Local and systemic recurrence following total neoadjuvant therapy (TNT) and resection for borderline resectable and locally advanced pancreatic adenocarcinoma: Long-term follow up from two phase II studies.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4133-4133
Author(s):  
Grace E. Ryan ◽  
Janet E. Murphy ◽  
Christine A. Ulysse ◽  
Beow Y. Yeap ◽  
Jennifer Yon-Li Wo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Therapy ◽  
Metastatic Disease ◽  
Locally Advanced ◽  
Vascular Involvement ◽  
R0 Resection ◽  
Borderline Resectable ◽  
Metastatic Recurrence ◽  
Total Neoadjuvant Therapy

4133 Background: With the advent of FOLFIRINOX, the management of pancreatic cancer has undergone a profound change. There has been a shift to TNT with FOLFIRINOX followed by radiation and an attempt at surgical resection. Recent trials of TNT have demonstrated an ability to resect locally advanced (LA) and borderline resectable disease. There is a lack of prospective data demonstrating local and systemic recurrence rates after TNT. Methods: Two previously reported prospective clinical trials (Murphy JE, et al, JAMA Oncol 2018, 2019) of total neoadjuvant therapy were conducted between 2012 and 2018 for borderline and LA disease (NCT01591733, NCT01821729). Patients received FOLFIRINOX for 8 cycles. Upon restaging, patients with resolution of vascular involvement received short-course chemoradiotherapy (5 Gy x 5 with protons or 3 Gy x 10 w photons) with capecitabine (N=34). Patients with persistent vascular involvement received long-course chemoradiotherapy with capecitabine (N=56). All patients were considered for resection after TNT except for those patients with metastatic or unresectable disease. Results: 97 eligible patients were enrolled and started treatment on the borderline resectable (n = 48) and locally advanced (n= 49) study. 90 patients completed therapy. 80 patients were taken to the operating room. 61 patients had R0 resection and 5 patients had R1 resection. The table shows the distribution of local recurrences, local recurrences and metastatic disease, and metastatic disease alone. With a median follow-up of 5.2 years (range: 2.4-6.0), of the 61 R0 patients, 22 patients remained alive and free of disease, 7 patients had a local recurrence, 4 patients had locoregional and metastatic recurrence, and 24 patients had a metastatic recurrence. 3 patients who underwent R0 resection died of unrelated causes. Median survival for patients undergoing R0 resection is 43.8 months. Conclusions: Total neoadjuvant therapy for locally advanced and borderline resectable pancreatic cancer is potentially curable and may change the pattern of spread.[Table: see text]

Neoadjuvant FOLFIRINOX and/or gemcitabine/nab-paclitaxel for advanced pancreatic adenocarcinoma.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 473-473 ◽  
Author(s):  
Keli Turner ◽  
Sumana Narayanan ◽  
Kristopher Attwood ◽  
Steven N. Hochwald ◽  
Renuka V. Iyer ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Surgical Resection ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
R0 Resection ◽  
Borderline Resectable ◽  
Biomarker Response

473 Background: Neoadjuvant chemotherapy is increasingly being utilized for locally advanced (LAPC)/borderline resectable pancreatic cancer (BRPC); however, long term follow up data is sparse. At our institution, we use FOLFIRINOX as the regimen of choice. Gemcitabine (Gem) and nab-Paclitaxel (Abraxane) is utilized in patients not suited for FOLFIRINOX or if they have poor radiographic response and/or develop significant toxicities to FOLFIRINOX. The aim of this study was to report our institutional experience with neoadjuvant therapy for patients with advanced pancreatic cancer. Methods: A retrospective review was performed of all patients with BRPC or LAPC who received FOLFIRINOX (or a modified regimen), Gem/nab-Paclitaxel, or both prior to surgical resection. FOLFIRINOX was typically given for 4 – 6 cycles while gem/nab-Paclitaxel was given for 2 cycles. Results: From January 2011 to December 2015, 39 patients were identified who met the study criteria. Eight patients received FOLFIRINOX alone (median age 62), 20 patients received FOLFIRINOX + Gem/nab-Paclitaxel, and 11 received only Gem/nab-Paclitaxel (median age 72). Eighteen patients (46%) completed the intended cycles of chemotherapy. Twenty two patients had a radiologic and/or biomarker response. Exploration was performed in 25 of 39 (64%) patients of whom 20 (51%) underwent curative resection. Of the 20 resected patients, there were no post-operative deaths. The median tumor size, median lymph node ratio, and R0 resection rates were 2.4 cm, 0, and 85% for the entire cohort. Median follow up was 20.7 months. The median overall survival for the resected cohort was not reached vs 13.5 months in the no resection group; two year overall survival for the resection vs. no resection groups was 87% vs 16% (p < .001). Conclusions: FOLFIRINOX and/or Gemcitabine/nab-Paclitaxel as neoadjuvant therapy for LAPC/BRPC is fairly well tolerated, leads to appreciable rates of margin negative surgical resection, and a significant overall survival advantage.

Association of total neoadjuvant therapy with major pathologic response and survival in localized pancreatic cancer: A multi-institutional analysis of 504 patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4145-4145
Author(s):  
Jashodeep Datta ◽  
Amber Collier ◽  
Joshua Kronenfeld ◽  
Gregory Wilson ◽  
Ugwuji Maduekwe ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Therapy ◽  
Performance Status ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Pathologic Response ◽  
Oncologic Outcomes ◽  
Borderline Resectable ◽  
Total Neoadjuvant Therapy ◽  
To Receive

4145 Background: Despite increased utilization of neoadjuvant therapy for pancreatic cancer (PC), a substantial proportion of patients never receive adjuvant therapy. We examined if total neoadjuvant therapy (TNT) would facilitate delivery of all prescribed (≥6 months) non-surgical therapy (NST: chemotherapy ± radiation) to improve oncologic outcomes. Methods: Patients receiving neoadjuvant FOLFIRINOX or gemcitabine/nab-paclitaxel ±radiation followed by pancreatectomy at 7 centers were reviewed. Patients receiving TNT (≥6 months NST pre-resection) were compared to those receiving < 6 months ( < TNT). Primary outcomes were major (complete/near-complete) pathologic response (MPR) and overall survival (OS). Results: Of 504 patients, 105 (21%) were selected for TNT. TNT and < TNT patients had similar performance status and rates of borderline resectable/locally advanced disease (82% vs. 80%). TNT patients were significantly more likely to receive ≥6 months NST (100% vs. 31%; p < 0.001) vs. < TNT. While selection of chemotherapy regimen (FOLFIRINOX or gemcitabine/nab-paclitaxel) did not differ between TNT and < TNT cohorts, TNT patients were more likely to receive neoadjuvant radiation (44% vs. 25%, p < 0.001). Rates of vascular resection, postoperative complications, and mortality were similar between groups. TNT was associated with decreased rates of lymphovascular/perineural invasion (p = 0.002) and nodal positivity (p = 0.001), and increased rates of MPR (41% vs. 23%; p = 0.001) and pathologic complete response (13% vs. 6%; p = 0.02). TNT was associated with improved OS compared with < TNT (median 38 vs. 30 months; p = 0.039). Both MPR (median 38 [MPR] vs. 28 [limited response] months; p = 0.002) and ≥6 months NST (TNT or peri-operative) (median 38 [≥6m] vs. 26 [ < 6m] months; p = 0.001) were associated with improved OS. Addition of radiation was not associated with MPR or OS. Conclusions: The TNT approach allows more patients with localized PC to receive ≥6 months NST and is associated with improved rates of MPR and OS. TNT should be considered for all patients with operable PC when possible.

Utility of [18F] flourodeoxyglucose positron emission tomography (FDG-PET) to predict resectability after neoadjuvant therapy in patients with unresectable pancreatic cancer on CT scans.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 357-357
Author(s):  
Mohamad Osama Khawandanah ◽  
Carla Kurkjian ◽  
Shyla Penaroza ◽  
Charles Arnold ◽  
Terence S. Herman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Therapy ◽  
Fdg Pet ◽  
Locally Advanced ◽  
Ct Scans ◽  
R0 Resection ◽  
Borderline Resectable ◽  
Unresectable Disease ◽  
Number Of Patients ◽  
Pet Ct

357 Background: The standard imaging approach in patients with pancreatic cancer is contrast enhanced computed tomography (CT), however, Response Evaluation Criteria in Solid Tumors (RECIST) may not be adequate in evaluating response to neoadjuvant therapy. A growing body of evidence exists to suggest that there is additional useful information to be gained from the use of FDG-PET scans in this setting. Methods: We conducted an IRB approved retrospective chart review of patients with locally advanced or borderline resectable pancreatic adenocarcinoma who underwent neoadjuvant therapy at the University of Oklahoma and who had PET/CT imaging before and/or after neoadjuvant therapy between September 2006 and September 2013. Complete remission (CR) was defined as decrease in SUV to ≤ 3.0 or background, and partial response (PR) was defined as decrease in SUV from baseline, but > 3.0. Results: A total of 13 patients underwent Whipple surgery after neoadjuvant therapy at our institution. Four patients (31%) had persistent unresectable disease on CT scans post-neoadjuvant therapy, but demonstrated CR (three patients) or PR (one patient; Pre-treatment SUV: 10.1, Post Treatment: 4.6) on the PET scan. These patients underwent Whipple surgery based on PET response. All four (100%) patients underwent R0 resection. Two patients (50%) received neoadjuvant chemo-radiation in addition to chemotherapy. Conclusions: Response on FDG-PET/CT can be a predictor of R0 resection in cases with evidence of unresectable disease on conventional CT scan. A protocol to study larger number of patients prospectively is being designed.

Outcomes for patients with borderline resectable (BR) and locally advanced (LA) pancreatic cancer (PC) treated with induction FOLFIRINOX (FFX) +/- radiation (RT) followed by surgery compared to induction FFX followed by consolidative RT.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 437-437
Author(s):  
Michael Cecchini ◽  
Joseph Miccio ◽  
Jay Pahade ◽  
Jill Lacy ◽  
Ronald R Salem ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Rank Test ◽  
Vascular Involvement ◽  
Cancer Center ◽  
R0 Resection ◽  
Borderline Resectable ◽  
Term Survival ◽  
Kaplan Meier

437 Background: Induction FFX for PC deemed either BR or LA at diagnosis provides an opportunity to downstage pts with the aim of an R0 surgery. The addition of RT after induction FFX may further downstage. However, there is a paucity of data regarding long-term survival for BR and LA patients successfully downstaged and resected. We performed a retrospective review of BR and LA PC treated with induction FFX +/- RT followed by surgery or consolidative RT at the Yale Cancer Center (YCC) to assess survival in these two cohorts. Methods: Clinical data was abstracted for pts with BR or LA PC who had surgery or received consolidative RT without surgery after induction FFX +/- RT at the YCC from 2010-2018. Surgical pts were re-reviewed by a radiologist to assess vascular involvement (BR vs. LA) using NCCN criteria. PFS and OS for surgery and consolidative RT were analyzed by the Kaplan-Meier method. Survival was compared via the log rank test. Results: 102 pts met inclusion criteria (BR=47, LA=55), 41 pts had surgery [BR=29/47 (62%) LA=12/55 (22%)] and 61 pts had consolidative RT [(BR= 18/47 (38%), LA= 43/55 (78%)] after induction FFX. 18 surgery pts received RT prior to resection and all surgery pts had R0 resection. Median follow up was 25 mo (range 5 – 97). Median PFS with surgery was 22 mo (95% CI 15 – 59) vs 14 mo (95% CI 10.9 – 20.1) with consolidative RT (p<0.001), while OS with surgery was 42 mo (95% CI 25-NR) vs 20 mo (95% CI 17-25) without surgery (p<0.001). For pts with ≥ 2 yr follow up, 12/22 (55%) surgery pts and 17/18 (94%) consolidative RT pts relapsed. For pts with ≥ 3 yr follow up, 6/12 (50%) surgery pts and 10/10 (100%) consolidative RT pts relapsed. 2 yr PFS and OS was 45% (95% CI 28-61) and 74% (95% CI 57 – 86) with surgery versus 15% (95% CI 7-27) and 40% (95% CI 26-53) with consolidative RT. Conclusions: Surgery was associated with a high R0 rate and prolonged PFS and OS compared to consolidative RT in pts with BR and LA PC after FFX +/- RT. However, survival benefit was not statistically significant when selecting only LA pts although numbers are limited.

Adjuvant and Neoadjuvant Therapy for Pancreatic Adenocarcinoma

2017 ◽  
Author(s):  
Gregory C Wilson ◽  
Brent T Xia ◽  
Syed A Ahmed
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Treatment Strategies ◽  
Ductal Adenocarcinoma ◽  
Borderline Resectable

Despite decades of advancement and research into the multimodal care of pancreatic cancer, mortality after the diagnosis of pancreatic ductal adenocarcinoma remains grim. The role of adjuvant therapy following surgical resection has been well established in the literature. However, adjuvant therapy is imperfect, and outside of a clinical trial, there are high rates of omission or delayed initiation of therapy. Neoadjuvant treatment strategies continue to be explored in the management of resectable, borderline-resectable, and locally advanced unresectable pancreatic adenocarcinoma. With improved resection rates and the possibility for tumor downstaging, neoadjuvant therapy has become standard for patients with borderline-resectable and locally advanced unresectable tumors. Additional benefits of neoadjuvant therapy in the treatment of resectable tumors include improved completion rates of systemic therapy and R0 resection rates. Future clinical trials, including the use of novel treatment agents and combination treatment strategies in both neoadjuvant and adjuvant regimens, will add value to the treatment of pancreatic adenocarcinoma. Key words: adjuvant therapy, borderline-resectable pancreatic cancer, locally advanced pancreatic cancer, neoadjuvant therapy, pancreatic adenocarcinoma, resectable disease 

Management of Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma

2019 ◽  
Author(s):  
Francis Igor Macedo ◽  
Danny Yakoub ◽  
Vikas Dudeja ◽  
Nipun B. Merchant
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
The United States ◽  
Locally Advanced Pancreatic Cancer ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Number Of Patients

The incidence of pancreatic cancer continues to rise, and it is now the third-leading cause of cancer-related deaths in the United States. Only 15 to 20% of patients are eligible to undergo potentially curative resection, as most tumors are deemed unresectable at the time of diagnosis because of either locally advanced disease or distant metastases. Improvements in preoperative CT imaging have enabled better determination of the extent of disease and allowed for better operative planning. Based on their relationship to the surrounding vasculature and structures and presence or absence of distant disease, pancreatic tumors are classified into four categories: resectable, borderline resectable pancreatic cancer (BRPC), locally advanced pancreatic cancer (LAPC), and metastatic. With the recent advent of more effective chemotherapy regimens, efforts have focused on using neoadjuvant therapy approaches to increase the likelihood of achieving an R0 in patients with BRPC and possibly convert unresectable, locally advanced tumors to potentially resectable tumors. Response with neoadjuvant therapy regimens has resulted in increased number of patients eligible for resection, many times requiring vascular resection. Herein, we describe recent changes in the classification, important surgical and pathologic considerations and updated multimodal therapeutic options in the complex management of BRPC and LAPC.  This review contains 5 figures, 2 tables, and 78 references. Key Words: borderline resectable pancreatic cancer, CA 19-9, FOLFIRINOX, locally advanced pancreatic cancer, nab-paclitaxel, neoadjuvant chemotherapy, pancreatectomy, portal vein resection, radiation therapy, gemcitabine

scholarly journals Current Clinical Strategies of Pancreatic Cancer Treatment and Open Molecular Questions

2019 ◽  
Vol 20 (18) ◽  
pp. 4543 ◽  
Author(s):  
Maximilian Brunner ◽  
Zhiyuan Wu ◽  
Christian Krautz ◽  
Christian Pilarsky ◽  
Robert Grützmann ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Carcinoma ◽  
Molecular Mechanisms ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Treatment Strategies ◽  
R0 Resection ◽  
Molecular Testing ◽  
Borderline Resectable ◽  
Tumor Biopsies

Pancreatic cancer is one of the most lethal malignancies and is associated with a poor prognosis. Surgery is considered the only potential curative treatment for pancreatic cancer, followed by adjuvant chemotherapy, but surgery is reserved for the minority of patients with non-metastatic resectable tumors. In the future, neoadjuvant treatment strategies based on molecular testing of tumor biopsies may increase the amount of patients becoming eligible for surgery. In the context of non-metastatic disease, patients with resectable or borderline resectable pancreatic carcinoma might benefit from neoadjuvant chemo- or chemoradiotherapy followed by surgeryPatients with locally advanced or (oligo-/poly-)metastatic tumors presenting significant response to (neoadjuvant) chemotherapy should undergo surgery if R0 resection seems to be achievable. New immunotherapeutic strategies to induce potent immune response to the tumors and investigation in molecular mechanisms driving tumorigenesis of pancreatic cancer may provide novel therapeutic opportunities in patients with pancreatic carcinoma and help patient selection for optimal treatment.

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