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https://www.readbyqxmd.com/read/29126306/the-future-of-radiobiology
#1
David G Kirsch, Max Diehn, Aparna H Kesarwala, Amit Maity, Meredith A Morgan, Julie K Schwarz, Robert Bristow, Sandra Demaria, Iris Eke, Robert J Griffin, Daphne Haas-Kogan, Geoff S Higgins, Alec C Kimmelman, Randall J Kimple, Isabelle M Lombaert, Li Ma, Brian Marples, Frank Pajonk, Catherine C Park, Dörthe Schaue, Eric J Bernhard
Innovation and progress in radiation oncology depend on discovery and insights realized through research in radiation biology. Radiobiology research has led to fundamental scientific insights, from the discovery of stem/progenitor cells to the definition of signal transduction pathways activated by ionizing radiation that are now recognized as integral to the DNA damage response (DDR). Radiobiological discoveries are guiding clinical trials that test radiation therapy combined with inhibitors of the DDR kinases DNA-dependent protein kinase (DNA-PK), ataxia telangiectasia mutated (ATM), ataxia telangiectasia related (ATR), and immune or cell cycle checkpoint inhibitors...
November 3, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28958992/identification-of-mek162-as-a-radiosensitizer-for-the-treatment-of-glioblastoma
#2
Ravi S Narayan, Ana Gasol, Paul L G Slangen, Fleur M G Cornelissen, Tonny Lagerweij, Hou Y Y E Veldman, Rogier Dik, Jaap van den Berg, Ben J Slotman, Thomas Wurdinger, Daphne Haas-Kogan, Lukas J A Stalpers, Brigitta G Baumert, Bart Westerman, Jan Theys, Peter Sminia
Glioblastoma (GBM) is a highly aggressive and lethal brain cancer type. PI3K and MAPK inhibitors have been studied pre-clinically in GBM as monotherapy, but not in combination with radiotherapy, which is a key component of the current standard treatment of GBM. In our study, GBM cell lines and patient representative primary cultures were grown as multicellular spheroids. Spheroids were treated with a panel of small molecule drugs including MK2206, RAD001, BEZ235, MLN0128 and MEK162, alone and in combination with irradiation...
September 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28871998/peripheral-blood-biomarkers-associated-with-toxicity-and-treatment-characteristics-after-131-i-metaiodobenzylguanidine-therapy-in-patients-with-neuroblastoma
#3
Kevin Campbell, Erin E Karski, Aleksandra Olow, David A Edmondson, Ayano C Kohlgruber, Matthew Coleman, Daphne A Haas-Kogan, Katherine K Matthay, Steven G DuBois
PURPOSE: Few tools exist to predict clinical outcomes after radiopharmaceutical therapy. Our goal was to identify associations between blood-based biomarkers of radiation effect and clinical outcomes after (131)I-metaiodobenzylguanidine ((131)I-MIBG) therapy in patients with neuroblastoma. METHODS AND MATERIALS: We conducted a prospective, single-center cohort study in children with advanced neuroblastoma treated with (131)I-MIBG as monotherapy or in combination with systemic putative radiation sensitizers...
October 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28860053/blood-brain-barrier-adapted-precision-medicine-therapy-for-pediatric-brain-tumors
#4
Bernard L Marini, Lydia L Benitez, Andrew H Zureick, Ralph Salloum, Angela C Gauthier, Julia Brown, Yi-Mi Wu, Dan R Robinson, Chandan Kumar, Robert Lonigro, Pankaj Vats, Xuhong Cao, Katayoon Kasaian, Bailey Anderson, Brendan Mullan, Benjamin Chandler, Joseph R Linzey, Sandra I Camelo-Piragua, Sriram Venneti, Paul E McKeever, Kathryn A McFadden, Andrew P Lieberman, Noah Brown, Lina Shao, Marcia A S Leonard, Larry Junck, Erin McKean, Cormac O Maher, Hugh J L Garton, Karin M Muraszko, Shawn Hervey-Jumper, Jean M Mulcahy-Levy, Adam Green, Lindsey M Hoffman, Katie Dorris, Nicholas A Vitanza, Joanne Wang, Jonathan Schwartz, Rishi Lulla, Natasha Pillay Smiley, Miriam Bornhorst, Daphne A Haas-Kogan, Patricia L Robertson, Arul M Chinnaiyan, Rajen Mody, Carl Koschmann
Targeted chemotherapeutics provide a promising new treatment option in neuro-oncology. The ability of these compounds to penetrate the blood-brain barrier is crucial for their successful incorporation into patient care. "CNS Targeted Agent Prediction" (CNS-TAP) is a multi-institutional and multidisciplinary translational program established at the University of Michigan for evaluating the central nervous system (CNS) activity of targeted therapies in neuro-oncology. In this report, we present the methodology of CNS-TAP in a series of pediatric and adolescent patients with high-risk brain tumors, for which molecular profiling (academic and commercial) was sought and targeted agents were incorporated...
October 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28759109/probing-the-phosphatidylinositol-3-kinase-mammalian-target-of-rapamycin-pathway-in-gliomas-a-phase-2-study-of-everolimus-for-recurrent-adult-low-grade-gliomas
#5
Michael Wahl, Susan M Chang, Joanna J Phillips, Annette M Molinaro, Joseph F Costello, Tali Mazor, Sanda Alexandrescu, Janine M Lupo, Sarah J Nelson, Mitchel Berger, Michael Prados, Jennie W Taylor, Nicholas Butowski, Jennifer L Clarke, Daphne Haas-Kogan
BACKGROUND: Activation of the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway is common in patients with low-grade gliomas (LGGs), but agents that inhibit this pathway, including mTOR inhibitors, have not been studied in this population. METHODS: Fifty-eight patients with pathologic evidence of recurrence after they had initially been diagnosed with World Health Organization (WHO) grade II gliomas were enrolled into a prospective phase 2 clinical trial and received daily everolimus (RAD001) for 1 year or until progression...
July 31, 2017: Cancer
https://www.readbyqxmd.com/read/28733870/rethinking-childhood-ependymoma-a-retrospective-multi-center-analysis-reveals-poor-long-term-overall-survival
#6
Amanda E Marinoff, Clement Ma, Dongjing Guo, Matija Snuderl, Karen D Wright, Peter E Manley, Hasan Al-Sayegh, Claire E Sinai, Nicole J Ullrich, Karen Marcus, Daphne Haas-Kogan, Liliana Goumnerova, Wendy B London, Mark W Kieran, Susan N Chi, Jason Fangusaro, Pratiti Bandopadhayay
Ependymoma is the third most common brain tumor in children, but there is a paucity of large studies with more than 10 years of follow-up examining the long-term survival and recurrence patterns of this disease. We conducted a retrospective chart review of 103 pediatric patients with WHO Grades II/III intracranial ependymoma, who were treated at Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Chicago's Ann & Robert H. Lurie Children's Hospital between 1985 and 2008, and an additional 360 ependymoma patients identified from the Surveillance Epidemiology and End Results (SEER) database...
October 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28723274/identifying-voxels-at-risk-for-progression-in-glioblastoma-based-on-dosimetry-physiologic-and-metabolic-mri
#7
Mekhail Anwar, Annette M Molinaro, Olivier Morin, Susan M Chang, Daphne A Haas-Kogan, Sarah J Nelson, Janine M Lupo
Despite the longstanding role of radiation in cancer treatment and the presence of advanced, high-resolution imaging techniques, delineation of voxels at-risk for progression remains purely a geometric expansion of anatomic images, missing subclinical disease at risk for recurrence while treating potentially uninvolved tissue and increasing toxicity. This remains despite the modern ability to precisely shape radiation fields. A striking example of this is the treatment of glioblastoma, a highly infiltrative tumor that may benefit from accurate identification of subclinical disease...
September 2017: Radiation Research
https://www.readbyqxmd.com/read/28594597/a-cautionary-tale-risks-of-radiation-therapy-de-escalation-in-pediatric-malignancies
#8
Daphne A Haas-Kogan, Christopher A Devine, Kevin X Liu, Stephanie A Terezakis
No abstract text is available yet for this article.
August 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28444227/incidence-and-prognosis-of-patients-with-brain-metastases-at-diagnosis-of-systemic-malignancy-a-population-based-study
#9
Daniel N Cagney, Allison M Martin, Paul J Catalano, Amanda J Redig, Nancy U Lin, Eudocia Q Lee, Patrick Y Wen, Ian F Dunn, Wenya Linda Bi, Stephanie E Weiss, Daphne A Haas-Kogan, Brian M Alexander, Ayal A Aizer
Background: Brain metastases are associated with significant morbidity and mortality. Population-level data describing the incidence and prognosis of patients with brain metastases are lacking. The aim of this study was to characterize the incidence and prognosis of patients with brain metastases at diagnosis of systemic malignancy using recently released data from the Surveillance, Epidemiology, and End Results (SEER) program. Methods: We identified 1302166 patients with diagnoses of nonhematologic malignancies originating outside of the CNS between 2010 and 2013 and described the incidence proportion and survival of patients with brain metastases...
October 19, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28422554/reply-to-j-stenman-et-al
#10
Michael P La Quaglia, Daphne Haas-Kogan, Julie Park, Susan G Kreissman, Daniel von Allmen, Andrew Davidoff, Wendy B London, Geetika Khanna
No abstract text is available yet for this article.
June 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28357536/pediatric-high-grade-glioma-current-molecular-landscape-and-therapeutic-approaches
#11
REVIEW
Steve Braunstein, David Raleigh, Ranjit Bindra, Sabine Mueller, Daphne Haas-Kogan
High-grade pediatric central nervous system glial tumors are comprised primarily of anaplastic astrocytomas (AA, WHO grade III) and glioblastomas (GBM, WHO grade IV). High-grade gliomas are most commonly diagnosed in the primary setting in children, but as in adults, they can also arise as a result of transformation of a low-grade malignancy, though with limited frequency in the pediatric population. The molecular genetics of high-grade gliomas in the pediatric population are distinct from their adult counterparts...
March 29, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28301662/brain-metastases-in-newly-diagnosed-breast-cancer-a-population-based-study
#12
Allison M Martin, Daniel N Cagney, Paul J Catalano, Laura E Warren, Jennifer R Bellon, Rinaa S Punglia, Elizabeth B Claus, Eudocia Q Lee, Patrick Y Wen, Daphne A Haas-Kogan, Brian M Alexander, Nancy U Lin, Ayal A Aizer
Importance: Population-based estimates of the incidence and prognosis of brain metastases at diagnosis of breast cancer are lacking. Objective: To characterize the incidence proportions and median survivals of patients with breast cancer and brain metastases at the time of cancer diagnosis. Design, Setting, and Participants: Patients with breast cancer and brain metastases at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute...
August 1, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28292440/a-kinase-inhibitor-targeted-to-mtorc1-drives-regression-in-glioblastoma
#13
QiWen Fan, Ozlem Aksoy, Robyn A Wong, Shirin Ilkhanizadeh, Chris J Novotny, William C Gustafson, Albert Yi-Que Truong, Geraldine Cayanan, Erin F Simonds, Daphne Haas-Kogan, Joanna J Phillips, Theodore Nicolaides, Masanori Okaniwa, Kevan M Shokat, William A Weiss
Although signaling from phosphatidylinositol 3-kinase (PI3K) and AKT to mechanistic target of rapamycin (mTOR) is prominently dysregulated in high-grade glial brain tumors, blockade of PI3K or AKT minimally affects downstream mTOR activity in glioma. Allosteric mTOR inhibitors, such as rapamycin, incompletely block mTORC1 compared with mTOR kinase inhibitors (TORKi). Here, we compared RapaLink-1, a TORKi linked to rapamycin, with earlier-generation mTOR inhibitors. Compared with rapamycin and Rapalink-1, TORKi showed poor durability...
March 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28156446/acute-pain-management-in-radiation-oncology-quality-of-care-and-the-impact-of-an-integrated-palliative-oncology-service
#14
Tracy A Balboni, Steve E Braunstein, Shannon E Fogh, Wendy Anderson, Steve Pantilat, Allison Taylor, Alexander Spektor, Monica Shalini Krishnan, Daphne A Haas-Kogan, Lauren Michelle Hertan
195 Background: Radiotherapy (RT) effectively palliates bone metastases, but relief may take weeks, frequently necessitating acute pain management (APM). NCCN Guidelines for Adult Cancer Pain (V2.2015) recommend initiation/titration of analgesics for patients with pain scale value (PSV) ≥ 4. We sought to evaluate how often symptomatic patients have analgesic regimens assessed and intervened upon at radiation oncology (RO) consult for bone metastases, and the impact of a dedicated palliative RO service on APM...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28068235/patterns-of-relapse-in-high-risk-neuroblastoma-patients-treated-with-and-without-total-body-irradiation
#15
MULTICENTER STUDY
Richard Li, Alexei Polishchuk, Steven DuBois, Randall Hawkins, Stephanie W Lee, Rochelle Bagatell, Suzanne Shusterman, Christine Hill-Kayser, Hasan Al-Sayegh, Lisa Diller, Daphne A Haas-Kogan, Katherine K Matthay, Wendy B London, Karen J Marcus
PURPOSE: External beam radiation therapy to initial sites of disease may influence relapse patterns in high-risk neuroblastoma. However, the effect of systemic irradiation by use of total body irradiation (TBI) on anatomic patterns of relapse has not previously been investigated. METHODS AND MATERIALS: We retrospectively analyzed patients receiving definitive treatment of high-risk neuroblastoma with subsequent relapse in bony metastatic sites, with a date of relapse between January 1, 1997, and December 31, 2012...
February 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27870572/impact-of-extent-of-resection-on-local-control-and-survival-in-patients-from-the-cog-a3973-study-with-high-risk-neuroblastoma
#16
Daniel von Allmen, Andrew M Davidoff, Wendy B London, Collin Van Ryn, Daphne A Haas-Kogan, Susan G Kreissman, Geetika Khanna, Nancy Rosen, Julie R Park, Michael P La Quaglia
Purpose This analysis of patients in the Children's Oncology Group A3973 study evaluated the impact of extent of primary tumor resection on local progression and survival and assessed concordance between clinical and central imaging review-based assessments of resection extent. Patients and Methods The analytic cohort (n = 220) included patients who had both central surgery review and resection of the primary tumor site. For this analysis, resection categories of < 90% and ≥ 90% were used, with data on resection extent derived from operating surgeons' assessments (all patients), as well as blinded central imaging review of computed tomography scans for a subset of 84 patients; assessment results were compared for concordance...
January 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27778212/survival-after-chemotherapy-and-stem-cell-transplant-followed-by-delayed-craniospinal-irradiation-is-comparable-to-upfront-craniospinal-irradiation-in-pediatric-embryonal-brain-tumor-patients
#17
David R Raleigh, Bryan Tomlin, Benedict Del Buono, Erika Roddy, Katherine Sear, Lennox Byer, Erin Felton, Anu Banerjee, Joseph Torkildson, David Samuel, Biljana Horn, Steve E Braunstein, Daphne A Haas-Kogan, Sabine Mueller
Pediatric embryonal brain tumor patients treated with craniospinal irradiation (CSI) are at risk for adverse effects, with greater severity in younger patients. Here we compare outcomes of CSI vs. high-dose chemotherapy (HD), stem cell transplant (SCT) and delayed CSI in newly diagnosed patients. Two hundred one consecutive patients treated for medulloblastoma (72 %), supratentorial primitive neuroectodermal tumor (sPNET; 18 %) or pineoblastoma (10 %) at two institutions between 1988 and 2014 were retrospectively identified...
January 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27683733/pediatric-low-grade-gliomas-implications-of-the-biologic-era
#18
Roger J Packer, Stephan Pfister, Eric Bouffet, Robert Avery, Pratiti Bandopadhayay, Miriam Bornhorst, Daniel C Bowers, David Ellison, Jason Fangusaro, Nicholas Foreman, Maryam Fouladi, Amar Gajjar, Daphne Haas-Kogan, Cynthia Hawkins, Cheng-Ying Ho, Eugene Hwang, Nada Jabado, Lindsay B Kilburn, Alvaro Lassaletta, Keith L Ligon, Maura Massimino, Schouten-van Meeteren, Sabine Mueller, Theo Nicolaides, Giorgio Perilongo, Uri Tabori, Gilbert Vezina, Katherine Warren, Olaf Witt, Yuan Zhu, David T Jones, Mark Kieran
For the past decade, it has been recognized that pediatric low-grade gliomas (LGGs) and glial-neuronal tumors carry distinct molecular alterations with resultant aberrant intracellular signaling in the Ras-mitogen-activated protein kinase pathway. The conclusions and recommendations of a consensus conference of how best to integrate the growing body of molecular genetic information into tumor classifications and, more importantly, for future treatment of pediatric LGGs are summarized here. There is uniform agreement that molecular characterization must be incorporated into classification and is increasingly critical for appropriate management...
June 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/27676047/omission-of-radiation-therapy-for-low-grade-gliomas-molecular-and-radiographic-correlates-of-treatment-response-and-disease-progression-on-a-phase-2-clinical-trial-of-adjuvant-temozolomide
#19
M Wahl, J Phillips, A Molinaro, Y Lin, A Perry, D A Haas-Kogan, J Costello, M Dayal, N Butowski, J Clarke, M Prados, M S Berger, S Nelson, S M Chang
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/27675857/high-dose-chemotherapy-with-stem-cell-transplant-to-delay-craniospinal-irradiation-in-pediatric-embryonal-brain-tumor-patients
#20
D Raleigh, B Tomlin, B Del Buono, E Roddy, K Sear, L Byer, E Felton, A Banerjee, J Torkildson, D Samuel, B Horn, S E Braunstein, D A Haas-Kogan, S Mueller
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
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