Yaung Stephanie J, Ju Christine, Gattam Sandeep, Nicholas Alan, Sommer Nicolas, Bendell Johanna C, Hurwitz Herbert I, Lee John J, Casey Fergal, Price Richard, Palma John F
Roche Sequencing Solutions, Inc., Pleasanton, CA 94588, USA.
Roche Molecular Systems, Inc., Pleasanton, CA 94588, USA.
Cancers (Basel). 2022 Apr 29;14(9):2240. doi: 10.3390/cancers14092240.
Sequencing circulating tumor DNA (ctDNA) from liquid biopsies may better assess tumor heterogeneity than limited sampling of tumor tissue. Here, we explore ctDNA-based heterogeneity and its correlation with treatment outcome in STEAM, which assessed efficacy and safety of concurrent and sequential FOLFOXIRI-bevacizumab (BEV) vs. FOLFOX-BEV for first-line treatment of metastatic colorectal cancer. We sequenced 146 pre-induction and 89 post-induction patient plasmas with a 198-kilobase capture-based assay, and applied Mutant-Allele Tumor Heterogeneity (MATH), a traditionally tissue-based calculation of allele frequency distribution, on somatic mutations detected in plasma. Higher levels of MATH, particularly in the post-induction sample, were associated with shorter progression-free survival (PFS). Patients with high MATH vs. low MATH in post-induction plasma had shorter PFS (7.2 vs. 11.7 months; hazard ratio, 3.23; 95% confidence interval, 1.85−5.63; log-rank p < 0.0001). These results suggest ctDNA-based tumor heterogeneity may have potential prognostic value in metastatic cancers.
对液体活检中的循环肿瘤DNA（ctDNA）进行测序，可能比有限的肿瘤组织采样能更好地评估肿瘤异质性。在此，我们在STEAM研究中探索基于ctDNA的异质性及其与治疗结果的相关性，该研究评估了同步和序贯使用FOLFOXIRI-贝伐单抗（BEV）与FOLFOX-BEV一线治疗转移性结直肠癌的疗效和安全性。我们采用基于198千碱基捕获的检测方法，对146例诱导治疗前和89例诱导治疗后的患者血浆进行了测序，并将突变等位基因肿瘤异质性（MATH，一种传统上基于组织的等位基因频率分布计算方法）应用于血浆中检测到的体细胞突变。较高水平的MATH，尤其是诱导治疗后的样本中，与较短的无进展生存期（PFS）相关。诱导治疗后血浆中高MATH与低MATH的患者相比，PFS更短（7.2个月对11.7个月；风险比，3.23；95%置信区间，1.85−5.63；对数秩p<0.0001）。这些结果表明，基于ctDNA的肿瘤异质性可能在转移性癌症中具有潜在的预后价值。
