Department of Medical Oncology, Santo Stefano Hospital, Prato, Italy.
Department of Medical Oncology, Centre Léon Bérard & Université Claude Bernard Lyon I, Lyon, France.
Oncologist. 2020 Nov;25(11):e1777-e1784. doi: 10.1634/theoncologist.2020-0352. Epub 2020 Jul 12.
This study aimed to review the activity of cytotoxic chemotherapy in patients with inflammatory myofibroblastic tumors (IMTs) treated at nine European sarcoma reference centers.
Patients of any age, with histologically proven IMT, treated with anthracycline-based methotrexate plus/minus vinorelbine/vinblastine (MTX-V) or other chemotherapeutic regimens between 1996 and 2018 were retrospectively reviewed. Diagnosis was confirmed at the local level by an expert pathologist. Response was retrospectively assessed by local investigators by RECIST v1.1. Progression-free survival (PFS), relapse-free survival (RFS), and overall survival (OS) were computed by Kaplan-Meier method.
Thirty-eight patients were included. Twenty-five patients (8 localized, 17 advanced disease) received an anthracycline-based regimen; 21 were evaluable for response. Overall response rate (ORR) was 10/21 (47.6%). At a 70.8-month median follow-up (FU), median RFS and median OS were not reached (NR) in patients with localized disease; median PFS and median OS were 6.3 (interquartile range [IQR]: 1.9-13.4) and 21.2 (IQR: 7.7-40.7) months in patients with advanced disease. Thirteen patients received MTX-V (4 localized, 9 advanced disease), all evaluable for response. ORR was 7/13 (53.8%). At a 56.6-month median FU, median RFS and median OS were 42.5 (IQR: 12.9-61.2) months and NR (no death events) in patients with localized disease, and NR (IQR: 24.9 to NR) and 83.4 months (IQR: 83.4 to NR) in patients with advanced disease. In the "other-regimens group," responses were seen in 3/4 patients treated with oral cyclophosphamide and 1/2 with docetaxel/gemcitabine.
Anthracycline-based and MTX-V regimens are very effective in IMT, with a similar ORR in both groups. MTX-V achieved a prolonged disease control. Responses were also seen with oral cyclophosphamide and docetaxel/gemcitabine, but few patients were treated with these schedules.
Inflammatory myofibroblastic tumor (IMT) is an ultrarare sarcoma with known sensitivity to anaplastic lymphoma kinase (ALK) inhibitors in ALK-fused cases, although ALK inhibitors are not licensed in the disease. The current knowledge on the activity of cytotoxic chemotherapy is limited. This multi-institutional retrospective study on pediatric and adult patients with IMT shows that cytotoxic chemotherapy, and in particular anthracycline-based and methotrexate plus/minus vinorelbine/vinblastine regimens, represents a treatment option and can be considered in IMT patients irrespectively from ALK status. This study provides a benchmark for future studies on new medical therapies.
本研究旨在回顾在欧洲 9 家肉瘤参考中心接受治疗的炎性肌纤维母细胞瘤（IMT）患者的细胞毒化疗活性。
回顾性分析了 1996 年至 2018 年间接受基于蒽环类药物的甲氨蝶呤加/不加长春碱/长春新碱（MTX-V）或其他化疗方案治疗的任何年龄、组织学证实的 IMT 患者。诊断由当地的专家病理学家在当地水平确认。通过 RECIST v1.1 由当地研究者对反应进行回顾性评估。无进展生存期（PFS）、无复发生存期（RFS）和总生存期（OS）通过 Kaplan-Meier 方法计算。
共纳入 38 例患者。25 例（8 例局限性疾病，17 例晚期疾病）接受了基于蒽环类药物的方案治疗；21 例可评估反应。总体缓解率（ORR）为 21/21（47.6%）。在中位随访 70.8 个月时，局限性疾病患者的中位 RFS 和中位 OS 未达到（NR）；晚期疾病患者的中位 PFS 和中位 OS 分别为 6.3（四分位距 [IQR]：1.9-13.4）和 21.2（IQR：7.7-40.7）个月。13 例接受 MTX-V（4 例局限性疾病，9 例晚期疾病）治疗的患者均可评估反应。ORR 为 13/13（53.8%）。在中位随访 56.6 个月时，局限性疾病患者的中位 RFS 和中位 OS 分别为 42.5（IQR：12.9-61.2）个月和 NR（无死亡事件）；晚期疾病患者的中位 OS 分别为 NR（IQR：24.9 至 NR）和 83.4 个月（IQR：83.4 至 NR）。在“其他方案组”中，接受口服环磷酰胺治疗的 4 例患者和接受多西他赛/吉西他滨治疗的 2 例患者中均观察到反应。
基于蒽环类药物和 MTX-V 的方案在 IMT 中非常有效，两组的 ORR 相似。MTX-V 实现了疾病的长期控制。口服环磷酰胺和多西他赛/吉西他滨也有反应，但很少有患者接受这些方案治疗。
炎性肌纤维母细胞瘤（IMT）是一种非常罕见的肉瘤，已知在 ALK 融合病例中对间变性淋巴瘤激酶（ALK）抑制剂敏感，尽管该疾病尚未获得 ALK 抑制剂的批准。目前对细胞毒化疗活性的了解有限。这项关于儿科和成人 IMT 患者的多机构回顾性研究表明，细胞毒化疗，特别是基于蒽环类药物和甲氨蝶呤加/不加长春碱/长春新碱的方案，是一种治疗选择，可以在 IMT 患者中考虑，无论 ALK 状态如何。本研究为新的药物治疗的未来研究提供了一个基准。
