Whelan Jeremy, Hackshaw Allan, McTiernan Anne, Grimer Robert, Spooner David, Bate Jessica, Ranft Andreas, Paulussen Michael, Juergens Herbert, Craft Alan, Lewis Ian
1Department of Oncology, University College Hospitals London NHS Foundation Trust, 250 Euston Road, London, NW1 2PG UK.
3Children's Cancer and Leukaemia Group Data Centre, Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK.
Clin Sarcoma Res. 2018 Mar 30;8:6. doi: 10.1186/s13569-018-0093-y. eCollection 2018.
Two national clinical trial groups, United Kingdom Children's Cancer and Leukaemia Group (CCLG) and the German Paediatric Oncology and Haematology Group (GPOH) together undertook a randomised trial, EICESS-92, which addressed chemotherapy options for Ewing's sarcoma. We sought the causes of unexpected survival differences between the study groups.
647 patients were randomised. Cox regression analyses were used to compare event-free survival (EFS) and overall survival (OS) between the two study groups.
5-year EFS rates were 43% (95% CI 36-50%) and 57% (95% CI 52-62) in the CCLG and GPOH patients, respectively; corresponding 5-year OS rates were 52% (95% CI 45-59%) and 66% (95% CI 61-71). CCLG patients were less likely to have both surgery and radiotherapy (18 vs. 59%), and more likely to have a single local therapy modality compared to the GPOH patients (72 vs. 35%). Forty-five percent of GPOH patients had pre-operative radiotherapy compared to 3% of CCLG patients. In the CCLG group local recurrence (either with or without metastases) was the first event in 22% of patients compared with 7% in the GPOH group. After allowing for the effects of age, metastases, primary site, histology and local treatment modality, the risk of an EFS event was 44% greater in the CCLG cohort (95% CI 10-89%, p = 0.009), and the risk of dying was 30% greater, but not statistically significant (95% CI 3-74%, p = 0.08).
Unexpected differences in EFS and OS occurred between two patient cohorts recruited within an international randomised trial. Failure to select or deliver appropriate local treatment modalities for Ewing's sarcoma may compromise chances of cure. Supported by Deutsche Krebshilfe (Grants No. DKH M43/92/Jü2 and DKH 70-2551 Jü3), and European Union Biomedicine and Health Programme (Grants No. BMH1-CT92-1341 and BMH4-983956), and Cancer Research United Kingdom. Clinical trial information can be found for the following: NCT0000251.
英国儿童癌症与白血病研究组（CCLG）和德国儿科肿瘤与血液学研究组（GPOH）这两个国家临床试验团队共同开展了一项随机试验EICESS - 92，该试验探讨了尤因肉瘤的化疗方案。我们探究了研究组之间意外生存差异的原因。
647例患者被随机分组。采用Cox回归分析比较两个研究组的无事件生存率（EFS）和总生存率（OS）。
CCLG组和GPOH组患者的5年EFS率分别为43%（95%CI 36 - 50%）和57%（95%CI 52 - 62）；相应的5年OS率分别为52%（95%CI 45 - 59%）和66%（95%CI 61 - 71）。与GPOH组患者相比，CCLG组患者接受手术和放疗的可能性较小（18%对59%），且更有可能采用单一局部治疗方式（72%对35%）。GPOH组45%的患者接受了术前放疗，而CCLG组这一比例为3%。在CCLG组中，22%的患者首次出现局部复发（无论有无转移），而在GPOH组中这一比例为7%。在考虑年龄、转移、原发部位、组织学和局部治疗方式的影响后，CCLG队列中发生EFS事件的风险高44%（95%CI 10 - 89%，p = 0.009），死亡风险高30%，但无统计学意义（95%CI 3 - 74%，p = 0.08）。
在一项国际随机试验招募的两个患者队列之间，EFS和OS出现了意外差异。未能为尤因肉瘤选择或提供合适的局部治疗方式可能会影响治愈机会。得到德国癌症援助组织（资助编号：DKH M43/92/Jü2和DKH 70 - 2551 Jü3）、欧盟生物医学与健康计划（资助编号：BMH1 - CT92 - 1341和BMH4 - 983956）以及英国癌症研究组织的支持。临床试验信息可在以下网址查询：NCT0000251。
