RESUMO
OBJECTIVE: Intraoperative molecular imaging (IMI) using tumor-targeted optical contrast agents can improve thoracic cancer resections. There are no large-scale studies to guide surgeons in patient selection or imaging agent choice. Here, we report our institutional experience with IMI for lung and pleural tumor resection in 500 patients over a decade. METHODS: Between December 2011 and November 2021, patients with lung or pleural nodules undergoing resection were preoperatively infused with 1 of 4 optical contrast tracers: EC17, TumorGlow, pafolacianine, or SGM-101. Then, during resection, IMI was used to identify pulmonary nodules, confirm margins, and identify synchronous lesions. We retrospectively reviewed patient demographic data, lesion diagnoses, and IMI tumor-to-background ratios (TBRs). RESULTS: Five hundred patients underwent resection of 677 lesions. We found that there were 4 types of clinical utility of IMI: detection of positive margins (n = 32, 6.4% of patients), identification of residual disease after resection (n = 37, 7.4%), detection of synchronous cancers not predicted on preoperative imaging (n = 26, 5.2%), and minimally invasive localization of nonpalpable lesions (n = 101 lesions, 14.9%). Pafolacianine was most effective for adenocarcinoma-spectrum malignancies (mean TBR, 2.84), and TumorGlow was most effective for metastatic disease and mesothelioma (TBR, 3.1). False-negative fluorescence was primarily seen in mucinous adenocarcinomas (mean TBR, 1.8), heavy smokers (>30 pack years; TBR, 1.9), and tumors greater than 2.0 cm from the pleural surface (TBR, 1.3). CONCLUSIONS: IMI may be effective in improving resection of lung and pleural tumors. The choice of IMI tracer should vary by the surgical indication and the primary clinical challenge.
Assuntos
Neoplasias Pulmonares , Neoplasias Pleurais , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Pulmão/patologia , Imagem Molecular/métodosRESUMO
BACKGROUND: Intraoperative molecular imaging (IMI) using tumor-targeted optical contrast agents can improve cancer resections. The optimal wavelength of the IMI tracer fluorophore has never been studied in humans and has major implications for the field. To address this question, we investigated 2 spectroscopically distinct fluorophores conjugated to the same targeting ligand. METHODS: Between December 2011 and November 2021, patients with primary lung cancer were preoperatively infused with 1 of 2 folate receptor-targeted contrast tracers: a short-wavelength folate-fluorescein (EC17; λ em =520 nm) or a long-wavelength folate-S0456 (pafolacianine; λ em =793 nm). During resection, IMI was utilized to identify pulmonary nodules and confirm margins. Demographic data, lesion diagnoses, and fluorescence data were collected prospectively. RESULTS: Two hundred eighty-two patients underwent resection of primary lung cancers with either folate-fluorescein (n=71, 25.2%) or pafolacianine (n=211, 74.8%). Most tumors (n=208, 73.8%) were invasive adenocarcinomas. We identified 2 clinical applications of IMI: localization of nonpalpable lesions (n=39 lesions, 13.8%) and detection of positive margins (n=11, 3.9%). In each application, the long-wavelength tracer was superior to the short-wavelength tracer regarding depth of penetration, signal-to-background ratio, and frequency of event. Pafolacianine was more effective for detecting subpleural lesions (mean signal-to-background ratio=2.71 vs 1.73 for folate-fluorescein, P <0.0001). Limit of signal detection was 1.8 cm from the pleural surface for pafolacianine and 0.3 cm for folate-fluorescein. CONCLUSIONS: Long-wavelength near-infrared fluorophores are superior to short-wavelength IMI fluorophores in human tissues. Therefore, future efforts in all human cancers should likely focus on long-wavelength agents.
Assuntos
Cuidados Intraoperatórios , Neoplasias Pulmonares , Fluoresceínas , Corantes Fluorescentes , Ácido Fólico , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Imagem Molecular/métodosRESUMO
BACKGROUND: Complete pulmonary metastasectomy for sarcoma metastases provides patients an opportunity for long-term survival and possible cure. Intraoperative localization of preoperatively identified metastases and identification of occult lesions can be challenging. In this trial, we evaluated the efficacy of near-infrared (NIR) intraoperative imaging using second window indocyanine green during metastasectomy to identify known metastases and to detect occult nodules. METHODS: Thirty patients with pulmonary nodules suspicious for sarcoma metastases were enrolled in an open-label, feasibility study (NCT02280954). All patients received intravenous indocyanine green (5 mg/kg) 24 hours before metastasectomy. Patients 1 through 10 (cohort 1) underwent metastasectomy via thoracotomy to assess fluorescence patterns of nodules detected by traditional methods (preoperative imaging and intraoperative visualization/bimanual palpation). After confirming reliability within cohort 1, patients 11 through 30 (cohort 2) underwent video-assisted thoracic surgery metastasectomy with NIR imaging. RESULTS: In cohort 1, 14 out of 16 preoperatively identified pulmonary metastases (87.5%) displayed tumor fluorescence. Nonfluorescent metastases were deeper than fluorescent metastases (2.1 cm vs 1.3 cm; P = .03). Five out of 5 metastases identified during thoracotomy displayed fluorescence. NIR imaging identified 3 additional occult lesions in this cohort. In cohort 2, 33 out of 37 known pulmonary metastases (89.1%) displayed fluorescence. Nonfluorescent tumors were deeper than 2.0 cm (P = .007). NIR imaging identified 24 additional occult lesions. Of 24 occult lesions, 21 (87.5%) were confirmed metastases and the remaining 3 nodules were lymphoid aggregates. CONCLUSIONS: NIR intraoperative imaging with indocyanine green (5 mg/kg and 24 hours before surgery) localizes known sarcoma pulmonary metastases and identifies otherwise occult lesions. This approach may be a useful intraoperative adjunct to improve metastasectomy.
Assuntos
Neoplasias Pulmonares/cirurgia , Metastasectomia/métodos , Nódulos Pulmonares Múltiplos/cirurgia , Imagem Óptica/métodos , Pneumonectomia , Sarcoma/cirurgia , Nódulo Pulmonar Solitário/cirurgia , Espectroscopia de Luz Próxima ao Infravermelho , Cirurgia Torácica Vídeoassistida , Toracotomia , Adulto , Idoso , Estudos de Viabilidade , Feminino , Corantes Fluorescentes/administração & dosagem , Humanos , Verde de Indocianina/administração & dosagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Masculino , Metastasectomia/efeitos adversos , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/secundário , Pneumonectomia/efeitos adversos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sarcoma/diagnóstico por imagem , Sarcoma/secundário , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/secundário , Cirurgia Torácica Vídeoassistida/efeitos adversos , Toracotomia/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Adulto JovemRESUMO
OBJECTIVE: To determine if intraoperative near-infrared (NIR) imaging carries benefit in resection of pancreatic neoplasms. BACKGROUND: Resection of pancreatic malignancies is hindered by high rates of local and distant recurrence from positive margins and unrecognized metastases. Improved tumor visualization could improve outcomes. We hypothesized that intraoperative NIR imaging with a clinically approved optical contrast agent could serve as a useful adjunct in assessing margins and extent of disease during pancreatic resections. METHODS: Twenty patients were enrolled in an open-label clinical trial from July 2016 to May 2018. Subjects received second window indocyanine green (ICG) (2.5-5âmg/kg) 24âhours prior to pancreatic resection. NIR imaging was performed during staging laparoscopy and after pancreas mobilization in situ and following resection ex vivo. Tumor fluorescence was quantified using tumor-to-background ratio (TBR). Fluorescence at the specimen margin was compared to pathology evaluation. RESULTS: Procedures included 9 pancreaticoduodenectomies, 10 distal pancreatectomies, and 1 total pancreatectomy; 21 total specimens were obtained. Three out of 8 noninvasive tumors were fluorescent (mean TBR 2.59â±â2.57). Twelve out of 13 invasive malignancies (n = 12 pancreatic adenocarcinoma, n = 1 cholangiocarcinoma) were fluorescent (mean TBR 4.42â±â2.91). Fluorescence at the transection margin correlated with final pathologic assessment in 12 of 13 patients. Following neoadjuvant therapy, 4 of 5 tumors were fluorescent; these 4 tumors showed no treatment response on pathology assessment. One tumor had a significant treatment response and showed no fluorescence. CONCLUSIONS: Second window ICG reliably accumulates in invasive pancreatic malignancies and provides real-time feedback during pancreatectomy. NIR imaging may help to assess the response to neoadjuvant therapy.
Assuntos
Adenocarcinoma/cirurgia , Cuidados Intraoperatórios/métodos , Imagem Óptica/métodos , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adenocarcinoma/diagnóstico por imagem , Adulto , Idoso , Estudos de Viabilidade , Feminino , Corantes Fluorescentes , Humanos , Verde de Indocianina , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico por imagem , Estudos ProspectivosRESUMO
OBJECTIVE: To propose a novel method to perform indocyanine green (ICG) based near-infrared (NIR) fluorescence imaging during pelvic lymph node dissection (PLND) for prostate cancer patients with lymph node metastasis (LNM). MATERIALS AND METHODS: A prostate cancer cell line PC3 was used to establish xenograft model in NOD/SCID mice. After tumor growth, the mice were injected with ICG through the tail vein. Xenografts and surrounding tissues were imaged with NIR camera 24 hours after intravenous ICG, and tumor-to-background ratios were calculated. We then performed a pilot human study to evaluate the role of NIR imaging in robotic PLND after systemic ICG in 4 patients with prostate cancer and preoperative lymphadenopathy. RESULTS: ICG localized to PC3 xenografts in the mice and all xenografts were highly fluorescent compared with surrounding tissues, with a median tumor-to-background ratio of 2.85 (interquartile range = 2.64-3.90). In the human study, intraoperative in vivo NIR imaging identified 3 of the 4 preoperative lymphadenopathies as fluorescence-positive, and back table ex vivo NIR imaging identified all 4 lymphadenopathies as fluorescence-positive. All the lymphadenopathies were found to be LNMs by pathologic examination. Two of the four cases had additional LNMs, all of which were fluorescence-positive with intraoperative in vivo NIR imaging. CONCLUSION: Intravenously administered ICG accumulates in prostate cancers in both a murine model and human patients. NIR fluorescence based on intravenous ICG may serve as a useful tool to facilitate the identification of positive nodes during PLND in patients with higher risk of LNMs.