Early Results of Simultaneous Integrated Boost Volumetric Modulated arc Therapy (SIB-VMAT) Combined with Temozolomide in the Postoperative Treatment of Grade 4 glioblastoma

Introduction. Glioblastoma refers to a neuroepithelial malignant brain tumor with an aggressive course and extremely unfavorable prognosis. The median overall survival comprises 14.6 months. Standard treatment demonstrates relatively poor efficiency due to high recurrence rate associated with the high repopulation rate of tumor cells as well as impossibility of eradication of primary tumor. Simultaneous integrated boost is recognized as a technique to enhance local control in gliomas. Materials and methods. The study analyzed data of 25 patients who received chemoradiotherapy for grade 4 glioblastoma in the Radiotherapy Unit No 1. Day hospital lasted from September 2021 to March 2023 (data were analyzed over a year). In group 1, 15 patients received chemoradiation treatment, including simultaneous integrated boost volumetric modulated arc therapy (SIB-VMAT). In group 2, 10 patients received standard fractionated radiation therapy. Results and discussion. Treatment tolerability appeared satisfactory: the target dose was administered in 100% of patients without forced interruptions, toxicity was comparable in both groups; 1-year locoregional control comprised 46.7% in the group with simultaneous integrated boost, 50% in the group of standard fractionated therapy; 1-year overall survival accounted for 66.7% in the group with simultaneous integrated boost, and 70% in the group of standard therapy. The follow-up period revealed no cases of radiation necrosis. The results obtained in the present study appear comparable with the data of relevant scientific publications on the issue. Conclusion. Radiation therapy using simultaneous integrated boost in the postoperative treatment of grade 4 glioblastoma is considered as an acceptable and safe method with moderate toxicity and satisfactory overall survival rate.

1. Yakovlenko Y.G. Glioblastoma: the current state of the problem. Medical Herald of the South of Russia. 2019;10(4):28–35 (In Russ.). DOI: 10.21886/2219-8075-2019-10-4-28-35

2. Ostrom Q.T., Gittleman H., Truitt G., Boscia A., Kruchko C., Barnholtz-Sloan J.S. CBTRUS Statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2011–2015. NeuroOncol. 2018;20(1):81–6. DOI: 10.1093/neuonc/noy131

3. Wang J.Z., Li X.A. Impact of tumor repopulation on radiotherapy planning. Int J Radiat Oncol Biol Phys. 2005;61(1):220–7. DOI: 10.1016/j.ijrobp.2004.09.043

4. Piroth M.D., Pinkawa M., Holy R., Stoffels G., Demirel C., Attieh C., et al. Integrated-boost IMRT or 3-D-CRT using FET-PET based autocontoured target volume delineation for glioblastoma multiforme — a dosimetric comparison. Radiation Oncology. 2019;4(2):57–9. DOI: 10.1186/1748-717X-4-57

5. Zhong L., Chen L., Shengqing L. Efficacy of moderately hypofractionated simultaneous integrated boost intensitymodulated radiotherapy combined with temozolomide for the postoperative treatment of glioblastoma multiforme: a single-institution experience. Radiation Oncology. 2019;14(1):104–8. DOI: 10.1186/s13014-019-1305-1

6. Cao J.Q., Fisher B.J., Bauman G.S., Megyesi J.F., Watling C.J., Macdonald D.R. Hypofractionated radiotherapy with or without concurrent temozolomide in elderly patients with glioblastoma multiforme: a review of ten-year single institutional experience. J Neurooncol. 2012;107(2):395–405. DOI: 10.1007/s11060-011-0766-3

7. Gregucci F., Bonaparte I., Laera L., Ciliberti M.P., Carbonara R., Gentile M.A., et al. Poor-prognosis patients affected by glioblastoma: retrospective study of hypofractionated radiotherapy with simultaneous integrated boost and concurrent/adjuvant temozolomide. J Pers Med. 2021;11(2):1145–52. DOI: 10.3390/jpm11111145

8. El-Ghany Khedr R.A., Sheta M.F., Elmorsy W. The outcomes of concomitant hypofractionated simultaneous integrated boost intensitymodulated radiotherapy with temozolomide for newly diagnosed high-grade gliomas. Oncol Radiother. 2015;12(1):20–9.

9. Shenouda G., Souhami L., Petrecca K., Owen S., Panet-Raymond V., Guiot M.C., et al. A phase 2 trial of neoadjuvant temozolomide followed by hypofractionated accelerated radiation therapy with concurrent and adjuvant temozolomide for patients with glioblastoma. Int J Radiat Oncol Biol Phys. 2017;97(3):487–94. DOI: 10.1016/j.ijrobp.2016.11.006

10. Nie E., Miao F., Jin X., Wu W., Zhou X., Zeng A., et al. Fstl1/DIP2A/ MGMT signaling pathway plays important roles in temozolomide resistance in glioblastoma. Oncogene. 2019;38(15):2706–21. DOI: 10.1038/s41388-018-0596-2

11. Dobelbower M.C., Burnet Iii O.L., Nordal R.A., Nabors L.B., Markert J.M., Hyatt M.D., et al. Patterns of failure for glioblastoma multiforme following concurrent radiation and temozolomide. J Med Imaging Radiat Oncol. 2011;55(1):77–81. DOI: 10.1111/j.1754-9485.2010.02232.x

12. Minniti G., Amelio D., Amichetti M., Salvati M., Muni R., Bozzao A., et al. Patterns of failure and comparison of different target volume delineations in patients with glioblastoma treated with conformal radiotherapy plus concomitant and adjuvant temozolomide. Radiother Oncol. 2010;97(3): 377–81. DOI: 10.1016/j.radonc.2010.08.020

13. Mallick S., Kunhiparambath H., Gupta S., Benson R., Sharma S., Laviraj M.A., et al. Hypofractionated accelerated radiotherapy (HART) with concurrent and adjuvant temozolomide in newly diagnosed glioblastoma: a phase II randomized trial (HART-GBM trial). J Neuro-Oncol. 2018;140(1):75–82. DOI: 10.1007/s11060-018-2932-3

14. Scoccianti S., Krengli M., Marrazzo L., Magrini S.M., Detti B., Fusco V., et al. Hypofractionated radiotherapy with simultaneous integrated boost (SIB) plus temozolomide in good prognosis patients with glioblastoma: a multicenter phase II study by the brain study Group of the Italian Association of radiation oncology (AIRO). Radiol Med. 2018;123(1):48–62. DOI: 10.1007/s11547-017-0806-y