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 18F-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. 18F-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 18F-FDG PET/CT parameters that significantly correlated with TRG1. Results: Early total-lesion glycolysis and its percentage change compared with baseline (ΔTLG-early) could discriminate TRG1 from TRG2-TRG5. Only receiver-operating-characteristic analysis of ΔTLG-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 (ΔTLG-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 18F-FDG PET/CT evaluation to predict pathologic response and survival in the preoperative treatment of patients with locally advanced rectal cancer. ΔTLG-early showed the best accuracy in predicting tumor regression and may be particularly useful in guiding treatment-modifying decisions during preoperative chemoradiotherapy based on expected response.

中文翻译：

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18F-FDG PET / CT是贝伐单抗对高危局限性局部直肠癌术前放化疗后病理性肿瘤反应和生存率的早期预测指标。

对于抗血管生成药物的临床益处的预测性生物标志物存在未满足的需求。本研究的目的是前瞻性评估贝伐单抗在术前放化疗期间和之后进行的18F-FDG PET / CT对MRI定义的高风险局部晚期直肠癌患者的完整病理学肿瘤消退和存活率的预测价值。方法：纳入在一项非随机II期研究（BRANCH）中并发或顺序（放化疗前4 d）给予贝伐单抗联合术前放化疗的患者。18F-FDG PET / CT在基线时，放化疗开始后11天（早期）和手术前（晚期）进行。将代谢变化与病理学完全肿瘤消退（TRG1）与不完全肿瘤消退（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显着相关的那些18F-FDG PET / CT参数的接收器操作特性曲线。结果：早期总病变糖酵解及其与基线相比的变化百分比（ΔTLG-early）可以将TRG1与TRG2-TRG5区分开。仅ΔTLG早期的接收者操作特征分析显示曲线下面积大于0.7（0.76），最佳临界值为59.5％（灵敏度为80％，特异性为71.4％），以识别TRG1。晚期代谢评估无法区分两组。中位随访98个月（范围77-132个月）后，发生代谢反应（ΔTLG-早期≥59。5％的患者）的10年无进展生存率（89.3％比63.6％，P = 0.02）和癌症特异性生存率（92.9％对72.6％，P = 0.04）显着高于不完全的代谢反应者。结论：我们的结果表明，早期代谢反应可以作为抗血管生成治疗益处的替代指标。这些发现为早期18F-FDG PET / CT评估在局部晚期直肠癌患者术前治疗中预测病理反应和生存提供了进一步的支持。ΔTLG-early在预测肿瘤消退方面显示出最高的准确性，并且在基于预期反应的术前放化疗期间指导修改治疗方案的决策中可能特别有用。02）和不完全代谢反应者的癌症特异性生存率（92.9％对72.6％，P = 0.04）。结论：我们的结果表明，早期代谢反应可以作为抗血管生成治疗益处的替代指标。这些发现为早期18F-FDG PET / CT评价在局部晚期直肠癌患者术前治疗中预测病理反应和生存提供了进一步的支持。ΔTLG-early在预测肿瘤消退方面显示出最高的准确性，并且在基于预期反应的术前放化疗期间指导修改治疗方案的决策中可能特别有用。02）和不完全代谢反应者的癌症特异性生存率（92.9％对72.6％，P = 0.04）。结论：我们的结果表明，早期代谢反应可以作为抗血管生成治疗益处的替代指标。这些发现为早期18F-FDG PET / CT评价在局部晚期直肠癌患者术前治疗中预测病理反应和生存提供了进一步的支持。ΔTLG-early在预测肿瘤消退方面显示出最高的准确性，并且在基于预期反应的术前放化疗期间指导修改治疗方案的决策中可能特别有用。这些发现为早期18F-FDG PET / CT评价在局部晚期直肠癌患者术前治疗中预测病理反应和生存提供了进一步的支持。ΔTLG-early在预测肿瘤消退方面显示出最高的准确性，并且在基于预期反应的术前放化疗期间指导修改治疗方案的决策中可能特别有用。这些发现为早期18F-FDG PET / CT评价在局部晚期直肠癌患者术前治疗中预测病理反应和生存提供了进一步的支持。ΔTLG-early在预测肿瘤消退方面显示出最高的准确性，并且在基于预期反应的术前放化疗期间指导修改治疗方案的决策中可能特别有用。