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The added value of 18F-FDG-PET/MRI to routine clinical workup when assessing the N-stage in rectal cancer
Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.ORCID iD: 0000-0003-3510-2165
2025 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
Tillägsvärdet av 18F-FDG-PET/MRI till klinisk rutinutredning för N-stadieindelning vid rektalcancer (Swedish)
Abstract [en]

Background: The evaluation of metastatic spread to locoregional lymph nodes in rectal cancer is essential for patient management. This thesis evaluated the added value of hybrid imaging using 18F-fluoro-2-deoxy-D-glucose-Positron Emission Tomography/Magnetic Resonance Imaging (FDG-PET/MRI) for nodal staging. To achieve this, we presented a method for the anatomical matching of individual mesorectal nodal structures between imaging and histopathology and evaluated the current European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus criteria for nodal staging.

Methods: Sixty-five patients (38 men, median age 70 years, interquartile range: 61–74) were consecutively included in Region Västerbotten as part of the prospective observational study RECTOPET (Rectal Cancer Trial on PET/MRI/CT). All patients had preoperative FDG-PET/CT and FDG-PET/MRI examinations, MRI of the surgical specimen, and a histopathological finding-by-finding description that facilitated anatomical matching of individual nodal structures between imaging and histopathology. Mixed-effects logistic regression models were used to evaluate the ESGAR consensus criteria for nodal staging, with histopathology as the gold standard. Additionally, the accuracy of FDG avidity (uptake above background level) and the combination of FDG avidity with ESGAR criteria (FDG-PET/MRI) for malignant nodal assessment was compared to standalone MRI.

Results: Study I described the feasibility of incorporating FDG-PET/CT and FDG-PET/MRI into the clinical workflow for patients with rectal cancer. Study II illustrated that the described methodology enabled the matching of 47% (92/197) of the mesorectal nodal structures detected at preoperative MRI; 25% (23/92) were malignant, with 48% (11/23) histopathologically verified tumour deposits. Study III demonstrated the strongest associations for nodal malignancy with a short-axis diameter of ≥ 5 mm (odds ratio [OR] 21.43; 95% confidence interval [CI] 4.13–111.29) and heterogeneous signal (OR 9.02; 95% CI 1.33–61.08). Additionally, the OR of malignant outcomes for nodes with positive ESGAR was 8.23 (95% CI 2.15–31.50), with corresponding sensitivity and specificity of 54% and 85%, respectively. In Study IV, N-staging with FDG-PET/MRI was equal to the histopathological nodal stage in 45% of the patients, compared to 37% for MRI alone. Furthermore, 75% (78/104) of the malignant nodal structures were FDG-avid, with a sensitivity of 75% and a specificity of 79% for FDG-PET.

Conclusion: The added value of FDG-PET/MRI in N-staging mainly lies in its ability to reduce the prevalence of false-negative nodes, which can be beneficial for organ preservation. 

Place, publisher, year, edition, pages
Umeå: Umeå University, 2025. , p. 58
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2355
Keywords [en]
metabolism, adenocarcinoma, rectum, staging, PET, MRI, tumour deposits, lymph nodes
National Category
Radiology and Medical Imaging
Research subject
Radiology
Identifiers
URN: urn:nbn:se:umu:diva-237427ISBN: 978-91-8070-648-3 (print)ISBN: 978-91-8070-649-0 (print)OAI: oai:DiVA.org:umu-237427DiVA, id: diva2:1950779
Public defence
2025-05-09, Betula, Medicinska Biblioteket, Norrlands Universitetssjukhus, 901 85 Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2025-04-16 Created: 2025-04-09 Last updated: 2025-04-09Bibliographically approved
List of papers
1. PET/MRI and PET/CT hybrid imaging of rectal cancer - description and initial observations from the RECTOPET (REctal Cancer trial on PET/MRI/CT) study
Open this publication in new window or tab >>PET/MRI and PET/CT hybrid imaging of rectal cancer - description and initial observations from the RECTOPET (REctal Cancer trial on PET/MRI/CT) study
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2019 (English)In: Cancer Imaging, ISSN 1740-5025, E-ISSN 1470-7330, Vol. 19, article id 52Article in journal (Refereed) Published
Abstract [en]

PurposeThe role of hybrid imaging using F-18-fluoro-2-deoxy-D-glucose positron-emission tomography (FDG-PET), computed tomography (CT) and magnetic resonance imaging (MRI) to improve preoperative evaluation of rectal cancer is largely unknown. To investigate this, the RECTOPET (REctal Cancer Trial on PET/MRI/CT) study has been launched with the aim to assess staging and restaging of primary rectal cancer. This report presents the study workflow and the initial experiences of the impact of PET/CT on staging and management of the first patients included in the RECTOPET study.MethodsThis prospective cohort study, initiated in September 2016, is actively recruiting patients from Region Vasterbotten in Sweden. This pilot study includes patients recruited and followed up until December 2017. All patients had a biopsy-verified rectal adenocarcinoma and underwent a minimum of one preoperative FDG-PET/CT and FDG-PET/MRI examination. These patients were referred to the colorectal cancer multidisciplinary team meeting at Umea University Hospital. All available data were evaluated when making management recommendations. The clinical course was noted and changes consequent to PET imaging were described; surgical specimens underwent dedicated MRI for anatomical matching between imaging and histopathology.ResultsTwenty-four patients have so far been included in the study. Four patients were deemed unresectable, while 19 patients underwent or were scheduled for surgery; one patient was enrolled in a watch-and-wait programme after restaging. Consequent to taking part in the study, two patients were upstaged to M1 disease: one patient was diagnosed with a solitary hepatic metastasis detected using PET/CT and underwent metastasectomy prior to rectal cancer surgery, while one patient with a small, but metabolically active, lung nodulus experienced no change of management. PET/MRI did not contribute to any recorded change in patient management.ConclusionsThe RECTOPET study investigating the role of PET/CT and PET/MRI for preoperative staging of primary rectal cancer patients will provide novel data that clarify the value of adding hybrid to conventional imaging, and the role of PET/CT versus PET/MRI.Trial registrationNCT03846882.

Place, publisher, year, edition, pages
BMC, 2019
Keywords
Rectal neoplasm, Rectal tumour, Staging, Lymph nodes, Tumour deposits, PET, CT, FDG-PET, CT, PET
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-161991 (URN)10.1186/s40644-019-0237-1 (DOI)000477054900002 ()31337428 (PubMedID)2-s2.0-85069762976 (Scopus ID)
Available from: 2019-08-13 Created: 2019-08-13 Last updated: 2025-04-09Bibliographically approved
2. Rectal cancer: a methodological approach to matching PET/MRI to histopathology
Open this publication in new window or tab >>Rectal cancer: a methodological approach to matching PET/MRI to histopathology
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2020 (English)In: Cancer Imaging, ISSN 1740-5025, E-ISSN 1470-7330, Vol. 20, no 1, article id 80Article in journal (Refereed) Published
Abstract [en]

Purpose: To enable the evaluation of locoregional disease in the on-going RECTOPET (REctal Cancer Trial on PET/MRI/CT) study; a methodology to match mesorectal imaging findings to histopathology is presented, along with initial observations.

Methods: FDG-PET/MRI examinations were performed in twenty-four consecutively included patients with rectal adenocarcinoma. In nine patients, of whom five received neoadjuvant treatment, a postoperative MRI of the surgical specimen was performed. The pathological cut-out was performed according to clinical routine with the addition of photo documentation of each slice of the surgical specimen, meticulously marking the location, size, and type of pathology of each mesorectal finding. This allowed matching individual nodal structures from preoperative MRI, via the specimen MRI, to histopathology.

Results: Preoperative MRI identified 197 mesorectal nodal structures, of which 92 (47%) could be anatomically matched to histopathology. Of the matched nodal structures identified in both MRI and histopathology, 25% were found to be malignant. These malignant structures consisted of lymph nodes (43%), tumour deposits (48%), and extramural venous invasion (9%). One hundred eleven nodal structures (55%) could not be matched anatomically. Of these, 97 (87%) were benign lymph nodes, and 14 (13%) were malignant nodal structures. Five were malignant lymph nodes, and nine were tumour deposits, all of which had a short axis diameter < 5 mm.

Conclusions: We designed a method able to anatomically match and study the characteristics of individual mesorectal nodal structures, enabling further research on the impact of each imaging modality. Initial observations suggest that small malignant nodal structures assessed as lymph nodes in MRI often comprise other forms of mesorectal tumour spread.

Trial registration: Clinical Trials Identifier: NCT03846882.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2020
Keywords
Rectal neoplasms, EMVI, Staging, Lymph nodes, Tumour deposits
National Category
Cancer and Oncology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-176783 (URN)10.1186/s40644-020-00347-6 (DOI)000583174400001 ()33129352 (PubMedID)2-s2.0-85094683721 (Scopus ID)
Funder
Knut and Alice Wallenberg FoundationCancerforskningsfonden i Norrland
Available from: 2020-11-26 Created: 2020-11-26 Last updated: 2025-04-09Bibliographically approved
3. Evaluation of MRI characterisation of histopathologically matched lymph nodes and other mesorectal nodal structures in rectal cancer
Open this publication in new window or tab >>Evaluation of MRI characterisation of histopathologically matched lymph nodes and other mesorectal nodal structures in rectal cancer
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2025 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, article id 80Article in journal (Refereed) Epub ahead of print
Abstract [en]

Purpose: To evaluate current MRI-based criteria for malignancy in mesorectal nodal structures in rectal cancer.

Method: Mesorectal nodal structures identified on baseline MRI as lymph nodes were anatomically compared to their corresponding structures histopathologically, reported as lymph nodes, tumour deposits or extramural venous invasion. All anatomically matched nodal structures from patients with primary surgery and all malignant nodal structures from patients with neoadjuvant treatment were included. Mixed-effects logistic regression models were used to evaluate the morphological criteria irregular margin, round shape, heterogeneous signal and nodal size, as well as the combined 2016 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus criteria, with histopathological nodal status as the gold standard.

Results: In total, 458 matched nodal structures were included from 46 patients (mean age, 67.7 years ± 1.5 [SD], 27 men), of which 19 received neoadjuvant treatment. The strongest associations in the univariable model were found for short-axis diameter ≥ 5 mm (OR 21.43; 95% CI: 4.13–111.29, p < 0.001) and heterogeneous signal (OR 9.02; 95% CI: 1.33–61.08, p = 0.024). Only size remained significant in multivariable analysis (OR 12.32; 95% CI: 2.03–74.57, p = 0.006). When applying the ESGAR consensus criteria to create a binary classification of nodal status, the OR of malignant outcome for nodes with positive ESGAR was 8.23 (95% CI: 2.15–31.50, p = 0.002), with corresponding sensitivity and specificity of 54% and 85%, respectively.

Conclusion: The results confirm the role of morphological and size criteria in predicting lymph node metastases. However, the current criteria might not be accurate enough for nodal staging.

Place, publisher, year, edition, pages
Springer Nature, 2025
Keywords
Extranodal extensions, Lymphatic metastasis, Magnetic resonance imaging, Neoplasm staging, Rectal neoplasms
National Category
Radiology and Medical Imaging Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-235683 (URN)10.1007/s00330-025-11361-2 (DOI)001402163400001 ()39838092 (PubMedID)2-s2.0-85217269680 (Scopus ID)
Funder
Cancerforskningsfonden i Norrland
Available from: 2025-02-25 Created: 2025-02-25 Last updated: 2025-04-09
4. FDG-PET/MRI in rectal cancer N-staging: results from the RECTOPET study with individual anatomical matching of lymph nodes and other mesorectal nodal structures between imaging and histopathology
Open this publication in new window or tab >>FDG-PET/MRI in rectal cancer N-staging: results from the RECTOPET study with individual anatomical matching of lymph nodes and other mesorectal nodal structures between imaging and histopathology
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(English)Manuscript (preprint) (Other academic)
National Category
Radiology and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-237422 (URN)
Available from: 2025-04-09 Created: 2025-04-09 Last updated: 2025-04-09Bibliographically approved

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