López Alfonso Juan Carlos, Poleszczuk Jan, Walker Rachel, Kim Sungjune, Pilon-Thomas Shari, Conejo-Garcia Jose J, Soliman Hatem, Czerniecki Brian, Harrison Louis B, Enderling Heiko
Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw, Poland.
JCO Clin Cancer Inform. 2019 Apr;3:1-16. doi: 10.1200/CCI.18.00075.
Early-stage cancers are routinely treated with surgery followed by radiotherapy (SR). Radiotherapy before surgery (RS) has been widely ignored for some cancers. We evaluate overall survival (OS) and disease-free survival (DFS) with SR and RS for different cancer types and simulate the plausibility of RS- and SR-induced antitumor immunity contributing to outcomes.
We analyzed a SEER data set of early-stage cancers treated with SR or RS. OS and DFS were calculated for cancers with sufficient numbers for statistical power (cancers of lung and bronchus, esophagus, rectum, cervix uteri, corpus uteri, and breast). We simulated the immunologic consequences of SR, RS, and radiotherapy alone in a mathematical model of tumor-immune interactions.
RS improved OS for cancers with low 20-year survival rates (lung: hazard ratio [HR], 0.88; P = .046) and improved DFS for cancers with higher survival (breast: HR = 0.64; P < .001). For rectal cancer, with intermediate 20-year survival, RS improved both OS (HR = 0.89; P = .006) and DFS (HR = 0.86; P = .04). Model simulations suggested that RS could increase OS by eliminating cancer for a broader range of model parameters and radiotherapy-induced antitumor immunity compared with SR for selected parameter combinations. This could create an immune memory that may explain increased DFS after RS for certain cancers.
Study results suggest plausibility that radiation to the bulk of the tumor could induce a more robust immune response and better harness the synergy of radiotherapy and antitumor immunity than postsurgical radiation to the tumor bed. This exploratory study provides motivation for prospective evaluation of immune activation of RS versus SR in controlled clinical studies.
早期癌症通常采用手术加放疗（SR）的方式进行治疗。对于某些癌症，术前放疗（RS）一直被广泛忽视。我们评估了不同癌症类型采用SR和RS治疗后的总生存期（OS）和无病生存期（DFS），并模拟了RS和SR诱导的抗肿瘤免疫对治疗结果产生影响的合理性。
我们分析了接受SR或RS治疗的早期癌症的监测、流行病学和最终结果（SEER）数据集。计算了具有足够数量以保证统计效力的癌症（肺癌和支气管癌、食管癌、直肠癌、子宫颈癌、子宫体癌和乳腺癌）的OS和DFS。我们在肿瘤 - 免疫相互作用的数学模型中模拟了SR、RS和单纯放疗的免疫后果。
RS改善了20年生存率较低的癌症的OS（肺癌：风险比[HR]，0.88；P = 0.046），并改善了生存率较高的癌症的DFS（乳腺癌：HR = 0.64；P < 0.001）。对于20年生存率中等的直肠癌，RS同时改善了OS（HR = 0.89；P = 0.006）和DFS（HR = 0.86；P = 0.04）。模型模拟表明，与SR相比，对于选定的参数组合，RS可以通过消除癌症以及放疗诱导的抗肿瘤免疫，在更广泛的模型参数范围内提高OS。这可能会产生免疫记忆，这可以解释某些癌症在RS后DFS增加的原因。
研究结果表明，与对肿瘤床进行术后放疗相比，对大部分肿瘤进行放疗可能会诱导更强的免疫反应，并更好地利用放疗和抗肿瘤免疫的协同作用。这项探索性研究为在对照临床研究中对RS与SR的免疫激活进行前瞻性评估提供了动力。
