Department of Hematology and Oncology, University Children's Hospital Tübingen, Tübingen, Germany.
Section of Pediatric Neurosurgery, Department of Neurosurgery, University Hospital Tübingen, Tübingen, Germany.
J Neurooncol. 2022 Dec;160(3):567-576. doi: 10.1007/s11060-022-04176-4. Epub 2022 Nov 1.
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.
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.
Mean preoperative TGV of 0.264 cm/month showed significant deceleration of tumor growth to 0.085 cm/month, 0.024 cm/month and -0.016 cm/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 cm 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 cm/month vs. 0.016 cm/month, p = 0.047).
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.
尽管小儿低级别胶质瘤(pLGG)的长期总生存率非常高,但在不完全切除(IR)后,其临床进展或衰老的表现存在很大差异。本研究回顾性分析了 pLGG 术前和术后的肿瘤生长速度(TGV),以研究手术范围、肿瘤位置和分子 BRAF 状态对术后残留肿瘤生长行为的影响。
在接受手术治疗的 172 例 pLGG 患者中,有 107 例行 IR(66%)。分别有 53 例和 94 例患者可纳入术前和术后队列,平均随访时间分别为 40.2 个月和 60.1 个月。对总共 407 次 MRI 扫描进行了基于三维 MRI 的肿瘤体积测量,以计算术前和术后 TGV。
平均术前 TGV 为 0.264 cm/月,在首次、第二次和第三次 IR 后,肿瘤生长速度分别显著减慢至 0.085 cm/月、0.024 cm/月和-0.016 cm/月(p<0.001)。在排除接受(新)辅助治疗的患者后,结果仍然具有统计学意义。切除范围与术后 TGV 降低相关(R=0.97,p<0.001)。ROC 分析确定残余肿瘤体积>2.03 cm 与 IR 后进展的风险较高相关(敏感性 78.6%,特异性 76.3%,AUC 0.88)。BRAF V600E 突变型 LGG 的术后 TGV 明显高于 BRAF 野生型 LGG(0.123 cm/月 vs. 0.016 cm/月,p=0.047)。
本研究数据表明,广泛的手术切除可能通过显著减缓肿瘤生长来影响不完全切除后小儿 LGG 的生长动力学。BRAF-V600E 突变可能是术后 TGV 较高的危险因素。