Surgical outcomes and rate of pathological response in resectable/borderline resectable pancreatic cancer patients undergoing neoadjuvant gemcitabine/nab-paclitaxel versus FOLFIRINOX: A retrospective institutional analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16247-e16247
Author(s):  
Abraham Attah Attah ◽  
Saleha Rizwan ◽  
Khaled Alhamad ◽  
Micheal Turk ◽  
Palash Asawa ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Treatment Response ◽  
Surgical Resection ◽  
Locally Advanced ◽  
Small Sample ◽  
Ductal Adenocarcinoma ◽  
Categorical Variables ◽  
Adjuvant Setting ◽  
Borderline Resectable ◽  
Significant Difference

e16247 Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal solid tumors, predicted to become the second leading cause of cancer related death in some regions of the world. It often presents at an advanced stage, which contributes to poor five-year survival rates of 2%-9%, ranking firmly last amongst all cancer sites in terms of prognostic outcomes for patients. Only about 20% of the cases are diagnosed early enough to undergo surgical resection leading to complete remission. While chemotherapy has an established role in the setting of metastatic disease, utilizing it in the neo-adjuvant setting has been adopted by most institutes for resectable/ borderline resectable cases. Ongoing trials are exploring the use of different regimens in the neo-adjuvant setting. The aim of our study was to identify patients with resectable/borderline resectable PDAC undergoing neoadjuvant chemotherapy and differences in surgical outcome based on the regimen received i.e gemcitabine/ nab-Paclitaxel vs FOLFIRINOX. Methods: A retrospective review was conducted of all patients diagnosed with PDAC from 2017-2019 at Allegheny General Hospital. Data analysis was completed using IBM SPSS v23. Summary statistics were presented using percentages for categorical variables and medians with interquartile ranges for continuous variables. Results: Out of 121 patients who received and completed treatment in our institution, 30 underwent neoadjuvant chemotherapy treatment followed by surgical intervention. 21 (70%) patients were found to be borderline resectable, 8 (27%) patients were resectable and 1 patient had locally advanced PDAC. 16 (53%) patients received FOLFIRINOX compared to 13 (43%) patients received gem/nab-paclitaxel. Among patients who received neoadjuvant FOLFIRINOX, 5 out of 16 (31%) patients had moderate to significant treatment response at the time of surgery compared to 7 out of 13 (54%) patients who received gemcitabine/nab-paclitaxel. Conclusions: Our study revealed no significant difference (p=0.21) between the patients who received neoadjuvant gemcitabine/nab-paclitaxel vs FOLFIRINOX in terms of treatment response assessed pathologically at the time surgical resection. We recognize the limitations of our study in terms of it being a retrospective analysis with a small sample size and therefore further prospective and randomized controlled trials are needed to determine the most suitable and effective regimen in the neoadjuvant setting for resectable/borderline resectable PDAC patients. Response to treatment among different chemotherapy groups.[Table: see text]

Retrospective review of FOLFIRINOX in local advanced pancreatic cancer: Single institution experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15714-e15714
Author(s):  
Ashish Manne ◽  
Sushanth Reddy ◽  
Martin Heslin ◽  
Rojymon Jacob ◽  
Selwyn M. Vickers ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Surgical Resection ◽  
Retrospective Review ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Metastatic Setting ◽  
Significant Difference ◽  
One Year

e15714 Background: Although combination of fluorouracil, irinotecan, Leucovorin and oxaliplatin [FOLFIRINOX] significantly increases survival in metastatic pancreatic cancer (MPC) compared to gemcitabine based on ACCORD trial, the efficacy and toxicities may be different in non-metastatic setting. We reviewed our institution’s experience with FOLFIRINOX in locally advanced pancreatic cancer (LAPC). Methods: We performed a retrospective review of clinical outcomes in patients diagnosed with LAPC and receiving between June 2010 and July 2015, with at least one year of follow up from diagnosis, at University of Alabama at Birmingham. Results: Total of 41 patients with ECOG performance scale of 0 or 1, who underwent neoadjuvant chemotherapy with FOLFIRINOX were assessed for clinical and pathological characteristics. Median age was 61 years (range 38-81) with 23 (56.1%) males, 28 (68.3%) Caucasians and 16 (39.0%) underwent surgery (whipple operation) post-neoadjuvant. Median OS (time of diagnosis to last follow up/death) is 83.5 months for whole cohort, survival rates are 94.9% at 1 year, 58.4% at 2 year, and 33.3% at 5 year.Median OS for those who underwent surgical resection following the chemotherapy is 38.6 months; 100% at one year, 85.1% at 2 year, 55.3% at 5 year; while median OS for those who did not undergo surgery is 21.8 months; 91.7% at one year, 41.5% at 2 year, 20.7% at 5 years. Among those who underwent surgery, the median recurrence free survival (time from surgery to relapse/progression) is 19.9 months with liver being common recurrence site (81%). There was no post-operative mortality in 30 days. Grade 3-4 toxicity occurred in 46% ( vomiting (12%), fatigue (28%) and neutropenia (54%), febrile neutropenia (9%)). There is a significant difference between surgery and non-surgery groups (p = 0.012) for improved OS by log-rank test. Conclusions: Neoadjuvant FOLFIRINOX treatment associated with high response rates leading to surgical resection in our cohort. Patients who underwent neoadjuvant chemotherapy followed by resection for LAPC have statistically significant improved OS compared to those who did not.

Treatment response and survival in patients with pancreatic adenocarcinoma receiving neoadjuvant chemotherapy or chemoradiation.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15715-e15715
Author(s):  
Ahmed Khattab ◽  
Sunita Patruni ◽  
Stephen Abel ◽  
Shaakir Hasan ◽  
Gene Grant Finley ◽  
...  
Keyword(s):  
Overall Survival ◽  
Logistic Regression ◽  
Neoadjuvant Chemotherapy ◽  
Treatment Response ◽  
Pathologic Complete Response ◽  
Multivariable Analysis ◽  
Ductal Adenocarcinoma ◽  
Multivariable Logistic Regression ◽  
Predictors Of Response ◽  
Significant Difference

e15715 Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis. Neoadjuvant chemotherapy (NeoChT) and chemoradiation (NeoCRT) have emerged as strategies to optimize resection, but data investigating predictors of treatment response and the overall survival (OS) impact are not well characterized. To investigate the effects of NeoChT/NeoCRT on primary tumor/nodal downstaging and OS, we analyzed the national cancer database (NCDB). Methods: We queried the NCDB for patients with PDAC receiving NeoChT/NeoCRT. Patients were classified as responders (T and/or N downstage), nonresponders (mixed/no response) and progressors (T and/or N upstage). Multivariable logistic regression identified predictors of response. Univariable and multivariable analyses identified characteristics predictive of OS. Results: 2,028 patients with PDAC receiving NeoChT/NeoCRT were analyzed. Univariable analysis of responders (n = 790) vs. nonresponders/progressors (n = 1,238) demonstrated a significant difference in median OS at 29.1 months vs. 25.3 months and 3-year overall survival of 40% vs. 34% [p = 0.006; HR: 0.95 (95% CI: 0.84-1.08)] respectively. When compared independently to both responders and nonresponders, progressors had a significantly decreased 3-year OS at 31% vs 40% and 37% respectively [p = 0.003; HR: 0.82 (95% CI: 0.70-0.96)]. Predictors of response on multivariable logistic regression included receipt of multiagent chemotherapy and receipt of NeoCRT. Only NeoCRT predicted for pathologic complete response (pCR). Multivariable analysis of patients with pCR demonstrated a trend towards increased OS (p = .08). Conclusions: Our results suggest that both response and progression following neoadjuvant therapy may predict for longer and shorter OS respectively. Randomized, prospective studies are needed to further validate these findings. [Table: see text]

Association of losartan use with outcomes in metastatic pancreatic cancer patients treated with chemotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16738-e16738
Author(s):  
Jessica Allen ◽  
Kathan Mehta ◽  
Shrikant Anant ◽  
Prasad Dandawate ◽  
Anwaar Saeed ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Metastatic Cancer ◽  
Statistical Significance ◽  
Objective Response ◽  
Locally Advanced ◽  
Small Sample ◽  
Ductal Adenocarcinoma ◽  
Control Group ◽  
100Mg Dose ◽  
Significant Difference

e16738 Background: A phase II trial has shown improved efficacy of neoadjuvant therapy when combined with losartan (by remodeling desmoplasia) in locally advanced pancreatic ductal adenocarcinoma (PDA). However, role of losartan is unknown in metastatic PDA. We examined the relationship between the use of the angiotensin II receptor antagonist, losartan, at time of diagnosis with clinical outcomes in metastatic PDA pts that received chemo. Methods: We retrospectively evaluated 114 metastatic PDA pts treated at our center between Jan 2000 and Nov 2019. We compared OS, PFS, objective response rate (ORR), and disease control rate (DCR) between pts using losartan at time of cancer diagnosis and a control group of pts not on losartan. A subanalysis was performed based on losartan dose: 100mg dose versus control pts. and based on chemo: FOLFIRINOX or gemcitabine+abraxane. Results: Table shows baseline demographics. No significant difference was found in OS [p = 0.455] or PFS [p = 0.919] in pts on losartan (median 274d, 83d) vs control (median 279d, 111d) [p = 0.466]. No significant difference was found in ORR [p = 0.621] or in DCR [p = 0.497]. No significant difference was found in OS [p = 0.771] or PFS [p = 0.064] in losartan pts (median 347d, 350d) vs control (median 333d, 101d) treated with FOLFIRINOX. No significant difference was found in OS [p = 0.916] or PFS [p = 0.341] in losartan (median 312d, 69d) vs control (median 221d, 136d) [p = 0.916] treated with gemcitabine+abraxane. No significant difference was found in OS [p = 0.727] or PFS [p = 0.790] in 100mg losartan pts (median 261d, 84d) vs control (median 279d, 111d). Conclusions: Pts on losartan at time of diagnosis had no significant difference in OS, PFS, ORR, DCR than control pts. However, a subanalysis of pts treated with FOLFIRINOX revealed a longer PFS with losartan than control but did not meet statistical significance, likely due to small sample size. To confirm if the benefit of losartan + FOLFIRINOX seen in neoadjuvant setting for locally advanced cancer also applies to metastatic cancer, our findings need to be validated in a larger cohort. [Table: see text]

Neoadjuvant chemotherapy and disease recurrence after curative-intent surgery in patients with pancreatic adenocarcinoma: A single-center retrospective review.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18610-e18610
Author(s):  
Khaled Alhamad ◽  
Nada Alrifai ◽  
Abraham Attah Attah ◽  
Karthik Shankar ◽  
Lynna Alnimer ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Retrospective Review ◽  
Early Stage ◽  
Disease Recurrence ◽  
Early Recurrence ◽  
Ductal Adenocarcinoma ◽  
Hospital Data ◽  
Borderline Resectable ◽  
Curative Intent ◽  
Significant Difference

e18610 Background: Early stage pancreatic ductal adenocarcinoma (PDAC) account for up to 30% of newly diagnosed patients. Until recently, the mainstay of treatment remained curative-intent surgery followed by adjuvant chemotherapy. More recently, the incorporation of neoadjuvant therapy (NAT) has demonstrated clinical benefit. The two commonly used regimens are 5-Fluorouracil, Leucovorin, Oxaliplatin and Irinotecan (FOLFIRINOX), or Gemcitabine and nab-Paclitaxel. Limited data is available to differentiate outcomes between the 2 common NAT regimens. We conducted a retrospective review to assess the rates of disease recurrence and progression after neoadjuvant chemotherapy and to identify any associations that may predict early recurrence. Methods: A retrospective review was conducted of all patients diagnosed with PDAC from 2017-2019 at Allegheny General Hospital. Data analysis was completed using IBM SPSS v23. Disease recurrence or progression was assessed radiologically, and time to progression was calculated as time (months) since diagnosis to evidence of radiological progression. Results: Out of 171 patients reviewed, 56 were deemed resectable or borderline resectable and underwent curative-intent surgery and were included in the analysis. Median age was 68, and 12 (41%) were male. Majority of the patients were white (90%). 29 (52%) patients received neoadjuvant chemotherapy: 16 (55%) received FOLFIRINOX, 12 (41%) received Gemcitabine with nab-Paclitaxel, and 1 received another regimen. 9 patients out of 16 (56%) that received FOLFIRINOX progressed, and 5 out of 12 patients (42%) who received Gemcitabine with nab-Paclitaxel progressed. Patterns of progression in those that received FOLFIRINOX: 1 (11%) within 6 months, 4 (44%) between 6-12 months, and 4 (44%) after 12 months. Of those that received Gemcitabine with nab-Paclitaxel, 2 (40%) progressed within 6 months, 1 (20%) progressed between 6-12 months, and 2 (40%) progressed after 12 months. On multivariate analysis, no association was identified to predict progression. Conclusions: There was no significant difference in disease progression rates among patients that received neoadjuvant FOLFIRINOX versus Gemcitabine and nab-Paclitaxel (42% vs. 56%; p = 0.46). No predictive associations were identified in patients with disease recurrence. Study limitations include a low sample size and retrospective analysis. Further, larger scale studies are warranted to better assess the difference in rates of progression after neoadjuvant FOLFIRINOX versus Gemcitabine and nab-Paclitaxel.[Table: see text]

scholarly journals Effect and limitation of neoadjuvant chemotherapy for pancreatic ductal adenocarcinoma: consideration from a new perspective

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yoshihiro Kurata ◽  
Takayuki Shiraki ◽  
Masanori Ichinose ◽  
Keiichi Kubota ◽  
Yasuo Imai
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Locally Advanced ◽  
Nodal Metastasis ◽  
Ductal Adenocarcinoma ◽  
Resected Specimen ◽  
Small Subset ◽  
Borderline Resectable ◽  
Postoperative Prognosis ◽  
Pathologic Stage

Abstract Background Effect of neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC) has remained under investigation. We investigated its effect from a unique perspective and discussed its application. Patients and methods We retrospecively analyzed consecutive 131 PDAC patients who underwent pancreatoduodenectomy and distal pancreatectomy. Clinicopathologic data at surgery and postoperative prognosis were compared between patients who underwent upfront surgery (UFS) (n = 64) and those who received NAC (n = 67), of which 62 (92.5%) received gemcitabine plus S-1 (GS). The GS regimen resulted in about 15% of partial response and 85% of stable disease in a previous study which analyzed a subset of this study subjects. Results Tumor size was marginally smaller, degree of nodal metastasis and rate of distant metastasis were significantly lower, and pathologic stage was significantly lower in the NAC group than in the UFS group. In contrast, significant differences were not observed in histopathologic features such as vessel and perineural invasions and differentiation grade. Notably, disease-free and overall survivals were similar between the two groups adjusted for the pathologic stage, suggesting that effects of NAC, including macroscopically undetectable ones such as control of micro-metastasis and devitalizing tumor cells, may not be remarkable in the majority of PDAC, at least with respect to the GS regimen. Conclusions NAC may be useful in downstaging and improving prognosis in a small subset of tumors. However, postoperative prognosis may be determined at the pathologic stage of resected specimen with or without NAC. Therefore, NAC may be applicable to borderline resectable and locally advanced PDAC for enabling surgical resection, but UFS would be desirable for primary resectable PDAC.

scholarly journals Neoadjuvant Chemotherapy Switch in Borderline Resectable/Locally Advanced Pancreatic Cancer

2021 ◽  
Author(s):  
Roberto Alva-Ruiz ◽  
Lavanya Yohanathan ◽  
Jennifer A. Yonkus ◽  
Amro M. Abdelrahman ◽  
Lindsey A. Gregory ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Surgical Resection ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Advanced Pancreatic Cancer ◽  
Preoperative Treatment ◽  
Borderline Resectable ◽  
Curative Intent ◽  
Chemotherapeutic Regimen

Abstract Background Neoadjuvant chemotherapy (NAC) is an integral part of preoperative treatment for patients with borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC). The identification of a chemotherapeutic regimen that is both effective and tolerable is critical for NAC to be of oncologic benefit. After initial first-line (FL) NAC, some patients have lack of response or therapeutic toxicities precluding further treatment with the same regimen; optimal decision making regarding this patient population is unclear. Chemotherapy switch (CS) may allow for a larger proportion of patients to undergo curative-intent resection after NAC. Methods We reviewed our surgical database for patients undergoing combinatorial NAC for BR/LA PDAC. Variant histologic exocrine carcinomas, intraductal papillary mucinous neoplasm-associated PDAC, and patients without research consent were excluded. Results Overall, 468 patients with BR/LA PDAC receiving FL chemotherapy were reviewed, of whom 70% (329/468) continued with FL chemotherapy followed by surgical resection. The remaining 30% (139/468) underwent CS, with 72% (100/139) of CS patients going on to curative-intent surgical resection. Recurrence-free survival (RFS) and overall survival (OS) were not significantly different between the resected FL and CS cohorts (30.0 vs. 19.1 months, p = 0.13, and 41.4 vs. 36.4 months, p = 0.94, respectively) and OS was significantly worse in those undergoing CS without subsequent resection (19 months, p < 0.0001). On multivariable analysis, carbohydrate antigen (CA) 19-9 and pathologic treatment responses were predictors of RFS and OS. Conclusion CS in patients undergoing NAC for BR/LA pancreatic cancer does not incur oncologic detriment. The incorporation of CS into NAC treatment sequencing may allow a greater proportion of patients to proceed to curative-intent surgery.

Predicting Surgical Margins in Patients With Borderline Resectable and Locally Advanced Pancreatic Cancer Undergoing Resection

2021 ◽  
pp. 000313482110111
Author(s):  
Weizheng Ren ◽  
Dimitrios Xourafas ◽  
Stanley W. Ashley ◽  
Thomas E. Clancy
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Ductal Adenocarcinoma ◽  
Resection Margins ◽  
Borderline Resectable ◽  
Stepwise Selection ◽  
R1 Resection ◽  
Positive Resection Margins

Background Many patients with borderline resectable/locally advanced pancreatic ductal adenocarcinoma (borderline resectable [BR]/locally advanced [LA] pancreatic ductal adenocarcinoma [PDAC]) undergoing resection will have positive resection margins (R1), which is associated with poor prognosis. It might be useful to preoperatively predict the margin (R) status. Methods Data from patients with BR/LA PDAC who underwent a pancreatectomy between 2008 and 2018 at Brigham and Women’s Hospital were retrospectively reviewed. Logistic regression analysis was used to evaluate the association between R status and relevant preoperative factors. Significant predictors of R1 resection on univariate analysis ( P < .1) were entered into a stepwise selection using the Akaike information criterion to define the final model. Results A total of 142 patients with BR/LA PDAC were included in the analysis, 60(42.3%) had R1 resections. In stepwise selection, the following factors were identified as positive predictors of an R1 resection: evidence of lymphadenopathy at diagnosis (OR = 2.06, 95% CI: 0.99-4.36, P = .056), the need for pancreaticoduodenectomy (OR = 3.81, 96% CI: 1.15-15.70, P = .040), extent of portal vein/superior mesenteric vein involvement at restaging (<180°, OR = 3.57, 95% CI: 1.00-17.00, P = .069, ≥180°, OR = 7,32, 95% CI: 1.75-39.87, P = .010), stable CA 19-9 serum levels (less than 50% decrease from diagnosis to restaging, OR = 2.27, 95% CI: 0.84-6.36 P = .107), and no preoperative FOLFIRINOX (OR = 2.17, 95% CI: 0.86-5.64, P = .103). The prognostic nomogram based on this model yielded a probability of achieving an R1 resection ranging from <5% (0 factors) to >70% (all 5 factors). Conclusions Relevant preoperative clinicopathological characteristics accurately predict positive resection margins in patients with BR/LA PDAC before resection. With further development, this model might be used to preoperatively guide surgical decision-making in patients with BR/LA PDAC.

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