A Clinical Trial of TumorGlow to Identify Residual Disease During Pleurectomy and Decortication

Our plain-English summary of A Clinical Trial of TumorGlow to Identify Residual Disease During Pleurectomy and Decortication, by J.D. Predina, A.D. Newton, C. Corbett, et al (The Annals of Thoracic Surgery, 2019).

The study

• Authors: J.D. Predina, A.D. Newton, C. Corbett, L. Xia, M. Shin, L.F. Sulfyok, O.T. Okusanya, K.A. Cengel, A. Haas, L. Litzky, J.C. Kucharczuk, S. Singhal
• Journal: The Annals of Thoracic Surgery
• Published: 2019;107(1):224-232
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

In plain English

This small, single-center, open-label feasibility trial at the University of Pennsylvania tested whether indocyanine green, a fluorescent dye given by vein about 24 hours before surgery, helped surgeons see malignant pleural mesothelioma under near-infrared light. The authors call this approach TumorGlow. Twenty patients took part between January 2016 and April 2017. In 7 patients having biopsies for suspected disease, all 22 mesothelioma biopsy samples glowed, but so did 7 benign samples. In 13 patients with early-stage epithelioid mesothelioma having pleurectomy and decortication, surgeons rechecked the chest with the camera after what they believed was complete removal of visible tumor. Glowing spots remained in 10 of the 13 patients. Of the 56 spots found, 32 were mesothelioma and 24 were benign tissue. One patient had pain at the injection site, and no other adverse events were reported. Imaging added a median of 7 minutes to surgery. The authors concluded the approach may be a safe and practical tool that may improve cytoreduction and potentially local recurrence rates. They noted a high false-positive rate and that the true false-negative rate could not be measured.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Nonrandomized, open-label, single-arm, single-center feasibility clinical trial (NCT02280954)
• Who was studied: 20 patients (14 male, median age 67.5 years) enrolled at the University of Pennsylvania, Philadelphia, between January 2016 and April 2017. Cohort 1 was 7 patients with a recurrent pleural effusion and suspected mesothelioma who had thoracoscopic pleural biopsy. Cohort 2 was 13 surgical candidates with stage I or stage II histologically confirmed epithelioid malignant pleural mesothelioma who had pleurectomy and decortication after preoperative chemotherapy.
• Exposure: The study tested intravenous indocyanine green (5 mg/kg) given about 24 hours before surgery, followed by near-infrared imaging during surgery. Asbestos exposure was not studied or discussed.
• Main results:
  • Cohort 1 (biopsies): of 29 fluorescent biopsy samples, 22 were mesothelioma and 7 were benign. All 11 nonfluorescent samples were noncancerous.
  • Cohort 1 test characteristics: sensitivity 100% (95% CI, 81.5% to 100%) and specificity 61.1% (95% CI, 36.1% to 81.7%).
  • Cohort 2 (resected specimens examined outside the body): of 82 fluorescent lesions, 59 (71.9%) were mesothelioma and 23 (28.0%) were benign inflamed mesothelial surface. All 25 nonfluorescent areas were benign.
  • Cohort 2 resected specimens: sensitivity 100%, specificity 52.1%, positive predictive value 71.9%, negative predictive value 100%.
  • Cohort 2 residual disease: after what surgeons believed was complete macroscopic resection, near-infrared imaging found residual fluorescent spots in 10 of 13 patients. There were 56 lesions in total, a median of 5.6 per patient (range 0 to 11), with a mean size of 0.3 cm (range 0.1 to 1.5 cm).
  • Of the 56 residual spots found by imaging in cohort 2, 32 were mesothelioma, 8 were benign lymph nodes, and 16 were inflamed pleura or fat tissue.
  • For residual spots in cohort 2, the positive predictive value of near-infrared imaging was 57.2%.
  • Safety: one patient (subject 7) had a grade I adverse event, pain at the injection site during infusion. No other adverse events were reported.
  • Imaging added a median of 7 minutes (range 4 to 13 minutes) to the operation.
• The authors' conclusion: The authors concluded that the approach may be a safe and practical tool that may improve cytoreduction and potentially local recurrence rates for malignant pleural mesothelioma.
• Limitations the authors state:
  • Patients had to be surgical candidates before enrollment, which may artificially inflate the test characteristics by increasing pretest probabilities.
  • The actual false-negative rate could not be determined.
  • Microscopic disease is likely too small for near-infrared detection.
  • The false-positive rate was high, which the authors attributed to dye building up in inflamed, noncancerous tissue.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Clinical Trial, Pleural Mesothelioma, Inflammation, Pleural Biopsy, Surgical Resection, Hemithorax, Mesothelioma, Cytoreductive Surgery.

Related studies

• Quality of life after radical pleurectomy decortication for malignant pleural mesothelioma — N.M. Mollberg, Y. Vigneswaran, et al. (2012)
• Thoracic shaping technique to avoid residual space after extended pleurectomy/decortication — S. Bölükbas, M. Eberlein, et al. (2013)
• Extrapleural pneumonectomy or pleurectomy/decortication for malignant pleural mesothelioma — S. Hasegawa (2014)
• Current Treatment of Mesothelioma: Extrapleural Pneumonectomy Versus Pleurectomy/Decortication — A.S. Wolf, R.M. Flores (2016)
• Non-incisional pleurectomy-decortication for malignant pleural mesothelioma — F. Tanaka, N. Imanishi, et al. (2018)
• Extended pleurectomy decortication for thymoma with pleural dissemination — N. Imanishi, Y. Nabe, et al. (2019)

Browse more research in The Annals of Thoracic Surgery, or return to medical research.