Predictors of recurrence and implications for overall survival in borderline resectable pancreatic cancer patients treated with total neoadjuvant therapy: A retrospective cohort study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16781-e16781
Author(s):  
Jori Lee Kaplan ◽  
Benjamin Powers ◽  
Wenyi Fan ◽  
Michael J. Schell ◽  
Barbara Centeno ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Treatment Effect ◽  
Pathologic Complete Response ◽  
Multivariable Analysis ◽  
Borderline Resectable ◽  
Risk Of Recurrence ◽  
Predictors Of Recurrence ◽  
Increased Risk

e16781 Background: Borderline resectable pancreatic ductal adenocarcinoma (BR PDAC) is a subset of pancreatic cancer with unique prognostic implications. A multimodality, neoadjuvant therapy (NAT) approach has known benefits such as downstaging tumors, reducing the risk of a positive margin, and treating micrometastatic disease. Patient selection and therapy sequencing are controversial owing to the high risk of recurrence. Therefore, we aimed to identify factors predicting recurrence and overall survival (OS) in BR PDAC patients undergoing NAT. Methods: We identified BR PDAC patients treated with NAT followed by surgery at Moffitt Cancer Center between 2008-2015. We evaluated clinical, demographic, and perioperative factors to identify predictors of recurrence and OS. Statistical analyses were performed with univariate and multivariable Cox regression models. Results: 117 patients with BR PDAC who received NAT were evaluated; 53 (45%) were female and 64 (55%) were male. Of those, 91 (78%) received gemcitabine/xeloda/taxotere and the remainder received other gemcitabine or 5FU regimens. 107 (91%) patients received neoadjuvant radiation, mainly 5-day dose painted SBRT. Post- NAT CA 19-9 normalized in 39 (33%) and 11 (9%) additional patients normalized after surgery. Pathologic treatment effect was appreciated in 85 (73%) patients and pathologic complete response (pCR) was seen in 18 (15%). 95 (81%) patients initiated adjuvant therapy. In multivariable analysis, the strongest predictor of recurrence was higher log(10) post-operative CA 19-9 (HR 2.29; 95% CI, 1.40-3.75). Time from initiation of NAT to surgery ≥ 5 months also predicted recurrence (HR 2.08; 95% CI, 1.16-3.72). In OS analysis, 71 patients had recurrence after multimodality treatment; 61 (86%) died and 10 (14%) were alive. In multivariable analysis, the strongest predictors of prolonged OS from recurrence were female gender (HR 0.47; 95% CI, 0.26-0.84) and presence of a treatment effect (HR 0.37; 95% CI, 0.15-0.93). Conclusions: We observed treatment effects and pCR comparable to other institutions, supporting a multimodality approach to BR PDAC. Higher post-operative CA 19-9 and time to surgery ≥ 5 months from initiation of NAT were associated with an increased risk of recurrence. These data suggest that timely receipt of surgery after completion of NAT may impact recurrence and OS in BR PDAC.

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.

Association of decline in serum Ca19-9 after neoadjuvant therapy with improved survival among borderline resectable pancreatic cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15082-e15082 ◽  
Author(s):  
Susan Tsai ◽  
Anna Mahmoud ◽  
Ben George ◽  
Tracy R. Kelly ◽  
Paul S. Ritch ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Cancer Patients ◽  
Response To Therapy ◽  
Proportional Hazard ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Cox Proportional Hazard ◽  
Localized Disease

e15082 Background: Serum Ca19-9 (19-9) decline in response to therapy has been associated with an increased overall survival in metastatic pancreatic cancer patients (pts). However, the prognostic value of a 19-9 decline after neoadjuvant therapy in pts with localized disease is less well defined. Methods: We evaluated 73 pts with NCCN defined BRPC who received neoadjuvant therapy with induction chemotherapy (CRX) followed by chemoradiation (CRT). Staging with CT and 19-9 was obtained at three defined time points: baseline (bilirubin normal), after CRX, and following CRT (pre-surgical). Change in 19-9 (δ19-9) was defined as: (baseline 19-9- pre-surgical 19-9)/baseline 19-9. δ19-9 was classified as: absent (δ19-9<0) or minimal (0 <δ19-9<0.25), low (0.25<δ19-9<0.50), moderate (0.50<δ19-9<0.75), high (δ19-9> 0.75). Results: Of the 73 pts, 20 pts had normal/undetectable 19-9 and were excluded from the analysis. Of the remaining 53 pts, mean 19-9 levels at baseline, after CRX, and after CRT were 956, 164, and 139 U/mL, respectively. The mean change in 19-9 after CRX was 44%. Changes in 19-9 after CRX correlated with continued decline in 19-9 after CRT (Spearman rho = 0.81, p<0.001). δ19-9 was high in 38 (71%), moderate in 9 (17%), min/low in 1 (2%), and absent in 5 (9%). Of the 53 pts, 49 (92%) were considered for surgery after neoadjuvant therapy and 38 (72%) underwent pancreatectomy. In a multivariate logistic regression, higher δ19-9 was associated with a 5.4 fold increased odds of completing all neoadjuvant therapy including surgery as compared to pts with no change in 19-9 (absent δ19-9; HR 5.4, p=0.12). Patients with absent δ19-9 had a worse overall survival than pts with minimal to high δ19-9 (median survival 11.5 mo vs. 30.1 mo, p = 0.0002). In a multivariate Cox proportional hazard, a decline in pre-surgical 19-9 from baseline was associated with improved survival (HR 0.21, p =0.02). Conclusions: Following neoadjuvant therapy, a decline in 19-9 is associated with surgical resection and improved overall survival. An increase in 19-9 above baseline (the absent δ19-9 group) prior to surgery is a poor prognostic marker and such patients may benefit from additional systemic therapy.

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.

Multi-agent neoadjuvant chemotherapy improves response and survival in patients with resectable pancreatic cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 409-409
Author(s):  
Taylor Maramara ◽  
Jamie Huston ◽  
Ravi Shridhar ◽  
Kenneth L Meredith
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Therapy ◽  
Tumor Size ◽  
Single Agent ◽  
Pathologic Complete Response ◽  
Multivariable Analysis ◽  
Response Rates ◽  
Resectable Pancreatic Cancer ◽  
Multi Agent ◽  
The Impact

409 Background: Neoadjuvant therapy (NT) for resectable pancreatic adenocarcinoma (PAC) continues to be debated. We sought to establish the impact of single agent (SAC) versus multi-agent chemotherapy (MAC) with or without radiation (RT) on survival in patients with resectable pancreatic cancer. Methods: Utilizing the National Cancer Database we identified patients with PAC who underwent up front surgery (UFS), SAC, or MAC ± RT followed by surgery. Patient characteristics and survival were compared with Mann-Whitney U, Pearson’s Chi-square, and the Kaplan-Meier method. Multivariable analysis (MVA) was developed to identify predictors of survival. All tests were two-sided and α < 0.05 was significant. Results: We identified 26,563 patients of which, 23,877 (89.9%) UFS, 1,482 (5.6%) NT+RT (SAC+RT 768, MAC+RT 560), and 1,204 (4.5%) chemo only (SAC 262, MAC 864) with a median age of 66 (25-90). The median tumor size was smaller, p = 0.003 and Charlson/Deyo was lower, p = 0.008 in the UFS. Despite this, the 90 day mortality was higher at 8% versus 7.5% in NT+RT and 4.8% in NT, p = 0.003. There were higher R0 resections in the NT+RT versus NT-RT or UFS, 82.4%, 80.5%, and 76%, p < 0.001. Additionally, there were less N1 disease in NT+RT 35.4%, 59.5%, and 68.1%, p < 0.001. Pathologic complete response (pCR) rates were higher in the NT+RT versus NT-RT, 3.1% versus 1.7%, p < 0.001. Examining the response rates by SAC±RT and MAC±RT, pCR was 0.5% in SAC, 2.8% SAC+RT, 2.2% MAC, and 3.3 MAC+RT, p = 0.004. The median survival was 22.2 mo in UFS, 23.1 mo in SAC, 26 mo in SAC+RT, 27.9 mo in MAC+RT, and 29.8 mo in MAC, p < 0.001. On multivariable analysis, age, Chalson/Deyo score, tumor size, grade, margin status, facility volume, and MAC were predictors of survival. Conclusions: Multi-agent chemotherapy with or without radiation improves overall survival, R0 resections rates, and complete pathological response rates in patients undergoing neoadjuvant therapy for resectable pancreatic cancer.

Assessing Treatment Effect in Pancreatic Cancer

2012 ◽  
Vol 136 (1) ◽  
pp. 100-109 ◽  
Author(s):  
Douglas J Hartman ◽  
Alyssa M Krasinskas
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Therapy ◽  
Treatment Effect ◽  
Neoadjuvant Chemoradiation ◽  
Rapid Progression ◽  
Borderline Resectable ◽  
Pancreatic Resections ◽  
Therapy Effect ◽  
Careful Assessment ◽  
Gross Examination

Context.—Pancreatic cancer is one of the most deadly forms of cancer (43 140 new cases per year; 36 800 deaths), and most people with pancreatic cancer do not survive past 5 years. New therapeutic regimens are constantly being evaluated in an attempt to reduce the rapid progression of this disease. Although some patients receive neoadjuvant therapy in an attempt to make a nonresectable or borderline-resectable tumor resectable, more patients with resectable disease are being enrolled in clinical trials that provide neoadjuvant therapy. This means more pancreatic resections must be evaluated for therapy effect. Histologic grading schemes for the assessment of posttherapy response have been described, but difficulties associated with determining the histologic features of treatment effect in pancreatic cancer have not been addressed. Objectives.—To critically review the diagnostic criteria for proposed grading schemes for pancreatic cancer treated with neoadjuvant chemoradiation therapy and to provide guidance to surgical pathologists who encounter treated pancreatic cancer resections. Data Sources.—Published peer-reviewed literature and the personal experience of the authors. Conclusions.—Assessment of treatment effect in pancreatic cancer is difficult. Pathologists need to be aware that some histologic features of treatment effect overlap with histologic features seen in untreated pancreatic cancer, such as tumor cell anaplasia, necrosis, and fibrosis. Careful assessment of pancreatic resections, including detailed gross examination and thorough histologic sampling, is important in accurately assessing treatment effect and improving patient outcomes.

scholarly journals Induction Chemotherapy for Primarily Unresectable Locally Advanced Pancreatic Adenocarcinoma—Who Will Benefit from a Secondary Resection?

Medicina ◽  
2021 ◽  
Vol 57 (1) ◽  
pp. 77
Author(s):  
Nathalie Rosumeck ◽  
Lea Timmermann ◽  
Fritz Klein ◽  
Marcus Bahra ◽  
Sebastian Stintzig ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Induction Therapy ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Comprehensive Cancer Center ◽  
Secondary Resection ◽  
Number Of Patients

Background and Objectives: An increasing number of patients (pts) with locally advanced pancreatic cancer (LAPC) are treated with an intensive neoadjuvant therapy to obtain a secondary curative resection. Only a certain number of patients benefit from this intention. The aim of this investigation was to identify prognostic factors which may predict a benefit for secondary resection. Materials and Methods: Survival time and clinicopathological data of pts with pancreatic cancer were prospective and consecutively collected in our Comprehensive Cancer Center Database. For this investigation, we screened for pts with primarily unresectable pancreatic cancer who underwent a secondary resection after receiving induction therapy in the time between March 2017 and May 2019. Results: 40 pts had a sufficient database to carry out a reliable analysis. The carbohydrate-antigen 19-9 (CA 19-9) level of the pts treated with induction therapy decreased by 44.7% from 4358.3 U/mL to 138.5 U/mL (p = 0.001). The local cancer extension was significantly reduced (p < 0.001), and the Eastern Cooperative Oncology Group (ECOG) performance status was lowered (p = 0.03). The median overall survival (mOS) was 20 months (95% CI: 17.2–22.9). Pts who showed a normal CA 19-9 level (<37 U/mL) at diagnosis and after neoadjuvant therapy or had a Body Mass Index (BMI) below 25 kg/m2 after chemotherapy had a significant prolonged overall survival (29 vs. 19 months, p = 0.02; 26 vs. 18 months, p = 0.04; 15 vs. 24 months, p = 0.01). Pts who still presented elevated CA 19-9 levels >400 U/mL after induction therapy did not profit from a secondary resection (24 vs. 7 months, p < 0.001). Nodal negativity as well as the performance of an adjuvant therapy lead to better mOS (25 vs. 15 months, p = 0.003; 10 vs. 25 months, p < 0.001). Conclusion: The pts in our investigation had different benefits from the multimodal treatment. We identified the CA 19-9 level at time of diagnosis and after neoadjuvant therapy as well as the preoperative BMI as predictive factors for overall survival. Furthermore, diagnostics of presurgical nodal status should gain more importance as nodal negativity is associated with better outcome.

scholarly journals Added Value of Radiotherapy Following Neoadjuvant FOLFIRINOX for Resectable and Borderline Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Quisette P. Janssen ◽  
Jacob L. van Dam ◽  
Isabelle G. Kivits ◽  
Marc G. Besselink ◽  
Casper H. J. van Eijck ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Meta Analysis ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Added Value ◽  
R0 Resection ◽  
Resection Rate ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer

Abstract Background The added value of radiotherapy following neoadjuvant FOLFIRINOX chemotherapy in patients with resectable or borderline resectable pancreatic cancer ((B)RPC) is unclear. The objective of this meta-analysis was to compare outcomes of patients who received neoadjuvant FOLFIRINOX alone or combined with radiotherapy. Methods A systematic literature search was performed in Embase, Medline (ovidSP), Web of Science, Scopus, Cochrane, and Google Scholar. The primary endpoint was pooled median overall survival (OS). Secondary endpoints included resection rate, R0 resection rate, and other pathologic outcomes. Results We included 512 patients with (B)RPC from 15 studies, of which 7 were prospective nonrandomized studies. In total, 351 patients (68.6%) were treated with FOLFIRINOX alone (8 studies) and 161 patients (31.4%) were treated with FOLFIRINOX and radiotherapy (7 studies). The pooled estimated median OS was 21.6 months (range 18.4–34.0 months) for FOLFIRINOX alone and 22.4 months (range 11.0–37.7 months) for FOLFIRINOX with radiotherapy. The pooled resection rate was similar (71.9% vs. 63.1%, p = 0.43) and the pooled R0 resection rate was higher for FOLFIRINOX with radiotherapy (88.0% vs. 97.6%, p = 0.045). Other pathological outcomes (ypN0, pathologic complete response, perineural invasion) were comparable. Conclusions In this meta-analysis, radiotherapy following neoadjuvant FOLFIRINOX was associated with an improved R0 resection rate as compared with neoadjuvant FOLFIRINOX alone, but a difference in survival could not be demonstrated. Randomized trials are needed to determine the added value of radiotherapy following neoadjuvant FOLFIRINOX in patients with (B)PRC.

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