Intraoperative Molecular Imaging Combined With Positron Emission Tomography Improves Surgical Management of Peripheral Malignant Pulmonary Nodules

被引:52
作者
Predina, Jarrod D. [1 ,2 ,3 ]
Newton, Andrew D. [1 ,4 ]
Keating, Jane [1 ,4 ]
Barbosa, Eduardo M., Jr. [5 ]
Okusanya, Olugbenga [1 ,2 ]
Xia, Leilei [1 ]
Dunbar, Ashley [1 ,2 ]
Connolly, Courtney [1 ,2 ]
Baldassari, Michael P. [1 ,2 ]
Mizelle, Jack [1 ,2 ]
Delikatny, Edward J. [5 ]
Kucharczuk, John C. [1 ,2 ]
Deshpande, Charuhas [6 ]
Kularatne, Sumith A. [7 ,8 ,9 ]
Low, Phillip [7 ,8 ,9 ]
Drebin, Jeffrey [1 ,4 ]
Singhal, Sunil [1 ,2 ]
机构
[1] Univ Penn, Ctr Precis Surg, Perelman Sch Med, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Surg, Div Thorac Surg, Perelman Sch Med, Philadelphia, PA 19104 USA
[3] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Boston, MA USA
[4] Univ Penn, Dept Surg, Perelman Sch Med, Philadelphia, PA 19104 USA
[5] Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA
[6] Univ Penn, Pathol & Lab Med Hosp, Philadelphia, PA 19104 USA
[7] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA
[8] Purdue Univ, Purdue Inst Drug Discovery, W Lafayette, IN 47907 USA
[9] Target Labs, W Lafayette, IN USA
关键词
folate receptor; molecular imaging; pulmonary adenocarcinoma; surgery; LUNG-CANCER; BREAST-CANCER; FDG-PET; TUMOR; DIAGNOSIS; EXPRESSION; ACCURACY; BIOPSY; HEAD;
D O I
10.1097/SLA.0000000000002382
中图分类号
R61 [外科手术学];
学科分类号
摘要
Objective: To determine if intraoperative molecular imaging (IMI) can improve detection of malignant pulmonary nodules. Background: 18-Fluorodeoxyglucose positron emission tomography (PET) is commonly utilized in preoperative assessment of patients with solid malignancies; however, false negatives and false positives remain major limitations. Using patients with pulmonary nodules as a study model, we hypothesized that IMI with a folate receptor targeted near-infrared contrast agent (OTL38) can improve malignant pulmonary nodule identification when combined with PET. Methods: Fifty patients with pulmonary nodules with imaging features suspicious for malignancy underwent preoperative PET. Patients then received OTL38 before pulmonary resection. During resection, IMI was utilized to evaluate known pulmonary nodules and identify synchronous lesions. Tumor size, PET standardized uptake value, and IMI tumor-to-background ratios were compared for known and synchronous nodules via paired and unpaired t tests, when appropriate. Test characteristics of PET and IMI with OTL38 were compared. Results: IMI identified 56 of 59 (94.9%) malignant pulmonary nodules identified by preoperative imaging. IMI located an additional 9 malignant lesions not identified preoperatively. Nodules only detected by IMI were smaller than nodules detected preoperatively (0.5 vs 2.4 cm; P < 0.01), but displayed similar fluorescence (tumor-to-background ratio 3.3 and 3.1; P = 0.50). Sensitivity of IMI and PET were 95.6% and 73.5% (P = 0.001), respectively; and positive predictive values were 94.2% and 89.3%, respectively (P > 0.05). Additionally, utilization of IMI clinically upstaged 6 (12%) subjects and improved management of 15 (30%) subjects. Conclusions: These data suggest that combining IMI with PET may provide superior oncologic outcomes for patients with resectable lung cancer.
引用
收藏
页码:479 / 488
页数:10
相关论文
共 30 条
[1]  
[Anonymous], CHEST, DOI DOI 10.1378/CHEST.07-1352
[2]   Concordance of folate receptor-α expression between biopsy, primary tumor and metastasis in breast cancer and lung cancer patients [J].
Boogerd, Leonora S. F. ;
Boonstra, Martin C. ;
Beck, Ann-Jean ;
Charehbili, Ayoub ;
Hoogstins, Charlotte E. S. ;
Prevoo, Hendrica A. J. M. ;
Singhal, Sunil ;
Low, Philip S. ;
van de Velde, Cornelis J. H. ;
Vahrmeijer, Alexander L. .
ONCOTARGET, 2016, 7 (14) :17442-17454
[3]   The maximum standardized uptake values on integrated FDG-PET/CT is useful in differentiating benign from malignant pulmonary nodules [J].
Bryant, Ayesha S. ;
Cerfolio, Robert James .
ANNALS OF THORACIC SURGERY, 2006, 82 (03) :1016-1020
[4]   Evaluation of follow-up strategies for patients with epithelial ovarian cancer following completion of primary treatment [J].
Clarke, Tilean ;
Galaal, Khadra ;
Bryant, Andrew ;
Naik, Raj .
COCHRANE DATABASE OF SYSTEMATIC REVIEWS, 2014, (09)
[5]   Accuracy of FDG-PET to Diagnose Lung Cancer in Areas With Infectious Lung Disease A Meta-analysis [J].
Deppen, Stephen A. ;
Blume, Jeffrey D. ;
Kensinger, Clark D. ;
Morgan, Ashley M. ;
Aldrich, Melinda C. ;
Massion, Pierre P. ;
Walker, Ronald C. ;
McPheeters, Melissa L. ;
Putnam, Joe B., Jr. ;
Grogan, Eric L. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2014, 312 (12) :1227-1236
[6]   Preoperative Staging of Lung Cancer with Combined PET-CT. [J].
Fischer, Barbara ;
Lassen, Ulrik ;
Mortensen, Jann ;
Larsen, Soren ;
Loft, Annika ;
Bertelsen, Anne ;
Ravn, Jesper ;
Clementsen, Paul ;
Hogholm, Asbjorn ;
Larsen, Klaus ;
Rasmussen, Torben ;
Keiding, Susanne ;
Dirksen, Asger ;
Gerke, Oke ;
Skov, Birgit ;
Steffensen, Ida ;
Hansen, Hanne ;
Vilmann, Peter ;
Jacobsen, Grete ;
Backer, Vibeke ;
Maltbaek, Niels ;
Pedersen, Jesper ;
Madsen, Henrik ;
Nielsen, Henrik ;
Hojgaard, Liselotte .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (01) :32-39
[7]   Positron Emission Tomography (PET) in Oncology [J].
Gallamini, Andrea ;
Zwarthoed, Colette ;
Borra, Anna .
CANCERS, 2014, 6 (04) :1821-1889
[8]   Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions - A meta-analysis [J].
Gould, MK ;
Maclean, CC ;
Kuschner, WG ;
Rydzak, CE ;
Owens, DK .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2001, 285 (07) :914-924
[9]   Early Lung Cancer Action Project: overall design and findings from baseline screening [J].
Henschke, CI ;
McCauley, DI ;
Yankelevitz, DF ;
Naidich, DP ;
McGuinness, G ;
Miettinen, OS ;
Libby, DM ;
Pasmantier, MW ;
Koizumi, J ;
Altorki, NK ;
Smith, JP .
LANCET, 1999, 354 (9173) :99-105
[10]   Effectiveness of positron emission tomography for the detection of melanoma metastases [J].
Holder, WD ;
White, RL ;
Zuger, JH ;
Easton, EJ ;
Greene, FL .
ANNALS OF SURGERY, 1998, 227 (05) :764-771