Metastatic pheochromocytomas and paragangliomas: Proceedings of the MEN2019 workshop

Patricia L.M. Dahia, Roderick Clifton-Bligh, Anne Paule Gimenez-Roqueplo, Mercedes Robledo, Camilo Jimenez

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

Pheochromocytomas and paragangliomas (PPGLs) are adrenal or extra-adrenal autonomous nervous system-derived tumors. Most PPGLs are benign, but approximately 15% progress with metastases (mPPGLs). mPPGLs are more likely to occur in patients with large pheochromocytomas, sympathetic paragangliomas, and norepinephrine-secreting tumors. Older subjects, those with larger tumors and synchronous metastases, advance more rapidly. Germline mutations of SDHB, FH, and possibly SLC25A11, or somatic MAML3 disruptions relate to a higher risk for metastatic disease. Ho wever, it is unclear whether these mutations predict outcome. Once diagnosed, there are no well-established predictors of outcome in mPPGLs, and aggressive tumors have few therapeutic options and limited response. High-specific activity (HSA) metaiodine-benzyl-guanidine (MIBG) is the first FDA approved treatment and shows clinical effectiveness for MIBG-avid mPPGLs. Ongoing and future investigations should involve validation of emerging candidate outcome biomarkers, including somatic ATRX, TERT, and microRNA disruptions and identification of novel prognostic indicators. Long-term effect of HSA-MIBG and the role of other radiopharmaceuticals should be investigated. Novel trials targeting molecular events prevalent in SDHB/FH mutant tumors, such as activated hypoxia inducible factor 2 (HIF2), angiogenesis, or other mitochondrial defects that might confer unique vulnerability to these tumors should be developed and initiated. As therapeutic options are anticipated to expand, multi-institutional collaborations and well-defined clinical and molecular endpoints will be critical to achieve higher success rates in improving care for patients with mPPGLs.

Original languageEnglish (US)
Pages (from-to)T41-T52
JournalEndocrine-Related Cancer
Volume27
Issue number8
DOIs
StatePublished - Aug 2020

Keywords

  • Metastatic
  • Mutation
  • Paragangliomas
  • Pheochromocytomas
  • SDHB
  • Therapy

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

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