Citations

We aimed to review the molecular characteristics of metastatic melanoma and the role of surgery in metastasectomy for metastatic melanoma. We performed a systematic literature search on PubMed to identify relevant studies focusing on several mutations, including NRAS, BRAF, NF1, MITF, PTEN, TP53, CDKN2A, TERT, TMB, EGFR, and c-KIT. This was performed in the context of metastatic melanoma and the role of metastasectomy in the metastatic melanoma population. A comprehensive review of these molecular characteristics is presented with a focus on their prognosis and role in surgical metastasectomy.

Abstract Purpose: Epithelioid hemangioendothelioma (EHE) is a rare vascular cancer with pathogenic TAZ–CAMTA1 (calmodulinbinding transcription activator 1) operating as an oncogenic driver through activation of the MAPK pathway. Trametinib is an inhibitor of MEK, a critical kinase in the MAPK pathway. We sought to evaluate the effect of trametinib in patients with EHE. Patients and Methods: A phase 2 trial of trametinib was conducted in patients with locally advanced or metastatic EHE. Eligibility requirements included evidence of tumor progression or presence of EHE-related pain requiring opiates for management before enrollment. The primary endpoint was objective response rate (ORR) as per RECIST1.1 in cases with TAZ– CAMTA1 confirmed by fusion-FISH. Secondary objectives were to estimate ORR for all patients, median progression-free survival (PFS), 2-year overall survival (OS) rate, patient safety, and change in patient-reported global health and pain scores per PROMIS questionnaires. Results: 44 patients enrolled and 42 started trametinib. TAZ– CAMTA1 was detected in 27 tumor samples. TheORRwas 3.7%[95% confidence interval (CI), 0.094–19.0], median PFS was 10.4 months (95%CI, 7.1–NA), and 2-year OS rate was 33.3%(95%CI, 19.1–58.2) in the target population. Median pain intensity and interference scores improved significantly after 4 weeks of trametinib in patients using opiates. Common adverse events related to trametinib were rash, fatigue, nausea/vomiting, diarrhea/constipation, alopecia, and edema; one grade 5 ARDS/pneumonitis was related to trametinib. Conclusions: Trametinib was associated with reduction in EHE-related pain and median PFS of more than 6 months, providing palliative benefit in patients with advanced EHE, but the trial did not meet the ORR goal. See related commentary by Van Tine and Haarberg, p. 4552

Introduction The coronavirus disease 2019 (COVID‐19) pandemic has had a global impact on healthcare systems. There is limited data on the influence of COVID‐19 on treatment and outcomes in patients with intracranial aneurysms. We aimed to investigate the impact of COVID‐19 on the overall complications, including ischemic stroke and subarachnoid hemorrhage (SAH) rates in patients treated for intracranial aneurysms (IAs). Methods This national, multicenter, retrospective cohort study included patients diagnosed and treated for IAs from January 2016 to December 2020 in the National Inpatient Sample (NIS). A total of 57,715 admissions were identified. Of these, 45,979 occurred pre‐COVID and 11,736 during the COVID pandemic period. The outcome data points included the occurrence of postprocedural ischemic strokes or SAHs, death, non‐routine discharge, total charges (US dollars), and length of stay (days). A 1:1 propensity score matching protocol was applied using a K‐nearest neighbor approach to evaluate differences in the outcome data points between the pre‐COVID and during COVID periods. The trends during the study period were assessed using piecewise joinpoint regression with the Mann‐Kendall test. Results Overall, the mean age was 65 years, with most of the patients (69.9%) being females. Endovascular interventions were performed in 82.9% of pre‐COVID IAs admissions compared to 82.4% during the COVID period, while open surgical treatment was performed in 17.1% of pre‐COVID and 17.6% of the patients during COVID (p=0.625). After matching, there were no differences in length of stay (p=0.266), non‐home discharge (p=0.475), and in‐hospital mortality rates (p=0.305) between the two periods; however, the overall complication rate was significantly higher during the pandemic (31.1% vs. 28.3%; p<0.001). From 2016 to 2020, an upward trend in hospitalizations for ischemic stroke was seen among patients treated for IAs (6.1% to 7.9%; p=0.04). No trends were observed with respect to the occurrence of SAH or death (p=0.31). Patients hospitalized after treatment of IAs during the COVID pandemic had significantly higher odds of ischemic strokes (OR 1.13; 95% CI 1.05 to 1.22; p=0.03) but not SAH (OR 0.97; 95% CI 0.88 to 1.06; p=0.89). Conclusion The COVID‐19 pandemic has significantly impacted the healthcare system. In patients receiving treatment for IAs, this analysis noted a correlation between the COVID‐19 pandemic and postoperative complications, notably ischemic strokes. Unraveling the pandemic’s “black box” leads to awareness of plausible breaches within the system, which acts as a crucial component in improving situational readiness and preparedness in the event of similar large‐scale crises.

OBJECTIVE Dural arteriovenous fistulas are rare vascular malformations that affect the brain and spinal cord. Spinal dural arteriovenous fistulas (sdAVFs) are the most frequently encountered vascular malformation affecting the spinal cord. The object of this study was to evaluate the impact of treatment delays on the long-term neurological outcomes of either open surgical or interventional treatment of sdAVFs. METHODS In this retrospective, population-based cohort study, the authors examined consecutive patients with diagnosed sdAVFs at a tertiary care center between 2005 and 2020. Patients were assessed using the Aminoff-Logue disability scale (ALS) at various time points including symptom onset, primary care visit, first specialist outpatient visit, as well as both short and long-term follow-ups. The postoperative long-term ALS gait and bladder grades constituted the primary outcomes of the study. RESULTS Among the 34 patients included in the study, the median age was 65 years, and there was a male predominance (71%). Most lesions were in the lumbar region (47%). Significant worsening in ALS gait and bladder grades was observed preoperatively, followed by postoperative improvements (p < 0.05). There was no difference in outcomes between surgical and endovascular treatments. Older age (OR 1.10, 95% CI 1.03–1.17, p = 0.007), worse preoperative ALS gait grades (OR 5.12, 95% CI 2.18–12.4, p < 0.001), and longer time from first specialist outpatient visit to first treatment (OR 1.00, 95% CI 1.00–1.01, p = 0.040) were independently associated with worse long-term gait outcomes. Only the preoperative ALS bladder score was a predictor of worse long-term bladder function (OR 92.7, 95% CI 28.0–306.7, p < 0.001). CONCLUSIONS Both surgical and endovascular treatments for sdAVFs led to significant neurological improvements. However, treatment delays were associated with less favorable long-term outcomes. Prompt diagnosis and early intervention prior to symptom progression may enhance recovery and help to preserve neurological function.

Objectives To investigate the impact of the COVID-19 pandemic as well as concomitant COVID-19 itself on stroke care, focusing on middle cerebral artery (MCA) territory infarctions. Design Registry-based study. Setting We used the National Inpatient Sample (NIS) database, which covers a wide range of hospitals within the USA. Participants The NIS was queried for patients with MCA strokes between 2016 and 2020. In total, 35 231 patients were included. Outcome measures Outcome measures were postprocedural complications, length of stays (LOSs), in-hospital mortality and non-routine discharge. Propensity score matching using all available baseline variables was performed to reduce confounders when comparing patients with and without concomitant COVID-19. Results Mechanical thrombectomy (MT) was performed in 48.4%, intravenous thrombolysis (IVT) in 38.2%, and both MT and IVT (MT+IVT) in 13.4% of patients. A gradual increase in the use of MT and an opposite decrease in the use of IVT (p<0.001) was detected during the study period. Overall, 25.0% of all patients were admitted for MCA strokes during the pandemic period (2020), of these 209 (2.4%) were concomitantly diagnosed with COVID-19. Patients with MCA strokes and concomitant COVID-19 were significantly younger (64.9 vs 70.0; p<0.001), had significantly worse NIH Stroke Severity scores, and worse outcomes in terms of LOS (12.3 vs 8.2; p<0.001), in-hospital mortality (26.3% vs 9.8%; p<0.001) and non-routine discharge (84.2% vs 76.9%; p=0.013), as compared with those without COVID-19. After matching, only in-hospital mortality rates remained significantly higher in patients with COVID-19 (26.7% vs 8.5%; p<0.001). Additionally, patients with COVID-19 had higher rates of thromboembolic (12.3% vs 7.6%; p=0.035) and respiratory (11.3% vs 6.6%; p=0.029) complications. Conclusions Among patients with MCA stroke, those with concomitant COVID-19 were significantly younger and had higher stroke severity scores. They were more likely to experience thromboembolic and respiratory complications and in-hospital mortality compared with matched controls.

BACKGROUND AND OBJECTIVES: Carotid endarterectomy (CEA) is a well-established treatment option for carotid stenosis. The choice between general anesthesia (GA) and nongeneral anesthesia (non-GA) during CEA remains a subject of debate, with concerns regarding perioperative complications, particularly myocardial infarctions. This study aimed to evaluate the outcomes associated with GA vs non-GA CEA using a large, nationwide database. METHODS: The National Surgical Quality Improvement Project database was queried for patients undergoing CEA between 2013 and 2020. Primary outcome measures including surgical outcomes and 30-day postoperative complications were compared between the 2 anesthesia methods, after 2:1 propensity score matching. RESULTS: After propensity score matching, a total of 25 356 patients (16 904 in the GA and 8452 in the non-GA group) were included. Non-GA compared with GA CEA was associated with significantly shorter operative times (101.9, 95% CI: 100.5-103.3 vs 115.8 95% CI: 114.4-117.2 minutes, P < .001), reduced length of hospital stays (2.3, 95% CI: 2.15-2.4 vs 2.5, 95% CI: 2.4-2.6 days, P < .001), and lower rates of 30-day postoperative complications, including myocardial infarctions (0.8% vs 1.2%, P = .003), unplanned intubations (0.8% vs 1.1%, P = .016), pneumonia (0.5% vs 1%, P < .001), and urinary tract infections (0.4% vs 0.7%, P = .003). These outcomes were notably more pronounced in the younger (≤70 years) and high morbidity (American Society of Anesthesiologists 3-5) cohorts. CONCLUSION: In this nationwide registry-based study, non-GA CEA was associated with better short-term outcomes in terms of perioperative complications, compared with GA CEA. The findings suggest that non-GA CEA may be a safer alternative, especially in younger patients and those with more comorbidities.

Background and purpose: A bolus is required when treating scalp lesions with photon radiation therapy. Traditional bolus materials face several issues, including air gaps and setup difficulty due to irregular, convex scalp geometry. A 3D-milled bolus is custom-formed to match individual patient anatomy, allowing improved dose coverage and homogeneity. Here, we describe the creation process of a 3D-milled bolus and report the outcomes for patients with scalp malignancies treated with Volumetric Modulated Arc Therapy (VMAT) utilizing a 3D-milled bolus. Materials and methods: Twenty-two patients treated from 2016 to 2022 using a 3D-milled bolus and VMAT were included. Histologies included squamous cell carcinoma (n = 14, 64%) and angiosarcoma (n = 8, 36%). A total of 7 (32%) patients were treated in the intact and 15 (68%) in the postoperative setting. The median prescription dose was 66.0 Gy (range: 60.0–69.96). Results: The target included the entire scalp for 8 (36%) patients; in the remaining 14 (64%), the median ratio of planning target volume to scalp volume was 35% (range: 25–90%). The median dose homogeneity index was 1.07 (range: 1.03–1.15). Six (27%) patients experienced acute grade 3 dermatitis and one (5%) patient experienced late grade 3 skin ulceration. With a median follow-up of 21.4 months (range: 4.0–75.4), the 18-month rates of locoregional control and overall survival were 75% and 79%, respectively. Conclusions: To our knowledge, this is the first study to report the clinical outcomes for patients with scalp malignancies treated with the combination of VMAT and a 3D-milled bolus. This technique resulted in favorable clinical outcomes and an acceptable toxicity profile in comparison with historic controls and warrants further investigation in a larger prospective study.

Abstract Background Although typically benign, 5% of spinal meningiomas (SMs) present with higher-grade features (World Health Organization grades 2 and 3). High-grade SMs are poorly studied and the role of adjuvant radiotherapy in their management remains controversial. We hence aimed to study the demographic characteristics of this rare tumor and investigate the outcomes associated with the use of surgery with adjuvant therapy in contrast to surgery alone. Methods The National Cancer Database was queried for patients with SMs from 2004 to 2017. Basic statistics were used to identify differences between low- and high-grade tumors in terms of baseline characteristics. Surgery with and without adjuvant radiotherapy were compared after (1:1) propensity-score matching. Kaplan–Meier survival analysis was conducted to study overall survival. All analyses were performed on R. Results A total of 13 184 patients diagnosed with SMs were included, of whom only 5% (n = 669) had high-grade SMs. Patients with high-grade SMs presented at a younger median age (57 years [IQR: 44–68] versus 65 years [54–75]; P &lt; .001) and were more commonly males (33% vs 20%; P &lt; .001). After propensity-score matching, survival analysis revealed similar overall survival outcomes in patients with high-grade SM undergoing both surgery and radiotherapy as compared to those only receiving surgery (P = .19). Conclusions This study reveals major demographic differences between high- and low-grade SMs. There were no benefits associated with the use of adjuvant radiotherapy. However, due to confounding, overall survival outcomes between patients receiving surgery alone and those receiving surgery with adjuvant radiotherapy are not causally interpretable.