Retrospective and integrative analyses of molecular characteristics and their specific imaging parameters in pediatric grade 1 gliomas

Abstract

Background Pediatric low‐grade gliomas (PLGG) are the most common brain tumors diagnosed during childhood and represent a heterogeneous group associating variable molecular abnormalities. To go further and develop specific statistical patterns between tumor molecular background, imaging features, and patient outcome, a retrospective study was performed in a group of non‐neurofibromatosis type 1 (non‐NF1) grade 1 PLGGs. Patients and methods Seventy‐eight children, followed from 2004 to 2017, were retrospectively reported. In this population, we analyzed radiological and molecular parameters. Their therapeutic management comprised surgery or surgery plus chemotherapies. Results Considering all 78 patients, 59 had only a surgical removal and 19 patients were treated with postoperative chemotherapy. Twelve progressions were reported in the partially resected and chemotherapeutic groups, whereas four deaths occurred only in the highly treated patients. As expected, in the global cohort, PLGG with BRAF p.V600E and/or CDKN2A loss exhibited poor outcomes and we evidenced significant associations between those molecular characteristics and their imaging presentation. In the chemo‐treated patients, when associating initial and 6‐month magnetic resonance imaging (MRI) parameters to the molecular features, the good risk situations were significantly linked to the presence of a large tumor cyst at diagnosis and the appearance during treatment of a higher cystic proportion that we called cystic conversion. Conclusion So, additionally to the presence of BRAF p.V600E or CDKN2A deletion in grade 1 PLGGs, the absence on diagnostic MRI of cystic parts and/or cystic conversion at 6‐month chemotherapy were significantly linked to a worst prognosis and response to treatment. These imaging features should be considered as prognostic markers in future PLGG studies.

p16 Immunohistochemical Expression as a Surrogate Assessment of CDKN2A Alteration in Gliomas Leading to Prognostic Significances

“…Our results therefore suggest that evaluating CDKN2A status in adult low-grade diffuse gliomas is not mandatory. Nevertheless, although CDKN2A homozygous deletion was rare in our cohort, with only one case of PA, its presence in cases of low-grade MAPK-induced gliomas showed a dramatic clinical evolution, pointing out the possibly strong prognostic impact of CDKN2A homozygous deletion in those populations [23,24]. CDKN2A heterozygous deletion was observed in many tumor types without any prognostic impact.…”

Unlocking the power of precision medicine for pediatric low-grade gliomas: molecular characterization for targeted therapies with enhanced safety and efficacy

“…Reports show that both these mutations are related with oncogene-induced senescence escape and poorer OS and PFS (38,45,62). Therefore, pLGGs with CDKN2A deletions, particularly those with p.V600E or possible high-grade histological characteristics, should be considered highrisk tumors requiring close clinical follow-up (63). Finally, some studies have reported rare cases of BRAF missense variants at the p.V600 residue, in which valine is replaced with other amino acids such as lysine (p.V600K), aspartic acid (p.V600D), or arginine (p.V600R).…”

Medical Treatment of Pediatric Low-Grade Glioma

“…KIAA1549-BRAF rearrangements results in constitutive activation of the BRAF kinase with downstream activation of MAPK signaling. BRAF V600E mutations are also tumorigenic driver particularly in the group of ganglioglioma and pilocytic astrocytoma [ 7 29 ] and are associated with worse outcome when accompanying alterations of CDKN2A [ 31 32 ].…”