Abstract：
The aim of the present study was to assess the value of interim 18F-FDG PET/CT performed after the first two cycles of ipilimumab treatment in the prediction of the final clinical response to this type of immunotherapy.
The study group comprised 41 patients with unresectable metastatic melanoma scheduled for ipilimumab therapy. Whole-body 18F-FDG PET/CT was performed before the start of ipilimumab treatment (baseline PET/CT) and after the initial two cycles of ipilimumab treatment (interim PET/CT). Evaluation of patient response to treatment was based on the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria for PET as well as the recently proposed PET Response Evaluation Criteria for Immunotherapy (PERCIMT). The patients\' best clinical response, assessed at a median of 21.4 months (range 6.3-41.9 months) was used as reference.
According to their best clinical response, the patients were divided into two groups: those showing clinical benefit (CB) including stable disease, partial response and complete response (31 patients), and those showing no clinical benefit (no-CB including progressive disease (10 patients). According to the EORTC criteria, interim PET/CT demonstrated progressive metabolic disease (PMD) in 20 patients, stable metabolic disease (SMD) in 11 patients, partial metabolic response (PMR) in 8 patients, and complete metabolic response (CMR) in 2 patients. According to the PERCIMT, interim PET/CT demonstrated PMD in 9 patients, SMD in 24 patients, PMR in 6 patients and CMR in 2 patients. On the basis of the interim PET, the patients were divided in a similar manner to the division according to clinical response into those showing metabolic benefit (MB) including SMD, PMR and CMR, and those showing no metabolic benefit (no-MB) including PMD. According to this dichotomization, the EORTC criteria showed a sensitivity (correctly predicting CB) of 64.5%, a specificity (correctly predicting no-CB) of 90.0%, a positive predictive value (PPV) of 95.2%, a negative predictive value (NPV) of 45.0% and an accuracy of 70.7% in predicting best clinical response. The PERCIMT showed a sensitivity of 93.6%, a specificity of 70.0%, a PPV of 90.6%, a NPV of 77.8% and an accuracy of 87.8%. The McNemar test showed that the PERCIMT had a significantly higher sensitivity than EORTC criteria (p = 0.004), while there was no significant difference in specificity (p = 0.5). The agreement between the two sets of criteria was poor (McNemar test p = 0.001, and accordingly kappa = 0.46).
The application of the recently proposed PERCIMT to interim 18F-FDG PET/CT provides a more sensitive predictor of final clinical response to immunotherapy than the application of the EORTC criteria in patients with metastatic melanoma.
The study group comprised 41 patients with unresectable metastatic melanoma scheduled for ipilimumab therapy. Whole-body 18F-FDG PET/CT was performed before the start of ipilimumab treatment (baseline PET/CT) and after the initial two cycles of ipilimumab treatment (interim PET/CT). Evaluation of patient response to treatment was based on the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria for PET as well as the recently proposed PET Response Evaluation Criteria for Immunotherapy (PERCIMT). The patients\' best clinical response, assessed at a median of 21.4 months (range 6.3-41.9 months) was used as reference.
According to their best clinical response, the patients were divided into two groups: those showing clinical benefit (CB) including stable disease, partial response and complete response (31 patients), and those showing no clinical benefit (no-CB including progressive disease (10 patients). According to the EORTC criteria, interim PET/CT demonstrated progressive metabolic disease (PMD) in 20 patients, stable metabolic disease (SMD) in 11 patients, partial metabolic response (PMR) in 8 patients, and complete metabolic response (CMR) in 2 patients. According to the PERCIMT, interim PET/CT demonstrated PMD in 9 patients, SMD in 24 patients, PMR in 6 patients and CMR in 2 patients. On the basis of the interim PET, the patients were divided in a similar manner to the division according to clinical response into those showing metabolic benefit (MB) including SMD, PMR and CMR, and those showing no metabolic benefit (no-MB) including PMD. According to this dichotomization, the EORTC criteria showed a sensitivity (correctly predicting CB) of 64.5%, a specificity (correctly predicting no-CB) of 90.0%, a positive predictive value (PPV) of 95.2%, a negative predictive value (NPV) of 45.0% and an accuracy of 70.7% in predicting best clinical response. The PERCIMT showed a sensitivity of 93.6%, a specificity of 70.0%, a PPV of 90.6%, a NPV of 77.8% and an accuracy of 87.8%. The McNemar test showed that the PERCIMT had a significantly higher sensitivity than EORTC criteria (p = 0.004), while there was no significant difference in specificity (p = 0.5). The agreement between the two sets of criteria was poor (McNemar test p = 0.001, and accordingly kappa = 0.46).
The application of the recently proposed PERCIMT to interim 18F-FDG PET/CT provides a more sensitive predictor of final clinical response to immunotherapy than the application of the EORTC criteria in patients with metastatic melanoma.
摘要：
本研究的目的是评估伊匹单抗治疗前两个周期后进行的临时18F-FDGPET/CT在预测此类免疫疗法的最终临床反应中的价值。
研究组包括41例不可切除的转移性黑色素瘤患者，计划接受伊匹单抗治疗。全身18F-FDGPET/CT在伊匹单抗治疗开始之前（基线PET/CT）和伊匹单抗治疗的最初两个周期（临时PET/CT）之后进行。患者对治疗的反应的评估基于欧洲癌症研究和治疗组织(EORTC)1999的PET标准以及最近提出的免疫疗法的PET反应评估标准(PERCIMT)。患者的最佳临床反应，以中位数21.4个月(范围6.3~41.9个月)作为参考.
根据他们的最佳临床反应，患者分为两组：显示临床获益（CB）的患者，包括稳定的疾病，部分反应和完全反应（31例），和那些没有临床获益的（无CB包括进行性疾病（10例）。根据EORTC标准，中期PET/CT显示20例患者的进行性代谢性疾病（PMD），稳定代谢病（SMD）11例，8例患者的部分代谢反应（PMR），2例患者完成代谢反应（CMR）。根据PERCIMT,中期PET/CT在9例患者中显示PMD，24名患者的SMD，PMR6例，CMR2例。在临时PET的基础上，根据临床反应将患者以类似的方式分为显示代谢益处（MB）的患者，包括SMD，PMR和CMR，和那些没有表现出代谢益处（无MB），包括PMD。根据这种二分法，EORTC标准显示出64.5%的灵敏度(正确预测CB)，特异性（正确预测无CB）为90.0%，阳性预测值(PPV)为95.2%，阴性预测值（NPV）为45.0％，预测最佳临床反应的准确性为70.7％。PERCIMT的灵敏度为93.6%,特异性为70.0%，PPV为90.6%，净现值为77.8%，准确率为87.8%。McNemar测试表明，PERCIMT的灵敏度明显高于EORTC标准（p=0.004），而特异性无显著差异(p=0.5)。两组标准之间的一致性较差(McNemar检验p=0.001,因此kappa=0.46)。
最近提出的PERCIMT在中期18F-FDGPET/CT中的应用提供了比在转移性黑色素瘤患者中应用EORTC标准更敏感的免疫治疗最终临床反应的预测指标。
研究组包括41例不可切除的转移性黑色素瘤患者，计划接受伊匹单抗治疗。全身18F-FDGPET/CT在伊匹单抗治疗开始之前（基线PET/CT）和伊匹单抗治疗的最初两个周期（临时PET/CT）之后进行。患者对治疗的反应的评估基于欧洲癌症研究和治疗组织(EORTC)1999的PET标准以及最近提出的免疫疗法的PET反应评估标准(PERCIMT)。患者的最佳临床反应，以中位数21.4个月(范围6.3~41.9个月)作为参考.
根据他们的最佳临床反应，患者分为两组：显示临床获益（CB）的患者，包括稳定的疾病，部分反应和完全反应（31例），和那些没有临床获益的（无CB包括进行性疾病（10例）。根据EORTC标准，中期PET/CT显示20例患者的进行性代谢性疾病（PMD），稳定代谢病（SMD）11例，8例患者的部分代谢反应（PMR），2例患者完成代谢反应（CMR）。根据PERCIMT,中期PET/CT在9例患者中显示PMD，24名患者的SMD，PMR6例，CMR2例。在临时PET的基础上，根据临床反应将患者以类似的方式分为显示代谢益处（MB）的患者，包括SMD，PMR和CMR，和那些没有表现出代谢益处（无MB），包括PMD。根据这种二分法，EORTC标准显示出64.5%的灵敏度(正确预测CB)，特异性（正确预测无CB）为90.0%，阳性预测值(PPV)为95.2%，阴性预测值（NPV）为45.0％，预测最佳临床反应的准确性为70.7％。PERCIMT的灵敏度为93.6%,特异性为70.0%，PPV为90.6%，净现值为77.8%，准确率为87.8%。McNemar测试表明，PERCIMT的灵敏度明显高于EORTC标准（p=0.004），而特异性无显著差异(p=0.5)。两组标准之间的一致性较差(McNemar检验p=0.001,因此kappa=0.46)。
最近提出的PERCIMT在中期18F-FDGPET/CT中的应用提供了比在转移性黑色素瘤患者中应用EORTC标准更敏感的免疫治疗最终临床反应的预测指标。
