Asher, Anthony L.

An estimated 20% of patients with cancer will develop brain metastases. Approximately 200,000 individuals in the United States alone receive whole-brain radiotherapy (WBRT) each year to treat brain metastases. Historically, the prognosis of patients with brain metastases has been poor; however, with new therapies, this is changing. Because patients are living longer following the diagnosis and treatment of brain metastases, there has been rising concern about treatment-related toxicities associated with WBRT, including neurocognitive toxicity. In addition, recent clinical trials have raised questions about the use of WBRT. To better understand this rapidly changing landscape, this review outlines the treatment roles and toxicities of WBRT and alternative therapies for the management of brain metastases.

Abstract Please see the full-text version of this guideline (https://www.cns.org/guidelines/guidelines-management-patients-vestibular-schwannoma/chapter_8) for the target population of each recommendation listed below. QUESTION 1 What surgical approaches for vestibular schwannomas (VS) are best for complete resection and facial nerve (FN) preservation when serviceable hearing is present? RECOMMENDATION There is insufficient evidence to support the superiority of either the middle fossa (MF) or the retrosigmoid (RS) approach for complete VS resection and FN preservation when serviceable hearing is present. QUESTION 2 Which surgical approach (RS or translabyrinthine [TL]) for VS is best for complete resection and FN preservation when serviceable hearing is not present? RECOMMENDATION There is insufficient evidence to support the superiority of either the RS or the TL approach for complete VS resection and FN preservation when serviceable hearing is not present. QUESTION 3 Does VS size matter for facial and vestibulocochlear nerve preservation with surgical resection? RECOMMENDATION Level 3: Patients with larger VS tumor size should be counseled about the greater than average risk of loss of serviceable hearing. QUESTION 4 Should small intracanalicular tumors (<1.5 cm) be surgically resected? RECOMMENDATION There are insufficient data to support a firm recommendation that surgery be the primary treatment for this subclass of VSs. QUESTION 5 Is hearing preservation routinely possible with VS surgical resection when serviceable hearing is present? RECOMMENDATION Level 3: Hearing preservation surgery via the MF or the RS approach may be attempted in patients with small tumor size (<1.5 cm) and good preoperative hearing. QUESTION 6 When should surgical resection be the initial treatment in patients with neurofibromatosis type 2 (NF2)? RECOMMENDATION There is insufficient evidence that surgical resection should be the initial treatment in patients with NF2. QUESTION 7 Does a multidisciplinary team, consisting of neurosurgery and neurotology, provides the best outcomes of complete resection and facial/vestibulocochlear nerve preservation for patients undergoing resection of VSs? RECOMMENDATION There is insufficient evidence to support stating that a multidisciplinary team, usually consisting of a neurosurgeon and a neurotologist, provides superior outcomes compared to either subspecialist working alone. QUESTION 8 Does a subtotal surgical resection of a VS followed by stereotactic radiosurgery (SRS) to the residual tumor provide comparable hearing and FN preservation to patients who undergo a complete surgical resection? RECOMMENDATION There is insufficient evidence to support subtotal resection (STR) followed by SRS provides comparable hearing and FN preservation to patients who undergo a complete surgical resection. QUESTION 9 Does surgical resection of VS treat preoperative balance problems more effectively than SRS? RECOMMENDATION There is insufficient evidence to support either surgical resection or SRS for treatment of preoperative balance problems. QUESTION 10 Does surgical resection of VS treat preoperative trigeminal neuralgia more effectively than SRS? RECOMMENDATION Level 3: Surgical resection of VSs may be used to better relieve symptoms of trigeminal neuralgia than SRS. QUESTION 11 Is surgical resection of VSs more difficult (associated with higher facial neuropathies and STR rates) after initial treatment with SRS? RECOMMENDATION Level 3: If microsurgical resection is necessary after SRS, it is recommended that patients be counseled that there is an increased likelihood of a STR and decreased FN function. The full guideline can be found at: https://www.cns.org/guidelines/guidelines-management-patients-vestibular-schwannoma/chapter_8.

OBJECTIVEIn this analysis the authors compare the characteristics of smokers to nonsmokers using demographic, socioeconomic, and comorbidity variables. They also investigate which of these characteristics are most strongly associated with smoking status. Finally, the authors investigate whether the association between known patient risk factors and disability outcome is differentially modified by patient smoking status for those who have undergone surgery for lumbar degeneration.METHODSA total of 7547 patients undergoing degenerative lumbar surgery were entered into a prospective multicenter registry (Quality Outcomes Database [QOD]). A retrospective analysis of the prospectively collected data was conducted. Patients were dichotomized as smokers (current smokers) and nonsmokers. Multivariable logistic regression analysis fitted for patient smoking status and subsequent measurement of variable importance was performed to identify the strongest patient characteristics associated with smoking status. Multivariable linear regression models fitted for 12-month Oswestry Disability Index (ODI) scores in subsets of smokers and nonsmokers was performed to investigate whether differential effects of risk factors by smoking status might be present.RESULTSIn total, 18% (n = 1365) of patients were smokers and 82% (n = 6182) were nonsmokers. In a multivariable logistic regression analysis, the factors significantly associated with patients’ smoking status were sex (p < 0.0001), age (p < 0.0001), body mass index (p < 0.0001), educational status (p < 0.0001), insurance status (p < 0.001), and employment/occupation (p = 0.0024). Patients with diabetes had lowers odds of being a smoker (p = 0.0008), while patients with coronary artery disease had greater odds of being a smoker (p = 0.044). Patients’ propensity for smoking was also significantly associated with higher American Society of Anesthesiologists (ASA) class (p < 0.0001), anterior-alone surgical approach (p = 0.018), greater number of levels (p = 0.0246), decompression only (p = 0.0001), and higher baseline ODI score (p < 0.0001). In a multivariable proportional odds logistic regression model, the adjusted odds ratio of risk factors and direction of improvement in 12-month ODI scores remained similar between the subsets of smokers and nonsmokers.CONCLUSIONSUsing a large, national, multiinstitutional registry, the authors described the profile of patients who undergo lumbar spine surgery and its association with their smoking status. Compared with nonsmokers, smokers were younger, male, nondiabetic, nonobese patients presenting with leg pain more so than back pain, with higher ASA classes, higher disability, less education, more likely to be unemployed, and with Medicaid/uninsured insurance status. Smoking status did not affect the association between these risk factors and 12-month ODI outcome, suggesting that interventions for modifiable risk factors are equally efficacious between smokers and nonsmokers.

OBJECTIVE Lumbar spondylolisthesis is a degenerative condition that can be surgically treated with either open or minimally invasive decompression and instrumented fusion. Minimally invasive surgery (MIS) approaches may shorten recovery, reduce blood loss, and minimize soft-tissue damage with resultant reduced postoperative pain and disability. METHODS The authors queried the national, multicenter Quality Outcomes Database (QOD) registry for patients undergoing posterior lumbar fusion between July 2014 and December 2015 for Grade I degenerative spondylolisthesis. The authors recorded baseline and 12-month patient-reported outcomes (PROs), including Oswestry Disability Index (ODI), EQ-5D, numeric rating scale (NRS)–back pain (NRS-BP), NRS–leg pain (NRS-LP), and satisfaction (North American Spine Society satisfaction questionnaire). Multivariable regression models were fitted for hospital length of stay (LOS), 12-month PROs, and 90-day return to work, after adjusting for an array of preoperative and surgical variables. RESULTS A total of 345 patients (open surgery, n = 254; MIS, n = 91) from 11 participating sites were identified in the QOD. The follow-up rate at 12 months was 84% (83.5% [open surgery]; 85% [MIS]). Overall, baseline patient demographics, comorbidities, and clinical characteristics were similarly distributed between the cohorts. Two hundred fifty seven patients underwent 1-level fusion (open surgery, n = 181; MIS, n = 76), and 88 patients underwent 2-level fusion (open surgery, n = 73; MIS, n = 15). Patients in both groups reported significant improvement in all primary outcomes (all p < 0.001). MIS was associated with a significantly lower mean intraoperative estimated blood loss and slightly longer operative times in both 1- and 2-level fusion subgroups. Although the LOS was shorter for MIS 1-level cases, this was not significantly different. No difference was detected with regard to the 12-month PROs between the 1-level MIS versus the 1-level open surgical groups. However, change in functional outcome scores for patients undergoing 2-level fusion was notably larger in the MIS cohort for ODI (−27 vs −16, p = 0.1), EQ-5D (0.27 vs 0.15, p = 0.08), and NRS-BP (−3.5 vs −2.7, p = 0.41); statistical significance was shown only for changes in NRS-LP scores (−4.9 vs −2.8, p = 0.02). On risk-adjusted analysis for 1-level fusion, open versus minimally invasive approach was not significant for 12-month PROs, LOS, and 90-day return to work. CONCLUSIONS Significant improvement was found in terms of all functional outcomes in patients undergoing open or MIS fusion for lumbar spondylolisthesis. No difference was detected between the 2 techniques for 1-level fusion in terms of patient-reported outcomes, LOS, and 90-day return to work. However, patients undergoing 2-level MIS fusion reported significantly better improvement in NRS-LP at 12 months than patients undergoing 2-level open surgery. Longer follow-up is needed to provide further insight into the comparative effectiveness of the 2 procedures.

OBJECTIVECurrent costs associated with spine care are unsustainable. Productivity loss and time away from work for patients who were once gainfully employed contributes greatly to the financial burden experienced by individuals and, more broadly, society. Therefore, it is vital to identify the factors associated with return to work (RTW) after lumbar spine surgery. In this analysis, the authors used data from a national prospective outcomes registry to create a predictive model of patients’ ability to RTW after undergoing lumbar spine surgery for degenerative spine disease.METHODSData from 4694 patients who underwent elective spine surgery for degenerative lumbar disease, who had been employed preoperatively, and who had completed a 3-month follow-up evaluation, were entered into a prospective, multicenter registry. Patient-reported outcomes—Oswestry Disability Index (ODI), numeric rating scale (NRS) for back pain (BP) and leg pain (LP), and EQ-5D scores—were recorded at baseline and at 3 months postoperatively. The time to RTW was defined as the period between operation and date of returning to work. A multivariable Cox proportional hazards regression model, including an array of preoperative factors, was fitted for RTW. The model performance was measured using the concordance index (c-index).RESULTSEighty-two percent of patients (n = 3855) returned to work within 3 months postoperatively. The risk-adjusted predictors of a lower likelihood of RTW were being preoperatively employed but not working at the time of presentation, manual labor as an occupation, worker’s compensation, liability insurance for disability, higher preoperative ODI score, higher preoperative NRS-BP score, and demographic factors such as female sex, African American race, history of diabetes, and higher American Society of Anesthesiologists score. The likelihood of a RTW within 3 months was higher in patients with higher education level than in those with less than high school–level education. The c-index of the model’s performance was 0.71.CONCLUSIONSThis study presents a novel predictive model for the probability of returning to work after lumbar spine surgery. Spine care providers can use this model to educate patients and encourage them in shared decision-making regarding the RTW outcome. This evidence-based decision support will result in better communication between patients and clinicians and improve postoperative recovery expectations, which will ultimately increase the likelihood of a positive RTW trajectory.

OBJECTIVEQuality and outcomes registry platforms lie at the center of many emerging evidence-driven reform models. Specifically, clinical registry data are progressively informing health care decision-making. In this analysis, the authors used data from a national prospective outcomes registry (the Quality Outcomes Database) to develop a predictive model for 12-month postoperative pain, disability, and quality of life (QOL) in patients undergoing elective lumbar spine surgery.METHODSIncluded in this analysis were 7618 patients who had completed 12 months of follow-up. The authors prospectively assessed baseline and 12-month patient-reported outcomes (PROs) via telephone interviews. The PROs assessed were those ascertained using the Oswestry Disability Index (ODI), EQ-5D, and numeric rating scale (NRS) for back pain (BP) and leg pain (LP). Variables analyzed for the predictive model included age, gender, body mass index, race, education level, history of prior surgery, smoking status, comorbid conditions, American Society of Anesthesiologists (ASA) score, symptom duration, indication for surgery, number of levels surgically treated, history of fusion surgery, surgical approach, receipt of workers’ compensation, liability insurance, insurance status, and ambulatory ability. To create a predictive model, each 12-month PRO was treated as an ordinal dependent variable and a separate proportional-odds ordinal logistic regression model was fitted for each PRO.RESULTSThere was a significant improvement in all PROs (p < 0.0001) at 12 months following lumbar spine surgery. The most important predictors of overall disability, QOL, and pain outcomes following lumbar spine surgery were employment status, baseline NRS-BP scores, psychological distress, baseline ODI scores, level of education, workers’ compensation status, symptom duration, race, baseline NRS-LP scores, ASA score, age, predominant symptom, smoking status, and insurance status. The prediction discrimination of the 4 separate novel predictive models was good, with a c-index of 0.69 for ODI, 0.69 for EQ-5D, 0.67 for NRS-BP, and 0.64 for NRS-LP (i.e., good concordance between predicted outcomes and observed outcomes).CONCLUSIONSThis study found that preoperative patient-specific factors derived from a prospective national outcomes registry significantly influence PRO measures of treatment effectiveness at 12 months after lumbar surgery. Novel predictive models constructed with these data hold the potential to improve surgical effectiveness and the overall value of spine surgery by optimizing patient selection and identifying important modifiable factors before a surgery even takes place. Furthermore, these models can advance patient-focused care when used as shared decision-making tools during preoperative patient counseling.

LBA4 Background: WBRT significantly improves tumor control in the brain after SRS, yet the role of adjuvant WBRT remains undefined due to concerns regarding neurocognitive risks. Methods: Patients with 1-3 brain metastases, each < 3 cm by contrast MRI, were randomized to SRS alone or SRS + WBRT and underwent cognitive testing before and after treatment. The primary endpoint was cognitive progression (CP) defined as decline > 1 SD from baseline in any of the 6 cognitive tests at 3 months. Time to CP was estimated using cumulative incidence adjusting for survival as a competing risk. Results: 213 patients were enrolled with 2 ineligible and 3 cancels prior to receiving treatment. Baseline characteristics were well-balanced between study arms. The median age was 60 and lung primary the most common (68%). CP at 3 months was more frequent after WBRT + SRS vs. SRS alone (88.0% vs. 61.9% respectively, p = 0.002). There was more deterioration in the WBRT + SRS arm in immediate recall (31% vs. 8%, p = 0.007), delayed recall (51% vs. 20%, p = 0.002), and verbal fluency (19% vs. 2%, p = 0.02). Intracranial tumor control at 6 and 12 months were 66.1% and 50.5% with SRS alone vs. 88.3% and 84.9% with SRS+WBRT (p < 0.001). Median OS was 10.7 for SRS alone vs. 7.5 months for SRS+WBRT respectively (HR = 1.02, p = 0.93). Conclusions: Decline in cognitive function, specifically immediate recall, memory and verbal fluency, was more frequent with the addition of WBRT to SRS. Adjuvant WBRT did not improve OS despite better brain control. Initial treatment with SRS and close monitoring is recommended to better preserve cognitive function in patients with newly diagnosed brain metastases that are amenable to SRS. Clinical trial information: NCT00377156.

Study Design. Retrospective analysis of prospectively collected data. Objective. The aim of this study was to determine whether 1-year patient-reported outcomes (PROs) can accurately assess effective care for patients undergoing surgery for degenerative lumbar spine disease. Summary of Background Data. Prospective longitudinal PROs registries provide a means to accurately assess outcomes and determine the relative effectiveness of various spine treatments. Obtaining long-term PROs can be costly and challenging. Methods. Patients enrolled into a prospective registry who underwent lumbar spine surgery for degenerative disease were included. Baseline, 1-year, and 2-year Oswestry Disability Index (ODI) scores were captured. Previously published minimum clinically important difference (MCID) for ODI (14.9) was used. Multivariable linear regression model was created to derive model-estimated 2-year ODI scores. Absolute differences between 1-year and 2-year ODI were compared to absolute differences between 2-year and model-estimated 2-year ODI. Concordance rates in achieving MCID at 1-year and 2-year and predictive values were calculated. Results. A total of 868 patients were analyzed. One-year ODI scores differed from 2-year scores by an absolute difference of 9.7 ± 8.9 points and predictive model-estimated 2-year scores differed from actual 2-year scores by 8.8 ± 7.3 points. The model-estimated 2-year ODI was significantly different than actual 1-year ODI in assessing actual 2-year ODI for all procedures ( P = 0.001) except for primary ( P = 0.932) and revision microdiscectomy ( P = 0.978) and primary laminectomy ( P = 0.267). The discordance rates of achieving or not achieving MCID for ODI ranged from 8% to 27%. Concordance rate was about 90% for primary and revision microdiscectomy. The positive and negative predictive value of 1-year ODI to predict 2-year ODI was 83% and 67% for all procedures and 92% and 67% for primary and 100% and 86% for revision microdiscectomy respectively. Conclusion. One-year disability outcomes can potentially estimate 2-year outcomes for patient populations, but cannot reliably predict 2-year outcomes for individual patients, except for patients undergoing primary and revision microdiscectomy. Level of Evidence: 4

OBJECTIVE Prospective longitudinal outcomes registries are at the center of evidence-driven health care reform. Obtaining real-world outcomes data at 12 months can be costly and challenging. In the present study, the authors analyzed whether 3-month outcome measurements sufficiently represent 12-month outcomes for patients with degenerative lumbar disease undergoing surgery. METHODS Data from 3073 patients undergoing elective spine surgery for degenerative lumbar disease were entered into a prospective multicenter registry (N2QOD). Baseline, 3-month, and 12-month follow-up Oswestry Disability Index (ODI) scores were recorded. The absolute differences between actual 12- and 3-month ODI scores was evaluated. Additionally, the authors analyzed the absolute difference between actual 12-month ODI scores and a model-predicted 12-month ODI score (the model used patients' baseline characteristics and actual 3-month scores). The minimal clinically important difference (MCID) for ODI of 12.8 points and the substantial clinical benefit (SCB) for ODI of 18.8 points were used based on the previously published values. The concordance rate of achieving MCID and SCB for ODI at 3-and 12-months was computed. RESULTS The 3-month ODI scores differed from 12-month scores by an absolute difference of 11.9 ± 10.8, and predictive modeling estimations of 12-month ODI scores differed from actual 12-month scores by a mean (± SD) of 10.7 ± 9.0 points (p = 0.001). Sixty-four percent of patients (n = 1982) achieved an MCID for ODI at 3 months in comparison with 67% of patients (n = 2088) by 12 months; 51% (n = 1731) and 61% (n = 1860) of patients achieved SCB for ODI at 3 months and 12 months, respectively. Almost 20% of patients had ODI scores that varied at least 20 points (the point span of an ODI functional category) between actual 3- and 12-month values. In the aggregate analysis of achieving MCID, 77% of patients were concordant and 23% were discordant in achieving or not achieving MCID at 3 and 12 months. The discordance rates of achieving or not achieving MCID for ODI were in the range of 19% to 27% for all diagnoses and treatments (decompression with and without fusion). The positive and negative predictive value of 3-months ODI to predict 12-month ODI was 86% and 60% for MCID and 82% and 67% for SCB. CONCLUSIONS Based on their findings, the authors conclude the following: 1) Predictive methods for functional outcome based on early patient experience (i.e., baseline and/or 3-month data) should be used to help evaluate the effectiveness of procedures in patient populations, rather than serving as a proxy for long-term individual patient experience. 2) Prospective longitudinal registries need to span at least 12 months to determine the effectiveness of spine care at the individual patient and practitioner level.