De Bernardi B, Conte M, Mancini A, Donfrancesco A, Alvisi P, Tomà P, Casale F, Cordero di Montezemolo L, Cornelli P E, Carli M
Department of Hematology-Oncology, Giannina Gaslini Children's Hospital, Genova, Italy.
J Clin Oncol. 1995 Apr;13(4):884-93. doi: 10.1200/JCO.1995.13.4.884.
To optimize treatment for children with localized resectable neuroblastoma in 21 Italian institutions using a common protocol based on previous experience.
Between January 1985 and December 1992, 152 children aged 0 to 15 years with nondisseminated neuroblastoma were entered onto this study following complete resection of tumor without tumor rupture (TR) (stage 1), or resection with minimal tumor residue, and/or tumor infiltration of regional lymph nodes (LN+), and/or TR (stage 2). Of 144 assessable children, 69 were classified as having stage 1 disease and 75 as stage 2. Of stage 2 children, 49 had low-risk (LR) characteristics (age, 0 to 11 months or 1 to 15 years but negative lymph nodes and no TR). Stage 1 and stage 2 LR children did not receive adjuvant therapy. The remaining 26 stage 2 children had high-risk (HR) characteristics (age, 1 to 15 years with LN+ and/or TR) and received adjuvant chemotherapy for 6 months.
Of 144 children, three died of therapy-related complications and 19 relapsed, of whom six died of disease. The estimated 5-year overall survival (OS) rate was 93% and the event-free survival (EFS) rate was 83%. Of 69 stage 1 children, one died postoperatively and five relapsed (one local and four disseminated, two of whom died), for 94% OS and 90% EFS rates. Of 49 stage 2 LR children, six relapsed (four local and two disseminated); relapses occurred in five of 20 infants with LN+, in one of four infants with TR, and in none of the remaining 25 children. One child died of disease and one of toxicity, for 96% OS and 85% EFS rates. Of 26 stage 2 HR children, eight relapsed (three of 20 with LN+, three of four with TR, and two of two with LN+ and TR), of whom three died of disease and one of toxicity, for 87% OS and 61% EFS rates.
Our data confirm the overall good prognosis of children with localized resectable neuroblastoma. LN+ and TR predisposed to relapse at all ages, but infants tended to have a less aggressive course after relapse. Stage 1 and 2 LR children had 94% and 96% OS rates, respectively, which justifies a policy of no adjuvant chemotherapy. Eight of 26 children with stage 2 HR relapsed despite 6 months of chemotherapy; for these children, more intensive chemotherapy may be required.
基于以往经验，采用通用方案优化21家意大利机构中局限性可切除神经母细胞瘤患儿的治疗。
1985年1月至1992年12月期间，152例0至15岁未播散性神经母细胞瘤患儿在肿瘤完整切除且无肿瘤破裂（TR）（1期）、或切除后肿瘤残留极少、和/或区域淋巴结（LN+）有肿瘤浸润、和/或TR（2期）后进入本研究。在144例可评估患儿中，69例被分类为1期疾病，75例为2期。在2期患儿中，49例具有低风险（LR）特征（年龄0至11个月或1至15岁，但淋巴结阴性且无TR）。1期和2期LR患儿未接受辅助治疗。其余26例2期患儿具有高风险（HR）特征（年龄1至15岁，伴有LN+和/或TR），并接受了6个月的辅助化疗。
144例患儿中，3例死于治疗相关并发症，19例复发，其中6例死于疾病。估计5年总生存率（OS）为93%，无事件生存率（EFS）为83%。69例1期患儿中，1例术后死亡，5例复发（1例局部复发，4例播散性复发，其中2例死亡），OS率为94%，EFS率为90%。49例2期LR患儿中，6例复发（4例局部复发，2例播散性复发）；20例伴有LN+ 的婴儿中有5例复发，4例有TR的婴儿中有1例复发，其余25例患儿均未复发。1例患儿死于疾病，1例死于毒性反应，OS率为96%，EFS率为85%。26例2期HR患儿中，8例复发（20例伴有LN+ 的患儿中有3例，4例有TR的患儿中有3例，2例同时伴有LN+ 和TR的患儿中有2例），其中3例死于疾病，1例死于毒性反应，OS率为87%，EFS率为61%。
我们的数据证实局限性可切除神经母细胞瘤患儿总体预后良好。LN+ 和TR在各年龄段均易导致复发，但婴儿复发后病程往往不那么凶险。1期和2期LR患儿的OS率分别为94%和96%，这证明不进行辅助化疗的策略是合理的。26例2期HR患儿中有8例尽管接受了6个月化疗仍复发；对于这些患儿，可能需要更强化的化疗。
