Qing H Meng, MD, PhD, DABCC, FADLM
Professor, Department of Laboratory Medicine
University of Texas MD Anderson Cancer Center
The diagnosis of gastroenteropancreatic neuroendocrine tumors (GEP-NET) relies on patient
demographics, symptom assessment, imaging results by CT or MRI, and laboratory testing.
However, the current recommendations for using serum chromogranin A (CgA) for patients with GEP-NET are equivocal. In this prospective, multicenter, blinded observational study, the CASPAR study, Dr. Meng and collaborators investigated the clinical utility of serum CgA
concentration changes in detection of disease progression in GEP-NET patients. The CASPAR study was performed from January 2019 to December 2021 at three study sites in the United States (The University of Texas MD Anderson Cancer Center, Mayo Clinic, and Stanford University Medical Center) and one study site in Germany (Charit´e-Universit¨atsmedizin Berlin). This study recruited 153 adult patients with a total of 612 visits and serum CgA measurement, including153 baseline and 459 follow-up measurement. Tumor progression was evaluated with RECIST 1.1 by CT/MRI, and CgA concentrations were measured with the automated B·R·A·H·M·S CgA II KRYPTOR immunofluorescence assay on a B·R·A·H·M·S KRYPTOR Compact Plus instrument. An increase ≥50% above the prior CgA concentration to a value >100 ng/mL in the following CgA concentration was considered positive. Using this prespecified cut-off, the CgA change (ΔCgA) for tumor progression showed a specificity of 93.4% (95% confidence interval, 90.4-95.5%; P< 0.001), sensitivity of 34.4% (25.6-44.3%), positive predictive value of 57.9% (45.0-69.8%), negative predictive value of 84.3% (80.5-87.6%), and AUC 0.73 (0.67-0.79). These results indicate that changes in serial measurements of serum CgA had a favorable specificity and negative predictive value, making this test a useful adjunct to routine radiographic monitoring. This study provides a critical prospective evaluation of CgA’s performance in GEP-NET patients. The authors also introduced a novel clinical algorithm, which in combination with imaging modalities may aid in the assessment of patients’ disease progression and timing of follow-up within the range of current practice guidelines, particularly when RECIST 1.1 is not the standard of care. For a patient without known confounding comorbidities or medication exposure, and in whom the clinician has a strong prior suspicion of progressive disease, a positive ΔCgA may indicate that a progression has occurred and therefore further assessment may be warranted, including additional imaging modalities such as PET-CT if standard images were negative or of poor resolution. A negative ΔCgA, together with routine clinical assessment, may support the exclusion of tumor progression and may support a decision to perform imaging at the next suitable follow-up visit. In summary, this study successfully validated circulating CgA as a surveillance biomarker in GEP-NET, making it a useful adjunct to routine radiographic monitoring.
血清嗜铬粒蛋白A作为类癌患者的监测标志物——CASPAR研究
胃肠胰神经内分泌肿瘤（GEP-NET）的诊断依赖于患者的年龄，性别，种族等人口统计学资料、症状评估、CT或MRI的影像结果以及实验室检测。目前关于使用血清嗜铬粒蛋白A（CgA）对GEP-NET患者的推荐尚不明确。在这项前瞻性、多中心、盲法观察研究，CASPAR研究中，孟博士及其合作者调查了血清CgA浓度变化在GEP-NET患者疾病进展检测中的临床应用价值。CASPAR研究于2019年1月至2021年12月在美国的三个研究中心（德克萨斯大学MD安德森癌症中心、梅奥诊所和斯坦福大学医学中心）以及德国的一个研究中心（柏林夏里特大学医学中心) 进行。 该研究招募了153名成年病人, 共计612次就诊及CgA 检测，包括153次基础检测和459次随访检测。肿瘤进展通过CT/MRI的RECIST 1.1进行评估。CgA浓度通过B·R·A·H·M·S CgA II KRYPTOR免疫荧光检测在B·R·A·H·M·S KRYPTOR Compact Plus仪器上测量。CgA浓度在随后的CgA浓度中增加≥50%并超过100 ng/mL被视为阳性。使用这一预设的临界值，肿瘤进展的CgA变化（ΔCgA）显示出93.4%的特异性（95%置信区间，90.4–95.5%；P<0.001），34.4%的敏感性（25.6–44.3%），57.9%的阳性预测值（45.0–69.8%），84.3%的阴性预测值（80.5–87.6%），以及AUC 0.73（0.67–0.79）。这些结果表明，血清CgA的连续测量变化具有良好的特异性和阴性预测值，使该检测成为常规影像监测的有用补充。本研究对GEP-NET患者CgA的表现进行了关键的前瞻性评估。作者还引入了一种新颖的临床算法，该算法结合影像学方法可帮助评估患者的疾病进展以及在当前实践指南范围内的随访时间安排，特别是在RECIST 1.1并非标准诊疗的情况下。对于没有已知混杂合并症或药物暴露的患者，并且临床医生对进展性疾病有强烈的先前怀疑，阳性的ΔCgA可能表明已发生进展，因此可能需要进一步评估，包括在标准影像为阴性或分辨率差的情况下进行额外的影像学检查，如PET-CT。阴性的ΔCgA结合常规临床评估，可能支持排除肿瘤进展，并可能支持在下次合适的随访访问中进行影像学检查的决定。总之，这项研究成功验证了血清CgA作为胃肠胰神经内分泌肿瘤的监测标志物的临床意义，使其成为常规影像学监测的有用补充。
References:
1. Meng QH, Halfdanarson TR, Bornhorst JA, Jann H, Shaheen S, Shi RZ, Schwabe A, Stade
K, Halperin DM. Circulating Chromogranin A as a Surveillance Biomarker in Patients with
Carcinoids-The CASPAR Study. Clin Cancer Res. 2024 Dec 16;30(24):5559-5567.
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