scholarly journals The effect of the low stromal ratio induced by neoadjuvant chemotherapy on recurrence patterns in borderline resectable pancreatic ductal adenocarcinoma

2022 ◽  
Author(s):  
Kenji Kawahara ◽  
Shigetsugu Takano ◽  
Katsunori Furukawa ◽  
Tsukasa Takayashiki ◽  
Satoshi Kuboki ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Neoadjuvant Chemotherapy ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Treatment Strategies ◽  
Early Recurrence ◽  
Ductal Adenocarcinoma ◽  
Borderline Resectable ◽  
Ki 67 ◽  
Free Survival ◽  
Recurrence Patterns

AbstractThe optimal regimens of neoadjuvant chemotherapy (NAC) and its biological and physiological modification of the tumor microenvironment (TME) in patients with borderline resectable pancreatic ductal adenocarcinoma (BR PDAC) remain unknown. A deeper understanding of the complex stromal biology of the TME will identify new avenues to establish treatment strategies for PDAC patients. Herein, we sought to clarify whether stromal remodeling by NAC affects recurrence patterns and prognosis in BR PDAC patients. We retrospectively analyzed data from 104 BR PDAC patients who underwent pancreatectomy with or without NAC (upfront surgery [UpS], n = 44; gemcitabine + nab-paclitaxel [GnP], n = 28; and gemcitabine + S-1 [GS], n = 32) to assess the correlations of treatment with early recurrence, the stromal ratio, and Ki-67 levels. Eighty-six patients experienced recurrence, and those with liver metastasis had significantly shorter recurrence-free survival than those with other recurrence patterns. The frequency of liver metastasis was significantly higher in patients with a low stromal ratio than in those with a high stromal ratio in the NAC group but not in the UpS group. Patients in the GnP group had significantly higher Ki-67 than those in the GS and UpS groups. A low stromal ratio was positively correlated with high Ki-67 in the NAC group but not in the UpS group. The low stromal ratio induced by NAC promoted early liver metastasis in patients with BR PDAC. Our findings provide new insights into the complexity of stromal biology, leading to consideration of the optimal NAC regimen.

Establishment of patient-derived tumor xenograft (PDX) model as artificially-created liver metastasis using cryopreserved pancreatic ductal adenocarcinoma.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 729-729
Author(s):  
Kenjiro Kimura ◽  
Ryota Tanaka ◽  
Ryosuke Amano ◽  
Shoji Kubo ◽  
Hiroaki Tanaka ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Liver Transplant ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Tumor Xenograft ◽  
Ductal Adenocarcinoma ◽  
Ki 67 ◽  
Nsg Mice ◽  
Patient Derived Xenograft ◽  
Pdx Model ◽  
Successful Establishment

729 Background: Translational research using patient-derived tumor xenograft (PDX) model is progressing rapidly, and is also becoming widespread in pancreatic cancer research. The purpose of this study was to establish the liver transplant PDX model as artificially-created liver metastasis with cryopreserved primary pancreatic ductal adenocarcinoma(PDAC). Methods: The primary PDAC from 10 patients were cryopreserved and transplanted into NSG mice using liver pocket method. For engraftment and similarity evaluation, H&E staining and immunohistochemical staining such as Ki-67, p53, SMAD4, and MUC1 were performed. Results: Patient-derived xenograft was succeeded in 6 cases (60%), 10 mice (33.3%). Ki-67 index of primary PDAC and the interval of cryopreservation were significantly related to successful engraftment, respectively (p = 0.003, p = 0.007). Conclusions: In this study, we succeeded in establishing a liver transplant PDX mouse model as a preclinical platform. The factors such as Ki-67 index and the interval of cryopreservation would affect the successful establishment.

scholarly journals Developing a preoperative serum metabolome-based recurrence-predicting nomogram for patients with resected pancreatic ductal adenocarcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Seoung Yoon Rho ◽  
Sang-Guk Lee ◽  
Minsu Park ◽  
Jinae Lee ◽  
Sung Hwan Lee ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Area Under The Curve ◽  
Pancreatic Head ◽  
Cancer Recurrence ◽  
Disease Free Survival ◽  
Early Recurrence ◽  
Ductal Adenocarcinoma ◽  
Free Survival ◽  
Preoperative Serum

AbstractWe investigated the potential application of preoperative serum metabolomes in predicting recurrence in patients with resected pancreatic cancer. From November 2012 to June 2014, patients who underwent potentially curative pancreatectomy for pancreatic ductal adenocarcinoma were examined. Among 57 patients, 32 were men; 42 had pancreatic head cancers. The 57 patients could be clearly categorized into two main clusters using 178 preoperative serum metabolomes. Patients within cluster 2 showed earlier tumor recurrence, compared with those within cluster 1 (p = 0.034). A nomogram was developed for predicting the probability of early disease-free survival in patients with resected pancreatic cancer. Preoperative cancer antigen (CA) 19–9 levels and serum metabolomes PC.aa.C38_4, PC.ae.C42_5, and PC.ae.C38_6 were the most powerful preoperative clinical variables with which to predict 6-month and 1-year cancer recurrence-free survival after radical pancreatectomy, with a Harrell’s concordance index of 0.823 (95% CI: 0.750–0.891) and integrated area under the curve of 0.816 (95% CI: 0.736–0.893). Patients with resected pancreatic cancer could be categorized according to their different metabolomes to predict early cancer recurrence. Preoperative detectable parameters, serum CA 19–9, PC.aa.C38_4, PC.ae.C42_5, and PC.ae.C38_6 were the most powerful predictors of early recurrence of pancreatic cancer.

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.

Tumor interface stability on CT imaging is an early marker of response to cytotoxic therapy in pancreatic ductal adenocarcinoma.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 284-284
Author(s):  
Christopher Wilke ◽  
Ahmed Amer ◽  
Dalia Elganainy ◽  
Priya Bhosale ◽  
Ott Le ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Treatment Strategies ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Response To Therapy ◽  
Ductal Adenocarcinoma ◽  
Free Survival ◽  
Interface Stability ◽  
Visual Scoring

284 Background: There is currently no reliable biomarker for assessing the response to therapy of pancreatic ductal adenocarcinoma (PDAC). Here, we investigated how changes in the tumor/parenchyma interface associate with response. Methods: We reviewed pre- and post-therapy scans of patients who received chemotherapy and/or chemoradiation for both localized and metastatic PDAC. We classified the interface between the PDAC tumor and surrounding pancreas parenchyma as stable (remains or becomes well-defined) or unstable (becomes poorly defined) using a novel visual scoring system and quantified changes in enhancement at this interface (Philips Intellispace Portal, quantitative European Association for the Study of Liver [qEASL]). Results: Three retrospective datasets were used to develop this method with consensus visual scoring performed by 3 radiologists. The first dataset included 99 patients with localized PDAC who received neoadjuvant chemoradiation. Patients who were classified as having a stable interface had significantly higher probability of achieving a complete or near-complete pathologic response (21% vs 0%, p = 0.01) and additionally demonstrated an improved median disease-free survival (DFS, 20.9 vs 7.9 mos., p < 0.01) and overall survival (OS, 47.7 vs 19.1 mos., p < 0.01). These results were validated in a separate dataset of 94 patients receiving protocol-based chemotherapy and chemoradiation (chemoRT cohort) and a cohort of 86 patients with stage IV disease. In both cohorts, a stable interface was associated with a significant improvement in progression free survival (PFS, Hazard Ratio [HR] 0.44, p = 0.01 for chemoRT and HR 0.70, p = 0.16 for stage IV) and OS (HR 0.42, p < 0.01 for chemoRT and HR 0.59, p = 0.05 for stage IV). Multivariate analyses for each cohort showed interface stability to be independently associated with both DFS/PFS and OS. Measurements obtained using qEASL were concordant with the visual scoring results. Conclusions: The interface stability of PDAC is an early readout of response to therapy. Integration of this imaging feature into clinical trials for localized and metastatic PDAC may aid in the future development of adaptive treatment strategies.

scholarly journals Randomized phase II study of gemcitabine and S-1 combination therapy versus gemcitabine and nanoparticle albumin-bound paclitaxel combination therapy as neoadjuvant chemotherapy for resectable/borderline resectable pancreatic ductal adenocarcinoma (PDAC-GS/GA-rP2, CSGO-HBP-015)

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Daisaku Yamada ◽  
Shogo Kobayashi ◽  
Hidenori Takahashi ◽  
Hirofumi Akita ◽  
Terumasa Yamada ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Combination Therapy ◽  
Survival Time ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Curative Resection ◽  
Phase Ii Study ◽  
Ductal Adenocarcinoma ◽  
Borderline Resectable ◽  
Randomized Phase Ii

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, and multimodal strategies, such as surgery plus neoadjuvant chemotherapy (NAC)/adjuvant chemotherapy, have been attempted to improve survival in patients with localized PDAC. To date, there is one prospective study providing evidence for the superiority of a neoadjuvant strategy over upfront surgery for localized PDAC. However, which NAC regimen is optimal remains unclear. Methods A randomized, exploratory trial is performed to examine the clinical benefits of two chemotherapy regimens, gemcitabine plus S-1 (GS) and gemcitabine plus nab-paclitaxel (GA), as NAC for patients with planned PDAC resection. Patients are enrolled after the diagnosis of resectable or borderline resectable PDAC. They are randomly assigned to either NAC regimen. Adjuvant chemotherapy after curative resection is highly recommended for 6 months in both arms. The primary endpoint is tumor progression-free survival time, and secondary endpoints include the rate of curative resection, the completion rate of protocol therapy, the recurrence type, the overall survival time, and safety. The target sample size is set as at least 100. Discussion This study is the first randomized phase II study comparing GS combination therapy with GA combination therapy as NAC for localized pancreatic cancer. Trial registration UMIN Clinical Trials Registry UMIN000021484. This trial began in April 2016.

scholarly journals Circulating tumour cells as an indicator of early and systemic recurrence after surgical resection in pancreatic ductal adenocarcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yejong Park ◽  
Hye Ryeong Jun ◽  
Hwi Wan Choi ◽  
Dae Wook Hwang ◽  
Jae Hoon Lee ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Surgical Resection ◽  
Distant Metastases ◽  
Early Recurrence ◽  
Tumour Cells ◽  
Ductal Adenocarcinoma ◽  
Circulating Tumour Cells ◽  
Active Monitoring ◽  
Systemic Recurrence ◽  
Recurrence Patterns

AbstractEarly recurrence in pancreatic ductal adenocarcinoma (PDAC) is a decisive factor in determining a patient's prognosis. We determined in our current study whether circulating tumour cells (CTCs) exist in the blood of PDAC patients and can be used as a predictor of recurrence patterns (i.e. time and site) after surgical resection. Between December 2017 and November 2018, the mononuclear cell layer was obtained from the peripheral blood of 36 patients diagnosed with PDAC. CTCs were then isolated using the CD-PRIME™ platform and detected via immunostaining. The patient records were analyzed to correlate these data with survival and recurrence patterns. Twelve patients were CTC-positive (33.3%) and showed a significantly frequent rate of systemic recurrence (distant metastases and peritoneal dissemination) (p = 0.025). On multi-variable logistic regression analysis, CTC positivity was an independent risk factor for early recurrence (p = 0.027) and for systemic recurrence (p = 0.033). In summary, the presence or absence of CTC in the blood of the patients with PDAC could help predict the recurrence pattern after surgery. PDAC patients with CTC positivity at tumour diagnosis should therefore undergo a comprehensive strategy for systemic therapy and active monitoring to detect possible early recurrence.

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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