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Radiosurgery for Cerebral Arteriovenous Malformations in A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA)-Eligible Patients: A Multicenter Study

Ding, Dale; Starke, Robert M; Kano, Hideyuki; Mathieu, David; Huang, Paul; Kondziolka, Douglas; Feliciano, Caleb; Rodriguez-Mercado, Rafael; Almodovar, Luis; Grills, Inga S; Silva, Danilo; Abbassy, Mahmoud; Missios, Symeon; Barnett, Gene H; Lunsford, L Dade; Sheehan, Jason P
BACKGROUND AND PURPOSE: The benefit of intervention for patients with unruptured cerebral arteriovenous malformations (AVMs) was challenged by results demonstrating superior clinical outcomes with conservative management from A Randomized Trial of Unruptured Brain AVMs (ARUBA). The aim of this multicenter, retrospective cohort study is to analyze the outcomes of stereotactic radiosurgery for ARUBA-eligible patients. METHODS: We combined AVM radiosurgery outcome data from 7 institutions participating in the International Gamma Knife Research Foundation. Patients with >/=12 months of follow-up were screened for ARUBA eligibility criteria. Favorable outcome was defined as AVM obliteration, no postradiosurgery hemorrhage, and no permanently symptomatic radiation-induced changes. Adverse neurological outcome was defined as any new or worsening neurological symptoms or death. RESULTS: The ARUBA-eligible cohort comprised 509 patients (mean age, 40 years). The Spetzler-Martin grade was I to II in 46% and III to IV in 54%. The mean radiosurgical margin dose was 22 Gy and follow-up was 86 months. AVM obliteration was achieved in 75%. The postradiosurgery hemorrhage rate during the latency period was 0.9% per year. Symptomatic and permanent radiation-induced changes occurred in 11% and 3%, respectively. The rates of favorable outcome, adverse neurological outcome, permanent neurological morbidity, and mortality were 70%, 13%, 5%, and 4%, respectively. CONCLUSIONS: Radiosurgery may provide durable clinical benefit in some ARUBA-eligible patients. On the basis of the natural history of untreated, unruptured AVMs in the medical arm of ARUBA, we estimate that a follow-up duration of 15 to 20 years is necessary to realize a potential benefit of radiosurgical intervention for conservative management in unruptured patients with AVM.
PMID: 26658441
ISSN: 1524-4628
CID: 1877732

A matched cohort comparison of facial nerve outcomes in salvage surgery after stereotactic radiosurgery for progressive vestibular schwannomas compared with microsurgery alone [Meeting Abstract]

Hill, T C; Shinseki, M; Rokosh, R; Choudhry, O; Roland, Jr J T; Kondziolka, D; Golfinos, J G; Sen, C; Pacione, D
Background: Salvage surgery for progressive symptoms or recurrent growth of vestibular schwannoma (VS) after stereotactic radiosurgery (SRS) is uncommon. It has been reported to be more difficult, the same or easier than expected compared with microsurgical resection (MS) of treatment-naive VS, with variable facial nerve outcomes. We conducted a matched cohort analysis to evaluate facial nerve outcomes for patients undergoing MS for progressive symptoms or recurrent growth of VS after SRS compared with MS for treatment-naive VS. Methods: We evaluated the records of 365 non-NF2 VS patients treated with MS from 2001 to 2014. All patients who had postoperative notes were considered to have "adequate follow-up" and included in the study. Nine patients underwent resection for VS after prior SRS (MS-POST SRS) with no prior intervention, 7 of which had adequate follow-up, and 331 patients that underwent MS for treatment naive VS (MS-NO SRS), 317 of which had adequate follow-up. From this dataset, we created propensity score matched cohorts to retrospectively compare facial nerve preservation and clinical outcomes. The propensity score model incorporated age at surgery, tumor size, and pre-operative HB grade, and cases were matched at a ratio of 4:1 MS-NO SRS to MS-POST SRS cases. Results: The MS-POST SRS (n = 7) and MS-NO SRS (n = 28) groups differed only in preoperative hearing status (p < 0.01). Preoperative HB grades were similar between MS-POST SRS and MS-NO SRS groups (p>0.3). The average time-to-intervention after SRS in the MS-POST SRS group was 44.4 months. The indication for MS after SRS was symptom progression with tumor growth in 4 cases, and only tumor growth in the remaining 3. Postoperatively, 3 cases in the MS-POST SRS group demonstrated improvement in HB grade and none became worse whereas 3 of 28 cases in the MS-NO SRS group demonstrated improvement and 12 cases had decrement in HB grade relative to baseline (p < 0.05). There was no significant difference in the extent of resection with both cohorts (MS-POST SRS and MS-NO SRS) attaining gross total resection in 85.7% of cases. Subsequent intervention was not required for any case in the MS-POST SRS group and 2 cases in the MS-NO SRS group, although this difference was not significant. Both cases requiring subsequent intervention in the MS-POST SRS group were gross total resections via the translabyrinthine approach, with subsequent intervention required at 62 and 48 months. There were no significant differences in the complication rate for individual complications or the overall complication rate between cohorts. Conclusions: At a center with high clinical volume, microsurgical resection of VS after prior SRS was associated with good postoperative facial nerve preservation and low morbidity, comparable to those observed in resection of treatment-naive VS. In addition there were similar outcomes in terms of extent of resection between the two groups. The good outcomes reported here may reflect a confluence of factors which include patient selection, the experience of the attending surgeons, the use of more contemporary SRS dosing protocols during initial treatment for these patients, and divergent goals of therapy between cohorts
EMBASE:72235252
ISSN: 2193-634x
CID: 2093722

Quantitative tumor volumetric responses after Gamma Knife radiosurgery for meningiomas

Harrison, Gillian; Kano, Hideyuki; Lunsford, L Dade; Flickinger, John C; Kondziolka, Douglas
OBJECT The reported tumor control rates for meningiomas after stereotactic radiosurgery (SRS) are high; however, early imaging assessment of tumor volumes may not accurately predict the eventual tumor response. The objective in this study was to quantitatively evaluate the volumetric responses of meningiomas after SRS and to determine whether early volume responses are predictive of longer-term tumor control. METHODS The authors performed a retrospective review of 252 patients (median age 56 years, range 14-87 years) who underwent Gamma Knife radiosurgery between 2002 and 2010. All patients had evaluable pre- and postoperative T1-weighted contrast-enhanced MRIs. The median baseline tumor volume was 3.5 cm3 (range 0.2-33.8 cm3) and the median follow-up was 19.5 months (range 0.1-104.6 months). Follow-up tumor volumes were compared with baseline volumes. Tumor volume percent change and the tumor volume rate of change were compared at 3-month intervals. Eventual tumor responses were classified as progressed for > 15% volume change, regressed for
PMID: 26162039
ISSN: 1933-0693
CID: 1668562

Evaluating innovation. Part 1: The concept of progressive scholarly acceptance

Schnurman, Zane; Kondziolka, Douglas
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.
PMID: 26252458
ISSN: 1933-0693
CID: 1709302

Evaluating innovation. Part 2: Development in neurosurgery

Schnurman, Zane; Kondziolka, Douglas
OBJECT 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.
PMID: 26252459
ISSN: 1933-0693
CID: 1709312

"Cure" of Intracranial Metastases of less than 100 mm(3) Treated by Stereotactic Radiosurgery [Meeting Abstract]

Wolf, Amparo Myrelle; Kvint, Svetlana; Silverman, Joshua; Kondziolka, Douglas
ISI:000372669100235
ISSN: 0022-3085
CID: 5526232

Quality of the Patient Experience during Radiosurgery: Measurement toward Improvement

Kondziolka, Douglas; LoPresti, Melissa; Tyburczy, Amy; Golden, Cassandra; Seto, Timmy; Boulio, Lynda; Doody, Caitlyn; Yeh, Brian; Silverman, Joshua
BACKGROUND: All physicians seek to improve the patient experience. In an awake surgical procedure, the patient has a unique opportunity to comment on all aspects of care. The provision of a positive experience is part of quality health care. Our purpose was to define this experience to determine areas for improvement. METHODS: We evaluated 125 patients who underwent stereotactic radiosurgery using a frame-based, gamma knife technique. Patients were surveyed by a nurse practitioner across all elements of their procedural experience prior to same-day discharge. RESULTS: The radiosurgery was completed in all patients with same-day discharge. In an initial 100-patient cohort, 89 patients said they had received adequate oral and/or intravenous sedation before the procedure. All 100 patients said that they felt comfortable before stereotactic frame application, and all patients later remembered frame application. These patients described frame application as very or adequately comfortable (n = 73), minimally uncomfortable (n = 18), or very uncomfortable (n = 9). Neuroimaging was described as very or adequately comfortable (n = 93), minimally uncomfortable (n = 3), or very uncomfortable (n = 4). Radiosurgery in the gamma knife unit was found to be very or adequately comfortable (n = 99) or very uncomfortable (n = 1). We evaluated how 8 separate factors may have contributed to survey responses related to procedural comfort. These factors included intravenous line placement, delivery of sedation medications, application of the head frame, having the MRI, having radiosurgery on the gamma knife bed, removal of the stereotactic frame, communication with caregivers, and knowing what to expect beforehand. We asked the patients to rate their nursing care during the radiosurgery experience, and 'excellent' was chosen by all initial 100 patients. Other elements of the procedure were also studied as well as suggestions for improvement. As a secondary objective, we then modified our protocol to include sodium bicarbonate added to the local anesthetic for frame application and evaluated an additional cohort of 25 patients. CONCLUSIONS: Utilizing a system of physician and nursing education, together with pharmacological sedation and efficient procedural steps, patients said that intravenous line placement (91%), stereotactic frame application (74%), MRI (93%), receiving radiosurgery in the unit (99%), frame removal (84%), communication with caregivers (100%), and knowing what to expect beforehand (97%) were either very or adequately comfortable. Specific evaluations of care processes can lead to care improvement.
PMID: 27172769
ISSN: 1423-0372
CID: 2107802

Outcomes of chronic subdural hematoma drainage in nonagenarians and centenarians: a multicenter study Response [Editorial]

Mansouri, Alireza; Kondziolka, Douglas
ISI:000368866300040
ISSN: 1933-0693
CID: 1942072

The Value of the History and Physical for Patients with Newly Diagnosed Brain Metastases Considering Radiosurgery

Paydar, Ima; Oermann, Eric Karl; Knoll, Miriam; Lee, James; Collins, Brian Timothy; Ewend, Matthew; Kondziolka, Douglas; Collins, Sean P
BACKGROUND: For patients with brain metastases, systemic disease burden has historically been accepted as a major determinant of overall survival (OS). However, less research has focused on specific history and physical findings made by clinicians and how such findings pertain to patient outcomes at a given time point. The aim of this study is to determine how the initial clinical assessment of patients with brain metastases, as part of the history and physical at the time of consultation, correlates to patient prognosis. METHODS: We evaluated a prospective, multi-institutional database of 1523 brain metastases in 507 patients who were treated with radiosurgery (Gamma Knife or CyberKnife) from 2001 to 2014. Relevant history of present illness (HPI) and past medical history (PMH) variables included comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status, and seizure history. Physical exam findings included a sensory exam, motor exam, and cognitive function. Univariate and multivariate Cox regression analyses were used to identify predictors of OS. RESULTS: Two hundred ninety-four patients were included in the final analysis with a median OS of 10.8 months (95% CI, 7.8-13.7 months). On univariate analysis, significant HPI predictors of OS included age, primary diagnosis, performance status, extracranial metastases, systemic disease status, and history of surgery. Significant predictors of OS from the PMH included cardiac, vascular, and infectious comorbidities. On a physical exam, findings consistent with cognitive deficits were predictive of worse OS. However, motor deficits or changes in vision were not predictive of worse OS. In the multivariate Cox regression analysis, predictors of worse OS were primary diagnosis (p = 0.002), ECOG performance status (OR 1.73, p < 0.001), and presence of extracranial metastases (OR 1.22, p = 0.009). CONCLUSION: Neurological deficits and systemic comorbidities noted at presentation are not associated with worse overall prognosis for patients with brain metastases undergoing radiosurgery. When encountering new patients with brain metastases, the most informative patient-related characteristics that determine prognosis remain performance status, primary diagnosis, and extent of extracranial disease.
PMCID:4773584
PMID: 26973811
ISSN: 2234-943x
CID: 2031322

Dose-Response Relationships for Meningioma Radiosurgery

Sethi, Rajni A; Rush, Stephen C; Liu, Shian; Sethi, Suresh A; Parker, Erik; Donahue, Bernadine; Narayana, Ashwatha; Silverman, Joshua; Kondziolka, Douglas; Golfinos, John G
OBJECTIVE: Dose-response relationships for meningioma radiosurgery are poorly characterized. We evaluated determinants of local recurrence for meningiomas treated with Gamma Knife radiosurgery (GKRS), to guide future treatment approaches to optimize tumor control. MATERIALS AND METHODS: A total of 101 consecutive patients (108 tumors) who underwent GKRS for benign, atypical, or malignant meningiomas between 1998 and 2011 were studied. Local recurrence was assessed. Cox proportional hazards and logistic regression analyses were used to determine the association of patient-related, tumor-related, and treatment-related characteristics with local recurrence. Acute and late toxicity was evaluated. RESULTS: World Health Organization (2007 classification) tumor grade was I (82%), II (11%), or III (7%). Median dose was 14 Gy (range, 10 to 18 Gy) for grade I tumors and 16 Gy (range, 12 to 20 Gy) for grade II and III tumors. Median follow-up was 25 months (maximum, 17 y). Two- /5-year actuarial local control rates were 100%/98% for grade I tumors and 76%/56% for grade II/III tumors. Higher tumor grade and lower GKRS dose were associated with local failure. In this cohort, there was a 42% relative reduction in local recurrence for each 1 Gy of dose escalation. CONCLUSIONS: Treatment was well tolerated with no moderate or severe toxicity. Tumor control was excellent in benign tumors and suboptimal in higher grade tumors. Because the main determinant of local recurrence was GKRS dose, we recommend dose escalation for atypical or malignant tumors to doses between 16 and 20 Gy where critical structures allow.
PMID: 26595685
ISSN: 1537-453x
CID: 1856322