Evidence map›Paper›PMID 24862545›Full record

Trial reportEuropean journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology2014

Real-time intraoperative detection of breast cancer using near-infrared fluorescence imaging and Methylene Blue.

Q R J G Tummers, F P R Verbeek, B E Schaafsma, M C Boonstra, J R van der Vorst, G-J Liefers, C J H van de Velde, J V Frangioni, A L Vahrmeijer

Abstract readClinical TrialComparative Study
In one paragraph

Trial report in European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 4 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

71 citing papers in PubMed, 4 syntheses or guidelines pooled it.

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  8. Fluorescence Imaging of Cancer.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2026
    Review
  9. Advances in Imaging of Traumatic Nerve Injuries.The Journal of the American Academy of Orthopaedic Surgeons · 2025
    Review
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11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Q R J G TummersDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
F P R VerbeekDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
B E SchaafsmaDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
M C BoonstraDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
J R van der VorstDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
G-J LiefersDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
C J H van de VeldeDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
J V FrangioniDepartment of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
A L VahrmeijerDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: a.l.vahrmeijer@lumc.nl.

Funding

Intraoperative Near-Infrared Fluorescence ImagingR01CA115296 · NCI · CURADEL, LLC · PI FRANGIONI, JOHN V · 2005 to 2014
$13.9M
NCI NIH HHS R01 CA115296NCI NIH HHS R01-CA-115296
6 · The paper itself

Abstract

backgroundDespite recent developments in preoperative breast cancer imaging, intraoperative localization of tumor tissue can be challenging, resulting in tumor-positive resection margins during breast conserving surgery. Based on certain physicochemical similarities between Technetium((99m)Tc)-sestamibi (MIBI), an SPECT radiodiagnostic with a sensitivity of 83-90% to detect breast cancer preoperatively, and the near-infrared (NIR) fluorophore Methylene Blue (MB), we hypothesized that MB might detect breast cancer intraoperatively using NIR fluorescence imaging.

methodsTwenty-four patients with breast cancer, planned for surgical resection, were included. Patients were divided in 2 administration groups, which differed with respect to the timing of MB administration. N = 12 patients per group were administered 1.0 mg/kg MB intravenously either immediately or 3 h before surgery. The mini-FLARE imaging system was used to identify the NIR fluorescent signal during surgery and on post-resected specimens transferred to the pathology department. Results were confirmed by NIR fluorescence microscopy.

results20/24 (83%) of breast tumors (carcinoma in N = 21 and ductal carcinoma in situ in N = 3) were identified in the resected specimen using NIR fluorescence imaging. Patients with non-detectable tumors were significantly older. No significant relation to receptor status or tumor grade was seen. Overall tumor-to-background ratio (TBR) was 2.4 ± 0.8. There was no significant difference between TBR and background signal between administration groups. In 2/4 patients with positive resection margins, breast cancer tissue identified in the wound bed during surgery would have changed surgical management. Histology confirmed the concordance of fluorescence signal and tumor tissue.

conclusionsThis feasibility study demonstrated an overall breast cancer identification rate using MB of 83%, with real-time intraoperative guidance having the potential to alter patient management.

Indexed as

Methylene BlueAdultAgedAged, 80 and overBiopsy, NeedleBreast NeoplasmsFemaleFluorescenceHumansImage EnhancementImmunohistochemistryInfusions, IntravenousIntraoperative CareMastectomy, Modified RadicalMastectomy, SegmentalMiddle AgedMethylene BlueBreast cancerImage-guided surgeryMethylene BlueNear-infrared fluorescence imaging

Identifiers

PMID24862545
PMCPMC4035701

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.