Highlight
- Specimen PET-CT imaging significantly improved intraoperative detection of positive margins in early-stage breast cancer surgeries.
- Success rates for achieving negative invasive ductal carcinoma margins increased to 95.2% with specimen PET-CT versus 83.3% without intraoperative assessment.
- Implementation of this imaging approach could reduce re-excision rates, thereby lowering patient morbidity and healthcare costs.
- Multicenter European trial confirms feasibility and clinical utility of low-dose 18F-FDG PET-CT imaging integrated into surgical workflow.
Study Background
Breast-conserving surgery (BCS) has become a cornerstone treatment for early-stage breast cancer, offering oncologic control while preserving breast aesthetics. However, achieving negative pathological margins remains a critical challenge; positive margins are reported in 12% to 30% of cases. Positive margins are strongly linked to increased local recurrence risk, often necessitating re-excision surgeries that carry additional morbidity, delay adjuvant therapies, and elevate healthcare costs. Current intraoperative margin assessment (IMA) techniques—such as frozen section analysis and imprint cytology—have limitations in sensitivity, turnaround time, and logistics. Consequently, there exists a pressing clinical need for an accurate, efficient, and practical modality that can be seamlessly integrated intraoperatively to optimize margin status.
Specimen positron emission tomography-computed tomography (PET-CT) using 18F-fluorodeoxyglucose (FDG) offers functional imaging combined with anatomical detail that may enable direct visualization of residual tumor at specimen margins. This technology could provide surgeons with immediate feedback and guide additional excision within the same operative session. The BrIMA nonrandomized clinical trial was designed to prospectively evaluate the clinical effectiveness and feasibility of specimen PET-CT imaging for intraoperative margin assessment in patients undergoing BCS for invasive ductal carcinoma and other early breast cancer subtypes.
Study Design
The BrIMA trial was a multicenter interventional nonrandomized study conducted across six European breast cancer centers from June 2022 to March 2025. It enrolled 148 female patients diagnosed with early-stage breast cancer (primarily invasive ductal carcinoma) who were scheduled for breast-conserving surgery. Patients received intravenous low-dose 18F-FDG (0.8 MBq/kg) injection prior to tumor excision. Immediately after tumor removal, the surgical specimen was subjected to intraoperative imaging with a dedicated specimen PET-CT system.
Surgeons interpreted PET-CT images intraoperatively to identify suspicious margins indicating residual tumor presence. When such margins were detected, additional resection of adjacent tissue was performed during the same surgery aiming to achieve clear margins. Routine margin assessment techniques were also employed according to institutional protocols. Final histopathology served as the reference standard for margin status determination. Patients were followed up two weeks postoperatively to monitor outcomes.
The primary endpoint was the success rate of specimen PET-CT in addressing positive margins for the invasive carcinoma component compared with no intraoperative margin assessment and standard-of-care techniques. Secondary endpoints included success rates for other breast cancer subtypes, overall positive margin rates, reoperation rates, and diagnostic performance metrics.
Key Findings
Among the cohort, the median patient age was 65 years (IQR 53-73), with a median tumor size of 17 mm (IQR 12-22). The trial revealed a statistically significant enhancement in achieving negative invasive margins when specimen PET-CT was integrated intraoperatively:
– Success rates for invasive ductal carcinoma margins were 83.3% without any IMA, 86.9% with routine IMA techniques, and 95.2% with specimen PET-CT imaging (P < .001 compared to no IMA).
– When considering all breast cancer subtypes, success rates improved from 76.4% without IMA to 81.8% with routine IMA and reached 91.9% with specimen PET-CT (P < .001 vs no IMA; P = .009 vs routine IMA).
These improvements translated into lower final positive margin rates and potentially fewer re-excisions, although the latter was not explicitly quantified in the published summary. The safety profile was favorable given the low-dose FDG administration and the noninvasive nature of specimen imaging.
The study thereby supports specimen PET-CT as a highly sensitive and feasible modality for real-time margin assessment, enabling surgeons to perform targeted additional resections intraoperatively, thereby minimizing the need for subsequent surgeries.
Expert Commentary
The BrIMA trial represents a significant advancement in intraoperative margin evaluation by introducing a functional imaging technique previously limited to diagnostic and staging contexts. The integration of specimen PET-CT addresses key pitfalls of conventional margin assessment: it provides comprehensive three-dimensional margin evaluation with the capability to detect biologically active tumor cells beyond gross morphology.
However, certain limitations warrant consideration. The nonrandomized design may introduce selection bias, and the role of surgeon interpretation could introduce variability unless standardized reading criteria are developed. Further investigation in randomized controlled trials could consolidate these findings. Additionally, cost-effectiveness analyses will be crucial to justify widespread adoption, balancing the PET-CT equipment and tracer expenses against savings from reduced reoperations.
Biologically, 18F-FDG uptake reflects tumor glycolytic activity, which correlates with tumor aggressiveness and viable malignant cells. This biological specificity enhances margin detection sensitivity compared to purely anatomical methods such as specimen X-ray or ultrasound.
Guideline committees may consider specimen PET-CT imaging as an adjunct to routine intraoperative assessment, especially in centers equipped with hybrid nuclear medicine and surgical infrastructure.
Conclusion
The BrIMA nonrandomized clinical trial demonstrates that specimen PET-CT imaging significantly improves intraoperative margin assessment accuracy in breast-conserving surgery for early-stage breast cancer. This innovative approach enhances the surgeon’s ability to detect residual invasive tumor at specimen margins, leading to higher success rates in obtaining negative margins and potentially reducing re-excision surgeries.
If validated in larger randomized studies and cost-effectiveness analyses, specimen PET-CT imaging could become an integral component of standard surgical practice, improving oncologic outcomes and patient quality of life. This trial marks an important translational step, harnessing advanced molecular imaging to resolve a persistent surgical challenge in breast cancer care.
Funding and ClinicalTrials.gov Registration
The study was supported by institutional and European collaborative funding. It is registered on ClinicalTrials.gov under the identifier NCT04999917.
References
1. Göker M, Hahn M, Kraemer XE, et al. Specimen PET-CT Imaging for Intraoperative Margin Assessment in Early-Stage Breast Cancer: The BrIMA Nonrandomized Clinical Trial. JAMA Surg. 2026 Jun 17. doi:10.1001/jamasurg.2026.42307959.
2. Morrow M, et al. Surgical margins in breast-conserving surgery: American Society of Clinical Oncology, Society of Surgical Oncology, and American Society for Radiation Oncology consensus guideline. J Clin Oncol. 2014 Jul 10;32(21):1507–15.
3. Liang J, et al. Intraoperative assessment of tumor margins in breast-conserving surgery: A systematic review of techniques. Breast. 2019 Aug;45:31–42.
4. Avril N, et al. Positron Emission Tomography for Breast Cancer Imaging in Specific Clinical Settings. Semin Nucl Med. 2015 Mar;45(2):146–53.
