Paulino Arnold C
Department of Radiation Oncology, Emory Clinic, Emory University and Children's Healthcare of Atlanta, 1365 Clifton Road NE, Atlanta, GA 30322, USA.
Int J Radiat Oncol Biol Phys. 2004 Sep 1;60(1):265-74. doi: 10.1016/j.ijrobp.2004.02.001.
To determine the long-term effects of radiotherapy (RT) in children treated for extremity sarcoma.
Between 1964 and 1997, 15 of 33 children treated with RT for extremity sarcomas at the University of Iowa have survived with a median follow-up was 20 years (range, 6-36 years). There were 10 boys and 5 girls with a median age of 13 years (range, 3.5-20 years) at the time of irradiation. The diagnosis was Ewing's sarcoma in 8 (53%), synovial sarcoma in 4 (27%), alveolar rhabdomyosarcoma in 2, and fibrosarcoma in 1. Location of primary tumor was lower extremity in 10 (67%) and upper extremity in 5 (33%). RT was given as the definitive therapy for 9 children (median dose, 55.8 Gy; range, 45-66 Gy) and as an adjuvant postoperative treatment in 6 (median, 63 Gy; range, 41.4-66.4 Gy). (60)Co was used in 6 (40%), 4 mV in 4, 6 mV in 2, and 250 kV photons in 2 patients; 1 child was treated with a combination of 12 and 15 MeV electrons for a Ewing's sarcoma of the distal femur. Another child had a 25 Gy intraoperative RT boost after 41.4 Gy conventional RT. Late effects to the muscle, soft tissue, and growing bone were assessed using the objective portion of the LENT-SOMA scale proposed by the Late Effects Consensus Conference.
Late effects were seen in all patients and included atrophy in 12 (80%), fibrosis in 12 (80%), bone growth abnormalities in 10 (67%), impairment of mobility and extremity function in 6 (40%), edema in 3 (20%), and peripheral nerve injury in 2 (13%). Ten of 15 (67%) children had Grade 1 or 2 growing bone, muscle, soft tissue, or peripheral nerve complications. Two patients (13%) had a Grade 3 mobility and extremity function score and had moderate to severe limitation of movement. Two children (13%) required epiphysiodesis because of a shorter treated leg. The patient who received an intraoperative RT boost of 25 Gy developed sensory dysfunction of the ulnar nerve 11 years after RT. Another developed radial nerve palsy 3 years after marginal resection and postoperative RT and required tendon transfer repair. One patient had radiation-induced vasculitis with popliteal artery thrombosis 23 years after RT. Five (33%) developed a fracture of the irradiated bone at a median time of 8 years after RT (range: 9 months to 22.2 years); all had Ewing's sarcoma, and 3 of these patients were subsequently found to have a secondary bone cancer (osteosarcoma 2, malignant fibrous histiocytoma 1) in the RT field. One of these patients also developed breast cancer 26 years after lung RT for metastatic Ewing's sarcoma. Overall, 11 surgical procedures in 8 children were performed to correct a limb preservation treatment toxicity.
Although most children treated with RT for a pediatric extremity sarcoma have minimal late toxicity by LENT-SOMA scale, approximately half required a surgical procedure to correct a late effect. A fracture in the irradiated bone may be the presenting sign or may precede a radiation-induced bone malignancy, as seen in 3 of the patients in this study.
确定放射治疗(RT)对接受肢体肉瘤治疗的儿童的长期影响。
1964年至1997年间,爱荷华大学接受RT治疗的33例肢体肉瘤患儿中有15例存活,中位随访时间为20年(范围6 - 36年)。放疗时,有10名男孩和5名女孩,中位年龄13岁(范围3.5 - 20岁)。诊断为尤因肉瘤8例(53%),滑膜肉瘤4例(27%),肺泡横纹肌肉瘤2例,纤维肉瘤1例。原发肿瘤位于下肢10例(67%),上肢5例(33%)。9例患儿接受RT作为根治性治疗(中位剂量55.8 Gy;范围45 - 66 Gy),6例接受RT作为辅助性术后治疗(中位剂量63 Gy;范围41.4 - 66.4 Gy)。6例(40%)使用钴 - 60,4例使用4 mV,2例使用6 mV,2例使用250 kV光子;1例患儿因股骨远端尤因肉瘤接受12 MeV和15 MeV电子联合治疗。另1例患儿在接受41.4 Gy常规RT后术中接受25 Gy的RT增强治疗。使用晚期效应共识会议提出的LENT - SOMA量表的客观部分评估对肌肉、软组织和生长中骨骼的晚期效应。
所有患者均出现晚期效应,包括萎缩12例(80%)、纤维化12例(80%)、骨生长异常10例(67%)、活动和肢体功能受损6例(40%)、水肿3例(20%)、周围神经损伤2例(13%)。15例患儿中有10例(67%)出现1级或2级生长中骨骼、肌肉、软组织或周围神经并发症。2例患者(13%)活动和肢体功能评分为3级,有中度至重度运动受限。2例患儿(13%)因治疗侧腿较短需要进行骨骺固定术。接受25 Gy术中RT增强治疗的患者在放疗后11年出现尺神经感觉功能障碍。另1例患者在边缘切除和术后放疗后3年出现桡神经麻痹,需要进行肌腱转移修复。1例患者在放疗后23年出现放射性血管炎伴腘动脉血栓形成。5例(33%)在放疗后中位时间8年(范围:9个月至22.2年)出现放疗部位骨骨折;所有患者均为尤因肉瘤,其中3例患者随后在放疗区域发生继发性骨癌(骨肉瘤2例,恶性纤维组织细胞瘤1例)。其中1例患者在因转移性尤因肉瘤接受肺部放疗26年后还发生了乳腺癌。总体而言,8例患儿共进行了11次手术以纠正保肢治疗的毒性反应。
尽管根据LENT - SOMA量表,大多数接受RT治疗的儿童肢体肉瘤患者晚期毒性较小,但约一半患者需要进行手术来纠正晚期效应。放疗部位的骨折可能是首发症状,也可能先于放射性骨恶性肿瘤出现,本研究中有3例患者出现这种情况。