儿童非横纹肌软组织肉瘤的美国儿童肿瘤协作组危险度评估与综合治疗单中心研究

Pediatric non - rhabdomyosarcoma soft tissue sarcomas： multimodality approach results and validation of American Children＇s Oncology Group risk stratifications a study of single - institutional series

目的 研究儿童非横纹肌软组织肉瘤（NRSTS）的临床特点、预后状况、生存影响因素及治疗策略。方法北京大学肿瘤医院骨与软组织肿瘤科2007年7月至2015年3月共收治34例NRSTS患儿，回顾性研究患儿临床与病理资料、手术与放化疗综合治疗结果，并分析生存影响因素。结果本组男21例，女13例；年龄7～18岁，中位年龄14岁。肿瘤最大径0．5～22．0cm，平均值5．0cm，中位值3．0cm。由9种不同的组织学亚型组成，以滑膜肉瘤最多[29．4％（10／34例）]。部位以四肢最多[67．6％（23／34例）]，其中下肢占50．0％（17／34例）。美国横纹肌肉瘤协作组（IRS）分组：I组28例，Ⅱ、Ⅲ、Ⅳ组各2例；美国儿童肿瘤协作组（COG）危险分层：低危组23例，中危组7例，高危组4例。随访时间6～96个月，中位随访时间35个月。术后发生复发2例，远处转移1例，淋巴结与远处转移2例，复发与远处转移1例，死亡3例。34例患儿2年总生存率为89．2％，低危组为100．0％，中高危组为70．0％。其中28例无淋巴结及远处转移患儿，术后2年局部无复发生存率及无远处转移生存率分别为96．4％、87．6％。分析生存影响因素，发现IRS分组、COG危险分层、肿瘤大小与预后相关。能够完整手术切除（P=0．007）、低度危险（P=0．014）、≤5．0cm（P=0．037）的肿瘤具有更好的生存预期。治疗：单纯手术14例，手术加化疗10例，手术加放化疗4例，手术加放疗2例，单纯放化疗2例，单纯化疗2例。化疗方案主要（17／18例）采用葸环类药＋异环磷酰胺方案（吡柔比星：40mg／m2，异环磷酰胺：10g／m2），每例总化疗2—12周期，平均4．6个周期。结论NRSTS患儿在手术、放疗及基于葸环类药物＋异环磷酰胺联合化疗的综合治疗后，可取得较好结果。本研究首次采用COG分层研究儿童NRSTS，并证实实肿瘤大小与COG危险度分层是重要的生存影响因素。应该依据NRSTS危险度评估预后，并设计综合治疗策略。

Objective To investigate the clinical characteristics, survival ,factors of prognosis and therapeuti- cal strategy of pediatric non - rhabdomyosarcoma soft tissue sarcomas （NRSTS）. Methods There were 34 cases of NRSTS treated in Department of Orthopaedic Oncology, Peking University Cancer Hospital during July 2007 and March 2015. The clinical and pathological data and outcome of muhimodality approach were retrospectively studied, the survival analysis was performed. Results There were 21 male and 13 female cases,and the median age was 14 years,ranging from 7 to 18 years old. Mean and median size was 5.0 cm and 3.0 cm ,ranged 0. 5 - 22.0 cm. Synovial sarcoma was the most common type among the 9 sorts of histologies [ 29. 4% （ 10/34 cases） ], and limb was the most common site [67.6% （23/34 cases） ,accounting for 50.0% （ 17/34 cases） by lower limb]. There were 28 cases,2 cases,2 cases,2 cases in Intergroup Rhabdomyosarcoma Study （IRG） group I , Ⅱ ,Ⅲ, Ⅳ, respectively, and 23 cases, 7 cases ,4 cases in Children＇s Oncology Group （COG） low, moderate and high risk group respectively. The median followup was 35 months, ranging from 6 to 96 months. There were 2 cases of local recurrence, 1 case of distant recurrence ,2 cases of metastases of lymph node and distant sites, and 1 case of local and distant recurrence. The 2 - year overall survival rate was 89.2%, 100.0% ,70.0% for total group, COG low risk group, COG moderate and high risk group, respectively. For 28 cases of tumors without any nodular or distant metastasis, the 2 - year local recurrence - free survival and distant re- currence - free survival rate was 96.4% and 87. 6% respectively. IRS group, COG risk group and size of tumor were associated with the prognosis. The groups of completely resected tumor（ P = 0. 007）, COG low risk （P = 0. 014） and tumors no larger than 5.0 cm in diameter（ P = 0. 037 ） had more favorable overall survivals. There were 14 cases, 10 cases ,4 cases ,2 cases ,2 cases ,2 cases who had surgery alone, surgery plus chemotherapy, surgery plus chemoradiotherapy, surgery plus radiation, chemoradiotherapy alone and chemotherapy alone, respectively, as multimodality approaches. Mesna ＋ Adriamycin ＋ Ifosfamide regimen （ Pirarubicin 40 mg/m2, Ifosfamide 10 g/m2 ） was the main （ 17/18 cases） choice as chemotherapy,with a total and mean cycles of chemotherapy for every case of 2- 12 and 4.6 respectively. Conclusions This series of NRSTS showed favorable oncological outcomes after a muhimodality approach composed of surgery, radiation and chemotherapy on MAI regimen. The COG risk stratifications were firstly adopted in domestic study of pediatric NRSTS,with prognostic efficacy being validated. Risk - based multimodality approach was also recommended.