External generalisability of detection rates of 18F-FDG-PET for occult malignancy in embolic stroke of undetermined source

External generalisability of detection rates of 18F-FDG-PET for occult malignancy in embolic stroke of undetermined source | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report External generalisability of detection rates of 18F-FDG-PET for occult malignancy in embolic stroke of undetermined source Darshan Shrestha, Jamie Bellinge, Sandy Patel, Rudy Goh, Amy Weber, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8572058/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: In embolic stroke of undetermined source (ESUS) 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET) may have a role in detecting several conditions, including malignancies. Currently, there are limited data and no guidelines to inform the use of 18F-FDG-PET in patients with ESUS. This study was conducted with the aim of determining which factors predict a significant abnormality on 18F-FDG-PET in patients with ESUS, to compare with existing literature from other regions. Patients and methods: This cohort study encompassed all public neurology inpatients in South Australia during a two-year period. Patients admitted with ESUS who received an 18F-FDG-PET were included in the study and underwent case note review for clinical, laboratory, and imaging features that may predict significant abnormalities on 18F-FDG-PET. Results: Of 6,786 eligible cases, 36 fulfilled inclusion criteria. In these patients, 8/36 (22.2%) had a significant abnormality on 18F-FDG-PET, all of which were malignancy. These findings informed the stroke aetiology in 7/8 (87.5%) cases. In 7/8 (87.5%) of these cases, the positive 18F-FDG-PET was preceded by alternative imaging evidence of a significant abnormality. The one case without a prior radiological abnormality was due to endometrial cancer. Of those with the three-territory sign, 75% (3/4) had a positive 18F-FDG-PET. Conversely, 90.9% (10/11) of cases with other systemic vascular events had no significant abnormalities on 18F-FDG-PET. Conclusions: In this cohort, nearly all cases with significant abnormalities detected on 18F-FDG-PET in patients with ESUS were preceded by other radiological findings suggestive of a significant abnormality. Nuclear medicine infarction aetiology cryptogenic workup Introduction In cases of embolic stroke of undetermined source (ESUS) a variety of complex diagnostic modalities may be employed to ascertain the aetiology of the ischaemic event, including 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET).While evidence exists regarding the diagnostic yield and potential indications for 18F-FDG-PET in the workup of other vascular events, such as deep vein thrombosis [1], there are currently limited data on the utility of this investigation in stroke. One recent study in a Spanish cohort revealed a detection rate of 18% for malignancy [2]. How this detection rate compares across geographic regions and healthcare systems is uncertain. There are currently no guidelines as to the use of 18F-FDG-PET in the workup of ESUS. However, at times, 18F-FDG-PET is employed in practice to screen for malignancy in the workup of ESUS. There are several diagnoses for which 18F-FDG-PET may provide uniquely useful information, revealing information that is not able to be otherwise obtained with alternative imaging modalities, in the workup of a patient with ESUS. The detection of underlying occult malignancy, as may contribute to a hypercoagulable state (Trousseau syndrome) or non-bacterial thrombotic endocarditis (NBTE, otherwise referred to as marantic endocarditis, Libman-Sacks endocarditis, and verrucous endocarditis), is perhaps the most well-known indication for 18F-FDG-PET in this cohort [3]. 18F-FDG-PET features may also predict ischaemic stroke [4]. 18F-FDG-PET can also have a role in the detection of vasculitides. The diagnosis of infective endocarditis can also be supported by 18F-FDG-PET [5], although, anecdotally, when used for such an indication, the diagnosis is typically already suspected on other grounds (such as a bacteraemia or echocardiogram findings) prior to the request for this investigation and hence is less likely to be unearthed in an ESUS workup. 18F-FDG-PET has also been investigated for high-risk features in carotid plaques in ESUS strokes [6]. Given the current paucity of data regarding the yield of 18F-FDG-PET in ESUS for the detection of occult malignancy, practice may differ significantly in the utilisation of this test. Further data would enable greater rationality in the use of this investigation. Aims This study was conducted with the aim of determining the frequency of significant abnormalities on 18F-FDG-PET in patients with ESUS. Methods Study setting and design This study encompassed all neurology inpatient services in the state of South Australia, for the financial years between 2022 and 2024. Patients were included if they were admitted under a stroke or neurology service for more than 24 hours with an ischaemic stroke, received an 18F-FDG-PET, and at the time of the 18F-FDG-PET were viewed as ESUS with respect to aetiology. Patients with a high degree of suspicion for infective endocarditis (as described in the case notes or by the presence of bacteraemia) were excluded. Data were collected via manual case note review by a consultant neurologist. All included cases had at least six months of follow-up, if possible, during which further investigations were undertaken to arrive at final diagnoses. Background details were collected from case notes including age, gender, past medical history (including the presence of known or previous cancer, active smoking, atrial fibrillation, and previous stroke), any family history of cancer, stroke characteristics (including territories affected, and recurrent ESUS), clinical features of malignancy (including weight loss), other vascular events occurring in the admission (both arterial and venous), selected laboratory tests (lactate dehydrogenase [LDH], C-reactive protein, total protein, albumin, and haemoglobin), echocardiogram findings, imaging preceding the 18F-FDG-PET, the aetiology of the stroke, and, if detected, subsequent cancer diagnosis. Statistical analysis The patients with significant abnormalities on 18F-FDG-PET were compared to those without significant abnormalities with descriptive statistics. Unpaired t-tests, Mann-Whitney U tests, and chi squared tests were also used to compare the groups as appropriate, although instances in which there were ten or fewer occurrences in the cohort were not subjected to statistical testing due to low sample size. Python and R were used to conduct analyses. Ethical approvals The Human Research Ethics Committees (HREC) of the Southern Adelaide Local Health Network and the Central Adelaide Local Health Network (reference numbers 35.22, and 14750/16860 respectively) provided ethics approval for this study. Results There were 6,786 admissions in the study period, of whom 147 patients received 18F-FDG-PET. 43/147 (29.3%) had a presenting issue of ischaemic stroke, and 36 individuals were ESUS at the time of 18F-FDG-PET and thus included in the study. In this stroke cohort the median age was 71.5 years (IQR 66 to 79.5 years). The number of female patients was 21/36 (58.3%). Overall, there were 8/36 (22.2%) of patients in whom the 18F-FDG-PET demonstrated a significant abnormality. The abnormalities found in these eight cases were metastatic pulmonary adenocarcinoma (2), pulmonary adenocarcinoma without metastases (2), metastatic breast cancer, adenocarcinoma of uncertain primary, metastatic pancreatic adenocarcinoma, and endometrial carcinoma. The characteristics of those with and without abnormal 18F-FDG-PET are summarised in Table 1 . When considering only those patients who had a positive PET, several factors supported the likelihood of a positive PET. Those with a prior scan supporting the presence of malignancy had a higher probability of abnormal PET, accounting for 7/8 (87.5%) of the positive PET cases (see Table 2 ). In other words, only one patient had a positive PET when there was no evidence of a significant abnormality on prior imaging. The single case that did not have prior imaging suggestive of malignancy was ultimately diagnosed with endometrial carcinoma following the PET. Additionally, there were significantly more patients in the group with a positive PET that had a multi-territory stroke than in those who had a PET without significant abnormalities, including 3/4 (75%) of patients with the three-territory sign who had an abnormal PET [ 7 ]. Conversely, patients with non-neurological systemic vascular events predominantly had PETs without significant abnormalities (10/11, 90.9%). In terms of the diagnoses reached, the aetiologies of the strokes in those with a positive PET, malignancy was a contributing cause in 7/8 (87.5%) of the cases. There were 3/8 (37.5%) cases with malignancy-associated hypercoagulability, 3/8 (37.5%) cases with NBTE, and one case with leptomeningeal carcinomatosis. There was one case in which the malignancy was considered incidental. Discussion These results have shown that approximately one quarter of 18F-FDG-PET performed for patients with ESUS returns with significant abnormalities, but that nearly all of these positive scans were preceded by other imaging abnormalities. The only case in which there was not a preceding radiological abnormality was an instance of endometrial cancer, which may have been detected should an alternative prior imaging modality have been employed (e.g., pelvic ultrasound scan). Both our statewide retrospective ESUS cohort and García-Cabo et al. address the same practical question – what is the real-world yield of whole-body 18F-FDG-PET/CT for occult malignancy in cryptogenic/ESUS stroke? Reassuringly, the cancer detection rates are similar (22.2% and 18.8%) [ 2 ]. The main differences between the studies are in how patient selection is operationalised: García-Cabo et al. conducted a single-centre study with 18F-FDG-PET within the first month after discharge, whereas the present study focussed on inpatient 18F-FDG-PET in a statewide cohort. Further complementing the findings of the García-Cabo et al. study, we describe the three-territory pattern as a significant predictor of positive 18F-FDG-PET, which may be additive to the coagulation study-based methods of patient selection describe in the Spanish cohort. These findings demonstrate that malignancy remains an important consideration in the ESUS workup, but that in most instances, imaging approaches other than PET elicit these abnormalities. Although the study is limited by sample size, the findings also highlight the importance of considering pelvic ultrasound as a component of the workup for ESUS, prior to PET when appropriate. Despite this study's limitations, the findings are, to an extent, reassuring regarding concerns about radiologically occult malignancies detectable only by PET in ESUS patients. When interpreting these findings, although the study included two years of data from all neurology and stroke inpatients for an entire state, the absolute numbers of patients with positive PETs remains low. In addition, theoretically, it is not possible to definitively declare that none of the patients who did not receive PET did not have a malignancy that may have otherwise been detected. In other words, this study reflects the selection practices of the neurologists of the region. Further studies from diverse cohorts would be useful. It is noteworthy that there are malignancies that can be occult on PET, such as bladder cancer. Furthermore, PET in patients with radiological features suggestive of malignancy (as opposed to searching for occult malignancy) can play several important roles, such as assisting with staging and identifying sites for biopsy. Conclusions In a two-year statewide cohort, nearly all cases of significant abnormalities detected on 18F-FDG-PET in patients with ESUS were preceded by other radiological findings suggestive of a significant abnormality. The abnormalities detected on 18F-FDG-PET in the ESUS cohort were all malignancies, to which the stroke was usually attributable. Further studies evaluating the rational use of 18F-FDG-PET in the workup of ESUS in diverse populations would be useful. Declarations Funding Declaration: Stephen Bacchi and Jamie Bellinge are supported by Fulbright Scholarships and Royal Australasian College of Physicians Research Establishment Fellowships. The study itself received no direct funding however. Conflict of interest: The authors declare that there is no conflict of interest. Data Availability declaration: The patient data detailed in this case report are not publicly available due to privacy reasons but are available from the corresponding author upon reasonable request. Ethics approval declaration: The Human Research Ethics Committees (HREC) of the Southern Adelaide Local Health Network and the Central Adelaide Local Health Network (reference numbers 35.22, and 14750/16860 respectively) provided ethics approval for this study. Human Ethics and Consent to Participate declarations: Individual patient consent was not required, as the study was deemed low risk and retrospective in nature, with no impact on patient treatment. Ethics approval for this approach was granted by the Human Research Ethics Committee without individual patient consent. Author contribution declaration: DS contributed to data acquisition and case identification. JB contributed to study conception and critical manuscript revision. SP , RG , and AW contributed to data collection and verification of clinical and imaging data. MC contributed to manuscript drafting, interpretation of results, and served as corresponding author. SB contributed to study conception, senior supervision, and critical revision of the manuscript. AI Disclosure: GPT5 was used to assist with manuscript preparation to improve clarity and communication. References Robin P, Kumar S, Salaun PY, Le Roux PY, Couturaud F, Planquette B, et al. In patients with unprovoked VTE, does the addition of FDG PET/CT to a limited occult cancer screening strategy offer good value for money? A cost-effectiveness analysis from the publicly funded health care systems. Thromb Res. 2018;171:97-102. doi:10.1016/j.thromres.2018.09.050. Garcia-Cabo C, Benavente L, Del Amor B, Vigil C, Sancho SN, Rico M, et al. Detection rate of FDG-PET/CT for occult cancer in patients with cryptogenic ischemic stroke. Eur J Nucl Med Mol Imaging. 2025. doi:10.1007/s00259-025-07558-8. Rioux B, Keezer M, Gioia L. Case report: Diagnosis of Occult Cancer in Acute Ischemic Stroke Using Positron Emission Tomography Combined with Computed Tomography. Neurology. 2020. doi:https://doi.org/10.1212/WNL.94.15_supplement.578. Kim J, Choi KH, Song HC, Kim JT, Park MS, Cho KH. (18)F-FDG PET/CT imaging factors that predict ischaemic stroke in cancer patients. Eur J Nucl Med Mol Imaging. 2016;43:2228-35. doi:10.1007/s00259-016-3460-z. Van Riet J, Hill EE, Gheysens O, Dymarkowski S, Herregods MC, Herijgers P, et al. (18)F-FDG PET/CT for early detection of embolism and metastatic infection in patients with infective endocarditis. Eur J Nucl Med Mol Imaging. 2010;37:1189-97. doi:10.1007/s00259-010-1380-x. Hyafil F, Schindler A, Sepp D, Obenhuber T, Bayer-Karpinska A, Boeckh-Behrens T, et al. High-risk plaque features can be detected in non-stenotic carotid plaques of patients with ischaemic stroke classified as cryptogenic using combined (18)F-FDG PET/MR imaging. Eur J Nucl Med Mol Imaging. 2016;43:270-9. doi:10.1007/s00259-015-3201-8. Nouh AM, Staff I, Finelli PF. Three Territory Sign: An MRI marker of malignancy-related ischemic stroke (Trousseau syndrome). Neurol Clin Pract. 2019;9:124-8. doi:10.1212/CPJ.0000000000000603. Tables Table 1 – Factors associated with significant abnormality on 18F-FDG-PET Variable No significant abnormalities on PET (n=28) Significant abnormality on PET (n=8) P value Age mean (SD) 71.4 (13.5) 71.6 (7.1) 0.96 Female number (%) 16 (57.1) 5 (62.5) 1.00 Past medical history of cancer number (%) 6 (21.4) 4 (50.0) - Past medical history of active cancer (%) 0 (0.0) 2 (25.0) - Active smoker number (%) 5 (17.9) 2 (25.0) - Multi-territory stroke number (%) 8 (28.6) 6 (75.0) 0.049 Three territory sign number (%) 1 (3.6) 3 (37.5) - Recurrent ESUS number (%) 2 (7.1) 1 (12.5) - Clinical features of malignancy number (%) 2 (7.1) 1 (12.5) - Imaging before PET suggestive of malignancy number (%) 4 (14.3) 7 (87.5) < 0.01 Systemic vascular events number (%) 10 (35.7) 1 (12.5) 0.41 Lactate dehydrogenase median (IQR) 231.5 (194.0 to 331.5) 286.5 (227.0 to 411.2) 0.30 C-reactive protein median (IQR) 0.9 (0.0 to 8.6) 1.0 (0.0 to 2.5) 0.98 Total protein median (IQR) 71.0 (65.0 to 72.0) 66.5 (61.0 to 72.8) 0.51 Albumin median (IQR) 33.0 (30.8 to 36.2) 35.5 (31.0 to 40.2) 0.35 Haemoglobin median (IQR) 132.5 (119.0 to 144.2) 117.5 (107.8 to 142.0) 0.37 Table 2 – Radiological findings first suggestive of abnormality that preceded PET Imaging modality Radiological abnormality CT stroke sequence Lymphadenopathy CXR, performed for viral respiratory symptoms Hilar enlargement CT stroke sequence Metastatic skull lesion identified CT stroke sequence Lymphadenopathy CT abdomen/pelvis, performed for abdominal pain Pancreatic lesion CT chest, performed for previous cancer Lung lesion CXR, performed seeking possible source of infection Lung lesion Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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of this investigation in stroke. One recent study in a Spanish cohort revealed a detection rate of 18% for malignancy [2]. How this detection rate compares across geographic regions and healthcare systems is uncertain. There are currently no guidelines as to the use of 18F-FDG-PET in the workup of ESUS. However, at times, 18F-FDG-PET is employed in practice to screen for malignancy in the workup of ESUS.\u003c/p\u003e\n\u003cp\u003eThere are several diagnoses for which 18F-FDG-PET may provide uniquely useful information, revealing information that is not able to be otherwise obtained with alternative imaging modalities, in the workup of a patient with ESUS. The detection of underlying occult malignancy, as may contribute to a hypercoagulable state (Trousseau syndrome) or non-bacterial thrombotic endocarditis (NBTE, otherwise referred to as marantic endocarditis, Libman-Sacks endocarditis, and verrucous endocarditis), is perhaps the most well-known indication for 18F-FDG-PET in this cohort [3]. 18F-FDG-PET features may also predict ischaemic stroke [4]. 18F-FDG-PET can also have a role in the detection of vasculitides. The diagnosis of infective endocarditis can also be supported by 18F-FDG-PET [5], although, anecdotally, when used for such an indication, the diagnosis is typically already suspected on other grounds (such as a bacteraemia or echocardiogram findings) prior to the request for this investigation and hence is less likely to be unearthed in an ESUS workup. 18F-FDG-PET has also been investigated for high-risk features in carotid plaques in ESUS strokes [6].\u003c/p\u003e\n\u003cp\u003eGiven the current paucity of data regarding the yield of 18F-FDG-PET in ESUS for the detection of occult malignancy, practice may differ significantly in the utilisation of this test. Further data would enable greater rationality in the use of this investigation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAims\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted with the aim of determining the frequency of significant abnormalities on 18F-FDG-PET in patients with ESUS.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cu\u003eStudy setting and design\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThis study encompassed all neurology inpatient services in the state of South Australia, for the financial years between 2022 and 2024. Patients were included if they were admitted under a stroke or neurology service for more than 24 hours with an ischaemic stroke, received an 18F-FDG-PET, and at the time of the 18F-FDG-PET were viewed as ESUS with respect to aetiology. Patients with a high degree of suspicion for infective endocarditis (as described in the case notes or by the presence of bacteraemia) were excluded.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData were collected via manual case note review by a consultant neurologist. All included cases had at least six months of follow-up, if possible, during which further investigations were undertaken to arrive at final diagnoses. Background details were collected from case notes including age, gender, past medical history (including the presence of known or previous cancer, active smoking, atrial fibrillation, and previous stroke), any family history of cancer, stroke characteristics (including territories affected, and recurrent ESUS), clinical features of malignancy (including weight loss), other vascular events occurring in the admission (both arterial and venous), selected laboratory tests (lactate dehydrogenase [LDH], C-reactive protein, total protein, albumin, and haemoglobin), echocardiogram findings, imaging preceding the 18F-FDG-PET, \u0026nbsp;the aetiology of the stroke, and, if detected, subsequent cancer diagnosis.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eStatistical analysis\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe patients with significant abnormalities on 18F-FDG-PET were compared to those without significant abnormalities with descriptive statistics. Unpaired t-tests, Mann-Whitney U tests, and chi squared tests were also used to compare the groups as appropriate, although instances in which there were ten or fewer occurrences in the cohort were not subjected to statistical testing due to low sample size. Python and R were used to conduct analyses.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eEthical approvals\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe Human Research Ethics Committees (HREC) of the Southern Adelaide Local Health Network and the Central Adelaide Local Health Network (reference numbers 35.22, and 14750/16860 respectively) provided ethics approval for this study.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThere were 6,786 admissions in the study period, of whom 147 patients received 18F-FDG-PET. 43/147 (29.3%) had a presenting issue of ischaemic stroke, and 36 individuals were ESUS at the time of 18F-FDG-PET and thus included in the study. In this stroke cohort the median age was 71.5 years (IQR 66 to 79.5 years). The number of female patients was 21/36 (58.3%).\u003c/p\u003e \u003cp\u003eOverall, there were 8/36 (22.2%) of patients in whom the 18F-FDG-PET demonstrated a significant abnormality. The abnormalities found in these eight cases were metastatic pulmonary adenocarcinoma (2), pulmonary adenocarcinoma without metastases (2), metastatic breast cancer, adenocarcinoma of uncertain primary, metastatic pancreatic adenocarcinoma, and endometrial carcinoma. The characteristics of those with and without abnormal 18F-FDG-PET are summarised in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eWhen considering only those patients who had a positive PET, several factors supported the likelihood of a positive PET. Those with a prior scan supporting the presence of malignancy had a higher probability of abnormal PET, accounting for 7/8 (87.5%) of the positive PET cases (see Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In other words, only one patient had a positive PET when there was no evidence of a significant abnormality on prior imaging. The single case that did not have prior imaging suggestive of malignancy was ultimately diagnosed with endometrial carcinoma following the PET. Additionally, there were significantly more patients in the group with a positive PET that had a multi-territory stroke than in those who had a PET without significant abnormalities, including 3/4 (75%) of patients with the three-territory sign who had an abnormal PET [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Conversely, patients with non-neurological systemic vascular events predominantly had PETs without significant abnormalities (10/11, 90.9%).\u003c/p\u003e \u003cp\u003eIn terms of the diagnoses reached, the aetiologies of the strokes in those with a positive PET, malignancy was a contributing cause in 7/8 (87.5%) of the cases. There were 3/8 (37.5%) cases with malignancy-associated hypercoagulability, 3/8 (37.5%) cases with NBTE, and one case with leptomeningeal carcinomatosis. There was one case in which the malignancy was considered incidental.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThese results have shown that approximately one quarter of 18F-FDG-PET performed for patients with ESUS returns with significant abnormalities, but that nearly all of these positive scans were preceded by other imaging abnormalities. The only case in which there was not a preceding radiological abnormality was an instance of endometrial cancer, which may have been detected should an alternative prior imaging modality have been employed (e.g., pelvic ultrasound scan).\u003c/p\u003e \u003cp\u003eBoth our statewide retrospective ESUS cohort and Garc\u0026iacute;a-Cabo et al. address the same practical question \u0026ndash; what is the real-world yield of whole-body 18F-FDG-PET/CT for occult malignancy in cryptogenic/ESUS stroke? Reassuringly, the cancer detection rates are similar (22.2% and 18.8%) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The main differences between the studies are in how patient selection is operationalised: Garc\u0026iacute;a-Cabo et al. conducted a single-centre study with 18F-FDG-PET within the first month after discharge, whereas the present study focussed on inpatient 18F-FDG-PET in a statewide cohort. Further complementing the findings of the Garc\u0026iacute;a-Cabo et al. study, we describe the three-territory pattern as a significant predictor of positive 18F-FDG-PET, which may be additive to the coagulation study-based methods of patient selection describe in the Spanish cohort.\u003c/p\u003e \u003cp\u003eThese findings demonstrate that malignancy remains an important consideration in the ESUS workup, but that in most instances, imaging approaches other than PET elicit these abnormalities. Although the study is limited by sample size, the findings also highlight the importance of considering pelvic ultrasound as a component of the workup for ESUS, prior to PET when appropriate. Despite this study's limitations, the findings are, to an extent, reassuring regarding concerns about radiologically occult malignancies detectable only by PET in ESUS patients.\u003c/p\u003e \u003cp\u003eWhen interpreting these findings, although the study included two years of data from all neurology and stroke inpatients for an entire state, the absolute numbers of patients with positive PETs remains low. In addition, theoretically, it is not possible to definitively declare that none of the patients who did \u003cem\u003enot\u003c/em\u003e receive PET did not have a malignancy that may have otherwise been detected. In other words, this study reflects the selection practices of the neurologists of the region. Further studies from diverse cohorts would be useful. It is noteworthy that there are malignancies that can be occult on PET, such as bladder cancer. Furthermore, PET in patients with radiological features suggestive of malignancy (as opposed to searching for occult malignancy) can play several important roles, such as assisting with staging and identifying sites for biopsy.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn a two-year statewide cohort, nearly all cases of significant abnormalities detected on 18F-FDG-PET in patients with ESUS were preceded by other radiological findings suggestive of a significant abnormality. The abnormalities detected on 18F-FDG-PET in the ESUS cohort were all malignancies, to which the stroke was usually attributable. Further studies evaluating the rational use of 18F-FDG-PET in the workup of ESUS in diverse populations would be useful.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding Declaration:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Stephen Bacchi and Jamie Bellinge are supported by Fulbright Scholarships and Royal Australasian College of Physicians Research Establishment Fellowships. The study itself received no direct funding however.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors declare that there is no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability declaration:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient data detailed in this case report are not publicly available due to privacy reasons but are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval declaration:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Human Research Ethics Committees (HREC) of the Southern Adelaide Local Health Network and the Central Adelaide Local Health Network (reference numbers 35.22, and 14750/16860 respectively) provided ethics approval for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate declarations:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIndividual patient consent was not required, as the study was deemed low risk and retrospective in nature, with no impact on patient treatment. Ethics approval for this approach was granted by the Human Research Ethics Committee without individual patient consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution declaration:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDS\u003c/strong\u003e contributed to data acquisition and case identification.\u003cbr\u003e\u003cstrong\u003eJB\u003c/strong\u003e contributed to study conception and critical manuscript revision.\u003cbr\u003e\u003cstrong\u003eSP\u003c/strong\u003e, \u003cstrong\u003eRG\u003c/strong\u003e, and\u0026nbsp;\u003cstrong\u003eAW\u003c/strong\u003e contributed to data collection and verification of clinical and imaging data.\u003cbr\u003e\u003cstrong\u003eMC\u003c/strong\u003e contributed to manuscript drafting, interpretation of results, and served as corresponding author.\u003cbr\u003e\u003cstrong\u003eSB\u003c/strong\u003e contributed to study conception, senior supervision, and critical revision of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAI Disclosure:\u003c/strong\u003e GPT5 was used to assist with manuscript preparation to improve clarity and communication.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRobin P, Kumar S, Salaun PY, Le Roux PY, Couturaud F, Planquette B, et al. In patients with unprovoked VTE, does the addition of FDG PET/CT to a limited occult cancer screening strategy offer good value for money? A cost-effectiveness analysis from the publicly funded health care systems. Thromb Res. 2018;171:97-102. doi:10.1016/j.thromres.2018.09.050.\u003c/li\u003e\n\u003cli\u003eGarcia-Cabo C, Benavente L, Del Amor B, Vigil C, Sancho SN, Rico M, et al. Detection rate of FDG-PET/CT for occult cancer in patients with cryptogenic ischemic stroke. Eur J Nucl Med Mol Imaging. 2025. doi:10.1007/s00259-025-07558-8.\u003c/li\u003e\n\u003cli\u003eRioux B, Keezer M, Gioia L. Case report: Diagnosis of Occult Cancer in Acute Ischemic Stroke Using Positron Emission Tomography Combined with Computed Tomography. Neurology. 2020. doi:https://doi.org/10.1212/WNL.94.15_supplement.578.\u003c/li\u003e\n\u003cli\u003eKim J, Choi KH, Song HC, Kim JT, Park MS, Cho KH. (18)F-FDG PET/CT imaging factors that predict ischaemic stroke in cancer patients. Eur J Nucl Med Mol Imaging. 2016;43:2228-35. doi:10.1007/s00259-016-3460-z.\u003c/li\u003e\n\u003cli\u003eVan Riet J, Hill EE, Gheysens O, Dymarkowski S, Herregods MC, Herijgers P, et al. (18)F-FDG PET/CT for early detection of embolism and metastatic infection in patients with infective endocarditis. Eur J Nucl Med Mol Imaging. 2010;37:1189-97. doi:10.1007/s00259-010-1380-x.\u003c/li\u003e\n\u003cli\u003eHyafil F, Schindler A, Sepp D, Obenhuber T, Bayer-Karpinska A, Boeckh-Behrens T, et al. High-risk plaque features can be detected in non-stenotic carotid plaques of patients with ischaemic stroke classified as cryptogenic using combined (18)F-FDG PET/MR imaging. Eur J Nucl Med Mol Imaging. 2016;43:270-9. doi:10.1007/s00259-015-3201-8.\u003c/li\u003e\n\u003cli\u003eNouh AM, Staff I, Finelli PF. Three Territory Sign: An MRI marker of malignancy-related ischemic stroke (Trousseau syndrome). Neurol Clin Pract. 2019;9:124-8. doi:10.1212/CPJ.0000000000000603.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e \u0026ndash; Factors associated with significant abnormality on 18F-FDG-PET\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"601\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 264px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 147px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo significant abnormalities on PET (n=28)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 127px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSignificant abnormality on PET (n=8)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 264px;\"\u003e\n \u003cp\u003eAge mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 147px;\"\u003e\n \u003cp\u003e71.4 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 127px;\"\u003e\n \u003cp\u003e71.6 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 62px;\"\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 264px;\"\u003e\n \u003cp\u003eFemale number (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 147px;\"\u003e\n \u003cp\u003e16 (57.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 127px;\"\u003e\n \u003cp\u003e5 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 62px;\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 264px;\"\u003e\n \u003cp\u003ePast medical history of cancer number (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 147px;\"\u003e\n \u003cp\u003e6 (21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 127px;\"\u003e\n \u003cp\u003e4 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 62px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 264px;\"\u003e\n \u003cp\u003ePast medical history of active cancer (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 147px;\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 127px;\"\u003e\n \u003cp\u003e2 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 62px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 264px;\"\u003e\n \u003cp\u003eActive smoker number (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 147px;\"\u003e\n \u003cp\u003e5 (17.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 127px;\"\u003e\n \u003cp\u003e2 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 62px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 264px;\"\u003e\n \u003cp\u003eMulti-territory stroke number (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 147px;\"\u003e\n \u003cp\u003e8 (28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 127px;\"\u003e\n \u003cp\u003e6 (75.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 62px;\"\u003e\n \u003cp\u003e0.049\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 264px;\"\u003e\n \u003cp\u003eThree territory sign number (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 147px;\"\u003e\n \u003cp\u003e1 (3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 127px;\"\u003e\n \u003cp\u003e3 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 62px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 264px;\"\u003e\n \u003cp\u003eRecurrent ESUS number (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 147px;\"\u003e\n \u003cp\u003e2 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 127px;\"\u003e\n \u003cp\u003e1 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 62px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 264px;\"\u003e\n \u003cp\u003eClinical features of malignancy number (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 147px;\"\u003e\n \u003cp\u003e2 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 127px;\"\u003e\n \u003cp\u003e1 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 62px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 264px;\"\u003e\n \u003cp\u003eImaging before PET suggestive of malignancy number (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 147px;\"\u003e\n \u003cp\u003e4 (14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 127px;\"\u003e\n \u003cp\u003e7 (87.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 62px;\"\u003e\n \u003cp\u003e\u0026lt; 0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 264px;\"\u003e\n \u003cp\u003eSystemic vascular events number (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 147px;\"\u003e\n \u003cp\u003e10 (35.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 127px;\"\u003e\n \u003cp\u003e1 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 62px;\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 264px;\"\u003e\n \u003cp\u003eLactate dehydrogenase median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 147px;\"\u003e\n \u003cp\u003e231.5 (194.0 to 331.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 127px;\"\u003e\n \u003cp\u003e286.5 (227.0 to 411.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 62px;\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 264px;\"\u003e\n \u003cp\u003eC-reactive protein median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 147px;\"\u003e\n \u003cp\u003e0.9 (0.0 to 8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 127px;\"\u003e\n \u003cp\u003e1.0 (0.0 to 2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 62px;\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 264px;\"\u003e\n \u003cp\u003eTotal protein median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 147px;\"\u003e\n \u003cp\u003e71.0 (65.0 to 72.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 127px;\"\u003e\n \u003cp\u003e66.5 (61.0 to 72.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 62px;\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 264px;\"\u003e\n \u003cp\u003eAlbumin median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 147px;\"\u003e\n \u003cp\u003e33.0 (30.8 to 36.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 127px;\"\u003e\n \u003cp\u003e35.5 (31.0 to 40.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 62px;\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 264px;\"\u003e\n \u003cp\u003eHaemoglobin median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 147px;\"\u003e\n \u003cp\u003e132.5 (119.0 to 144.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 127px;\"\u003e\n \u003cp\u003e117.5 (107.8 to 142.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 62px;\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 \u0026ndash;\u0026nbsp;\u003c/strong\u003eRadiological findings \u003cem\u003efirst\u003c/em\u003e suggestive of abnormality that preceded PET\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"601\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 302px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eImaging modality\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 299px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRadiological abnormality\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 302px;\"\u003e\n \u003cp\u003eCT stroke sequence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 299px;\"\u003e\n \u003cp\u003eLymphadenopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 302px;\"\u003e\n \u003cp\u003eCXR, performed for viral respiratory symptoms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 299px;\"\u003e\n \u003cp\u003eHilar enlargement\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 302px;\"\u003e\n \u003cp\u003eCT stroke sequence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 299px;\"\u003e\n \u003cp\u003eMetastatic skull lesion identified\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 302px;\"\u003e\n \u003cp\u003eCT stroke sequence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 299px;\"\u003e\n \u003cp\u003eLymphadenopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 302px;\"\u003e\n \u003cp\u003eCT abdomen/pelvis, performed for abdominal pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 299px;\"\u003e\n \u003cp\u003ePancreatic lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 302px;\"\u003e\n \u003cp\u003eCT chest, performed for previous cancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 299px;\"\u003e\n \u003cp\u003eLung lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 302px;\"\u003e\n \u003cp\u003eCXR, performed seeking possible source of infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 299px;\"\u003e\n \u003cp\u003eLung lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Nuclear medicine, infarction, aetiology, cryptogenic, workup","lastPublishedDoi":"10.21203/rs.3.rs-8572058/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8572058/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction: \u003c/strong\u003eIn embolic stroke of undetermined source (ESUS) 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET) may have a role in detecting several conditions, including malignancies. Currently, there are limited data and no guidelines to inform the use of 18F-FDG-PET in patients with ESUS. This study was conducted with the aim of determining which factors predict a significant abnormality on 18F-FDG-PET in patients with ESUS, to compare with existing literature from other regions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatients and methods: \u003c/strong\u003eThis cohort study encompassed all public neurology inpatients in South Australia during a two-year period. Patients admitted with ESUS who received an 18F-FDG-PET were included in the study and underwent case note review for clinical, laboratory, and imaging features that may predict significant abnormalities on 18F-FDG-PET.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eOf 6,786 eligible cases, 36 fulfilled inclusion criteria. In these patients, 8/36 (22.2%) had a significant abnormality on 18F-FDG-PET, all of which were malignancy. These findings informed the stroke aetiology in 7/8 (87.5%) cases. In 7/8 (87.5%) of these cases, the positive 18F-FDG-PET was preceded by alternative imaging evidence of a significant abnormality. The one case without a prior radiological abnormality was due to endometrial cancer. Of those with the three-territory sign, 75% (3/4) had a positive 18F-FDG-PET. Conversely, 90.9% (10/11) of cases with other systemic vascular events had no significant abnormalities on 18F-FDG-PET.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eIn this cohort, nearly all cases with significant abnormalities detected on 18F-FDG-PET in patients with ESUS were preceded by other radiological findings suggestive of a significant abnormality.\u003c/p\u003e","manuscriptTitle":"External generalisability of detection rates of 18F-FDG-PET for occult malignancy in embolic stroke of undetermined source","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-19 08:36:42","doi":"10.21203/rs.3.rs-8572058/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3bd0711d-f45f-40be-bcd9-eb336a63e457","owner":[],"postedDate":"January 19th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-28T09:49:39+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-19 08:36:42","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8572058","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8572058","identity":"rs-8572058","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}