Complete Response to Sequential Peptide Receptor Radionuclide Therapy and Sunitinib in SDHB-mutated Metastatic Paraganglioma

ABSTRACT We report a rare case of SDHB-related metastatic abdominal paraganglioma (PGL) in a 24-year-old male patient that demonstrates the clinical significance of precision medicine in oncology. The patient presented with a retroperitoneal mass and widespread metastatic disease involving bone and lymph nodes. Histopathological examination confirmed PGL with characteristic neuroendocrine features. Comprehensive genetic testing revealed a heterozygous pathogenic nonsense mutation in exon 4 of the SDHB gene (c.343C>T; p. Arg115Ter), causing premature protein termination at amino acid 115 instead of the normal 280 amino acids, resulting in loss of major functional domains. Next-generation sequencing of somatic tissue confirmed the mutation with 71% allelic burden, along with several variants of uncertain significance in other genes. The patient initially received peptide receptor radionuclide therapy (PRRT) with Lutetium-177 DOTATATE for 8 months, showing initial response followed by disease progression. Subsequently, combination therapy with somatostatin analogues and targeted sunitinib therapy (37.5 mg, 21-day cycles) achieved complete resolution of metastatic lesions. This case emphasizes the critical role of genetic testing in young patients with PGL, as SDHB mutations confer high malignancy risk and influence treatment selection. The successful response to sequential targeted therapies following PRRT failure highlights the importance of personalized treatment approaches in SDHB-related PGLs. Comprehensive genetic counseling and family screening are essential given the autosomal dominant inheritance pattern and family history of cancer. This case contributes to the growing evidence supporting precision medicine approaches in rare neuroendocrine tumors.