Preoperative chemoradiotherapy to improve overall survival in pancreatic cancer: Long-term results of the multicenter randomized phase III PREOPANC trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4016-4016
Author(s):  
Casper H.J. Van Eijck ◽  
Eva Versteijne ◽  
Mustafa Suker ◽  
Karin Groothuis ◽  
Marc G.H. Besselink ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Preoperative Chemoradiotherapy ◽  
Phase Iii ◽  
Long Term Results ◽  
Resectable Pancreatic Cancer ◽  
Free Interval ◽  
Immediate Surgery

4016 Background: Preoperative chemoradiotherapy (CRT) may improve overall survival in resectable pancreatic cancer (RPC) and borderline resectable pancreatic cancer (BRPC). Long term results are presented. Methods: In this multicenter phase III trial, patients with RPC or BRPC were randomized between preoperative CRT, (gemcitabine 1000 mg/m2 weekly for 7 of 10 weeks, and 15x2.4 Gy radiotherapy in week 4 to 6), followed by surgery and four cycles of adjuvant gemcitabine (1000 mg/m2 weekly for 3 of 4 weeks), or immediate surgery followed by 6 cycles of adjuvant gemcitabine (1000 mg/m2 weekly for 3 of 4 weeks). Primary endpoint was overall survival by intention-to-treat (ITT). Results: From April 2013 to July 2017, 246 eligible patients were accrued by 16 Dutch centers and randomized, 119 to preoperative CRT and 127 to immediate surgery. After a median follow up of 56 months (35.3-92.0 months), 210 patients have died, 93 (78%) in the preoperative CRT arm and 117 (92%) in the immediate surgery arm. Three- and five-year overall survival ITT was 27.7% and 20.5% after preoperative CRT versus 16.5% and 6.5% after immediate surgery (HR 0.73; 95% CI 0.56 to 0.96; p = 0.025). In addition, disease-free survival (HR 0.70; p = 0.009) locoregional failure-free interval (HR 0.57; p = 0.004) and distant metastases free interval (HR 0.74; p = 0.071) improved after preoperative CRT. Also in the stratified subsets RPC and BRPC, preoperative CRT improved OS: RPC (n = 133, HR 0.79; 95% CI 0.54 to 1.16; P = 0.23). BRPC (n = 113, HR 0.67; 95% CI 0.45 to 0.99; p = 0.045). We could not demonstrate a difference in treatment effect between these subsets (interaction test p = 0.56). Conclusions: Preoperative gemcitabine-based CRT for RPC or BRPC improves long term overall survival compared to immediate surgery with adjuvant gemcitabine. 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.

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 Improved Overall Survival in Pancreatic Cancer with Preoperative Chemoradiotherapy: Long-term Results of the PREOPANC Trial

HPB ◽  
2021 ◽  
Vol 23 ◽  
pp. S672-S673
Author(s):  
E. Versteijne ◽  
J.L. van Dam ◽  
M. Suker ◽  
Q.P. Janssen ◽  
K.B.C. Groothuis ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Preoperative Chemoradiotherapy ◽  
Long Term Results

Long-term results of Intergroup RTOG 91–11: A phase III trial to preserve the larynx—Induction cisplatin/5-FU and radiation therapy versus concurrent cisplatin and radiation therapy versus radiation therapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5517-5517 ◽  
Author(s):  
A. A. Forastiere ◽  
M. Maor ◽  
R. S. Weber ◽  
T. Pajak ◽  
B. Glisson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Survival Rates ◽  
Disease Free Survival ◽  
High Volume ◽  
Phase Iii ◽  
Long Term Results ◽  
Free Survival ◽  
Significant Difference ◽  
Lower Death Rate

5517 Background: The 2-year results of Intergroup RTOG 91–11 were published in 2003 (NEJM 349:2091–8,2003). We now present the 5-year results (after median follow-up for surviving patients of 6.9 years) of 515 eligible pts with resectable stage III or IV (excluding T1 and high volume T4), cancer of the glottic or supraglottic larynx. Methods: Patients were randomized to induction cisplatin/5-FU (CF) with responders then receiving RT (I+RT) (n = 173); or concurrent cisplatin (100 mg/m2 q 21 days × 3) and RT (CRT) (n = 171); or RT alone (R) (n = 171). Laryngectomy was performed for < partial response to induction CF, for persistent/recurrent disease or for laryngeal dysfunction. Results: At 5 years, laryngectomy-free survival (LFS) was significantly better with either I+RT (44.6%, p = 0.011) or CRT (46.6%, p = 0.011) compared to R (33.9%). There was no difference in LFS between I+RT and CRT (p = 0.98). Laryngeal preservation (LP) was significantly better with CRT (83.6%) compared to I+RT (70.5%, p = 0.0029) or R (65.7%, p = 0.00017). Local-regional control (LRC) was significantly better with CRT (68.8%) compared to I+RT (54.9%, p = 0.0018) or R (51%, p = 0.0005). I+RT compared to R for LP and LRC showed no significant difference (p = 0.37 and 0.62, respectively). The distant metastatic rate was low (I+RT 14.3%, CRT 13.2%, R 22.3%) with a trend (p ∼0.06) for benefit from chemotherapy. Disease-free survival (DFS) was significantly better with either I+RT (38.6%, p = 0.016) or CRT (39%, p = 0.0058) compared to R (27.3%). Overall survival rates were similar for the first 5 years (I+RT 59.2%, CRT 54.6%, R 53.5%); thereafter I+RT had a non-significant lower death rate. Compared to CRT, significantly more pts in the R group died of their cancer (34% vs 58.3%, p = 0.0007); the rate for I+RT was 43.8%. Conclusion: These 5-year results differ from the 2-year analysis by a significant improvement in LFS now seen for both I+RT and CRT treatments compared to R. For the endpoints of LP and LRC, CRT is still the superior treatment with no advantage seen to the addition of induction CF to R. There is no significant difference in overall survival. [Table: see text]

Multimodality therapy for borderline resectable pancreatic cancer: A single-institution experience.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 280-280
Author(s):  
Jose Mario Pimiento ◽  
Tai Hutchinson ◽  
Jill M. Weber ◽  
Manish R. Patel ◽  
Pamela Joy Hodul ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Multimodality Therapy ◽  
Cancer Center ◽  
R0 Resection ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer

280 Background: Multimodality therapy has been advocated for borderline resectable pancreatic cancer (BRCP); however, specific regimens vary widely by institution. Outcomes of these interventions need to be examined to inform future investigation of the optimal therapy for these patients. This study represents the experience of multimodality therapy for BRPC at an NCI designated cancer center. Methods: We identified all patients (pts) with operable pancreatic ductal adenocarcinoma (PDA) from 2006 to 2011. Patients were divided into two groups: resectable group and BRPC group as per the NCCN and AHPBA consensus guidelines. Primary outcomes were resection rate, microscopic negative margin (R0) resection rate, overall survival (OS), and disease free survival (DFS). Fisher's exact and chi-square were used for group comparison while Kaplan-Meier estimates was used for survival analysis. Results: 160pts were identified with operable PDA. 100 (63%) pts had resectable tumors, and 60 (37%) pts had borderline resectable tumors. Neoadjuvant therapy (NT) was administered to 0% in the group with resectable tumors, and 100% in the group with borderline resectable tumors. The resection rate was 100% in pts with resectable tumors and 58% in pts with borderline resectable tumors. R0 resection rates were 80% in the resectable tumors and 97% in the borderline resectable tumors following NT. Perioperative mortality was <1% (1/125) for resectable tumors and 0% in borderline resectable tumors. Median OS was 22.6 months (m) for pts that had resectable tumors and 13.9m for all pts with borderline resectable tumors (p=0.017); however, the median OS for resected pts with borderline resectable tumors was 21.5m (p=0.6). Improved DFS was seen in patients with resectable tumors when compared with resected borderline resectable tumors (15 vs. 9.5m; p=0.04). Conclusions: Multimodality therapy leads to high rates of R0 resections in borderline resectable pancreatic cancer; however 42% of patients progressed during NT. The overall survival for patients with resected borderline resectable pancreatic cancer following NT is similar to patients who undergo resection for resectable pancreatic cancer.

scholarly journals CRITICAL EVALUATION OF LONG-TERM RESULTS OF MALIGNANT HEPATIC TUMORS TREATED BY MEANS CURATIVE LAPAROSCOPIC HEPATECTOMY

2017 ◽  
Vol 30 (3) ◽  
pp. 205-210 ◽  
Author(s):  
Sergio Renato PAIS-COSTA ◽  
Sergio Luiz Melo ARAÚJO ◽  
Olímpia Alves Teixeira LIMA ◽  
Sandro José MARTINS
Keyword(s):  
Overall Survival ◽  
Tumor Recurrence ◽  
Malignant Tumors ◽  
Laparoscopic Hepatectomy ◽  
Disease Free Survival ◽  
Long Term Results ◽  
Colorectal Metastases ◽  
Free Survival ◽  
Disease Free

ABSTRACT Background: Laparoscopic hepatectomy has presented great importance for treating malignant hepatic lesions. Aim: To evaluate its impact in relation to overall survival or disease free of the patients operated due different hepatic malignant tumors. Methods: Thirty-four laparoscopic hepatectomies were performed in 31 patients with malignant neoplasm. Patients were distributed as: Group 1 - colorectal metastases (n=14); Group 2 - hepatocellular carcinoma (n=8); and Group 3 - non-colorectal metastases and intrahepatic cholangiocarcinoma (n=9). The conversion rate, morbidity, mortality and tumor recurrence were also evaluated. Results: Conversion to open surgery was 6%; morbidity 22%; postoperative mortality 3%. There was tumor recurrence in 11 cases. Medians of overall survival and disease free survival were respectively 60 and 46 m; however, there was no difference among studied groups (p>0,05). Conclusion: Long-term outcomes of laparoscopic hepatectomy for treating hepatic malignant tumors are satisfactory. There is no statistical difference in relation of both overall and disease free survival among different groups of hepatic neoplasms.

Overall survival benefit with masitinib mesylate in imatinib-naive, locally advanced, or metastatic gastrointestinal stromal tumor (GIST): 4-years follow-up of the French Sarcoma Group phase II trial.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 85-85 ◽  
Author(s):  
J. Blay ◽  
A. Le Cesne ◽  
N. Bin Bui ◽  
O. Bouche ◽  
A. Adenis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Locally Advanced ◽  
Phase Iii ◽  
Long Term Results ◽  
First Line ◽  
Juxtamembrane Region ◽  
Metastatic Gist

85 Background: Masitinib is a novel tyrosine kinase inhibitor which, in vitro, has greater activity and selectivity than imatinib (IM) against both wild-type KIT receptor and its mutated form in the juxtamembrane region (IC 50=100 nM versus 200 nM for IM, 3 nM versus 27nM and 40 nM versus 120nM, respectively, for exons 9,11, and 13). This multicenter phase II study evaluated efficacy and safety of masitinib as a first-line treatment of advanced GIST. Methods: IM-naïve patients with inoperable, locally advanced or metastatic GIST received oral masitinib (7.5 mg/kg/day) until progression, refusal or toxicity. Efficacy variables included response rate, best response (RECIST), progression-free survival (PFS) and overall survival (OS). Initial results were previously reported in EJC 2010. We present here the same series with updated PFS and OS (median follow up of 48 months). Results: 30 patients with a median age of 58 years (60% of males) were included from June 2005 to April 2007 in five French institutions. At the cut-off date (31 august 2010), 9 patients are still under treatment with a median treatment duration of 41 months (min=33, max=52). Two additional progressions have been reported for a total of 14 events (13 progressions and 1 death). Updated median PFS is 41 months (95% CI: [17.5; NR]) with PFS rates of 60% [39; 77], 56% [35; 73] and 45% [24; 64] respectively at 2, 3 and 4 years. With 8 patients dead, median OS is not yet reached with OS rates of 90% [72; 97], 87% [68; 95] and 74% [52; 87], respectively, at 2, 3, and 4 years. The main frequent relevant grade 3 toxicities were: rash (10%), neutropenia (7%) and abdominal pain (7%) with one patient presented a grade 4 skin exfoliation. No other relevant long-term toxicities were reported and no more patients discontinued treatment due to suspected toxicity. Conclusions: The long term results observed with masitinib confirm a very interesting activity with prolonged PFS and OS. These results support the head to head comparison with imatinib in the currently ongoing phase III randomized clinical trial in first line locally advanced or metastatic GIST patients. [Table: see text]

A phase II trial of gemcitabine and S-1 therapy in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer (JSAP-03).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 263-263
Author(s):  
Akio Saiura ◽  
Hideki Ueno ◽  
Tomoo Kosuge ◽  
Yutaka Matsuyama ◽  
Hiroshi Ishii ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Adjuvant Therapy ◽  
Adverse Events ◽  
Phase Ii ◽  
Adverse Reactions ◽  
Advanced Pancreatic Cancer ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria

263 Background: Although anti-tumor effect of gemcitabine (G) and S-1 (S) therapy is high for advanced pancreatic cancer (PC) patients, safety and effectiveness of postoperative GS adjuvant therapy has not been fully examined. Methods: Eligibility criteria included macroscopically curative resection of invasive ductal PC and no prior chemotherapy. Patients were recruited in 19 institutes. The primary endpoint was overall survival (OS). The patients received G (800 mg/m2/week) intravenously over 30 min on day 1 and S (60 mg/m2/day) orally twice daily from days 1 to 7 every 14 days for 12 cycles. Results: Fifty-five patients were enrolled in this study. One patient was excluded from the analysis due to no malignant pathology. Remaining 54 patients were analyzed. Deaths were observed in 17 patients (31.5%). Median overall survival was not reached. Estimated 1-year and 2-year OS were 88.9% (95% CI, 76.9-94.8) and 72.1% (95%CI, 58.1-82.2), respectively. Recurrences were observed in 31 patients (57.4%). Estimated 1-year and 2-year disease-free survival were 57.4% (95% CI, 43.2-69.3) and 44.4% (95%CI, 30.9-57.0), respectively. G3 febrile neutropenia was observed in 1.9 % of the patients, whereas the most common adverse reactions were neutropenia (G3/4: 59.2%, G4: 25.9%). There were no G4 adverse events except neutropenia and hyperkalemia (1.9%). G3 adverse events included anemia (3.7%), alanine aminotransferase elevation (3.6%), fatigue (1.9%), nausea (1.9%), vomiting (1.9%) and infection without neutropenia (1.9%). The protocol treatments could not finish in 6 patients due to adverse reactions. Conclusions: Our phase II results suggest that the postoperative GS therapy is a promising regimen that merits further investigation. Phase III trial of postoperative G versus GS therapy is now going on (JSAP-04).

Effect of algenpantucel-L immunotherapy for pancreatic cancer on anti-mesothelin antibody (Ab) titers and correlation with improved overall survival.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3007-3007 ◽  
Author(s):  
Gabriela R. Rossi ◽  
Jeffrey M Hardacre ◽  
Mary Frances Mulcahy ◽  
Mark S. Talamonti ◽  
Jennifer Carrie Obel ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Defense Mechanism ◽  
Disease Free Survival ◽  
Immune Defense ◽  
Response To Therapy ◽  
Phase Iii ◽  
Open Label ◽  
Immunological Monitoring

3007 Background: Hyperacute rejection of tissues expressing the carbohydrate α(1,3)Gal xenoantigen is a potent innate immune defense mechanism that was leveraged to treat resected pancreatic cancer patients by immunization with genetically modified allogeneic tumor cells expressing αGal moieties (algenpantucel-L). We propose that adding algenpantucel-L to SOC adjuvant therapy may improve survival and induce immunological biomarkers that positively correlate with improved median overall survival (OS). Methods: Open-label, multicenter phase II study evaluating algenpantucel-L+SOC (RTOG-9704: gemcitabine + 5-FU-XRT) for resected pancreatic cancer patients. Endpoints: 1°) disease-free survival (DFS) at 1 year; 2°) OS, toxicity and immunologic analysis. Biomarkers were evaluated including total IgG, complement, CA19-9 levels, anti-αGal Ab, anti-CEA Ab, and anti-membrane-bound recombinant mesothelin (MSLN) Ab. Results: Patients received gemcitabine with 5-FU modulated radiation therapy plus algenpantucel-L. The primary endpoint, 12-month DFS, was 62% and 12-month OS was 86%. All evaluable patients have been in follow-up for ≥ 3 years. We now report OS rates at 3 years of 39% and DFS of 26% at 3 years. Evaluable patients (n=64) were tested for the induction of anti-MSLN Ab where ≥ 25% increase in the anti-MSLN Ab compared to baseline was considered significant (p<0.001). Twenty of 64 patients (31%) had increased anti-MSLN Ab. Patients responding with anti-MSLN Ab had a median OS of 42 months compared to 20 months for patients without sero-conversion. The positive correlation between increased anti-MSLN Ab and improved median OS was statistically significant (p=0.027). Conclusions: The addition of algenpantucel-L to SOC for resected pancreatic cancer may improve survival. In 20/64 patients, algenpantucel-L-induced anti-MSLN Ab responses that correlates with improved survival (median OS 42 vs 20 months). Immunological monitoring of algenpantucel-L immunotherapy with this biomarker is feasible and might predict patient response to therapy. A multi-institutional, phase III study is currently underway (ClinicalTrials.gov NCT01072981). Clinical trial information: NCT00569387.

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