Tumor downsizing following neoadjuvant therapy for borderline-resectable pancreatic adenocarcinoma.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 690-690
Author(s):  
Joseph Arturo Reza ◽  
Alberto Monreal ◽  
Patrick Hunter Meyer ◽  
Swati Patel ◽  
Ahmed Zakari ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Surgical Resection ◽  
Pearson Correlation ◽  
Similar Rate ◽  
Chi Square ◽  
Borderline Resectable ◽  
Neoadjuvant Systemic Therapy ◽  
Tumor Downsizing

690 Background: Downstaging of pancreatic adenocarcinoma in patients presenting with nonmetastatic, unresectable disease has proven to be associated with improved clinical outcomes. Efforts at rescuing these patients to become surgical candidates are commonly attempted with a combination of systemic and radiation strategies. In this study, we aimed to determine tumor downsizing in patients that underwent neoadjuvant systemic therapy followed by a curative-intended surgical resection. Methods: A retrospective review of consecutive patients that underwent surgical resection for pancreatic adenocarcinoma following a course of neoadjuvant therapy was performed. Basic demographics, endoscopic ultrasound (EUS) findings, chemotherapy regimens and duration, rates of radiotherapy, type of surgical procedure and pathologic results were recorded. Tumor response to neoadjuvant therapy was established by correlating EUS- to pathologic tumor dimensions. Analysis of the data was done using Mann-Whitney U test, Pearson correlation and Chi-square when indicated. Results: A total of 97 patients were analyzed; 40 underwent neoadjuvant chemotherapy (13 patients also received concurrent radiation therapy). In those 57 patients that were resected upfront, EUS tended to underestimate tumor sizes significantly compared to pathologic dimensions, with an average difference between dimensions of 0.66 cm (p = 0.0004). Within the group treated with neoadjuvant chemotherapy, 90% of patients had downsizing at an average of 8% of tumor size. There were no differences in rates of tumor downsizing between FOLFIRINOX or Gemcitabine/Nac-paclitaxel treated patients. In addition, there were no correlations in margin status (R0) based on chemotherapy used, with both regimens achieving a similar rate of R0 resections (mean 61%). The type of chemotherapy regimen used did not affect the ratio of positive lymph nodes harvested. Conclusions: In patients that present with borderline resectable pancreatic adenocarcinoma, a course of neoadjuvant therapy results in tumor downsizing in a significant number allowing for margin negative resections. These results were seen regardless of the chemotherapeutic regimens utilized.

scholarly journals Total Neoadjuvant Therapy With FOLFIRINOX Followed by Individualized Chemoradiotherapy for Borderline Resectable Pancreatic Adenocarcinoma

JAMA Oncology ◽  
2018 ◽  
Vol 4 (7) ◽  
pp. 963 ◽  
Author(s):  
Janet E. Murphy ◽  
Jennifer Y. Wo ◽  
David P. Ryan ◽  
Wenqing Jiang ◽  
Beow Y. Yeap ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Borderline Resectable ◽  
Total Neoadjuvant Therapy

Adjuvant and Neoadjuvant Therapy for Pancreatic Adenocarcinoma

2017 ◽  
Author(s):  
Gregory C Wilson ◽  
Brent T Xia ◽  
Syed A Ahmed
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Treatment Strategies ◽  
Ductal Adenocarcinoma ◽  
Borderline Resectable

Despite decades of advancement and research into the multimodal care of pancreatic cancer, mortality after the diagnosis of pancreatic ductal adenocarcinoma remains grim. The role of adjuvant therapy following surgical resection has been well established in the literature. However, adjuvant therapy is imperfect, and outside of a clinical trial, there are high rates of omission or delayed initiation of therapy. Neoadjuvant treatment strategies continue to be explored in the management of resectable, borderline-resectable, and locally advanced unresectable pancreatic adenocarcinoma. With improved resection rates and the possibility for tumor downstaging, neoadjuvant therapy has become standard for patients with borderline-resectable and locally advanced unresectable tumors. Additional benefits of neoadjuvant therapy in the treatment of resectable tumors include improved completion rates of systemic therapy and R0 resection rates. Future clinical trials, including the use of novel treatment agents and combination treatment strategies in both neoadjuvant and adjuvant regimens, will add value to the treatment of pancreatic adenocarcinoma. Key words: adjuvant therapy, borderline-resectable pancreatic cancer, locally advanced pancreatic cancer, neoadjuvant therapy, pancreatic adenocarcinoma, resectable disease 

Feasibility and efficacy of neoadjuvant cabozantinib and nivolumab in patients with borderline resectable or locally advanced hepatocellular carcinoma (HCC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 335-335
Author(s):  
Mark Yarchoan ◽  
Qingfeng Zhu ◽  
Jennifer N. Durham ◽  
Nicole Gross ◽  
Soren Charmsaz ◽  
...  
Keyword(s):  
T Cells ◽  
Adverse Event ◽  
Neoadjuvant Therapy ◽  
Surgical Resection ◽  
Primary Endpoint ◽  
Locally Advanced ◽  
Borderline Resectable ◽  
Advanced Hcc ◽  
Surgical Evaluation ◽  
Systemic Therapies

335 Background: Only 10-15% of newly diagnosed HCC patients are candidates for a potentially curative resection, and most patients who receive resection eventually recur. Historical systemic therapies including sorafenib, as well as locoregional therapies, have not demonstrated benefit in the perioperative setting. Novel combinations of targeted therapies and immunotherapies demonstrate higher response rates than sorafenib in HCC. Here, we report the feasibility and efficacy of neoadjuvant combination therapy with cabozantinib plus nivolumab, followed by surgical resection, in patients with borderline resectable or locally advanced HCC. Methods: We conducted an open-label, single-arm, phase I study in patients with HCC with borderline resectable or locally advanced HCC (including multinodular disease, portal vein involvement, or other high-risk features). Patients received 8 weeks of therapy with cabozantinib 40 mg oral daily plus nivolumab 240 mg IV every two weeks, followed by restaging and possible surgical resection. The primary endpoint was feasibility, defined by the percentage of patients experiencing a treatment-related adverse event that precluded continuing on to surgery within 60 days of the planned date for surgical evaluation. Results: We enrolled 15 patients of whom 14 patients completed neoadjuvant therapy and underwent surgical evaluation. Adverse events were consistent with prior experience with these agents, and the trial met its primary endpoint, with no patients experiencing a treatment-related adverse event that precluded timely surgical assessment. Of patients completing neoadjuvant therapy, 1 patient declined surgery, 1 tumor could not be resected, and 12 patients underwent successful R0 surgical resection. 5/12 (41.7%) resected patients had a major or complete pathologic response. At a median follow up of one year, 4/5 pathologic responders are without recurrence. We performed an in-depth profiling of the surgical resection biospecimens and identified an enrichment of IFNγ+ effector memory CD4+ and granzyme B+ effector CD8+ T cells as well as tertiary lymphoid aggregates in the pathologic responders. We further analyzed the spatial relationships of cell types in responders and non-responders, which identified distinct spatial arrangement of B cells in responders, and proximity of arginase-1 expressing myeloid cells to T cells in nonresponders. Conclusions: This study is, to our knowledge, the first use of a targeted therapy in combination with an immune checkpoint inhibitor in the neoadjuvant setting in HCC, and the first use of modern systemic therapies to expand surgical resection criteria. Neoadjuvant cabozantinib and nivolumab is feasible, and may result in pathologic responses and long-term disease-free survival in a group of patients who may be outside traditional resection criteria. Clinical trial information: NCT03299946.

Neoadjuvant therapy for borderline resectable pancreatic adenocarcinoma. Preliminary results

Pancreatology ◽  
2015 ◽  
Vol 15 (3) ◽  
pp. e4-e5
Author(s):  
J. Busquets ◽  
N. Peláez ◽  
B. Laquente ◽  
H. Verdaguer ◽  
L. Secanella ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Borderline Resectable ◽  
Preliminary Results

Trends from NSQIP 2015 to 2017 in neoadjuvant therapy use before pancreatic adenocarcinoma resection.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15685-e15685
Author(s):  
Rebecca C Gologorsky ◽  
Sora Ely ◽  
Dana Dominguez ◽  
Michelle Huyser ◽  
CK Chang
Keyword(s):  
Neoadjuvant Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Clinical Decision Making ◽  
Neoadjuvant Treatment ◽  
Multidisciplinary Care ◽  
Response To Therapy ◽  
R0 Resection ◽  
Borderline Resectable ◽  
Improvement Project ◽  
Over Time

e15685 Background: Morbidity and mortality associated with surgical resection of pancreatic adenocarcinoma remains high, and prognosis is poor even after R0 resection. Preoperative chemoradiation, previously only indicated to downstage borderline-resectable disease, has been increasingly used even in cases that appear resectable at time of diagnosis. Response to therapy can be prognostic and guide clinical decision-making. We investigated significant trends over time in neoadjuvant treatment of patients within the National Surgical Quality Improvement Project (NSQIP) database treated surgically for pancreatic adenocarcinoma. Methods: We queried NSQIP data for patients who underwent pancreaticoduodenectomy or subtotal pancreatectomy for pancreatic adenocarcinoma in 2015-2017. We examined differences by year in neoadjuvant treatment use with Chi-square test. Results: There were 8626 patients included. Use of neoadjuvant treatment (chemotherapy or chemoradiotherapy) increased over the study period, and complication by pancreatic fistula and delayed gastric emptying decreased qualitatively over the same time (12% to 9%; 14% to 12%). This increase in use of neoadjuvant chemotherapy was significant among patients with T1, T2, and T3 tumors (Table 1). However, despite NCCN/ASCO guidelines recommending neoadjuvant for all patients with T4 tumors, only about a quarter of these patients received it, and this proportion did not change over time. Conclusions: Preoperative chemotherapy is particularly important in ≥T3 disease because of low rates (50%) of adjuvant therapy, likely secondary to postoperative morbidity. The NSQIP data reflects the trend toward increasing neoadjuvant therapy in lower-T stage disease, but not among patients with T4 disease. This may be because NSQIP data largely reflects community hospital populations, and this practice was first adopted by academic institutions. Based on our findings, it is important that medical oncology be involved early in the multidisciplinary care of patients with pancreatic adenocarcinoma.[Table: see text]

A randomized, phase II clinical trial of preoperative stereotactic body radiation therapy versus conventionally fractionated chemoradiation for resectable, borderline-resectable, or locally advanced type a pancreatic adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS4167-TPS4167
Author(s):  
William Adrian Hall ◽  
Susan Tsai ◽  
Anjishnu Banerjee ◽  
Ben George ◽  
Paul S. Ritch ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Radiation Therapy ◽  
Neoadjuvant Chemotherapy ◽  
Pancreatic Adenocarcinoma ◽  
Phase Ii ◽  
Stereotactic Body Radiation Therapy ◽  
Locally Advanced ◽  
Phase Ii Clinical Trial ◽  
Borderline Resectable ◽  
Conventionally Fractionated

TPS4167 Background: There is growing consensus for the use of neoadjuvant therapy in patients with potentially operable pancreatic adenocarcinoma (PC). However, there is not consensus on the type and duration of chemotherapy or radiation therapy (RT) dose. Stereotactic body radiation therapy (SBRT) has gained popularity despite the absence of prospective data for its use in the preoperative setting. Furthermore, SBRT preoperatively has not been standardized. At present, there exists no randomized data comparing preoperative SBRT with conventionally fractionated concurrent chemo-RT. We designed this trial to examine differences between pre-op RT dose and fractionation schedules. Methods: This study is a prospective, randomized, two-arm, phase II clinical trial. Eligible patients must have cytologically confirmed PC and be deemed suitable for surgical resection with resectable, borderline resectable, or locally advanced type A disease, based on cross-sectional imaging. Before randomization patients are stratified by clinical node positivity, neoadjuvant chemotherapy, and stage of disease. Patients are then randomized to either 50.4 Gy over 28 fractions with concurrent weekly Gemcitabine vs SBRT to a total dose of 25-35 Gy over 5 fractions. The primary endpoint of the study is pathologic node positivity. We hypothesize that patients treated with neoadjuvant chemotherapy followed by conventionally fractionated chemo-RT will have a lower rate of pathologic node positivity as compared to those patients treated with neoadjuvant chemotherapy followed by SBRT. Secondary endpoints include patient reported quality of life, local recurrence, primary tumor pathologic response, margin status, surgical complications, MR based treatment response, and overall survival. We anticipate a node positivity rate of 37% when using preoperative chemotherapy followed by SBRT. We hypothesize that treatment with chemotherapy followed by conventionally fractionated chemo-RT will reduce the rate of node positivity to 17%. Using a one-sided Type I error rate of 0.1, approximately 88 total patients (44 per arm) provide an 80% power to detect the hypothesized difference in pathologic node positivity between the two arms. To address patient dropout, an additional 14 patients (about 15%) will be enrolled for a total target accrual of 102 patients. The trial opened in November 2018 and 8 of the planned 102 patients have been enrolled. Clinical trial information: NCT03704662.

scholarly journals Analysis of the Curative Effect of Neoadjuvant Therapy on Pancreatic Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Liqiong Yang ◽  
Yun Bai ◽  
Qing Li ◽  
Jie Chen ◽  
Fangfang Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Adverse Reactions ◽  
Neoadjuvant Chemoradiotherapy ◽  
Primary Treatment ◽  
R0 Resection ◽  
Resectable Pancreatic Cancer ◽  
Recurrence Rates ◽  
Borderline Resectable

The prevalence of pancreatic cancer is sharply increasing recently, which significantly increases the economic burden of the population. At present, the primary treatment of resectable pancreatic cancer is surgical resection, followed by chemotherapy with or without radiation. However, the recurrence rates remain high even after R0 resection. This treatment strategy does not distinguish undetected metastatic disease, and it is prone to postoperative complications. Neoadjuvant therapies, including neoadjuvant chemotherapy and radiotherapy, is being increasingly utilized in borderline resectable as well as resectable pancreatic cancer. This review summarized and discussed clinical trials of neoadjuvant therapy for pancreatic cancer, comparing resection rates, outcome measures, and adverse reactions between neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy.

scholarly journals Impact of perioperative blood transfusions on survival in patients with borderline resectable pancreatic adenocarcinoma after neoadjuvant therapy

HPB ◽  
2018 ◽  
Vol 20 ◽  
pp. S43-S44
Author(s):  
R.A. Snyder ◽  
L.R. Prakash ◽  
N. Narula ◽  
B.J. Kim ◽  
M.P. Kim ◽  
...  
Keyword(s):  
Neoadjuvant Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Blood Transfusions ◽  
Borderline Resectable
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