de Vreeze Ronald S A, de Jong Daphne, Haas Rick L, Stewart Fiona, van Coevorden Frits
Department of Surgical Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Int J Radiat Oncol Biol Phys. 2008 Dec 1;72(5):1480-7. doi: 10.1016/j.ijrobp.2008.03.008. Epub 2008 Apr 28.
Surgery and adjuvant radiotherapy (RT) have long been the standard treatment for most deep-seated sarcomas; however, since the randomized trial from the National Cancer Institute of Canada, which described similar local control for pre- vs. postoperative RT, both modalities are now widely accepted. As a group, sarcomas are classified as radiation resistant. The subgroup of myxoid liposarcoma (MLS), a sarcoma with a typical vascular crow's feet pattern, is highly radiosensitive, but a mechanism for this phenomenon is unknown. Here we describe our results with preoperative RT and propose a mechanism explaining the high sensitivity based on the distinctive vascularization pattern of MLS.
Between 2002 and 2006, 31 sarcoma patients, including 10 with MLS, underwent preoperative RT at our institute. Resected specimens were histologically evaluated, focusing on classification, grade, and vascularization patterns.
Twenty sarcomas showed more than 80% pathologic response after preoperative RT. A pathologic complete response was found in all "pure" MLS specimens after preoperative RT (n = 8). There were no pathologic complete responses in the remaining sarcoma patients (n = 23), although 12 showed 80% to 90% pathologic response. In contrast to the remaining RT-resistant sarcomas, the highly responding specimens contained branching vasculature, partial thrombus formation and inflammation of medium sized arterioles, similar to the vascular changes in MLS.
Both MLS and sarcomas with MLS-like vasculature are highly radiosensitive. Radiation sensitivity may be explained by changes in medium-sized arterioles, obstructing the specific crow's feet vascularization and inducing hypoxia with secondary tumor cell death.
手术及辅助放疗长期以来一直是大多数深部肉瘤的标准治疗方法；然而，自加拿大国立癌症研究所的随机试验描述了术前与术后放疗的局部控制效果相似以来，这两种治疗方式目前均被广泛接受。作为一个整体，肉瘤被归类为放射抗拒性肿瘤。黏液样脂肪肉瘤（MLS）亚组，一种具有典型血管鱼尾纹模式的肉瘤，对放疗高度敏感，但其发生机制尚不清楚。在此，我们描述术前放疗的结果，并基于MLS独特的血管化模式提出一种解释其高敏感性的机制。
2002年至2006年期间，31例肉瘤患者，包括10例MLS患者，在我们研究所接受了术前放疗。对切除标本进行组织学评估，重点关注分类、分级和血管化模式。
20例肉瘤在术前放疗后显示出超过80%的病理反应。术前放疗后，所有“纯”MLS标本（n = 8）均出现病理完全缓解。其余肉瘤患者（n = 23）均未出现病理完全缓解，尽管有12例显示出80%至90%的病理反应。与其余放射抗拒性肉瘤不同，高反应标本含有分支状血管、部分血栓形成以及中等大小小动脉的炎症，类似于MLS中的血管变化。
MLS以及具有MLS样血管的肉瘤均对放疗高度敏感。放射敏感性可能由中等大小小动脉的变化来解释，这些变化阻碍了特定的鱼尾纹血管化并诱导缺氧，继而导致肿瘤细胞死亡。
