scholarly journals PEGPH20, a PEGylated Human Hyaluronidase, Induces Radiosensitization by Reoxygenation In Pancreatic Cancer Xenografts. A Molecular Imaging Study

2022 ◽  
Author(s):  
Tomohiro Seki ◽  
Yu Saida ◽  
Shun Kishimoto ◽  
Jisook Lee ◽  
Yasunori Otowa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Radiation Therapy ◽  
Blood Volume ◽  
Radiation Treatment ◽  
Photoacoustic Imaging ◽  
Imaging Study ◽  
Tumor Oxygenation ◽  
Glycolytic Flux ◽  
Wild Type ◽  
Survival Times

PEGylated human hyaluronidase (PEGPH20) enzymatically depletes hyaluronan, an important component of the extracellular matrix, in tumors. The resultant improvement in vascular patency and perfusion has been shown to increase the delivery of therapeutic molecules. We show that PEGPH20 also improves the efficacy of radiation therapy in a human pancreatic adenocarcinoma BxPC3 mouse model overexpressing hyaluronan synthase 3 (BxPC3-HAS3) while exerting little effect on the corresponding wild type tumors. Mice overexpressing HAS3 developed fast growing, radiation resistant tumors that became rapidly more hypoxic as time progressed. Treatment with PEGPH20 increased survival times when used in combination with radiation therapy, significantly more than either radiation therapy or PEGPH20 alone. Radiosensitization in BxPC3-HAS3 tumors was attributed to an increase in local pO2 as studied by by EPR imaging. No effect on survival, radiation treatment, or pO2 was seen in wild type tumors after PEGPH20 treatment. Dynamic contrast enhanced (DCE) MRI and MRI based blood volume imaging showed improved perfusion/permeability and local blood volume, respectively, in BxPC3-HAS3 tumors after PEGPH20 treatment, accounting for the increase in tumor oxygenation. Photoacoustic imaging indicated immediate changes in tumor oxygenation after treatment. Metabolic MRI using hyperpolarized [1-13C] pyruvate suggested a metabolic shift towards decreased glycolytic flux after PEGPH20 treatment. In summary, the results showed that PEGPH20 may be useful for radiosensitization of pancreatic cancer but only in the subset of tumors with substantial hyaluronan accumulation and the response of the treatment may potentially be monitored non-invasive imaging of the hemodynamic and metabolic changes in the tumor microenvironment.

Use of trans sodium crocetinate for sensitizing glioblastoma multiforme to radiation

2008 ◽  
Vol 108 (5) ◽  
pp. 972-978 ◽  
Author(s):  
Jason Sheehan ◽  
Adina Ionescu ◽  
Nader Pouratian ◽  
D. Kojo Hamilton ◽  
David Schlesinger ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Mr Imaging ◽  
Median Survival ◽  
Oxygen Diffusion ◽  
Radiation Treatment ◽  
Tumor Regression ◽  
C6 Glioma ◽  
C6 Glioma Cells ◽  
Survival Times ◽  
Moderate Dose

Object Adjuvant treatment with radiation (radiation therapy or radiosurgery) is a mainstay of treatment for patients harboring glioblastomas multiforme (GBM). Hypoxic regions within the tumor make cells less sensitive to radiation therapy. Trans sodium crocetinate (TSC) has been shown to increase oxygen diffusion in the brain and elevate the partial brain oxygen level. The goal of this study was to evaluate the radiosensitizing effects of TSC on GBM tumors. Methods A rat C6 glioma model was used, in which C6 glioma cells were stereotactically injected into the rat brain to create a tumor. Following creation of a right frontal tumor, animals were randomized into 1 of 4 groups: 1) TSC alone (animal treated with moderate-dose TSC only); 2) radiation (animals receiving 8 Gy of cranial radiation); 3) radiation and low-dose TSC (animals receiving 8 Gy of radiation and 50 μg/kg of TSC); or 4) radiation and moderate-dose TSC (animals receiving 8 Gy of radiation and 100 μg/kg of TSC). Animals were observed clinically for 60 days or until death. Magnetic resonance (MR) imaging was performed at 2-week intervals on each animal and quantitatively evaluated for tumor response. Immunohistochemical analysis was performed on all brain tumors. Survival differences were also evaluated using the Kaplan–Meier method. Results On MR imaging, a statistically significant reduction in tumor size was seen in the group receiving moderate-dose TSC and radiation treatment compared with the group receiving radiation treatment alone. The rate of tumor growth was significantly less for the combination of TSC and radiation treatment compared with either modality alone. Median survival times for the TSC-only and the radiation therapy–only groups were 15 and 30 days, respectively. The 60-day median survival times for the groups receiving a combination of either low- or moderate-dose TSC with radiation therapy were statistically improved compared with those for the other treatment groups. Conclusions Use of TSC improves the extent of GBM tumor regression following radiation therapy and enhances survival. Radiosensitization of hypoxic tumors through increased oxygen diffusion may have clinical utility in patients with GBM tumors but must be explored in a clinical trial.

Improved survival with radiation therapy in early pancreatic adenocarcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15036-15036
Author(s):  
A. Artinyan ◽  
M. Hellan ◽  
P. Mojica-Manosa ◽  
J. Ellenhorn ◽  
J. Kim
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Radiation Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Radiation Treatment ◽  
Prognostic Significance ◽  
Adjuvant Radiation ◽  
Cox Regression Analysis ◽  
Adjuvant Radiation Therapy

15036 Background: Although chemoradiation is often used following pancreatic cancer resection, recent studies have questioned the role of radiation therapy in this setting. The objective of this study was to determine the effect of adjuvant radiation therapy following pancreatectomy in patients with node-negative (N0) pancreatic cancer. Methods: The Surveillance, Epidemiology, and End Results (SEER) registry was used to identify patients with N0 pancreatic adenocarcinoma who had undergone curative-intent resection between 1988–2003. Kaplan-Meier survival curves were constructed to compare overall survival between patients ± adjuvant radiation therapy. Multivariate Cox regression analysis was performed to determine the prognostic significance of radiation therapy when additional clinicopathologic factors were assessed. The analysis also examined the potential treatment selection bias of patients with survival <3 months. Results: Query of the SEER database identified 2342 surgical patients with N0 disease. The median survival for these patients was 18 months. 889 (60.1%) patients were treated with radiation. There was no difference in gender or grade between radiation and non-radiation groups; however, radiation patients were younger (63 vs. 67 years, p<0.001) and had a greater proportion of T3 lesions (p=0.002). Radiation patients had significantly improved survival compared to non-radiation patients (20.0 vs. 15.0 months, p<0.001). On multivariate analysis, radiation therapy (HR 0.72, p<0.001), age, grade, T-stage, and tumor location were independent predictors of survival. When patients with survival <3 months were excluded from analysis, no difference in survival between radiation and non- radiation was noted (20.0 vs. 19.0 months, p=0.096). However, on subset analysis, patients with T3 tumors demonstrated improved survival with the addition of radiation (24.0 vs 16.0 months, p=0.002) and on multivariate analysis radiation therapy was an independent predictor of improved overall survival (HR 0.87, p=0.027). Conclusions: Radiation treatment is associated with improved survival in operable N0 pancreatic cancer and its use should be considered in patients with early stage N0 disease. The greatest impact of radiation therapy use appears to occur with T3 tumors. No significant financial relationships to disclose.

Nano-sheets of graphene oxide enhances the combined effect of hyperthermia and radiation treatment in pancreatic cancer cell lines.

2021 ◽  
Vol 16 ◽  
Author(s):  
Mohammad H. Haqiqian ◽  
Dariush Sardari ◽  
Mohammad Houshyari ◽  
R. Moghadasali
Keyword(s):  
Pancreatic Cancer ◽  
Radiation Therapy ◽  
Graphene Oxide ◽  
Cell Viability ◽  
Cell Survival ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Radiation Treatment ◽  
Cancerous Cell

Background: Pancreatic cancer leaves little hope for survival among patients. This is due to its cancerous cell resistance to radiation and chemicals. Objective: Synergistic effect between three modalities of pancreatic cancer treatment is investigated. These are radiation therapy, Hyperthermia and graphene oxide nanosheets. The aim is to overcome resistance of pancreatic cancer cell against radiation therapy. Methods: Cancerous cell lines were treated by each one of three modalities separately. Other samples were treated with various combinations of these modalities. Hyperthermia accomplished with placing cell lines for 15 min in 42°C. In the course of radiation therapy, the cancerous cells were irradiated by 6 MV Linac for two cases of 2 Gy and 3 Gy. The cell line viability was readout by MTT assay in 24 hours and 48 hours after treatment. Results: In single modality treatment it was shown that 24h after the treatment, the group treated by RT 3 Gy had the highest cell killing result. Following up the result in 48h readout, hyperthermia and 3 Gy radiotherapy had similar result. In double modality treatment, for both 24h and 48h viability readout, the group graphene-oxide plus 2 Gy radiotherapy showed cell survival amounting to 69% and 43% respectively being the lowest cell survival among all double combinations. Conclusion: In triple modality treatment, the cell viability for 24h showed no significant improvement but in 48h the hyperthermia plus Graphene-oxide and 3 Gy radiotherapy had very low cell viability. Significant sensitizing effect for GO when combined by radiation therapy was observed.

scholarly journals Vertebral body and splenic irradiation are associated with lymphopenia in localized pancreatic cancer treated with stereotactic body radiation therapy

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Abhinav V. Reddy ◽  
Matthew P. Deek ◽  
Juan F. Jackson ◽  
Colin S. Hill ◽  
Shuchi Sehgal ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Radiation Therapy ◽  
Vertebral Body ◽  
Stereotactic Body Radiation Therapy ◽  
Radiation Treatment ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Absolute Lymphocyte Count ◽  
Borderline Resectable ◽  
Stereotactic Body Radiation

Abstract Objectives The purpose of this study was to determine if vertebral body and splenic dosimetry was associated with the development of lymphopenia in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiation therapy (SBRT). Methods Patients with BRPC/LAPC who were treated with SBRT and who had lymphocyte counts and radiation treatment plans available for review were included in the study. Vertebral body levels T11-L3 and the spleen were retrospectively contoured for each patient. Univariate (UVA) and multivariable analyses (MVA) were performed to identify associations between vertebral body and splenic dosimetric parameters with absolute lymphocyte count (ALC) and grade ≥ 2 lymphopenia. Receiver operator characteristic curves were generated to identify dose-volume thresholds in predicting grade ≥ 2 lymphopenia. Results A total of 132 patients were included in the study. On UVA and MVA, vertebral V15 (regression coefficient [β]: − 0.026, 95% CI − 0.044 to − 0.009, p = 0.003), vertebral V2.5 (β: − 0.011, 95% CI − 0.020 to − 0.002, p = 0.015), and log10PTV (β: − 0.15, 95% CI − 0.30 to − 0.005, p = 0.042) were associated with post-SBRT ALC. On UVA and MVA, vertebral V15 (odds ratio [OR]: 3.98, 95% CI 1.09–14.51, p = 0.027), vertebral V2.5 (OR: 1.04, 95% CI 1.00–1.09, p = 0.032), and spleen V10 (OR: 1.05, 95% CI 1.09–1.95, p = 0.004) were associated with development of grade ≥ 2 lymphopenia. Development of grade ≥ 2 lymphopenia was more likely in patients with vertebral V15 ≥ 5.84% (65.5% vs 34.0%, p = 0.002), vertebral V2.5 ≥ 48.36% (48.9% vs 23.8%, p = 0.005), and spleen V10 ≥ 4.17% (56.2% vs 26.9%, p < 0.001). Conclusions Increasing radiation dose to vertebral bodies and spleen were associated with the development of lymphopenia in BRPC/LAPC treated with SBRT. Optimization of vertebral body and splenic dosimetry may reduce the risk of developing lymphopenia and improve clinical outcomes in this population.

Exosome-based photoacoustic imaging guided photodynamic and immunotherapy for the treatment of pancreatic cancer

2021 ◽  
Vol 330 ◽  
pp. 293-304
Author(s):  
Yongho Jang ◽  
Haemin Kim ◽  
Semi Yoon ◽  
Hohyeon Lee ◽  
Jangsun Hwang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Photoacoustic Imaging

scholarly journals Development of an Objective Scoring System for Endoscopic Assessment of Radiation-Induced Upper Gastrointestinal Toxicity

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2136
Author(s):  
Daniel Lin ◽  
Shalini Moningi ◽  
Joseph Abi Jaoude ◽  
Ben S. Singh ◽  
Irina M. Cazacu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Radiation Therapy ◽  
Scoring System ◽  
Interobserver Agreement ◽  
Locally Advanced ◽  
Severe Toxicity ◽  
Cancer Trial ◽  
Gi Toxicity ◽  
Upper Gastrointestinal ◽  
Toxicity Scoring

We developed and implemented an objective toxicity scoring system to be used during endoscopic evaluation of the upper gastrointestinal (GI) tract in order to directly assess changes in toxicity during the radiation treatment of pancreatic cancer. We assessed and validated the upper GI toxicity of 19 locally advanced pancreatic cancer trial patients undergoing stereotactic body radiation therapy (SBRT). Wilcoxon-signed rank tests were used to compare pre- and post-SBRT scores. Comparison of the toxicity scores measured before and after SBRT revealed a mild increase in toxicity in the stomach and duodenum (p < 0.005), with no cases of severe toxicity observed. Kappa and AC1 statistics analysis were used to evaluate interobserver agreement. Our toxicity scoring system was reliable in determining GI toxicity with a good overall interobserver agreement for pre-treatment scores (stomach, κ = 0.71, p < 0.005; duodenum, κ = 0.88, p < 0.005) and post-treatment scores (stomach, κ = 0.71, p < 0.005; duodenum, κ = 0.76, p < 0.005). The AC1 statistics yielded similar results. With future usage, we hope this scoring system will be a useful tool for objectively and reliably assessing changes in GI toxicity during the treatment of pancreatic cancer and for GI toxicity assessments and comparisons during radiation therapy research trials.

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