Gong Matthew F, Li William T, Bhogal Sumail, Royes Brittany, Heim Tanya, Silvaggio Maria, Malek Marcus, Dhupar Rajeev, Lee Stella J, McGough Richard L, Weiss Kurt R
Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA.
Department of Pediatric General and Thoracic Surgery, Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA.
Cancers (Basel). 2023 Jan 18;15(3):582. doi: 10.3390/cancers15030582.
Soft tissue sarcomas (STS) are rare malignant tumors often associated with poor outcomes and high local recurrence rates. Current tools for intraoperative and definitive margin assessment include intraoperative frozen section and permanent pathology, respectively. Indocyanine green dye (ICG) is a historically safe fluorophore dye that has demonstrated efficacy for intraoperative margin assessment in the surgical management of both breast and gastrointestinal cancers. The utility of ICG in the surgical management of sarcoma surgery has primarily been studied in pre-clinical mouse models and warrants further investigation as a potential adjunct to achieving negative margins. This study is a prospective, non-randomized clinical study conducted on patients with confirmed or suspected STS. Patients younger than 18 years, with a prior adverse reaction to iodine or fluorescein, or with renal disease were excluded from the study. Intravenous ICG was infused approximately three hours prior to surgery at a dosage of 2.0-2.5 mg/kg, and following tumor resection, the excised tumor and tumor bed were imaged for fluorescence intensity. When scanning the tumor bed, a threshold of 77% calibrated to the region of maximum intensity in the resected tumor was defined as a positive ICG margin, according to published protocols from the breast cancer literature. ICG results were then compared with the surgeon's clinical impression of margin status and permanent pathology results. Out of 26 subjects recruited for the original study, 18 soft tissue sarcomas (STS) were included for analysis. Three subjects were excluded for having bone sarcomas, and five subjects were excluded due to final pathology, which was ultimately inconsistent with sarcoma. The average age of patients was 64.1 years old (range: 28-83), with an average ICG dose of 201.8 mg. In 56% (10/18) of patients, ICG margins were consistent with the permanent pathology margins, with 89% specificity. The use of ICG as an intraoperative adjunct to obtaining negative margins in soft tissue sarcoma surgery is promising. However, studies with larger sample sizes are warranted to further delineate the accuracy, optimal dosage, timing, and types of sarcoma in which this diagnostic tool may be most useful.
软组织肉瘤(STS)是罕见的恶性肿瘤,通常预后较差且局部复发率高。目前用于术中及最终切缘评估的工具分别是术中冰冻切片和永久病理检查。吲哚菁绿染料(ICG)是一种长期以来被认为安全的荧光染料,已证明其在乳腺癌和胃肠道癌手术管理中用于术中切缘评估的有效性。ICG在肉瘤手术管理中的效用主要在临床前小鼠模型中进行了研究,作为实现阴性切缘的潜在辅助手段,值得进一步研究。本研究是一项针对确诊或疑似STS患者的前瞻性、非随机临床研究。年龄小于18岁、既往对碘或荧光素有不良反应或患有肾脏疾病的患者被排除在研究之外。在手术前约三小时以2.0 - 2.5mg/kg的剂量静脉注射ICG,肿瘤切除后,对切除的肿瘤和肿瘤床进行荧光强度成像。根据乳腺癌文献公布的方案,在扫描肿瘤床时,以切除肿瘤中最大强度区域校准的77%阈值定义为ICG阳性切缘。然后将ICG结果与外科医生对切缘状态的临床印象和永久病理结果进行比较。在最初招募的26名受试者中,有18例软组织肉瘤(STS)纳入分析。3名受试者因患有骨肉瘤被排除,5名受试者因最终病理结果与肉瘤最终不符而被排除。患者的平均年龄为64.1岁(范围:28 - 83岁),平均ICG剂量为201.8mg。在56%(即10/18)的患者中,ICG切缘与永久病理切缘一致,特异性为89%。在软组织肉瘤手术中使用ICG作为获得阴性切缘的术中辅助手段是有前景的。然而,需要更大样本量的研究来进一步明确这种诊断工具在哪些肉瘤中最有用,以及其准确性、最佳剂量、时机和类型。