Stages of stereotactic radiosurgery in the treatment of recurrent glioblastomas




Objective: to evaluate the effectiveness of stereotactic radiosurgery as a therapy method taking into account overall survival in patients with recurrent glioblastoma at all stages of treatment.

Materials and methods. A sample of patients (66 ailments) who were treated in 2016-2021 with a molecularly confirmed diagnosis of wild-type glioblastoma was analyzed. Only patients, who, were treated in several stages and as a rule, underwent stereotaxic radiosurgery (SRS), or SRS alone after a biopsy, or SRS in case of relapse, after surgery and radiotherapy, or SRS for subsequent relapses were selected. When evaluating the results, the following were taken into account: 1) age at the diagnosis, 2) volume of surgical resection, 3) use of radiation therapy, 4) use of adjuvant chemotherapy after SRS and response evluation criteria in solid tumors. Overall survival (OS) was assessed after diagnosis and at the time of SRS.

Results. Patients received SRS at an average 10 months after initial diagnosis. Median duration of follow-up was 8 months after SRS and 12 months after diagnosis, median OS for all patients was nine months (1 to 42 months) after SRS and 20 months (4 to 64 months) respectively. The median survival after SRS was 9 months (p=0.008; χ2=7.008). The median OS for younger patients (<50 years) was 32.5 months, for elderly patients  (>50 years)  was 14.8 months  (p=0.04; χ2=3.870). The median overall survival rate was 32.2 months in patients who received SRS 10 months after the diagnosis was made, and 16 months in those who received SRS earlier than 10 months (p=0.004, χ2=8.145). Radiosurgical doses ≥15 Gy were correlated with a mean survival rate of nine months and seven months in patients treated at doses <15 Gy (p=0.01; χ2=6.756).  In patients who received adjuvant therapy with bevacizumab and/or chemotherapy after SRS, the median OS was 12 months, in patients who did not receive additional therapy after SRS, it was 7 months (p=0.04, χ2=4.19).

Conclusions. Stereotactic radiosurgery promotes the effectiveness of glioblastoma treatment due to the possibility of carrying out this method at various stages of treatment. The overall survival of our patients depended on the period of SRS after diagnosis, patient age, radiation dose, and adjuvant chemotherapy.

Author Biographies

Andriy B. Gryazov, Romodanov Neurosurgery Institute, Kyiv

Department of Radioneurosurgery, Romodanov Neurosurgery Institute, Kyiv, Ukraine

Oksana V. Zemskova, Romodanov Neurosurgery Institute, Kyiv

Department of Radioneurosurgery, Romodanov Neurosurgery Institute, Kyiv, Ukraine

Andriy A. Gryazov, Romodanov Neurosurgery Institute, Kyiv

Department of Radioneurosurgery, Romodanov Neurosurgery Institute, Kyiv, Ukraine


Shah JL, Li G, Shaffer JL, Azoulay MI, Gibbs IC, Nagpal S, Soltys SG. Stereotactic Radiosurgery and Hypofractionated Radiotherapy for Glioblastoma. Neurosurgery. 2018 Jan 1;82(1):24-34. doi: 10.1093/neuros/nyx115

Abbassy M, Missios S, Barnett GH, Brewer C, Peereboom DM, Ahluwalia M, Neyman G, Chao ST, Suh JH, Vogelbaum MA. Phase I Trial of Radiosurgery Dose Escalation Plus Bevacizumab in Patients With Recurrent/Progressive Glioblastoma. Neurosurgery. 2018 Sep 1;83(3):385-392. doi: 10.1093/neuros/nyx369

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. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330

Tamimi AF, Juweid M. Epidemiology and Outcome of Glioblastoma. In: De Vleeschouwer S, editor. Glioblastoma [Internet]. Brisbane (AU): Codon Publications; 2017 Sep 27. Chapter 8. doi: 10.15586/codon.glioblastoma.2017.ch8

Bunevicius A, Sheehan JP. Radiosurgery for Glioblastoma. Neurosurg Clin N Am. 2021 Jan;32(1):117-128. doi: 10.1016/

Imber BS, Kanungo I, Braunstein S, Barani IJ, Fogh SE, Nakamura JL, Berger MS, Chang EF, Molinaro AM, Cabrera JR, McDermott MW, Sneed PK, Aghi MK. Indications and Efficacy of Gamma Knife Stereotactic Radiosurgery for Recurrent Glioblastoma: 2 Decades of Institutional Experience. Neurosurgery. 2017 Jan 1;80(1):129-139. doi: 10.1227/NEU.0000000000001344

Fernandes C, Costa A, Osório L, Lago RC, Linhares P, Carvalho B, Caeiro C. Current Standards of Care in Glioblastoma Therapy. In: De Vleeschouwer S, editor. Glioblastoma [Internet]. Brisbane (AU): Codon Publications; 2017 Sep 27. Chapter 11. doi: 10.15586/codon.glioblastoma.2017.ch11

Regev O, Merkin V, Blumenthal DT, Melamed I, Kaisman-Elbaz T. Tumor-Treating Fields for the treatment of glioblastoma: a systematic review and meta-analysis. Neurooncol Pract. 2021 Apr 20;8(4):426-440. doi: 10.1093/nop/npab026

Braun K, Ahluwalia MS. Treatment of Glioblastoma in Older Adults. Curr Oncol Rep. 2017 Oct 26;19(12):81. doi: 10.1007/s11912-017-0644-z

Fetcko K, Lukas RV, Watson GA, Zhang L, Dey M. Survival and complications of stereotactic radiosurgery: A systematic review of stereotactic radiosurgery for newly diagnosed and recurrent high-grade gliomas. Medicine (Baltimore). 2017 Oct;96(43):e8293. doi: 10.1097/MD.0000000000008293

Guan Y, Xiong J, Pan M, Shi W, Li J, Zhu H, Gong X, Li C, Mei G, Liu X, Pan L, Dai J, Wang Y, Wang E, Wang X. Safety and efficacy of Hypofractionated stereotactic radiosurgery for high-grade Gliomas at first recurrence: a single-center experience. BMC Cancer. 2021 Feb 5;21(1):123. doi: 10.1186/s12885-021-07856-y

Souhami L, Seiferheld W, Brachman D, Podgorsak EB, Werner-Wasik M, Lustig R, Schultz CJ, Sause W, Okunieff P, Buckner J, Zamorano L, Mehta MP, Curran WJ Jr. Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: report of Radiation Therapy Oncology Group 93-05 protocol. Int J Radiat Oncol Biol Phys. 2004 Nov 1;60(3):853-60. doi: 10.1016/j.ijrobp.2004.04.011

Niranjan A, Monaco EA III, Kano H, Flickinger JC, Lunsford LD. Stereotactic Radiosurgery in the Multimodality Management of Residual or Recurrent Glioblastoma Multiforme. Prog Neurol Surg. 2018;31:48-61. doi: 10.1159/000466998

Guseynova K, Liscak R, Simonova G, Novotny J Jr. Gamma knife radiosurgery for local recurrence of glioblastoma. Neuro Endocrinol Lett. 2018 Oct;39(4):281-287.

Kong DS, Lee JI, Park K, Kim JH, Lim DH, Nam DH. Efficacy of stereotactic radiosurgery as a salvage treatment for recurrent malignant gliomas. Cancer. 2008 May 1;112(9):2046-51. doi: 10.1002/cncr.23402

Cuneo KC, Vredenburgh JJ, Sampson JH, Reardon DA, Desjardins A, Peters KB, Friedman HS, Willett CG, Kirkpatrick JP. Safety and efficacy of stereotactic radiosurgery and adjuvant bevacizumab in patients with recurrent malignant gliomas. Int J Radiat Oncol Biol Phys. 2012 Apr 1;82(5):2018-24. doi: 10.1016/j.ijrobp.2010.12.074

Gutin PH, Iwamoto FM, Beal K, Mohile NA, Karimi S, Hou BL, Lymberis S, Yamada Y, Chang J, Abrey LE. Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas. Int J Radiat Oncol Biol Phys. 2009 Sep 1;75(1):156-63. doi: 10.1016/j.ijrobp.2008.10.043

Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature. 2000 Sep 14;407(6801):249-57. doi: 10.1038/35025220

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. Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell. 2004 Dec;6(6):553-63. doi: 10.1016/j.ccr.2004.10.011

Gonzalez J, Kumar AJ, Conrad CA, Levin VA. Effect of bevacizumab on radiation necrosis of the brain. Int J Radiat Oncol Biol Phys. 2007 Feb 1;67(2):323-6. doi: 10.1016/j.ijrobp.2006.10.010

Gerstner ER, Duda DG, di Tomaso E, Ryg PA, Loeffler JS, Sorensen AG, Ivy P, Jain RK, Batchelor TT. VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer. Nat Rev Clin Oncol. 2009 Apr;6(4):229-36. doi: 10.1038/nrclinonc.2009.14

Cabrera AR, Cuneo KC, Vredenburgh JJ, Sampson JH, Kirkpatrick JP. Stereotactic radiosurgery and bevacizumab for recurrent glioblastoma multiforme. J Natl Compr Canc Netw. 2012 Jun 1;10(6):695-9. doi: 10.6004/jnccn.2012.0072

Kirkpatrick JP, Meyer JJ, Marks LB. The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery. Semin Radiat Oncol. 2008 Oct;18(4):240-3. doi: 10.1016/j.semradonc.2008.04.005

Niranjan A, Kano H, Iyer A, Kondziolka D, Flickinger JC, Lunsford LD. Role of adjuvant or salvage radiosurgery in the management of unresected residual or progressive glioblastoma multiforme in the pre-bevacizumab era. J Neurosurg. 2015 Apr;122(4):757-65. doi: 10.3171/2014.11.JNS13295

Skeie BS, Enger PØ, Brøgger J, Ganz JC, Thorsen F, Heggdal JI, Pedersen PH. γ knife surgery versus reoperation for recurrent glioblastoma multiforme. World Neurosurg. 2012 Dec;78(6):658-69. doi: 10.1016/j.wneu.2012.03.024

Koga T, Maruyama K, Tanaka M, Ino Y, Saito N, Nakagawa K, Shibahara J, Todo T. Extended field stereotactic radiosurgery for recurrent glioblastoma. Cancer. 2012 Sep 1;118(17):4193-200. doi: 10.1002/cncr.27372

Cabrera AR, Cuneo KC, Desjardins A, Sampson JH, McSherry F, Herndon JE 2nd, Peters KB, Allen K, Hoang JK, Chang Z, Craciunescu O, Vredenburgh JJ, Friedman HS, Kirkpatrick JP. Concurrent stereotactic radiosurgery and bevacizumab in recurrent malignant gliomas: a prospective trial. Int J Radiat Oncol Biol Phys. 2013 Aug 1;86(5):873-9. doi: 10.1016/j.ijrobp.2013.04.029

Martínez-Carrillo M, Tovar-Martín I, Zurita-Herrera M, Del Moral-Ávila R, Guerrero-Tejada R, Saura-Rojas E, Osorio-Ceballos JL, Arrebola-Moreno JP, Expósito-Hernández J. Salvage radiosurgery for selected patients with recurrent malignant gliomas. Biomed Res Int. 2014;2014:657953. doi: 10.1155/2014/657953

Elliott RE, Parker EC, Rush SC, Kalhorn SP, Moshel YA, Narayana A, Donahue B, Golfinos JG. Efficacy of gamma knife radiosurgery for small-volume recurrent malignant gliomas after initial radical resection. World Neurosurg. 2011 Jul-Aug;76(1-2):128-40; discussion 61-2. doi: 10.1016/j.wneu.2010.12.053



How to Cite

Gryazov, A. B., Zemskova, O. V., & Gryazov, A. A. (2022). Stages of stereotactic radiosurgery in the treatment of recurrent glioblastomas. Ukrainian Neurosurgical Journal, 28(2), 46–53.



Original articles