Multiinstitutional Phase 2 Clinical Trial of Intraoperative Molecular Imaging of Lung Cancer

Abstract

Background: Intraoperative molecular imaging (IMI) may improve surgical outcomes during pulmonary resection for lung cancer. A multiinstitutional phase 2 IMI clinical trial was conducted using a near-infrared, folate receptor-targeted contrast agent for lung adenocarcinomas, OTL38. The primary goal was to determine whether OTL38 improved surgeons' ability to identify difficult to find nodules, occult cancers, and positive margins.

Methods: Patients with lung nodules received OTL38 (0.025 mg/kg) preoperatively. Patients had IMI sequentially during lung inspection, tumor resection, and margin check. Efficacy was evaluated by occurrence of clinically significant events, occurrences that caused the surgeon to modify the operation or upstage the patient's cancer. Safety was assessed for a single intravenous dose of OTL38.

Results: Of 110 patients recruited, 92 were eligible for analysis. During lung inspection, IMI found 24 additional nodules, 9 (10%) of which were cancers that had not been known preoperatively. During tumor resection, IMI located 11 (12%) lesions that the surgeon could not find. During the margin check, IMI revealed 8 positive margins (9%) that the surgeon thought were negative. Benefits of IMI were pronounced in patients undergoing sublobar pulmonary resections and in patients with ground-glass opacities. There were no serious adverse events. All surgeons felt comfortable with the procedures by 10 cases.

Conclusions: In this phase 2 clinical trial, IMI improved outcomes for 26% of patients. A randomized, multiinstitutional phase 3 clinical trial is underway.

Figure 1:

Utilization of Intraoperative Molecular Imaging (IMI) during standard steps of a pulmonary resection

Figure 2:

CONSORT diagram.

Figure 3:

Synchronous Lesion clinically significant event. 1a) Known LUL pulmonary nodule on CAT/PET scan. 1b) Incidental LUL pulmonary nodule. 1c) Excised LLL pulmonary nodule. 1d) H&E and FR-α immunohistochemistry.

Figure 4:

Localization clinically significant event. 2a) LUL ground glass opacity on CAT scan and PET scan. 2b) Intraoperative localization using Intraoperative Molecular Imaging. 2c) Ex vivo image of lung wedge. 2d) Ex vivo imaging of slice of lung nodule.

Figure 5:

Margins clinically significant event. 3a) Example of negative margins. 3b) Example of close margins on back-table analysis. 3c) Example of positive margins on back-table analysis.

Figure 6:

Clinical significant events