BACKGROUND:The management of most solid tumors of the anterior mediastinum involves complete resection. Because of their location near mediastinal structures, wide resection is not possible; therefore, surgeons must use subjective visual and tactile cues to determine disease extent. This clinical trial explored intraoperative near-infrared (NIR) imaging as an approach to improving tumor delineation during mediastinal tumor resection. METHODS: Twenty-five subjects with anterior mediastinal lesions suspicious for malignancy were enrolled in an open-label feasibility trial. Subjects were administered indocyanine green (ICG) at a dose of 5 mg/kg, 24 hours before resection (via a technique called TumorGlow). The NIR imaging systems included Artemis (Quest, Middenmeer, the Netherlands) and Iridium (VisionSense Corp, Philadelphia, Pennsylvania). Intratumoral ICG uptake was evaluated. The clinical value was determined via an assessment of the ability of NIR imaging to detect phrenic nerve involvement or incomplete resection. Clinical and histopathologic variables were analyzed to determine predictors of tumor fluorescence. RESULTS: No drug-related toxicity was observed. Optical imaging added a mean of 10 minutes to case duration. Among the subjects with solid tumors, 19 of 20 accumulated ICG. Fluorescent tumors included thymomas (n = 13), thymic carcinomas (n = 4), and liposarcomas (n = 2). NIR feedback improved phrenic nerve dissection (n = 4) and identified residual disease (n = 2). There were no false-positives or false-negatives. ICG preferentially accumulated in solid tumors; this was independent of clinical and pathologic variables. CONCLUSIONS: NIR imaging for anterior mediastinal neoplasms is safe and feasible. This technology may provide a real-time tool capable of determining tumor extent and specifically identify phrenic nerve involvement and residual disease. Cancer 2019;125:807-817.
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.
Evidence for immunotherapy in metastatic nonesmall-cell lung cancer (mNSCLC) with brain metastases (BM) is limited. Within a cohort of 570 patients with mNSCLC undergoing pembrolizumab-based therapy, patients with (n [ 126) and without (n [ 444) BM did not have significantly different survival. Patients with mNSCLC with BM should be considered for pembrolizumab-based therapy; cranial irradiation can be administered either before or after pembrolizumab initiation. Background: Patients with metastatic nonesmall-cell lung cancer (mNSCLC) and untreated brain metastases (BM) have been excluded from most trials of immune checkpoint inhibitors (ICIs). Real-world evidence on efficacy and survival outcomes of ICIs in patients with BM is limited. Patients and Methods: We conducted a single-center retrospective study of patients with mNSCLC treated with pembrolizumab with or without chemotherapy and compared progression-free survival (PFS) and overall survival (OS) between patients with and without BM using Kaplan-Meier and Cox methodology. We also characterized systemic and intracranial objective response rate (ORR) and treatment details, including timing of cranial irradiation. Results: Between Augutst 2013 and December 2018, 570 patients with mNSCLC treated with pembrolizumab-based therapy were analyzed. Of 126 (22.1%) patients with BM, 96 (76.2%) had treated BM (local therapy prior to pembrolizumab), and 30 (23.8%) had untreated BM. Of patients with untreated BM, 17 (56.7%) underwent radiation within 30 days after pembrolizumab initiation. In the remaining 13 (43.3%) treated with pembrolizumab-based therapy alone, intracranial ORR was 36.4%. Patients with and without BM did not have significantly different systemic ORR (27.8% vs. 29.7%; P ¼ .671), PFS (mPFS 9.2 vs. 7.7 months; P ¼ .609), or OS (mOS 18.0 vs. 18.7 months; P ¼ .966). Factors associated with improved survival on Cox analysis included female gender, performance status, adenocarcinoma histology, and first-line therapy. Conclusions: Patients with BM did not have inferior survival to patients without BM after treatment with pembrolizumab-based therapy. In the current era, BM may not automatically confer inferior survival, and should not exclude patients from receiving pembrolizumab-based therapy.
Fluorescence guided surgery is an emerging technology that may improve accuracy of pulmonary resection for non-small cell lung cancer (NSCLC). Herein we explore optical imaging for NSCLC surgery using the well-studied protoporphyrin IX (PPIX)/5-aminiolevulinic acid (5-ALA) system. More specifically, we evaluate fluorescent patterns observed when using (1) commonly utilized in vitro and murine NSCLC models and with (2) spontaneous canine NSCLCs, which closely mimic human disease. Using flow cytometry and fluorescent microscopy, we confirmed that NSCLC models fluoresce after exposure to 5-ALA in vitro . High levels of fluorescence were similarly observed in murine tumors within 2 hours of systemic 5-ALA delivery. When evaluating this approach in spontaneous canine NSCLC, tumor fluorescence was observed in 6 of 7 canines. Tumor fluorescence, however, was heterogenous owing to intratumoral variations in cellularity and necrosis. Margin and lymph node detection was inaccurate. These data demonstrate the importance of incorporating reliable cancer models into preclinical evaluations of optical agents. Utilization of spontaneous large animal models of cancer may further provide an important intermediate in the path to human translation of optical contrast agents.
9599 Background: Patients (pts) with mNSCLC with active brain metastases (BM) are often excluded from clinical trials; data on efficacy and safety of immunotherapy in this population are limited. We compared outcomes of pts with mNSCLC with and without BM who received pembrolizumab-based therapy. Methods: We conducted a retrospective single-center study of pts with mNSCLC treated with pembrolizumab (P) with or without chemotherapy. Progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier methodology and compared using multivariable Cox regression and log rank testing. Results: We identified 587 consecutive pts with mNSCLC who began P-based therapy between 8/2013 and 12/2018: 306 (52%) female, median age 67 years (range 32-98), 437 (74%) adenocarcinoma, and 508 (87%) former/current smokers. 388 (66%) patients received P in first line therapy, and 334 (57%) received single-agent P. 131 pts (22%) had detectable BM at baseline (start of P-based therapy). Pts with BM were younger (median 65 y vs 68 y, p < 0.01) and more likely to have adenocarcinoma (86% vs. 71%, p < 0.01) and baseline steroid use (22% vs 1%, p < 0.01). Presence of BM did not differ by race, sex, line of therapy, treatment regimen, or PD-L1 status. Of the 131 patients with detectable BM on pre-treatment brain MRI, 55 (42%) had stable BM as a result of prior local therapy, while 76 (58%) had active (new or growing) BM on pre-treatment imaging. Most patients with active BM underwent radiation therapy (RT) in either the 30 days before (n = 46) or 30 days after (n = 17) P start; of the remaining 13 treated with P-based therapy alone, intracranial responses included 2 CR, 2 PR, 3 SD, and 4 PD. As of 1/1/2020, with 15-month median follow up, there was no difference in mPFS (9.2 vs 7.3 months, p = 0.41) or mOS (18.3 vs 18.0 mo, p = 0.67) between pts with and without BM in our P-treated cohort. On multivariable analysis, female sex, ECOG 0-1, adenocarcinoma histology, and P as first line therapy were associated with improved PFS and OS. Presence of BM, baseline steroid use, and timing of local RT (before vs. after P) were not associated with inferior survival. Conclusions: In our single-center experience of pts with mNSCLC treated with P, pts with and without BM had similar PFS and OS. We observed several intracranial responses to P-based therapy alone, but most pts with active BM underwent local RT. mNSCLC pts with BM should be considered for P-based therapy; BM may be treated with RT immediately before or even after P with similar survival outcomes.
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