Resection extent and BRAF V600E mutation status determine postoperative tumor growth velocity in pediatric low-grade glioma: results from a single-center cohort analysis

Abstract

Purpose Despite excellent long-term overall survival rates, pediatric low-grade gliomas (pLGG) show high variety of clinical behavior regarding progress or senescence post incomplete resection (IR). This study retrospectively analyzes tumor growth velocity (TGV) of pLGG before surgery and after IR to investigate the impact of surgical extent, tumor location and molecular BRAF status on postoperative residual tumor growth behavior. Methods Of a total of 172 patients with pLGG receiving surgical treatment, 107 underwent IR (66%). Fifty-three vs 94 patients could be included in the pre- and post-operative cohort, respectively, and were observed over a mean follow-up time of 40.2 vs 60.1 months. Sequential three-dimensional MRI-based tumor volumetry of a total of 407 MRI scans was performed to calculate pre- and postoperative TGV. Results Mean preoperative TGV of 0.264 cm3/month showed significant deceleration of tumor growth to 0.085 cm3/month, 0.024 cm3/month and −0.016 cm3/month after 1st, 2nd, and 3rd IR, respectively (p < 0.001). Results remained significant after excluding patients undergoing (neo)adjuvant treatment. Resection extent showed correlation with postoperative reduction of TGV (R = 0.97, p < 0.001). ROC analysis identified a residual cut-off tumor volume > 2.03 cm3 associated with a higher risk of progress post IR (sensitivity 78,6%, specificity 76.3%, AUC 0.88). Postoperative TGV of BRAF V600E-mutant LGG was significantly higher than of BRAF wild-type LGG (0.123 cm3/month vs. 0.016 cm3/month, p = 0.047). Conclusion This data suggests that extensive surgical resection may impact pediatric LGG growth kinetics post incomplete resection by inducing a significant deceleration of tumor growth. BRAF-V600E mutation may be a risk factor for higher postoperative TGV.

Neurosurgical morbidity in pediatric supratentorial midline low‐grade glioma: Results from the German LGG studies

“…In line with this, of all patient‐ and procedure‐related factors that predicted the development of postoperative complications, preoperative tumor volume >80 cm 3 and complete resection correlated strongly with an increased number of neurosurgical morbidity. On the other hand, if radical resections are to be avoided, available evidence indicates that the percentage of residual tumor is less important for long‐term prognosis 14,18,45 . Thus, (re‐)resections have to be restricted with regard to the complication/impairments and the limited options for re‐intervention in the SML.…”

“…On the other hand, if radical resections are to be avoided, available evidence indicates that the percentage of residual tumor is less important for long-term prognosis. 14,18,45 Thus, (re-) resections have to be restricted with regard to the complication/ impairments and the limited options for re-intervention in the SML.…”

“…[13][14][15][16][17] Key drivers for tumor regrowth or relapse and patterns of behavior of the various tumor subtypes are not fully understood, yet size and site of tumor remnants play a significant role. 15,16,18 Thus, the benefit of extended surgical resection needs to be balanced against the risks of complications and late-effects. They need to be addressed besides all other management issues of pLGG including the indication for and the timing of other therapeutic interventions.…”

BRAF Landscape and Its Implications among Patients with Pediatric Low-Grade Gliomas: A Comprehensive Review of the Literature

“…67 In 2022, Gorodezki et al analyzed the tumor growth velocity of pediatric LGGs to evaluate the impact of BRAF V600E mutation and KIAA1549:BRAF fusion on tumor progression following subtotal resection. 80 The authors found that BRAF V600E mutant pediatric LGGs showed higher regrowth rates compared with BRAF wildtype pediatric LGGs. 80 The authors also reported that there was no significant difference in regrowth rates between pediatric LGGs that harbored KIAA1549:BRAF fusion and those that did not.…”

“…80 The authors found that BRAF V600E mutant pediatric LGGs showed higher regrowth rates compared with BRAF wildtype pediatric LGGs. 80 The authors also reported that there was no significant difference in regrowth rates between pediatric LGGs that harbored KIAA1549:BRAF fusion and those that did not. 80…”