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Background: Clinical studies have demonstrated that intraoperative molecular imaging (IMI) with pafolacianine identifies occult pulmonary lesions that are not identified by preoperative computed tomography or by intraoperative inspection techniques in ∼20% of patients. This study describes occult lesion clinical data and evaluates characteristics so that surgeons can better incorporate this emerging technology into clinical decision making., Methods: Participants (n = 100) enrolled in a phase 3 trial of IMI with pafolacianine during pulmonary resection (Enabling Lung Cancer Identification Using Folate Receptor Targeting [ELUCIDATE]; NCT04241315) were identified. Participants underwent preoperative computed tomography with 1.25-mm slices. Patient and lesion characteristics were analyzed. Positive predictive value and false positive rates were tabulated for IMI fluorescent lesions, with predictors of malignant vs benign occult lesions described., Results: IMI identified 29 occult lesions in 23 (23%) participants. Seventeen of 29 (58%) lesions were identified within the same lobe as known lesions; 12 of 29 (42%) were identified in a different lobe from the suspicious nodule known by preoperative assessment. Twenty-three of 29 (79%) of occult lesions found by IMI were resected with an additional wedge resection. Ten of 29 (34%) lesions identified by IMI were malignant. There was no additional morbidity in participants with lesions resected. With pafolacianine, 7 participants had a synchronous primary stage I lung cancer identified, and 1 participant had additional metastases identified., Conclusions: IMI with pafolacianine identifies occult malignant lesions during pulmonary resection despite thorough preoperative imaging and intraoperative assessment by experienced surgeons., Competing Interests: Disclosures Linda W. Martin reports a relationship with Bristol Myers Squibb that includes: consulting or advisory. Michael I. Ebright reports a relationship with On Target Laboratories that includes: consulting or advisory; and with Medtronic that includes: consulting or advisory. Tommy Lee reports a relationship with On Target Laboratories LLC that includes: employment and equity or stocks. Jarrod D. Predina reports a relationship with On Target Laboratories LLC that includes: consulting or advisory; and with Olympus that includes: consulting or advisory. All other authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: We describe use, patients, and outcome of diagnostic lobectomy for suspected lung cancer without pathologic confirmation., Methods: A retrospective review of consecutive lobectomy or bilobectomy for suspected or confirmed primary pulmonary malignancy was conducted using our participant's sample of The Society of Thoracic Surgeons database. Surgeons performed lobectomy based on clinical diagnosis or confirmation on a biopsy specimen. Lung cancer confirmed by biopsy specimen was compared with cases clinically suspected. Univariate and multivariate analyses identified variables associated with lobectomy without biopsy specimen confirmation., Results: Among 2651 lobectomies performed between 2006 and 2019 in 2617 patients, lung cancer was confirmed by preoperative biopsy specimen in 51.6% (1368 of 2651) or was clinically suspected before the operation in 48.4% (1283 of 2651). The intraoperative biopsy specimen in 585 of 1283 cases (45.6%) proved lung cancer before lobectomy, whereas lobectomy proceeded in 698 cases (54.4%) without a diagnosis. Final pathology proved lung cancer in 90% (628 of 698) without a diagnosis before lobectomy and nonmalignant disease in 10% (70 of 698). Nonneoplastic pathology included granulomas (30 of 70 [43%]), pneumonia (12 of 70 [17%]), bronchiectasis (7 of 70 [10%]), and other lesions (21 of 70 [30%]). Operative mortality was 0.94% (25 of 2651) for the cohort and 1.0% (7 of 698) for diagnostic lobectomy only. Multivariate analysis identified patient age, type of lobectomy (right middle lobe), and the intermediate study tercile as associated with diagnostic lobectomy., Conclusions: Lobectomy for suspected lung cancer without diagnosis is common, represents practice variation, and infrequently (10% diagnostic, 2.6% all lobectomies) removes nonmalignant disease. Tissue confirmation before lobectomy is preferred, particularly when operative risk is increased. Diagnostic lobectomy is acceptable in carefully selected patients and lesions., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Macroscopic complete resection can improve survival in a select group of patients with malignant pleural mesothelioma. During resection, differentiating residual tumor from inflammation or scar can be challenging. This trial evaluated near-infrared (NIR) intraoperative imaging using TumorGlow (a novel NIR imaging approach utilizing high-dose indocyanine green and delayed imaging) technology to improve detection of macroscopic residual disease., Methods: Twenty subjects were enrolled in an open-label clinical trial of NIR intraoperative imaging with TumorGlow (Indocyanine Green for Solid Tumors [NCT02280954]). Twenty-four hours before pleural biopsy or pleurectomy and decortication (P/D), patients received intravenous indocyanine green. All specimens identified during standard-of-care surgical resection and with NIR imaging underwent histopathologic profiling and correlative microscopic fluorescent tomographic evaluation. For subjects undergoing P/D (n = 13), the hemithorax was evaluated with NIR imaging during P/D to assess for residual disease. When possible, additional fluorescent lesions were resected., Results: Of 203 resected specimens submitted for evaluation, indocyanine green accumulated within 113 of 113 of resected mesothelioma specimens, with a mean signal-to-background fluorescence ratio of 3.1 (SD, 2.2 to 4.8). The mean signal-to-background fluorescence ratio of benign tissues was 2.2 (SD, 1.4 to 2.4), which was significantly lower than in malignant specimens (p = 0.001). NIR imaging identified occult macroscopic residual disease in 10 of 13 subjects. A median of 5.6 resectable residual deposits per patient (range, 0 to 11 deposits per patient), with a mean size of 0.3 cm (range, 0.1 to 1.5 cm), were identified., Conclusions: TumorGlow for malignant pleural mesothelioma is safe and feasible. Excellent sensitivity allows for to reliable detection of macroscopic residual disease during cytoreductive surgical procedures., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: Intraoperative localization and resection of ill-defined pulmonary ground-glass opacities (GGOs) during minimally invasive pulmonary resection is technically challenging. Current preoperative techniques to facilitate localization of GGOs include microcoil and hook wire placement, both of which have logistic limitations, carry safety concerns, and do not help with margin assessment. In this clinical trial, we explored an alternative method involving near-infrared molecular imaging with a folate receptor-targeted agent, OTL38, to improve localization of GGOs and confirmation of resection margins., Methods: In a human trial, 20 subjects with pulmonary GGOs who were eligible for video-assisted thoracoscopic surgery (VATS) resection received 0.025 mg/kg of OTL38 before the resection. The primary objectives were to (1) determine whether use of OTL38 allows safe localization of GGOs and assessment of margins during VATS and (2) determine patient, radiographic, and histopathologic variables that predict the amount of fluorescence during near-infrared imaging., Results: We observed no toxicity. Of the 21 GGOs, 20 accumulated OTL38 and displayed fluorescence upon in situ or back table evaluation. Intraoperatively, near-infrared imaging localized 15 of 21 lesions whereas VATS alone localized 10 of 21 (p = 0.05). The addition of molecular imaging affected care of nine of 21 subjects by improving intraoperative localization (n = 6) and identifying close margins (n = 3). This approach was most effective for subpleural lesions measuring less than 2 cm. For lesions deeper than 1.5 cm from the pleural surface, intraoperative localization using fluorescent feedback was limited., Conclusions: This approach provides a safe alternative for intraoperative localization of small, peripherally located pulmonary lesions. In contrast to alternative localization techniques, use of OTL38 also allows confirmation of adequate margins. Future studies will compare this approach to alternative localization techniques in a clinical trial., (Copyright © 2018 International Association for the Study of Lung Cancer. All rights reserved.)

Background: Intraoperative identification of pulmonary nodules, particularly small lesions, can be challenging. We hypothesize that folate receptor-targeted intraoperative molecular imagining can be safe and improve localization of pulmonary nodules during resection., Methods: Twenty subjects with biopsy-proven pulmonary adenocarcinomas were enrolled in a phase I clinical trial to test the safety and feasibility of OTL38, a novel folate receptor-α (FRα) targeted optical contrast agent. During resection, tumors were imaged in situ and ex vivo and fluorescence was quantified. Resected specimens were analyzed to confirm diagnosis, and immunohistochemistry was utilized to quantify FRα expression. A multivariate analysis using clinical and tumor data was performed to determine variables impacting tumor fluorescence., Results: Of the 20 subjects, three grade I adverse events were observed: all transient nausea/abdominal pain. All symptoms resolved after completing the infusion. Sixteen of 20 subjects (80%) had tumors with in situ fluorescence with a mean tumor-to-background fluorescence level of 2.9 (interquartile range, 2.1 to 4.2). The remaining 4 subjects' tumors fluoresced ex vivo. In situ fluorescence was dependent on depth from the pleural surface. Four subcentimeter nodules not identified on preoperative imaging were detected with intraoperative imaging., Conclusions: This phase I trial provides preliminary evidence suggesting that folate receptor-targeted molecular imaging with OTL38 is safe, with tolerable grade I toxicity. These data also suggest that OTL38 accumulates in known lung cancers and may improve identification of synchronous malignancies. Our group is initiating a five-center, phase II study to better understand the clinical implications of intraoperative molecular imaging using OTL38., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The virtual patient (VP) is a web-based tool that allows students to test their clinical decision-making skills using simulated patients., Methods: Three VP cases were developed using commercially available software to simulate common surgical scenarios. Surgical clerks volunteered to complete VP cases. Upon case completion, an individual performance score (IPS, 0-100) was generated and a 16-item survey was administered. Surgery shelf exam scores of clerks who completed VP cases were compared with a cohort of students who did not have exposure to VP cases. Descriptive statistics were performed to characterize survey results and mean IPS., Results: Surgical clerks felt that the VP platform was simple to use, and both the content and images were well presented. They also felt that VPs enhanced learning and were helpful in understanding surgical concepts. Mean IPS at conclusion of the surgery clerkship was 69.2 (SD 26.5). Mean performance on the surgery shelf exam for the student cohort who had exposure to VPs was 86.5 (SD 7.4), whereas mean performance for the unexposed student cohort was 83.5 (SD 9)., Discussion: The VP platform represents a new educational tool that allows surgical clerks to direct case progression and receive feedback regarding clinical-management decisions. Its use as an assessment tool will require further validation., (Published by Elsevier Inc.)

Surgery is the most effective therapy for cancer in the United States, but disease still recurs in more than 40% of patients within 5 years after resection. Chemotherapy is given postoperatively to prevent relapses; however, this approach has had marginal success. After surgery, recurrent tumors depend on rapid neovascular proliferation to deliver nutrients and oxygen. Phosphatidylserine (PS) is exposed on the vascular endothelial cells in the tumor microenvironment but is notably absent on blood vessels in normal tissues. Thus, PS is an attractive target for cancer therapy after surgery. Syngeneic mice bearing TC1 lung cancer tumors were treated with mch1N11 (a novel mouse chimeric monoclonal antibody that targets PS), cisplatin (cis), or combination after surgery. Tumor relapses and disease progression were decreased 90% by combination therapy compared with a 50% response rate for cis alone (P = .02). Mice receiving postoperative mch1N11 had no wound-related complications or added systemic toxicity in comparison to control animals. Mechanistic studies demonstrated that the effects of mch1N11 were associated with a dense infiltration of inflammatory cells, particularly granulocytes. This strategy was independent of the adaptive immune system. Together, these data suggest that vascular-targeted strategies directed against exposed PS may be a powerful adjunct to postoperative chemotherapy in preventing relapses after cancer surgery.

Introduction: Survival after pulmonary metastasectomy for soft tissue sarcoma (STS) has been lower than in osteosarcoma (14-40% versus 40-50%). With improved patient selection criteria and advanced chemotherapy agents, we hypothesized that survival after metastasectomy for STS has improved in recent years., Methods: Retrospective study of 48 patients undergoing pulmonary metastasectomy for STS between 1995 and 2007. Potential predictors of overall survival and disease-free survival (DFS) were examined using the log-rank test or Cox regression. Multivariate analysis was conducted using Cox regression., Results: Overall survival after initial metastasectomy was 67% and 52% at 3 and 5 years, respectively; DFS was 17% and 10% at 3 and 5 years. Univariate analysis indicated that ≤2 pulmonary metastases (p = 0.03), diameter of largest metastasis ≤2 cm (p = 0.09), and the absence of extrapulmonary metastases (p = 0.10) were associated with longer overall survival. Absence of extrapulmonary metastases (p = 0.07) and smaller size of the largest pulmonary metastasis (p = 0.06) were associated with longer DFS. Before 2001, 46.7% of patients received adjuvant chemotherapy versus 72.7% after (p = 0.10). Neither use of chemotherapy nor chemotherapy type was related to overall survival or DFS., Conclusion: Five-year overall survival is substantially higher after pulmonary metastasectomy for STS in our study relative to previously published results (52% versus 14-40%). This improvement does not seem to be the result of greater use of, or newer, chemotherapeutic regimens. Among potential explanations, improved patient selection is the most likely factor.