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Phase II study of neoadjuvant bevacizumab and radiotherapy for resectable soft tissue sarcomas.

Publication ,  Journal Article
Yoon, SS; Duda, DG; Karl, DL; Kim, T-M; Kambadakone, AR; Chen, Y-L; Rothrock, C; Rosenberg, AE; Nielsen, GP; Kirsch, DG; Choy, E; Harmon, DC ...
Published in: Int J Radiat Oncol Biol Phys
November 15, 2011

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 ≥5 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 ≥80% 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 62-72% (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.

Duke Scholars

Published In

Int J Radiat Oncol Biol Phys

DOI

EISSN

1879-355X

Publication Date

November 15, 2011

Volume

81

Issue

4

Start / End Page

1081 / 1090

Location

United States

Related Subject Headings

  • Tumor Burden
  • Treatment Outcome
  • Soft Tissue Neoplasms
  • Sarcoma
  • Radiotherapy Dosage
  • Postoperative Complications
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Neoadjuvant Therapy
  • Middle Aged
 

Citation

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Yoon, S. S., Duda, D. G., Karl, D. L., Kim, T.-M., Kambadakone, A. R., Chen, Y.-L., … Delaney, T. F. (2011). Phase II study of neoadjuvant bevacizumab and radiotherapy for resectable soft tissue sarcomas. Int J Radiat Oncol Biol Phys, 81(4), 1081–1090. https://doi.org/10.1016/j.ijrobp.2010.07.024
Yoon, Sam S., Dan G. Duda, Daniel L. Karl, Tae-Min Kim, Avinash R. Kambadakone, Yen-Lin Chen, Courtney Rothrock, et al. “Phase II study of neoadjuvant bevacizumab and radiotherapy for resectable soft tissue sarcomas.Int J Radiat Oncol Biol Phys 81, no. 4 (November 15, 2011): 1081–90. https://doi.org/10.1016/j.ijrobp.2010.07.024.
Yoon SS, Duda DG, Karl DL, Kim T-M, Kambadakone AR, Chen Y-L, et al. Phase II study of neoadjuvant bevacizumab and radiotherapy for resectable soft tissue sarcomas. Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):1081–90.
Yoon, Sam S., et al. “Phase II study of neoadjuvant bevacizumab and radiotherapy for resectable soft tissue sarcomas.Int J Radiat Oncol Biol Phys, vol. 81, no. 4, Nov. 2011, pp. 1081–90. Pubmed, doi:10.1016/j.ijrobp.2010.07.024.
Yoon SS, Duda DG, Karl DL, Kim T-M, Kambadakone AR, Chen Y-L, Rothrock C, Rosenberg AE, Nielsen GP, Kirsch DG, Choy E, Harmon DC, Hornicek FJ, Dreyfuss J, Ancukiewicz M, Sahani DV, Park PJ, Jain RK, Delaney TF. Phase II study of neoadjuvant bevacizumab and radiotherapy for resectable soft tissue sarcomas. Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):1081–1090.
Journal cover image

Published In

Int J Radiat Oncol Biol Phys

DOI

EISSN

1879-355X

Publication Date

November 15, 2011

Volume

81

Issue

4

Start / End Page

1081 / 1090

Location

United States

Related Subject Headings

  • Tumor Burden
  • Treatment Outcome
  • Soft Tissue Neoplasms
  • Sarcoma
  • Radiotherapy Dosage
  • Postoperative Complications
  • Oncology & Carcinogenesis
  • Neoplasm Recurrence, Local
  • Neoadjuvant Therapy
  • Middle Aged