Application of the AHA-Proposed Cancer-Related Ischemic Stroke Classification: Reclassification and Prognostic Impact

Q: What are the key findings of this study?

Patients classified with cancer-related ischemic stroke had significantly worse 3-month survival (37.5%) compared to those with conventional etiologies (86.2%) or cryptogenic stroke (89.2%).

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Acute ischemic stroke and active cancer (n=132). Intervention: Cancer-Related Ischemic Stroke (CRIS) classification vs. Conventional stroke etiologies and cryptogenic stroke. Primary outcome: 3-month survival rate (p=<0.001).

Q: What does this research mean for the field?

The AHA-proposed cancer-related ischemic stroke (CRIS) classification reduces the proportion of strokes categorized as cryptogenic and effectively identifies a patient subgroup with markedly worse survival outcomes. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To evaluate the clinical and prognostic utility of the American Heart Association's proposed cancer-related ischemic stroke (CRIS) etiological classification compared to the standard TOAST system.

Yasufumi Gon; Tomohiro Kawano; Hiroshi Yamagami; Tsutomu Sasaki; Manabu Sakaguchi

doi:10.1161/strokeaha.126.055707

June 3, 2026StrokeOpen Access

Application of the AHA-Proposed Cancer-Related Ischemic Stroke Classification: Reclassification and Prognostic Impact

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Key result

Cancer-related ischemic stroke is linked to markedly lower 3-month survival at ~38% vs. noncancer etiologies.

P<0.001
n=132

Figures

Why the study?

Ischemic stroke in active cancer is heterogeneous and often classified as cryptogenic under TOAST, prompting evaluation of the clinical and prognostic implications of the AHA-proposed CRIS classification.

Does the AHA-proposed cancer-related ischemic stroke (CRIS) classification improve prognostic stratification for survival in patients with acute ischemic stroke and active cancer?

Key Points

To evaluate the clinical and prognostic utility of the American Heart Association's proposed cancer-related ischemic stroke (CRIS) etiological classification compared to the standard TOAST system.
Analyzed 132 patients (median age 75 years; 37.9% female) with acute ischemic stroke and active cancer with available D-dimer data from the prospective multicenter SCAN study in Japan.
Reclassified stroke etiologies initially categorized by TOAST criteria into the CRIS framework (probable or possible CRIS).
Evaluated 1-year survival differences across stroke categories using Kaplan-Meier survival curves and log-rank tests.
Reclassification shifted 46 patients previously diagnosed with cryptogenic stroke and 2 with other determined causes (due to DIC) into the CRIS category (48 total: 6 probable, 42 possible), reducing cryptogenic stroke from 49.2% (65/132) to 14.4% (19/132).
Patients classified as CRIS had significantly worse 1-year survival compared to conventional etiologies and cryptogenic stroke (global log-rank, P <0.001).
The 3-month survival rate was 37.5% (95% CI, 26.0%–54.0%) in the CRIS group compared to 89.2% (95% CI, 76.0%–100.0%) in the reclassified cryptogenic stroke group and 86.2% (95% CI, 78.2%–95.0%) in conventional causes.

Study Design

Type

Observational (n=132)

Multicenter

Yes

Structured PICO

Does the AHA-proposed cancer-related ischemic stroke (CRIS) classification improve prognostic stratification for survival in patients with acute ischemic stroke and active cancer?

P

Population

132 adults with acute ischemic stroke and active cancer were followed for 1 year to evaluate the prognostic utility of the American Heart Association cancer-related ischemic stroke classification.

E

Exposure

Reclassification of stroke etiology using the AHA-proposed cancer-related ischemic stroke (CRIS) classification framework

C

Comparator

Original TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification criteria

O

Outcome

1-year survival after stroke onsethard clinical

Main Result

Absolute Event Rate: 37.5% vs 89.2%

p-value: p=<0.001

Applying the AHA-proposed CRIS classification to patients with active cancer and acute ischemic stroke successfully reclassifies a large proportion of cryptogenic strokes, identifying a high-risk subgroup with markedly worse survival.

Limitations

Retrospective analysis of a prospective registry, which led to missing variables required for full classification (e.g., DIC diagnosis, susceptibility vessel sign)
Relatively small sample size after subgroup stratification limits statistical power
Patients were enrolled exclusively from Japanese stroke centers, limiting generalizability
Retrospective analysis of the cohort
Not all CRIS criteria were available (variables required for DIC diagnosis, locally progressive cancer, or susceptibility vessel sign were unavailable)
Relatively small sample size limiting statistical power
Generalizability may be limited as patients were enrolled exclusively from Japanese stroke centers

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Implication

CRIS classification flags high-mortality cancer-related strokes; leaves open whether it improves management over TOAST pending prospective validation.

Abstract

BACKGROUND: Ischemic stroke in patients with active cancer is heterogeneous and frequently classified as cryptogenic under the TOAST classification (Trial of Org 10172 in Acute Stroke Treatment). The American Heart Association recently proposed an etiological classification for cancer-related ischemic stroke (CRIS). This study aimed to evaluate its clinical and prognostic implications. METHODS: We analyzed data from the prospective SCAN study (Ischemic Stroke in Patients With Cancer and Neoplasia), which enrolled patients with acute ischemic stroke and active cancer in Japan. Among the registered patients, those with available D-dimer data were included in the analysis. Stroke subtypes initially classified according to the TOAST criteria were reclassified using the CRIS framework. Kaplan-Meier survival curves were constructed, and differences were assessed using the log-rank test. RESULTS: Of 135 enrolled patients, 132 (median age, 75; 37.9% female) were included. Under the TOAST classification, 9 patients had small vessel occlusion, 20 large artery atherosclerosis, 28 cardioembolism, 10 other determined cause, and 65 cryptogenic strokes. After reclassification, 2 patients originally categorized as other determined etiology due to disseminated intravascular coagulation, and 46 patients previously classified as cryptogenic stroke were reclassified as CRIS. Patients classified as CRIS demonstrated significantly worse 1-year survival than those classified as conventional etiologies or cryptogenic stroke (global log-rank, P <0.001). The 3-month survival rate was 37.5% in the CRIS group and 89.2% in the reclassified cryptogenic stroke group. CONCLUSIONS: The newly proposed CRIS classification reduced the proportion of cryptogenic strokes under the TOAST system and enabled prognostic stratification by identifying a subgroup with markedly worse outcomes.

Discussion

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Cite This Study

Gon et al. (2026) conducted an observational in Acute ischemic stroke and active cancer (n=132). Cancer-Related Ischemic Stroke (CRIS) classification vs. Conventional stroke etiologies and cryptogenic stroke was evaluated on 3-month survival rate (p=<0.001). Patients classified with cancer-related ischemic stroke had significantly worse 3-month survival (37.5%) compared to those with conventional etiologies (86.2%) or cryptogenic stroke (89.2%).

synapsesocial.com/papers/6a2269a2763171746d548455 https://doi.org/10.1161/strokeaha.126.055707

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Application of the AHA-Proposed Cancer-Related Ischemic Stroke Classification: Reclassification and Prognostic Impact

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Application of the AHA-Proposed Cancer-Related Ischemic Stroke Classification: Reclassification and Prognostic Impact

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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