Coagulopathycontributes to 44% of subdural hematomas (SDHs) in cancer patients.1一个lthough surgical evacuation is the treatment of choice for large symptomatic SDHs, this is not feasible in cancer patients with transfusion-refractory coagulopathy owing to increased risk of postoperative hematoma expansion.2,3However, absent any intervention, a significant portion of SDHs will expand and evolve into chronic lesions.4脑膜中动脉embolization (MMAE) has recently emerged as a potential treatment of patients with chronic SDH.5通过消除血管subdu的血液供应ral membranes, this technique targets the underlying pathophysiological basis for SDH expansion and evolution. Several studies have demonstrated significantly improved rates of chronic SDH resolution and decreased recurrence after MMAE compared with surgical evacuation,6–9and this alternative treatment may be an ideal solution for this group of cancer patients with transfusion-refractory thrombocytopenia and chronic SDH. The objective of this study was to evaluate the safety and efficacy of MMAE in this particular cohort.
开云体育世界杯赔率
Patients
一个ll consecutive cases of MMAE for chronic SDH (defined as lesions with mixed hyperdense, isodense, and hypodense components on CT head), performed at Baylor College of Medicine or MD Anderson Cancer Center as a primary or rescue treatment from January 2018 to December 2020, were entered into a registry; clinical and radiographic outcomes were collected prospectively. This registry was reviewed for patients who met the following inclusion criteria: 1) diagnosis of cancer, 2) transfusion-refractory thrombocytopenia, and 3) baseline platelet count < 75 K/µl. The indications for MMAE were chronic SDH causing clinical symptoms, radiographic progression, and/or midline shift.
MMAE Procedure
VIDEO 1.Transradial approach for particle embolization of the right middle meningeal artery. Copyright Sungho Lee. Published with permission. Clickhereto view.
Embolization was considered technically successful when flow stasis was observed in all target middle meningeal artery branches.
Outcomes Assessment
The primary outcome was treatment failure, defined as radiographic increase in SDH size after MMAE. The secondary outcomes were need for surgery after MMAE, reduction in SDH size > 50%, and procedure-related complications (including new neurological deficit or evidence of new ischemic or hemorrhagic findings on postprocedural imaging). The outcomes were assessed on the basis of clinical and radiographic follow-up at 24 hours, 2 weeks, 6 weeks, and 90 days after the procedure. All patients were followed for at least 2 weeks, except for 3 patients who had earlier died of cancer-related complications.
Statistical Analysis
Statistical analyses were performed with GraphPad Prism using the D’Agostino and Pearson test to check normality, Mann-Whitney test to compare continuous variables, chi-square test to compare categorical variables, and Wilcoxon test to compare survival. The multivariable logistic regression model was created with increased or decreased SDH size as a binary outcome, with procedural indications (presence or absence of neurological deficit), type of malignancy (hematological or solid), and platelet count as dependent variables. In this study, p < 0.05 was considered significant.
Results
The characteristics of the 22 patients who underwent MMAE for SDH are summarized inTable 1. Six were female (27%), and the mean ± SD (range) age was 63.9 ± 12.3 (37–79) years. The most common primary indication for the procedure was headache, which occurred in 36% of the patients, followed by radiographic progression in 32%. Neurological deficit manifested as focal weakness in 18% of patients and altered mental status in 14%. The mean ± SD (range) platelet count was 42.1 ± 18.3 (9–74) K/µl (Supplementary Figure 1). Sixteen patients (73%) were previously diagnosed with a hematological malignancy, and the other patients had metastatic carcinoma. Four patients were receiving antiplatelet therapy prior to MMAE, which was not discontinued.
Patient characteristics
| Characteristic | Value |
|---|---|
| Sex | |
| Female | 6 (27) |
| Male | 16 (73) |
| 一个ge, yrs | 63.9 (12.3) (37–79) |
| Primary indication | |
| Headache | 8 (36) |
| Radiographic progression | 7 (32) |
| Focal weakness | 4 (18) |
| Altered mental status | 3 (14) |
| Platelet count, K/µl | 42.1 (18.3) (9–74) |
| Cancer type | |
| Hematologic | 15 (68) |
| Metastatic carcinoma | 7 (32) |
| 一个ntiplatelet therapy | 4 (18) |
Values are shown as number (percent) or mean (SD) (range).
一个total of 31 SDHs were treated in 22 patients (Table 2). Nine patients presented with bilateral SDHs, which were analyzed separately. The mean ± SD maximum width of the SDHs was 13.5 ± 4.6 mm, with midline shift of 3.9 ± 4.1 mm. Three patients (14%) underwent prior surgical evacuation.
Characteristics of SDHs treated with MMAE
| Characteristic | Value |
|---|---|
| Laterality | |
| Lt | 7 (32) |
| Rt | 6 (27) |
| Bilat | 9 (41) |
| Imaging findings | |
| 宽度,毫米 | 13.5 (4.6) (6–23) |
| Midline shift, mm | 3.9 (4.1) (0–13) |
| Previous surgery | 3 (14) |
Values are shown as number (percent) or mean (SD) (range).
一个fter MMAE, 24 of 31 SDHs (77%) regressed in size, and 15 (48%) regressed by more than 50% (Table 3,Fig. 1A and B). Two patients required surgical evacuation after MMAE: 1 patient had hematoma expansion (Fig. 1C–E), and the other had persistently altered mental status (despite improvement in SDH). In 1 patient, an unrecognized fistulous connection between the middle meningeal artery and cortical vein resulted in embolization of the cortical vein during the procedure, causing a small stroke. This was not observed with the initial external carotid or middle meningeal artery injections. Rather, this microscopic connection was visualized only after injection of the liquid embolic agent.
Outcomes after procedure
| Outcome Variable | No. (%) |
|---|---|
| SDH size | |
| Increased | 7 (23) |
| Decreased | 24 (77) |
| Reduction in size >50% | 15 (48) |
| Needed surgery | 2 (6) |
| Procedure-related complication | 1 (3) |
CT images showing presentation and treatment of cases of SDH. A patient with myelodysplastic syndrome presented with a right-sided SDH (maximum width 20 mm, midline shift 13 mm) after an assault (一个). Three months after particle and coil embolization of the right middle meningeal artery, SDH nearly resolved (B). Another patient with acute lymphoid leukemia presented with headache and was found to have bilateral SDH (maximum width 8 mm on the right side and 14 mm on the left side) (C). Six weeks after bilateral MMAE, the right-sided SDH had resolved, but the left-sided SDH had expanded with significant mass effect and required burr hole drainage (D). Four months later, the left-sided SDH had resolved (E).
Sixteen patients died between 5 and 453 days after the procedure; all patients died of complications related to their underlying cancer. The median survival of the entire cohort was 124 days. Decreased SDH size after MMAE was associated with significantly longer median survival compared with increased SDH size (185 vs 24 days, p = 0.029;Fig. 2). Four of 5 patients who died within 30 days after MMAE met the criteria for systemic inflammatory response syndrome prior to the procedure, compared with 4 of 17 patients who lived longer than 30 days (p = 0.039, chi-square test). In multivariable logistic regression analysis, presence of a neurological deficit (focal weakness or altered mental status) was significantly associated with increased risk of MMAE treatment failure (OR 8.32, 95% CI 1.2–80; p = 0.041;Table 4).
Overall survival after MMAE, according to whether SDH improved (solid line) or worsened (dotted line) (p = 0.029, Wilcoxon test).
Multivariable logistic regression estimates of the associations between clinical characteristics and MMAE treatment failure
| Clinical Characteristic | OR (95% CI) | p Value |
|---|---|---|
| Neurological deficit | 8.32 (1.2–80) | 0.041 |
| Hematologic malignancy | 0.25 (0.017–2.7) | 0.26 |
| Platelet count | 0.97 (0.89–1.0) | 0.34 |
Fourteen SDHs were treated via femoral access and 17 via radial access (Table 5). Length of procedure, technical success rate, frequency of SDH reduction, and complication rate were not significantly different between the two approaches. No patients in either group had access site–related complications.
Comparisons between patients who underwent MMAE with femoral and radial access
| Characteristic | Femoral | Radial | p Value |
|---|---|---|---|
| Total | 14 | 17 | |
| Length of procedure, mins | 78.4 ± 25.8 | 71.3 ± 16.6 | 0.52* |
| Technical success | |||
| Yes | 13 (93) | 17 (100) | 0.45† |
| No | 1 (7) | 0 (0) | |
| Complications | |||
| Yes | 0 (0) | 1 (6) | 0.99† |
| No | 14 (100) | 16 (94) | |
| SDH size | |||
| Decreased | 11 (79) | 13 (76) | 0.99† |
| Increased | 3 (21) | 4 (24) |
Values are shown as number, mean ± SD, or number (percent).
Determined with the Mann-Whitney test.
Determined with the chi-square test.
Discussion
We present the largest series of MMAE for chronic SDH in patients with refractory, cancer-related thrombocytopenia. The overall failure rate was 23%, which is significantly higher than the rates of 0%–9% reported in previous studies.6–10这不是意外由于出血素质in this group of patients. However, MMAE warrants consideration as a therapeutic option for patients with contraindications for surgical evaluation, especially given the survival benefit for patients whose SDHs decrease in size. Whether this is a truly meaningful clinical improvement needs to be examined in prospective studies with quality-of-life measures. Unfortunately, most current MMAE clinical trials excluded patients with limited life expectancy and thrombocytopenia, so efforts are currently underway at our institutions to specifically recruit these patients. The candidates will need to be screened carefully and counseled extensively in a multidisciplinary setting; in particular, neurological deficit and concurrent systemic inflammatory response syndrome were associated with poor outcomes in our analyses.
SDH occurs in approximately 2% of patients with cancer.11Coagulopathy is a major primary or contributing etiology in cancer patients, unlike patients from the general population who mostly have SDH due to trauma.1Coagulopathy in cancer patients encompasses a wide range of pathologies, including thrombocytopenia related to bone marrow suppression, immune-mediated platelet destruction, and treatment-related side effects.12Unfortunately, this type of coagulopathy is often uncorrectable, and surgical evacuation of SDH in patients with refractory coagulopathy has poor outcomes.3However, nonsurgical management is also unsatisfactory: 1 in 8 patients with conservatively managed SDH is readmitted, and half ultimately require surgery.4These findings likely reflect the formation and growth of chronic SDH.
一个fter the initial accumulation of blood in the subdural space, subsequent reactive inflammatory response and angiogenesis drive the formation of vessel-laden membranes that exude fluid and blood products, leading to the development of chronic SDH.13Histological studies have revealed that the blood supply to these membranes is derived from the middle meningeal artery.14Therefore, MMAE has emerged as a treatment option for chronic SDH. Initial efforts were directed toward its potential role as salvage therapy for recurrent chronic SDH after surgical evacuation,15,16but more recent case series have also demonstrated its efficacy as an initial therapy.10Compared with surgical evacuation, MMAE has a significantly lower recurrence rate of chronic SDH.6–9Importantly, MMAE may be the only therapeutic option for cancer patients with refractory coagulopathy, because it does not require a fully functional clotting cascade or platelets.
一个lthough MMAE is a minimally invasive procedure, the standard transfemoral approach is associated with a small but significant risk of access site complications, including pseudoaneurysm, arteriovenous fistula, and retroperitoneal hematoma.17t患者凝血病的风险较高hese complications and require prolonged groin compression and bedrest for hemostasis.18In cardiology, there has been a recent paradigm shift toward the use of the transradial approach over the transfemoral approach for coronary interventions; this is due to recent randomized controlled trials that demonstrated significantly reduced rates of access site complications with the transradial approach.19–21Similarly, the transradial approach was rapidly adopted for neurointerventional procedures, too.22For patients with refractory cancer-associated coagulopathy, the benefits of radial artery access such as avoiding the dreaded complications of groin and retroperitoneal hematomas warrant its consideration as a first option. Since adopting the radial-first approach, MMAE has been performed successfully in patients with platelet counts as low as 9 K/µl. Therefore, we do not have a strict lower limit for the platelet count. In this small study, radial and femoral interventions had comparable outcomes, and neither technique was associated with access site complications.
The main limitation of our study is the small number of patients, despite the use of data gathered from two large tertiary centers. In addition, our study was retrospective in nature and no comparisons were made with a control group. Furthermore, the interventions (choice of embolic agent, anesthesia, and access site) were left to the discretion of the treating surgeon.
Conclusions
一个lthough MMAE is an increasingly recognized technique for treating SDH, our report highlights its unique application in a group of patients without other satisfactory therapeutic options. Compared with MMAE for patients without malignancy and thrombocytopenia, the failure rate was significantly higher, and more than half the patients ultimately died of cancer-related complications. Given the relative contraindications to surgical evacuation and the survival benefit for patients with decreased SDH, we believe that MMAE warrants consideration as a therapeutic option for select patients; however, its benefits may be limited in patients with high disease burden and poor prognosis.
Disclosures
Dr. Chen is a consultant for Boston Scientific Corporation.
一个uthor Contributions
Conception and design: Kan. Acquisition of data: Kan, Srivatsan, Srinivasan, Chen, Burkhardt, Johnson, Raper. Analysis and interpretation of data: Kan, Lee, Srivatsan, Srinivasan. Drafting the article: Kan, Lee. Critically revising the article: Kan, Lee, Srivatsan, Srinivasan, Chen, Raper, Weinberg. Reviewed submitted version of manuscript: Kan, Lee, Srivatsan, Srinivasan, Chen, Burkhardt, Johnson, Weinberg. Approved the final version of the manuscript on behalf of all authors: Kan. Statistical analysis: Lee. Study supervision: Kan, Chen, Weinberg.
Supplemental Information
Videos
Video 1.https://vimeo.com/548795997.
Online-Only Content
Supplemental material is available with the online version of the article.
Supplementary Figure 1.//www.prize-show.com/doi/suppl/10.3171/2021.5.JNS21109.
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