Felicella, Michelle M.

Abstract Background DNA methylation profiling can be used to robustly predict postsurgical outcomes and response to radiotherapy (RT) for meningioma patients. To allow for seamless integration of these complementary models into clinical practice, a practical framework is needed. Methods We leveraged a cohort of nearly 2000 surgically-treated meningiomas with DNA methylation profiling and clinical outcomes data. Existing methylation-based prediction models were dichotomized to yield four risk groups: low and high recurrent risk, each with RT sensitive and resistant subgroups. Risk groups were correlated with progression-free survival in the context of existing biomarkers including extent of resection and WHO grade. Results We first demonstrated that all risk groups benefit from gross total resection. All “high-risk, RT sensitive” tumors (n = 306, 15.7%) also benefited from adjuvant RT: after GTR, median PFS increased from 4.68 (4.13-9.48) years to not reached (P = .003); after subtotal resection (STR), from 2.12 (1.59-3.02) to 4.09 (3.41-not reached) years (P = .004). “Low-risk, RT sensitive cases” (n = 1207, 61.8%) also benefited from RT after STR (median PFS 7.39 (6.66-12.8) vs. 16.53 (10.35-not reached) years, P = .03), suggesting that RT be considered in these patients. Neither “low-risk RT resistant” (n = 84, 4.3%) nor “high-risk RT resistant” (n = 356, 18.2%) cases benefited from RT, and the latter group was associated with universally poor outcomes. Conclusions We identify methylation-defined risk groups of meningioma for which additional benefit is gained from adjuvant RT, leading to a clinical decision-making framework for straightforward integration of molecular models into clinical practice.

BACKGROUND Malignant peripheral nerve sheath tumors (MPNSTs) are rare and highly malignant tumors of neural crest origin. No matter their anatomical location, they are difficult to treat and carry a poor prognosis. OBSERVATIONS This report highlights the complexities of the diagnosis and management of a patient with MPNST of the cauda equina. The tumor retained the expression of H3K27me3, which is expected in spinal MPNSTs but uncommon in most sporadic and neurofibromatosis type 1–driven MPNSTs. LESSONS The described diagnostic nuance should be taken into consideration in patients with suspected MPNST of the cauda equina, as these tumors require swift neurosurgical intervention in order to maintain neurological function. Additional treatment modalities include neoadjuvant and adjuvant chemotherapy and radiotherapy. Although improvements in local control and progression-free survival have been reported, the role of radiation therapy and chemotherapy has been underinvestigated due to the rarity of MPNSTs presenting in this region. https://thejns.org/doi/10.3171/CASE24723