Sidhu Gangadharan1, Inderpal N Sarkaria2, David Rice3, Sudish Murthy4, Jerry Braun5, John Kucharczuk6, Jarrod Predina6, Sunil Singhal7. 1. Division of Thoracic Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 2. Division of Thoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania. 3. Division of Thoracic Surgery, MD Anderson Cancer Center, Houston, Texas. 4. Division of Thoracic Surgery, Cleveland Clinic, Cleveland, Ohio. 5. Division of Thoracic Surgery, University of Leiden, Leiden, the Netherlands. 6. Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. 7. Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. Electronic address: sunil.singhal@uphs.upenn.edu.
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.
RCT Entities:
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.
Authors: Gregory T Kennedy; Feredun S Azari; Elizabeth Bernstein; Bilal Nadeem; Ashley E Chang; Alix Segil; Neil Sullivan; Isvita Marfatia; Azra Din; Charuhas Desphande; John C Kucharczuk; Philip S Low; Sunil Singhal Journal: Mol Cancer Ther Date: 2022-04-01 Impact factor: 6.009
Authors: Gregory T Kennedy; Feredun S Azari; Elizabeth Bernstein; Charuhas Desphande; Azra Din; Isvita Marfatia; John C Kucharczuk; Edward J Delikatny; Philip S Low; Sunil Singhal Journal: Ann Thorac Surg Date: 2021-11-10 Impact factor: 5.102
Authors: Gregory T Kennedy; Feredun S Azari; Elizabeth Bernstein; Bilal Nadeem; Ashley Chang; Alix Segil; Sean Carlin; Neil T Sullivan; Emmanuel Encarnado; Charuhas Desphande; Sumith Kularatne; Pravin Gagare; Mini Thomas; John C Kucharczuk; Gaetan Christien; Francois Lacombe; Kaela Leonard; Philip S Low; Aline Criton; Sunil Singhal Journal: Nat Commun Date: 2022-05-17 Impact factor: 17.694
Authors: Gregory T Kennedy; Feredun S Azari; Elizabeth Bernstein; Isvita Marfatia; Azra Din; Charuhas Deshpande; Nikki Galvis; Jonathan Sorger; John C Kucharczuk; Sunil Singhal Journal: Transl Lung Cancer Res Date: 2022-08
Authors: Lisanne K A Neijenhuis; Lysanne D A N de Myunck; Okker D Bijlstra; Peter J K Kuppen; Denise E Hilling; Frank J Borm; Danielle Cohen; J Sven D Mieog; Willem H Steup; Jerry Braun; Jacobus Burggraaf; Alexander L Vahrmeijer; Merlijn Hutteman Journal: Life (Basel) Date: 2022-03-17