Borderline Pancreatic Ductal Adenocarcinoma Research Articles

Feasibility of laparoscopic versus open pancreatoduodenectomy following neoadjuvant chemotherapy for borderline resectable pancreatic cancer: a retrospective cohort study

BackgroundThere is no evidence supporting the feasibility of laparoscopic pancreaticoduodenectomy (LPD) compared to open pancreatoduodenectomy (OPD) following neoadjuvant chemotherapy (NACT) for pancreatic ductal adenocarcinoma (PDAC).MethodsThe clinical data of consecutive patients with borderline resectable PDAC who received NACT and underwent either LPD or OPD between January 2020 and December 2022 at Fudan University Shanghai Cancer Center was prospectively collected and retrospectively analyzed.ResultsThe analysis included 57 patients in the OPD group and 20 in the LPD group. Following NACT, the LPD group exhibited a higher median CA19-9 decrease rate compared to the OPD group (85.3% vs. 66.9%, P = 0.042). Furthermore, 3 anatomically borderline PDACs in the LPD group and 5 in the OPD group were downstaged into resectable status (30.0% vs. 12.3%, P = 0.069). According to RECIST criteria, 51 (66.2%) patients in the entire cohort were evaluated as having stable disease. The median operation time for the LPD group was longer than the OPD group (419 vs. 325 min, P < 0.001), while the venous resection rate was 35.0% vs. 43.9%, respectively (P = 0.489). There was no difference in the number of retrieved lymph nodes, with a median number of 18.5 in the LPD group and 22 in the OPD group, and the R1 margin rate (15.0% vs. 12.3%) was also comparable. The incidence of Clavien-Dindo complications (35.0% vs. 66.7%, P = 0.018) was lower in the LPD group compared to the OPD group. Multivariable regression analysis revealed that a tumor diameter > 3 cm before NACT (HR 2.185) and poor tumor differentiation (HR 1.805) were independent risk factors for recurrence-free survival, and a decrease rate of CA19-9 > 70% (OR 0.309) was a protective factor for early tumor recurrence and overall survival.ConclusionsLPD for PDAC following NACT is feasible and oncologically equivalent to OPD. Effective control of CA19-9 levels is beneficial in reducing early tumor recurrence and improving overall survival.

Refined TNM-staging for pancreatic adenocarcinoma – Real progress or much ado about nothing?

In order to provide optimal cancer care and prognostication, it is necessary to stage the disease. The 8th edition of the TNM-staging for exocrine pancreatic ductal adenocarcinoma (PDAC) system has refined size-based T-stages and number-based N-categories. However, several impediments to the value of this may exist. For one, even at small size (e.g. <0.5 cm), PDACs readily metastasize, making size unreliable to predict behavior. The increasing shift towards neoadjuvant treatments for both resectable and borderline PDAC, and use of conversion therapy for locally advanced disease, suggest the need for additional biological predictors. Here we discuss whether recent changes in the TNM system for PDAC are along the lines of changes seen in contemporary management. Also, with the particular aggressive biology seen in PDAC, it is questioned whether the minute details in TNM refinement represents true progress or merely shuffles the cards.

Patient outcome according to the 2017 international consensus on the definition of borderline resectable pancreatic ductal adenocarcinoma

Background/objectiveWe evaluated the usefulness of the 2017 definition of borderline pancreatic ductal adenocarcinoma (BR-PDAC) in fit patients (performance status 0–1) based on anatomical (A) and biological dimensions (B). MethodsFrom 2011 to 2018, 139 resected patients with BR-PDAC according to the 2017 definition were included: 18 patients underwent upfront pancreatectomy (CA 19-9 > 500 U/mL and/or regional lymph node metastasis; BR-B group), and 121 received FOLFIRINOX (FX) induction chemotherapy and were divided into BR-A (CA 19-9 < 500 U/mL, no regional lymph node metastasis; n = 68) and BR-AB (CA 19-9 > 500 U/mL and/or regional lymph node metastasis; n = 53) groups. ResultsThe 3 groups were comparable according to patient characteristics (except for back pain (P < .01) and CA 19-9 (P < .01)), intraoperative data, and postoperative courses. BR-AB patients required more venous resections (P < .01). The 3 groups were comparable on pathologic findings, except that BR-B patients had more lymph node invasions (P = .02). Median overall survival (OS) of the 121 patients was 45 months. In multivariate analysis, venous resection (P = .039) and R1 resection (P = .012) were poorly linked with OS, whereas BR-A classification (P < .01) independently favored OS. Median survival times of BR-A, BR-AB, and BR-B groups were undetermined, 27 months, and 20 months (P < .001), respectively. ConclusionsThe 2017 definition was relevant for sub-classifying patients with BR-PDAC. The anatomical dimension (BR-A) was a favorable prognostic factor, whereas the biological dimension (BR-AB and BR-B) poorly impacted survival.

Contemporary management of borderline resectable pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive tumors, with a low rate of survival, likely due to the tendency of the tumor for early local and distant spread. Pancreatic cancer accounts for about 3% of all cancers in the US and about 7% of all cancer deaths. Surgical resection still represents the best curative treatment for PDAC, although only 10–20% of patients are upfront resectable at diagnosis, 50% has metastatic disease and 35% locally advanced cancer. The 5-year overall survival (OS) after curative resection is limited to 20%. Moreover among patients who undergo surgery, 30% develop early recurrence while most of them will eventually relapse. The risk of early failure after surgery could be associated with inadequate preoperative radiological staging, lack of radical surgery and differences in tumor aggressiveness. In recent years, more accurate patient categorization due to sophisticated imaging tools and techniques increase the survival rate while neoadjuvant treatment can help surgeons select patients who will benefit most from surgery. Neoadjuvant therapy includes chemotherapy alone, chemoradiotherapy, chemotherapy with chemoradiation and targeted therapies. The aim of this review is to present the available data concerning the management of patients with borderline PDAC.

Neoadjuvant chemotherapy with gemcitabine and S-1 for resectable and borderline pancreatic ductal adenocarcinoma: A prospective, multi-institutional, phase II trial.

283 Background: Although surgical resection is the only curative treatment for pancreatic ductal adenocarcinoma (PDAC), recurrence rates are very high even if complete resection is performed. Accordingly, a new therapeutic strategy against PDAC is needed. Combination with gemcitabine and S-1 (GS) as first line chemotherapy is promising. The purpose of this study is to evaluate the feasibility and efficacy of GS for resectable and borderline PDAC in the neoadjuvant chemotherapy (NAC). Methods: This study is a prospective, multi-institutional, single-arm, phase II trial. Neoadjuvant chemotherapy with gemcitabine and S-1(NAC-GS) for resectable and borderline PDAC was performed as follows. Gemcitabine was given at a dose of 1,000 mg/m2 on days 1 and 8 of each cycle. S-1 was administered orally at a dose of 40 mg/m2 twice daily for the first 14 consecutive days followed by a 7-day rest. Each cycle was repeated every 21 days. The primary endpoint was the 2-year survival rate. Secondary endpoints were feasibility, resection rate, pathological effect, recurrence-free survival and tumor marker status. Results: 36 patients were enrolled between 2008 and 2010. 35 were eligible for participation in this trial. The most common toxicity was neutropenia in response to 90% of the relative dose intensity. Radiological tumor shrinkage and decreases of CA19-9 levels were seen in 69% and 89%, respectively. R0 resection rate was 87%, and the morbidity rate (40%) was acceptable. The 2-year survival rate of the total cohort was 45.7%. Patients undergoing surgical resection without distant metastases after NAC-GS (n=27) showed an increased median overall survival (34.7 months), compared with 10.0 months for resection with distant metastases or non-resection (p=0.0017). Conclusions: NAC-GS is safe and well tolerated in a multi-institutional setting. NAC-GS is encouraging patients with resectable and borderline PDAC because of better outcomes. Clinical trial information: UMIN-000001504.

Neoadjuvant Chemotherapy with Gemcitabine and S-1 for Resectable and Borderline Pancreatic Ductal Adenocarcinoma: Results from a Prospective Multi-institutional Phase 2 Trial

Surgical resection is the only curative strategy for pancreatic ductal adenocarcinoma (PDAC), but recurrence rates are high even after purported curative resection. First-line treatment with gemcitabine and S-1 (GS) is associated with promising antitumor activity with a high response rate. The aim of this study was to assess the feasibility and efficacy of GS in the neoadjuvant setting. In a multi-institutional single-arm phase 2 study, neoadjuvant chemotherapy (NAC) with gemcitabine and S-1, repeated every 21 days, was administered for two cycles (NAC-GS) to patients with resectable and borderline PDAC. The primary end point was the 2-year survival rate. Secondary end points were feasibility, resection rate, pathological effect, recurrence-free survival, and tumor marker status. Of 36 patients enrolled, 35 were eligible for this clinical trial conducted between 2008 and 2010. The most common toxicity was neutropenia in response to 90% of the relative dose intensity. Responses to NAC included radiological tumor shrinkage (69%) and decreases in CA19-9 levels (89%). R0 resection was performed for 87% in resection, and the morbidity rate (40%) was acceptable. The 2-year survival rate of the total cohort was 45.7%. Patients who underwent resection without metastases after NAC-GS (n = 27) had an increased median overall survival (34.7 months) compared with those who did not undergo resection (P = 0.0017). NAC-GS was well tolerated and safe when used in a multi-institutional setting. The R0 resection rate and the 2-year survival rate analysis are encouraging for patients with resectable and borderline PDAC.