Abstract：
BACKGROUND: For patients with peritoneal carcinomatosis, extent of disease and completeness of cytoreductive surgery (CRS) are major prognostic factors for long-term survival. Assessment of these factors could be improved using imaging agents. Pegsitacianine is a pH-sensitive polymeric micelle conjugated to the fluorophore indocyanine green. The micelle disassembles in acidic microenvironments, such as tumors, resulting in localized fluorescence unmasking. We assessed the utility of pegsitacianine in detecting residual disease following CRS.
METHODS: NCT04950166 was a phase II, non-randomized, open-label, multicenter US study. Patients eligible for CRS were administered an intravenous dose of pegsitacianine at 1 mg/kg 24-72 h before surgery. Following CRS, the peritoneal cavity was reexamined under near-infrared (NIR) illumination to evaluate for fluorescent tissue. Fluorescent tissue identified was excised and evaluated by histopathology. The primary outcome was the rate of clinically significant events (CSE), defined as detection of histologically confirmed residual disease excised with pegsitacianine or a revision in the assessment of completeness of CRS. Secondary outcomes included acceptable safety and pegsitacianine performance.
RESULTS: A total of 53 patients were screened, 50 enrolled, and 40 were evaluable for CSE across six primary tumor types. Residual disease was detected with pegsitacianine in 20 of 40 (50%) patients. Pegsitacianine showed high sensitivity and was well tolerated with no serious adverse events (SAEs). Transient treatment-related, non-anaphylactic infusion reactions occurred in 28% of patients.
CONCLUSIONS: Pegsitacianine was well tolerated and facilitated the recognition of occult residual disease following CRS. The high rate of residual disease detected suggests that the use of pegsitacianine augmented surgeon assessment and performance during CRS.
METHODS: NCT04950166 was a phase II, non-randomized, open-label, multicenter US study. Patients eligible for CRS were administered an intravenous dose of pegsitacianine at 1 mg/kg 24-72 h before surgery. Following CRS, the peritoneal cavity was reexamined under near-infrared (NIR) illumination to evaluate for fluorescent tissue. Fluorescent tissue identified was excised and evaluated by histopathology. The primary outcome was the rate of clinically significant events (CSE), defined as detection of histologically confirmed residual disease excised with pegsitacianine or a revision in the assessment of completeness of CRS. Secondary outcomes included acceptable safety and pegsitacianine performance.
RESULTS: A total of 53 patients were screened, 50 enrolled, and 40 were evaluable for CSE across six primary tumor types. Residual disease was detected with pegsitacianine in 20 of 40 (50%) patients. Pegsitacianine showed high sensitivity and was well tolerated with no serious adverse events (SAEs). Transient treatment-related, non-anaphylactic infusion reactions occurred in 28% of patients.
CONCLUSIONS: Pegsitacianine was well tolerated and facilitated the recognition of occult residual disease following CRS. The high rate of residual disease detected suggests that the use of pegsitacianine augmented surgeon assessment and performance during CRS.
摘要：
背景：对于腹膜癌病患者，疾病的程度和细胞减灭术（CRS）的完整性是长期生存的主要预后因素。使用显像剂可以改善对这些因素的评估。Pegsitacianine是一种pH敏感的聚合物胶束，与荧光团吲哚菁绿结合。胶束在酸性微环境中分解，如肿瘤，导致局部荧光解掩蔽。我们评估了pegsitacianine在检测CRS后残留疾病中的实用性。
方法：NCT04950166为II期，非随机化，开放标签，美国多中心研究。符合CRS条件的患者在手术前24-72小时以1mg/kg的剂量静脉内给药。在CRS之后,在近红外（NIR）照明下重新检查腹膜腔，以评估荧光组织。切除鉴定的荧光组织并通过组织病理学评估。主要结果是临床重大事件（CSE）的发生率，定义为检测经组织学证实的残留疾病，并切除pegsitacianine或在CRS完整性评估中进行修订。次要结果包括可接受的安全性和pegsitacianine性能。
结果：共筛查了53例患者，50名注册，在六种原发性肿瘤类型中，有40种可评估CSE。在40例患者中的20例（50％）中，使用pegsitacianine检测到残留疾病。Pegsitacianine显示出高敏感性，耐受性良好，无严重不良事件（SAE）。短暂性治疗相关，28%的患者发生非过敏性输液反应.
结论：Pegsitacianine具有良好的耐受性，并促进了CRS后隐匿性残留病的识别。检测到的残留疾病的高比率表明，在CRS期间使用pegsitacianine增强了外科医生的评估和表现。
方法：NCT04950166为II期，非随机化，开放标签，美国多中心研究。符合CRS条件的患者在手术前24-72小时以1mg/kg的剂量静脉内给药。在CRS之后,在近红外（NIR）照明下重新检查腹膜腔，以评估荧光组织。切除鉴定的荧光组织并通过组织病理学评估。主要结果是临床重大事件（CSE）的发生率，定义为检测经组织学证实的残留疾病，并切除pegsitacianine或在CRS完整性评估中进行修订。次要结果包括可接受的安全性和pegsitacianine性能。
结果：共筛查了53例患者，50名注册，在六种原发性肿瘤类型中，有40种可评估CSE。在40例患者中的20例（50％）中，使用pegsitacianine检测到残留疾病。Pegsitacianine显示出高敏感性，耐受性良好，无严重不良事件（SAE）。短暂性治疗相关，28%的患者发生非过敏性输液反应.
结论：Pegsitacianine具有良好的耐受性，并促进了CRS后隐匿性残留病的识别。检测到的残留疾病的高比率表明，在CRS期间使用pegsitacianine增强了外科医生的评估和表现。
