Bertuzzi Alexia, Castagna Luca, Nozza Andrea, Quagliuolo Vittorio, Siracusano Licia, Balzarotti Monica, Compasso Silvana, Alloisio Marco, Soto Parra Hector, Santoro Armando
Department of Medical Oncology and Hematology, Istituto Clinico Humanitas, Rozzano, Milan, Italy.
J Clin Oncol. 2002 Apr 15;20(8):2181-8. doi: 10.1200/JCO.2002.08.033.
The prognosis of metastatic/high-risk localized small round-cell tumors (SRCTs) treated conventionally is dismal. In this phase II study, we explored a high-dose chemotherapy (HD-CT) approach and analyzed the clinical significance of fusion transcripts detection.
From June 1997 to November 1999, 28 SRCT patients (median age, 26 years; 14 peripheral primitive neuroectodermal tumors [pPNETs], seven rhabdomyosarcomas [RMSs], and seven desmoplastic small round-cell tumors [DSRCTs]) received induction chemotherapy with ifosfamide, epirubicin, and vincristine followed by HD-CT. Local treatment (radiotherapy and/or surgery) was performed when possible. Molecular analysis was performed on peripheral-blood and leukapheresis products by reverse-transcriptase polymerase chain reaction.
Overall response (OR) was 65% (18 of 28), with 40% complete response and 25% partial response. According to histology, the OR rate was 86% in pPNET and 43% in both RMS DSRCT. With a median follow-up of 35 months, median overall survival was 16 months and median progression-free survival (PFS) was 10 months. PFS was statistically better in pPNET than other histologic types (P =.0045). No correlation was found between the fusion transcript and clinical outcome during follow-up. Furthermore, transcript detection in leukapheretic products was not of prognostic significance.
Intensive HD-CT seems to enhance the response rate and survival when compared with conventional treatment in poor-prognosis pPNET. The poor results of this treatment in RMS and DSRCT do not support the inclusion of such an approach in these patient subsets. No definitive conclusions can currently be drawn concerning the clinical implications of the detection of fusion transcripts during treatment or follow-up.
传统治疗的转移性/高危局限性小圆细胞肿瘤（SRCT）预后不佳。在这项II期研究中，我们探索了一种高剂量化疗（HD-CT）方法，并分析了融合转录本检测的临床意义。
1997年6月至1999年11月，28例SRCT患者（中位年龄26岁；14例外周原始神经外胚层肿瘤[pPNET]、7例横纹肌肉瘤[RMS]和7例促纤维增生性小圆细胞肿瘤[DSRCT]）接受了异环磷酰胺、表柔比星和长春新碱诱导化疗，随后进行HD-CT。尽可能进行局部治疗（放疗和/或手术）。通过逆转录聚合酶链反应对外周血和白细胞分离产物进行分子分析。
总缓解率（OR）为65%（28例中的18例），完全缓解率为40%，部分缓解率为25%。根据组织学类型，pPNET的OR率为86%，RMS和DSRCT均为43%。中位随访35个月，中位总生存期为16个月，中位无进展生存期（PFS）为10个月。pPNET的PFS在统计学上优于其他组织学类型（P = 0.0045）。随访期间未发现融合转录本与临床结局之间存在相关性。此外，白细胞分离产物中的转录本检测无预后意义。
与传统治疗相比，强化HD-CT似乎能提高预后不良的pPNET的缓解率和生存率。该治疗方法在RMS和DSRCT中的不良结果不支持将其纳入这些患者亚组。目前关于治疗或随访期间融合转录本检测的临床意义尚无明确结论。
