Skip to main content

Advertisement

Log in

Salvage gamma knife stereotactic radiosurgery followed by bevacizumab for recurrent glioblastoma multiforme: a case–control study

  • Clinical Study - Patient Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

We evaluated the efficacy and safety of gamma knife stereotactic radiosurgery (GKSR) followed by bevacizumab combined with chemotherapy in 11 patients with recurrent glioblastoma multiforme who experienced tumor progression despite aggressive initial multi-modality treatment. Our experience included eight male and three female patients. The median patient age at GKSR was 62 years (range 46–72 years). At the time of GKSR, seven patients had a first recurrence and four had two or more recurrences. The median interval from the initial diagnosis until GKSR was 17 months (range 5–34.5 months). The median tumor volume was 13.6 cm3 (range 1.2–45.1 cm3) and the median margin dose of GKSR was 16 Gy (range 13–18 Gy). Following GKSR, bevacizumab was administrated with irinotecan in nine patients and with temozolomide in one patient. One patient was treated with bevacizumab monotherapy. The treatment outcomes were compared to 44 case-matched controls who underwent GKSR without additional bevacizumab. At a median of 13.7 months (range 4.6–28.3 months) after radiosurgery, tumor progression was evident in seven patients. The median progression-free survival (PFS) was 15 months (95% confidential interval (CI), 6.5–23.3 months). Six-month and 1-year PFS rates were 73 and 55%, respectively. The median overall survival (OS) from GKSR was 18 months (95% CI, 10.1–25.7 months) and 1-year OS rate was 73%. One patient (9%) experienced grade III toxicity and one patient (9%) had major adverse radiation effects. Compared with patients who did not receive bevacizumab, the patients who received bevacizumab had significantly prolonged PFS (15 months vs. 7 months, P = 0.035) and OS (18 months vs. 12 months, P = 0.005), and were less likely to develop an adverse radiation effect (9 vs. 46%, P = 0.037). The combination of salvage GKSR followed by bevacizumab added potential benefit and little additional risk in a small group of patients with progressive glioblastoma. Further experience is needed to define the efficacy and long-term toxicity with this strategy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Biswas T, Okunieff P, Schell MC, Smudzin T, Pilcher WH, Bakos RS, Vates GE, Walter KA, Wensel A, Korones DN, Milano MT (2009) Stereotactic radiosurgery for glioblastoma: retrospective analysis. Radiat Oncol 4:11

    Article  PubMed  Google Scholar 

  2. Combs SE, Widmer V, Thilmann C, Hof H, Debus J, Schulz-Ertner D (2005) Stereotactic radiosurgery (SRS): treatment option for recurrent glioblastoma multiforme (GBM). Cancer 104:2168–2173

    Article  PubMed  Google Scholar 

  3. Kong DS, Lee JI, Park K, Kim JH, Lim DH, Nam DH (2008) Efficacy of stereotactic radiosurgery as a salvage treatment for recurrent malignant gliomas. Cancer 112:2046–2051

    Article  PubMed  Google Scholar 

  4. Ferrara N (2005) VEGF as a therapeutic target in cancer. Oncology 69(Suppl 3):11–16

    Article  PubMed  CAS  Google Scholar 

  5. Poon RT, Fan ST, Wong J (2001) Clinical implications of circulating angiogenic factors in cancer patients. J Clin Oncol 19:1207–1225

    PubMed  CAS  Google Scholar 

  6. Pradeep CR, Sunila ES, Kuttan G (2005) Expression of vascular endothelial growth factor (VEGF) and VEGF receptors in tumor angiogenesis and malignancies. Integr Cancer Ther 4:315–321

    Article  PubMed  CAS  Google Scholar 

  7. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342

    Article  PubMed  CAS  Google Scholar 

  8. Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:2666–2676

    Article  PubMed  CAS  Google Scholar 

  9. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550

    Article  PubMed  CAS  Google Scholar 

  10. Desjardins A, Reardon DA, Herndon JE II, Marcello J, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Sampson J, Bailey L, Bigner DD, Friedman AH, Friedman HS, Vredenburgh JJ (2008) Bevacizumab plus irinotecan in recurrent WHO grade 3 malignant gliomas. Clin Cancer Res 14:7068–7073

    Article  PubMed  CAS  Google Scholar 

  11. Vredenburgh JJ, Desjardins A, Herndon JE II, Marcello J, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Sampson J, Wagner M, Bailey L, Bigner DD, Friedman AH, Friedman HS (2007) Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 25:4722–4729

    Article  PubMed  CAS  Google Scholar 

  12. Gorski DH, Beckett MA, Jaskowiak NT, Calvin DP, Mauceri HJ, Salloum RM, Seetharam S, Koons A, Hari DM, Kufe DW, Weichselbaum RR (1999) Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res 59:3374–3378

    PubMed  CAS  Google Scholar 

  13. Moeller BJ, Cao Y, Li CY, Dewhirst MW (2004) Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules. Cancer Cell 5:429–441

    Article  PubMed  CAS  Google Scholar 

  14. Ahn GO, Brown JM (2008) Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: role of bone marrow-derived myelomonocytic cells. Cancer Cell 13:193–205

    Article  PubMed  CAS  Google Scholar 

  15. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996

    Article  PubMed  CAS  Google Scholar 

  16. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972

    Article  PubMed  Google Scholar 

  17. Bauman GS, Sneed PK, Wara WM, Stalpers LJ, Chang SM, McDermott MW, Gutin PH, Larson DA (1996) Reirradiation of primary CNS tumors. Int J Radiat Oncol Biol Phys 36:433–441

    Article  PubMed  CAS  Google Scholar 

  18. Mayer R, Sminia P (2008) Reirradiation tolerance of the human brain. Int J Radiat Oncol Biol Phys 70:1350–1360

    Article  PubMed  CAS  Google Scholar 

  19. Kondziolka D, Flickinger JC, Bissonette DJ, Bozik M, Lunsford LD (1997) Survival benefit of stereotactic radiosurgery for patients with malignant glial neoplasms. Neurosurgery 41:776–783 Discussion 783–775

    Article  PubMed  CAS  Google Scholar 

  20. Nwokedi EC, DiBiase SJ, Jabbour S, Herman J, Amin P, Chin LS (2002) Gamma knife stereotactic radiosurgery for patients with glioblastoma multiforme. Neurosurgery 50:41–46 Discussion 46–47

    PubMed  Google Scholar 

  21. Larson DA, Prados M, Lamborn KR, Smith V, Sneed PK, Chang S, Nicholas KM, Wara WM, Devriendt D, Kunwar S, Berger M, McDermott MW (2002) Phase II study of high central dose gamma knife radiosurgery and marimastat in patients with recurrent malignant glioma. Int J Radiat Oncol Biol Phys 54:1397–1404

    Article  PubMed  Google Scholar 

  22. Tsao MN, Mehta MP, Whelan TJ, Morris DE, Hayman JA, Flickinger JC, Mills M, Rogers CL, Souhami L (2005) The American society for therapeutic radiology and oncology (ASTRO) evidence-based review of the role of radiosurgery for malignant glioma. Int J Radiat Oncol Biol Phys 63:47–55

    Article  PubMed  Google Scholar 

  23. Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA (2009) Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 27:740–745

    Article  PubMed  CAS  Google Scholar 

  24. Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407:249–257

    Article  PubMed  CAS  Google Scholar 

  25. Winkler F, Kozin SV, Tong RT, Chae SS, Booth MF, Garkavtsev I, Xu L, Hicklin DJ, Fukumura D, di Tomaso E, Munn LL, Jain RK (2004) Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 6:553–563

    PubMed  CAS  Google Scholar 

  26. Wong ET, Brem S (2007) Taming glioblastoma: targeting angiogenesis. J Clin Oncol 25:4705–4706

    Article  PubMed  CAS  Google Scholar 

  27. Vredenburgh JJ, Desjardins A, Herndon JE II, Dowell JM, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Wagner M, Bigner DD, Friedman AH, Friedman HS (2007) Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res 13:1253–1259

    Article  PubMed  CAS  Google Scholar 

  28. Gutin PH, Iwamoto FM, Beal K, Mohile NA, Karimi S, Hou BL, Lymberis S, Yamada Y, Chang J, Abrey LE (2009) Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas. Int J Radiat Oncol Biol Phys 75:156–163

    Article  PubMed  CAS  Google Scholar 

  29. Steiner HH, Karcher S, Mueller MM, Nalbantis E, Kunze S, Herold-Mende C (2004) Autocrine pathways of the vascular endothelial growth factor (VEGF) in glioblastoma multiforme: clinical relevance of radiation-induced increase of VEGF levels. J Neurooncol 66:129–138

    Article  PubMed  Google Scholar 

  30. Senan S, Smit EF (2007) Design of clinical trials of radiation combined with antiangiogenic therapy. Oncologist 12:465–477

    Article  PubMed  CAS  Google Scholar 

  31. Hovinga KE, Stalpers LJ, van Bree C, Donker M, Verhoeff JJ, Rodermond HM, Bosch DA, van Furth WR (2005) Radiation-enhanced vascular endothelial growth factor (VEGF) secretion in glioblastoma multiforme cell lines–a clue to radioresistance? J Neurooncol 74:99–103

    Article  PubMed  CAS  Google Scholar 

  32. Wachsberger PR, Burd R, Cardi C, Thakur M, Daskalakis C, Holash J, Yancopoulos GD, Dicker AP (2007) VEGF trap in combination with radiotherapy improves tumor control in u87 glioblastoma. Int J Radiat Oncol Biol Phys 67:1526–1537

    Article  PubMed  CAS  Google Scholar 

  33. Nieder C, Wiedenmann N, Andratschke N, Molls M (2006) Current status of angiogenesis inhibitors combined with radiation therapy. Cancer Treat Rev 32:348–364

    Article  PubMed  CAS  Google Scholar 

  34. Cuneo KC, Vredenburgh JJ, Sampson JH, Reardon DA, Desjardins A, Peters KB, Friedman HS, Willett CG, Kirkpatrick JP (2011) Safety and efficacy of stereotactic radiosurgery and adjuvant bevacizumab in patients with recurrent malignant gliomas. Int J Radiat Oncol Biol Phys. doi:10.1016/j.ijrobp.2010.12.074

  35. Fogh SE, Andrews DW, Glass J, Curran W, Glass C, Champ C, Evans JJ, Hyslop T, Pequignot E, Downes B, Comber E, Maltenfort M, Dicker AP, Werner-Wasik M (2010) Hypofractionated stereotactic radiation therapy: an effective therapy for recurrent high-grade gliomas. J Clin Oncol 28:3048–3053

    Article  PubMed  Google Scholar 

  36. Hall WA, Djalilian HR, Sperduto PW, Cho KH, Gerbi BJ, Gibbons JP, Rohr M, Clark HB (1995) Stereotactic radiosurgery for recurrent malignant gliomas. J Clin Oncol 13:1642–1648

    PubMed  CAS  Google Scholar 

  37. Hsieh PC, Chandler JP, Bhangoo S, Panagiotopoulos K, Kalapurakal JA, Marymont MH, Cozzens JW, Levy RM, Salehi S (2005) Adjuvant gamma knife stereotactic radiosurgery at the time of tumor progression potentially improves survival for patients with glioblastoma multiforme. Neurosurgery 57:684–692

    Article  PubMed  Google Scholar 

  38. Mahajan A, McCutcheon IE, Suki D, Chang EL, Hassenbusch SJ, Weinberg JS, Shiu A, Maor MH, Woo SY (2005) Case-control study of stereotactic radiosurgery for recurrent glioblastoma multiforme. J Neurosurg 103:210–217

    Article  PubMed  Google Scholar 

  39. Patel M, Siddiqui F, Jin JY, Mikkelsen T, Rosenblum M, Movsas B, Ryu S (2009) Salvage reirradiation for recurrent glioblastoma with radiosurgery: radiographic response and improved survival. J Neurooncol 92:185–191

    Article  PubMed  Google Scholar 

  40. Pouratian N, Crowley RW, Sherman JH, Jagannathan J, Sheehan JP (2009) Gamma knife radiosurgery after radiation therapy as an adjunctive treatment for glioblastoma. J Neurooncol 94:409–418

    Article  PubMed  CAS  Google Scholar 

  41. Vordermark D, Kolbl O, Ruprecht K, Vince GH, Bratengeier K, Flentje M (2005) Hypofractionated stereotactic re-irradiation: treatment option in recurrent malignant glioma. BMC Cancer 5:55

    Article  PubMed  Google Scholar 

  42. Shrieve DC, Alexander E III, Wen PY, Fine HA, Kooy HM, Black PM, Loeffler JS (1995) Comparison of stereotactic radiosurgery and brachytherapy in the treatment of recurrent glioblastoma multiforme. Neurosurgery 36:275–282; discussion 282–274

    Article  PubMed  CAS  Google Scholar 

  43. Gonzalez J, Kumar AJ, Conrad CA, Levin VA (2007) Effect of bevacizumab on radiation necrosis of the brain. Int J Radiat Oncol Biol Phys 67:323–326

    Article  PubMed  CAS  Google Scholar 

  44. Silbergeld DL, Chicoine MR (1997) Isolation and characterization of human malignant glioma cells from histologically normal brain. J Neurosurg 86:525–531

    Article  PubMed  CAS  Google Scholar 

Download references

Conflicts of interest

Drs. Lunsford, Kondziolka, and Niranjan are consultants with AB Elekta. Dr. Lunsford is a stockholder in AB Elekta.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Douglas Kondziolka.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Park, KJ., Kano, H., Iyer, A. et al. Salvage gamma knife stereotactic radiosurgery followed by bevacizumab for recurrent glioblastoma multiforme: a case–control study. J Neurooncol 107, 323–333 (2012). https://doi.org/10.1007/s11060-011-0744-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-011-0744-9

Keywords

Navigation