Wafik Zaky

Intensive induction chemotherapy followed by myeloablative chemotherapy with autologous hematopoietic progenitor cell rescue for young children newly‐diagnosed with central nervous system atypical teratoid/rhabdoid tumors: The head start III experience

Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system (CNS) is a rare embryonal neoplasm of early childhood with dismal outcome and no current uniformly accepted treatment. Given its highly aggressive nature and predilection for dissemination at diagnosis, intensive multimodal therapy is required.

Choroid plexus carcinoma in children: the Head Start experience.

Choroid plexus carcinoma (CPC) is a rare aggressive intracranial neoplasm with a predilection for young children and a historically poor outcome. Currently, no defined optimal therapeutic strategy exists. The Head Start (HS) regimens have included irradiation‐avoiding strategies in young children with malignant brain tumors using high dose chemotherapy to improve survival and minimize neurocognitive sequelae.

Choroid plexus carcinoma in children

Choroid plexus carcinoma (CPC) is a rare aggressive intracranial neoplasm with a predilection for young children and a historically poor outcome. Currently, no defined optimal therapeutic strategy exists. The Head Start (HS) regimens have included irradiation‐avoiding strategies in young children with malignant brain tumors using high dose chemotherapy to improve survival and minimize neurocognitive sequelae.

Treatment of Children with Diffuse Intrinsic Pontine Gliomas with Chemoradiotherapy Followed by a Combination of Temozolomide, Irinotecan, and Bevacizumab

Background: Diffuse intrinsic pontine gliomas (DIPG) are inoperable and highly resistant tumors to chemotherapy and irradiation. DIPG has the worst prognosis among all pediatric brain tumors and the overwhelming majority of patients die within 6–18 months after diagnosis. Methods: We retrospectively reviewed the charts of six DIPG patients treated with chemoradiotherapy (daily carboplatin and oral etoposide in five patients and temozolomide in one patient) followed by maintenance chemotherapy consisting of irinotecan, temozolomide, and bevacizumab at our institution between January 2007 until December 2007. Results: Event-free survival (EFS) and overall survival (OS) were 10.4 ± 3.08 and 14.6 ± 3.55 months, respectively. Side effects in the patients included hypertension in two, abdominal cramping and diarrhea in four, and neutropenia in five patients. Conclusions: This augmented regimen was associated with increased but tolerable toxicity and a modest increase in EFS and OS when compared with published literature in patients with DIPG (median EFS and OS of 6.1 and 9.6 months, respectively). More effective therapies are desperately needed.

Ikaros deletions in BCR–ABL-negative childhood acute lymphoblastic leukemia are associated with a distinct gene expression signature but do not result in intrinsic chemoresistance

Ikaros, the product of IKZF1, is a regulator of lymphoid development and polymorphisms in the gene have been associated with the acute lymphoblastic leukemia (ALL). Additionally, IKZF1 deletions and mutations identify high‐risk biological subsets of childhood ALL [Georgopoulos et al. Cell 1995;83(2):289–299; Mullighan et al. N Engl J Md 2009;360(5):470–480].

Preliminary experience with diffusion tensor imaging before and after re-irradiation treatments in children with progressive diffuse pontine glioma

PurposeThe purpose of this study is to evaluate quantitative changes in diffusion tensor imaging (DTI) tractography and fractional anisotropy (FA) of the pons along with clinical correlation, in patients who receive re-irradiation for progressive diffuse intrinsic pontine glioma (DIPG).MethodsA retrospective case review of children with progressive DIPG who received re-irradiation at our institution from 2007 to 2011 after approval from the Institutional Review Board was performed. Tractography analysis and FA were analyzed pre and post-re-irradiation, and correlation with clinical features and MR imaging was performed.ResultsDTI analysis showed reduced values of FA on tumor progression. Increase in the FA values was noted after re-irradiation in these patients. This correlated with clinical improvement. These changes were concordant with the 3D tractography analysis which showed better visualization of the corticospinal tracts as they course through brainstem and posterior transverse pontine fibers following re-irradiation.ConclusionSerial changes in the FA values using DTI could provide clinically more correlative information in patients with progressive DIPG, who receive re-irradiation. Though the use and results of this modality has been reported in the newly diagnosed DIPG before, evaluation of DTI in children who receive re-irradiation for progressive DIPG has not been reported earlier. Though limited by the small sample size and treatment variability, this study for the first time shows the preliminary experience, potential, and likely efficacy of complementing DTI analysis to routine neuroimaging also in patients re-irradiated for progressive DIPG to better assess treatment response.

Diffuse intrinsic pontine glioma: time for therapeutic optimism.

Diffuse intrinsic pontine glioma (DIPG) is an aggressive tumor that is universally fatal, and to-date we are at a virtual standstill in improving its grim prognosis. Dearth of tissue due to rarity of biopsy has precluded understanding the elusive biology and frustration continues in reproducing faithful animal models for translational research. Furthermore the intricate anatomy of the pons has forestalled locoregional therapy and drug penetration. Over the last few years, biopsy-driven targeted therapy, development of vitro and xenograft animal models for therapeutic testing, profiling immunotherapeutic strategies and locoregional infusion of drugs in brain stem tumors, now provide a sense of hope in the years ahead. This review aims to discuss current status and advances in the management of these tumors.

The biologic era of childhood medulloblastoma and clues to novel therapies

Currently, the treatment of childhood medulloblastoma (MB) is tailored to risk groups defined by clinical parameters. Growing evidence of tumoral heterogeneity is apparent as response remains varied and unpredictable based on current treatment strategies, indicating the lack of understanding of the elusive biology that drives oncogenesis of these tumors. Advances in genomic technologies are revealing newer insights into the molecular pathogenesis of MB. Utilization of the genomic machinery has enabled the definition of new molecular markers and signaling pathways, resulting in a paradigm shift in the classification of childhood MB. Recent focus into the postgenomic era has revealed varied perturbations in the epigenetic machinery in these subtypes as likely predictive biomarkers and potential therapeutic targets. Ahead lies the task and challenge in the ability to comprehensively evaluate all these data, which could provide clues to profile the next-generation clinical trials combining conventional with molecularly targeted novel therapies.

Radiotherapy after high-dose chemotherapy with autologous hematopoietic cell rescue: Quality assessment of Head Start III

The use of high‐dose chemotherapy with autologous hematopoietic cell rescue (AuHCR) in Head Start III is a potentially curative approach for the management of young children with central nervous system neoplasms. We report the potential influence of quality and timing of radiation therapy on the survival of patients treated on the study.

Pediatric choroid plexus carcinoma: Biologically and clinically in need of new perspectives

Choroid plexus (CP) carcinoma is a rare pediatric brain neoplasm. Recent studies have highlighted the potential of genome‐wide methylation and gene expression profiling to provide additional layers of information to improve tumor risk‐stratification. There is a lack of data regarding the best therapy, and approaches have been heterogeneous. Despite multidisciplinary treatment approaches, the outcome remains guarded and treatments have been based on case series and expert opinions. In this study, we discuss the recent wealth of data regarding CP carcinoma molecular biology and current management. We also briefly highlight the remaining barriers to formulate the best treatment strategies, and future therapeutic potentials.