18F-FDG PET/CT Is an Early Predictor of Pathologic Tumor Response and Survival After Preoperative Radiochemotherapy with Bevacizumab in High-Risk Locally Advanced Rectal Cancer
18F-FDG PET/CT Is an Early Predictor of Pathologic Tumor Response and Survival After Preoperative Radiochemotherapy with Bevacizumab in High-Risk Locally Advanced Rectal Cancer
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DOI：
10.2967/jnumed.118.222604
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发表时间：
2019-11-01
影响因子：
9.3
通讯作者：
Lastoria, Secondo
中科院分区：
文献类型：
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作者：
Avallone, Antonio;Aloj, Luigi;Lastoria, Secondo
对抗血管生成药物临床获益的预测性生物标志物的需求尚未得到满足。本研究的目的是前瞻性评估术前贝伐单抗放化疗期间和之后进行的F-18-FDG PET/CT对mri定义的高危局部晚期直肠癌患者肿瘤完全病理性消退和生存的预测价值。方法：在一项非随机II期研究（BRANCH）中，61例患者在术前放化疗的同时或顺序（放化疗前4天）给予贝伐单抗。F-18-FDG PET/CT分别在基线、放化疗开始后11 d（早期）和手术前（晚期）进行。将代谢变化与病理性肿瘤完全消退（TRG1）和不完全肿瘤消退（TRG2-TRG5）、无进展生存期、癌症特异性生存期和总生存期进行比较。计算与TRG1显著相关的F-18-FDG PET/CT参数的受者工作特征曲线。结果：早期全病变糖酵解及其与基线相比的百分比变化（DTLG-early）可以区分TRG1和TRG2-TRG5。只有DTLG-early的受体工作特征分析显示曲线下面积大于0.7(0.76)，识别TRG1的最佳截止值为59.5%（敏感性80%，特异性71.4%）。晚期代谢评估在两组间无明显差异。在中位随访98个月（范围77-132个月）后，代谢应答者（dtlg -早期$59.5%）的10年无进展生存率（89.3% vs. 63.6%, P = 0.02）和癌症特异性生存率（92.9% vs. 72.6%, P = 0.04）明显高于不完全代谢应答者。结论：我们的研究结果表明，早期代谢反应可以作为抗血管生成治疗效果的替代标志。本研究结果进一步支持在局部晚期直肠癌患者术前使用早期F-18-FDG PET/CT评估来预测病理反应和生存。Delta TLG-early在预测肿瘤消退方面显示出最好的准确性，并且可能在指导术前基于预期反应的放化疗的治疗修改决策方面特别有用。
There is an unmet need for predictive biomarkers of the clinical benefit of antiangiogenic drugs. The aim of the present study was to prospectively evaluate the value of F-18-FDG PET/CT performed during and after preoperative chemoradiotherapy with bevacizumab for the prediction of complete pathologic tumor regression and survival in patients with MRI-defined high-risk locally advanced rectal cancer. Methods: Sixty-one patients treated in a nonrandomized phase II study (BRANCH) with concomitant or sequential (4 d before chemoradiotherapy) administration of bevacizumab with preoperative chemoradiotherapy were included. F-18-FDG PET/CT was performed at baseline, 11 d after the beginning of chemoradiotherapy (early), and before surgery (late). Metabolic changes were compared with pathologic complete tumor regression (TRG1) versus incomplete tumor regression (TRG2-TRG5), progression-free survival, cancer-specific survival, and overall survival. Receiver-operating-characteristic curves were calculated for those F-18-FDG PET/CT parameters that significantly correlated with TRG1. Results: Early total-lesion glycolysis and its percentage change compared with baseline (DTLG-early) could discriminate TRG1 from TRG2-TRG5. Only receiver-operating-characteristic analysis of DTLG-early showed an area under the curve greater than 0.7 (0.76), with an optimal cutoff at 59.5% (80% sensitivity, 71.4% specificity), for identifying TRG1. Late metabolic assessment could not discriminate between the 2 groups. After a median follow-up of 98 mo (range, 77-132 mo), metabolic responders (DTLG-early $59.5%) demonstrated a significantly higher 10-y progression-free survival (89.3% vs. 63.6%, P = 0.02) and cancer-specific survival (92.9% vs. 72.6%, P = 0.04) than incomplete metabolic responders. Conclusion: Our results suggest that early metabolic response can act as a surrogate marker of the benefit of antiangiogenic therapy. The findings provide further support for the use of early F-18-FDG PET/CT evaluation to predict pathologic response and survival in the preoperative treatment of patients with locally advanced rectal cancer. Delta TLG-early showed the best accuracy in predicting tumor regression and may be particularly useful in guiding treatmentmodifying decisions during preoperative chemoradiotherapy based on expected response.