Prospective International Cohort Study Demonstrates Inability of Interim PET to Predict Treatment Failure in Diffuse Large B-Cell Lymphoma
Prospective International Cohort Study Demonstrates Inability of Interim PET to Predict Treatment Failure in Diffuse Large B-Cell Lymphoma
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DOI：
10.2967/jnumed.114.145326
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发表时间：
2014-12-01
影响因子：
9.3
通讯作者：
Dondi, Maurizio
中科院分区：
文献类型：
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作者：
Carr, Robert;Fanti, Stefano;Dondi, Maurizio
国际原子能机构赞助了一项大型、跨国、前瞻性研究，以进一步定义PET对弥漫性大b细胞淋巴瘤的风险分层，并检验国际生物多样性或医疗保健系统多样性可能影响中期PET （I-PET）评估的治疗反应动力学的假设。方法：巴西、智利、匈牙利、印度、意大利、菲律宾、韩国和泰国的癌症中心遵循基于R-CHOP（环磷酰胺、羟阿霉素、长春新碱、泼尼松龙联合利妥昔单抗）治疗的共同方案，化疗2-3个周期后使用I-PET，化疗结束时目视评分。结果：所有327例患者的两年生存率（中位随访35个月）为无事件生存期（EFS）的79%(95%置信区间[CI]， 74%-83%)，总生存期（OS）的86% （95% CI, 81%-89%）。i - pet阴性210例（64%），阳性117例（36%）。i - pet阴性的2年EFS为90% (95% CI, 85%-93%)， i - pet阳性的2年EFS为58% (95% CI, 48%-66%)，风险比为5.31 （95% CI, 3.29-8.56）。i - pet阴性患者2年OS为93% (95% CI, 88%-96%)， i - pet阳性患者2年OS为72% (95% CI, 63%-80%)，风险比为3.86 （95% CI, 2.12-7.03）。在序贯监测中，312例患者中有192例（62%）在I-PET和化疗末期PET均有完全缓解，EFS为97% (95% CI, 92%-98%)；其中110例临床指标良好，EFS为98% （95% CI, 92%-100%）。相比之下，107例i - pet阳性病例分为两组：58例（54%）在化疗结束时达到pet阴性完全缓解（EFS, 86%; 95% CI, 73%-93%）；46%保持pet阳性（EFS, 35%; 95% CI, 22%-48%）。异质性分析发现，以I-PET分层的结果在不同国家之间没有显著差异。结论：这项大型国际队列研究提供了3个新发现：I-PET评估的治疗反应在不同的医疗保健系统中是可比较的，其次，I-PET阴性结果加上良好的临床状态确定了EFS为98%的组，第三，单次I-PET扫描不能区分化疗耐药淋巴瘤和完全缓解，不能用于指导风险适应治疗。
The International Atomic Energy Agency sponsored a large, multinational, prospective study to further define PET for risk stratification of diffuse large B-cell lymphoma and to test the hypothesis that international biological diversity or diversity of healthcare systems may influence the kinetics of treatment response as assessed by interim PET (I-PET). Methods: Cancer centers in Brazil, Chile, Hungary, India, Italy, the Philippines, South Korea, and Thailand followed a common protocol based on treatment with R-CHOP (cyclophosphamide, hydroxyadriamycin, vincristine, prednisolone with rituximab), with I-PET after 2-3 cycles of chemotherapy and at the end of chemotherapy scored visually. Results: Two-year survivals for all 327 patients (median follow-up, 35 mo) were 79% (95% confidence interval [CI], 74%-83%) for event-free survival (EFS) and 86% (95% CI, 81%-89%) for overall survival (OS). Two hundred ten patients (64%) were I-PET-negative, and 117 (36%) were I-PET-positive. Two-year EFS was 90% (95% CI, 85%-93%) for I-PET-negative and 58% (95% CI, 48%-66%) for I-PET-positive, with a hazard ratio of 5.31 (95% CI, 3.29-8.56). Two-year OS was 93% (95% CI, 88%-96%) for I-PET-negative and 72% (95% CI, 63%-80%) for I-PET-positive, with a hazard ratio of 3.86 (95% CI, 2.12-7.03). On sequential monitoring, 192 of 312 (62%) patients had complete response at both I-PET and end-of-chemotherapy PET, with an EFS of 97% (95% CI, 92%-98%); 110 of these with favorable clinical indicators had an EFS of 98% (95% CI, 92%-100%). In contrast, the 107 I-PET-positive cases segregated into 2 groups: 58 (54%) achieved PET-negative complete remission at the end of chemotherapy (EFS, 86%; 95% CI, 73%-93%); 46% remained PET-positive (EFS, 35%; 95% CI, 22%-48%). Heterogeneity analysis found no significant difference between countries for outcomes stratified by I-PET. Conclusion: This large international cohort delivers 3 novel findings: treatment response assessed by I-PET is comparable across disparate healthcare systems, secondly a negative I-PET findings together with good clinical status identifies a group with an EFS of 98%, and thirdly a single I-PET scan does not differentiate chemoresistant lymphoma from complete response and cannot be used to guide risk-adapted therapy.