Toward the revaluation of radiosurgery
JNSPG 75th Anniversary Invited Review Article
Stereotactic radiosurgery emerged as a neurosurgical discipline in order to utilize energy for the manipulation of brain or nerve tissue, with the goal of minimal access and safe and effective care of a spectrum of neurosurgical disorders. Perhaps no other branch of neurosurgery has been so disruptive across the entire discipline of brain tumor care, treatment of vascular disorders, and management of functional problems. Radiosurgery is mainstream, supported by thousands of peer-reviewed outcomes reports. This article reviews current practice with a focus on challenges, emerging trends, and areas of investigation.
Douglas S. Kondziolka
Zane Schnurman and Douglas Kondziolka
Understanding how the relevant medical community accepts new therapies is vital to patients, physicians, and society. Increasingly, focus is placed on how medical innovations are evaluated. But recognizing when a treatment has become accepted practice—essentially, acceptance by the scientific community—remains a challenge and a barrierto investigating treatment development. This report aims to demonstrate the theory, method, and limitations of a model for measuring a new metric that the authors term “progressive scholarly acceptance.”
A model was developed to identify when the scientific community has accepted an innovation, by observing when researchers have moved beyond the initial study of efficacy.
This model could enable further investigations into the methods and influences of treatment development.
Zane Schnurman and Douglas Kondziolka
Patients, practitioners, payers, and regulators are advocating for reform in how medical advances are evaluated. Because surgery does not adhere to a standardized developmental pathway, how the medical community accepts a procedure remains unclear. The authors developed a new model, using publication data and patterns, that quantifies this process. Using this technique, the authors identified common archetypes and influences on neurosurgical progress from idea inception to acceptance.
Seven neurosurgical procedures developed in the past 15–25 years were used as developmental case studies (endovascular coil, deep brain stimulation, vagus nerve stimulation, 1,3-bis(2-chloroethyl)-l-nitrosourea wafer, and 3 radiosurgery procedures), and the literature on each topic was evaluated. A new metric the authors termed “progressive scholarly acceptance” (PSA) was used as an end point for community acceptance. PSA was reached when the number of investigations that refine or improve a procedure eclipsed the total number of reports assessing initial efficacy. Report characteristics, including the number of patients studied, study design, and number of authoring groups from the first report to the point of PSA, were assessed.
Publication data implicated factors that had an outsized influence on acceptance. First, procedural accessibility to investigators was found to influence the number of reports, number of patients studied, and number of authoring groups contributing. Barriers to accessibility included target disease rarity, regulatory restrictions, and cost. Second, the ease or difficulty in applying a randomized controlled trial had an impact on study design. Based on these 2 factors, 3 developmental archetypes were characterized to generally describe the development of surgery.
Common surgical development archetypes can be described based on factors that impact investigative methods, data accumulation, and ultimate acceptance by society. The approach and proposed terminologies in this report could inform future procedural development as well as any attempts to regulate surgical innovation.
Douglas Kondziolka and Juan M. Bilbao
✓ Monoclonal and polyclonal antisera were used against 12 cases of neuroepithelial (colloid) cysts to determine the specific antigenic profile of the cyst epithelium. Intermediate filament markers (cytokeratin, vimentin, neurofilament, and glial fibrillary acidic protein) and epithelial markers (epithelial membrane antigen and monoclonal antibody lu-5) demonstrated that colloid cyst epithelium has a unique antigenic profile in contrast to that of choroid plexus or glial tissue. Theories raised to explain the etiology of colloid cysts have included derivation from the embryonic paraphysis, detachments of developing neuroepithelium from the tela choroidea, and remnants of respiratory epithelium; a more recent theory suggests that these cysts are products of developing choroid plexus or ependyma. The present study shows that colloid cyst epithelium is distinct from that of choroid plexus or ependyma and therefore does not represent a product of their formation, nor does it represent a form of immature glia. This finding supports the conclusion that colloid cysts in any ventricular location represent a developmental anomaly of primitive neuroectoderm in the embryo, which remains unique from other products of neuroectodermal derivation.
Douglas Kondziolka and L. Dade Lunsford
✓ Stereotactic aspiration is a valuable surgical alternative for colloid cysts when used alone or in conjunction with microsurgical resection. Since 1981, the authors have performed computerized tomography (CT)-guided stereotactic aspiration as the initial procedure in 22 patients with colloid cysts; stereotactic aspiration alone was successful in 11 patients (50%). Of the 11 patients in whom aspiration failed, stereotactic endoscopic resection was attempted in three and was successful in one. Seven patients required a craniotomy and microsurgical removal of the cyst performed via a transcortical approach.
The preoperative CT appearance in eight cases of a hypodense or isodense cyst correlated favorably with successful aspiration of the cyst in six patients. A hyperdense appearance on the preoperative CT scan in 14 cases was associated with subtotal aspiration in 13 patients; five required craniotomy for removal. Preoperative magnetic resonance (MR) imaging in eight patients provided excellent anatomical definition of the cyst and its relationship to other structures of the third ventricle, but it was not possible to correlate successful aspiration with cyst appearance on MR images with short or long relaxation time sequences. The authors' 9-year experience suggests that preoperative CT studies accurately determine size, predict viscosity, and help to define a group of colloid cyst patients for whom stereotactic cyst aspiration will likely be successful. Unsuccessful stereotactic aspiration was related to two features: the high viscosity of the intracystic colloid material (nine patients), or deviation of the cyst away from the aspiration needle due to small cyst volume (two patients). Because of its simplicity and low risk, stereotactic surgery can be offered to selected patients as the initial procedure of choice. Craniotomy can be reserved for those whose imaging studies predict failure or for those whose cyst cannot be aspirated.
W. Jeffrey Elias
Christopher P. Deibert and Douglas Kondziolka
Intrinsic meningiomas of the superior sagittal sinus pose a significant technical challenge, particularly in the posterior two-thirds of the sinus. Resection is curative but frequently is not possible because of the involvement of critical vascular structures. Here, the authors present the case of a 49-year-old woman with a recurrent meningioma located exclusively in the posterior two-thirds of the sagittal sinus. The patient was treated with a margin dose of 12 Gy and a maximum dose of 24 Gy to the length of the tumor, which measured 16 cm. Five years after treatment, the tumor remains stable and the patient is symptom free. This case demonstrates the unique role that stereotactic radiosurgery can play in the management of meningiomas that are surgically unresectable and have no accepted form of treatment. To the authors' knowledge, 16 cm also represents the longest segment of tumor treated using stereotactic radiosurgery.
Zane Schnurman, Michael L. Smith and Douglas Kondziolka
Off-label therapies are widely used in clinical practice by spinal surgeons. Some patients and practitioners have advocated for increased regulation of their use, and payers have increasingly questioned reimbursment for off-label therapies. In this study, the authors applied a model that quantifies publication data to analyze the developmental process from initial on-label use to off-label innovation, using as an example recombinant human bone morphogenetic protein 2 (rhBMP-2) because of its wide off-label use.
As a case study of off-label innovation, the developmental patterns of rhBMP-2 from FDA-approved use for anterior lumbar interbody fusion to several of its off-label uses, including posterolateral lumbar fusion, anterior cervical discectomy and fusion, and posterior lumbar interbody fusion/transforaminal lumbar interbody fusion, were evaluated using the “progressive scholarly acceptance” (PSA) model. In this model, PSA is used as an end point indicating acceptance of a therapy or procedure by the relevant scientific community and is reached when the total number of peer-reviewed studies devoted to refinement or improvement of a therapy surpasses the total number assessing initial efficacy. Report characteristics, including the number of patients studied and study design, were assessed in addition to the time to and pattern of community acceptance, and results compared with previous developmental study findings. Disclosures and reported conflicts of interest for all articles were reviewed, and these data were also used in the analysis.
Publication data indicated that the acceptance of rhBMP-2 off-label therapies occurred more rapidly and with less evidence than previously studied on-label therapies. Additionally, the community appeared to respond more robustly (by rapidly changing publication patterns) to reports of adverse events than to new questions of efficacy.
The development of off-label therapies, including the influence of investigative methods, regulation, and changing perspectives, can be characterized on the basis of publication patterns. The approach and findings in this report could inform future off-label development of therapies and procedures as well as attempts to regulate off-label use.