Evaluation of OTL38-Generated Tumor-to-Background Ratio in Intraoperative Molecular Imaging-Guided Lung Cancer Resections.
Evaluation of OTL38-Generated Tumor-to-Background Ratio in Intraoperative Molecular Imaging-Guided Lung Cancer Resections.
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DOI：
10.1007/s11307-021-01618-9
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发表时间：
2023-03
影响因子：
3.1
通讯作者：
Singhal S
中科院分区：
文献类型：
--
作者：
Azari F;Kennedy G;Bernstein E;Delikatny J;Lee JYK;Kucharczuk J;Low PS;Singhal S
癌症手术面临多重挑战，包括定位小病灶、确保阴性切缘以及识别同步癌症。为解决这些问题而提出的工具之一是术中分子成像（IMI）。 IMI 的一个重要考虑因素是在手术过程中对肿瘤荧光进行量化，并使用该数据来增加临床价值。目前，最常引用的量化指标是肿瘤与背景比（TBR）。我们的目标是评估肺癌切除过程中使用 OTL38 NIR 示踪剂测量的 TBR 的临床价值。术中数据是从前瞻性收集的 5 年数据库中进行回顾性审查的。 2015 年至 2020 年间，该研究纳入了 279 名患者。为了标准化，所有患者在肺癌切除术中均输注相同的靶向分子光学造影剂（OTL38），然后计算肿瘤和背景组织的平均荧光强度。为了评估 TBR 计算的临床疗效，将结果与患者、生物、肿瘤和技术因素相关。对于肺部手术，性别、年龄、吸烟史、输注OTL38到手术的时间等患者因素对预测手术期间的TBR没有任何统计学意义。此外，TBR 测量值与肺部肿瘤的位置无关（p=0.123）。术前正电子发射断层扫描测量值[标准化摄取值]与术中 TBR 没有统计学相关性。然而，原位TBR测量与病变距器官表面的距离存在统计学上显着的负相关性(p<0.001)。与其他 NSCLC 恶性肿瘤相比，腺癌谱系病变总体上与原位荧光具有统计学显着相关性 (p<0.01)，但 TBR 测量无法在单变量分析中识别组织病理学亚型 (p=0.089)。中分化和高分化腺癌谱系病变存在原位荧光趋势，但这没有统计学意义。当比较肺部良性结节与恶性结节的原位TBR时，没有统计学上显着的相关性（p=0.145）。在子集分析中，与其他组织学亚型相比，OTL38 的腺癌谱病变倾向于发出更亮的荧光。在我们的各种迭代中，我们的回顾性分析结果并未表明 OTL38 引导手术期间的 TBR 测量可提供有关结节或癌症性质的临床有用信息。 IMI 的真正价值在于外科医生能够使用荧光引导外科医生到达肿瘤和边缘，但荧光量的复杂量化可能没有临床实用性。
Cancer surgery has multiple challenges including localizing small lesions, ensuring negative margins, and identifying synchronous cancers. One of the tools proposed to address these issues is intraoperative molecular imaging (IMI). An important consideration in IMI is the quantification of the tumor fluorescence during the procedure and using that data to add clinical value. Currently, the most commonly cited measure of quantification is the tumor-to-background ratio (TBR). Our goal was to evaluate the clinical value of TBR measured with OTL38 NIR tracer during a lung cancer resection. Intraoperative data was retrospectively reviewed from a prospectively collected 5-year database. Between 2015 and 2020, 279 patients were included in the study. For standardization, all patients underwent infusion of the same targeted molecular optical contrast agent (OTL38) for lung cancer resections, then, the Mean Fluorescence Intensity of the tumors and background tissues were calculated. To evaluate the clinical efficacy of the TBR calculation, the results were correlated with patient, biologic, tumor, and technological factors. For pulmonary surgery, patient factors such as gender, age, smoking history, and time from infusion of OTL38 to surgery did not have any statistical significance in predicting the TBR during surgery. In addition, TBR measurements did not correlate with location of the tumor in the lung (p=0.123). There was no statistical correlation of preoperative positron emission tomography measurements [standardized uptake value] with intraoperative TBR. However, there was statistically significant negative correlation of in-situ TBR measurement and the distance of the lesion from the surface of the organ (p<0.001). Adenocarcinoma spectrum lesions overall had statistically significant correlation with in-situ fluorescence compared to other NSCLC malignancies (p<0.01) but TBR measurements could not identify histopathologic subtype on univariate analysis (p=0.089). There was a tendency for in-situ fluorescence for moderately and well-differentiated adenocarcinoma spectrum lesions, but this was not statistically significant. When comparing the in-situ TBR of benign to malignant nodules in the lung, there was no statistically significant association(p=0.145). In subset analysis, adenocarcinoma spectrum lesions tend to fluoresce at brighter with OTL38 compared to other histologic subtypes. In our various iterations, the results of our retrospective analysis did not show that TBR measurements during OTL38 guided surgery provide clinically useful information about the nature of the nodule or cancer. The true value of IMI is in the ability for the surgeon to use the fluorescence to guide to the surgeon to the tumor and margins, but that sophisticated quantification of the amount of fluorescence may not have clinical utility.
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