Nassif Elise F, Auclin Edouard, Bahleda Rastilav, Honoré Charles, Mir Olivier, Dumont Sarah, Mery Benoite, Hodroj Khalil, Brahmi Mehdi, Trédan Olivier, Ray-Coquard Isabelle, Blay Jean-Yves, Massard Christophe, Le Cesne Axel, Dufresne Armelle
Centre Léon Bérard, Medical Oncology Department, 69008 Lyon, France.
Oncology Department, Hopital Européen Georges Pompidou, 75015 Paris, France.
Cancers (Basel). 2021 Jul 5;13(13):3362. doi: 10.3390/cancers13133362.
(1) Background: locally resected high-grade sarcomas relapse in 40% of cases. There is no prognostic or predictive genomic marker for response to peri-operative chemotherapy. (2) Methods: MOSCATO and ProfiLER are pan-tumor prospective precision medicine trials for advanced tumors. Molecular analysis in both trials comprised targeted next-generation sequencing and comparative genomic hybridization array. We investigated if molecular alterations identified in these trials in sarcomas were associated with disease-free survival (DFS) and response to anthracyclines. (3) Results: this analysis included 215 sarcomas, amongst which 53 leiomyosarcomas, 27 rhabdomyosarcomas, 20 undifferentiated pleomorphic sarcomas, and 17 liposarcomas. The most frequently altered gene was (46 mutations and eight deletions). There were 149 surgically resected localized sarcomas. Median DFS in wild type (WT), deleted, and mutated sarcomas was 16, 10, and 10 months, respectively ( = 0.028; deletions: HR = 1.55; 95% CI = 0.75-3.19; mutations: HR = 1.70; 95%CI = 1.13-2.64). In multivariate analysis, mutations remained associated with shorter DFS ( = 0.027; HR = 2.30; 95%CI = 1.10-4.82). There were 161 localized and advanced sarcomas evaluable for response to anthracyclines. Objective response rates were 35% and 55% in WT and mutated sarcomas, respectively (OR = 2.24; 95%CI = 1.01-5.03; = 0.05). In multivariate analysis, mutations remained associated with increased response (OR = 3.24; 95%CI = 1.30-8.45; = 0.01). (4) Conclusions: mutations are associated with shorter DFS and increased response to anthracyclines. Post-validation, these findings could assist in decision-making for peri-operative treatments.
(1) 背景：局部切除的高级别肉瘤有40%的病例会复发。目前尚无用于预测围手术期化疗反应的预后或预测性基因组标志物。(2) 方法：MOSCATO和ProfiLER是针对晚期肿瘤的全肿瘤前瞻性精准医学试验。两项试验中的分子分析均包括靶向二代测序和比较基因组杂交阵列。我们研究了在这些试验中肉瘤所鉴定出的分子改变是否与无病生存期（DFS）及对蒽环类药物的反应相关。(3) 结果：该分析纳入了215例肉瘤，其中53例平滑肌肉瘤、27例横纹肌肉瘤、20例未分化多形性肉瘤和17例脂肪肉瘤。最常发生改变的基因是（46个突变和8个缺失）。有149例经手术切除的局限性肉瘤。野生型（WT）、缺失型和突变型肉瘤的中位DFS分别为16个月、10个月和10个月（P = 0.028；缺失：HR = 1.55；95%CI = 0.75 - 3.19；突变：HR = 1.70；95%CI = 1.13 - 2.64）。在多变量分析中，突变仍与较短的DFS相关（P = 0.027；HR = 2.30；95%CI = 1.10 - 4.82）。有161例局限性和晚期肉瘤可评估对蒽环类药物的反应。WT和突变型肉瘤的客观缓解率分别为35%和55%（OR = 2.24；95%CI = 1.01 - 5.03；P = 0.05）。在多变量分析中，突变仍与缓解增加相关（OR = 3.24；95%CI = 1.30 - 8.45；P = 0.01）。(4) 结论：突变与较短的DFS及对蒽环类药物反应增加相关。经过验证后，这些发现可有助于围手术期治疗的决策制定。
