Smith L M, Donaldson S S, Egbert P R, Link M P, Bagshaw M A
Department of Radiation Oncology, Stanford University Medical Center, CA 94305.
Int J Radiat Oncol Biol Phys. 1989 Sep;17(3):499-505. doi: 10.1016/0360-3016(89)90100-4.
Survivors of hereditary retinoblastoma are at increased risk for the development of second primary tumors, most commonly osteosarcoma. Recent molecular genetic data demonstrate that a pleiotrophic effect of the retinoblastoma gene may be responsible for the development of these sarcomas. This report describes the incidence of second nonocular malignancies among 53 infants seen at Stanford University Medical Center who have been followed a median of 11.7 years. Of these, 42 initially had bilateral disease and eleven had unilateral disease. Of 53 infants, 50 received irradiation either as part of the initial therapy or as treatment for recurrent disease. The actuarial survival for the entire group is 67% at 30 year follow-up with a median survival of 79% at 11.7 years. Eight patients developed eleven second primary tumors. All occurred in the group having hereditary retinoblastoma. Eight were within the previously irradiated field and three were at distant sites. The second tumors included seven osteosarcomas, one angiosarcoma, one rhabdomyosarcoma, one malignant fibrous histiocytoma, and one unclassifiable round blue cell tumor. The actuarial incidence of the development of a second primary malignancy was 6% at 10 years, 19% at 20 years, and 38% at 30 years. The latent period from treatment of retinoblastoma to the diagnosis of malignancy ranged from 5.2 years to 36.2 years (median 16 years). An aggressive approach with combined modality therapy including radical resection, re-irradiation and/or chemotherapy was used to treat these second primary tumors in five of eight patients. In four of the five, there was no evidence of disease at 22-72 months following treatment. In the three patients who did not receive aggressive combined treatment, there were no survivors. These data confirm the previously reported risk of developing a second primary tumor among survivors with hereditary retinoblastoma. Careful long-term follow-up for this genetically susceptible group is essential for early detection and implementation of curative therapy.
遗传性视网膜母细胞瘤幸存者发生第二原发性肿瘤的风险增加，最常见的是骨肉瘤。最近的分子遗传学数据表明，视网膜母细胞瘤基因的多效性作用可能是这些肉瘤发生的原因。本报告描述了斯坦福大学医学中心诊治的53例婴儿中第二非眼恶性肿瘤的发生率，这些婴儿的中位随访时间为11.7年。其中，42例最初为双侧病变，11例为单侧病变。53例婴儿中，50例接受了放疗，作为初始治疗的一部分或复发性疾病的治疗。整个组在30年随访时的精算生存率为67%，在11.7年时的中位生存率为79%。8例患者发生了11例第二原发性肿瘤。所有病例均发生在遗传性视网膜母细胞瘤组。8例发生在先前接受放疗的区域内，3例发生在远处部位。第二肿瘤包括7例骨肉瘤、1例血管肉瘤、1例横纹肌肉瘤、1例恶性纤维组织细胞瘤和1例无法分类的圆形蓝细胞瘤。第二原发性恶性肿瘤发生的精算发生率在10年时为6%，20年时为19%，30年时为38%。从视网膜母细胞瘤治疗到恶性肿瘤诊断的潜伏期为5.2年至36.2年（中位16年）。8例患者中有5例采用了包括根治性切除、再次放疗和/或化疗在内的综合治疗方法积极治疗这些第二原发性肿瘤。5例中有4例在治疗后22 - 72个月无疾病证据。在未接受积极联合治疗的3例患者中，无幸存者。这些数据证实了先前报道的遗传性视网膜母细胞瘤幸存者发生第二原发性肿瘤的风险。对这一遗传易感性群体进行仔细的长期随访对于早期发现和实施治愈性治疗至关重要。
