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Observational Study
. 2024 Dec 16;30(24):5559-5567.
doi: 10.1158/1078-0432.CCR-24-1875.

Circulating Chromogranin A as a Surveillance Biomarker in Patients with Carcinoids-The CASPAR Study

Qing H Meng  1 , Thorvardur R Halfdanarson  2 , Joshua A Bornhorst  3 , Henning Jann  4 , Shagufta Shaheen  5 , Run Zhang Shi  6 , Andrej Schwabe  7 , Katrin Stade  7 , Daniel M Halperin  8
Affiliations
Observational Study

Circulating Chromogranin A as a Surveillance Biomarker in Patients with Carcinoids-The CASPAR Study

Qing H Meng et al. Clin Cancer Res. .

Abstract

Purpose: Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are relatively indolent but can be more aggressive. The current recommendations for using serum chromogranin A (CgA) for patients with GEP-NET are equivocal. This study was designed to validate an automated CgA immunofluorescence assay for monitoring disease progression in patients with GEP-NET.

Patients and methods: A prospective, multicenter, blinded observational study was designed to validate an automated CgA immunofluorescence assay for monitoring disease progression in patients with GEP-NET. Tumor progression was evaluated with RECIST 1.1 by CT/MRI. An increase ≥50% above the prior CgA concentration to a value >100 ng/mL in the following CgA concentration was considered positive.

Results: A total of 153 patients with GEP-NET were enrolled. Using the prespecified cut-off of CgA change for tumor progression, specificity was 93.4% (95% confidence interval, 90.4%-95.5%; P < 0.001), sensitivity 34.4% (25.6%-44.3%), positive predictive value 57.9% (45.0-69.8), negative predictive value 84.3% (80.5-87.6), and AUC 0.73 (0.67-0.79).

Conclusions: 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.

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Conflict of interest statement

Q.H. Meng reports grants from Thermo Fisher Scientific during the conduct of the study and grants from the NIH outside the submitted work. T.R. Halfdanarson reports grants from Perspective Therapeutics, Thermo Fisher Scientific, Camurus, ITM Isotopen Technologien Muenchen, Crinetics, Novartis, and RayzeBio and personal fees from Exelixis, Curium, and TerSera during the conduct of the study and consulting fees, but no personal fees, from ITM, Ipsen, Novartis, Camurus, and Crinetics (fees went to Mayo Clinic). J.A. Bornhorst reports nonfinancial support from Thermo Fisher Scientific outside the submitted work. H. Jann reports nonfinancial support from Thermo Fisher Scientific during the conduct of the study and personal fees from Ipsen and Novartis outside the submitted work. A. Schwabe reports personal fees from Thermo Fisher Scientific during the conduct of the study. K. Stade reports personal fees from Thermo Fisher Scientific Germany during the conduct of the study and is an employee of Thermo Fisher Scientific (Germany) at the Medical Affairs Department. In his role as Medical Affairs Manager, he manages clinical study projects, such as the CASPAR study in which biomarker products of Thermo Fisher Scientific are being used. He usually provides scientific advice on biomarker products to Thermo Fisher Scientific’s academic cooperation partners/clinicians during the study. However, in his role as Medical Affairs Manager, he is not involved in commercial activities with the academic institutions/cooperation partners he works with. D.M. Halperin reports grants from Thermo Fisher Scientific during the conduct of the study and grants and personal fees from Novartis, ITM, and Camurus; grants from RayzeBio; personal fees from Exelixis, Chimeric Therapeutics, Crinetics, Lantheus, Harpoon Therapeutics, Radiomedix, and Amryt outside the submitted work. No disclosures were reported by the other authors.

Figures

Figure 1.
Figure 1.
A, Clinical trial profile. Inclusion and exclusion criteria. B, Study site visit information for intention-to-diagnose population. ECOG, Eastern Cooperative Oncology Group.
Figure 2.
Figure 2.
A, ROC curves for diagnosis of tumor progression in the intention-to-diagnose population with corresponding AUC. B, Box plots of continuous ΔCgA, simple ΔCgA, and CgA concentrations are shown with log-scaled axes. Strata of follow-up visits of the intention-to-diagnose population: no progression (blue) and progression (red). The horizontal gray lines show the prespecified cut-off 50% for ΔCgA.
Figure 3.
Figure 3.
Kaplan–Meier plots with proportion of progression-free patients with GEP-NET (%) during 24 months of follow-up in the intention-to-diagnose population, with stratification by primary tumor site (A; largest subgroups—pancreas and small intestine), presence of autonomous hormone secretion syndrome (B), tumor grade (C), treatment type (D), binary CgA at baseline (E), and binary ΔCgA at the first follow-up visit (F). The gray part in F indicates the period when 75% of the first follow-up visits after baseline occurred in the test-positive group (2–7 months, comparable time window in the test-negative group). Below each panel, the numbers of patients at risk are indicated for each timepoint and stratum. HR for comparison of the second (red) vs. the first stratum (blue), with 95% CI in brackets; P values are obtained from log-rank tests. D, HR for comparison with stratum “no agent and no procedure:” “only SSA” 0.66 (P = 0.37), “other agents or combinations” 1.19 (P = 0.70), and “procedure with or without SSA” 1.03 (P = 0.96). SSA, somatostatin analogues.
Figure 4.
Figure 4.
Clinical algorithm.
See this image and copyright information in PMC

References

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