Circulating cell free tumor DNA detection as a prognostic tool in advanced pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4130-4130
Author(s):  
Gehan Botrus ◽  
Pedro Luiz Serrano Uson Junior ◽  
Puneet Raman ◽  
Adrienne Kaufman ◽  
Heidi E. Kosiorek ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Systemic Treatment ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Genetic Alterations ◽  
Genomic Alterations ◽  
Systemic Treatments ◽  
Investigation Methods ◽  
The Impact ◽  
Tumor Dna

4130 Background: Circulating cell-free tumor DNA (ctDNA) genomic profiling is an emerging tool for pancreatic cancer. The impact of detected genomic alterations in tumor response to systemic treatments and outcomes is under investigation. Methods: Patients with advanced pancreatic cancer and ctDNA collected at time of initial diagnosis were retrospectively evaluated. Results of ctDNA analysis were correlated with patients’ demographics, systemic treatment response, progression-free survival (PFS) and overall survival (OS). Results: A total of 104 patients were included in the analysis. The mean age was 70.5 years (SD: 8.3), 50% were male, 37% with locally advanced disease and 63% with metastatic disease. Somatic alterations were detected in 84.6 % of the patients, no genetic alterations were detected in 15.4%, and were associated more with locally advanced pancreatic cancer as opposed to metastatic, p = 0.025. 60.6 % of the cohort had ≥ 2 genomic alterations detected. 28% were treated with FOLFIRINOX and 63% with gemcitabine plus nab-paclitaxel as first-line systemic treatment. Patients with any detectable genomic alterations when compared to patients with no detectable variant had worse median PFS (6.2 versus 15.3 months, p = 0.005) and patients with ≥ 2 detectable genomic alterations had worse median PFS (5.6 versus 11.0 months, p < 0.001) and worse median OS (11.5 versus 24.2 months, p = 0.001). KRAS was detected in 62.5% of the patients and was associated with PD to systemic treatments (80.4% vs 19.6%, p = 0.006), worse median PFS (5.8 versus 13.0 months, p < 0.001) and worse median OS (11.5 versus 26.3 months, p = 0.002). TP53 was detected in 60% of patients and was associated with worse median PFS (5.9 versus 10.9 months, p = 0.02) and worse median OS (13.5 versus 24.2 months, p = 0.001). CCND2 was detected in 14% of the patients and was associated with worse median PFS (3.6 versus 8.2 months, p = 0.004). Conclusions: Our study showed that initial detection of ctDNA may identify different genomic alterations that help predict disease outcomes, confirmation of these findings in larger studies are warranted.

The impact of pancreatic cancer resection in the era of effective systemic treatment.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 722-722
Author(s):  
Yaacov Richard Lawrence ◽  
Ofer Margalit ◽  
Galia Jacobson ◽  
Liat Hamer ◽  
Uri Amit ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Surgical Resection ◽  
Systemic Treatment ◽  
Locally Advanced ◽  
Tumor Resection ◽  
Phase Iii ◽  
Term Survival ◽  
Systemic Treatments ◽  
Metastatic Setting ◽  
The Impact

722 Background: Surgical resection is the only curative modality in pancreatic cancer, yet the vast majority of patients undergoing surgery succumb of their disease. No randomized studies have been performed to assess the survival impact of the procedure. We hypothesized that in the era of effective systemic treatments, the survival advantage of surgical resection would be lessened. Methods: A meta-analysis of published phase III clinical trials in pancreatic cancer in both the post resection adjuvant setting and the locally advanced metastatic setting, based upon indirect aggregate data. Data was stratified based upon the systemic agents used. Patients from trials arms for which there were not complementary data sets with/without surgical resection were excluded. Primary endpoint was 3 year overall survival (OS). Results: Trials were published between 1997 and 2018. A total of 2722 patients were included in the data analysis, of whom 1645 underwent tumor resection and 814 were metastatic. Median follow-up was 40 months. Analyses were performed of five systemic options with / without tumor resection. Across the trials averaged 3 yr OS was 0%, 0.8%, 0%, and 3.8% for 5FU, gemcitabine, gemcitabine + capecitabine, & FOLFIRINOX respectively; and 18.1%, 30.0%, 37.9%, 42.5%, and 62.5% for the same systemic treatments delivered following surgical resection. Hence the additive impact of surgical resection on absolute 3 yr OS was only 18.1% in the absence of systemic treatment, but 30.0%, 37.1%, 42.5% and 58.8% in the presence of 5FU, gemcitabine, gemcitabine + capecitabine, FOLFIRINOX respectively. Conclusions: Within the limitations of this analysis, it appears that our hypothesis was incorrect, and that the opposite is true. The introduction of effective systemic therapies has greatly increased the impact of pancreatic surgery on long-term survival in pancreatic cancer. Consequently, every effort should be made to bring patients to curative resection.

scholarly journals Intraoperative Irreversible Electroporation in Locally Advanced Pancreatic Cancer: A Guide for the Interventional Radiologist

2019 ◽  
Vol 36 (05) ◽  
pp. 386-391
Author(s):  
Gregory T. Frey ◽  
Carlos A. Padula ◽  
John A. Stauffer ◽  
Beau B. Toskich
Keyword(s):  
Pancreatic Cancer ◽  
Tertiary Care ◽  
Multidisciplinary Treatment ◽  
Locally Advanced ◽  
Irreversible Electroporation ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Locoregional Therapy ◽  
Systemic Treatments ◽  
Tertiary Care Institution

AbstractEfforts to improve mortality associated with locally advanced pancreatic cancer (LAPC) have shown minimal gains despite advances in surgical technique, systemic treatments, and radiation therapy. Locoregional therapy with ablation has not been routinely adopted due to the high risk of complications associated with thermal destruction of the pancreas. Irreversible electroporation (IRE) is an emerging, nonthermal, ablative technology that has demonstrated the ability to generate controlled ablation of LAPC while preserving pancreatic parenchymal integrity. IRE may be performed percutaneously or via laparotomy and will commonly involve multidisciplinary treatment teams. This article will describe the technical aspects of how multidisciplinary IRE is performed during laparotomy at a single tertiary care institution.

scholarly journals Competing Risk Analysis of Outcomes of Unresectable Pancreatic Cancer Patients Undergoing Definitive Radiotherapy

2022 ◽  
Vol 11 ◽  
Author(s):  
Yi-Lun Chen ◽  
Chiao-Ling Tsai ◽  
Jason Chia-Hsien Cheng ◽  
Chun-Wei Wang ◽  
Shih-Hung Yang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Prognostic Factors ◽  
Cox Regression ◽  
Locally Advanced ◽  
Reduction Rate ◽  
Advanced Pancreatic Cancer ◽  
Competing Risk ◽  
Treatment Modalities ◽  
Definitive Radiotherapy ◽  
Systemic Treatments

PurposeWe investigated potential factors, including clinicopathological features, treatment modalities, neutrophil-to-lymphocyte ratio (NLR), carbohydrate antigen (CA) 19-9 level, tumor responses correlating with overall survival (OS), local progression (LP), and distant metastases (DMs), in patients with locally advanced pancreatic cancer (LAPC) who received definitive radiotherapy (RT).MethodsWe retrospectively analyzed demographic characteristics; biologically effective doses (BED10, calculated with an α/β of 10) of RT; and clinical outcomes of 57 unresectable LAPC (all pancreatic adenocarcinoma) patients receiving definitive RT using modern techniques with and without systemic therapy between January 2009 and March 2019 at our institution. We used Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 to evaluate the radiographic tumor response after RT. The association between prognostic factors and OS was assessed using the Kaplan–Meier analysis and a Cox regression model, whereas baseline characteristics and treatment details were collected for competing-risk regression of the association with LP and DM using the Fine–Gray model.ResultsA median BED10 of 67.1 Gy resulted in a disease control rate of 87.7%, and the median OS was 11.8 months after a median follow-up of 32.1 months. The 1-year OS rate, cumulative incidences of LP, and DM were 49.2%, 38.5%, and 62.9%, respectively. Multivariate analyses showed that pre-RT NLR ≥3.5 (adjusted hazard ratio [HR] = 8.245, p &lt; 0.001), CA19-9 reduction rate ≥50% (adjusted HR = 0.261, p = 0.005), RT without concurrent chemoradiotherapy (adjusted HR = 5.903, p = 0.004), and administration of chemotherapy after RT (adjusted HR = 0.207, p = 0.03) were independent prognostic factors for OS. Positive lymph nodal metastases (adjusted subdistribution HR [sHR] = 3.712, p = 0.003) and higher tumor reduction after RT (adjusted sHR = 0.922, p &lt; 0.001) were significant prognostic factors for LP, whereas BED10 ≥ 67.1 Gy (adjusted sHR = 0.297, p = 0.002), CA19-9 reduction rate ≥50% (adjusted sHR = 0.334, p = 0.023), and RT alone (adjusted sHR = 2.633, p = 0.047) were significant prognostic factors for DM.ConclusionOur results indicate that pre-RT NLR and post-RT monitoring of CA19-9 and tumor size reduction can help identify whether patients belong to the good or poor prognostic group of LAPC. The incorporation of new systemic treatments during and after a higher BED10 RT dose for LAPC patients is warranted.

Neoadjuvant chemoradiation and intraoperative electron irradiation for locally unresectable/borderline resectable pancreas adenocarcinoma.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 327-327
Author(s):  
Jonathan Ben Ashman ◽  
Adyr A Moss ◽  
Matthew D. Callister ◽  
Kunam S Reddy ◽  
David C Mulligan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Electron Irradiation ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Local Therapy ◽  
Borderline Resectable ◽  
Pancreas Adenocarcinoma ◽  
The Impact

327 Background: The use of preoperative therapy for pancreatic cancer remains controversial. This study reviews our experience using neoadjuvant chemotherapy and chemoradiation (CRT) followed by surgery with intraoperative electron irradiation (IOERT) for patients with borderline resectable (BR) or unresectable (UR) tumors. Methods: A retrospective review identified 48 patients (pts) with primary BR/UR pancreas adenocarcinoma treated with preop CRT with intent to proceed to curative surgery with IOERT. Seventeen patients did not undergo attempted resection and are excluded (disease progression, 12; medically inoperable, 3; declined surgery, 2). Thirty-one patients proceeded to resection attempt and are the subject of this analysis. Kaplan-Meier survival analysis was performed using log rank test for significance. Median follow up was 19 months (mo). Results: Complete resection (R0) was achieved in 11 pts, R1 in 5, and R2 or not resected (IOERT alone) in 15 patients. Twenty-six pts died (23 of disease, 2 unrelated causes, 1 uncertain). Median overall survival (OS) was 19 mo for all pts. Local progression was detected in only 5 patients (16%) while distant disease developed in 24 (77%). Resection status significantly correlated with OS; R0/R1 patients had a median survival of 23 mo vs. 10 mo for R2/unresected tumors (p = 0.002). Three-year OS was 35% vs. 0%, respectively. Survival was not influenced by tumor location, CA19-9 baseline or response, tumor size, or initial judgment of resectability (BR vs. UR). BR tumors were resectable after neoadjuvant therapy in 9 of 11 patients (R0, 8; R1, 1) while 8 of 20 initially UR tumors underwent resection (R0, 3; R1, 4; R2, 1). Conclusions: Neoadjuvant therapy combined with IOERT has the possibility to improve patient selection for surgical resection and to optimize local therapy. Although the prognosis for locally advanced pancreatic cancer remains poor, survival was superior among patients for whom R0 or R1 resection was achieved. Distant metastasis remained the dominant pattern of failure, and novel systemic agents are needed. Prospective evaluation of the impact of neoadjuvant chemotherapy, CRT, and IOERT is warranted.

Impact of duodenal invasion on outcomes in patients with pancreatic cancer treated with stereotactic body radiotherapy.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 408-408 ◽  
Author(s):  
Gilbert Murimwa ◽  
Eric Albert Mellon ◽  
Jessica M. Frakes ◽  
Will Jin ◽  
Pamela Joy Hodul ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Bleeding Risk ◽  
Rank Test ◽  
Gi Bleeding ◽  
Borderline Resectable ◽  
Duodenal Invasion ◽  
The Impact

408 Background: Clinical trials for pancreatic adenocarcinoma patients treated with a uniform SBRT tumor dose prescription exclude tumors invading the duodenum due to potential for increased GI mucosal complications. We analyzed our non-trial patients to determine the impact of SBRT in the setting of known duodenal invasion. Methods: An IRB-approved institutional database was queried identifying all 220 localized borderline resectable or locally advanced pancreatic cancer patients treated with SBRT from 2009 to 2015. Eligibility included patients with head tumors, a minimum of 6 months of follow up, and duodenal invasion on pretreatment endoscopic ultrasound (EUS). Dose painted SBRT delivered 25-30 Gy to tumor abutting the duodenum and up to 50 Gy to focal tumor/vessel abutment. Analysis evaluated whether patients with duodenal invasion had increased incidence of grade ≥ 3 (G3+) toxicity, GI ulceration or bleeding, or worsened overall survival (OS). Fisher’s Exact Test (2-tailed) compared patient characteristics and binary outcomes. Survival estimates by Kaplan-Meier were compared using log-rank test. Results: The study population included 126 patients (median F/U 14.1 months). Of 23 patients with duodenal invasion, 14 (61%) underwent resection, 3 (13%) developed G3+ toxicity and 1 (4%) had acute pre-op G3 GI bleeding that was controlled endoscopically prior to surgery. Of 103 without duodenal invasion, 48 (47%) underwent resection, 9 (9%) suffered G3+ toxicity and 7 (7%) had any GI bleed or ulceration. None of the 7 patients with GI bleeding or ulceration underwent pancreatectomy, and 3 had bleeding from tumor progression into the duodenum. There was no association between duodenal invasion and the incidence of G3+ toxicity (p = 0.76) or GI ulceration/bleeding (p = 1.0). There was no worsened OS (p = 0.17) or G3+ toxicity (p = 0.22) for patients with duodenal invasion on EUS. Patients with a GI bleeding or ulceration event had decreased OS (p = .014). Conclusions: Duodenal invasion on EUS prior to SBRT did not worsen GI bleeding risk or survival. Our data suggests that excluding pancreatic adenocarcinoma patients with duodenal invasion from SBRT when using a dose-painted approach is unnecessary.

scholarly journals Combination of gemcitabine, nab-paclitaxel, and S-1(GAS) as the first-line treatment for patients with locally advanced or advanced pancreatic ductal adenocarcinoma: study protocol for an open-label, single-arm phase I study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chen Chang ◽  
Xiaofen Li ◽  
Dan Cao
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Objective Response ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Chinese Patients ◽  
Ductal Adenocarcinoma ◽  
Open Label ◽  
Systemic Treatments

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is still a highly fatal malignancy among the most common cancers. More powerful treatments are expecting to bring hope for patients. Biweekly gemcitabine/nab-paclitaxel/S-1 (GAS) was proved safe and effective for patients with locally advanced pancreatic cancer in Japan. The objective of this study is to evaluate the feasibility and toxicity of GAS (repeated every 3 weeks) in the treatment of locally advanced or advanced pancreatic cancer and determine the recommended dose of S-1 in this combination. Methods This is an open-label, single-arm, and single-center phase I trial. Patients who have been diagnosed with locally advanced or advanced PDAC pathologically without previous systemic treatments will be enrolled and be treated with GAS chemotherapy every 3 weeks (nab-paclitaxel 125 mg/m 2, ivgtt, day1, 8; gemcitabine 1000 mg/m2, day1, 8; different doses of S-1 within a dose escalation scheme) until the presence of disease progression (PD), intolerable adverse events (AEs), or requirement of patients and researchers. The primary endpoints are maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). The secondary endpoints include safety, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Discussion This trial will adjust the administration of GAS to make it more effective for Chinese patients, while exploring the toxicity and feasibility of this adjustment. Trial registration ChiCTR, (ChiCTR1900027833). Registered 30 November 2019.

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