1978P - Identification of SDH-deficient GIST increases after the implementation of diagnostic algorithm in Life Raft Group (LRG) patient registry data

Background

Succinate dehydrogenase (SDH) deficient GISTs account for less than 10% of all GISTs and exhibit distinct biological features when compared to those that harbor KIT/PDGFRA mutations. SDH-deficient GIST commonly affects young adolescents with a baseline metastatic presentation and are frequently insensitive to tyrosine kinase inhibitors. The immunohistochemical (IHC) loss of SDH subunit B (SDHB) is a characteristic marker of SDH-deficient GIST, which is suggestive of the loss of function in the entire SDH-complex. With data from the LRG Patient Registry, a diagnostic algorithm illustrating the need for wider use of targeted diagnostic procedures was implemented in the College of American Pathologists (CAP) guidelines to facilitate the identification and treatment of SDH-deficient patients. Here, we aim to evaluate the results within our data after the implementation of such an algorithm.

Methods

The LRG Patient Registry is a global longitudinal natural history study that is supported by medical records, including pathology and genomic reports. Two datasets from the LRG Patient Registry were used in this study, with the data cutoff points being 2017 and 2022. A comparison of the total number of SDHx patients reported in each dataset was conducted. SDH-deficient patients reported an SDHx mutation and/or loss of SDHB IHC expression.

Results

Out of the (n=750) global patients that reported their mutation in 2017, 28 (3.7%) were identified as SDH-deficient. When comparing with the 2022 dataset, (n = 1387 with mutational results) 83 (6.0%) were identified as SDH-deficient. This represents a 60% increase in identified patients.

Conclusions

The absence of SDHB IHC staining as part of the regular pathology protocol led to the under-identification of SDH-deficient patients. This study emphasizes the significance of SDHB IHC staining and advanced mutational testing in the LRG Patient Registry population. It is encouraged that the use of SDHB IHC should be included in additional guidelines to optimize the identification, diagnosis, and management of SDH-deficient GIST patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.