scholarly journals P-P42 Neo-adjuvant Chemoradiation for Borderline Resectable Pancreatic Adenocarcinoma: A UK Tertiary Surgical Oncology Centre Series

2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Marina Likos-Corbett ◽  
Pranav Patel ◽  
Rachna Goburdhun ◽  
Satvinder Mudan ◽  
Amir Khan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Disease Free Survival ◽  
Ductal Adenocarcinoma ◽  
R0 Resection ◽  
Positive Surgical Margin ◽  
Resection Rate ◽  
Adjuvant Chemoradiation ◽  
Borderline Resectable ◽  
Term Survival

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is associated with a historically poor long-term survival of 5-10%, despite surgical resection. Borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) is reported as potentially resectable disease with a degree of vascular involvement, increasing the risk of a positive surgical margin. This cohort of patients have the worst survival despite curative resection and adjuvant chemotherapy. Emerging evidence suggests that neo-adjuvant chemoradiation (NCR) improves R0 resection rates in BR-PDAC patients. We evaluated the R0 resection rate, disease free survival (DFS) and overall survival (OS) in our patients, who had undergone NCR for BR-PDAC at our institution. Methods Data was collected retrospectively for all patients undergoing NCR for BR-PDAC between Jan 2010 to Mar 2020 for this study. Surgical management was ratified by clinical assessment and cross-sectional imaging in a pancreatic multidisciplinary team meeting (MDM). Patients underwent NCR by a number of standardised regimens. Patients with proven regressive or stable disease on imaging underwent a pancreatic resection. All BR-PDAC patients underwent resection in the form of classical Whipple’s or pylorus preserving pancreaticoduodenectomy (PPPD) depending on intra-operative findings. Patient morbidity, R0 resection rate, histological parameters, DFS and OS were evaluated. Results 29 patients were included in the study (16 men and 13 women), with a median age of 65 years (range, 46-74 years). 17 patients received FOLFIRINOX and 12 patients received gemcitabine (GEM) based NCR regimens. All patients received chemoradiation at the end of chemotherapy (range 45-56Gy). 75% had an R0 resection, with a greater proportion in the FOLFIRINOX group. Whole cohort median DFS was 35 months, survival was superior in the FOLFIRINOX group (42 months). Median OS was 30 months for the whole group, with a greater median OS in the FOLFIRINOX versus the GEM cohort (42 versus 29 months). Conclusions We present a single centre retrospective study utilising NCR for BR-PDAC, we reiterate the strong association of an R0 resection with superior patient overall survival following surgery in this cohort. We show that in patients with BR-PDAC, NCR results in superior R0 resection rates with an associated increase in patient survival. Our results show that survival advantage is greatest in BR-PDAC patients who received neo-adjuvant FOLFIRINOX.  Our findings affirm the advantage of NCR prior to surgery, particularly FOLFIRINOX based treatment, in this cohort of patients.

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.

CONKO-005: Adjuvant Chemotherapy With Gemcitabine Plus Erlotinib Versus Gemcitabine Alone in Patients After R0 Resection of Pancreatic Cancer: A Multicenter Randomized Phase III Trial

2017 ◽  
Vol 35 (29) ◽  
pp. 3330-3337 ◽  
Author(s):  
Marianne Sinn ◽  
Marcus Bahra ◽  
Torsten Liersch ◽  
Klaus Gellert ◽  
Helmut Messmann ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Treatment ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
R0 Resection ◽  
Open Label ◽  
Term Survival

Purpose Gemcitabine is standard of care in the adjuvant treatment of resectable pancreatic ductal adenocarcinoma (PDAC). The epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in combination with gemcitabine has shown efficacy in the treatment of advanced PDAC and was considered to improve survival in patients with primarily resectable PDAC after R0 resection. Patients and Methods In an open-label, multicenter trial, patients were randomly assigned to one of two study arms: gemcitabine 1,000 mg/m2 days 1, 8, 15, every 4 weeks plus erlotinib 100 mg once per day (GemErlo) or gemcitabine (Gem) alone for six cycles. The primary end point of the study was to improve disease-free survival (DFS) from 14 to 18 months by adding erlotinib to gemcitabine. Results In all, 436 patients were randomly assigned at 57 study centers between April 2008 and July 2013. A total of 361 instances (83%) of disease recurrence were observed after a median follow-up of 54 months. Median treatment duration was 22 weeks in both arms. There was no difference in median DFS (GemErlo 11.4 months; Gem 11.4 months) or median overall survival (GemErlo 24.5 months; Gem 26.5 months). There was a trend toward long-term survival in favor of GemErlo (estimated survival after 1, 2, and 5 years for GemErlo was 77%, 53%, and 25% v 79%, 54%, and 20% for Gem, respectively). The occurrence or the grade of rash was not associated with a better survival in the GemErlo arm. Conclusion To the best of our knowledge, CONKO-005 is the first study to investigate the combination of chemotherapy and a targeted therapy in the adjuvant treatment of PDAC. GemErlo for 24 weeks did not improve DFS or overall survival over Gem.

Retrospective determination of the correlation between the distance of tumor manifestation to peripancreatic arteries and overall survival in primary resected pancreatic ductal adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15745-e15745
Author(s):  
Uwe A Wittel ◽  
Michael Uhl ◽  
Frank Makowiec ◽  
Ulrich Theodor Hopt ◽  
Stefan Fichtner-Feigl ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Median Survival ◽  
Average Distance ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Resection Margins ◽  
R0 Resection ◽  
Borderline Resectable ◽  
R1 Resection

e15745 Background: Current guidelines determine the resectability of PDAC by evaluating the contact of the tumor to peripancreatic vasculature. We wanted to evaluate the influence of this distance of the tumor to peripancreatic arteries on the overall survival of patients with primary resection of pancreatic ductal adenocarcinoma. Methods: Preoperative radiographs of 208 consecutive patients after distal pancreatectomy and/or pancreatoduodenectomy operated between 2007 and 2014 were included in the analysis. In reconstructions of CT and MRI data 90° planes to the centerline of the celiac trunc (CT), hepatic artery(HA) and superior mesenteric artery(SMA) were computed with Aquarius Intuition Viewer (V4.4.11, Terarecon). The closest distance between the tumor and the CT /HA and SMA was determined by an experienced pancreatic surgeon and radiologist independently and upon a deviation greater than 3 mm consent was reached by additional review in 33,2% (69/208) of the cases. Results: 176 CT and 32 MRI scans of 208 patients were evaluated. 2.4 % (5/208) of the radiographs were excluded due to insufficient quality. Average distance of the tumor to the CT/HA and SMA was 16.3 and 6.5 mm for PD and 12.7 and 11.0 mm for DP. Distance between the artery and the tumor did not influence the R0 resection rates (overall R0 > 1mm resection margin 64%) and median overall survival was 24.0 months after R0 resection and 13.5 months after R1 resection (log-rank test P < 0.05). Borderline resectable patients (n = 57) showed a median survival of 13.4 months, patients with their tumor 1-5mm distant to the closest artery (n = 65) and greater than 5 mm distance (n = 81) showed a median survival of 20.3 and 32.9 months respectively. Patients with 0-5 and greater than 5 mm distance between arteries and tumor showed a survival benefit from R0 resection (R0/R1 0-5mm 20.3/13.5 months; > 5mm 37.3/12.8 months) while R0 resected borderline resectable patients showed a similar survival than R1 resected patients (R0 12.7months, R1 15.1 months). Conclusions: The negative resection margins in borderline resectable patients not increase the survival when compared to R1 resected patients. Patients with primary R0 resection and initially large distance of the tumor to peripancreatic vasculature show a prolonged survival.

Precursors of pancreatic cancer in background of chronic opisthorchiasis

2021 ◽  
Vol 22 (1) ◽  
pp. 118-121
Author(s):  
V. U. Rayn ◽  
◽  
M. A. Persidskiy ◽  
E. V. Malakhova ◽  
I. V. Anuchina ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Disease Free Survival ◽  
Morphological Data ◽  
Small Samples ◽  
Ductal Adenocarcinoma ◽  
Preneoplastic Lesions ◽  
Opisthorchis Felineus ◽  
Disease Free

Aim. To establish the association between pancreatic cancer precursor lesions and chronic opisthorchiasis. Materials and methods. A single center case-control study was conducted at a low-volume pancreatic surgery center in Khanty-Mansiysk. We retrospectively collected morphological data from 47 pancreatoduodenectomies performed for pancreatic ductal adenocarcinoma. The study group included 23 cases of pancreatic ductal adenocarcinoma with concomitant chronic Opisthorchis felineus invasion which were compared to 24 controls consisting of “pure” cancer. Qualitative analysis was performed using χ2 Pearson criterion. Exact Fisher test was used for small samples. Time to progression and overall survival rates were calculated using Kaplan-Meier survival analysis. Data were collected and analyzed in Statistica 7.0. Results. PanINs were seen in 41,7% pancreata resected for ductal adenocarcinoma of the head and in 95,7% cases of pancreatic cancer in background of chronic opisthorchiasis (р = 0,000; 95% CI 3,5-268). PanIN high grade were observed only in opisthorchiasis group. In mixed pathology invasive cancer component tended to be more dedifferentiated and advanced when compared to pure cancer group (p = 0,029). Median disease free survival was 9 mo. in both groups and overall survival was 13 mo. in non-opisthorchiasis group and 15,3 mo. in opisthorchiasis group (р = 0,437). Conclusion. Chronic opisthorchiasis is associated with pancreatic intraepithelial neoplasia. Pancreatic ductal adenocarcinoma in background of opisthorchiasis with preneoplastic lesions tend to be more advanced in stage and poorly differentiated. Disease free and overall survival have no statistically significant differences in patients with and without Opisthorchis felineus invasion.

Long-term survival of patients receiving multimodality neoadjuvant therapy for resectable or borderline resectable pancreatic ductal adenocarcinoma.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 309-309
Author(s):  
Kinsey McCormick ◽  
Samuel H. Whiting ◽  
Grace Gyurkey ◽  
Wui-Jin Koh ◽  
Mika Sinanan ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Survival Rates ◽  
Ductal Adenocarcinoma ◽  
Wound Complications ◽  
R0 Resection ◽  
Surgical Morbidity ◽  
Borderline Resectable ◽  
Term Survival

309 Background: While surgery offers the only chance for cure in localized PDA, outcomes remain poor for those who have undergone surgical resection (SR). Neoadjuvant therapy (NATx) has several advantages, including early treatment of micrometastatic disease, the potential for tumor downstaging, and improved selection of patients (pts) for surgery by excluding those with chemotherapy-refractory disease. Methods: We report long-term follow-up on consecutive pts with resectable or borderline resectable (R/BR) PDA treated at our institution with an off-protocol, but defined regimen of multi-modality NATx. Demographic, clinical and outcomes data were extracted from medical records. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier analysis. Results: 16 pts with R/BR PDA were treated with NATx; median follow-up is now 41 months (mo) (7.9-91.5). The median age was 57, 50% were female, and all had an ECOG PS <2. Fourteen (88%) had BR disease, and 9 (56%) had radiographic evidence of nodal involvement. All pts received NA gemcitabine, docetaxel and capecitabine and 13 (81%) also received NA chemoradiotherapy with capecitabine +/- oxaliplatin. 14 pts (88%) underwent SR; of those, 11 (79%) received adjuvant chemotherapy. The median decline in CA19-9 over the course of NATx was 80%. An R0 resection was achieved in 11 pts (79%), and there were 2 pCR. To date, 12 pts have died, 4 are alive (including 2 with CA19-9 >1000 at dx), and 3 are without recurrence. The mPFS and mOS were 27.4 and 41 mo, respectively. 1- and 3-year survival rates were 94% and 56%, respectively. When analyses were restricted to pts who underwent SR, the mPFS and mOS were 29 mo and 47.8 mo, respectively. There were no surgery-related deaths. 3 pts had postoperative wound complications. Conclusions: In this series of mostly BR pancreatic cancer pts, treatment with multi-modality NATx resulted in an almost doubling of mOS when compared to historical controls. NATx was also safe, and did not increase surgical morbidity or mortality. Based on these encouraging results, a phase II protocol of multi-modality NATx for R/BR PDA was initiated and has now completed accrual.

Outcomes with FOLFIRINOX for locally advanced pancreatic cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 256-256
Author(s):  
Brian A. Boone ◽  
Jennifer Steve ◽  
Alyssa M. Krasinskas ◽  
Amer H. Zureikat ◽  
Barry C. Lembersky ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Response Rates ◽  
Biologically Active ◽  
Ductal Adenocarcinoma ◽  
R0 Resection ◽  
Borderline Resectable

256 Background: Trials examining the use of FOLFIRINOX in metastatic pancreatic ductal adenocarcinoma demonstrate significantly higher response rates compared to gemcitabine-based regimens. These high response rates may be particularly important for patients with locally advanced pancreatic ductal adenocarcinoma (LAPD), in which there is currently limited experience with FOLFIRINOX. We examined the outcomes of patients with LAPD treated with neoadjuvant FOLFIRINOX at our high volume clinic. Methods: Retrospective review of a prospectively maintained pancreatic cancer database was used to identify patients who were recommended neoadjuvant treatment with FOLFIRINOX. Clinical outcomes were reviewed. Resectability was determined using SSO criteria. Results: Between 2/2011 and 9/2012 FOLFIRINOX was recommended for 25 patients with LAPD, 13 (52%) unresectable (UR) and 12 (48%) borderline resectable (BR). Median age was 59. 4 patients (16%) either refused treatment or were lost to follow up. 21 patients (84%) were treated with a median of 4.7 cycles (Range: 2-8). 5 patients (24%) required dose reductions secondary to toxicity. 2 patients (9%) were unable to tolerate treatment and 3 patients (14%) had disease progression on treatment. Of the remaining 16 patients, 13 patients (62%) displayed a radiologic response allowing for surgical exploration, 4 (31%) of which were initially unresectable. 6 of these patients (29%) received additional chemotherapy and/or radiation therapy prior to surgery. Peritoneal metastases were discovered at surgery in 2 (8%) patients. Of the patients who were BR, 7/8 (88%) had a R0 resection. Of the 10 UR patients, 3 (33%) underwent surgical resection, with 2 (20%) R0 resections. Overall R0 resection rate was 43%. A total of 4 patients (19%) demonstrated a major pathologic response (2 complete responses and 2 near complete responses) and 8 other patients (73%) had some pathological response. Conclusions: FOLFIRINOX alone or as part of multimodality approach is a biologically active regimen in LAPD with encouraging R0 resection rates, especially in BR LAPD. Further research is needed to determine the utility of additional chemoradiotherapy with FOLFIRINOX and to identify predictors of response in UR patients.

The correlation between the proportion of patients with pancreatic ductal adenocarcinoma who received neoadjuvant therapy and overall survival between 2004 and 2015.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 395-395
Author(s):  
George Molina ◽  
Akhil Chawla ◽  
Thomas E. Clancy ◽  
Jiping Wang
Keyword(s):  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Neoadjuvant Therapy ◽  
Population Level ◽  
Ductal Adenocarcinoma ◽  
R0 Resection ◽  
Positive Correlation ◽  
R1 Resection ◽  
Spearman's Rho ◽  
Spearman’S Rho

395 Background: Neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) is associated with improved overall survival (OS), and this has led to its rising use. The aim of this study was to evaluate the correlation between use of NAT and OS among patients with PDAC. Methods: This population-level study evaluated the Spearman correlation between the annual proportion of patients receiving NAT and the annual 1-year and 5-year OS, respectively, using the 2004-2015 National Cancer Database. Annual 1-year and 5-year OS was calculated from year of diagnosis using Kaplan-Meier survival analysis. All patients with a confirmed diagnosis of PDAC (histology code 8500), without any metastasis, and who underwent an R0 or R1 resection were included. Results: A total of 18,852 patients (median age 67 (IQR 60–74); 49.4% female) with PDAC underwent an R0/R1 resection from 2004 to 2015. Among these patients, there was a significantly positive correlation between the proportion of patients who received NAT (12.1%; n = 2,133) and 1-year OS (Spearman’s rho = 0.9091; P = 0.0001) and 5-year OS (Spearman’s rho = 0.7833; P = 0.01), respectively. Patients who underwent R0 resection (n = 14,547; median age 67 (IQR 60-74); 49.9% female) had a significantly positive correlation between those who received NAT (13.1%; n = 1,773) and 1-year OS (Spearman’s rho = 0.8818; P = 0.0003) and 5-year OS (Spearman’s rho = 0.7333; P = 0.02), respectively. Among 9,142 patients who had upfront resectable disease with R0 resection margin status (median age 68 (IQR 60–75); 49.8% female), there was a significantly positive correlation between proportion of patients who received NAT (9.1%; n = 781) and 1-year OS (Spearman’s rho = 0.7273; P = 0.01) and 5-year OS (Spearman’s rho = 0.8000; P = 0.0096), respectively. Conclusions: Between 2004 and 2015 there has been an increase in the use of NAT for patients with PDAC. Concurrently, the OS has also increased during this time period. This study demonstrates that there is a statistically significant and positive correlation between the proportion of patients with R0/R1 resected PDAC who received NAT and 1-year OS and 5-year OS, respectively.

Phase II study of preoperative chemotherapy with nab-paclitaxel and gemcitabine followed by chemoradiation for borderline resectable or node-positive pancreatic ductal adenocarcinoma.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 697-697
Author(s):  
Emerson Yu-sheng Chen ◽  
Garth William Tormoen ◽  
Adel Kardosh ◽  
Nima Nabavizadeh ◽  
Bryan Foster ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Operative Treatment ◽  
Phase Ii ◽  
Metastatic Disease ◽  
Pancreatic Resection ◽  
Operative Therapy ◽  
Ductal Adenocarcinoma ◽  
R0 Resection ◽  
Borderline Resectable ◽  
Node Positive

697 Background: Pre-operative therapy for resectable pancreatic ductal adenocarcinoma (PDAC) may eliminate micro-metastatic disease early and help achieve negative surgical margins. The present study is based on the hypothesis that gemcitabine/nab-paclitaxel chemotherapy followed by chemo-radiation with fluoropyrimidine is a feasible and efficacious pre-operative treatment for borderline resectable or node-positive PDAC. Methods: This is a single-arm phase II trial to evaluate pre-operative treatment with 2 cycles of gemcitabine 1000 mg/m2 and nab-paclitaxel 125 mg/m2 on days 1, 8, 15 every 28 days followed by 50.4 Gy of intensity-modulated radiation therapy over 28 fractions with concurrent 5-fluorouracil or capecitabine prior to pancreatic resection. Patients were eligible if they met borderline resectable criteria or had abnormal regional nodes visible on contrast CT. After surgery, they were eligible to receive up to 4 additional cycles of gemcitabine/nab-paclitaxel. The primary endpoint was the R0 resection rate. Secondary endpoints included response to pre-operative therapy, overall toxicities, relapse-free survival, and overall survival. Results: Nineteen of 24 screened patients have been enrolled. Median age was 68, 10 (53%) were female, and 4 (21%) were non-Caucasian. Eleven (78%) had head of pancreas cancers, 13 (68%) exhibited both arterial and venous involvement, and 12 (63%) had positive clinical nodes. All 19 patients received 2 months of gemcitabine/nab-paclitaxel, of which 17 patients continued to chemo-radiation (1 developed metastatic disease and 1 moved out of state). In the interval between chemo-radiation and surgery, 3 developed metastatic disease, 1 became unresectable, 1 withdrew from study, and 1 was deemed too frail for surgery. Nine have undergone successful pancreatic resection, and 2 are pending resection. Conclusions: Pre-operative gemcitabine/nab-paclitaxel followed by chemo-radiation with fluoropyrimidine is feasible in patients with borderline resectable PDAC and represents another strategy to FOLFIRINOX-based therapy. A planned interim analysis is ongoing. Clinical trial information: NCT02427841.

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