Murray Matthew J, Bailey Shivani, Heinemann Katja, Mann Jillian, Göbel Ulrich K, Saran Frank, Hale Juliet P, Calaminus Gabriele, Nicholson James C
Department of Paediatric Haematology and Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 0QQ, United Kingdom.
Department of Paediatric Haematology and Oncology, University Children's Hospital, Robert Koch Strasse, Bonn, Germany.
Int J Cancer. 2017 Aug 1;141(3):621-635. doi: 10.1002/ijc.30755. Epub 2017 May 15.
We aimed to retrospectively assess treatments/outcomes, including the value of high-dose-chemotherapy and autologous-stem-cell-rescue (HDC + AuSCR) and re-irradiation, in a large, European patient-cohort with relapsed intracranial germ-cell-tumors (GCTs) receiving uniform first-line therapy, including radiotherapy as standard-of-care. Fifty-eight UK/German patients (48 male/10 female) with relapsed intracranial-GCTs [13 germinoma/45 non-germinomatous GCT (NGGCT)] treated 1996-2010 as per the SIOP-CNS-GCT-96 protocol were evaluated. For germinoma, six patients relapsed with germinoma and five with NGGCT (one palliative, one teratoma patient excluded). Five-year overall-survival (OS) for the whole-group (n = 11) was 55%. Four of six germinoma relapses and two of five relapsing with NGGCT were salvaged; patients were salvaged with either standard-dose-chemotherapy (SDC) and re-irradiation or HDC + AuSCR with/without re-irradiation. Of 45 relapsed NGGCT patients, 13 were excluded (three non-protocol adherence, five teratoma, five palliation). Five-year OS for the remaining 32 relapsed malignant NGGCT patients treated with curative intent was 9% (95%CI: 2-26%). By treatment received, 5-year OS for the 10 patients receiving SDC and 22 patients treated with intention for HDC + AuSCR was 0% (0-0%) and 14% (3-36%), respectively. The three relapsed NGGCT survivors had raised HCG markers alone; two received additional irradiation. Patients with relapsed germinoma had better 5-year OS than those with relapsed NGGCT (55 vs. 9%; p = 0.007). Patients with relapsed germinoma were salvaged both with SDC and re-irradiation or HDC + AuSCR with/without re-irradiation; both represent valid treatment options. Outcomes for malignant relapse following initial diagnosis of NGGCT were exceptionally poor; the few survivors received thiotepa-based HDC + AuSCR, which is a treatment option at first malignant relapse for such patients, with further surgery/irradiation where feasible.
我们旨在对一大群接受统一一线治疗（包括以放疗作为标准治疗）的复发性颅内生殖细胞肿瘤（GCT）欧洲患者队列进行回顾性评估治疗方法/结果，包括大剂量化疗和自体干细胞救援（HDC + AuSCR）以及再放疗的价值。对1996年至2010年期间按照SIOP-CNS-GCT-96方案治疗的58例英国/德国复发性颅内GCT患者（48例男性/10例女性）进行了评估，其中13例为生殖细胞瘤，45例为非生殖细胞瘤性GCT（NGGCT）。对于生殖细胞瘤，6例生殖细胞瘤复发，5例NGGCT复发（1例姑息治疗、1例畸胎瘤患者排除）。整个组（n = 11）的5年总生存率（OS）为55%。6例生殖细胞瘤复发患者中有4例以及5例NGGCT复发患者中有2例得到挽救；患者通过标准剂量化疗（SDC）和再放疗或HDC + AuSCR联合/不联合再放疗得到挽救。在45例复发的NGGCT患者中，13例被排除（3例未遵循方案、5例畸胎瘤、5例姑息治疗）。其余32例接受根治性治疗的复发恶性NGGCT患者的5年OS为9%（95%CI：2 - 26%）。按接受的治疗方式，10例接受SDC的患者和22例接受HDC + AuSCR治疗的患者的5年OS分别为0%（0 - 0%）和14%（3 - 36%）。三名复发的NGGCT幸存者仅HCG标志物升高；2例接受了额外放疗。复发生殖细胞瘤患者的5年OS优于复发NGGCT患者（55%对9%；p = 0.007）。复发生殖细胞瘤患者通过SDC和再放疗或HDC + AuSCR联合/不联合再放疗均得到挽救；两者均为有效的治疗选择。NGGCT初始诊断后恶性复发的结果非常差；少数幸存者接受了基于噻替派的HDC + AuSCR，这是此类患者首次恶性复发时的一种治疗选择，可行时可进一步进行手术/放疗。
