Surgical Complications in a Multicenter Randomized Trial Comparing Preoperative Chemoradiotherapy and Immediate Surgery in Patients With Resectable and Borderline Resectable Pancreatic Cancer (PREOPANC Trial)

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Jelle C. van Dongen ◽  
Mustafa Suker ◽  
Eva Versteijne ◽  
Bert A. Bonsing ◽  
J. Sven D. Mieog ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Randomized Trial ◽  
Surgical Complications ◽  
Preoperative Chemoradiotherapy ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Multicenter Randomized Trial ◽  
Immediate Surgery

Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1): A randomized, controlled, multicenter phase III trial.

2018 ◽  
Vol 36 (18_suppl) ◽  
pp. LBA4002-LBA4002 ◽  
Author(s):  
Geertjan Van Tienhoven ◽  
Eva Versteijne ◽  
Mustafa Suker ◽  
Karin B.C. Groothuis ◽  
Olivier R. Busch ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Phase Iii ◽  
R0 Resection ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Randomized Controlled ◽  
Immediate Surgery

LBA4002 Background: Standard of care for patients with (borderline) resectable pancreatic adenocarcinoma is resection followed by adjuvant chemotherapy. Previous studies suggest a benefit of neoadjuvant treatment. We conducted a multicenter phase III randomized controlled trial to evaluate the effect of preoperative chemoradiotherapy. Methods: Patients with (borderline) resectable pancreatic cancer, pathologically confirmed, were randomized between immediate surgery (arm A) and preoperative chemoradiotherapy (arm B), both followed by adjuvant chemotherapy. The preoperative chemoradiotherapy consisted of 15 times of 2.4 Gray (Gy) combined with gemcitabine, 1,000 mg/m2 on days 1, 8 and 15, preceded and followed by a cycle of gemcitabine. Primary endpoint was overall survival (OS), secondary endpoints were (R0) resection rate, disease free survival (DFS), distant metastases free interval (DMFI), locoregional recurrence free interval (LRFI) and toxicity. Accrual was completed between April 23, 2013 and July 25, 2017. Results: In total, 246 patients were included in the intention-to-treat analysis (127 patients in arm A and 119 in arm B). Currently, 142 of the 176 needed events for the primary outcome are observed. OS was significantly better in arm B (median 13.5 vs. 17.1 months; HR 0.71; p = 0.047). This was also the case for R0 resection rate (31% vs. 65%, p = < 0.001), DFS (median 7.9 vs. 11.2 months; HR 0.67; p = 0.010), DMFI (median 10.2 vs 17.1 months; HR 0.63; p = 0.012) and LRFI (median 11.8 vs not reached; HR 0.47; p < 0.001). Resection rates were 72% (91/127) in arm A vs. 62% (74/119) in arm B (p = 0.15). No significant difference was observed in grade ≥ 3 adverse events between both groups (p = 0.17). A subgroup analysis of patients who actually underwent a resection was performed which showed a median OS of 16.8 and 29.9 months respectively (p < 0.001). Conclusion: Our preliminary data show that preoperative chemoradiotherapy significantly improves outcome in (borderline) resectable pancreatic cancer compared to immediate surgery. Updated results will be presented at the meeting. Clinical trial information: NTR3709.

scholarly journals Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial

2020 ◽  
Vol 38 (16) ◽  
pp. 1763-1773 ◽  
Author(s):  
Eva Versteijne ◽  
Mustafa Suker ◽  
Karin Groothuis ◽  
Janine M. Akkermans-Vogelaar ◽  
Marc G. Besselink ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Preoperative Chemoradiotherapy ◽  
Phase Iii ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Intention To Treat ◽  
Immediate Surgery

PURPOSE Preoperative chemoradiotherapy may improve the radical resection rate for resectable or borderline resectable pancreatic cancer, but the overall benefit is unproven. PATIENTS AND METHODS In this randomized phase III trial in 16 centers, patients with resectable or borderline resectable pancreatic cancer were randomly assigned to receive preoperative chemoradiotherapy, which consisted of 3 courses of gemcitabine, the second combined with 15 × 2.4 Gy radiotherapy, followed by surgery and 4 courses of adjuvant gemcitabine or to immediate surgery and 6 courses of adjuvant gemcitabine. The primary end point was overall survival by intention to treat. RESULTS Between April 2013 and July 2017, 246 eligible patients were randomly assigned; 119 were assigned to preoperative chemoradiotherapy and 127 to immediate surgery. Median overall survival by intention to treat was 16.0 months with preoperative chemoradiotherapy and 14.3 months with immediate surgery (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; P = .096). The resection rate was 61% and 72% ( P = .058). The R0 resection rate was 71% (51 of 72) in patients who received preoperative chemoradiotherapy and 40% (37 of 92) in patients assigned to immediate surgery ( P < .001). Preoperative chemoradiotherapy was associated with significantly better disease-free survival and locoregional failure-free interval as well as with significantly lower rates of pathologic lymph nodes, perineural invasion, and venous invasion. Survival analysis of patients who underwent tumor resection and started adjuvant chemotherapy showed improved survival with preoperative chemoradiotherapy (35.2 v 19.8 months; P = .029). The proportion of patients who suffered serious adverse events was 52% versus 41% ( P = .096). CONCLUSION Preoperative chemoradiotherapy for resectable or borderline resectable pancreatic cancer did not show a significant overall survival benefit. Although the outcomes of the secondary end points and predefined subgroup analyses suggest an advantage of the neoadjuvant approach, additional evidence is required.

ESPAC-5F: Four-arm, prospective, multicenter, international randomized phase II trial of immediate surgery compared with neoadjuvant gemcitabine plus capecitabine (GEMCAP) or FOLFIRINOX or chemoradiotherapy (CRT) in patients with borderline resectable pancreatic cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4505-4505 ◽  
Author(s):  
Paula Ghaneh ◽  
Daniel H. Palmer ◽  
Silvia Cicconi ◽  
Christopher Halloran ◽  
Eftychia Eirini Psarelli ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Therapy ◽  
Recruitment Rate ◽  
Rank Test ◽  
R0 Resection ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Immediate Surgery

4505 Background: Patients with borderline resectable pancreatic cancer have poor survival and low resection rates. Neoadjuvant therapy may improve the outcome for these patients. The aim of this trial was to determine the feasibility and efficacy of a comparison of immediate surgery versus neoadjuvant GEMCAP or FOLFIRINOX or CRT. Methods: Eligible patients with NCCN defined borderline resectable (following central review of the baseline CT scan) and biopsy proven pancreatic cancer were randomised (stratified by centre) to receive immediate surgery, or neoadjuvant therapy of either 2 cycles of GEMCAP, or 4 cycles of FOLFIRINOX or 50.4Gy capecitabine-based CRT in 28 daily fractions over 5 ½ weeks. Patients were restaged at 4-6 weeks and underwent surgical exploration if still borderline resectable. Resected patients received adjuvant therapy. Follow up was 12 months. There was quality assurance of surgery and CRT. Primary endpoints were recruitment rate and resection rate (R1/R0). Secondary endpoints included overall survival and toxicity. A target of 90 patients was set to determine feasibility and resection rates. Rates will be presented as point estimates and survival compared across treatment arms using a log-rank test. Analyses will be on an ITT basis. Results: Between August 2014 and December 2018, 90 patients were randomised with 88 included in the full analysis set (32 immediate surgery, 20 GEMCAP, 20 FOLFIRINOX, 16 CRT). Median age was 63 years, 44% were men. WHO performance status was 0 and 1 in 45% and 55% respectively. Median CA19-9 was 603 kU/L at baseline. 44 (79%) patients completed neoadjuvant therapy. Recruitment rate was 21 patients per year. Resection rate was 62% for immediate surgery and 55% for neoadjuvant therapy (p=0.668). R0 resection rate on resected patients was 15% and 23% respectively (p=0.721). One year survival rate was 40% [95% CI, 26% – 62%] for immediate surgery and 77% [95%CI, 66% - 89%] for neoadjuvant therapy. Log-rank analysis showed an HR=0.27 [95% CI, 0.13 – 0.55]; χ2 (1) = 14.91, P<0.001. 9 out of the 51 neoadjuvant patients included in the safety set reported 12 serious adverse events of grade 3 or above. Conclusions: There was no difference in resection rate between arms, however neoadjuvant therapy had a significant survival benefit compared with immediate surgery. Clinical trial information: 89500674 .

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