Tr-14 * a Feasibility and Randomized Phase Ii Study of Vorinostat, Bevacizumab, or Temozolomide During Radiation Followed by Maintenance Chemotherapy in Newly-Diagnosed Pediatric High-Grade Glioma: Children's Oncology Group Study Acns0822

Hoffman, Lindsey M.; Geller, James I.; Leach, James; Boué, Daniel R.; Drissi, Rachid; Chen, Lu; Krailo, Mark; Panandiker, Atmaram Pai; Chow, Lionel M.L.; Haas‐Kogan, Daphne A.; Jogal, Sachin; Nelson, Marvin D.; Jakacki, Reggie; Kieran, Mark W.; Cohen, Kenneth J.; Pollack, Ian; Gajjar, Amar; Fouladi, Maryam

doi:10.1093/neuonc/nov061.159

Cited by 16 publications

(13 citation statements)

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“…Bevacizumab is often used along with temozolomide for maintenance therapy following the accepted adult model for tumor recurrence [14]. However, a recent feasibility and Phase II trial demonstrated that neither bevacizumab nor vorinostat proved superior to temozolomide as a radiosensitizer in pediatric high-grade glioma [15]. Fortunately, in our patient's case, there is evidence to suggest that CNS tumors in the young with combined features of malignant glioma and PNET, although rare and poorly characterized, 10.2217/cns-2016-0018 may ultimately respond better to platinum-based chemotherapy such as cisplatin than to temozolomide [16].…”

Section: Resultsmentioning

confidence: 99%

First report of tumor treating fields use in combination with bevacizumab in a pediatric patient: a case report

et al. 2016

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We report the first case of a pediatric patient with glioblastoma (GBM; WHO grade IV astrocytoma) successfully treated with tumor treating fields (TTF). The patient was diagnosed with GBM when 13 years of age and progressed through surgical resection, radiotherapy and chemotherapy. Discrete tumor growth visualized on MRI with stable neurological examination was monitored for 6 months with subsequent stable disease observed radiographically and clinically for 7 months while adherent to Optune (TTF). TTF thereby played a role in forestalling recurrent GBM growth in this young woman for 7 months without significant adverse effects. We propose that TTF therapy is a potential valuable treatment in this small, but sick, patient population.

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Section: Resultsmentioning

confidence: 99%

First report of tumor treating fields use in combination with bevacizumab in a pediatric patient: a case report

et al. 2016

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“…The follow-up COG trial (ACNS0822), which compared the use of vorinostat or bevacizumab plus RT with the use of temozolomide plus RT followed by bevacizumab and temozolomide after RT, was equally discouraging, showing no survival advantage in the experimental arms compared to the temozolomide arm, although significant differences in outcome were noted as a function of tumor molecular features. 23 More recently, the multinational randomized HERBY trial () evaluated the addition of bevacizumab to RT plus temozolomide for children with newly diagnosed HGG. Unfortunately, no PFS or survival benefit for the addition of bevacizumab was observed.…”

Section: High-grade Glioma and Diffuse Intrinsic Pontine Gliomamentioning

confidence: 99%

Childhood brain tumors: current management, biological insights, and future directions

Pollack¹,

Agnihotri²,

Broniscer³

2019

Journal of Neurosurgery: Pediatrics

219

193

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Brain tumors are the most common solid tumors in children, and, unfortunately, many subtypes continue to have a suboptimal long-term outcome. During the last several years, however, remarkable advances in our understanding of the molecular underpinnings of these tumors have occurred as a result of high-resolution genomic, epigenetic, and transcriptomic profiling, which have provided insights for improved tumor categorization and molecularly directed therapies. While tumors such as medulloblastomas have been historically grouped into standard- and high-risk categories, it is now recognized that these tumors encompass four or more molecular subsets with distinct clinical and molecular characteristics. Likewise, high-grade glioma, which for decades was considered a single high-risk entity, is now known to comprise multiple subsets of tumors that differ in terms of patient age, tumor location, and prognosis. The situation is even more complex for ependymoma, for which at least nine subsets of tumors have been described. Conversely, the majority of pilocytic astrocytomas appear to result from genetic changes that alter a single, therapeutically targetable molecular pathway. Accordingly, the present era is one in which treatment is evolving from the historical standard of radiation and conventional chemotherapy to a more nuanced approach in which these modalities are applied in a risk-adapted framework and molecularly targeted therapies are implemented to augment or, in some cases, replace conventional therapy. Herein, the authors review advances in the categorization and treatment of several of the more common pediatric brain tumors and discuss current and future directions in tumor management that hold significant promise for patients with these challenging tumors.

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“…The study was initially planned as a “pick-the-winner” phase II design to be advanced into phase III testing, but the study was permanently closed in 2014 during phase II, as no arm showed any clear superiority. 74 …”

Section: A Clinical Conundrum and A Way Forwardmentioning

confidence: 99%

Pediatric high-grade glioma: biologically and clinically in need of new thinking

et al. 2016

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High-grade gliomas in children are different from those that arise in adults. Recent collaborative molecular analyses of these rare cancers have revealed previously unappreciated connections among chromatin regulation, developmental signaling, and tumorigenesis. As we begin to unravel the unique developmental origins and distinct biological drivers of this heterogeneous group of tumors, clinical trials need to keep pace. It is important to avoid therapeutic strategies developed purely using data obtained from studies on adult glioblastoma. This approach has resulted in repetitive trials and ineffective treatments being applied to these children, with limited improvement in clinical outcome. The authors of this perspective, comprising biology and clinical expertise in the disease, recently convened to discuss the most effective ways to translate the emerging molecular insights into patient benefit. This article reviews our current understanding of pediatric high-grade glioma and suggests approaches for innovative clinical management.

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Tr-14 * a Feasibility and Randomized Phase Ii Study of Vorinostat, Bevacizumab, or Temozolomide During Radiation Followed by Maintenance Chemotherapy in Newly-Diagnosed Pediatric High-Grade Glioma: Children's Oncology Group Study Acns0822

Cited by 16 publications

References 0 publications

First report of tumor treating fields use in combination with bevacizumab in a pediatric patient: a case report

First report of tumor treating fields use in combination with bevacizumab in a pediatric patient: a case report

Childhood brain tumors: current management, biological insights, and future directions

Pediatric high-grade glioma: biologically and clinically in need of new thinking

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