The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Anand Mahadevan - One of the best experts on this subject based on the ideXlab platform.
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Stereotactic Body Radiotherapy (SBRT) Reirradiation for Recurrent Pancreas Cancer.
Journal of Cancer, 2016Co-Authors: Nergiz Dagoglu, Mark P. Callery, James Moser, Jennifer F. Tseng, Tara S. Kent, Andrea J. Bullock, Rebecca A. Miksad, Joseph D. Mancias, Anand MahadevanAbstract:Objectives: After adjuvant or definitive radiation for Pancreas Cancer, there are limited conventional treatment options for recurrent Pancreas Cancer. We explored the role of (Stereotactic Body Radiotherapy) SBRT for reirradiation of recurrent Pancreas Cancer. Methods: This is a retrospective study of patients reirradiated with SBRT for recurrent Pancreas Cancer. All patients were deemed unresectable and treated with systemic therapy. Fiducial gold markers were used. CT simulation was performed with oral and IV contrast and patients were treated with respiratory motion tracking in the CyberknifeTM system. Results: 30 patients (17 men and 13 women) with a median age of 67 years were included in the study. The median target volume was 41.29cc. The median prescription dose was 25Gy (24-36Gy) in a median of 5 fractions prescribed to a mean 78% isodose line. The median overall survival was 14 months. The 1 and 2 year local control was 78%. The worst toxicity included 3/30(10%) Grade III acute toxicity for pain, bleeding and vomiting. There was 2/30 (7%) Grade III long-term bowel obstructions. Conclusions: SBRT can be a useful and tolerable option for patients with recurrent Pancreas Cancer after prior radiation.
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Stereotactic body radiotherapy (SBRT) reirradiation for recurrent Pancreas Cancer.
Journal of Clinical Oncology, 2015Co-Authors: Rabia N Dagoglu, Mark P. Callery, James Moser, Jennifer F. Tseng, Tara S. Kent, Andrea J. Bullock, Rebecca A. Miksad, Joseph D. Mancias, Anand MahadevanAbstract:451 Background: After adjuvant or definitive radiation for Pancreas Cancer, there are limited conventional treatment options for recurrent Pancreas Cancer. We explored the role of (Stereotactic Body Radiotherapy) SBRT for reirradiation of recurrent Pancreas Cancer. Methods: Our institutional IRB approved database was retrospectively reviewed. All patients were deemed unresectable and treated with systemic therapy. Fiducial gold markers were used. CT simulation was performed with oral and IV contrast and patients were treated with respiratory motion tracking.The choice of fractionation was based on tumor volume, location of the tumor and prior radiation dose, interval between prior RT, adjacent normal tissue, patients’ performance status and co morbidities. The irradiation dose was prescribed to the isodose line covering at least 95% of the target volume. Maximum point dose to the gastric and duodenal walls was kept at or below prescription dose. Results: This study included 30 patients reirradiated for re...
Sunil R. Hingorani - One of the best experts on this subject based on the ideXlab platform.
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Cholesterol Biosynthesis Influences Subtype Specificity and Plasticity in Pancreas Cancer
Cancer cell, 2020Co-Authors: Sita Kugel, Sunil R. HingoraniAbstract:Cellular plasticity contributes to intratumoral heterogeneity, metastatic spread, and treatment resistance of Cancers. In this issue of Cancer Cell, Gabitova-Cornell et al. identify the potential to inadvertently develop an undifferentiated and more aggressive Pancreas Cancer with agents commonly prescribed to manage heart disease risk.
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Tension and Transformation in Pancreas Cancer: Can Phenotype Break Free from the Chrysalis of Genotype?
Cancer cell, 2016Co-Authors: Christopher C. Dufort, Sunil R. HingoraniAbstract:A recent study finds that impaired TGFβ signaling can initiate a positive feedback loop between increasing ECM stiffness and epithelial cell contractility in Pancreas Cancer. Even more surprising is the possibility that this phenotype can liberate the epithelium from dependence on the genetic events that transformed it.
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Abstract A67: Defining signaling pathways governing metastatic potential in Pancreas Cancer
Heterogeneity in Tumor Progression, 2015Co-Authors: Martin C. Whittle, Markus A. Carlson, Sunil R. HingoraniAbstract:Pancreas Cancer is an aggressively metastatic disease in which circulating tumor cells (CTC) often colonize distant organs long before diagnosis. Approximately 45% of patients present at diagnosis with metastatic disease, and this increases to 90% at the time of death. Even after surgical resection of the primary tumor, local and distant recurrence develops in approximately two thirds of cases. These sobering statistics highlight the need to define mechanisms and vulnerabilities of metastasis that can be targeted to improve patient outcomes. To better understand the process of pancreatic Cancer metastasis, we study the Kras LSL-G12D/+ ; Trp53 LSL-R172H/+ ; Pdx1-Cre ( KPC ) model of autochthonous Pancreas Cancer. KPC mice spontaneously develop invasive and metastatic disease to numerous sites, including the liver and lungs, at rates similar to those seen in humans. Lineage tracing, performed by selectively expressing fluorescent reporters in pancreatic cells of KPC mice, has revealed a rare population of CTC that may be precursors to these metastatic foci. Building on this model, we show that alteration of TGFβ pathway components significantly affects the metastatic potential of autochthonous tumors, and that the timing and balance of signaling is critical in the metastatic process. These differences in metastatic potential are reflected in the numbers and functional properties of the respective CTC. Our distinct models with drastically different metastatic potentials provide clues to understanding the signaling mechanisms driving metastasis in Pancreas Cancer. Citation Format: Martin C. Whittle, Markus Carlson, Sunil R. Hingorani. Defining signaling pathways governing metastatic potential in Pancreas Cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A67.
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stromal reengineering to treat Pancreas Cancer
Carcinogenesis, 2014Co-Authors: Ingunn M Stromnes, Sunil R. Hingorani, Kathleen E Delgiorno, Philip D GreenbergAbstract:Pancreatic ductal adenocarcinoma co-opts multiple cellular and extracellular mechanisms to create a complex Cancer organ with an unusual proclivity for metastasis and resistance to therapy. Cell-autonomous events are essential for the initiation and maintenance of pancreatic ductal adenocarcinoma, but recent studies have implicated critical non-cell autonomous processes within the robust desmoplastic stroma that promote disease pathogenesis and resistance. Thus, non-malignant cells and associated factors are culprits in tumor growth, immunosuppression and invasion. However, even this increasing awareness of non-cell autonomous contributions to disease progression is tempered by the conflicting roles stromal elements can play. A greater understanding of stromal complexity and complicity has been aided in part by studies in highly faithful genetically engineered mouse models of pancreatic ductal adenocarcinoma. Insights gleaned from such studies are spurring the development of therapies designed to reengineer the Pancreas Cancer stroma and render it permissive to agents targeting cell-autonomous events or to reinstate immunosurveillance. Integrating conventional and immunological treatments in the context of stromal targeting may provide the key to a durable clinical impact on this formidable disease.
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A New Preclinical Paradigm for Pancreas Cancer
Drug Discovery in Pancreatic Cancer, 2010Co-Authors: Sunil R. HingoraniAbstract:Pancreas Cancer confounds patient and physician alike. With an almost identical annual incidence and mortality, the disease has heretofore thwarted attempts to cure and even contain it. The approach to the patient with Pancreas Cancer is the same as for any Cancer: detect it early, diagnose it accurately and eradicate it through a combination of surgery and chemical and radiotherapies. However, Cancer of this organ eludes early detection, runs the risk of significant collateral injury when attempting to biopsy it for diagnosis, and resists all current forms of conventional chemotherapy and radiation. Moreover, the disease is as difficult to study in patients as it is to treat. Although classical experimental model systems have yielded significant information on genetic mutations of interest, they have not proved as useful in screening for drugs likely to be effective in patients. Mammalian model systems that faithfully mimic the full spectrum of the human disease from inception to invasion are needed. This chapter describes an integrated translational approach to developing and testing early detection, molecular diagnostic, chemopreventive and therapeutic strategies using state-of-the-art genetically engineered mouse models.
George A Fisher - One of the best experts on this subject based on the ideXlab platform.
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detection of circulating tumor dna in Pancreas Cancer
Journal of Clinical Oncology, 2020Co-Authors: Daniel A King, Ash A Alizadeh, George A FisherAbstract:645Background: Pancreas Cancer remains a leading cause of Cancer-related death. Improved detection of early relapse or early failure of chemotherapy also has the potential to further improve outcom...
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abstract c29 development of a circulating tumor dna assay in Pancreas Cancer
Cancer Research, 2019Co-Authors: Daniel A King, George A Fisher, Mari Olsen, Max Diehn, Ash A AlizadehAbstract:Pancreas Cancer is the third most common cause of Cancer-related death, owing in part to high rates of unresectable disease at time of diagnosis and poor long-term response to chemotherapy. Biomarkers are needed to sensitively identify and monitor disease burden, and to measure response to therapy. The CA19-9 tumor marker lacks sufficient positive or negative predictive value to guide treatment decisions, and digital droplet PCR (ddPCR) assessment of circulating KRAS mutations suffers poor sensitivity on account of only assessing a single DNA locus. We hypothesize that a multitargeted circulating tumor DNA assay can outperform CA19-9 and ddPCR as biomarker for the detection and monitoring of Pancreas Cancer. Our lab has developed the Cancer personalized profiling by deep sequencing (CAPP-Seq) method, which combines high-depth sequencing with several strategies of error-suppression to identify minute amounts of tumor DNA circulating in patients’ blood. The development of our CAPP-Seq targeted sequencing panel hinged primarily on capturing regions of the genome known to be recurrently mutated in pancreatic ductal adenocarcinoma (PDAC), based on The Cancer Genome Atlas project. These regions contain mutations in KRAS, TP53, SMAD4, and by a long-tail of mutations in many other genes for which we contributed approximately 200 kb of selector space. In addition to recurrent SNVs, we also contributed approximately 35 kb for recurrent copy number variant locations, 10 kb for recurrent noncoding variants, and 20 kb for regions with aberrant expression patterns in PDAC based on TCGA RNA-sequencing data. This purpose of this study is to employ CAPP-Seq in two Pancreas Cancer cohorts: patients who underwent resection at Stanford and had blood drawn before and after surgical resection (n=30), and a cohort of patients with metastatic disease who are undergoing chemotherapy with blood draws at multiple time-points (n=20). The former cohort will assess prediction of recurrence based on ctDNA level, and the latter will assess patients with early development of resistance to chemotherapy. Before assessing this ctDNA detection assay in patients with Pancreas Cancer, we first evaluated the CAPP-Seq approach on two healthy research subjects and achieved on average 4000x de-duplicated sequencing depth, for a theoretical limit of detection of 0.03% circulating tumor fraction. We next sequenced samples from 7 patients with resectable disease and 8 with metastatic disease, with results expected in early July. Citation Format: Dan King, Mari Olsen, George Fisher, Max Diehn, Ash Alizadeh. Development of a circulating tumor DNA assay in Pancreas Cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C29.
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18fluorodeoxyglucose pet is prognostic of progression free and overall survival in locally advanced Pancreas Cancer treated with stereotactic radiotherapy
International Journal of Radiation Oncology Biology Physics, 2010Co-Authors: Devin Schellenberg, George A Fisher, Andrew Quon, Yuriko A Minn, Edward E Graves, Pamela L Kunz, James M Ford, Karyn A Goodman, Albert C Koong, Daniel T ChangAbstract:Purpose This study analyzed the prognostic value of positron emission tomography (PET) for locally advanced Pancreas Cancer patients undergoing stereotactic body radiotherapy (SBRT). Patients and Methods Fifty-five previously untreated, unresectable Pancreas Cancer patients received a single fraction of 25-Gy SBRT sequentially with gemcitabine-based chemotherapy. On the preradiation PET-CT, the tumor was contoured and the maximum standardized uptake value (SUVmax) and metabolic tumor burden (MTB) were calculated using an in-house software application. High-SUVmax and low-SUVmax subgroups were created by categorizing patients above or below the median SUVmax. The analysis was repeated to form high-MTB and low-MTB subgroups as well as clinically relevant subgroups with SUVmax values of 10. Multivariate analysis analyzing SUVmax, MTB, age, chemotherapy cycles, and pretreatment carbohydrate antigen (CA)19-9 was performed. Results For the entire population, median survival was 12.7 months. Median survival was 9.8 vs.15.3 months for the high- and low- SUVmax subgroups ( p p 10, 9.5 months with SUVmax 5.0–10.0, and 17.7 months in those with SUVmax p p = 0.03) and progression-free survival ( p = 0.03). Conclusion PET scan parameters can predict for length of survival in locally advanced Pancreas Cancer patients.
Rabia N Dagoglu - One of the best experts on this subject based on the ideXlab platform.
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Stereotactic body radiotherapy (SBRT) reirradiation for recurrent Pancreas Cancer.
Journal of Clinical Oncology, 2015Co-Authors: Rabia N Dagoglu, Mark P. Callery, James Moser, Jennifer F. Tseng, Tara S. Kent, Andrea J. Bullock, Rebecca A. Miksad, Joseph D. Mancias, Anand MahadevanAbstract:451 Background: After adjuvant or definitive radiation for Pancreas Cancer, there are limited conventional treatment options for recurrent Pancreas Cancer. We explored the role of (Stereotactic Body Radiotherapy) SBRT for reirradiation of recurrent Pancreas Cancer. Methods: Our institutional IRB approved database was retrospectively reviewed. All patients were deemed unresectable and treated with systemic therapy. Fiducial gold markers were used. CT simulation was performed with oral and IV contrast and patients were treated with respiratory motion tracking.The choice of fractionation was based on tumor volume, location of the tumor and prior radiation dose, interval between prior RT, adjacent normal tissue, patients’ performance status and co morbidities. The irradiation dose was prescribed to the isodose line covering at least 95% of the target volume. Maximum point dose to the gastric and duodenal walls was kept at or below prescription dose. Results: This study included 30 patients reirradiated for re...
Mace L Rothenberg - One of the best experts on this subject based on the ideXlab platform.
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improvements in survival and clinical benefit with gemcitabine as first line therapy for patients with advanced Pancreas Cancer a randomized trial
Journal of Clinical Oncology, 1997Co-Authors: H.a. Burris, Mace L Rothenberg, Malcolm J Moore, M C Cripps, J S Andersen, Russell K Portenoy, Mark R Green, M R Modiano, Anna Maria Storniolo, P TarassoffAbstract:PURPOSEMost patients with advanced Pancreas Cancer experience pain and must limit their daily activities because of tumor-related symptoms. To date, no treatment has had a significant impact on the disease. In early studies with gemcitabine, patients with Pancreas Cancer experienced an improvement in disease-related symptoms. Based on those findings, a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced Pancreas Cancer.PATIENTS AND METHODSOne hundred twenty-six patients with advanced symptomatic Pancreas Cancer completed a lead-in period to characterize and stabilize pain and were randomized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest, then weekly x 3 every 4 weeks thereafter (63 patients), or to fluorouracil (5-FU) 600 mg/m2 once weekly (63 patients). The primary efficacy measure was clinical benefit response, which was a composite of measurements of pain (analgesic consumption and pain intensity), Karnofs...
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a phase ii trial of gemcitabine in patients with 5 fu refractory Pancreas Cancer
Annals of Oncology, 1996Co-Authors: Mace L Rothenberg, Malcolm J Moore, M C Cripps, J S Andersen, Russell K Portenoy, H A Burriss, Mark R Green, P Tarassoff, T D Brown, Ephraim S CasperAbstract:PURPOSE: To assess the effect of gemcitabine in patients with metastatic Pancreas Cancer that had progressed despite prior treatment with 5-FU. PATIENTS AND METHODS: Seventy-four patients were enrolled in this multicenter trial. Alleviation of Cancer-related symptoms was the primary endpoint. Sixty-three patients completed a pain stabilization period and were treated with gemcitabine. Clinical Benefit Response was defined as a > or = 50% reduction in pain intensity, > or = 50% reduction in daily analgesic consumption, or > or = 20 point improvement in KPS that was sustained for > or = 4 consecutive weeks. RESULTS: Seventeen of 63 pts (27.0%) attained a Clinical Benefit Response (95% CI: 16.0%-38.0%). The median duration of Clinical Benefit Response was 14 weeks (range: 4-69 weeks). Median survival for patients treated with gemcitabine was 3.85 months (range: 0.3-18.0+ months). Therapy was generally well-tolerated with a low incidence of grade 3 or 4 toxicities. CONCLUSION: Systematic assessment of subjective outcomes can be used to evaluate the clinical impact of new therapies for Pancreas Cancer, a highly symptomatic disease. Our findings suggest that gemcitabine is a useful palliative agent in patients with 5-FU-refractory Pancreas Cancer.
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550 Gemcitabine is effective as palliative therapy for 5FU-refractory Pancreas Cancer patients
European Journal of Cancer, 1995Co-Authors: H.a. Burris, Mace L RothenbergAbstract:In a previous phase II trial of gemcitabine in Pancreas Cancer, numerous patients experienced a reduction in Cancer-related symptoms and improvement in performance status. Since Pancreas Cancer is highly symptomatic, and therapy is difficult to assess using traditional endpoints, we designed and conducted a prospective, multicentre phase II trial with clinical benefit as the primary endpoint. Clinical benefit response was defined as a ≥ 50% reduction in pain (measured on a visual analogue scale), a ≥ 50% reduction in daily analgesic consumption, or a ≥ 20 point improvement in Kamofsky performance score (KPS), that was sustained for ≥4 weeks without worsening in any other component. Gemcitabine 1000 mg/m 2 (30 min infusion) was administered q wk × 7 followed by 1 wk rest, and thereafter in cycles q wk × 3 followed by a 1 wk rest. 63 pts (32 M, 31 F) with pancreatic adenocarcinoma that had progressed despite 1 prior 5-FU-based therapy were enrolled. Median age: 62 (range 33–77). Median KPS: 70 (range 50−90), median baseline pain intensity: 29 on a 100 point scale (range3−68), median baseline analgesic requirement: 60 mg morphine-equivalents/day (range 0−1159). Therapy was very well tolerated with grade 4 toxicities reported for nausea, vomiting, neutropenia, bleeding or anaemia (each in 1 pt, 2%). Grade 3 toxicities included neutropenia (25% pts), anaemia (10%), thrombocytopenia (5%), and nausea/vomiting (6%). Under these stringent criteria, 17 of 63 pts (27%) attained a clinical benefit response (95% CI: 16−38%). We conclude that objective criteria can be used to evaluate new therapies for Pancreas Cancer, and that gemcitabine has substantial activity as a palliative agent.
