Borderline Resectable Pancreatic Adenocarcinoma Research Articles

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.

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.

Abstract A001: Preoperative treatment with mFOLFIRINOX +/- isotoxic high-dose stereotactic body radiation therapy (iHD-SBRT) for borderline resectable pancreatic adenocarcinoma (the STEREOPAC trial): A randomized comparative multicenter phase II trial

Abstract Background: Surgical resection is the only potentially curative treatment for patients with pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant therapy is a rapidly emerging concept that needs to be explored and validated in terms of therapeutic options and survival benefit. In this setting, preoperative modified FOLFIRINOX (mFFX) seems to be feasible and can be followed by radiation therapy with promising benefit for patients in terms of R0 resection, local control and survival. However, the best therapeutic sequence is not yet known and the role of adding high-dose SBRT to chemotherapy in the neoadjuvant strategy requires assessment in randomized trials. The aim of the study is to evaluate the impact and efficacy of adding isotoxic high-dose SBRT (iHD-SBRT) to neoadjuvant mFFX in patients with borderline resectable PDAC. Methods: This is a randomized comparative multicentre phase II trial, planning to enrol patients (n= 256) diagnosed with a borderline resectable biopsy-confirmed PDAC. Patients will receive 4 cycles of mFFX (or 6 doses of gemcitabine/nab-paclitaxel [Gem/Nab-P] in case of intolerance). After full disease restaging, non-progressive patients will be randomized for receiving either 4 additional mFFX cycles (or 6 doses of Gem/Nab-P) (Arm A), or 2 mFFX cycles (or 3 doses of Gem/Nab-P) + iHD-SBRT (35 to 55Gy in 5 fractions) + 2 mFFX cycles (or 3 doses of Gem/Nab-P) (Arm B). Then curative surgery will be performed followed by adjuvant chemotherapy according to patient’s condition. The co-primary endpoints are R0 resection and disease-free survival after the complete sequence strategy. The secondary endpoints include resection rate, overall survival, locoregional failure/distant metastasis free interval, pathologic complete response, toxicity, postoperative complications and quality of life assessment. Discussion: This trial will help define the best neoadjuvant treatment sequence for borderline resectable PDAC and aims to evaluate if a total neoadjuvant treatment integrating iHD-SBRT improves the patients’ oncological outcomes. Trial registration: The study was registered at ClinicalTrails.gov (NCT05083247) on October 19th, 2021, and in the Clinical Trials Information System (CTIS) EU CT database (2022-501181-22-01) on July 2022. The first patient was included on March 24, 2023. Citation Format: Christelle Bouchart, Julie Navez, Ivan Borbath, Karen Geboes, Timon Vandamme, Jean Closset, Luigi Moretti, Pieter Demetter, Marianne Paesmans, Jean-Luc Van Laethem. Preoperative treatment with mFOLFIRINOX +/- isotoxic high-dose stereotactic body radiation therapy (iHD-SBRT) for borderline resectable pancreatic adenocarcinoma (the STEREOPAC trial): A randomized comparative multicenter phase II trial [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 A001.

Association between neoadjuvant radiotherapy and survival in patients with resectable and borderline resectable pancreatic adenocarcinoma

Association between neoadjuvant radiotherapy and survival in patients with resectable and borderline resectable pancreatic adenocarcinoma

Multicenter randomized controlled trial of neoadjuvant chemoradiotherapy alone or in combination with pembrolizumab in patients with resectable or borderline resectable pancreatic adenocarcinoma

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a challenging target for immunotherapy because it has an immunosuppressive tumor microenvironment. Neoadjuvant chemoradiotherapy can increase tumor-infiltrating lymphocyte (TIL) density, which may predict overall survival...

Currently Debated Topics on Surgical Treatment of Pancreatic Ductal Adenocarcinoma: A Narrative Review on Surgical Treatment of Borderline Resectable, Locally Advanced, and Synchronous or Metachronous Oligometastatic Tumor.

Previously considered inoperable patients (borderline resectable, locally advanced, synchronous oligometastatic or metachronous pancreatic adenocarcinoma (PDAC)) are starting to become resectable thanks to advances in chemo/radiotherapy and the reduction in operative mortality. This narrative review presents a chosen literature selection, giving a picture of the current state of treatment of these patients. Neoadjuvant therapy (NAT) is generally recognized as the treatment of choice before surgery. However, despite the increased efficacy, the best pathological response is still limited to 10.9-27.9% of patients. There are still limited data on the selection of possible NAT responders and how to diagnose non-responders early. Multidetector computed tomography has high sensitivity and low specificity in evaluating resectability after NAT, limiting the resection rate of resectable patients. Ca 19-9 and Positron emission tomography are giving promising results. The prediction of early recurrence after a radical resection of synchronous or metachronous metastatic PDAC, thus identifying patients with poor prognosis and saving them from a resection of little benefit, is still ongoing, although some promising data are available. In conclusion, high-level evidence demonstrating the benefit of the surgical treatment of such patients is still lacking and should not be performed outside of high-volume centers with interdisciplinary teams of surgeons and oncologists.

Preoperative treatment with mFOLFIRINOX or Gemcitabine/Nab-paclitaxel +/- isotoxic high-dose stereotactic body Radiation Therapy (iHD-SBRT) for borderline resectable pancreatic adenocarcinoma (the STEREOPAC trial): study protocol for a randomised comparative multicenter phase II trial

BackgroundFor patients with pancreatic ductal adenocarcinoma (PDAC), surgical resection remains the only potentially curative treatment. Surgery is generally followed by postoperative chemotherapy associated with improved survival, yet neoadjuvant therapy is a rapidly emerging concept requiring to be explored and validated in terms of treatment options and oncological outcomes. In this context, stereotactic body radiation (SBRT) appears feasible and can be safely integrated into a neoadjuvant chemotherapy regimen of modified FOLFIRINOX (mFFX) with promising benefits in terms of R0 resection, local control and survival. However, the optimal therapeutic sequence is still not known, especially for borderline resectable PDAC, and the role of adding SBRT to chemotherapy in the neoadjuvant setting needs to be evaluated in randomised controlled trials. The aim of the STEREOPAC trial is to assess the impact and efficacy of adding isotoxic high-dose SBRT (iHD-SBRT) to neoadjuvant mFFX or Gemcitabine/Nab-Paclitaxel (Gem/Nab-P) in patients with borderline resectable PDAC.MethodsThis is a randomised comparative multicentre phase II trial, planning to enrol patients (n = 256) diagnosed with a borderline resectable biopsy-confirmed PDAC. Patients will receive 4 cycles of mFFX (or 6 doses of Gem/Nab-P). After full disease restaging, non-progressive patients will be randomised for receiving either 4 additional mFFX cycles (or 6 doses of Gem/Nab-P) (Arm A), or 2 mFFX cycles (or 3 doses of Gem/Nab-P) + iHD-SBRT (35 to 55 Gy in 5 fractions) + 2 mFFX cycles (or 3 doses of Gem/Nab-P) (Arm B). Then curative surgery will be performed followed by adjuvant chemotherapy according to patient’s condition. The co-primary endpoints are R0 resection and disease-free survival after the complete sequence strategy. The secondary endpoints include resection rate, overall survival, locoregional failure / distant metastasis free interval, pathologic complete response, toxicity, postoperative complications and quality of life assessment.DiscussionThis trial will help define the best neoadjuvant treatment sequence for borderline resectable PDAC and aims to evaluate if a total neoadjuvant treatment integrating iHD-SBRT improves the patients’ oncological outcomes.Trial registrationThe study was registered at ClinicalTrails.gov (NCT05083247) on October 19th, 2021, and in the Clinical Trials Information System (CTIS) EU CT database (2022-501181-22-01) on July 2022.

Portal Vein or Superior Mesenteric Vein Thrombosis with Dose-Escalated Radiation for Borderline or Locally Advanced Pancreatic Cancer

PurposePortal vein and superior mesenteric vein thrombosis (PVT/SMVT) are potentially morbid complications of radiation dose–escalated local therapy for pancreatic cancer. We retrospectively reviewed records for patients treated with and without intraoperative radiation (IORT) to identify risk factors for PVT/SMVT. MethodsNinety-six patients with locally advanced or borderline resectable pancreatic adenocarcinoma received neoadjuvant therapy followed by surgical exploration from 2009 to 2014. Patients at risk for close or positive surgical margins received IORT boost to a biologically effective dose (BED10) > 100. Prognostic factors for PVT/SMVT were evaluated using competing risks regression. ResultsMedian follow-up was 79 months for surviving patients. Fifty-six patients (58%) received IORT. Twenty-nine patients (30%) developed PVT/SMVT at a median time of 18 months. On univariate competing risks regression, operative blood loss and venous repair with a vascular interposition graft, but not IORT dose escalation or diabetes history, were significantly associated with PVT/SMVT. The development of thrombosis in the absence of recurrence was significantly associated with a longstanding diabetes history, post-neoadjuvant treatment CA19-9, and operative blood loss. All 4 patients who underwent both IORT and vascular repair with a graft developed PVT/SMVT. PVT/SMVT in the absence of recurrence is not associated with significantly worsened overall survival but led to frequent medical interventions. ConclusionsApproximately 30% of patients who underwent neoadjuvant chemoradiation for PDAC developed PVT/SMVT a median of 18 months following surgery. This was significantly associated with venous reconstruction with vascular grafts, but not with escalating radiation dose. PVT/SMVT in the absence of recurrence was associated with significant morbidity.

Overall survival (OS) and pathologic response rate from a phase II clinical trial of neoadjuvant GVAX pancreas vaccine (with cyclophosphamide) in combination with nivolumab and stereotactic body radiation therapy (SBRT) followed by definitive resection for patients with borderline resectable pancreatic adenocarcinoma (BR-PDAC).

e16309 Background: The optimal management of BR-PDAC remains undefined due to the high rate of local progression and/or metastasis with upfront surgery alone. Given the limited activity of single agent PD-1 blockade in PDAC, combination strategies aimed at increasing high-avidity T-cells in the tumor microenvironment (TME) are under investigation. GVAX is an allogenic, whole cell, GM-CSF-secreting vaccine that activates T-cell immunity against tumor-associated antigens. Prior work has shown that GVAX in combination with low-dose cyclophosphamide (Cy) can inhibit T-regulatory cells and induce both PD-L1 expression and the formation of tertiary lymphoid aggregates. This multi-center phase II clinical trial evaluates the safety and clinical efficacy of the addition of GVAX/Cy/nivolumab and SBRT to neoadjuvant chemotherapy in patients with BR-PDAC. Methods: Patients received neoadjuvant mFOLFIRINOX or gemcitabine/abraxane if intolerant to mFOLFIRINOX. Two to six weeks after chemotherapy, the first dose combination immunotherapy with Cy (200 mg/m2), nivolumab (240mg) and GVAX (5 x 108 vaccine cells) was given. Three weeks later, patients received the second dose of combined immunotherapy concurrently with SBRT (6.6 Gy x 5 days) prior to surgical resection. The primary endpoint is CD8+ T-cell density (CD8) in surgical specimens compared with CD8 in historical control samples treated with neoadjuvant mFOLFIRINOX and SBRT only. Additional endpoints include pathologic response rates, adverse events (AEs) as graded by NCI CTCAE version 4.03, OS, and evaluation of immune changes to the TME. Results: 31 patients were enrolled from 2/2/2018 to 7/27/2021. Of these, 18 patients received at least one dose of combination immunotherapy. Following study treatment, one patient had progressive disease, three had occult intra-operative metastatic disease and 14 underwent definitive surgical resection (13 R0 resections and one R1 resection). The major pathologic response rate was 35% (defined as <10% residual viable tumor), including one pathologic complete response (pCR). At a median follow-up of 20.5 months, median OS was 20.4 months (95% CI 18.2, NA). There were two grade 3 or higher AEs (one case of nivolumab-related autoimmune hepatitis and one case of SBRT-related pancytopenia). Conclusions: The addition of combined immunotherapy and SBRT to chemotherapy was safe and feasible in BR-PDAC. Observed median OS, pCR and R0 resection rates were comparable to contemporary studies administering neoadjuvant mFOLFIRINOX and SBRT. Additional immune correlative data will be available and reported at the time of the conference, guiding future applications of novel vaccine approaches. Clinical trial information: NCT03161379 .

An adaptive approach to neoadjuvant therapy to maximize resection rates for pancreatic adenocarcinoma: A phase II trial.

TPS771 Background: Curative treatment for potentially resectable (resectable or borderline resectable) pancreatic adenocarcinoma, despite recent advances, leads to only suboptimal outcomes. Recent US national cooperative group trials have demonstrated the safety and feasibility of neoadjuvant chemotherapy (PMID 33475684, PMID 35834226), and also show that the two frontline regimens, FOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin) and gemcitabine/nab-paclitaxel (GnP), are comparable in this setting. Finally, ability to undergo resection remains the key driver of cure. Therefore, an approach that selects chemotherapy based on early response assessment, to maximize the probability of resection, is likely to improve curative outcomes. Methods: This is a phase II study intended to maximize the probability of surgical resection for pancreatic cancer. Key eligibility requirements include adult patients with a confirmed histopathologic diagnosis of pancreatic carcinoma or adenocarcinoma, an ECOG PS ≤ 1, resectable or borderline resectable disease by central radiology review, no prior therapy for index pancreatic cancer, and adequate bone marrow, liver and kidney function. Treatment includes 4 doses (~ 2 months total treatment time) of FOLFIRINOX (“Chemo1”). After a re-evaluation, using radiologic response, CA19.9 response, and chemotherapy toxicity, patients will either continue with “Chemo1” for another 4 cycles (8 doses) or switch to GnP (“Chemo2”) which will be administered for 4 cycles (12 doses, for ~4 month total treatment time), followed by surgical resection. Primary outcome will measure the proportion of patients undergoing surgical resection using historical dated compared to 32 patients in a current study with a time frame of 16 months. Using historical data, the expected proportion of patients undergoing resection is ~60%. The goal of this study is to increase this to 80% or higher. With a one-sided of 0.05 and power of 80%, 32 patients will be needed to demonstrate this difference. Key translational correlatives will include serial circulating tumor DNA assessment and extensive tumor molecular profiling. Clinical trial information: NCT04594772 .

Evolution of Carbohydrate Antigen 19-9 Levels during Neoadjuvant Treatment Can Predict Resectability and Survival in Borderline Resectable Pancreatic Adenocarcinoma

Evolution of Carbohydrate Antigen 19-9 Levels during Neoadjuvant Treatment Can Predict Resectability and Survival in Borderline Resectable Pancreatic Adenocarcinoma

Survival After Minimally Invasive vs Open Surgery for Pancreatic Adenocarcinoma

Only a few high-volume centers have reported on long-term oncologic outcomes after minimally invasive pancreatic surgery (MIPS) for pancreatic adenocarcinoma, but none of them have shown superior long-term overall survival (OS) compared with open pancreatic surgery (OPS). To study long-term survival after MIPS and OPS with curative intent among patients with pancreatic adenocarcinoma. This comparative effectiveness study used a retrospective analysis of a prospectively maintained electronic database of patient data collected between January 2010 and December 2019. Consecutive patients from a high-volume pancreatic cancer referral center were included. Data analysis was conducted from March to October 2022. Median follow-up time was 56.8 months. Patients were matched using propensity score models to study long-term survival. Survival outcomes were analyzed using the Cox proportional hazards model. Variables used for propensity score correction were TNM stage, tumor dimension, lymph node status, type of operation, simultaneous vascular resection, neoadjuvant chemotherapy, adjuvant chemotherapy, sex, age, and American Society of Anesthesiologists score. Additional corrections were made for year of surgery and type of adjuvant chemotherapy. After propensity score matching the sample of 396 patients, there were 198 patients in the MIPS group (89 [44.9%] men; median [range] age, 68 [32-87] years) and 198 in the OPS group (94 [47.5%] men; median [range] age, 67 [39-84] years). Median OS in the MIPS group was 30.7 (95% CI, 26.2-36.8) months compared with 20.3 (95% CI, 17.6-23.5) months after OPS (hazard ratio [HR], 0.70; 95% CI, 0.56-0.87; P = .002). Median disease-free survival (DFS) after MIPS vs OPS was 14.8 (95% CI, 11.8-17.0) months vs 10.7 (95% CI, 9.0-12.1) months (HR, 0.71; 95% CI, 0.57-0.89; P = .003). Additional corrections for year of surgery and type of adjuvant chemotherapy showed better OS (year of surgery: HR, 0.74; 95% CI, 0.57-0.96; P = .02; adjuvant chemotherapy: HR, 0.71; 95% CI, 0.56-0.90; P = .005) and DFS (year of surgery: HR, 0.77; 95% CI, 0.59-0.99; P = .04; adjuvant chemotherapy: HR, 0.72; 95% CI, 0.57-0.92; P = .009) for patients undergoing minimally invasive vs open surgery. In this study of 396 patients with borderline resectable and resectable pancreatic adenocarcinoma, MIPS was associated with better OS and DFS than OPS. Centralization of MIPS should be stimulated, and pancreatic surgeons should be encouraged to pass the learning curve before implementing MIPS for pancreatic adenocarcinoma in daily clinical practice.

A patient-centered, multidisciplinary approach to treating borderline resectable pancreatic adenocarcinoma

The cancer-related death rate for pancreatic ductal adenocarcinoma (PDAC) has shown little improvement over the past decade, and PDAC is expected to be the second leading cause of cancer-related deaths by 2030. This is partly because most patients with PDAC present with metastatic (40%) or locally advanced (40%) disease, and only a minority of patients (20%) present with resectable or borderline resectable (BR) PDAC and are considered potential candidates for pancreatectomy, the only curative treatment available. Borderline resectability is a unique category within pancreatic cancer staging that represents tumors that are technically resectable, with or without vascular resection and reconstruction, but that are at high risk of harboring occult metastases at the time of diagnosis or positive margins if pancreatectomy is performed de novo. It assesses multiple dimensions of resectability including anatomy, biology, and condition. A multidisciplinary approach is essential to optimize each dimension and improve outcomes among patients with BR pancreatic adenocarcinoma. Here, we outline the evolution of the pancreatic cancer staging system as it pertains to surgical resectability, describe the influence this staging system has had on treatment, and review the evidence that guides a multidisciplinary approach to workup, staging, and treatment of patients with BR PDAC.

Circulating tumor DNA: a help to guide therapeutic strategy in patients with borderline and locally advanced pancreatic adenocarcinoma?

prognostic biomarkers could be useful to better select patients with borderline resectable (BR) or locally advanced (LA) pancreatic adenocarcinoma (PA) for chemoradiotherapy (CRT) and/or secondary resection. The main objective of this work was to study characteristics, received treatments and prognostic of patients with BR or LA PA according to their baseline circulating tumor DNA status and, for secondary objective, neutrophil-to-lymphocyte Ratio (NLR). ctDNA status at baseline was determined using Next Generation Sequencing in a consecutive monocentric cohort of patients with a BR or LA PA. 69 patients were included, 31 with BR PA and 38 with LA PA. 14 (20.3%) patients had baseline positive ctDNA. Five (7.8%) patients had NLR> 5. Patients with positive ctDNA had 3.7 months shorter progression free survival (p=0.006). Patients with positive ctDNA had earlier progression after the beginning of CRT (4.4vs 7.1 months; p=0.068) and shorter relapse free survival after secondary resection (9.2vs 22.9 months; p=0.016). positive ctDNA at baseline was associated with a worse prognosis in patients with BR or LA PA. These data are exploratory and must be confirmed in further prospective trials.

Current status and future perspective of neoadjuvant therapy in locally advanced and borderline resectable pancreatic adenocarcinoma: a narrative review.

The concept of neoadjuvant approach for patients with locally advanced pancreatic cancer (LAPC) has been evolving with the advancement in therapeutic modalities. In this narrative review, we aimed to discuss the updates and future perspectives on the treatment of LAPC. We discussed the recent literature and up-to-date evidence along with the future perspectives for the treatment of LAPC using the neoadjuvant approach. Reviewed literatures were searched by systematic search of PubMed and Google Scholar, including articles published in English between January 1st, 2013, and October 31st, 2021. We aimed to review the efficacy outcomes of modern-era chemotherapy regimens and chemoradiation therapy for LAPC based on the results of up-to-date clinical trials and pivotal observational studies. Moreover, we aimed to discuss the role of conversion surgery and studies on the prediction of resectability after neoadjuvant therapy along with the necessity of adjuvant therapy for patients who have received neoadjuvant systemic treatments. Finally, we have addressed several unanswered questions regarding the optimal management of patients with LAPC and determined the future directions by introducing some ongoing trials. Current chemotherapy and chemoradiation therapy has improved clinical outcomes and the conversion surgery rate in patients with LAPC. Future randomized clinical trials and biomarker studies are needed to provide better evidence that can aid in the selection of optimal treatment modalities for individual patients.

Evolution of carbohidrated antigen 19-9 levels during neoadjuvant treatment can predict resectability and survival in borderline resectable pancreatic adenocarcinoma

Evolution of carbohidrated antigen 19-9 levels during neoadjuvant treatment can predict resectability and survival in borderline resectable pancreatic adenocarcinoma

Yale Precision Medicine Tumor Board: reawakening the guardian of the genome.

A 56-year-old man was diagnosed with a borderline resectable pancreatic adenocarcinoma and underwent neoadjuvant chemotherapy with fluorouracil, oxaliplatin, and irinotecan (modified FOLFIRINOX) followed by successful pancreaticoduodenectomy. He had a family cancer history of early-onset breast cancer in a maternal aunt and glioblastoma in his father and a paternal first cousin. Thus, his blood was analysed at a reference laboratory (Invitae, San Francisco, CA, USA) by an 83-gene hereditary cancer predisposition panel, which showed a heterozygous pathogenic variant associated with Li Fraumeni syndrome, TP53 Y220C.

Total neoadjuvant therapy for pancreatic adenocarcinoma increases probability for a complete pathologic response

BackgroundMultiple neoadjuvant therapy protocols have been proposed in the treatment of pancreatic adenocarcinoma, including chemotherapy (CT), chemoradiation (CRT), and total neoadjuvant therapy (TNT), defined as a CT plus CRT. A pathologic complete response (pCR) can be achieved in a minority of cases. We hypothesize that TNT is more likely to confer pCR than other neoadjuvant therapies, which may improve overall survival (OS). MethodsA retrospective review of the National Cancer Database (NCDB) from 2006 to 2016 was performed, identifying patients who underwent any neoadjuvant therapy followed by definitive pancreatic resection for locally advanced or borderline resectable pancreatic adenocarcinoma. A pathologic complete response was defined as down-staging from any clinical stage to pathologic stage 0. ResultsA total of 5402 patients who received neoadjuvant therapy followed by resection were identified. 177 patients (3.3%) achieved a pCR. Of the patients who achieved a pCR, 57 received CT, 41 CRT and 79 received TNT. On multivariate analysis, TNT was more likely to confer a pCR than CRT (OR 1.67, CI 1.13–2.46, p = 0.0103) or CT (OR 2.61, CI 1.83–3.71, p < 0.0001). Patients who achieved pCR had a significantly higher OS, with median survival of 64.9 months, compared to 21.6 months in patients who did not achieve pCR (p < 0.0001). ConclusionTNT may be more likely to achieve a pCR than CT or CRT. Patients who achieve a pCR have a significant OS benefit as compared to those who have residual disease. TNT should be considered for patients requiring neoadjuvant therapy, as it may increase the likelihood of achieving a pCR, thus potentially improving OS.

Disparities in Receipt of Neoadjuvant Chemotherapy in Patients with Borderline Resectable Pancreatic Cancer

Introduction: Neoadjuvant chemotherapy (NT) in patients with borderline resectable pancreatic adenocarcinoma (BR) is associated with improved outcomes compared to surgery-first. Despite known benefit of NT, it remains unknown if socioeconomic disparities exist concerning administration of NT in patients with BR. Methods: Data from National Cancer Database identified patients with BR who underwent surgical resection. BR was defined as having venous or arterial involvement. Demographic factors of patients receiving NT was compared to surgery-first approach. Multivariable analysis was performed to identify characteristics associated with receipt of NT. Results: Of the 2,924 patient identified, 49.3% received NT. Age was associated with likelihood of receiving NT, with those ≥70 being less likely to receive NT compared to those ≤59 (OR 0.51, p<.001). Geographic location was associated with receipt of NT in the Northeast, Southwest, and West compared to treatment in Central Western United States (p<.05). Lastly, patients treated at community hospitals were significantly less likely to receive NT compared to those treated at academic institutions (OR 0.49, p<.001). Sex, race, insurance status, and education were not associated with likelihood of receiving NT (p>0.5). Those who received NT were more likely to be downstaged, have negative margin resection, and have a node negative disease compared to those who did not receive NT (p<.001). Discussion: This study reaffirms that use of NT in BR is associated with improved oncologic outcomes. Identification of existing disparities in the use of NT in patients with BR allows directed efforts to decrease disparities and increase access to NT.

The Fate of Resectable Pancreatic Adenocarcinoma Following Neoadjuvant Chemotherapy

Background: Pancreatic cancer continues to be a major cause of cancer-related mortality. There has been a greater implementation of upfront chemotherapy for pancreatic adenocarcinoma patients. Although there are many theoretical benefits to neoadjuvant chemotherapy, its clinical impact is uncertain. We sought to understand the outcomes of patients with resectable and borderline-resectable pancreatic adenocarcinoma who undergo neoadjuvant chemotherapy. Methods: Patients were collected in a secure database from September 2018 to May 2020. Patients were excluded if they presented with locally advanced or metastatic disease, inability to complete chemotherapy or if they were not a surgical candidate. Anatomic resectability was determined by the 2017 International Consensus Definition. Results: 66 patients with resectable disease underwent chemotherapy. FOLFIRINOX was used in 41 (62%) patients, gemcitabine-based regimens in 28 (42%) patients (total greater than 100% as some patients underwent both regimens). Following re-staging, 47 patients (71.2%) were thought to have resectable disease. Of these patients, 36 have been successfully resected to date. Metastatic disease was found in 12 patients (18.2%) and 6 patients (9.1%) had locally advanced disease. Conclusion: Most patients with resectable pancreatic cancer are resected after neoadjuvant chemotherapy, but a subset will develop local or distant progression. Further studies will be needed to determine which patients will progress locally and may benefit from an upfront surgical approach.