A decade of diversity: using statistical indices to compare neurosurgery to other surgical specialties.

OBJECTIVE: Studies have demonstrated the benefits of diversity in neurosurgery. However, recruitment of minoritized groups within the neurosurgical workforce consistently lags other surgical specialties. While racial and gender demographics of neurosurgical residents are well documented, there has been minimal exploration into the multidimensional nature of diversity. The current study will evaluate the longitudinal diversity changes in neurosurgery residency programs compared with other surgical fields with validated diversity indices. METHODS: Nationwide reports including data about resident physicians were obtained from the American Medical Association and the Association of American Medical Colleges for the academic years 2008-2021. Self-reported race, biological sex, and medical school affiliation were recorded for surgical residents in the 10 commonly recognized surgical fields. The Gini-Simpson Diversity Index was used to calculate the effective counts (ECs) of races, sexes, and medical school types for each field. A Composite Diversity Index (CDI) comprising the aforementioned diversity traits was used to calculate the percentage of characteristics upon which two randomly selected residents within each specialty would differ. CDIs were calculated for each field in every year from 2008 to 2021. Median CDIs were compared between fields using Kruskal-Wallis testing, and p values < 0.05 were deemed statistically significant. RESULTS: Plastic surgery had the highest median sex EC (1.92, interquartile range [IQR] 1.78-1.95), indicating greater diversity, while neurosurgery had the third lowest sex EC (1.40, IQR 1.35-1.41). All surgical fields examined had fewer than 3 races effectively represented among their residents, despite there being 8 races present. Neurosurgery ranked among the top fields in effective racial diversity (EC 2.17, IQR 2.09-2.21) and medical school type diversity (EC 1.25, IQR 1.21-1.26). There were statistically significant differences in the sex, race, and school ECs between surgical specialties. While neurosurgery had a relatively low median overall diversity (CDI = 32.7, IQR 32.0-34.6), there was a consistent longitudinal increase in CDI from 2015 to 2021. CONCLUSIONS: Neurosurgery resident physicians have become increasingly diverse in the past decade but are more homogenous than residents in other surgical fields. The continued use of diversity indices to more accurately track diversity progress over time may better inform leaders in the field of how they may best focus their equity and inclusion efforts.

The epidemiology of crib-related head injuries: A ten-year nationwide analysis.

INTRODUCTION: Falls from cribs resulting in head injury are understudied and poorly characterized. The purpose of this study was to advance current understanding of the prevalence, descriptive characteristics of injury victims, and the types of crib fall-related head injuries (CFHI) using queried patient cases from the National Electronic Injury Surveillance System (NEISS) database. METHODS: Using the US Consumer Product Safety Commission's System NEISS database, we queried all CFHIs among children from over 100 emergency departments (EDs). Patient information regarding age, race, sex, location of the incident, diagnoses, ED disposition, and sequelae were analyzed. The number of CFHI from all US EDs during each year was also collected from the database. RESULTS: There were an estimated 54,799 (95% CI: 30,228-79,369) total visits to EDs for CFHIs between 2012 and 2021, with a decrease in incidence of approximately 20% during the onset of the COVID-19 pandemic (2019: 5616 cases, 2020: 4459 cases). The annual incidence of injuries showed no significant trend over the 10-year study period. An available subset of 1782 cases of head injuries from approximately 100 EDs was analyzed, and 1442 cases were included in final analysis. Injuries were sorted into three primary categories: unspecified closed head injury (e.g., closed head injury, blunt head trauma, or traumatic brain injury), concussion, or open head injury and skull fracture. Unspecified closed head injuries were the most common of all head injuries (95.4%, 1376/1442). Open head injuries (14/1442, 0.97%) and concussions 3.6% (52/1442, 3.6%) were rare. Most injuries involved children under the age of 1 (42.6%) compared to children who were 1, 2, 3, or 4-years old. About a fourth of patients had other diagnoses in addition to their primary injury including scalp/forehead hematomas, emesis, and contusions. Female patients were more likely to present with other diagnoses in addition to their primary head injury (Difference: 12.3%, 95% CI: 9.87%-15.4%, p < .0001). CONCLUSION: Despite minimum rail height requirements set by the Consumer Safety Product Commission (CPSC), head injuries associated with crib falls are prevalent in the United States. However, most injuries were minor with a vast majority of patients being released following examination and treatment.

Performance of ChatGPT and GPT-4 on Neurosurgery Written Board Examinations.

BACKGROUND AND OBJECTIVES: Interest surrounding generative large language models (LLMs) has rapidly grown. Although ChatGPT (GPT-3.5), a general LLM, has shown near-passing performance on medical student board examinations, the performance of ChatGPT or its successor GPT-4 on specialized examinations and the factors affecting accuracy remain unclear. This study aims to assess the performance of ChatGPT and GPT-4 on a 500-question mock neurosurgical written board examination. METHODS: The Self-Assessment Neurosurgery Examinations (SANS) American Board of Neurological Surgery Self-Assessment Examination 1 was used to evaluate ChatGPT and GPT-4. Questions were in single best answer, multiple-choice format. χ 2 , Fisher exact, and univariable logistic regression tests were used to assess performance differences in relation to question characteristics. RESULTS: ChatGPT (GPT-3.5) and GPT-4 achieved scores of 73.4% (95% CI: 69.3%-77.2%) and 83.4% (95% CI: 79.8%-86.5%), respectively, relative to the user average of 72.8% (95% CI: 68.6%-76.6%). Both LLMs exceeded last year's passing threshold of 69%. Although scores between ChatGPT and question bank users were equivalent ( P = .963), GPT-4 outperformed both (both P < .001). GPT-4 answered every question answered correctly by ChatGPT and 37.6% (50/133) of remaining incorrect questions correctly. Among 12 question categories, GPT-4 significantly outperformed users in each but performed comparably with ChatGPT in 3 (functional, other general, and spine) and outperformed both users and ChatGPT for tumor questions. Increased word count (odds ratio = 0.89 of answering a question correctly per +10 words) and higher-order problem-solving (odds ratio = 0.40, P = .009) were associated with lower accuracy for ChatGPT, but not for GPT-4 (both P > .005). Multimodal input was not available at the time of this study; hence, on questions with image content, ChatGPT and GPT-4 answered 49.5% and 56.8% of questions correctly based on contextual context clues alone. CONCLUSION: LLMs achieved passing scores on a mock 500-question neurosurgical written board examination, with GPT-4 significantly outperforming ChatGPT.

Performance of ChatGPT, GPT-4, and Google Bard on a Neurosurgery Oral Boards Preparation Question Bank.

BACKGROUND AND OBJECTIVES: General large language models (LLMs), such as ChatGPT (GPT-3.5), have demonstrated the capability to pass multiple-choice medical board examinations. However, comparative accuracy of different LLMs and LLM performance on assessments of predominantly higher-order management questions is poorly understood. We aimed to assess the performance of 3 LLMs (GPT-3.5, GPT-4, and Google Bard) on a question bank designed specifically for neurosurgery oral boards examination preparation. METHODS: The 149-question Self-Assessment Neurosurgery Examination Indications Examination was used to query LLM accuracy. Questions were inputted in a single best answer, multiple-choice format. χ 2 , Fisher exact, and univariable logistic regression tests assessed differences in performance by question characteristics. RESULTS: On a question bank with predominantly higher-order questions (85.2%), ChatGPT (GPT-3.5) and GPT-4 answered 62.4% (95% CI: 54.1%-70.1%) and 82.6% (95% CI: 75.2%-88.1%) of questions correctly, respectively. By contrast, Bard scored 44.2% (66/149, 95% CI: 36.2%-52.6%). GPT-3.5 and GPT-4 demonstrated significantly higher scores than Bard (both P < .01), and GPT-4 outperformed GPT-3.5 ( P = .023). Among 6 subspecialties, GPT-4 had significantly higher accuracy in the Spine category relative to GPT-3.5 and in 4 categories relative to Bard (all P < .01). Incorporation of higher-order problem solving was associated with lower question accuracy for GPT-3.5 (odds ratio [OR] = 0.80, P = .042) and Bard (OR = 0.76, P = .014), but not GPT-4 (OR = 0.86, P = .085). GPT-4's performance on imaging-related questions surpassed GPT-3.5's (68.6% vs 47.1%, P = .044) and was comparable with Bard's (68.6% vs 66.7%, P = 1.000). However, GPT-4 demonstrated significantly lower rates of "hallucination" on imaging-related questions than both GPT-3.5 (2.3% vs 57.1%, P < .001) and Bard (2.3% vs 27.3%, P = .002). Lack of question text description for questions predicted significantly higher odds of hallucination for GPT-3.5 (OR = 1.45, P = .012) and Bard (OR = 2.09, P < .001). CONCLUSION: On a question bank of predominantly higher-order management case scenarios for neurosurgery oral boards preparation, GPT-4 achieved a score of 82.6%, outperforming ChatGPT and Google Bard.

Pediatric all-terrain vehicle (ATV) related head injury rates and patterns: A 10-year nationwide analysis.

INTRODUCTION: The use of all-terrain vehicles (ATVs) carries significant risk of permanent injury and death, disproportionately affecting children. These injuries commonly affect the head and are especially severe among children as they are often unhelmeted and more likely than adults to experience rollover injuries. Many studies examining patients with ATV-related injuries are single-center cohort studies, with few focusing specifically on head injuries. In the present study, we aimed to characterize the annual incidence of ATV-related head injuries between 2012 and 2021, classify and compare head injury types, and identify descriptive characteristics of ATV-related head injury victims. METHODS: Using the US Consumer Product Safety Commission's National Electronic Injury Surveillance System (NEISS) database, we queried all head injuries associated with operating or riding an ATV in children under 18 years-old from over 100 emergency departments (EDs). Patient information regarding age, race, sex, location of incident, diagnoses, and sequelae were analyzed. We also collected the estimated number of ATV-related head injuries from all US EDs using the NEISS algorithm provided by the database. RESULTS: Using the NEISS algorithm we identified 67,957 (95% CI: 43,608 - 92,305) total pediatric ATV-related head injuries between 2012 and 2021. The annual incidence of ATV-related head injury was similar throughout this study period except for a 20% increase during the COVID-19 pandemic period of 2019-2021 (2019: 6382 injuries, 2020: 6757 injuries, 2021: 7600 injuries). A subset of 1890 cases from approximately 100 EDs were then analyzed. Unspecified closed head injuries were the prevailing type of injury (38%, 900/1890), followed by concussions (27%, 510/1890). More severe injuries included intracranial hemorrhages in 91 children (3.8%, 91/1890). Injuries of all types were predominantly seen in 14-17 year-old's (780/1890, 41%) and in males (64.1%, 1211/1890). In addition, ATV-associated injuries were significantly more common in those coded as white (58.0%, 1096/1890) than any other racial group. ATV-associated accidents among children younger than 9 more commonly occurred at the home compared to accidents involving children older than 9 (57% vs. 32%, p < 0.0001). CONCLUSION: ATV-related head injuries cause a significant annual burden among children, with growing incidence in recent years. Further research may wish to explore potential benefits of helmet use and supervision of younger children in possible prevention of these accidents and their associated economic and non-economic costs.

The burden of unhelmeted motorcycle injury: A nationwide scoring-based analysis of helmet safety legislation.

INTRODUCTION: Motorcycle collisions comprise a large portion of motor vehicle injuries and fatalities with over 80,000 injuries and 5,500 fatalities per year in the United States. Unhelmeted riders have poor medical outcomes and generate billions in costs. Despite helmet use having been shown to lower the risk of neurological injury and death, helmet compliance is not universal, and legislation concerning helmet use also varies widely across the United States. METHODS: In this study, we systematically reviewed helmet-related statutes from all US jurisdictions. We evaluated the stringency of these statutes using a legislative scoring system termed the Helmet Safety Score (HSS) ranging from 0-7 points, with higher scores denoting more stringent statutes. Regression modeling was used to predict unhelmeted mortality using our safety scores. RESULTS: The mean score across all jurisdictions was 4.73. We found jurisdictions with higher HSS's generally had lower percentages of unhelmeted fatalities in terms of total fatalities as well as per 100,000 people and 100,000 registered motorcycles. In contrast, some lower-scoring jurisdictions had over 100 times more unhelmeted fatalities than higher-scoring jurisdictions. Our HSS significantly predicted unhelmeted motorcycle fatalities per 100,000 people (ß = -0.228 per 1-point increase, 95% CI: -0.288 to -0.169, p < .0001) and per 100,000 registered motorcycles (ß = -6.17 per 1-point increase, 95% CI: -8.37 to -3.98, p < .0001) in each state. Aspects of our score concerning helmet exemptions for riders and motorcycle-type vehicles independently predicted higher fatalities (p < .0001). Higher safety scores predicted lower unhelmeted fatalities. CONCLUSION: Stringent helmet laws may be an effective mechanism for decreasing unhelmeted mortality. Therefore, universal helmet laws may be one such mechanism to decrease motorcycle-related neurological injury and fatality burden. In states with existing helmet laws, elimination of exemptions for certain riders and motorcycle-type vehicles may also decrease fatalities.

Incidence, Characteristics, and Outcomes of Pseudomeningocele and Cerebrospinal Fluid Fistula after Posterior Fossa Surgery.

OBJECTIVE: Posterior fossa approaches are common neurosurgical procedures. Rates of postoperative infection, pseudomeningocele, and cerebrospinal fluid (CSF) fistula are high; however, evidence regarding predisposing risk factors and treatment outcomes remain sparse. METHODS: A retrospective cohort study was carried out of all posterior fossa surgeries conducted at a single institution between January 2015 and October 2019. Univariate statistical methods and stepwise logistic regression were used to assess which factors contributed most to risk of development of postoperative complications. RESULTS: A total of 269 patients were included; 18.6% experienced any postoperative complication, 13% developed either pseudomeningocele or CSF fistula, and 9.7% developed an infection. In multivariate analysis, development of a pseudomeningocele was significantly associated with previous cranial surgery (hazard ratio [HR], 3.15; 95% confidence interval [CI], 1.12-9.28; P = 0.0391). Development of a CSF fistula was significantly associated with index surgery for resection of neoplasm (HR, 7.65; 95% CI, 1.86-22.31; P = 0.0174). Development of an infection was significantly associated with concurrent CSF fistula (HR, 7.16; 95% CI, 1.91-23.19; P = 0.0041) and concurrent pseudomeningocele (HR, 3.41; 95% CI, 1.37-5.95; P = 0.0082) and nonsignificantly associated with diabetes requiring treatment (HR, 2.42; 95% CI, 0.69-8.50; P = 0.168). Other hypothesized risk factors for these complications, such as nonmidline approaches to the posterior fossa, watertight duraplasty, use of dural fibrin sealant, and cranioplasty were not associated with these complications on multivariate analysis. Although many patients with pseudomeningocele were successfully managed with observation, only 38% of patients in whom CSF diversion was attempted avoided surgery. CONCLUSIONS: History of diabetes, cranioplasty, revision surgery, and surgery for tumor resection are identified as risk factors for the development of infection, pseudomeningocele, and CSF fistula, respectively.

Evidence of Linear Bone Flap Resorption in Patients Undergoing Autologous Cranioplasty Following Decompressive Craniectomy: A 3D Slicer Segmented Analysis of Serial Computed Tomography Images.

OBJECTIVE: Autologous cranioplasty (CP) following decompressive craniectomy (DC) carries a risk of bone flap resorption (BFR). The current literature offers limited information regarding the natural progression of BFR and the rate at which it occurs. We aim to characterize the progression of BFR over time and elucidate risk factors for accelerated BFR. METHODS: A retrospective analysis was conducted on patients who underwent DC and autologous CP. Serial computed tomography (CT) images were used to quantify the degree of BFR over time. Risk factors included age, diabetes, smoking status, flap fragmentation, defect size, and DC-CP time interval. χ2 analyses and Student's t-tests were performed to examine differences between patients who experienced BFR and those who did not. RESULTS: Overall, 82% of patients demonstrated evidence of clinically relevant resorption on CT. On average, the bone flap decreased in volume by 36.7% within the first year, with a linear loss in volume after multiple years of follow-up. Individuals who developed greater BFR were significantly younger (43 ± 17 vs. 56 ± 12, P = 0.022), had a lower incidence of diabetes (5.9% vs. 43%, P = 0.037), and had more bone flap fragments (1.4 ± 0.67 vs. 1.00 ± 0, P < 0.001) than those who did not. CONCLUSIONS: Resorption following CP with cryopreserved bone appears to progress in a fairly linear and continuous fashion over time. Using serial CT images, we found a resorption rate of 82% at our institution. We identified several possible risk factors for resorption, including flap fragmentation, younger age, and absence of diabetes.

Emergency medical services protocols for traumatic brain injury in the United States: A call for standardization.

BACKGROUND: Traumatic brain injury (TBI) with acute elevation in intracranial pressure (ICP) is a neurologic emergency associated with significant morbidity and mortality. In addition to indicated trauma resuscitation, emergency department (ED) management includes empiric administration of hyperosmolar agents, rapid diagnostic imaging, anticoagulation reversal, and early neurosurgical consultation. Despite optimization of in-hospital care, patient outcomes may be worsened by variation in prehospital management. In this study, we evaluate geographic variation between emergency medical services (EMS) protocols for patients with suspected TBI. METHODS: We performed a cross-sectional analysis of statewide EMS protocols in the United States in December 2020 and included all complete protocols published on government websites. Outcome measures were defined to include protocols or orders for the following interventions, given TBI: (1) hyperventilation and end-tidal capnography (EtCO2) goals, (2) administration of hyperosmolar agents, (3) tranexamic acid (TXA) administration for isolated head injury, (4) non-invasive management including head-of-bed elevation, and (5) hemodynamic goals. RESULTS: We identified 32 statewide protocols including Washington, D.C., 4 of which did not include specific guidance for TBI. Of 28 states providing ventilatory guidance, 22/28 (78.6%) recommend hyperventilation, with 17/22 (77.3%) restricting hyperventilation to signs of acute herniation. The remaining 6 states prohibited hyperventilation. Regarding EtCO2 goals among states permitting hyperventilation, 17/22 (77.3%) targeted an EtCO2 of < 35 mmHg, while 5/22 (22.7%) provided no guide EtCO2 for hyperventilation. Rhode Island was the only state identified that included hypertonic saline (3%), and Delaware was the only state that allowed TXA in the setting of isolated TBI with GCS ≤ 12. Only 15/32 (46.9%) identified states recommend head-of-bed elevation. For blood pressure goals, 12/28 (42.9%) of states set minimum systolic blood pressure at 90 mmHg, while 10/28 (35.7%) set other SBP goals. The remaining 6/28 (21.4%) did not provide TBI-specific SBP goals. CONCLUSIONS: There is wide variation among civilian prehospital protocols for traumatic brain injury. Prehospital care within the first "golden hour" may dramatically affect patient outcomes. Neurocritical care providers should be mindful of geographic variation in local protocols when designing and evaluating quality improvement interventions and should aim to standardize prehospital care protocols.

Nanoliposomal Irinotecan and Metronomic Temozolomide for Patients With Recurrent Glioblastoma: BrUOG329, A Phase I Brown University Oncology Research Group Trial.

BACKGROUND: Liposomal formulations may improve the solubility and bioavailability of drugs potentially increasing their ability to cross the blood-brain barrier. We performed a phase I study to determine the maximum tolerated dose and preliminary efficacy of pegylated nanoliposomal irinotecan (nal-IRI)+metronomic temozolomide (TMZ) in patients with recurrent glioblastoma. PATIENTS AND METHODS: Patients with glioblastoma who progressed after at least 1 line of therapy were eligible. All patients received TMZ 50 mg/m2/d until disease progression. Three dose levels of nal-IRI were planned, 50, 70, and 80 mg/m2, intravenously every 2 weeks. Patients were accrued in a 3+3 design. The study included a preliminary assessment after the first 13 evaluable patients. The trial would be terminated early if 0 or 1 responses were observed in these patients. RESULTS: Twelve patients were treated over 2 dose levels (nal-IRI 50 and 70 mg/m2). At dose level 2, nal-IRI 70 mg/m2, 2 of 3 patients developed dose-limiting toxicities including 1 patient who developed grade 4 neutropenia and grade 3 diarrhea and anorexia and 1 patient with grade 3 diarrhea, hypokalemia fatigue, and anorexia. Accrual to dose level 1 was expanded to 9 patients. The Drug Safety Monitoring Board (DSMB) reviewed the data of the initial 12 patients-there were 0/12 responses (0%) and the median progression-free survival was 2 months and accrual was halted. CONCLUSIONS: The maximum tolerated dose of nal-IRI was 50 mg/m2 every 2 weeks with TMZ 50 mg/m2/d. The dose-limiting toxicities were diarrhea and neutropenia. No activity was seen at interim analysis and the study was terminated.

A Transforaminal Endoscopic Surgical Technique for Treating Lumbar Disc Herniation in the Setting of Spina Bifida.

Recent literature suggests that adult patients with spina bifida receive surgery for degenerative disc disease at higher rates than the general population. However, sometimes the complex anatomic features of co-occurring spina bifida and lumbar disc herniation can significantly challenge standard surgical techniques. Here, the technical steps are presented for treating a foraminal lumbar 4-5-disc herniation in the setting of a patient with multifaceted degenerative and spina bifida occulta anatomy. Utilized is a minimally invasive approach that does not require general anesthesia or fusion and allows the patient to leave the same day. To the best of our knowledge, this is the first-reported case of endoscopic surgical decompression of a lumbar disc in a patient with spina bifida.

The Role of Radiation Therapy in the Treatment of Metastatic Brain Disease.

Brain metastasis is the most frequent central nervous system malignancy. Although surgery and chemotherapy have roles to play in the treatment of brain metastasis, radiation therapy remains a mainstay of therapy. We will review the role of fractionated radiotherapy and stereotactic radiosurgery in the treatment of newly diagnosed and recurrent brain metastasis. [Full article available at http://rimed.org/rimedicaljournal-2017-06.asp].

Repeat Stereotactic Radiosurgery for Locally Recurrent Brain Metastases.

PURPOSE/OBJECTIVES: The outcomes of repeat stereotactic radiosurgery (SRS) after failure of previous SRS are not well established. We report our overall experience using SRS for the retreatment of locally recurrent brain metastases. METHODS: Patients with brain metastases diagnosed between 2003 and 2015 who underwent repeat SRS for local tumor progression following prior SRS were identified. Rates of local control, radiation necrosis, and overall survival were analyzed. Factors affecting local failure and radiation necrosis were assessed by chi-square test. RESULTS: Twenty-four lesions in 22 patients underwent repeat SRS in a single fraction. Median age was 59 years. The median SRS-1 dose was 18 Gy, and the median SRS-2 dose was 15.5 Gy. The median SRS-1 target volume was 2.25 cm3, and the median SRS-2 target volume was 3.30 cm3. The median follow-up from SRS-2 was 8.8 months. The actuarial local controls for SRS-2 were 94.1% and 61.1% at 6 and 12 months, respectively. The incidences of actuarial radiation necrosis were 9.2% and 9.2% at 6 and 12 months, respectively. Volume of tumor >4 cm3 correlated with increased risk of local failure (P = 0.006) with no local failures recorded with volumes ≤4 cm3. SRS-2 dose, cumulative SRS dose, receipt of whole brain radiotherapy, and use of SRS-2 as boost after surgery did not correlate with local failure or radiation necrosis. Median overall survival after SRS-2 was 8.78 months. CONCLUSION: Repeat SRS is feasible for select patients, particularly for those with tumor volume ≤4 cm3. Further evaluation is needed to establish the most appropriate treatment doses and volumes for this approach.

Multi-institutional Nomogram Predicting Survival Free From Salvage Whole Brain Radiation After Radiosurgery in Patients With Brain Metastases.

PURPOSE: Optimal patient selection for stereotactic radiosurgery (SRS) as the initial treatment for brain metastases is complicated and controversial. This study aimed to develop a nomogram that predicts survival without salvage whole brain radiation therapy (WBRT) after upfront SRS. METHODS AND MATERIALS: Multi-institutional data were analyzed from 895 patients with 2095 lesions treated with SRS without prior or planned WBRT. Cox proportional hazards regression model was used to identify independent pre-SRS predictors of WBRT-free survival, which were integrated to build a nomogram that was subjected to bootstrap validation. RESULTS: Median WBRT-free survival was 8 months (range, 0.1-139 months). Significant independent predictors for inferior WBRT-free survival were age (hazard ratio [HR] 1.1 for each 10-year increase), HER2(-) breast cancer (HR 1.6 relative to other histologic features), colorectal cancer (HR 1.4 relative to other histologic features), increasing number of brain metastases (HR 1.09, 1.32, 1.37, and 1.87 for 2, 3, 4, and 5+ lesions, respectively), presence of neurologic symptoms (HR 1.26), progressive systemic disease (HR 1.35), and increasing extracranial disease burden (HR 1.31 for oligometastatic and HR 1.56 for widespread). Additionally, HER2(+) breast cancer (HR 0.81) and melanoma (HR 1.11) trended toward significance. The independently weighted hazard ratios were used to create a nomogram to display estimated probabilities of 6-month and 12-month WBRT-free survival with a corrected Harrell's C concordance statistic of 0.62. CONCLUSIONS: Our nomogram can be used at initial evaluation to help select patients best suited for upfront SRS for brain metastases while reducing expense and morbidity in patients who derive minimal or no benefit.

Patients with Long-Term Control of Systemic Disease Are a Favorable Prognostic Group for Treatment of Brain Metastases with Stereotactic Radiosurgery Alone.

BACKGROUND: Stereotactic radiosurgery (SRS) alone is an attractive option for treatment of brain metastases. SRS avoids whole-brain radiotherapy (WBRT)-associated morbidity, but is limited by regional central nervous system (CNS) failures and short survival in some patients. We evaluated a subgroup of patients with controlled systemic disease that could represent a favorable patient population for SRS alone. METHODS: All patients with brain metastases treated with SRS without WBRT at our institution between 2004 and 2014 were grouped into two cohorts: those with controlled systemic disease (CSD) for 1 year or longer before prior to presentation with brain metastases and those without (i.e., uncontrolled systemic disease [USD]). Rates of local and regional CNS failure, and overall survival were assessed with χ2 and Student t tests. Cox regression analysis was performed to evaluate independent predictors of regional control and overall survival. RESULTS: Two hundred ninety-four patients underwent SRS to 697 lesions, of which 65 patients had CSD. Median follow-up was 9.7 months. There was no difference in local control between the two cohorts (P = 0.795). Regional CNS control was significantly better for patients with CSD (68% vs. 48%; P = 0.001). Overall survival at 1 and 5 years for CSD were 65% and 13% with USD yielding 41% and 7%, respectively (P < 0.001). Multivariate analysis demonstrated that USD (relative CSD) independently predicts regional failure (hazard ratio [HR], 1.75; P = 0.008) and shorter overall survival (HR, 1.55; P = 0.007). CONCLUSIONS: Patients with brain metastases after 1 year or longer of primary and systemic disease control represent a particularly favorable cohort, with lower regional CNS failure and prolonged survival, for an approach of SRS alone.

Management approach for recurrent brain metastases following upfront radiosurgery may affect risk of subsequent radiation necrosis.

PURPOSE: Many patients treated with stereotactic radiosurgery (SRS) alone as initial treatment require 1 or more subsequent salvage therapies. This study aimed to determine if commonly used salvage strategies are associated with differing risks of radiation necrosis (RN). METHODS AND MATERIALS: All patients treated with upfront SRS alone for brain metastases at our institution were retrospectively analyzed. Salvage treatment details were obtained for brain failures. Patients who underwent repeat SRS to the same lesion were excluded. RN was determined based on pathological confirmation or advanced brain imaging consistent with RN in a symptomatic patient. Patients were grouped according to salvage treatment and rates of RN were compared via Fisher's exact tests. RESULTS: Of 284 patients treated with upfront SRS alone, 132 received salvage therapy and 44 received multiple salvage treatments. This included 31 repeat SRS alone, 58 whole brain radiation therapy (WBRT) alone, 28 SRS and WBRT, 7 surgery alone, and 8 surgery with adjuvant radiation. With a median follow-up of 10 months, the rate of RN among all patients was 3.17% (9/284), salvaged patients 4.55% (6/132), and never salvaged patients 1.97% (3/152). Receiving salvage therapy did not significantly increase RN risk (P = .31). Of the patients requiring salvage treatments, the highest RN rate was among patients that had both salvage SRS and WBRT (delivered as separate salvage therapies) (6/28, 21.42%). RN rate in this group was significantly higher than in those treated with repeat SRS alone (0/31), WBRT alone (0/58), surgery alone (0/7), and surgery with adjuvant radiation (0/8). Comparing salvage WBRT doses <30 Gy versus ≥30 Gy revealed no effect of dose on RN rate. Additionally, among patients who received multiple SRS treatments, number of treated lesions was not predictive of RN incidence. CONCLUSION: Our results suggest that initial management approach for recurrent brain metastasis after upfront SRS does not affect the rate of RN. However, the risk of RN significantly increases when patients are treated with both repeat SRS and salvage WBRT. Methods to improve prediction of toxicity and optimize patient selection for salvage treatments are needed.

Stereotactic radiosurgery for large brain metastases.

We evaluated patient outcomes following stereotactic radiosurgery (SRS)-treatment of large brain metastasis (⩾3 cm) at our institution. SRS is an established treatment for limited brain metastases. However, large tumors pose a challenge for this approach. For this study, 343 patients with 754 total brain metastases were treated with SRS, of which 93 had large tumors. The tumor size was 3-3.5, 3.5-4, and ⩾4 cm in 29%, 32%, and 39% of these patients. Surgical resection was performed prior to SRS in 68% of patients, and 53% achieved a gross total resection. The local control of large metastases was inferior compared to smaller tumors, with 1 year local control of 68 versus 86%, respectively (p<0.001). Among the patients with large metastases, no correlation between local control and surgical resection (p=0.747), or extent of surgery (gross total versus subtotal resection; p=0.120), was identified. Histology (p=0.939), tumor size (3-4 versus >4 cm; p=0.551), and SRS dose (⩽16 versus >16 Gy; p=0.539) also showed no correlation with local failure. The overall survival at 1, 2, and 5 years was 46%, 29% and 5%, respectively. Prolonged survival was seen in patients with age <65 years (p=0.009), primary treatment compared with salvage (p=0.077), and controlled primary tumors (p=0.022). Radiation necrosis developed in 10 patients (11.8%). For patients with large brain metastases, SRS is well tolerated and can achieve local central nervous system disease control in the majority of patients, and extended survival in some, though the local control rate is suboptimal. Further strategies to improve the outcomes in this subgroup of patients are needed.

Predictors for long-term survival free from whole brain radiation therapy in patients treated with radiosurgery for limited brain metastases.

PURPOSE: To identify predictors for prolonged survival free from salvage whole brain radiation therapy (WBRT) in patients with brain metastases treated with stereotactic radiosurgery (SRS) as their initial radiotherapy approach. MATERIALS AND METHODS: Patients with brain metastases treated with SRS from 2001 to 2013 at our institution were identified. SRS without WBRT was typically offered to patients with 1-4 brain metastases, Karnofsky performance status ≥70, and life expectancy ≥3 months. Three hundred and eight patients met inclusion criteria for analysis. Medical records were reviewed for patient, disease, and treatment information. Two comparison groups were identified: those with ≥1-year WBRT-free survival (N = 104), and those who died or required salvage WBRT within 3 months of SRS (N = 56). Differences between these groups were assessed by univariate and multivariate analyses. RESULTS: Median survival for all patients was 11 months. Among patients with ≥1-year WBRT-free survival, median survival was 33 months (12-107 months) with only 21% requiring salvage WBRT. Factors significantly associated with prolonged WBRT-free survival on univariate analysis (p < 0.05) included younger age, asymptomatic presentation, RTOG RPA class I, fewer brain metastases, surgical resection, breast primary, new or controlled primary, absence of extracranial metastatic disease, and oligometastatic disease burden (≤5 metastatic lesions). After controlling for covariates, asymptomatic presentation, breast primary, single brain metastasis, absence of extracranial metastases, and oligometastatic disease burden remained independent predictors for favorable WBRT-free survival. CONCLUSION: A subset of patients with brain metastases can achieve long-term survival after upfront SRS without the need for salvage WBRT. Predictors identified in this study can help select patients that might benefit most from a treatment strategy of SRS alone.