cancer in patients undergoing upfront surgery.

The purpose of this study was to compare the different versions of the National Comprehensive Cancer Network (NCCN) guidelines for defining resectability of pancreatic ductal adenocarcinoma (PDAC) in predicting margin-negative (R0) resection, and to assess inter-reader agreement. This retrospective study included 283 patients (mean age, 65.1 years ± 9.4 [SD]; 155 men) who underwent upfront pancreatectomy for PDAC between 2017 and 2019. Two radiologists independently determined the resectability on preoperative CT according to the 2017, 2019, and 2020 NCCN guidelines. The sensitivity and specificity for R0 resection were analyzed using a multivariable logistic regression analysis with generalized estimating equations. Inter-reader agreement was assessed using kappa statistics. R0 resection was accomplished in 239 patients (84.5%). The sensitivity and specificity averaged across two readers were, respectively, 76.6% and 29.5% for the 2020 guidelines, 74.1% and 32.9% for the 2019 guidelines, and 72.6% and 34.1% for the 2017 guidelines. Compared with the 2020 guidelines, both 2019 and 2017 guidelines showed significantly lower sensitivity for R0 resection (p ≤ .009). Specificity was significantly higher with the 2017 guidelines (p = .043) than with the 2020 guidelines. Inter-reader agreements for determining the resectability of PDCA were strong (k ≥ 0.83) with all guidelines, being highest with the 2020 guidelines (k = 0.91). The 2020 NCCN guidelines showed significantly higher sensitivity for prediction of R0 resection than the 2017 and 2019 guidelines.

Effectiveness of endoscopic ultrasound-guided tissue acquisition with stereomicroscopic on-site evaluation for preoperative diagnosis of resectable or borderline resectable pancreatic cancer: a prospective study.

To validate endoscopic ultrasound-guided tissue acquisition (EUS-TA) used in conjunction with stereomicroscopic on-site evaluation (SOSE) as a preoperative diagnostic tool for resectable pancreatic cancer (R-PC) and borderline resectable PC (BR-PC). Seventy-eight consecutive patients who underwent EUS-TA for suspected R-PC or BR-PC were enrolled. The primary endpoint was the sensitivity of EUS-TA together with SOSE based on the stereomicroscopically visible white core (SVWC) cutoff value. One or two sites were punctured by using a 22-gauge biopsy needle for EUS-TA, based on the SOSE findings. We collected 99 specimens from 56 and 22 patients with R-PC and BR-PC, respectively. Based on the SOSE results, we performed 57 procedures with one puncture. The SVWC cutoff values were met in 73.7% and 73.1% of all specimens and in those obtained during the first puncture, respectively. The final diagnoses were malignant and benign tumors in 76 and two patients, respectively. The overall sensitivity, specificity, and accuracy of EUS-TA for the 78 lesions were 90.8%, 100%, and 91.0%, respectively. The sensitivity for malignant diagnosis based on the SVWC cutoff value were 89.5% and 90.4% for the first puncture and all specimens, respectively. The sensitivity of EUS-TA in conjunction with SOSE for malignancy diagnosis in patients with suspected R-PC or BR-PC was 90.4%.

Adjuvant Chemotherapy With or Without Radiotherapy for Resected Pancreatic Cancer After Multiagent Neoadjuvant Chemotherapy.

Adjuvant therapy is associated with improved pancreatic cancer survival after neoadjuvant chemotherapy and surgery. However, whether adjuvant treatment should include radiotherapy is unclear in this setting. This study queried the National Cancer Database for pancreatic adenocarcinoma patients who underwent curative resection after multiagent neoadjuvant chemotherapy between 2010 and 2019 and received adjuvant treatment. Adjuvant chemotherapy plus radiotherapy (external beam, 45-50.4 gray) was compared with adjuvant chemotherapy alone. Uni- and multivariable Cox regression was used to assess survival associations. Analyses were repeated in a propensity score-matched subgroup. Of 1983 patients who received adjuvant treatment after multiagent neoadjuvant chemotherapy and resection, 1502 (75.7%) received adjuvant chemotherapy alone and 481 (24.3%) received concomitant adjuvant radiotherapy (chemoradiotherapy). The patients treated with adjuvant chemoradiotherapy were younger, were treated at non-academic facilities more often, and had higher rates of lymph node metastasis (ypN1-2), positive resection margins (R1), and lymphovascular invasion (LVI+). The median survival was shorter for the chemoradiotherapy-treated patients according to the unadjusted analysis (26.8 vs 33.2 months; p = 0.0017). After adjustment for confounders, chemoradiotherapy was associated with better outcomes in the multivariable model (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.61-0.93; p = 0.008). The association between chemoradiotherapy and improved outcomes was stronger for the patients with grade III tumors (HR, 0.53; 95% CI, 0.37-0.74) or LVI+ tumors (HR, 0.58; 95% CI, 0.44-0.75). In a subgroup of 396 propensity-matched patients, chemoradiotherapy was associated with a survival benefit only for the patients with LVI+ or grade III tumors. After multiagent neoadjuvant chemotherapy and resection for pancreatic cancer, additional adjuvant chemoradiotherapy versus adjuvant chemotherapy alone is associated with improved survival for patients with LVI+ or grade III tumors.

Outcomes of Visceral Arterial Interposition Graft Reconstruction for Locally Advanced Pancreatic Cancer.

The aim of this study is to determine perioperative outcomes and the patency of interposition conduits for visceral arterial reconstruction in this setting. Visceral arterial encasement in locally advanced pancreatic cancer was historically a contraindication for surgery. With modern effective neoadjuvant strategies, our recent experience has made advanced vascular resection and reconstruction feasible in selected patients. A retrospective review was performed of patients undergoing pancreatic tumor resection with en bloc arterial resection and interposition revascularization between 6/2002-10/2022. Endpoints included graft patency, vascular-related complications, reinterventions, morbidity, and mortality. Visceral arterial reconstruction with interposition grafting was performed in 111 patients undergoing en bloc arterial resections for pancreatic cancer. Graft types included autologous arterial conduits (n=66, 58 superficial femoral artery (SFA) and 8 splenic artery), cryopreserved arterial allografts (n=24), autologous saphenous veins (n=12), synthetic conduits (n=8), and composite autologous artery and synthetic (n=1). Perioperative 90-day mortality decreased significantly over time to 5% in the last six years. Vascular complications related to arterial reconstruction occurred in 11% (n=12) and included pseudoaneurysm (n=6), graft thrombus (n=2), stenosis requiring reintervention (n=2), hepatic failure (n=1), and hepatic and intestinal ischemia (n=1). Nine (8%) patients underwent vascular-related reinterventions. After median follow-up of 17-months, primary patency was 81% for the entire cohort and was highest in the SFA group (95%). The donor limb/harvest site complication rate was 8% with 100% primary patency. Visceral arterial resection with interposition reconstruction for locally advanced pancreatic cancer can be performed with acceptable vascular morbidity and durable patency. Autologous SFA was the most suitable conduit for reconstructions in our experience, with highest primary patency.

A Predictive Noninvasive Single-Nucleotide Variation-Based Biomarker Signature for Resectable Pancreatic Cancer: Protocol for a Prospective Validation Study.

Single-nucleotide variations (SNVs; formerly SNPs) are inherited genetic variants that can be easily determined in routine clinical practice using a simple blood or saliva test. SNVs have potential to serve as noninvasive biomarkers for predicting cancer-specific patient outcomes after resection of pancreatic ductal adenocarcinoma (PDAC). Two recent analyses led to the identification and validation of three SNVs in the CD44 and CHI3L2 genes (rs187115, rs353630, and rs684559), which can be used as predictive biomarkers to help select patients most likely to benefit from pancreatic resection. These variants were associated with an over 2-fold increased risk for tumor-related death in three independent PDAC study cohorts from Europe and the United States, including The Cancer Genome Atlas cohorts (reaching a P value of 1×10-8). However, these analyses were limited by the inherent biases of a retrospective study design, such as selection and publication biases, thereby limiting the clinical use of these promising biomarkers in guiding PDAC therapy. To overcome the limitations of previous retrospectively designed studies and translate the findings into clinical practice, we aim to validate the association of the identified SNVs with survival in a controlled setting using a prospective cohort of patients with PDAC following pancreatic resection. All patients with PDAC who will undergo pancreatic resection at three participating hospitals in Switzerland and fulfill the inclusion criteria will be included in the study consecutively. The SNV genotypes will be determined using standard genotyping techniques from patient blood samples. For each genotyped locus, log-rank and Cox multivariate regression tests will be performed, accounting for the relevant covariates American Joint Committee on Cancer stage and resection status. Clinical follow-up data will be collected for at least 3 years. Sample size calculation resulted in a required sample of 150 patients to sufficiently power the analysis. The follow-up data collection started in August 2019 and the estimated end of data collection will be in May 2027. The study is still recruiting participants and 142 patients have been recruited as of November 2023. The DNA extraction and genotyping of the SNVs will be performed after inclusion of the last patient. Since no SNV genotypes have been determined, no data analysis has been performed to date. The results are expected to be published in 2027. This is the first prospective study of the CD44 and CHI3L2 SNV-based biomarker signature in PDAC. A prospective validation of this signature would enable its clinical use as a noninvasive predictive biomarker of survival after pancreatic resection that is readily available at the time of diagnosis and can assist in guiding PDAC therapy. The results of this study may help to individualize treatment decisions and potentially improve patient outcomes. DERR1-10.2196/54042.

Scoring system to predict positive peritoneal cytology in patients with resectable and borderline resectable pancreatic cancer.

The aim of this study was to evaluate factors to predict positive peritoneal cytology, whcih would determine the indication for staging laparoscopy in pancreatic cancer. A total of 430 patients that underwent pancreatectomy for resectable and borderline resectable pancreatic cancer were retrospectively reviewed. Among 430 patients, 36 had positive cytology (8.4%). Median survival time in negative cytology was 24.7 months, compared with 15.1 months in positive cytology (p = .004). Factors to predict positive cytology in pancreatic cancer according to multivariate analysis were tumor location (body, tail; OR 2.66; 95% CI: 1.21-5.85; p = .015), tumor size ≥30 mm (OR 2.95; 95% CI: 1.35-6.47; p = .007) and radiographic other-organ invasion (HR 2.79; 95% CI: 1.01-7.67; p = .047). Patients were scored 0 to 3 corresponding with these factors. Rates of positive cytology increases in each score were: score 0: 2.9%, score 1: 6.7%, score 2: 18.3%, score 3: 36.8%. Tumor location (body or tail), tumor size ≥30 mm, and radiographic other-organ invasions were risk factors for positive cytology in pancreatic cancer. This scoring system might be a useful indicator to perform staging laparoscopy to diagnose positive cytology.

BNCT pancreatic cancer treatment strategy with glucose-conjugated boron drug

Multidisciplinary therapy centered on radical surgery for resectable pancreatic cancer is expected to prolong prognosis, but relies on CA19-9 biomarker levels to determine treatment strategy. Boron neutron capture therapy (BNCT) is a chemoradiotherapy using tumor hyperaccumulator boron drugs and neutron irradiation. The purpose of this study is to investigate novel boron drug agents for BNCT for pancreatic cancer. Bioinformatics was used to evaluate the uptake of current boron amino acid (BPA) drugs for BNCT into pancreatic cancer. The expression of the amino acid transporter LAT1, a BPA uptake transporter, was low in pancreatic cancer and even lower in high CA19-9 pancreatic cancer. In contrast, the glucose transporter was high in high CA19-9 pancreatic cancers and inversely correlated with LAT1 expression. Considering the low EPR effect in pancreatic cancer, we synthesized a small molecule Glucose-BSH, which is boron BSH bound to glucose, and confirmed its specific uptake in pancreatic cancer. uptake of Glucose-BSH was confirmed in an environment compatible with the tumor microenvironment. The therapeutic efficacy and safety of Glucose-BSH by therapeutic neutron irradiation were confirmed with BNCT. We report Glucose-BSH boron drug discovery study of a Precision Medicine BNCT with application to high CA19-9 pancreatic cancer.

Adjuvant chemotherapy omission after pancreatic cancer resection: a French nationwide study

BackgroundAdjuvant chemotherapy (AC) improves the prognosis after pancreatic ductal adenocarcinoma (PDAC) resection. However, previous studies have shown that a large proportion of patients do not receive or complete AC. This national study examined the risk factors for the omission or interruption of AC.MethodsData of all patients who underwent pancreatic surgery for PDAC in France between January 2012 and December 2017 were extracted from the French National Administrative Database. We considered “omission of adjuvant chemotherapy” (OAC) all patients who failed to receive any course of gemcitabine within 12 postoperative weeks and “interruption of AC” (IAC) was defined as less than 18 courses of AC.ResultsA total of 11 599 patients were included in this study. Pancreaticoduodenectomy was the most common procedure (76.3%), and 31% of the patients experienced major postoperative complications. OACs and IACs affected 42% and 68% of the patients, respectively. Ultimately, only 18.6% of the cohort completed AC. Patients who underwent surgery in a high-volume centers were less affected by postoperative complications, with no impact on the likelihood of receiving AC. Multivariate analysis showed that age ≥ 80 years, Charlson comorbidity index (CCI) ≥ 4, and major complications were associated with OAC (OR = 2.19; CI95%[1.79–2.68]; OR = 1.75; CI95%[1.41–2.18] and OR = 2.37; CI95%[2.15–2.62] respectively). Moreover, age ≥ 80 years and CCI 2–3 or ≥ 4 were also independent risk factors for IAC (OR = 1.54, CI95%[1.1–2.15]; OR = 1.43, CI95%[1.21–1.68]; OR = 1.47, CI95%[1.02–2.12], respectively).ConclusionSequence surgery followed by chemotherapy is associated with a high dropout rate, especially in octogenarian and comorbid patients.

Comparison of laparoscopic versus open pancreaticoduodenectomy combined with portal vein/superior mesenteric vein resection and reconstruction for pancreatic cancer: a propensity score matching analysis

Comparison of laparoscopic versus open pancreaticoduodenectomy combined with portal vein/superior mesenteric vein resection and reconstruction for pancreatic cancer: a propensity score matching analysis

Failure to Undergo Resection Following Neoadjuvant Therapy for Resectable Pancreatic Cancer: A Secondary Analysis of SWOG S1505.

Neoadjuvant therapy (NT) is increasingly used for patients with pancreatic ductal adenocarcinoma (PDAC), and yet reasons for not undergoing subsequent pancreatectomy are poorly understood. Given the importance of completing multimodality therapy, we investigated factors associated with failure to undergo surgical resection following NT for PDAC. SWOG S1505 was a multicenter phase II randomized trial of preoperative mFOLFIRINOX or gemcitabine/nab-paclitaxel prior to planned pancreatectomy for patients with potentially resectable PDAC. Associations between clinical, demographic, and hospital-level characteristics and receipt of surgical resection were estimated via multiple logistic regression. Differences in overall survival from 18 weeks postrandomization (scheduled time of surgery) according to resection status were assessed via Cox regression models. Among 102 eligible patients, 73 (71.6%) underwent successful pancreatectomy, whereas 29 (28.4%) did not, primarily because of progression (n=11; 10.8%) or toxicity during NT (n=9; 8.8%). Weight loss during NT (odds ratio [OR], 0.34; 95% CI, 0.11-0.93) and the hospital's city size (small: OR, 0.24 [95% CI, 0.07-0.80] and large: OR, 0.28 [95% CI, 0.10-0.79] compared with midsize) were significantly associated with a lower probability of surgical resection in adjusted models, whereas age, sex, race, body mass index, performance status, insurance type, geographic region, treatment arm, tumor location, chemotherapy delays/modifications, and hospital characteristics were not. Surgical resection following NT was associated with improved overall survival (median, 23.8 vs 10.8 months; P<.01) even after adjusting for grade 3-5 adverse events during NT, performance status, and body mass index (hazard ratio, 0.55; 95% CI, 0.32-0.95). Failure to undergo resection following NT was relatively common among patients with potentially resectable PDAC and associated with worse survival. Although few predictive factors were identified in this secondary analysis of the SWOG S1505 randomized trial, further research must focus on risk factors for severe toxicities during NT that preclude surgical resection so that patient-centered interventions can be delivered or alternate treatment sequencing can be recommended.