Background/Objectives:Treatment of locally advanced rectal cancer (LARC) very often requires a neoadjuvant multimodal approach. Neoadjuvant treatment (NAT) encompasses treatments like chemoradiotherapy (CRT), short-course radiotherapy (SCRT), radiotherapy (RT) or a combination of either of these two with additional induction or consolidation chemotherapy, namely total neoadjuvant treatment (TNT). In case of complete radiological and clinical response, the non-operative watch-and-wait strategy can be adopted in selected patients. This strategy is impacted by a regrowth rate of approximately 30%. Predicting biomarkers of tumor response to NAT could improve guidance of clinicians during clinical decision making, improving treatment outcomes and decreasing unnecessary treatment exposure. To this day, there is no validated biomarker to predict tumor response to any NAT strategies in clinical use. Most research focused on CRT neglects the study of other regimens.Methods: We conducted a narrative literature review which aimed at summarizing the status of biomarkers predicting tumor response to NAT other than CRT in LARC.Results: Two hundred and fourteen articles were identified. After screening, twenty-one full-text articles were included. Statistically significant markers associated with improved tumor response pre-treatment were as follows: low circulating CEA levels; BCL-2 expression; high cellular expression of Ku70, MIB-1(Ki-67) and EGFR; low cellular expression of VEGF, hPEBP4 and nuclear β-catenin; the absence of TP53, SMAD4, KRAS and LRP1B mutations; the presence of the G-allel of LCS-6; and MRI features such as the conventional biexponential fitting pseudodiffusion (Dp) mean value and standard deviation (SD), the variable projection Dp mean value and lymph node characteristics (short axis, smooth contour, homogeneity and Zhang et al. radiomic score). In the interval post-treatment and before surgery, significant markers were as follows: a reduction in the median value of circulating free DNA, higher presence of monocytic myeloid-derived suppressor cells, lower presence of CTLA4+ or PD1+ regulatory T cells and standardized index of shape changes on MRI.Conclusions: Responders to neoadjuvant SCRT and RT tended to have a tumor microenvironment with an immune–active phenotype, whereas responders to TNT tended to have a less active tumor profile. Although some biomarkers hold great promise, scarce publications, inconsistent results, low statistical power, and low reproducibility prevent them from reliably predicting tumor response following NAT.
背景/目的：局部晚期直肠癌（LARC）的治疗通常需要新辅助多模式疗法。新辅助治疗（NAT）包括放化疗（CRT）、短程放疗（SCRT）、单纯放疗（RT）或上述任一疗法联合诱导或巩固化疗，即全新辅助治疗（TNT）。若患者达到完全的影像学和临床缓解，部分患者可选择非手术的“观察等待”策略。该策略受约30%的肿瘤再生率影响。预测肿瘤对NAT反应的生物标志物可辅助临床决策，改善治疗效果并减少不必要的治疗暴露。迄今为止，尚无经过验证的生物标志物可预测临床应用中任何NAT策略的肿瘤反应。多数研究集中于CRT，而忽视了其他方案的研究。 方法：我们进行了一项叙述性文献综述，旨在总结除CRT外，预测LARC肿瘤对NAT反应的生物标志物研究现状。 结果：共检索到214篇文献，经筛选后纳入21篇全文文献。与治疗前肿瘤反应改善相关的统计学显著标志物包括：低循环CEA水平；BCL-2表达；Ku70、MIB-1（Ki-67）和EGFR的高细胞表达；VEGF、hPEBP4和核β-连环蛋白的低细胞表达；TP53、SMAD4、KRAS和LRP1B突变缺失；LCS-6的G等位基因存在；以及MRI特征，如常规双指数拟合伪扩散（Dp）平均值和标准差（SD）、变量投影Dp平均值、淋巴结特征（短轴、光滑轮廓、均匀性）及张等人提出的放射组学评分。在治疗后至手术前的间隔期内，显著标志物包括：循环游离DNA中位值降低、单核髓源性抑制细胞比例较高、CTLA4+或PD1+调节性T细胞比例较低，以及MRI上形状变化的标准化指数。 结论：对新辅助SCRT和RT有反应者的肿瘤微环境倾向于具有免疫活性表型，而对TNT有反应者的肿瘤活性则相对较低。尽管部分生物标志物前景广阔，但由于发表文献有限、结果不一致、统计效力低及可重复性差，目前尚无法可靠预测NAT后的肿瘤反应。
肿瘤(癌症)患者之家