Prognostic Significance of Circulating Tumor Cells for Locally Advanced Pancreatic Cancer with High-dose Hypofractionated Radiotherapy

2020 ◽  
Vol 108 (3) ◽  
pp. e595-e596
Author(s):  
G. Ren ◽  
Y. Wang ◽  
T. Xia ◽  
X. Li ◽  
Y. Wang
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Locally Advanced ◽  
Prognostic Significance ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Hypofractionated Radiotherapy ◽  
High Dose

scholarly journals Expansion of Circulating Tumor Cells from Patients with Locally Advanced Pancreatic Cancer Enable Patient Derived Xenografts and Functional Studies for Personalized Medicine

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1011 ◽  
Author(s):  
Lianette Rivera-Báez ◽  
Ines Lohse ◽  
Eric Lin ◽  
Shreya Raghavan ◽  
Sarah Owen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Ex Vivo ◽  
Functional Characterization ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Predictive Biomarkers ◽  
Locally Advanced Pancreatic Cancer ◽  
Preclinical Model

Improvement in pancreatic cancer treatment represents an urgent medical goal that has been hampered by the lack of predictive biomarkers. Circulating Tumor Cells (CTCs) may be able to overcome this issue by allowing the monitoring of therapeutic response and tumor aggressiveness through ex vivo expansion. The successful expansion of CTCs is challenging, due to their low numbers in blood and the high abundance of blood cells. Here, we explored the utility of pancreatic CTC cultures as a preclinical model for treatment response. CTCs were isolated from ten patients with locally advanced pancreatic cancer using the Labyrinth, a biomarker independent, size based, inertial microfluidic separation device. Three patient-derived CTC samples were successfully expanded in adherent and spheroid cultures. Molecular and functional characterization was performed on the expanded CTC lines. CTC lines exhibited KRAS mutations, consistent with pancreatic cancers. Additionally, we evaluated take rate and metastatic potential in vivo and examined the utility of CTC lines for cytotoxicity assays. Patient derived expanded CTCs successfully generated patient derived xenograft (PDX) models with a 100% take rate. Our results demonstrate that CTC cultures are possible and provide a valuable resource for translational pancreatic cancer research, while also providing meaningful insight into the development of distant metastasis, as well as treatment resistance.

Hypofractionated radiotherapy for patients with locally advanced pancreatic cancer using tomotherapy Hi-Art and CyberKnife: A study of the treatment outcome and failure patterns.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 342-342
Author(s):  
H. Jang
Keyword(s):  
Pancreatic Cancer ◽  
Treatment Outcome ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Hypofractionated Radiotherapy ◽  
Ulcer Bleeding ◽  
Survival Duration ◽  
Response Evaluation ◽  
One Year

342 Background: To evaluate the treatment outcome and pattern of failure in the patients with locally advanced pancreatic cancer, who were treated with hypofractionated radiotherapy (RT) using TomoTherapy Hi-Art and Cyberknife. Methods: From April 2004 to May 2010, Twenty four patients with locally advanced pancreatic cancer received hypofractionated RT using TomoTherapy Hi-Art and Cyberknife at Seoul St. Mary's Hospital, the Catholic University of Korea. Eleven patients (45.8%) were treated using TomoTherapy Hi-Art and 13 patients (54.2%) using Cyberknife. The total dose delivered were 45∼55 Gy (median: 50 Gy) in 15∼22 fractions with TomoTherapy Hi-Art and 24∼40 Gy (median 30 Gy) in 3∼5 fractions with Cyberknife. The RECIST version 1.1 was used for the response evaluation. The follow-up duration was 3.0∼77.1 months (median: 34 months). Results: In the initial response evaluation, the rates of partial response, stable disease and progressive disease were 45.8%, 54.2% and 0%, respectively. Median survival duration was 11.1 months. One year and two year survival rates were 39.4% and 21.1%, respectively. Two patients (8.3%) had local failures and 11 patients (45.8%) had distant failures. Distant failures were main cause of failures. Median time to distant failures was 7.8 months and one year distant progression-free survival rate was 35.1%. The difference of the treatment outcome between TomoTherapy Hi-Art and Cyberknife was not statistically significant. Most patients experienced abdominal discomfort and pain after RT. However, no severe gastrointestinal complication such as ulcer, bleeding, perforation and fistula were noted. Conclusions: Hypofractionated RT for the patients with locally advanced pancreatic cancer showed excellent local control. However, overall survival still remains poor because of distant failures. Therefore, effective systemic chemotherapy should be considered with RT, either concurrently or sequentially. No significant financial relationships to disclose.

Phase I/II trial of carbon-ion radiotherapy with concurrent gemcitabine for patients with locally advanced pancreatic cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15008-e15008
Author(s):  
Makoto Shinoto ◽  
Shigeru Yamada ◽  
Shigeo Yasuda ◽  
Hiroshi Imada ◽  
Yoshiyuki Shioyama ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Survival Rate ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Carbon Ion Radiotherapy ◽  
Hematological Toxicity ◽  
High Dose ◽  
Carbon Ion ◽  
Grade 3

e15008 Background: Carbon-ion radiotherapy (CIRT) offers the potential advantage of improved dose localization and enhanced biologic effect. The purpose of this trial was to establish the recommended dose of gemcitabine and CIRT, evaluating the tolerance and efficacy of gemcitabine combined with CIRT for the treatment of the patients with locally advanced pancreatic cancer. Methods: Patients with histopathologically proven, locally advanced pancreatic adenocarcinoma, which involved the celiac trunk or superior mesenteric artery without distant metastasis, were eligible for this trial. The radiation fractions were fixed at 12 fractions in 3 weeks, and the dose of gemcitabine and radiation were gradually increased. First, the dose was fixed at 43.2GyE/8 fractions and the gemcitabine dose was increased from 400, to 700 to 1000mg/m2. Subsequently, the gemcitabine dose was fixed at 1000mg/m2 and the radiation dose was increased from 43.2GyE to 55.2GyE by 5% increments. Gemcitabine was administered for 3 consecutive weeks, once a week. Results: Seventy-five patients were registered from April 2007 through February 2012. Of these patients, 71 were clinically eligible for the study. The most common Grade 3 acute toxicities were hematological toxicity (51%) and anorexia (8%). Dose limiting toxicity developed in three patients: Grade 3 gastric ulcer in 1 and Grade 4 leukopenia in 2. No other serious side effects were found. The two-year local control rate and two-year overall survival rate were 40% and 40% in all patients. The median survival time was 21 months. In the high dose group (n=47), in which patients were irradiated with at least 45.6 GyE, the two-year survival rate was 62%. Conclusions: CIRT was well tolerable even when concomitantly administered with the highest dose of gemcitabine (1000mg/m2).

scholarly journals EGLN Inhibition Reduces Gastrointestinal Radiation Toxicity and Improves Survival in a Murine Model of Locally Advanced Pancreatic Cancer

2017 ◽  
Author(s):  
Tara N. Fujimoto ◽  
Lauren E. Colbert ◽  
Jessica M. Molkentine ◽  
Laura Baseler ◽  
Amit Deorukukhar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
High Dose ◽  
Radiation Toxicity ◽  
Selective Protection ◽  
Local Progression ◽  
Molecule Inhibitor ◽  
Radiation Treatments

AbstractLocally advanced pancreatic cancer (LAPC) almost always fatal since it is unresectable and chemotherapy is only modestly effective. The efficacy of radiation therapy (RT) for LAPC is limited by the potentially fatal toxicity to nearby intestines. There are no FDA-approved medications that can prevent this radiotoxicity, but we find that FG-4592, a small molecule inhibitor of EGLN proteins, significantly reduces radiation damage to the intestines without radioprotecting tumors. KPC (KrasLSL/+; Trp53FL/+; Ptf1aCre/+) animals received dose-escalated radiation treatments with and without FG-4592 for radioprotection. High-dose RT reduced death from local progression, improved survival, and shifted the patterns of failure to a late metastatic death compared to controls. The addition of FG-4592 to RT further improved survival compared to vehicle controls by eliminating radiation-induced gastrointestinal toxicity. Thus, selective protection of the intestinal tract by EGLN inhibition may enable higher, and potentially definitive doses of cytotoxic therapy to be delivered to LAPC.One Sentence SummaryThe EGLN inhibitor FG-4592 allows higher, and potentially definitive, doses of radiation to be delivered to pancreatic cancer by reducing normal tissue toxicity without protecting tumors.

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