Abdallah Hussein M, Gersey Zachary C, Muthiah Nallammai, McDowell Michael M, Pearce Thomas, Costacou Tina, Snyderman Carl H, Wang Eric W, Gardner Paul A, Zenonos Georgios A
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States.
Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
J Neurol Surg B Skull Base. 2021 Jun 22;82(6):601-607. doi: 10.1055/s-0041-1730958. eCollection 2021 Dec.
Previous work categorized skull base chordoma (SBC) into three genetic risk groups based on 1p36 and homozygous 9p21(p16) deletions, accounting for a wide variability in prognosis (A = low-risk, B = intermediate-risk, C = high-risk). However, it remains unclear how these groups could guide management. By integrating surgical outcome and adjuvant radiation (AdjXRT) information with genetic data on 152 tumors, we sought to develop an evidence-based management algorithm for SBC. Gross total resections (GTRs) were associated with improved progression free survival (PFS) in all genetic groups. For Group C tumors, GTR and AdjXRT independently contributed to PFS (multivariate Cox proportional hazard ratio [HR] = 0.14, = 0.002, and HR = 0.40, = 0.047, respectively). For Group B tumors, AdjXRT improved outcomes only when GTR was not feasible (log-rank = 0.008), but not following GTR (log-rank = 0.54). However, 24 of 25 Group A tumors underwent GTR, and AdjXRT for these did not confer any benefit (log-Rank = 0.285). The high GTR rates in Group A could be explained by smaller tumor sizes (mean = 0.98cc/4.08cc/4.92cc for Group A/B/C, respectively, = 0.031) and lack of invasiveness. Group A tumors were also more frequently diagnosed in young people ( = 0.002) as asymptomatic lesions ( = 0.001), suggesting that they could be precursors to tumors in higher risk groups. Genotypic grouping by 1p36 and homozygous 9p21(p16) deletions can predict prognosis in SBC and guide management. GTR remains the cornerstone of SBC treatment and can be sufficient without AdjXRT in low and intermediate risk tumors. Low-risk tumors are associated with a less invasive phenotype, which makes them more amenable to GTR.
先前的研究根据1p36和纯合9p21（p16）缺失将颅底脊索瘤（SBC）分为三个遗传风险组，这解释了预后的广泛差异（A =低风险，B =中度风险，C =高风险）。然而，目前尚不清楚这些分组如何指导治疗。通过将152例肿瘤的手术结果和辅助放疗（AdjXRT）信息与遗传数据相结合，我们试图为SBC开发一种基于证据的治疗算法。
在所有遗传组中，全切除（GTR）与无进展生存期（PFS）的改善相关。对于C组肿瘤，GTR和AdjXRT分别独立地对PFS有贡献（多变量Cox比例风险比[HR] = 0.14，P = 0.002，HR = 0.40，P = 0.047）。对于B组肿瘤，仅当GTR不可行时，AdjXRT才改善预后（对数秩检验P = 0.008），而在GTR之后则不然（对数秩检验P = 0.54）。然而，25例A组肿瘤中有24例接受了GTR，对这些肿瘤进行AdjXRT并未带来任何益处（对数秩检验P = 0.285）。A组的高GTR率可以通过较小的肿瘤大小（A/B/C组的平均大小分别为0.98cc/4.08cc/4.92cc，P = 0.031）和缺乏侵袭性来解释。A组肿瘤在年轻人中也更频繁地被诊断为无症状病变（P = 0.002，P = 0.001），这表明它们可能是高风险组肿瘤的前体。
通过1p36和纯合9p21（p16）缺失进行基因分组可以预测SBC的预后并指导治疗。GTR仍然是SBC治疗的基石，在低风险和中度风险肿瘤中，无需AdjXRT可能就足够了。低风险肿瘤与侵袭性较小的表型相关，这使得它们更适合进行GTR。
