RECURRENT GLIOBLASTOMA MANAGEMENT USING STEREOTACTIC RADIOSURGERY AND SYSTEMIC TREATMENT

Oleksandr Glavatskyi, Oksana Zemskova

Abstract


Glioblastoma multiforme (GBM) is the most common primary malignant tumor of the central nervous system in adults. Dismal survival rates and poor prognosis for recurrent GBM patients still remains a challenging problem. Despite aggressive initial treatment, above 100 % GBM patients have development of recurrent diseases. Management of GBM recurrence is still debatable. The multimodality approaches using combination of stereotactic radiosurgery (SRS), cytostatic agents (Тemozolomide (TMZ)) and antiangiogenic therapy (bevacizumab (BEV)) are often beneficial for such patients and may achieve survival improving.

Aim of research: to assess the efficacy and toxicity of combination therapy approach using stereotactic radiosurgery (SRS) and systemic treatment (chemotherapy and antiangiogenic therapy) in glioblastoma multiforme recurrence treatment.

Materials and methods: at the State Institution “Institute of Neurosurgery named after acad. A.P. Romodanov of NAMS of Ukraine” (Kyiv, Ukraine) 21 patients (pts) with GBM recurrence were treated (8 females and 11 men; median age at time of diagnosis 52.4 (29.7–69.3) from January 2014 till December 2017. The initial surgical treatment as gross total tumor resection was performed in 12 pts (57.1 %), subtotal resection – 5 pts (23.9 %), biopsy – 4 pts (19 %). 12 pts (57.1 %) were MGMT methylated and 9 pts (42.9 %) were MGMT unmethylated. In all cases adjuvant radiation therapy (60 Gy in 30 fractions) were used, 12 pts of them (57.1 %) – in combination with TMZ followed by 6-12 courses of chemotherapy (TMZ) according Stupp protocol. Recurrent disease was treated by SRS followed by TMZ + BEV. SRS was performed by means of “Trilogy” LINAC (“Varian”, USA) with a median dose and fractions of 19.2 Gy (range, 12.0–36.0) in 1 to 5 fractions.

Results: median survival after initial diagnosis was 18.3 months, and 1- and 2-year survival rates of 85.7 % (18 from 21 pts) and 38.1 % (8 from 21 pts) respectively. The median survival from the time of recurrence treatment was 8.3 months. The 6‐ and 12‐months overall survival from SRS were 95.2 % (20 from 21 pts) and 23.8 % (5 from 21 pts), respectively. Adverse radiation effects were noted in 6 (28.6 %) pts and were controlled with corticosteroids. Adverse events grade 1-2 related to the systemic therapy included hematological complications, fatigue, hypertension and proteinuria were observed in 23.8 % (5 from 21 pts) without the occurrence of grade 3 events.

Conclusion: recurrent GBM management using combination of SRS, chemotherapy and antiangiogenic therapy is a promising multimodal treatment approach providing survival improving whereas appropriate toxicity ratio. Further studies of combined treatment of GBM relapse are needed.


Keywords


glioblastoma multiforme recurrence; multimodality approaches; radiosurgery; temozolomide; bevacizumab; toxicity

Full Text:

PDF

References


Touat, M., Idbaih, A., Sanson, M., Ligon, K. L. (2017). Glioblastoma targeted therapy: updated approaches from recent biological insights. Annals of Oncology, 28 (7), 1457–1472. doi: https://doi.org/10.1093/annonc/mdx106

Wen, P. Y., DeAngelis, L. M. (2007). Chemotherapy for low-grade gliomas: Emerging consensus on its benefits. Neurology, 68 (21), 1762–1763. doi: https://doi.org/10.1212/01.wnl.0000266866.13748.a9

Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J. B. et. al. (2005). Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. New England Journal of Medicine, 352 (10), 987–996. doi: https://doi.org/10.1056/nejmoa043330

Niyazi, M., Siefert, A., Schwarz, S. B., Ganswindt, U., Kreth, F.-W., Tonn, J.-C., Belka, C. (2011). Therapeutic options for recurrent malignant glioma. Radiotherapy and Oncology, 98 (1), 1–14. doi: https://doi.org/10.1016/j.radonc.2010.11.006

Imber, B. S., Kanungo, I., Braunstein, S., Barani, I. J., Fogh, S. E., Nakamura, J. L. et. al. (2016). Indications and Efficacy of Gamma Knife Stereotactic Radiosurgery for Recurrent Glioblastoma: 2 Decades of Institutional Experience. Neurosurgery, 80 (1), 129–139. doi: https://doi.org/10.1227/neu.0000000000001344

Ghosh, D., Nandi, S., Bhattacharjee, S. (2018). Combination therapy to checkmate Glioblastoma: clinical challenges and advances. Clinical and Translational Medicine, 7 (1). doi: https://doi.org/10.1186/s40169-018-0211-8

Kong, D.-S., Lee, J.-I., Park, K., Kim, J. H., Lim, D.-H., Nam, D.-H. (2008). Efficacy of stereotactic radiosurgery as a salvage treatment for recurrent malignant gliomas. Cancer, 112 (9), 2046–2051. doi: https://doi.org/10.1002/cncr.23402

Bokstein, F., Blumenthal, D. T., Corn, B. W., Gez, E., Matceyevsky, D., Shtraus, N. et. al. (2015). Stereotactic radiosurgery (SRS) in high-grade glioma: judicious selection of small target volumes improves results. Journal of Neuro-Oncology, 126 (3), 551–557. doi: https://doi.org/10.1007/s11060-015-1997-5

Cheon, Y.-J., Jung, T.-Y., Jung, S., Kim, I.-Y., Moon, K.-S., Lim, S.-H. (2018). Efficacy of Gamma Knife Radiosurgery for Recurrent High-Grade Gliomas with Limited Tumor Volume. Journal of Korean Neurosurgical Society, 61 (4), 516–524. doi: https://doi.org/10.3340/jkns.2017.0259

Dodoo, E., Huffmann, B., Peredo, I., Grinaker, H., Sinclair, G., Machinis, T. et. al. (2014). Increased Survival Using Delayed Gamma Knife Radiosurgery for Recurrent High-Grade Glioma: A Feasibility Study. World Neurosurgery, 82 (5), e623–e632. doi: https://doi.org/10.1016/j.wneu.2014.06.011

Sheehan, J. P., Lee, C.-C. (2014). Stereotactic Radiosurgery for Recurrent High-Grade Gliomas. World Neurosurgery, 82 (5), e593–e595. doi: https://doi.org/10.1016/j.wneu.2014.06.042

Barker, F. G., Chang, S. M., Gutin, P. H., Malec, M. K., McDermott, M. W., Prados, M. D., Wilson, C. B. (1998). Survival and Functional Status after Resection of Recurrent Glioblastoma Multiforme. Neurosurgery, 42 (4), 709–719. doi: https://doi.org/10.1097/00006123-199804000-00013

Dirks, P., Bernstein, M., Muller, P. J., Tucker, W. S. (1993). The value of reoperation for recurrent glioblastoma. Canadian Journal of Surgery, 36 (3), 271–275.

Young, B., Oldfield, E. H., Markesbery, W. R., Haack, D., Tibbs, P. A., McCombs, P. et. al. (1981). Reoperation for glioblastoma. Journal of Neurosurgery, 55 (6), 917–921. doi: https://doi.org/10.3171/jns.1981.55.6.0917

Heron, D., Holt, D., Bernard, M., Quan, K., Clump, D., Engh, J., Burton, S. (2016). Salvage stereotactic radiosurgery for recurrent glioblastoma multiforme with prior radiation therapy. Journal of Cancer Research and Therapeutics, 12 (4), 1243. doi: https://doi.org/10.4103/0973-1482.199537

Park, K.-J., Kano, H., Iyer, A., Liu, X., Niranjan, A., Flickinger, J. C. et. al. (2011). Salvage gamma knife stereotactic radiosurgery followed by bevacizumab for recurrent glioblastoma multiforme: a case–control study. Journal of Neuro-Oncology, 107 (2), 323–333. doi: https://doi.org/10.1007/s11060-011-0744-9




DOI: http://dx.doi.org/10.21303/2585-663.2018.00764

Refbacks

  • There are currently no refbacks.


Copyright (c) 2018 Oleksandr Glavatskyi, Oksana Zemskova

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

ISSN 2585-6634 (Online), ISSN 2585-6626 (Print)