A multidisciplinary study investigating radiotherapy in Ewing's sarcoma: End results of POG #8346
A multidisciplinary study investigating radiotherapy in Ewing's sarcoma: End results of POG #8346
复制标题
DOI：
10.1016/s0360-3016(98)00191-6
复制
发表时间：
1998-08-01
影响因子：
7
通讯作者：
Shuster, JJ
中科院分区：
文献类型：
--
作者：
Donaldson, SS;Torrey, M;Shuster, JJ
目的：确定在局部肿瘤控制中，受累野放射（IF）是否等同于标准全骨放射（SF）;确定治疗后失败的模式;确定尤文肉瘤多学科治疗的反应、无事件生存率（EFS）和总生存率。方法和材料：在1983年至1988年期间，184名患有尤文氏肉瘤的儿童被纳入儿科肿瘤组8346（POG 8346）。共有178例（97%）符合合格标准; 6例患有尤文肉瘤以外的病理学。环磷酰胺/多柔比星（阿霉素）（C/A）诱导化疗12周，随后进行局部治疗，手术或放射治疗，C/A，更生霉素和长春新碱50周。对于原发性小肿瘤的患者，如果没有功能损失，建议切除。40例患者随机接受SF，全骨放射39.6戈伊加16.2戈伊的提升（总55.8戈伊）或LF到55.8戈伊，其余被分配到IF radiation.Results：在178个合格的患者，141（79%）有局部疾病和37（21%）有转移在介绍。其5年EFS分别为51%（SE 5%）和23%（SE 7%）。诱导化疗的有效率为88%（28%完全，60%部分），但放疗后的有效率增加到98%。37例局部患者接受了切除术，其中16例（43%）需要术后放疗;这些手术患者的5年EFS为80%（SE 7%）。其余104例局部患者有资格随机化或分配接受放疗;这些患者的5年EFS为41%（SE 5%），随机分配至SF组与IF组的患者之间的EFS无显著差异。原发性肿瘤部位与5年EFS相关：远端65%（SE 8%），中央63%（SE 10%），近端46%（SE 8%），骨盆-骶骨24%（SE 10%）（p = 0.004）。初始肿瘤大小与EFS无显著相关性。141名局部患者的失败模式显示，23%的患者经历了局部失败，而40%的患者发生了全身性失败。手术+/-术后放疗患者的5年局部控制率为88%（SE 6%），而单纯放疗患者的5年局部控制率为65%（SE 7%）。随机分配至SF组与IF组的患者之间的局部控制无差异。骨盆-骶骨肿瘤患者的5年局部控制率为44%（SE 15%），明显低于中央肿瘤患者的局部控制率82%（SE 8%）、远端肿瘤患者的局部控制率80%（SE 8%）或近端肿瘤患者的局部控制率69%（SE 9%）（p = 0.023）。然而，放射治疗的质量与结果相关;接受适当放射治疗的患者的5年局部控制率为80%（SE 7%），而轻微偏差的患者的5年局部控制率为48%（SE 14%），而严重偏差的患者的5年局部控制率仅为16%（SE 15%）（p = 0.005）。62%的局部失败发生在照射区域内，24%的局部失败发生在照射区域外，14%的局部失败无法确定。结论：由于尤文肉瘤的失败大多数是全身性的，改善EFS需要更有效的全身化疗。充分的IP放疗需要治疗到MRI成像和全辐射剂量定义的适当体积。治疗前由肌肉骨骼放射科医师对影像学检查进行回顾，以确定适当的肿瘤体积，以及使用适形放射治疗技术对改善预后非常重要。(C)1998年爱思唯尔科学公司
Purpose: To determine if involved field radiation (IF) is equivalent to standard whole bone radiation (SF) in local tumor control; to establish patterns of failure following treatment; and to determine response, event-free survival (EFS), and overall survival rates from multidisciplinary therapy in Ewing's sarcoma.Methods and Materials: Between 1983 and 1988, 184 children with Ewing's sarcoma were enrolled onto Pediatric Oncology Group 8346 (POG 8346). A total of 178 (97%) met eligibility criteria; 6 had pathology other than Ewing's sarcoma. Induction chemotherapy of cyclophosphamide/doxorubicin (adriamycin)(C/A) x 12 weeks was followed by local treatment either surgery or radiation therapy and C/A, dactinomycin, and vincristine for 50 weeks. Resection was advised for patients with small primary tumors if accomplished without functional loss. Forty patients were randomized to receive SF, whole bone radiation to 39.6 Gy plus a 16.2 Gy boost (total 55.8 Gy) or LF to 55.8 Gy, and the remainder were assigned to IF radiation.Results: Of 178 eligible patients; 141 (79%) had localized disease and 37 (21%) had metastases at presentation. Their 5-year EFS was 51% (SE 5%)and 23% (SE 7%) respectively. The response rate to induction chemotherapy was 88% (28% complete, 60% partial), but after radiotherapy the response rate increased to 98%. Thirty-seven of the localized patients underwent resection, of whom 16 (43%) required postoperative radiotherapy; the 5-year EFS of these surgical patients was 80% (SE 7%). The remaining 104 localized patients were eligible for randomization or assignment to receive radiotherapy; the 5-year EFS of these patients was 41% (SE 5%), with no significant difference in EFS between those randomized to SF vs. IF. Site of primary tumor correlated with 5-year EFS:;distal extremity 65% (SE 8%), central 63 % (SE 10 %), proximal extremity 46% (SE 8%), and pelvic-sacral 24% (SE 10%) (p = 0.004). Initial tumor size did not correlate significantly with EFS. Patterns of failure among the 141 localized patients revealed 23% of patients experienced a local failure, while 40% had a systemic failure. The 5-year local control rate for the surgical patients +/- postoperative radiotherapy was 88% (SE 6%), while for the patients undergoing radiotherapy alone it was 65% (SE 7%). There was no difference in local control between those randomized to SF vs. IF. The 5-year local control rate for the patients with pelvic-sacral tumors was 44% (SE 15%), significantly worse than the local control rates for those with central tumors 82% (SE 8%), distal extremity 80% (SE 8%), or proximal extremity 69% (SE 9%) (p = 0.023). However, quality of radiotherapy correlated with outcome; Patients who had appropriate radiotherapy had a 5-year local control of 80% (SE 7%), while those with minor deviations had 5-year local control of 48% (SE 14%), and those,vith major deviations had a local control of only 16% (SE 15%) (p = 0.005). The local failure was within an irradiated volume in 62% of patients, outside the irradiated volume in 24% of cases, while the precise location could not be determined in the remaining 14%.Conclusions: As most failures in Ewing's sarcoma are systemic, improved EFS requires more effective systemic chemotherapy. Adequate IP radiotherapy requires treatment to appropriate volumes as defined by MRI imaging and full radiation doses. Pretreatment review of radiologic images with a musculoskeletal radiologist to determine appropriate tumor volumes, as well as use of conformal radiotherapy techniques are important for improved outcome. (C) 1998 Elsevier Science Inc.