- 作者：Sam S. Yoon M.D.&lowast ; ; ; &dagger ; &dagger ; ; ; syoon@partners.org ; Dan G. Duda Ph.D.&dagger ; ; Daniel L. Karl B.S.&lowast ; ; Tae-Min Kim Ph.D.&Dagger ; ; Avinash R. Kambadakone M.D.§ ; ; Yen-Lin Chen M.D.&dagger ; ; Courtney Rothrock B.S.&lowast ; ; Andrew E. Rosenberg M.D.¶ ; ; G. Petur Nielsen M.D.¶ ; ; David G. Kirsch M.D. ; Ph.D.?/sup> ; Edwin Choy M.D. ; Ph.D.# ; David C. Harmon M.D.# ; Francis J. Hornicek M.D. ; Ph.D.&lowast ; &lowast ; ; Jonathan Dreyfuss M.S.&Dagger ; ; Marek Ancukiewicz Ph.D.&dagger ; ; Dushyant V. Sahani M.D.§ ; ; Peter J. Park Ph.D.&Dagger ; ; Rakesh K. Jain Ph.D.&dagger ; ; Thomas F. DeLaney M.D.&dagger ;
- 刊名：International Journal of Radiation Oncology*Biology*Physics
- 出版年：2011
- 出版时间：15 November 2011
- 年：2011
- 卷：81
- 期：4
- 页码：1081-1090
- 全文大小：1447 K
Purpose
Numerous preclinical studies have demonstrated that angiogenesis inhibitors can increase the efficacy of radiotherapy (RT). We sought to examine the safety and efficacy of bevacizumab (BV) and RT in soft tissue sarcomas and explore biomarkers to help determine the treatment response.Methods and Materials
Patients with ? cm, intermediate- or high-grade soft tissue sarcomas at significant risk of local recurrence received neoadjuvant BV alone followed by BV plus RT before surgical resection. Correlative science studies included analysis of the serial blood and tumor samples and serial perfusion computed tomography scans.
Results
The 20 patients had a median tumor size of 8.25 cm, with 13 extremity, 1 trunk, and 6 retroperitoneal/pelvis tumors. The neoadjuvant treatment was well tolerated, with only 4 patients having Grade 3 toxicities (hypertension, liver function test elevation). BV plus RT resulted in ?0 % pathologic necrosis in 9 (45 % ) of 20 tumors, more than double the historical rate seen with RT alone. Three patients had a complete pathologic response. The median microvessel density decreased 53 % after BV alone (p <.05). After combination therapy, the median tumor cell proliferation decreased by 73 % , apoptosis increased 10.4-fold, and the blood flow, blood volume, and permeability surface area decreased by 62?2 % (p <.05). Analysis of gene expression microarrays of untreated tumors identified a 24-gene signature for treatment response. The microvessel density and circulating progenitor cells at baseline and the reduction in microvessel density and plasma soluble c-KIT with BV therapy also correlated with a good pathologic response (p <.05). After a median follow-up of 20 months, only 1 patient had developed local recurrence.
Conclusions
The results from the present exploratory study indicated that BV increases the efficacy of RT against soft tissue sarcomas and might reduce the incidence of local recurrence. Thus, this regimen warrants additional investigation. Gene expression profiles and other tissue and circulating biomarkers showed promising correlations with treatment response.