Among patients with spondylolisthesis and lumbar spinal stenosis, laminectomy with fusion was associated with modestly greater improvement in physical health–related quality of life than laminectomy ...alone but not with significantly greater reduction in disability related to back pain.
The increased use of the lumbar spinal fusion procedure in the United States, along with the wide variation in practice, is attracting interest from multiple stakeholders, including patients, physicians, payers, and policymakers. In a report published in 2014, spinal fusion (465,000 hospital-based procedures in 2011) accounted for the highest aggregate hospital costs ($12.8 billion in 2011) of any surgical procedure performed in U.S. hospitals.
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The randomized, controlled Spine Patient Outcomes Research Trial (SPORT) showed that surgery was superior to nonoperative care for the management of lumbar degenerative spondylolisthesis.
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In SPORT, most patients in the surgical group were treated by means . . .
IMPORTANCE: Cervical spondylotic myelopathy is the most common cause of spinal cord dysfunction worldwide. It remains unknown whether a ventral or dorsal surgical approach provides the best results. ...OBJECTIVE: To determine whether a ventral surgical approach compared with a dorsal surgical approach for treatment of cervical spondylotic myelopathy improves patient-reported physical functioning at 1 year. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of patients aged 45 to 80 years with multilevel cervical spondylotic myelopathy enrolled at 15 large North American hospitals from April 1, 2014, to March 30, 2018; final follow-up was April 15, 2020. INTERVENTIONS: Patients were randomized to undergo ventral surgery (n = 63) or dorsal surgery (n = 100). Ventral surgery involved anterior cervical disk removal and instrumented fusion. Dorsal surgery involved laminectomy with instrumented fusion or open-door laminoplasty. Type of dorsal surgery (fusion or laminoplasty) was at surgeon’s discretion. MAIN OUTCOMES AND MEASURES: The primary outcome was 1-year change in the Short Form 36 physical component summary (SF-36 PCS) score (range, 0 worst to 100 best; minimum clinically important difference = 5). Secondary outcomes included 1-year change in modified Japanese Orthopaedic Association scale score, complications, work status, sagittal vertical axis, health resource utilization, and 1- and 2-year changes in the Neck Disability Index and the EuroQol 5 Dimensions score. RESULTS: Among 163 patients who were randomized (mean age, 62 years; 80 49% women), 155 (95%) completed the trial at 1 year (80% at 2 years). All patients had surgery, but 5 patients did not receive their allocated surgery (ventral: n = 1; dorsal: n = 4). One-year SF-36 PCS mean improvement was not significantly different between ventral surgery (5.9 points) and dorsal surgery (6.2 points) (estimated mean difference, 0.3; 95% CI, −2.6 to 3.1; P = .86). Of 7 prespecified secondary outcomes, 6 showed no significant difference. Rates of complications in the ventral and dorsal surgery groups, respectively, were 48% vs 24% (difference, 24%; 95% CI, 8.7%-38.5%; P = .002) and included dysphagia (41% vs 0%), new neurological deficit (2% vs 9%), reoperations (6% vs 4%), and readmissions within 30 days (0% vs 7%). CONCLUSIONS AND RELEVANCE: Among patients with cervical spondylotic myelopathy undergoing cervical spinal surgery, a ventral surgical approach did not significantly improve patient-reported physical functioning at 1 year compared with outcomes after a dorsal surgical approach. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02076113
OBJECTIVE:We pooled the results of studies on natural history of cavernous malformations (CM) to calculate point estimates and investigate main sources of heterogeneity.
METHODS:We searched MEDLINE, ...EMBASE, and ISI Web of Science for relevant studies published before May 2015. We used fixed or random effects models and meta-regression to pool the data.
RESULTS:Twenty-five studies were entered into the meta-analysis (90–1,295 patients depending on the analysis). Bleeding was defined as symptomatic hemorrhage plus radiologic evidence of hemorrhage. Sources of heterogeneity were identified as mixture of hemorrhage and rehemorrhage, mixture of rehemorrhage before and after 2 years of first bleeding, brainstem vs other locations, and calculation method. The rehemorrhage rate was higher than the hemorrhage rate (incidence rate ratio 16.5, p < 0.001, 95% confidence interval CI 9.7–28.0). Rehemorrhage within 2 years of the first hemorrhage was higher than after that (incidence rate ratio 1.8, p = 0.042, 95% CI 1.5–2.0). In two metaregression models, rough estimate of the annual incidence rate of hemorrhage was 0.3% (95% CI 0.1%–0.5%) and 2.8% (2.5%–3.3%) per person year in nonbrainstem and brainstem lesions and rough estimate of annual rehemorrhage rate per person year was 6.3% (3%–13.2%) and 32.3% (19.8%–52.7%) in nonbrainstem and brainstem lesions. Median time to rehemorrhage was 10.5 months. Posthemorrhage full recovery was 38.8%/person-year (28.7%–48.8%). Posthemorrhage full recovery or minimal disability was 79.5%/person-year (74.3%–84.8%). Mortality after bleeding was 2.2%.
CONCLUSIONS:The incidence of symptomatic hemorrhage or rehemorrhage is higher in brainstem lesions. First symptomatic hemorrhage increases the chance of symptomatic rehemorrhage, which decreases after 2 years.
Whole brain radiotherapy (WBRT) is the standard of care to improve intracranial control following resection of brain metastasis. However, stereotactic radiosurgery (SRS) to the surgical cavity is ...widely used in an attempt to reduce cognitive toxicity, despite the absence of high-level comparative data substantiating efficacy in the postoperative setting. We aimed to establish the effect of SRS on survival and cognitive outcomes compared with WBRT in patients with resected brain metastasis.
In this randomised, controlled, phase 3 trial, adult patients (aged 18 years or older) from 48 institutions in the USA and Canada with one resected brain metastasis and a resection cavity less than 5·0 cm in maximal extent were randomly assigned (1:1) to either postoperative SRS (12–20 Gy single fraction with dose determined by surgical cavity volume) or WBRT (30 Gy in ten daily fractions or 37·5 Gy in 15 daily fractions of 2·5 Gy; fractionation schedule predetermined for all patients at treating centre). We randomised patients using a dynamic allocation strategy with stratification factors of age, duration of extracranial disease control, number of brain metastases, histology, maximal resection cavity diameter, and treatment centre. Patients and investigators were not masked to treatment allocation. The co-primary endpoints were cognitive-deterioration-free survival and overall survival, and analyses were done by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT01372774.
Between Nov 10, 2011, and Nov 16, 2015, 194 patients were enrolled and randomly assigned to SRS (98 patients) or WBRT (96 patients). Median follow-up was 11·1 months (IQR 5·1–18·0). Cognitive-deterioration-free survival was longer in patients assigned to SRS (median 3·7 months 95% CI 3·45–5·06, 93 events) than in patients assigned to WBRT (median 3·0 months 2·86–3·25, 93 events; hazard ratio HR 0·47 95% CI 0·35–0·63; p<0·0001), and cognitive deterioration at 6 months was less frequent in patients who received SRS than those who received WBRT (28 52% of 54 evaluable patients assigned to SRS vs 41 85% of 48 evaluable patients assigned to WBRT; difference −33·6% 95% CI −45·3 to −21·8, p<0·00031). Median overall survival was 12·2 months (95% CI 9·7–16·0, 69 deaths) for SRS and 11·6 months (9·9–18·0, 67 deaths) for WBRT (HR 1·07 95% CI 0·76–1·50; p=0·70). The most common grade 3 or 4 adverse events reported with a relative frequency greater than 4% were hearing impairment (three 3% of 93 patients in the SRS group vs eight 9% of 92 patients in the WBRT group) and cognitive disturbance (three 3% vs five 5%). There were no treatment-related deaths.
Decline in cognitive function was more frequent with WBRT than with SRS and there was no difference in overall survival between the treatment groups. After resection of a brain metastasis, SRS radiosurgery should be considered one of the standards of care as a less toxic alternative to WBRT for this patient population.
National Cancer Institute.
IMPORTANCE: Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in ...the treatment of patients with brain metastases remains controversial. OBJECTIVE: To determine whether there is less cognitive deterioration at 3 months after SRS alone vs SRS plus WBRT. DESIGN, SETTING, AND PARTICIPANTS: At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013. INTERVENTIONS: The WBRT dose schedule was 30 Gy in 12 fractions; the SRS dose was 18 to 22 Gy in the SRS plus WBRT group and 20 to 24 Gy for SRS alone. MAIN OUTCOMES AND MEASURES: The primary end point was cognitive deterioration (decline >1 SD from baseline on at least 1 cognitive test at 3 months) in participants who completed the baseline and 3-month assessments. Secondary end points included time to intracranial failure, quality of life, functional independence, long-term cognitive status, and overall survival. RESULTS: There were 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102) with a mean age of 60.6 years (SD, 10.5 years); 103 (48%) were women. There was less cognitive deterioration at 3 months after SRS alone (40/63 patients 63.5%) than when combined with WBRT (44/48 patients 91.7%; difference, −28.2%; 90% CI, −41.9% to −14.4%; P < .001). Quality of life was higher at 3 months with SRS alone, including overall quality of life (mean change from baseline, −1.3 vs −10.9 points; mean difference, 9.6; 95% CI, 3.6-15.6 points; P = .002). Time to intracranial failure was significantly shorter for SRS alone compared with SRS plus WBRT (hazard ratio, 3.6; 95% CI, 2.2-5.9; P < .001). There was no significant difference in functional independence at 3 months between the treatment groups (mean change from baseline, −1.5 points for SRS alone vs −4.2 points for SRS plus WBRT; mean difference, 2.7 points; 95% CI, −2.0 to 7.4 points; P = .26). Median overall survival was 10.4 months for SRS alone and 7.4 months for SRS plus WBRT (hazard ratio, 1.02; 95% CI, 0.75-1.38; P = .92). For long-term survivors, the incidence of cognitive deterioration was less after SRS alone at 3 months (5/11 45.5% vs 16/17 94.1%; difference, −48.7%; 95% CI, −87.6% to −9.7%; P = .007) and at 12 months (6/10 60% vs 17/18 94.4%; difference, −34.4%; 95% CI, −74.4% to 5.5%; P = .04). CONCLUSIONS AND RELEVANCE: Among patients with 1 to 3 brain metastases, the use of SRS alone, compared with SRS combined with WBRT, resulted in less cognitive deterioration at 3 months. In the absence of a difference in overall survival, these findings suggest that for patients with 1 to 3 brain metastases amenable to radiosurgery, SRS alone may be a preferred strategy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00377156
Papillary craniopharyngiomas (PCPs) are characterized by the presence of BRAF V600E mutations, which are emerging as a useful guide for diagnosis and treatment decision making. The ongoing ...multicenter phase 2 Alliance A071601 trial is evaluating the efficacy of BRAF and mitogen‐activated protein kinase kinase (MEK) inhibitors for patients with PCPs. With continued successful responses, it is proposed that BRAF (and MEK) inhibitors be evaluated for the neoadjuvant treatment of patients with PCPs.
We recently reported that BRAF V600E is the principal oncogenic driver of papillary craniopharyngioma, a highly morbid intracranial tumor commonly refractory to treatment. Here, we describe our ...treatment of a man age 39 years with multiply recurrent BRAF V600E craniopharyngioma using dabrafenib (150mg, orally twice daily) and trametinib (2mg, orally twice daily). After 35 days of treatment, tumor volume was reduced by 85%. Mutations that commonly mediate resistance to MAPK pathway inhibition were not detected in a post-treatment sample by whole exome sequencing. A blood-based BRAF V600E assay detected circulating BRAF V600E in the patient's blood. Re-evaluation of the existing management paradigms for craniopharyngioma is warranted, as patient morbidity might be reduced by noninvasive mutation testing and neoadjuvant-targeted treatment.
After determining that vascular endothelial growth factor (VEGF) was expressed in vestibular schwannomas, the investigators administered bevacizumab, an anti-VEGF monoclonal antibody, to 10 ...consecutive patients who had neurofibromatosis 2 and vestibular schwannomas. Some patients had a reduction in tumor volume and improvement in hearing.
The investigators administered bevacizumab, an anti-VEGF monoclonal antibody, to 10 consecutive patients who had neurofibromatosis type 2 and vestibular schwannomas. Some patients had a reduction in tumor volume and improvement in hearing.
Neurofibromatosis type 2 is a dominantly inherited genetic condition with a birth prevalence of 1 in 25,000.
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Bilateral vestibular schwannomas (also known as acoustic neuromas), which are benign tumors composed of neoplastic Schwann cells that arise from the eighth cranial nerve, are the hallmark of neurofibromatosis 2. These tumors cause progressive hearing loss in most patients with neurofibromatosis type 2, who commonly lose all functional hearing during early adulthood or middle age. Standard therapy for growing sporadic, unilateral vestibular schwannomas includes surgical removal or radiation therapy. Both treatments usually achieve tumor control, but at the frequent cost of hearing loss . . .
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