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Awake Craniotomy for Glioblastoma

Introduction The goal of modern surgery for glioblastoma is maximal safe resection. Neurosurgeons are keenly aware of the dramatic negative effects that postoperative neurologic deficits have on survival and quality of life. In contrast, achieving a complete or near-complete resection of enhancing tumor has been associated with improved survival in patients with glioblastoma. Tumor resection using the technique of awake craniotomy may allow oncologic surgeons to enhance the…

Principles of Surgical Treatment

Preoperative surgical evaluation The initial evaluation of a patient with suspected glioblastoma includes history and physical examination, anatomic imaging, and symptom management with seizure medications and corticosteroids. Clinical presentation of glioblastoma is highly variable, depending on tumor size, location, and the amount of peritumoral edema. Glioblastomas are rarely discovered incidentally (3.8% of patients). Seizures and neurocognitive changes are the most common presenting symptom, occurring in more…

Recurrent Glioblastoma

Given the aggressive nature of glioblastoma, it is nearly a certainty that all patients will need to be evaluated for potential treatment of recurrent disease. There is currently no definitive standard of care for recurrent glioblastoma. Unlike in other solid tumors that have benefited from genomic or molecular profiling and targeted therapy, it is often the case that the recurrent tumor no longer reflects the index…

Antiangiogenic Therapy for Glioblastoma

Introduction This chapter reviews the history of angiogenesis and how it was recognized as an essential mechanism for tumor establishment and growth. From the initial recognition of tumor vascularity to the purification of vascular endothelial growth factor (VEGF), this chapter begins with a historical overview of the key scientific discoveries. Focusing on the development of the anti-VEGF monoclonal antibody, bevacizumab, it then discusses how it came…

Chemotherapeutics and Their Efficacy

Introduction Glioblastoma (GBM), the most common primary brain malignancy, carries a poor prognosis and has therefore been the subject of numerous studies attempting to improve outcomes. Although a plethora of investigative studies and clinical trials have focused on this patient population, the median overall survival from time of diagnosis has remained largely unchanged over many decades, with a current range of 15 to 17 months and a…

Principles and Tenets of Radiation Treatment in Glioblastoma

Standard-of-care radiation regimens Historical Context of Radiation Therapy and Dose Historically, standard treatment for glioblastoma (GBM) was surgical resection alone. The first randomized trial to show a survival benefit with adjuvant radiation therapy (RT) was the Brain Tumor Study Group trial published in 1978, which showed a median survival of 37.5 weeks for RT alone, 25 weeks for adjuvant carmustine [1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)] chemotherapy alone, and 17 weeks for supportive…

Radiographic Detection and Advanced Imaging of Glioblastoma

Acknowledgments The authors would like to acknowledge our colleagues and teachers in neuroradiology at the University of Pennsylvania for their insights on brain tumor imaging, particularly Drs Ronald Wolf, Linda Bagley, Suyash Mohan, and John Woo. Introduction Neuroimaging plays a critical role at each stage of glioblastoma (GBM) diagnosis and therapy. Imaging provides the first definitive evidence of GBM in most cases, facilitates maximal safe surgical…

Current Standards of Care in Glioblastoma Therapy

Introduction With an incidence of 3 to 5 per 100,000, glioblastoma fulfills the criteria of a rare cancer. Despite this, glioblastoma is the most common and most aggressive primary brain tumor and accounts for 12% to 15% of all intracranial neoplasms and 45% to 50% of all gliomas. Patients of any age may be affected, but it is most commonly observed in individuals over the age…

Multimodality Targeting of Glioma Cells

Acknowledgments This work was supported by National Institutes of Health grants R00HL103792 and R01NS094533 , University of Pennsylvania Neuro-oncology Innovation Award, and McCabe Award (to Y. Fan). Glioma is the most common malignant primary tumor in the central nervous system, accounting for about 80% of total malignant brain tumors. The World Health Organization (WHO) classification divides glioma into 4 grades according to the degree of malignancy:…

Translating Molecular Biomarkers of Gliomas to Clinical Practice

Acknowledgments The authors are grateful to their NYU Langone Medical Center colleagues Matija Snuderl, MD, for contributing illustrated cases of cytogenetics analysis and methylation array; Cyrus Hedvat, MD, PhD, for providing an illustrated case of loss of heterozygosity analysis; and Elad Mashiach for assisting with the preparation of images and diagrams, and the editing of the chapter. Glioma classification and grading have traditionally been based on…

The Molecular Pathogenesis of Glioblastoma

The cellular origin of glioblastoma is complex. Despite decades of research, the understanding of the cellular, molecular, and pathogenetic architecture of this lethal disease is still evolving. Other chapters discuss the epidemiology, risk factors, associated clinical outcomes, and molecular targeting for glioblastoma. There are also chapters that describe the mechanisms of small molecule inhibitors, targets for therapeutics and their molecular basis, immune evasion, and mechanisms of…

Epidemiology of Glioblastoma and Trends in Glioblastoma Survivorship

Incidence of glioblastoma Gliomas are the most common type of malignant brain tumor in adults. Of the gliomas, glioblastoma (astrocytoma grade IV) is the most common, and represents approximately 27% of all primary brain tumors, and 80% of malignant primary brain tumors in the United States. Incidence of glioblastoma in the United States varies significantly by sex, race, ethnicity, and age ( Fig. 2.1 ). From 2006 to 2012,…

The Story of Glioblastoma: History and Modern Correlates

Glioblastoma remains a formidable pathologic entity. Without the tools necessary to make a neurologic diagnosis, early medical and surgical clinicians were likely not only puzzled but also appalled by the downward trajectory of patients affected by this tumor. The development of neurosurgery and neuropathology served as the first necessary steps in understanding glioblastoma. Despite major diagnostic and therapeutic advances, clinicians continue to struggle in providing favorable…

Final Thoughts and Conclusions

The original excitement of participating in large, complex and long surgical cases to treat craniosynostosis during our training years gave way to disappointment, frustration, and dissatisfaction with the long-term clinical results of these surgeries. Even though the patients immediately looked great and had significant improvement at the end of the surgical procedure, for most patients, the improvement began to deteriorate consistently over time. The seemingly rounded…

Complications and Avoidance

Introduction Review of complications associated with the surgical treatment of craniosynostosis varies widely due to reports that extend over many years and epochs, as well as there being a large number of different procedures being reported during these periods. A 2015 publication in the Journal of Neurosurgery by Lin Y, et al., analyzed and compared the complication rates of patients under 12 months of age undergoing treatment…

Postoperative Cranial Orthotic Therapy

Introduction to Cranial Remolding Programs Cranial remolding orthoses (CROs) were first described in the treatment of deformational plagiocephaly in 1979. The underlying principle of “directed growth” is accomplished by designing the internal surface of the orthosis to maintain total contact over the prominent areas and provide void spaces over the flattened areas of the infant’s developing skull. With continued brain and skull growth, asymmetrical and disproportionate…

Multiple Suture Nonsyndromic Craniosynostosis

Introduction As previously discussed in other chapters, single suture nonsyndromic craniosynostosis has the highest prevalence of the craniosynostosis, with sagittal synostosis being the most common followed by metopic, coronal, and lastly, lambdoid stenosis. In the multiple suture synostosis group, bilateral coronal synostosis (typically associated with a craniofacial syndrome) is the most common type. There is yet another subset of multiple suture synostosis that does not appear…

Lambdoid Craniosynostosis

Introduction Perhaps of all single suture nonsyndromic craniosynostosis cases, premature closure of the lambdoid suture is one of the most difficult ones to diagnose. The primary reason is the confusion of the posterior plagiocephaly from lambdoid synostosis with that of positional deformational plagiocephaly. Since 1992, when the American Academy of Pediatrics recommended that infants sleep supine in order to minimize the incidence of SIDS, there has…

Bicoronal Syndromic Craniosynostosis

Introduction Syndromic craniosynostosis accounts for 8% to 24% of all patients with craniosynostosis. , The cause for syndromic synostosis is frequently genetic and often due to one of six frequently mutated genes: FGFR2, FGFR3, TWIST1, EFNB1, TCF12, and ERF. There are five major clinical syndromes associated with craniosynostosis and these frequently mutated genes; Apert, Crouzon, Muenke, Pfeiffer, and Saethre-Chotzen syndrome, although as we learn more about…

Nonsyndromic Bicoronal Craniosynostosis

Introduction Premature closure of both coronal sutures is most commonly seen in association with craniofacial syndromes and is known as syndromic bicoronal craniosynostosis (SBCS). A smaller subgroup of patients affected with this condition who do not have an associated or well-known syndrome are known as nonsyndromic bicoronal craniosynostosis (NSBCS). The classical phenotypic presentation includes brachycephaly, turricephaly, supraorbital recession bilaterally, exorbitism, slight hypertelorism, bulging temporal fossa (…