Mechanical thrombectomy (MT) is the standard treatment for large vessel occlusion (LVO) acute ischemic stroke. Patients with active malignancy have an increased risk of stroke but were excluded from MT trials.
We searched the National Readmission Database for LVO patients treated with MT between 2016–2018 and compared the characteristics and outcomes of cancer-free patients to those with metastatic cancer (MC). Primary outcomes were all-cause in-hospital mortality and favorable outcome, defined as a routine discharge to home (regardless of whether home services were provided or not). Multivariate regression was used to adjust for confounders.
Of 40,537 LVO patients treated with MT, 933 (2.3%) had MC diagnosis. Compared to cancer-free patients, MC patients were similar in age and stroke severity but had greater overall disease severity. Hospital complications that occurred more frequently in MC included pneumonia, sepsis, acute coronary syndrome, deep vein thrombosis, and pulmonary embolism (
LVO patients with MC have higher mortality and more infectious and thrombotic complications than cancer-free patients. MT nonetheless can result in survival with good outcome in slightly over one-third of patients.
Acute ischemic stroke (AIS) is common in patients with active malignancy, occurring in 15% of all cancer patients [
Patients with cancer tend to be excluded from receiving tissue plasminogen activator (tPA) as they carry a high risk for bleeding secondary to brain metastases, thrombocytopenia, coagulopathy, therapeutic anticoagulation, and recent surgeries [
Patients with cancer and reduced life expectancy were excluded or underrepresented from the seminal clinical trials that established the efficacy of MT for large vessel occlusion (LVO) stroke [
Our study aimed to investigate the outcomes and in-hospital complications of patients with metastatic cancer (MC) treated with MT for LVO AIS in a large, cross-sectional USA nationwide database. Our hypothesis was that thrombectomy in MC patients results in a comparable rate of discharge to home compared to cancer-free LVO patients, despite higher in-hospital mortality.
This is a retrospective cohort study using the Agency for Healthcare Cost and Utilization Project (HCUP) Nationwide Readmission Database (NRD) for the years 2016–2018 [
Our primary study population was all USA admissions for incident AIS who underwent MT during the 3-year study period. Index admission was defined as the first admission with the primary diagnosis of AIS during the study period; subsequent admissions for stroke were not included. Admissions were excluded if age was <18 years, the patient had a prior history of stroke, or the file had missing data. In the NRD, patient identifiers cannot be linked across years; hence index admissions on October 1st or beyond were excluded to allow a minimum of 3 months of follow-up. In accordance with the HCUP data user agreement, we excluded reporting any variables containing a small number of observations (≤10) that could pose a risk of personal identification or a data privacy violation.
For analysis, we divided the cohort into two groups. We selected MC as the diagnosis of interest to ensure that we would focus on a more homogeneous population of cancer patients with advanced disease. Patients with a cancer diagnosis without metastases were excluded to allow us to focus only on patients with the most severe disease. The diagnosis of interest (n=933) was patients with MC and LVO stroke who were treated with MT. This group was compared to LVO stroke cancer-free patients who were treated with MT (n=38,166). International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes were utilized to capture the diagnoses of interest, including MC (
Baseline demographic data including age and sex were collected. Race was not included as it is not available in the NRD. Baseline illness severity was determined using All Patient Refined Diagnosis Related Group (APR-DRG) subclasses. This system uses weighted diagnostic codes to capture admission diagnosis, complications, and risk of mortality at discharge, and classifies patients into four clinically meaningful severity groups ranging from 1 (mild illness) to 4 (extreme illness) [
The primary outcomes were all cause in-hospital mortality and favorable outcome, which was defined as a routine discharge to home (regardless of whether home services were provided or not). Secondary outcomes included hospital length of stay, non-home discharge (defined as non-routine discharge to a rehabilitation hospital; a short, intermediate, or long term nursing facility; or hospice), development of intracerebral hemorrhage (ICH), the need to undergo decompressive hemicraniectomy, and 90-day hospital readmission. Tertiary outcomes included the frequency of a variety of acute hospital complications, which were captured by their corresponding ICD-10 codes (
We compared MT-treated patients with MC and MT-treated cancer-free patients. Continuous variables were compared using Student’s t-test, and categorical variables were compared using the
Our analysis identified 1,056,011 eligible patients admitted for AIS during the 3-year study period, 40,537 (3.8%) of whom underwent MT (
We compared the 933 MT-treated patients with MC to 38,166 cancer-free stroke patients treated with MT (
In-hospital mortality was significantly higher in MC patients (26% vs. 14%,
To explore the independent role of MC in explaining death or discharge to a facility among MT-treated stroke patients, we created a stepwise backward multivariate logistic regression model that included demographics, MC, stroke and illness severity, and specific complications and procedures (
AIS is the second most common complication that involves the central nervous system in cancer patients, the first being cerebral metastases [
Hypercoagulability in patients with cancer is hypothesized to be due to tumor cell-derived cytokines, elevated D-dimer levels, tumor embolism, chemotherapy, as well as vascular risk factors like diabetes and hypertension [
Stroke patients with cancer are often excluded from receiving thrombolytic therapy due to concerns about brain metastasis, thrombocytopenia, coagulopathy, recent surgery, or overall poor prognosis [
The most important question addressed by our study is whether it is worthwhile and beneficial to perform MT in MC patients who experience LVO stroke, given their poor prognosis and comorbidities. The two groups were highly comparable with regard to age, sex, and stroke severity (
In-hospital death was significantly greater in the MC cohort treated with thrombectomy (26% vs. 14%). It is also notable that tracheostomy and PEG were performed significantly less frequently in MC patients, presumably due to more withholding of life sustain therapy. Despite this, the frequency of home discharge was only slightly lower in MC versus non-MC patients: 36% versus 42% overall, which translates into a 49% versus 48% rate of discharge home among those who survived their hospitalization. These encouraging results are consistent with other studies that have addressed clinical and safety outcomes in patients with AIS and active cancer after endovascular treatment. Of 2,583 stroke patients who underwent MT in the MR CLEAN registry, 4.8% had active cancer (diagnosed <12 months prior to stroke, with metastases, or under active treatment), which is comparable to the 2.3% frequency of MC that we observed [
A smaller single-center study from Korea reported a 7.1% frequency of current malignancy out of a total of 378 AIS patients treated with MT [
Our study has many limitations. First, inherent to the use of administrative databases such as the NRD, diagnostic accuracy may be affected by coding errors, the absence of detailed neurological and imaging data, and the lack of independent auditing and verification of key outcome measures. Also, temporal relationships that occur during hospitalization cannot be elucidated. Second, the NRD lacks data on stroke and medical illness severity scales, location and size of ischemic lesions, baseline or discharge destination, procedural success, timing of acute treatment, concurrent medical treatments such as anticoagulation, and long-term functional outcome. Hence, the results of our regression analysis should be interpreted with caution. Third, we could not distinguish between mortality as a result of stroke complications or from mortality due to withdrawal of care due to patients and family wishes. Fourth, our results are applicable to patients with advanced cancer with metastases, and may not accurately reflect the clinical course of stroke patients with early stage non-MC. Fifth, MC patients were less likely to undergo PEG or tracheostomy placement, which may have confounded the outcome, most likely reflecting decisions to pursue comfort care. Sixth, the NRD does not link patients identifiers across years. Seventh, in the NRD it is not possible to differentiate whether a diagnosis of MC is a new or historical diagnosis. Finally, discharge to home hospice is included under the routine discharge to home classification (inpatient hospice is in a separate category under non-routine discharge) in the NRD, which does not constitute a favorable outcome as we defined it. However, discharge to home hospice is rare in our clinical experience. Despite these limitations and lack of granularity in the NRD, administrative database studies offer strength in numbers, generalizability, and insight into real-world practices, especially for uncommon conditions in which randomized clinical trials are not practical to conduct.
In summary, MC patients with LVO stroke treated with MT are discharged home at a similar rate to cancer-free patients, suggesting that they can benefit from the procedure. Given the many limitations of an administrative database such as the NRD, this analysis should be viewed as preliminary and inconclusive. Pending the publication of more detailed prospective registries and clinical trials, our data may hopefully help clinicians, patients, and caregivers alike make more thoughtful and informed decisions regarding the risks and benefits of MT in stroke patients with MC.
Supplementary materials related to this article can be found online at
The RECORD statement: checklist of items, extended from the STROBE statement, that should be reported in observational studies using routinely collected health data*
International Classification of Disease, Tenth Revision (ICD-10) codes
Breakdown of cancer types
S.A.M. receives consulting fees from Biogen for effort as a member of the independent safety monitoring committee for the CHARM trial. The other authors have no relationships to disclose.
Dr. Aboul-Nour created the idea of the project, contributed to methodology, design, statistical planning, and manuscript writing. Dr. Maraey contributed by analyzing the NRD data, statistical planning and analysis. Dr. Jumah contributed to methodology and design, literature review, and manuscript writing. Dr. Khalil contributed by statistical planning and analysis, ICD-10 codes extractions, and revision. Dr. Elzanaty contributed by analyzing the NRD data. Dr. Elsharnoby contributed by analyzing the NRD data. Dr. Almufti, Dr. Chebl, Dr. Miller, and Dr. Mayer contributed to scientific writing and project supervision. Dr. Mayer supervised the entire project, contributed to methodology, design, statistical planning, and manuscript writing. All authors contributed to data interpretation, composition and revision of the article. The manuscript was approved by all authors.
Cascade diagram showing patient grouping. Of all acute ischemic stroke (AIS) patients who underwent thrombectomy, the primary analysis compared 933 patients with 38,166 patients with no cancer. The 1,438 patients with a cancer diagnosis but no metastases were excluded. The secondary analysis of metastatic cancer patients compared the 933 thrombectomy-treated patients with 25,731 patients treated medically for AIS.
Hospital complications, interventions, and outcomes among stroke patients treated with mechanical thrombectomy, with or without metastatic cancer
Metastatic cancer (n=933) | Cancer-free (n=38,166) | ||
---|---|---|---|
Demographics | |||
Age (yr) | 68.6±10.7 | 68.5±14.0 | 0.932 |
Female sex | 483 (52) | 19,277 (50) | 0.685 |
Disease severity | |||
APR-DRG severity=4 |
488 (52) | 14,992 (39) | <0.001 |
Severe stroke |
895 (96) | 36,121 (95) | 0.331 |
Paralysis/paresis | 813 (87) | 31,261 (82) | 0.003 |
Aphasia | 627 (67) | 26,397 (69) | 0.405 |
Cerebral edema | 204 (22) | 8,128 (21) | 0.812 |
Herniation | 64 (7) | 3,214 (8) | 0.257 |
Hospital complications | |||
Intracerebral hemorrhage | 186 (20) | 8,017 (21) | 0.605 |
Acute kidney injury | 134 (14) | 5,891 (15) | 0.367 |
Urinary tract infection | 118 (13) | 5,330 (14) | 0.446 |
Pneumonia | 125 (13) | 2,702 (7) | <0.001 |
Sepsis | 102 (11) | 1,823 (5) | <0.001 |
Deep vein thrombosis | 191 (20) | 1,735 (5) | <0.001 |
Acute coronary syndrome | 92 (10) | 1,721 (5) | <0.001 |
Pulmonary embolism | 117 (13) | 601 (2) | <0.001 |
Coagulopathy | 373 (40) | 3,456 (9) | <0.001 |
Thrombocytopenia | 155 (17) | 2,108 (6) | <0.001 |
Interventions | |||
tPA use | 120 (13) | 8,939 (23) | <0.001 |
Mechanical ventilation | 207 (22) | 9,581 (25) | 0.147 |
PEG | 43 (5) | 4,288 (11) | <0.001 |
Tracheostomy | 11 (<1) | 1,466 (4) | <0.001 |
Outcomes |
|||
In-hospital death | 247 (26) | 5,243 (14) | <0.001 |
Discharge to a facility | 352 (38) | 17,021 (45) | 0.005 |
Discharge to home | 334 (36) | 15,902 (42) | 0.014 |
LOS ≥75th percentile | 275 (29) | 11,031 (29) | 0.833 |
90-day readmission | 195 (21) | 7,486 (20) | 0.026 |
Data are mean±SD or n (%).
APR-DRG, All Patient Refined Diagnosis Related Group; tPA, tissue plasminogen activator; PEG, percutaneous endoscopic gastrostomy; LOS, length of stay.
Baseline illness severity determined using APR-DRG subclass of 4 is used as an indicator of severe illness (see Methods for more details);
Severe stroke was defined as having one or more of the following elements: paralysis/paresis, aphasia, cerebral edema, cerebral herniation, requiring mechanical ventilation, and/or coma;
Refer to Methods for definitions of poor and favorable outcome.
Multivariate logistic regression analysis comparing mechanical thrombectomy-treated stroke patients with versus without metastatic cancer
Outcome measure | Unadjusted OR | Adjusted OR |
||
---|---|---|---|---|
In-hospital mortality | 2.26 (1.81–2.83) | <0.001 | 2.83 (2.21–3.64) | <0.001 |
Death and discharge to facility | 1.28 (1.05–1.56) | 0.014 | 1.11 (0.89–1.37) | 0.343 |
Discharge to home |
1.01 (0.81–1.26) | 0.918 | 1.13 (0.89–1.44) | 0.314 |
Intracerebral hemorrhage | 0.94 (0.73–1.20) | 0.605 | 0.79 (0.60–1.02) | 0.074 |
Hemicraniectomy | 0.92 (0.13–6.46) | 0.931 | 1.11 (0.16–7.68) | 0.918 |
All-cause 90-day readmission | 1.35 (1.04–1.75) | 0.027 | 1.30 (0.99–1.71) | 0.052 |
LOS >75th percentile |
1.03 (0.81–1.31) | 0.832 | 0.93 (0.71–1.20) | 0.573 |
OR, odds ratio; LOS, length of stay; APR-DRG, All Patient Refined Diagnosis Related Group; tPA, tissue plasminogen activator.
Excluding in-hospital mortality;
75th percentile corresponds to 14 days;
Adjusted for age, sex, stroke severity, APR-DRG=4, and tPA use.
Multivariate model for prediction of death or discharge to a facility
Variable | Adjusted OR (95% CI) | |
---|---|---|
Age, per year | 1.035 (1.032–1.038) | <0.001 |
Female sex | 1.14 (1.05–1.24) | 0.001 |
Metastatic cancer | 0.96 (0.76–1.20) | 0.711 |
Severe stroke |
1.94 (1.64–2.29) | <0.001 |
Deep vein thrombosis | 1.46 (1.22–1.76) | <0.001 |
Pneumonia | 1.59 (1.34–1.91) | <0.001 |
Sepsis | 1.70 (1.36–2.13) | <0.001 |
Urinary tract infection | 1.34 (1.21–1.49) | <0.001 |
PEG | 5.63 (4.79–6.62) | <0.001 |
Tracheostomy | 7.01 (4.90–10.02) | <0.001 |
Intracerebral hemorrhage | 1.88 (1.69–2.07) | <0.001 |
Variables that were excluded from the final model due to lack of significance included acute kidney injury, pulmonary embolism, and acute coronary syndrome.
OR, odds ratio; CI, confidence interval; PEG, percutaneous endoscopic gastrostomy.
Severe stroke was defined as having one or more of the following elements: paralysis/paresis, aphasia, cerebral edema, cerebral herniation, requiring mechanical ventilation, and/or coma.