Impacts of genotypic variants on survival following reoperation for recurrent glioblastoma.
Impacts of genotypic variants on survival following reoperation for recurrent glioblastoma.
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复发性胶质母细胞瘤再手术后基因型变异对生存率的影响。
DOI：
10.1007/s11060-021-03917-1
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发表时间：
2022-01
影响因子：
3.9
通讯作者：
Tandon, Nitin
中科院分区：
文献类型：
--
作者：
Dono, Antonio;Zhu, Ping;Holmes, Emma;Takayasu, Takeshi;Zhu, Jay-Jiguang;Blanco, Angel, I;Hsu, Sigmund;Bhattacharjee, Meenakshi B.;Ballester, Leomar Y.;Kim, Dong H.;Esquenazi, Yoshua;Tandon, Nitin
复发性胶质母细胞瘤（rGBM）的预后很差。在缺乏有效的辅助治疗rGBM，再切除仍然是突出的，在我们的阿森纳。本研究评估了考虑rGBM基因组成的再手术对进展后生存期（PPS）的影响。为了评估遗传异质性和治疗相关变化（TRC）在再次手术或药物管理的rGBM中的作用，我们汇编了2005年1月至2019年10月这些肿瘤的人口统计学，临床，组织病理学和下一代基因测序（NGS）特征。使用常规和随机生存森林分析（RSF）分析生存数据和再次手术。携带CDKN 2 A/B缺失（p = 0.017）和KDR突变（p = 0.031）的患者生存期明显较短。再次手术或贝伐珠单抗与PPS时间延长相关（11.2 vs 7.4个月，p = 0.006; 13.1 vs 6.2，p < 0.001）。再次手术的患者更年轻，有更好的性能状态和更大的初始切除。在136/273例（49%）接受再次手术的rGBM中，CDKN 2 A/B缺失（p = 0.03）和KDR突变（p = 0.02）与较短的生存期相关。在具有NGS数据的IDH-WT rGBM中（n = 166），再次手术导致生存期比药物治疗长7.0个月（p = 0.004）。通过RSF分析独立确定了这种再手术受益。分层分析显示，EGFR突变体、CDKN 2A/B突变体、NF 1-WT和TP 53-WT rGBM IDH-WT亚组从再次手术中获益最大（p = 0.03）。最后，再次手术时TRC是否显著对PPS没有任何显著影响（10.5 vs. 11.5个月，p = 0.77）。无论基因组成如何，最大安全性再切除术均显著延长PPS，但再手术尤其有益于具有EGFR和CDKN 2A/B突变的IDH-WT rGBM（具有TP 53-WT和NF 1-WT）。复发时的组织病理学可能无法完美衡量疾病进展时的严重程度，而成像进展可能更能反映预后。
Recurrent glioblastoma (rGBM) prognosis is dismal. In the absence of effective adjuvant treatments for rGBM, re-resections remain prominent in our arsenal. This study evaluates the impact of reoperation on post-progression survival (PPS) considering rGBM genetic makeup. To assess the genetic heterogeneity and treatment-related changes (TRC) roles in re-operated or medically managed rGBMs, we compiled demographic, clinical, histopathological, and next-generation genetic sequencing (NGS) characteristics of these tumors from 01/2005 to 10/2019. Survival data and reoperation were analyzed using conventional and random survival forest analysis (RSF). Patients harboring CDKN2A/B loss (p = 0.017) and KDR mutations (p = 0.031) had notably shorter survival. Reoperation or bevacizumab were associated with longer PPS (11.2 vs. 7.4-months, p = 0.006; 13.1 vs 6.2, p < 0.001). Reoperated patients were younger, had better performance status and greater initial resection. In 136/273 (49%) rGBMs undergoing re-operation, CDKN2A/B loss (p = 0.03) and KDR mutations (p = 0.02) were associated with shorter survival. In IDH-WT rGBMs with NGS data (n = 166), reoperation resulted in 7.0-month longer survival (p = 0.004) than those managed medically. This reoperation benefit was independently identified by RSF analysis. Stratification analysis revealed that EGFR-mutant, CDKN2A/B-mutant, NF1-WT, and TP53-WT rGBM IDH-WT subgroups benefit most from reoperation (p = 0.03). Lastly, whether or not TRC was prominent at re-operation does not have any significant impact on PPS (10.5 vs. 11.5-months, p = 0.77). Maximal safe re-resection significantly lengthens PPS regardless of genetic makeup, but reoperations are especially beneficial for IDH-WT rGBMs with EGFR and CDKN2A/B mutations with TP53-WT, and NF1-WT. Histopathology at recurrence may be an imperfect gauge of disease severity at progression and the imaging progression may be more reflective of the prognosis.
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影响因子：
4.1
作者：
Chaichana KL;Zadnik P;Weingart JD;Olivi A;Gallia GL;Blakeley J;Lim M;Brem H;Quiñones-Hinojosa A
通讯作者：
Quiñones-Hinojosa A
影响因子：
4.1
作者：
Chang, SM;Parney, IF;Berger, M
通讯作者：
Berger, M
影响因子：
2
作者：
Delgado-Fernandez, Juan;Angeles Garcia-Pallero, Maria;Sola, Rafael G.
通讯作者：
Sola, Rafael G.
影响因子：
3.9
作者：
Azoulay, M.;Santos, F.;Abdulkarim, Bassam S.
通讯作者：
Abdulkarim, Bassam S.
影响因子：
46.9
作者：
Frampton GM;Fichtenholtz A;Otto GA;Wang K;Downing SR;He J;Schnall-Levin M;White J;Sanford EM;An P;Sun J;Juhn F;Brennan K;Iwanik K;Maillet A;Buell J;White E;Zhao M;Balasubramanian S;Terzic S;Richards T;Banning V;Garcia L;Mahoney K;Zwirko Z;Donahue A;Beltran H;Mosquera JM;Rubin MA;Dogan S;Hedvat CV;Berger MF;Pusztai L;Lechner M;Boshoff C;Jarosz M;Vietz C;Parker A;Miller VA;Ross JS;Curran J;Cronin MT;Stephens PJ;Lipson D;Yelensky R
通讯作者：
Yelensky R