Treatment of borderline resectable (BR) and locally advanced (LA) pancreatic cancer in the era of FOLFIRINOX and gemcitabine plus nab-paclitaxel: A multi-institutional study.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 451-451 ◽  
Author(s):  
Kamran Idrees ◽  
Alexander A. Parikh ◽  
Lauren McLendon Postlewait ◽  
Sharon M. Weber ◽  
Clifford Suhyun Cho ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Surgical Resection ◽  
Residual Disease ◽  
Locally Advanced ◽  
R0 Resection ◽  
Recurrence Rates ◽  
Borderline Resectable ◽  
Venous Resection ◽  
Term Survival ◽  
Treatment Protocols

451 Background: FOLFIRINOX or Gemcitabine+nab-Paclitaxel (Gem/nPac) has superior overall survival (OS) compared with gemcitabine alone in pts with Stage 4 pancreatic cancer (PC). Based on these results, FOLFIRINOX or Gem/nPac has been utilized in neoadjuvant (NA) setting for BR and LA PC. This report describes our multi-institutional experience with NA treatment with FOLFIRINOX or Gem/nPac followed by surgical resection. Methods: Pts with BR and LA PC who received NA FOLFIRINOX or Gem/nPac and underwent surgical resection between 2011 and 2015 at 7 high volume pancreas centers were reviewed. Pre-operative chemoradiation therapy (pCXRT) was administered selectively based on radiographic response (RR). Near-complete (minimal residual disease) or complete pathologic response (PR) was categorized as marked PR. Results: 86 pts received either NA FOLFIRINOX (69%) or Gem/nPac therapy (31%) for BR (67%), LA (32%) PC. pCXRT was administered in 71% of pts. Pts received a median of 4 cycles of FOLFIRINOX (range 1-28) and 3 cycles of Gem/nPac (range 2-13). No grade 4-5 toxicities were noted. The majority of pts underwent pancreaticoduodenectomy (84%) and vascular resection was performed in 53% - 40 with venous resection and 6 with arterial resection. R0 resection rate was 86% with no difference between two treatment groups (p = 0.9). Reduction in CA 19-9 or RR did not correlate with pathological response (p = 0.8). A marked PR was seen in 12 pts – 13.6% vs. 15.4% for FOLFIRINOX and Gem/nPac, respectively (p = 0.8). Adjuvant chemotherapy or CXRT was administered in 44% of pts. With a median follow up of 20 months (mo), OS was 27.4 mo with median OS in marked PR was 53 vs. 25 mo in moderate PR/non-responders (p = 0.04). Recurrence was noted in 45 pts – 49% had distant recurrence, 20% had local recurrence and 31% had both. Conclusions: Neoadjuvant FOLFIRINOX or Gem/nPac therapy in conjunction with aggressive surgical resection in BR and select LA PDAC pts result in significant long-term survival especially in marked pathologic responders. Further, optimization of treatment protocols in the neoadjuvant and adjuvant setting is warranted since recurrence rates are high.

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.

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.

scholarly journals Analysis of the Curative Effect of Neoadjuvant Therapy on Pancreatic Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Liqiong Yang ◽  
Yun Bai ◽  
Qing Li ◽  
Jie Chen ◽  
Fangfang Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Adverse Reactions ◽  
Neoadjuvant Chemoradiotherapy ◽  
Primary Treatment ◽  
R0 Resection ◽  
Resectable Pancreatic Cancer ◽  
Recurrence Rates ◽  
Borderline Resectable

The prevalence of pancreatic cancer is sharply increasing recently, which significantly increases the economic burden of the population. At present, the primary treatment of resectable pancreatic cancer is surgical resection, followed by chemotherapy with or without radiation. However, the recurrence rates remain high even after R0 resection. This treatment strategy does not distinguish undetected metastatic disease, and it is prone to postoperative complications. Neoadjuvant therapies, including neoadjuvant chemotherapy and radiotherapy, is being increasingly utilized in borderline resectable as well as resectable pancreatic cancer. This review summarized and discussed clinical trials of neoadjuvant therapy for pancreatic cancer, comparing resection rates, outcome measures, and adverse reactions between neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy.

A phase II study of neoadjuvant gemcitabine/5-fluorouracil followed by 5-fluorouracil/oxaliplatin concurrent with radiation in patients with locally advanced pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 259-259
Author(s):  
C. Lin ◽  
B. M. Kos ◽  
A. R. Sasson ◽  
J. L. Meza ◽  
J. L. Grem
Keyword(s):  
Pancreatic Cancer ◽  
Continuous Infusion ◽  
Pancreatic Adenocarcinoma ◽  
Phase Ii ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
R0 Resection ◽  
Borderline Resectable ◽  
R1 Resection

259 Background: We designed this phase II trial to determine the efficacy and safety of a neoadjuvant regimen involving gemcitabine, infusional 5-fluorouracil (5-FU), oxaliplatin and radiation therapy (RT) in patients with locally advanced pancreatic adenocarcinoma Methods: Induction chemotherapy (CT) consisted of two 3-week cycles of weekly gemcitabine with 24-hour continuous infusion of 5 FU for 2 of 3 weeks. Chemoradiation (CRT) consisted of RT of 50.4 Gy in 28 fractions or 50 Gy in 25 fractions and weekly oxaliplatin with 24-hour continuous infusion of 5 FU throughout RT. The first 7 patients also received celecoxib 200 mg BID throughout induction CT and CRT. Upon completion of CRT, surgical candidates underwent a pancreatoduodenectomy. Response rate was assessed according to RECIST criteria 4 weeks after the end of CRT. CTC AE v3 was used to grade the acute side effects. The failure-free survival (FFS), overall survival (OS) and median survival were analyzed by the Kaplan Meier method. Results: Twenty-nine patients who had borderline resectable pancreatic adenocarcinoma at the UNMC were enrolled and received induction CT. Twenty-four patients completed CRT. Nineteen patients had surgical exploration: 4 were unresectable, 6 had intra-abdominal metastases, and 9 had resection (seven had R0 resection, 2 had R1 resection, and 6 had negative nodes). The median follow up was 27 months. There were maximum 48% acute grade 3-4 toxicities during induction CT and CRT. The median FFS and OS were 7 and 10 months and the 2-year FFS and OS were 17% and 28%. Median OS and FFS for patients with and without resection was 26 vs. 9 months, p=0.06; and 19 vs. 5 months, p=0.01. Patients with CA19-9 above 90 U/L throughout treatment had significantly shorter FFS and OS than patients with CA19-9 less than 90 throughout treatment or had a decline from baseline to less than 90 after treatment. Conclusions: Induction gemcitabine/5-FU followed by 5-FU/oxaliplatin concurrent with RT led to down staging in 31% patients with subsequent resection. Further innovative strategies are needed to improve the outcome of patients with locally advanced pancreatic cancer. No significant financial relationships to disclose.

Phase II study of neoadjuvant chemotherapy with modified FOLFOXIRI in borderline resectable or unresectable stage III pancreatic cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4062-4062 ◽  
Author(s):  
Enrico Vasile ◽  
Nelide De Lio ◽  
Carla Cappelli ◽  
Luca Pollina ◽  
Niccola Funel ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Surgical Resection ◽  
Phase Ii ◽  
Locally Advanced ◽  
Local Treatment ◽  
Stage Iii ◽  
Borderline Resectable ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Radical Surgical Resection

4062 Background: FOLFIRINOX has shown high activity in metastatic pancreatic cancer (PC) patients and could be an interesting regimen also for patients with inoperable locally advanced disease. Our group had developed a similar schedule in metastatic colorectal cancer named FOLFOXIRI with good tolerance and activity. Therefore, we have decided to perform a phase II trial to prospectively evaluate the activity of modified FOLFOXIRI in borderline resectable or unresectable PC. Methods: Modified FOLFOXIRI consisted of a lower dose of irinotecan (150 mg/sqm) and of infusional 5-fluorouracil (2800 mg/sqm as a 48-hour continuous infusion on days 1 to 3) with no bolus 5-fluorouracil. Folinic acid and oxaliplatin (85 mg/sqm) remained unchanged. The study enrolled patients with diagnosis of pancreatic adenocarcinoma, stage III borderline resectable or unresectable disease (cT4,cN0-1,cM0), ECOG PS 0-1, age 18-75. The primary end-point of the study was the percent of patients who undergo radical surgical resection after chemotherapy. Results: Thirty-two patients have been enrolled; M/F=12/20; PS 0/1=16/16. Median age was 60 years (range 44-75). Median number of FOLFOXIRI cycles was 6 (range 2-14). Grade 3-4 toxicities was experienced by 20 patients during chemotherapy. Twelve partial responses (37%) and 14 stable diseases (45%) have been observed; 2 patients had progressive diseases (6%). The remaining 4 patients (12%) have not been yet evaluated because are still in the first months of treatment. A local treatment was received after chemotherapy by 18 patients until now: 13 (41%) received radical surgical resection and 5 received concomitant chemo-radiotherapy. Three explorative laparotomy showed occult metastases. In other 7 cases surgery is planned while 2 patients refused surgery. Median progression-free survival is 14.0 months and median overall survival is 24.2 months with a two-year survival rate of 54%. Conclusions: Chemotherapy with FOLFOXIRI seems active in locally advanced PC and may allow to obtain a downstaging of disease leading to achieve a curative surgical resection in some cases. Longer follow up is needed to better evaluate long-term outcome of this strategy.

scholarly journals What Should Guide the Performance of Venous Resection During Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma with Venous Contact?

2021 ◽  
Author(s):  
Julie Navez ◽  
Christelle Bouchart ◽  
Diane Lorenzo ◽  
Maria Antonietta Bali ◽  
Jean Closset ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Surgical Resection ◽  
Tumor Biology ◽  
Surgical Techniques ◽  
Surgical Margin ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Tumors ◽  
R0 Resection ◽  
Venous Resection ◽  
Increased Risk

AbstractComplete surgical resection, most often associated with perioperative chemotherapy, is the only way to offer a chance of cure for patients with pancreatic cancer. One of the most important factors in determining survival outcome that can be influenced by the surgeon is the R0 resection. However, the proximity of mesenteric vessels in cephalic pancreatic tumors, especially the mesenterico-portal venous axis, results in an increased risk of vein involvement and/or the presence of malignant cells in the venous bed margin. A concomitant venous resection can be performed to decrease the risk of a positive margin. Given the additional technical difficulty that this implies, many surgeons seek a path between the tumor and the vein, hoping for the absence of tumor infiltration into the perivascular tissue on pathologic analysis, particularly in cases with administration of neoadjuvant therapy. The definition of optimal surgical margin remains a subject of debate, but at least 1 mm is an independent predictor of survival after pancreatic cancer surgical resection. Although preoperative radiologic assessment is essential for accurate planning of a pancreatic resection, intraoperative decision-making with regard to resection of the mesenterico-portal vein in tumors with a venous contact remains unclear and variable. Although venous histologic involvement and perivascular infiltration are not accurately predictable preoperatively, clinicians must examine the existing criteria and normograms to guide their surgical management according to the integration of new imaging techniques, preoperative chemotherapy use, tumor biology and molecular histopathology, and surgical techniques.

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]

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