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14 results on '"Eva Galanis"'

1. External validation and recalibration of an incidental meningioma prognostic model – IMPACT: protocol for an international multicentre retrospective cohort study

Author

Julie Woodfield, Boris Krischek, Giles Critchley, Damian Holliman, Angelos Kolias, Thomas Santarius, Ola Rominiyi, Michael McDermott, Michael D Jenkinson, Jörg-Christian Tonn, Mohsen Javadpour, Andrea Saladino, Tiit Illimar Mathiesen, Rory Piper, Michael Vogelbaum, Chaya Brodie, Sara Venturini, Daniel M Fountain, Roland Goldbrunner, Elliot Tilling, Felix Sahm, Priscilla Brastianos, Rory J Piper, Antonio Santoro, Sylvia Kurz, Pierfrancesco Lapolla, Andrea Mingoli, Jennifer Brown, Debraj Mukherjee, Simon Walling, Andrew Morokoff, Patrick Wen, Ghazaleh Tabatabai, Jill Barnholtz-Sloan, Ryan K Mathew, Alexander Smedley, Helen Shih, William Taylor, Minh Nguyen, Bryony Ford, Samantha J Mills, Tamara Ali, Ruwanthi Kolamunnage-Dona, Josephine Jung, Muhammed Elhadi, Erminia Albanese, Aswin Chari, David Rowland, Melissa Gough, Michael Cearns, Simon Lammy, Yasir Chowdhury, Christian Mawrin, Mahmoud Saleh, Jens Schittenhelm, Farshad Nassiri, Raymond Huang, Pietro Familiari, Manfred Westphal, Warren Selman, Daniel Brown, Nathan McSorley, Oliver Hanemann, Richard Pullicino, Francesco Gaillard, Mirjam Renovanz, Chris Barrett, Christine Jungk, Aaron Cohen-Gadol, Javier Martín-Alonso, Gelareh Zadeh, Hytham Hamid, Abdurrahman I Islim, Christopher P Millward, Shaveta Mehta, Usama Ali, Shelli Diane Koszdin, Theo Georgious, Andrew R Brodbelt, Mohamed Abdelsadg, Suhaib Abualsaud, Amro Abuleil, Kevin Agyemang, Hanan Akbari, Likhith Alakandy, Clarissa Alfonso, Arousa Ali, Michael Amoo, Mohamed A. R. Arbab, Mutiu Asha, Kareem Austin, Khaled Badran, Jarnail Bal, Parameswaran Bhattathiri, Paul M. Brennan, Andrew R. Brodbelt, Ferran Brugada-Bellsolà, Placido Bruzzaniti, Annabel Butcher, Rory S. Cairns, Michael Canty, Sachiv Chakravarti, Rebecca Chave-Cox, Anna Craig-McQuade, Peter Crossley, Elizabeth Culpin, Alessia D'Amico, Bassam Dabbous, Pedro David Delgado-López, Mohamed Draz, Katharine J. Drummond, Rusiru T. Ekanayaka, Ibrahim Elmaadawi, Omar Elmandouh, Mazin Elsharif, Daisy Evans, Andreas Fahlström, Fleur L. Fisher, Daniel M. Fountain, Keiko Fox, Chloé Gelder, Shamayitri Ghosh, Aimee Goel, Athanasios Grivas, Andrew Gvozdanovic, Allan Hall, Liv Hartrick, Samih Hassan, Jack Henry, Abdurrahman I. Islim, Asgeir S. Jakola, Michael D. Jenkinson, Sanjeeva Jeyaretna, Adrian Jimenez, Andranik Kahramanian, Neeraj Kalra, David O. Kamson, Oliver Kennion, Adham M. Khalafallah, Sarah Kingdon, Howra Ktayen, Aditaya Kumar, Jun Yi Lau, Jing Xian Lee, Ryan Leyden, Patricia Littlechild, Sophie Liu, Darmanin Lora-Kay, Vivia Lung, Stephen T. Magill, Hani J. Marcus, Fawaz E. Marhoom, Ryan K. Mathew, Calan Mathieson, Tobias Mederer, Torstien R. Meling, Samantha J. Mills, Christopher P. Millward, Mujtaba Mohammad, Amir H. Zamanipoor Najafabadi, Olivia Näslund, Imran Noorani, Gildas Patet, Omar N. Pathmanaban, Andrea Perera, Amit Persad, See Yung Phang, Rory J. Piper, Jonathan Pollock, Benjamin Price, Martin Proescholdt, James Robins, Bobby Sachdev, Fozia Saeed, Ieva Sataite, Antony Kevin Scafa, Verena Schadewaldt, Syed Wajahat Shah, Mustafa El Sheikh, Zenab Sher, Bente Sandvei Skeie, Agbolahan Sofela, Jerome St George, Torbjørn Strømsnes, Nigel Suttner, Philip Theodosopoulos, Manjul Tripathi, Ismail Ughratdar, James Ulrich, Adithya Varma, Anil Varma, Maria Velicu, Esther Wu, Jacob Young, Giuseppa Zancana, Catherine Zhang, Karolyn Au, Felix Behling, Linda Bi, Nicholas Butowski, Ana Castro, Marta Couce, Francesco Dimeco, Katherine J. Drummond, Ian Dunn, Craig Erker, Michelle Felicella, Eva Galanis, Norbert Galldiks, Caterina Giannini, Christel Herold-Mende, Luke Hnenny, Craig Horbinski, Gerhard Jungwirth, Timothy Kaufmann, Daniel Lachance, Christian Lafougere, Katrin Lamszus, Serge Makarenko, Tathiana Malta, Jennifer Moliterno-Gunel, HK Ng, Houtan Noushmehr, Arie Perry, Laila Poisson, Bianco Pollo, Aditya Ragunathan, David Raleigh, Franz Ricklefs, Antonio Santacroce, Christian Schichor, Nils Schimdt, Andrew Sloan, Matija Snuderl, Jim Snyder, Erik Sulman, Suganth Suppiah, Marcos Tatagiba, Marco Timmer, Andreas Von Deimling, Tobias Walbert, Justin Z. Wang, Stephen Yip, Gabriel Zada, Viktor Zherebitskiy, and Michael T.C. Poon

Subjects
Medicine
Published
2022
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2. Oncolytic Measles Virotherapy and Opposition to Measles Vaccination

Author

Minetta C. Liu, Stephen J. Russell, Corey Raffel, Alice Bexon, David Dingli, Miguel Ángel Muñoz-Alía, Dusica Babovic-Vuksanovic, Mark J. Federspiel, Angela Dispenzieri, Sabine Mueller, Paul R. Young, Tobias Peikert, Guy Ungerechts, Tanner C. Miest, Kah Whye Peng, Julian R. Molina, Eva Galanis, Nandakumar Packiriswamy, Roberto Cattaneo, Yumei Zhou, Bradley C. Leibovich, David R. Deyle, Martha Q. Lacy, Frits van Rhee, Scott H. Okuno, and Adele K. Fielding

Subjects
biology, business.industry, Cancer, General Medicine, 030204 cardiovascular system & hematology, medicine.disease, biology.organism_classification, Measles, Oncolytic virus, Vaccination, Measles virus, 03 medical and health sciences, 0302 clinical medicine, Immunity, Environmental health, medicine, 030212 general & internal medicine, Misinformation, Virotherapy, business
Abstract

Recent measles epidemics in US and European cities where vaccination coverage has declined are providing a harsh reminder for the need to maintain protective levels of immunity across the entire population. Vaccine uptake rates have been declining in large part because of public misinformation regarding a possible association between measles vaccination and autism for which there is no scientific basis. The purpose of this article is to address a new misinformed antivaccination argument-that measles immunity is undesirable because measles virus is protective against cancer. Having worked for many years to develop engineered measles viruses as anticancer therapies, we have concluded (1) that measles is not protective against cancer and (2) that its potential utility as a cancer therapy will be enhanced, not diminished, by prior vaccination.

Published
2019
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3. Abstract P6-21-03: Phase I trial of intratumoral (IT) administration of a NIS-expressing derivative manufactured from a genetically engineered strain of measles virus (MV)

Author

Scott H. Okuno, Yingke Zhou, Charles L. Loprinzi, MC Liu, Kathryn J. Ruddy, Prema P. Peethambaram, Nandakumar Packiriswamy, Bethany Brunton, Stephen J. Russell, Mark J. Federspiel, Eva Galanis, Joleen M. Hubbard, K-W Peng, and Jacob B. Allred

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, business.industry, Cancer, Viremia, medicine.disease, Metastatic breast cancer, Virus, Oncolytic virus, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Breast cancer, Tolerability, 030220 oncology & carcinogenesis, Internal medicine, medicine, Viral shedding, business
Abstract

Background: The live attenuated non-pathogenic Edmonston MV vaccine strain has advantages as an oncolytic platform given its tumor specificity, potent bystander effect, and ability to be engineered and retargeted. MV-NIS expresses the human thyroidal sodium-iodide symporter (NIS) and is selectively oncolytic, entering tumor cells through CD46 (overexpressed on many cancers, including breast cancer of all subtypes) and Nectin-4. NIS expression in MV-NIS infected cells permits noninvasive monitoring of virus spread by SPECT-CT imaging of Tc-99m pertechnetate or I-123 uptake. Methods: NCT01846091 is a standard 3+3 phase I trial of a single IT administration of MV-NIS in pts with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) or metastatic breast cancer (MBC). Primary objectives are (a) safety and tolerability and (b) maximally tolerated single dose. The secondary clinical objective is to preliminarily assess antitumor efficacy at and away from the MV injection site. Key eligibility criteria were: absence of standard therapy with life prolonging intent; at least one lesion >1 cm amenable to percutaneous injection; and no impending visceral crisis. MV-NIS was administered on D1 with mandatory SPECT-CT at baseline (BL) and on D3&D8; repeat SPECT-CT on D15&D21 if the prior result was positive; mandatory tumor biopsies on D3&D21; optional tumor biopsies on D8&D15; assessments for viremia and viral shedding at BL and on D3,D8,D15,D21; and standard imaging for restaging at BL,D21,W6,W12. Results: Accrual completed with 12 evaluable pts (6 SCCHN and 6 MBC) at 3 dose levels (108, 3x108, 109 TCID50). The MBC group included 5 HR+/HER2- pts and 1 pt with mixed HR+/HER2- and HR+/HER2+ disease. 5 pts had evidence of disease progression prior to study participation. No dose limiting toxicities were observed among the MBC pts; AEs possibly related to MV-NIS in this group were gr2 fatigue, gr1 flu-like illness, gr2 lymphopenia (all n=1). No SCCHN responses were observed. Best response for the MBC pts was: stable disease (SD) >6 wks, n=4; clinical response, n=1; progression, n=1. One MBC pt with SD for 12 wks had positive SPECT/CT imaging at and away from the injection site on D3&D8 and was the only pt seronegative for measles IgG antibodies prior to MV-NIS exposure. The MBC pt who responded after initial MV-NIS exposure was the only pt with low viral RNA in blood (D3); she received additional doses at W9&W13 without toxicity through an expanded access protocol exemption and had disease progression by W19. No viral shedding was detected from mouth rinse or urine in any pt. MV was detected in tumor samples from all pts treated at the highest dose level. Additional blood and tissue analyses are in progress. Conclusion: These results demonstrate the safety of IT MV-NIS administration, provide early evidence of biologic activity in MBC, and support the possibility of viral replication in tumors remote from the IT injection site. A MV strain encoding the immunomodulatory neutrophil activating protein transgene has been constructed (MV-s-NAP) with preclinical evidence of improved antitumor activity and immunogenicity. The phase I MV-s-NAP trial will start recruitment in Fall 2018. Citation Format: Liu MC, Peng K-W, Federspiel MJ, Russell SJ, Brunton BA, Zhou Y, Packiriswamy N, Hubbard JM, Loprinzi CL, Peethambaram PP, Ruddy KJ, Allred JB, Galanis E, Okuno SH. Phase I trial of intratumoral (IT) administration of a NIS-expressing derivative manufactured from a genetically engineered strain of measles virus (MV) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-21-03.

Published
2019
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4. Effect of Stereotactic Radiosurgery Compared to Whole-brain Radiotherapy for Limited Brain Metastasis on Long Term Cognition and Quality of Life: A Pooled Analysis of NCCTG N107C/CEC.3 and N0574 (Alliance) Randomized Clinical Trials

Author

David Roberge, K.S. Anderson, Karla V. Ballman, Caroline Chung, J.B. Ashman, Fred G. Barker, Anthony L. Asher, Joshua D. Palmer, Stuart H. Burri, N.N. Laack, Jean-Paul Bahary, Ian F. Parney, Jeffrey Greenspoon, Jane H. Cerhan, Anthony Whitton, Paul D. Brown, Volker W. Stieber, Eva Galanis, Bruce E. Pollock, and Brett Klamer

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Radiation, business.industry, medicine.medical_treatment, Whole brain radiotherapy, Cognition, medicine.disease, Radiosurgery, law.invention, Term (time), Pooled analysis, Randomized controlled trial, Quality of life, law, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, business, Brain metastasis
Published
2020
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5. Local Control After Resection And Adjuvant Radiosurgery Compared To Radiosurgery Alone For Brain Metastasis: Exploratory Analysis Of Alliance NCCTG N107C

Author

Elana Farace, Stephanie E. Weiss, Costas G. Hadjipanayis, K.S. Anderson, Eva Galanis, Jeffrey Greenspoon, Ian F. Parney, C.C. Hansen, Paul D. Brown, Xiomara W. Carrero, N.N. Laack, Fred G. Barker, James J. Urbanic, Karla V. Ballman, Caterina Giannini, Deepak Khuntia, J.B. Ashman, Jean-Paul Bahary, Anthony Whitton, Jan C. Buckner, Jane H. Cerhan, and David Roberge

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Radiation, business.industry, medicine.medical_treatment, Exploratory analysis, medicine.disease, Radiosurgery, Resection, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, business, Adjuvant, Brain metastasis
Published
2020
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6. State of the Art: The evolving role of RT in combined modality therapy for GBM

Author

Ranjit S. Bindra, Eva Galanis, and Minesh P. Mehta

Subjects
Cancer Research, medicine.medical_specialty, business.industry, Brain Neoplasms, Combined Modality Therapy, Article, Text mining, Neurology, Oncology, Medicine, Humans, Medical physics, Neurology (clinical), State (computer science), business, Glioblastoma
Published
2017

7. Abstract P2-09-07: Inhibition of aurora-A by MLN8237 decreases SMAD5 expression and increases effectiveness of chemotherapeutic agents in breast cancer cells

Author

Eva Galanis, JN Ingle, Mateusz Opyrchal, Ianko D. Iankov, and A B D'Assoro

Subjects
Cancer Research, Chemotherapy, business.industry, medicine.medical_treatment, Cancer, medicine.disease, chemistry.chemical_compound, Breast cancer, Oncology, chemistry, Paclitaxel, embryonic structures, Alisertib, Cancer cell, Immunology, Cancer research, Medicine, Epithelial–mesenchymal transition, business, Adjuvant
Abstract

BACKGROUND: Breast cancer affects thousands of women each year. Epithelial to Mesenchymal transition (EMT) has been associated with increased metastatic potential of cancer cells as well as resistance to chemotherapy. Predicatively, presence of EMT leads to worse prognosis in patients with breast cancer. We have recently showed that Aurora-A plays a key role in development of EMT and increased ability of breast cancer cells for self renewal. Therefore we hypothesized that inhibition of Aurora-A in breast cancer cells will lead to increased sensitivity to chemotherapy. RESULTS: Increased Aurora-A expression, as assessed by IHC staining, in patients with locally advanced disease was associated with worse prognosis. We show that in ER+ cell line, MCF7, activating MAPK pathway through overexpression of Raf1 leads to increase in Aurora-A activity. These cells have decreased sensitivity to treatment with paclitaxel when compared to untransfected cells in MTT assays. This effect is even more exacerbated with over-expression of Aurora-A. The sensitivity to paclitaxel was restored with inhibition of Aurora-A by specific inhibitor, Alisertib. This was further explored in triple negative (MDA-MB-231) or Her-2/neu expressing (SUM149) cell lines. These cells express higher levels of Aurora-A. Inhibition of Aurora-A activity in combination with paclitaxel was superior when compared to either therapy alone. Similar effect was seen with use of anthracyclines. Inhibition of Aurora-A resulted in decreased SMAD5 expression as well as decreased Akt phosphorylation. Current studies are looking at a role of Aurora-A in activating SMAD5 and its role in resistance to chemotherapy. In vivo experiments evaluating combination therapies in breast cancer animal model are ongoing. CONCLUSIONS: Inhibition of Aurora-A by a specific inhibitor, MLN8237, resulted in decreased SMAD5 expression and increased effectiveness of chemotherapeutic agents in breast cancer cells. These results contribute to better understanding of signaling pathways involved in resistance of breast cancer cells to chemotherapy. This knowledge could be very useful in developing more effective treatments for breast cancer patients in neo-adjuvant, adjuvant and metastatic settings. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-09-07.

Published
2013
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8. BMET-05NCCTG N0574 (ALLIANCE): A PHASE III RANDOMIZED TRIAL OF WHOLE BRAIN RADIATION THERAPY (WBRT) IN ADDITION TO RADIOSURGERY (SRS) IN PATIENTS WITH 1 TO 3 BRAIN METASTASES

Author

Elana Farace, Stuart H. Burri, Eva Galanis, S. Keith Anderson, Anthony L. Asher, Fred G. Barker, Kurt A. Jaeckle, Karla V. Ballman, Xiomara W. Carrero, Caroline Chung, Cynthia Ménard, Paul D. Brown, Jan C. Buckner, Volker W. Stieber, Bruce E. Pollock, Jane H. Cerhan, and Richard L. Deming

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Intracranial tumor, business.industry, medicine.medical_treatment, Radiosurgery, Surgery, law.invention, Randomized controlled trial, law, Internal medicine, parasitic diseases, medicine, Verbal fluency test, Cumulative incidence, In patient, Neurology (clinical), business, Whole brain radiation therapy, Neurocognitive, Abstracts from the 20th Annual Scientific Meeting of the Society for Neuro-Oncology
Abstract

BACKGROUND: WBRT significantly improves tumor control in the brain after SRS, yet the role of adjuvant WBRT remains undefined due to concerns regarding neurocognitive risks. METHODS: Patients with 1-3 brain metastases, each 1 SD from baseline in any of the 6 cognitive tests at 3 months. Time to CP was estimated using cumulative incidence adjusting for survival as a competing risk. RESULTS: 213 patients were enrolled with 2 ineligible and 3 cancels prior to receiving treatment. Baseline characteristics were well-balanced between study arms. The median age was 60 and lung primary the most common (68%). CP at 3 months was more frequent after WBRT + SRS vs. SRS alone (91.7% vs. 63.5% respectively, p = 0.0007). There was more deterioration in the WBRT + SRS arm in immediate recall (30% vs. 8%, p = 0.0043), delayed recall (51% vs. 20%, p = 0.0009), and verbal fluency (19% vs. 2%, p = 0.0098). After WBRT + SRS there was more deterioration in overall QOL (p = 0.001) and functional well-being (p = 0.006) at 3months. Intracranial tumor control at 3 and 6 months were 75.3% and 64.7% with SRS alone vs. 93.7% and 88.4% with SRS + WBRT (p < 0.0001). Median OS was 10.4 for SRS alone vs. 7.4 months for SRS + WBRT respectively (HR = 1.02, p = 0.92). CONCLUSIONS: Decline in QOL and cognitive function, specifically immediate recall, memory and verbal fluency, was more frequent with the addition of WBRT to SRS. Adjuvant WBRT did not improve OS despite better brain control. Initial treatment with SRS and close monitoring is recommended to better preserve cognitive function in patients with newly diagnosed brain metastases that are amenable to SRS.

Published
2015

9. EP-1354: Impact of evaluation timing in determining patterns of failure in glioblastoma

Author

Eva Galanis, J.N. Sarkaria, S. K. Anderson, Tomas Kazda, Debra H. Brinkmann, Maasa Seaberg, Nadia N. Laack, Peter de Nully Brown, and Deanna H. Pafundi

Subjects
Oncology, Patterns of failure, medicine.medical_specialty, business.industry, Radiology Nuclear Medicine and imaging, Internal medicine, Medicine, Radiology, Nuclear Medicine and imaging, Hematology, business, medicine.disease, Glioblastoma
Published
2015
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10. Adult patients with supratentorial pilocytic astrocytoma: Long-term follow-up of ospective multicenter clinical trial NCCTG-867251 (alliance)

Author

Walter J. Curran, Ross A. Abrams, Eva Galanis, Sunjay Shah, Caterina Giannini, Edward G. Shaw, Jan C. Buckner, Brian P. O'Neill, S. Keith Anderson, Paul D. Brown, Xiomara W. Carrero, Brown P.D., Anderson S.K., Carrero X.W., O'Neill B.P., Giannini C., Galanis E., Shah S.A., Abrams R.A., Curran W.J., Buckner J.C., and Shaw E.G.

Subjects
medicine.medical_specialty, Pediatrics, Pilocytic astrocytoma, medicine.diagnostic_test, Radiotherapy, business.industry, medicine.medical_treatment, Medicine (miscellaneous), Articles, medicine.disease, Resection, Surgery, Clinical trial, Radiation therapy, Prospective, Cohort, Biopsy, medicine, Adjuvant therapy, Cyst, business, Cause of death
Abstract

Background Pilocytic astrocytoma is a rare tumor in adults. This report is of a prospective clinical trial with long-term follow-up. Methods Between 1986 and 1994, 20 eligible adults with supratentorial pilocytic astrocytomas were enrolled in a prospective intergroup trial of radiotherapy (RT) after biopsy (3 patients) or observation after gross (11 patients) or subtotal (6 patients) resection. Results At the time of analysis (median follow-up, 20.8 years), 2 patients (10%) have died and 18 patients (90%) are alive. Neurologic and cognitive function were stable or improved over time for the majority of patients. No toxic effects of treatment or malignant transformations have been recorded at last follow-up. For the entire cohort the 20-year time to progression and overall survival rates are 95% and 90% respectively. The cause of death (2.2 and 16.1 years after enrollment) in both patients was unrelated to tumor although both were biopsy-only patients. One subtotally resected tumor progressed 1 month after enrollment requiring P32 injection into an enlarging cyst. Because of further progression this patient required RT 18 months later. This patient is alive without evidence of progression 18 years after RT. Conclusion The long-term follow-up results of this prospective trial confirm that adults with pilocytic astrocytomas have a favorable prognosis with regard to survival and neurologic function. Close observation is recommended for adults with pilocytic astrocytomas, reserving RT for salvage, as the majority remain stable after gross or subtotal resection and no adjuvant therapy.

Published
2015

11. BI-20GENETIC PROFILING FOR EARLY EVEROLIMUS SENSITIVITY IN NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS ENROLLED ON NCCTG N057K

Author

Jann N. Sarkaria, Caterina Giannini, Daniel J. Ma, Eva Galanis, Keith L. Ligon, and Patrick J. Peller

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Pathology, Phosphoinositide 3-kinase, Temozolomide, Everolimus, biology, business.industry, Phases of clinical research, mTORC1, Abstracts, Internal medicine, medicine, biology.protein, PTEN, Neurology (clinical), business, Protein kinase B, PI3K/AKT/mTOR pathway, medicine.drug
Abstract

BACKGROUND: Mammalian target of rapamycin (mTOR) signaling plays a critical role in tumor cell function and mTOR inhibitors have demonstrated promising activity in glioblastoma multiforme (GBM). Nevertheless, robust genetic predictors for sensitivity to mTOR inhibition remain elusive. As part of the biomarker discovery process, the North Central Cancer Treatment Group (NCCTG) incorporated functional imaging with 18FLT-PET/CT and focused exon sequencing into N057K, a Phase II clinical trial evaluating the mTORC1 inhibitor everolimus in combination with radiation(RT) and temozolomide(TMZ) in newly diagnosed GBM patients. METHODS: N057K began weekly everolimus one week prior to standard RT/TMZ. Patients who had >1cm3 of residual tumor were imaged with 18FLT-PET/CT before and after the initial two doses of everolimus, before initiating RT/TMZ. Imaged patients with a ΔSUVmax of >25% were classified as metabolic responders adapted from EORTC criteria for FDG-PET. Imaged patients with sufficient tumor samples also underwent immunohistochemical and focused exon sequencing analysis using the Seqwright 201 gene panel. Tertiary analysis focused on genes implicated in the PI3K/Akt/mTOR pathway (PTEN, PIK3CA, AKT, mTOR, Raptor/Rictor, S6, TSC1/2, NF1, CCND1, FGFR1/2). RESULTS: Nine patients had 18FLT-PET/CT imaging of which 4/9 had a metabolic response to everolimus alone. Six patients had sufficient tumor samples for further analysis, of which 3/6 had response. On IHC, 18FLT-PET responders had higher levels of PTEN expression and lower levels of pAKT and Ki-67 expression in comparison to non-responders. Focused exon sequencing found 1,458 coding alterations in 454 genes when compared to the reference genome. Only one 18FLT-PET responder had any genetic alterations within a PI3K/Akt/mTOR-implicated pathway, while all 18FLT-PET non-responders had multiple alterations within PI3K/Akt/mTOR-implicated pathways. CONCLUSIONS: 18FLT-PET successfully identified cohorts of patients who had robust, early metabolic responses to mTOR inhibition alone. These responders had robust PTEN expression on IHC and were less likely to have alterations within PI3K/Akt/mTOR-implicated pathways.

Published
2014

12. NEURO/MEDICAL ONCOLOGY

Author

Irene Helenowski, Naoya Hashimoto, Jan J. Heimans, Toshiki Yoshimine, Johan A F Koekkoek, Evelyne Emery, José L. Asencio, Andrea Chamczuck, Carly Bridge, Gilbert Faure, Barbara-Ann Millar, Arthur Rosiello, Michela Casanova, John Freymann, Giulio Bertani, Jun-ich Adachi, Christian LaFougere, Julianne Bloom, Paul Vincent Opinaldo, Tobey J. McDonald, Alexander Khandji, Maciej M. Mrugala, Agnieszka Kowalska, Clifford G. Robinson, Josef Pichler, Jayesh Mehta, Lisa M. DeAngelis, Katie Slusarz, Rachel Grossman, Juan Armando Mejía, Sadhana Kannan, In Ah Kim, Pierre Soubeyran, Nabil Ahmed, Matthew J. Matasar, David A. Reardon, Marie-Laure Tanguy, Andrea Pace, Vani Santosh, Tackeun Kim, Adrienne C. Lahti, John E. Donahue, Pavlina Poloskova, Marc H. A. Jansen, Nilanjana Banerji, Margaret Schwartz, Matthias Kirsch, Robert Jeraj, Guus A.M.S. van Dongen, Samuel Singer, Tom J. Snijders, Santosh Kesari, Riccardo Soffetti, Takashi Sasayama, Diana Ly, Kaoru Kurisu, Carsten Friedrich, Shinji Kawabata, Cedric Revil, Michael A. Jacobs, Ryuichi Hirayama, Wan-Soo Yoon, Kathleen Lupica, Christopher Reilly, Takuichiro Hideo, Miguel Gil, Josep Garcia, Ming Zheng, Edward K. Avila, Mairéad G McNamara, Hartmut Uschmann, Jeffrey S. Weinberg, Craig H. Moskowitz, Jörg Hense, Manmeet Ahluwalia, Georg Bjarnason, David Corwin, Shakti Ramkissoon, Jad Alshami, Eric C. Leuthardt, Paul Dilfer, Margaret Patton, Lindsey Heathcock, Cees van Montfort, Rakesh Kumar Gupta, Akihiko Yoshida, Carmine Maria Carapella, Guy K. Mckhann, Marian Hajduch, Meinhard Nevinny-Stickel, Patricia Bruns, Ashish Suri, Hernán Carranza, David A. Gutman, Carlos Yepes, Patrick Y. Wen, T. Cloughesy, Anna Kaltenboeck, Carlos Bartels, Paul D. Brown, Lisa Fichtel, Lorenzo Giammattei, Steven Hamilton, Nobuyuki Takayama, Nan Lin, Jan Drappatz, Roland Eils, Akihiro Tsuboi, Patrick Urban, Minesh P. Mehta, Remy Gressin, Zarnie Lwin, Clarence Eng, Ian F. Dunn, Sin-Soo Jeun, Alva B. Weir, Elisa Trevisan, silviya Meletath, Fumiyuki Yamasaki, Scott N. Hwang, Navya Nambudiri, Timothy F. Cloughesy, Paolo Rampini, Kathryn J. Ruddy, Justin Kirby, Marc C. Huisman, Normand Laperriere, Abajo Guijarro, Alberto González-Aguilar, David M. Peereboom, Antoine F. Carpentier, Steven M. Greenberg, Chikashi Ishioka, Sarah C. Gaffey, Sneha Arya, Guy M. McKhann, Richard Curry, Takashi Watanabe, Keishi Makino, Radek Trojanec, Hideo Takeshima, Joseph F. Megyesi, Jasmina I. Ivanova, Victor Rodriguez Berrocal, Marcel Kool, Eric Burton, Sandra K. Johnston, Hideyuki Arita, Konstantina Karabatsou, Robert C. Rostomily, Sean Grimm, Ralph G. Dacey, Karl Olson, Sonia Gómez, Harry C. Schouten, Christof M. Kramm, Fred H. Hochberg, Darren Hargrave, Kazuhiko Sugiyama, Wilhelm Boogerd, Stefano Tiziani, Christine McCluskey, Albert H. Kim, Tejpal Gupta, Ida Martinelli, Friedrich-Wilhelm Kreth, Lennea Coombs, Keith L. Ligon, J. Manuel Sarmiento, David R. Macdonald, Holly Dickinson, Cristian Massacesi, Basile Wittwer, Jung-Il Lee, Volker Hovestadt, Mark Smolkin, Sampath Somanna, Ingo K. Mellinghoff, Nancy Ann Oberheim Bush, Sanjeev Francis, Roland Goldbrunner, Jai Ho Choi, John Sampson, Roy Allan Dominique Torcuator, Kathleen R. Lamborn, Simon V. Liubinas, Daniel J. Sargent, Christina K. Cramer, Francine Armentano, Heather Leeper, Stefan Rutkowski, Prakash Shetty, Arivazhagan Arimappamagan, Alicia Ortega, Enrique Jiménez, Kazuhiro Tanaka, Kolette D. Fly, Seunggu Han, Nicolas U. Gerber, David Schiff, Antonella Castellano, Isabel Arrillaga-Romany, Robert J. Wechsler-Reya, Sophie Taillibert, Macarena de la Fuente, Wolfgang Wick, Monica Bennett, Francesco Cognetti, John de Groot, Michael Gonzales, Leon D. Ortiz, Yoshiaki Shiokawa, George Sachs, Ivo Tremont, Charles A. Conrad, Michael D. Taylor, Igor J. Barani, Shannon Langmead, Lisa Sturla, Doosik Kong, Rebecca D. Folkerth, Garrett Riggs, Yoon-La Choi, Carole Soussain, Calvin Soh, Peter Canoll, Mariza Daras, Melissa Hoag, James Rigas, Dana Cernea, Liu Diane, Kenji Wakiya, Sandra Silberman, Ivan A. Reveles, Jeffrey S. Wefel, Wenting Wu, Marie Blonski, MA Majaid, Vanessa A. Nestor, Maurits W.C.B. Sanders, Cynthia Harrison, Ruxandra Costa, Andrea Hawkins-Daarud, Mark R. Gilbert, Ruth Katz, Masayuki Kanamori, Tomek Janicki, Aaron C. Spalding, Dong-Sup Chung, Lauren Foresman, Fateme Salehi, Allan H. Friedman, Eric P. Winer, Robert Kwiecien, Joachim Kuehl, Motoo Nagane, Stanislaw Burzynski, Tomokazu Aoki, Gregory N. Fuller, Nina Paleologos, Darell D. Bigner, Max Wintermark, Adam E. Flanders, Eiichi Ishikawa, Subramanian Hariharan, Doreen Pachow, Glen Stevens, Ulrich Schüller, Jennifer Lycette, Jennifer Garst, Jeffery T. Williams, Gordana Vlahovic, Tjeerd J. Postma, Tribhwan Vats, Isabel Arrilaga, Krista Follmer, Henry S. Friedman, Kenneth Schwartz, James Perry, Jonas M. Sheehan, Christian Grommes, Annette M. Molinaro, Seung-Ho Yang, Peter Lichter, Naoki Kagawa, Trish Whitcomb, Monica Loghin, Amanda L. Bergner, Miroslav Vaverka, Jayashree Kalpathy-Cramer, Chitra Sarkar, Thomas Davidson, Nithya Ramnath, Leland Rogers, Roberta Rudà, Steven A. Toms, Martin Gore, Khê Hoang-Xuan, Emmanuel Gyan, Hani Malone, Jun-ichi Adachi, Jennifer Rifenburg, Stefan M. Pfister, Luis Carlos Mayor, Vanja Vaccaro, Hannah E. Goldstein, Karen Fink, Eva Dombi, Timothy Cloughsey, Sabina Eigenbrod, Jiri Ehrmann, Li Li, Pamela R. Jackson, Makoto Ohno, Craig Nolan, Gerald P. Linette, Tatjana Seute, Eric Bouffet, Patricia M. M. B. Soetekouw, David J. Pisapia, Marc Remke, Susan Snodgras, David Tran, Keiichi Kobayashi, Warren P. Mason, Setsu Sakamoto, Chiara Bosa, Gabriele Schackert, Alfred Yung, David Cachia, Toshihiko Kuroiwa, María Ángeles Vaz Salgado, F. Lonnqvist, Francesca Piludu, Alvina Acquaye, Keisuke Ueki, Jung Ho Han, Kathy Newell, Mythili Shastry, Yoon Jae Cho, Marco Riva, Laura M. Fayad, Kristin Diefes, André O. von Bueren, Ina Ly, Beatrix Lutiger, Hiroyoshi Suzuki, Jeanette K. Doorduijn, Eiji Kohmura, Olivier Chinot, Ichiyo Shibahara, Nathalie Jansen, Marta Del Álamo de Pedro, Scott L. Pomeroy, Andreas Zwergal, Terri S. Armstrong, Elmar Kirches, Daniel P. Cahill, Howard A. Fine, Cezary Szczylik, Stéphane Oudard, Gregg C. Shepard, Mark G. Kris, Andrea Milbourne, Dominique Jennings, Marco Locatelli, Dereck Amakye, Takumi Kudo, Simon Bailey, Alessandra Fabi, Taketoshi Maehara, Soumen Khatua, Caroline Houllier, Klaus J. Müller, Jaishri O. Blakeley, Karen Kelly, Jonathon Yun, Thomas Gergel, Diane Liu, Eric T. Wong, Alin Borha, Brian J. Williams, Rakesh Jalali, Birgit Geoerger, Naosuke Nonoguchi, Julie Walker, Jasmin Jo, Manmohan Singh, Mary Noel, Denise Lally-Goss, Tracy T. Batchelor, Andrea Falini, Maximilian Niyazi, Jeffrey Raizer, Martin J. van den Bent, Aleksandra Gruslova, Phioanh L. Nghiemphu, Kristin R. Swanson, Maaike J. Vos, Jethro Hu, Rebeca Alcalce Pampliega, Craig S. Sauter, Leena Ketonen, Michael A. Vogelbaum, Donald Picker, Robert Hawkins, Chris Halpin, Otto S. Hoekstra, Elizabeth Vera-Bolanos, Ahmad Awada, Sawan Kumar, Alexandra Benouaich-Amiel, Joseph Pernicone, Noriyuki Kawabata, Andrew H. Kaye, David Brachman, Kurt A. Jaeckle, Cameron J. Nowell, Maria Carlo, Tom Mikkelsen, Jorg Dietrich, Tomonari Suzuki, Kohei Fukuoka, Philippe Aftimos, Christine Schmid-Tannwald, Vera Wenter, Valeria Conte, Scott Turner, Brian J A Gill, John D. Cullen, Jiayi Huang, Saurabh Dahiya, Vincent Delwail, Lien Bekaert, Priya Kumthekar, Roberta Seidman, Scott R. Plotkin, Priya Deshpande, Christopher Zalewski, Vaibhav Patel, Peter Kurniali, Martha Nowosielski, Zvi Ram, Susan M. Chang, Dannis G. van Vuurden, Stuart A. Grossman, Vaishali Suri, Rajan Jain, Christine Carico, Ying Yuan, Yoji Yamashita, Bojana Milojkovic-Kerklaan, Yannick Kerloeguen, Michael B. Sisti, Rameen Beroukhim, Andrea Artoni, Frances McSherry, John J. Evans, Mark E. Shaffrey, Lauren E. Abrey, Akshal S. Patel, Laura Bernal-Vaca, Rolf-Dieter Kortmann, Robert Grubb, Mimi Lee, Jörg-Christian Tonn, Shinobu Yamada, Andrés Quintero, Kazuhiko Mishima, Ania Marszalek, Stephen Gancher, Amal Melhem-Bertrandt, Takamitsu Fujimaki, Monika Warmuth-Metz, George Avgeropoulos, Rifaquat Rahman, Franck Bourdeaut, Frank Feleppa, Jennifer Clarke, Meredith A. Reid, Maria Werner-Wasik, Andrew D. Norden, Kenneth D. Swanson, Jeffrey N. Bruce, Chae-Yong Kim, Steven S. Rosenfeld, Haiyan Jiang, Oliver Schnell, Toshihiro Kumabe, Michael J. Sullivan, W. Gladdines, Glenn J. Lesser, Chang-Ho Yun, Epari Sridhar, Sophie Lebouvier-Sadot, Andrea Baldwin, Chirag G. Patil, Thomas Smith, Shin-Ichi Miyatake, Renato LaRocca, Kent C. Shih, Russell C. Rockne, Katsu Mizukawa, Antonio Omuro, Ryuta Saito, Mohamed H. Hamza, Eunju Hurh, Silke Soucek, Michel Lacroix, Brian J. Scott, Thomas Kaley, Tetsuya Yamamoto, Gregory J. Zipfel, Andrew Lin, Elena Pentsova, Carlos Emilio Restrepo, Utkarsh Bhagat, Masao Matsutani, Andrew B. Lassman, Stephanie L. Pugh, Yasuji Miyakita, Manabu Kinoshita, Christian Hagel, D. Brandsma, Jorge M. Otero, Marco Timmer, Ke Zhang, S. Altintas, Thierry Lamy, Hirofumi Hirano, Mehar Chand Sharma, Wafik S. El-Deiry, Peter A. Sims, Evanthia Galanis, Yong-Kil Hong, Terence J. O'Brien, Haruo Sugiyama, Dieta Brandsma, Loretta Barron, Joshua J. Jacobs, Roger Henriksson, Albert Lai, David White, Xiao-Tang Kong, John D. Hainsworth, Petronella J Lugtenburg, Paul A. Northcott, Maryline Barrie, Kenneth J. Cohen, Tanuj Saaraswat, Xiaobu Ye, Sandra Ruland, Diana M. Haninger, Surasak Phuphanich, Marc C. Chamberlain, Kenneth Aldape, Ewa Matczak, Phyo Kim, Peter Bartenstein, Lumir Hrabalek, Howard Y. Chang, Donatella Tampieri, Fumi Higuchi, Katherine S. Panageas, Allicia C. Girvan, Majid Khan, Stevie Threatt, Tareq Juratli, Mitchel S. Berger, Linda Dirven, Michele Nikolai, Emmanuelle DiTomaso, Sarah Leary, Jan H.M. Schellens, Chuanlu Jiang, Michael Glantz, Harald Sontheimer, Michael D. Prados, Mauricio Lema, Marie-Christine Guiot, Shesh N. Rai, Minhee Won, Carlos Vargas, Eva Galanis, Kazunori Arita, David I. Sandberg, Gianluca Ardolino, Sylvain Choquet, Ondrej Kalita, Michael Rytting, Lorenzo Bello, Luis Ley Urzaiz, Martin J.B. Taphoorn, Kourosh Jafari-Khouzani, Alfred Rademaker, Juan Martinez San Millan, Isabelle Aerts, Sergio Bracarda, John Norton, Mark D. Anderson, Barbara Zarino, Jun Ichi Kuratsu, Nicholas Butowski, Derek R. Johnson, James E. Herndon, Diana Giannarelli, Debra LaFrankie, Filippo Cogiamanian, Yasuyoshi Chiba, Hideo Nakamura, Agnes Jager, Caroline Chung, Paula Warren, Frans S. S. Leijten, Peter Hau, Yusuke Oji, Yuichi Hirose, Kathryn Gilliland, Sadao Kaneko, W. K. Alfred Yung, Roger Stupp, Amy Chung, Yutaka Hata, Mary Frances McAleer, Hee-Won Jung, Miloslava Zlevorová, Brendan Killory, Raymond Sawaya, Anita Chawla, John Trusheim, H. Ian Robins, Judy Lima, Prakash Ambady, Barbara O'Brien, Sonia Bermúdez, Howard Colman, Matthias Gromeier, Jean-Sébastien Guillamo, Maria C. Pietanza, Antonello Vidiri, Laura Guyman, Kristin Swanson, Paul Rosenblatt, Joshua L. Dowling, Lakshmi Nayak, Ashlee Drawz, Yu Jung Kim, Mikael L. Rinne, Shlomit Yust-Katz, Jessi Stevens, Katharine J. Drummond, Patricia Wing, Sarah Taylor, Joshua E. Allen, Ron Schaafsma, John DeGroot, Shigetoshi Yano, Paula Rauschkolb, Anupam Kumar, Soichiro Shibui, M. E. van Linde, Shirish M. Gadgeel, Yoshitaka Narita, Nicholas G. Avgeropoulos, Luca Bertero, Hongjun Wang, Jason K. Rockhill, Suriya Jeyapalan, Yukihiko Sonoda, Hikaru Sasaki, Shirley L. Markant, Masamitsu Nishihara, Daniel J. Brat, Alexandra Flowers, Monica Sierra del Rio, Morgan Prust, Adam M. Sonabend, Pierre A. Robe, James J. Dignam, Julia C. Chisholm, Gregory J. Riely, Mary Gerard, Sajeel Chowdhary, Natalie Jäger, Giovanna M. D'Abaco, James J. Culhane, Tatsunori Okamura, Erik P. Sulman, L. Adriana Esparza, Ivo W. Tremont-Lukats, Emily Porensky, Yoshihiro Oka, Marcelo De Carvalho, Brigitte C. Widemann, Stacey Kalambakas, Rolf D. Kortmann, Stewart Goldman, Jaap C. Reijneveld, Andrew Brenner, Jacob Mandel, Riccardo Draghi, Yunus Arik, Shinji Yamashita, Torsten Pietsch, Tanweer Zaidi, Dawid Schellingerhout, Marta Penas-Prado, Veronica Villani, Adriana Olar, Vanessa L. Merker, Matthias Holdhoff, Joke W. Baars, Katrina H. Smith, Arnab Chakravarti, Giorgio Carrabba, Gertjan J.L. Kaspers, Susan Boulton, Peter A. Forsyth, David T.W. Jones, Anne Baldock, Meier Hsu, Soham Dasgupta, Jeremy Rudnick, Arun Rai, Jessica Sun, Naoki Shinojima, Christian Mawrin, Eita Uchida, Jaswinder Jutla, Koichi Ichimura, Alona Muzikansky, Jean Philippe Maire, Louis B. Nabors, Yuko Matsushita, Emilie Le Rhun, Annick Desjardins, Magali Lecavalier-Barsoum, Laurie Rice, Bradford A. Moffat, Kelly Hempfling, Andrew A. Kanner, Mark W. Kieran, Stephanie M. Robert, Hervé Ghesquières, Alba A. Brandes, E. Sander Connolly, Jingxia Liu, David T. Dicker, Katherine B. Peters, Gregory S. Burzynski, Charles Sweeley, Deborah T. Blumenthal, Nicolás Useche, Tulika Ranjan, Thierry Muanza, Mercedes Garcia Villanueva, Fernando Hakim, Yana Krutoshinskaya, Shintaro Fukushima, Ryo Nishikawa, Damien C. Weber, Michael R. Chicoine, Motomasa Furuse, André Busson, Joseph R. Simpson, Gabriele Röhn, Susanne Koeppen, Arjun Sahgal, Fabio M. Iwamoto, Leland Graves, Sarah Iglseder, Taro Yanagawa, Michael Lahn, Ramaswamy Govindan, Eduardo Roberts Cervantes, Eric S. Wong, Nadine Kliese, Feng Tai, Katja von Hoff, Vincenzo Anelli, Trevor J. Pugh, Andrés F. Cardona, Gebra Cuyun Carter, Yuko Watanabe, Bogdana Suchorska, Manuela Caroli, José Luis Asencio, Eudocia Q. Lee, John Floyd, Lucas Moreno, Samantha J Mills, Jun-ichiro Kuroda, Susan Chi, David N. Louis, Aanchal Kakkar, Elizabeth R. Gerstner, Annika Schlamann, Robert Cavaliere, John L. Villano, Asha Das, Petr Kavan, Takaaki Yanagisawa, Luc Taillandier, Jonathan Fratkin, Günther Stockhammer, Tomasz Janicki, Sherese Fralin, Wafik Zaky, Lisa Scarpace, Kazunari Yoshida, Magalie Hilton, Andrey Korshunov, Aliasgar Moiyadi, Alexandra Gorelick, Alfredo Carrato Mena, Yuya Nishiyama, Riccardo Soffietti, Marina Donativi, Andrew S. Chi, Lauren Schaff, Andrew P. Morokoff, Sophie E. M. Veldhuijzen van Zanten, Hans-Joachim Reimers, John G. Stewart, Clare Ferrigno, Jackson Hamilton, Do-Hyun Nam, Samantha Hammond, Regina Krel, Mika Watanabe, Anna K. Nowak, Elina Tsyvkin, Michael W. McDermott, Jacoline E C Bromberg, Teiji Tominaga, Laila M. Poisson, Lisa Doherty, Alessia Lodi, Vino Apok, Magdalena Kneblova, Michelle Bell, Carl Jaffe, Sunita Dahr, Maria Koh, Pedro Garciarena, J. Gregory Cairncross, Ana Gómez Rueda, Augustus Perez, Ho Jun Seol, Frank Saran, Camillo Porta, Grace Elzinga, Michael Cloney, and Charles P. Hart

Subjects
Cancer Research, medicine.medical_specialty, business.industry, 010403 inorganic & nuclear chemistry, 01 natural sciences, 0104 chemical sciences, 03 medical and health sciences, Abstracts, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, medicine, Medical physics, Neurology (clinical), business
Published
2013

13. Validation of Updated Response Assessment Criteria for Glioblastoma (GBM) and Implications for Clinical Trial Reporting

Author

Maasa Seaberg, Ryan S. Youland, Eva Galanis, Timothy J. Kaufmann, N.N. Laack, and Debra H. Brinkmann

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Radiation, business.industry, medicine.disease, Clinical trial, Response assessment, Internal medicine, medicine, Radiology, Nuclear Medicine and imaging, business, Glioblastoma
Published
2016
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14. Hepatic arterial infusion of a replication-selective oncolytic adenovirus (dl1520): phase II viral, immunologic, and clinical endpoints

Author

Tony, Reid, Eva, Galanis, James, Abbruzzese, Dan, Sze, Lawrence M, Wein, James, Andrews, Britta, Randlev, Carla, Heise, Margaret, Uprichard, Michael, Hatfield, Larry, Rome, Joseph, Rubin, and David, Kirn

Subjects
Adult, Male, Adenoviruses, Human, Liver Neoplasms, Leucovorin, Genome, Viral, Middle Aged, Antibodies, Viral, Virus Replication, Combined Modality Therapy, Hepatic Artery, Antineoplastic Combined Chemotherapy Protocols, Cytokines, Humans, Infusions, Intra-Arterial, Female, Fluorouracil, Colorectal Neoplasms, Aged
Abstract

Replication-selective oncolytic adenoviruses are being developed for the treatment of cancer, but the safety and feasibility of repeated adenovirus delivery to tumors via the bloodstream was unknown, particularly in light of a patient death after hepatic artery infusion of a replication-defective adenovirus vector. We performed a Phase II trial of an oncolytic replication-selective adenovirus (dl1520, also known as Onyx-015) administered by hepatic artery infusion in patients with gastrointestinal carcinoma metastatic to the liver (n = 27). dl1520 was infused into the hepatic artery (2 x 10(12) particles) on days 1 and 8 as a single agent, and thereafter starting on day 22 in combination with i.v. 5-fluorouracil and leucovorin every 28 days. Repeated viral infusions were feasible, and no deaths occurred on study; reversible grade 3/4 hyperbilirubinemia occurred in 2 patients. Systemic inflammatory cytokine responses varied greatly between patients and even between cycles within a given patient. Proinflammatory cytokines [e.g., tumor necrosis factor, IFN-gamma, and interleukin (IL) 6] typically rose within 3 h and were followed at 18 h by a rise in IL-10. However, in the single patient who suffered a severe but reversible systemic inflammatory response, a unique cytokine profile was detected: marked acute increases of IL-6 (20-fold higher than average for all of the patients) and inhibition of IL-10 production. Delayed secondary peaks of viremia were reproducibly detected 3-6 days after treatment, even in the presence of high level neutralizing antibody titers and antiviral cytokines. Mathematical modeling was used to calculate the number of virus particles produced and shed into the blood with each replication cycle. The combination of virotherapy and chemotherapy had antitumoral activity in some chemotherapy-resistant colorectal tumors. The intra-arterial infusion of oncolytic adenoviruses warrants additional study.

Published
2002

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