Sex, Age, Anatomic Location, and Extent of Resection Influence Outcomes in Children With High-grade Glioma
BACKGROUND: Survival duration and prognostic factors in adult high-grade glioma have been comprehensively analyzed, but less is known about factors contributing to overall survival (OS) and progression-free survival (PFS) in pediatric patients.
OBJECTIVE: To identify these factors in the pediatric population.
METHODS: We retrospectively reviewed institutional databases evaluating all patients ≤21 years with high-grade glioma treated between 1988 and 2010. Kaplan-Meier curves and log-rank statistics were used to compare groups univariately. Multivariate analyses were completed using Cox proportional hazards regression models.
RESULTS: Ninety-seven patients were identified with a median age of 11 years. Median OS was 1.7 years, and median PFS was 272 days. Location was significant for OS (P < .001). Patients with gross total resection (GTR) had a median OS of 3.4 years vs 1.6 years for subtotal resection and 1.3 years for biopsy patients (P < .001). Female patients had improved OS (P = .01). Female patients with GTR had a mean OS of 8.1 years vs 2.4 years for male patients with GTR and 1.4 years for all other female patients and male patients (P = .001). PFS favored patients ≤3 and ≥13 years and females (P = .003 and .001).
CONCLUSION: OS was significantly correlated with the location of the tumor and the extent of resection. GTR significantly improved overall survival for both glioblastoma multiforme and anaplastic astrocytoma patients, and female patients showed a much larger survival benefit from GTR than male patients. Read full text...
McCrea, Heather J. MD, PhD; Bander, Evan D. BA; Venn, Rachael A. ScB; et al. (2015). Sex, Age, Anatomic Location, and Extent of Resection Influence Outcomes in Children With High-grade Glioma. Neurosurgery: September 2015 - Volume 77 - Issue 3 - p 443–453
NCI convened a workshop February 4-5, 2015, of representative research teams that have been leaders in defining the genomic landscape of childhood cancers to discuss the influence of genomic discoveries on the future of childhood cancer research.
Workshop participants also included clinical researchers, members of regulatory agencies, and members of the childhood cancer research advocacy community. The participants are listed at the end of this document.
The workshop focused on the identification of gaps in current understanding and opportunities for future research.
Workshop participants identified the following research gaps and opportunities as areas that warrant future research focus:
- Continued discovery research to more comprehensively characterize the genomic and epigenomic alterations that are present in childhood cancers and their clinically relevant subsets
- Clinical research protocols focused on identifying the genomic landscape of childhood cancers at relapse and on evaluating therapeutic strategies for genomically-defined patient subsets at relapse
- A childhood cancer Genomic Data Commons to facilitate collaboration across research teams and to facilitate the identification and clinical relevance of low-frequency genomic alterations
- Preclinical models that faithfully replicate the relevant genomic alterations of childhood cancers
- Identification of treatments to directly or indirectly target pediatric cancer driver genomic alterations for which there are currently no available targeted agents, including the fusion genes that characterize selected pediatric sarcomas (e.g., Ewing sarcoma, synovial sarcoma, and alveolar rhabdomyosarcoma) and childhood leukemias, the mutated histones found in pediatric high-grade gliomas, and the SMARCB1 alterations found in rhabdoid tumors
- Further definition of germline dominant and recessive lesions that predispose to cancer and the maintenance of this information within accessible databases, and the enhancement of the genetic counseling capabilities of institutions that treat children with cancer
Specific objectives of the workshop included identifying new opportunities created by molecular studies that might allow more effective diagnosis and treatment of childhood cancers.
Clinical translation of genomic discoveries for childhood cancers was also discussed. The text that follows summarizes the key issues addressed at the workshop and focuses on the future research directions highlighted by workshop participants
The summary is provided to inform the childhood cancer community about important areas that warrant further research investment.
National Cancer Institute (www.cancer.gov)
“Personalized brain tumor treatment has been made possible by the capability to identify specific cancer genetic signatures, which allows neuro-oncologists to choose one chemotherapeutic drug over another, a dramatic change in the way we treat primary and metastatic brain tumors,” says fellowship-trained neuro-oncologist Sigmund Hsu, M.D., an assistant professor in the Vivian L. Smith Department of Neurosurgery at UTHealth Medical School.
“Before the discovery of these signatures, we made decisions about treatment based on the location of the tumor in the body and how it looked under the microscope during pathological examination. Advancements made through cancer research have allowed us to move away from the shotgun approach to treatment and moved us a step closer to finding the silver bullet.”
Advancements in Pediatric Brain Tumor Treatment
In the pediatric arena, the promising results of translational studies conducted by David Sandberg, M.D., FAANS, FACS, FAAP, director of pediatric neurosurgery at Children’s Memorial Hermann Hospital in the Texas Medical Center, have demonstrated the safety of infusing chemotherapeutic agents directly into the fourth ventricle of the brain. This radically new approach to chemotherapy allows Dr. Sandberg and team members to circumvent the blood-brain barrier and deliver agents directly to the site of disease, minimizing side effects by decreasing systemic drug exposure. Read more...
Diffuse intrinsic pontine glioma: poised for progress.
Diffuse intrinsic pontine gliomas (DIPGs) are amongst the most challenging tumors to treat. Surgery is not an option, the effects of radiation therapy are temporary, and no chemotherapeutic agent has demonstrated significant efficacy.
Numerous clinical trials of new agents and novel therapeutic approaches have been performed over the course of several decades in efforts to improve the outcome of children with DIPG, yet without success.
The diagnosis of DIPG is based on radiographic findings in the setting of a typical clinical presentation, and tissue is not routinely obtained as the standard of care. The paradigm for treating children with these tumors has been based on that for supratentorial high-grade gliomas in adults as the biology of these lesions were presumed to be similar. However, recent pivotal studies demonstrate that DIPGs appear to be their own entity.
Simply identifying this fact releases a number of constraints and opens opportunities for biologic investigation of these lesions, setting the stage to move forward in identifying DIPG-specific treatments. This review will summarize the current state of knowledge of DIPG, discuss obstacles to therapy, and summarize results of recent biologic studies. Full Text...
Warren, Katherine E. “Diffuse Intrinsic Pontine Glioma: Poised for Progress.” Frontiers in Oncology 2 (2012): 205. PMC. Web. 21 Aug. 2015.