Targeted Intraoperative Molecular Imaging for Localizing Nonpalpable Tumors and Quantifying Resection Margin Distances
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Published on: September 19, 2014
Gregory T Kennedy1, Feredun S Azari1, Elizabeth Bernstein1
1Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Importance:
Complete (R0) resection is the dominant prognostic factor for survival across solid tumor types. Achieving adequate tumor clearance with appropriate margins is particularly difficult in nonpalpable tumors or in situ disease. Previous methods to address this problem have proven time consumptive, impractical, or ineffective.
Objective:
To assess the capability of intraoperative molecular imaging (IMI), a novel technology using a fluorescent tracer targeted to malignant cells, to localize visually occult, nonpalpable tumors and quantify margin distances during resection.
Design, Setting, And Participants:
This nonrandomized open-label trial of IMI using a folate receptor-targeted fluorescent tracer enrolled patients between May 2017 and June 2020 at a single referral center. Eligible patients included those with a small (T1) lung lesion suspicious for malignant neoplasms and with radiographic features suggestive of a nonpalpable lesion.
Interventions:
Patients were preoperatively infused with a folate receptor-targeted near-infrared tracer. Intraoperatively, surgeons used thoracoscopic visualization and palpation to identify lesions. IMI was performed to detect the lesion in situ, and lesions were imaged ex vivo. Margins were assessed by IMI before comparison with those reported on final histopathologic analysis.
Main Outcomes And Measures:
The main outcomes were whether IMI could (1) localize nonpalpable lung lesions in situ and (2) quantify margin distance with comparison with final pathology as the criterion standard. Patient demographic information and lesion characteristics were prospectively recorded.
Results:
Of 40 patients, 26 (65%) were female, and the median (interquartile range) age was 66.5 (62-72) years. Conventional surgical methods localized 22 of 40 lesions (55%), while IMI localized 36 of 40 (90%). Of 18 nonpalpable lesions, 15 (83.3%) were identified by IMI. Both palpable and nonpalpable lesions demonstrated mean signal-to-background ratio more than 2. An IMI margin was able to be calculated for 39 of 40 patients (95%). IMI margins were nearly identical to margins reported on final pathology (R2 = 0.9593), with median (interquartile range) difference of 1.3 (0.7-2.0) mm. IMI detected 2 margins in nonpalpable tumors that were clinically unacceptable and would have had a high probability of recurrence.
Conclusions And Relevance:
To our knowledge, this study presents the first clinical use of IMI for nonpalpable tumors and provides proof of principle for the utility of IMI across the field of surgical oncology in identifying occult disease and tumor-positive margins.
Insights
Intraoperative molecular imaging (IMI) successfully located nonpalpable lung tumors and accurately measured surgical margins. This novel technology improves tumor resection by identifying occult disease and guiding surgeons to achieve complete tumor removal.
Area of Science:
- Surgical Oncology
- Molecular Imaging
- Diagnostic Technology
Background:
- Complete tumor resection (R0) is critical for patient survival in solid tumors.
- Achieving adequate margins is challenging for nonpalpable or in situ tumors.
- Existing methods for margin assessment are often inefficient or inadequate.
Purpose of the Study:
- To evaluate intraoperative molecular imaging (IMI) for localizing nonpalpable tumors.
- To assess IMI's ability to quantify surgical margin distances during resection.
- To determine the efficacy of a folate receptor-targeted fluorescent tracer in IMI.
Main Methods:
- A nonrandomized trial involving patients with small, suspicious lung lesions.
- Patients received a folate receptor-targeted near-infrared fluorescent tracer preoperatively.
- Surgeons used IMI for intraoperative lesion detection (in situ and ex vivo) and margin assessment.
Main Results:
- IMI localized 90% of lesions (36/40), significantly outperforming conventional methods (55%).
- IMI identified 83.3% of nonpalpable lesions (15/18).
- IMI provided accurate margin quantification, with a median difference of 1.3 mm compared to final pathology, and identified two unacceptable margins.
Conclusions:
- This study demonstrates the first clinical application of IMI for nonpalpable tumors.
- IMI is a valuable tool for identifying occult disease and assessing tumor margins in surgical oncology.
- IMI offers a promising approach to improve the completeness of tumor resection.
