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Proton beam therapy with concurrent chemotherapy for glioblastoma multiforme: comparison of nimustine hydrochloride and temozolomide

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Abstract

To evaluate the safety and efficacy of postoperative proton beam therapy (PBT) combined with nimustine hydrochloride (ACNU) or temozolomide (TMZ) for glioblastoma multiforme (GBM). The subjects were 46 patients with GBM who were treated with high dose (96.6 GyE) PBT. There were 24 males and 22 females, and the median age was 58 years old (range 24–76). The Karnofsky performance status was 60, 70, 80, 90 and 100 in 5, 10, 12, 11 and 8 patients, respectively. Total resection, partial resection, and biopsy were performed for 31, 14 and 1 patients, respectively. Photon beams were delivered to high intensity areas on T2-weighted magnetic resonance imaging (MRI) in the morning (50.4 Gy in 28 fractions). More than 6 h later, PBT was delivered to the enhanced area plus a 10 mm margin in the first half of the protocol (23.1 GyE in 14 fractions) and to the enhanced volume in the second half (23.1 GyE in 14 fraction). Concurrent chemotherapy with ACNU during weeks 1 and 4 or daily TMZ was administered in 23 and 23 patients, respectively. The overall 1 and 2 year survival rates were 82.6 and 47.6 %, respectively. Median survival was 21.1 months (95 % CI 13.1–29.2), with no significant difference in survival between the ACNU and TMZ groups. The patient characteristics were similar in the two groups. Late radiation necrosis occurred in 11 patients (six ACNU, five TMZ), but was controlled by necrotomy and therapy including bevacizumab. PBT concurrent with ACNU or TMZ was tolerable and beneficial for carefully selected patients with GBM.

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References

  1. Walker MD, Strike TA, Sheline GE (1979) An analysis of dose–effect relationship in the radiotherapy of malignant gliomas. Int J Radiat Oncol Biol Phys 5:1725–1731

    Article  CAS  PubMed  Google Scholar 

  2. Walker MD, Green SB, Byar DP et al (1980) Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med 303:1323–1329

    Article  CAS  PubMed  Google Scholar 

  3. Keime-Guibert F, Chinot O, Taillandier L et al (2007) Radiotherapy for glioblastoma in the elderly. N Engl J Med 356:1527–1535

    Article  CAS  PubMed  Google Scholar 

  4. Fine HA, Dear KB, Loeffler JS et al (1993) Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults. Cancer 71:2585–2597

    Article  CAS  PubMed  Google Scholar 

  5. Stewart LA (2002) Chemotherapy in adult high-grade glioma: a systematic review and meta-analysis of individual patient data from 12 randomised trials. Lancet 359:1011–1018

    Article  CAS  PubMed  Google Scholar 

  6. Athanassiou H, Synodinou M, Maragoudakis E et al (2005) Randomized phase II study of temozolomide and radiotherapy compared with radiotherapy alone in newly diagnosed glioblastoma multiforme. J Clin Oncol 23:2372–2377

    Article  CAS  PubMed  Google Scholar 

  7. Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996

    Article  CAS  PubMed  Google Scholar 

  8. Stupp R, Dietrich PY, Ostermann Kraljevic S et al (2002) Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol 20:1375–1382

    Article  CAS  PubMed  Google Scholar 

  9. Gilbert MR, Dignam JJ, Armstrong TS et al (2014) A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl Med 370:699–708

    Article  CAS  Google Scholar 

  10. Chinot OL, Wick W, Mason W et al (2014) Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl Med 370:709–722

    Article  CAS  Google Scholar 

  11. Tanaka M, Ino Y, Nakagawa K et al (2005) High-dose conformal radiotherapy for supratentorial malignant glioma: a historical comparison. Lancet 6:953–960

    Article  PubMed  Google Scholar 

  12. Fitzek MM, Thornton AF, Rabinov JD et al (1999) Accelerated fractionated proton/photon irradiation to 90 cobalt gray equivalent for glioblastoma multiforme: results of a phase II prospective trial. J Neurosurg 91:251–260

    Article  CAS  PubMed  Google Scholar 

  13. Iuchi T, Hatano K, Kodama T et al (2014) Phase 2 trial of hypofractionated high-dose intensity modulated radiation therapy with concurrent and adjuvant temozolomide for newly diagnosed glioblastoma. Int J Radiat Oncol Biol Phys 88:793–800

    Article  CAS  PubMed  Google Scholar 

  14. Mizumoto M, Tsuboi K, Igaki H et al (2010) Phase I/II trial of hyperfractionated concomitant boost proton radiotherapy for supratentorial glioblastoma multiforme. Int J Radiat Oncol Biol Phys 77:98–105

    Article  PubMed  Google Scholar 

  15. Mizumoto M, Yamamoto T, Takano S et al (2015) Long-term survival after treatment of glioblastoma multiforme with hyperfractionated concomitant boost proton beam therapy. Pract Radiat Oncol 5:e9–e16

    Article  PubMed  Google Scholar 

  16. Cancer Therapy Evaluation Program (2006) Common terminology criteria for adverse events v3.0 (CTCAE). Cancer Therapy Evaluation Program, Bethesda, MD. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm

  17. Sultanem K, Patrocinio H, Lambert C et al (2004) The use of hypofractionated intensity-modulated irradiation in the treatment of glioblastoma multiforme: preliminary results of a prospective trial. Int J Radiat Oncol Biol Phys 58:247–252

    Article  PubMed  Google Scholar 

  18. Mirimanoff RO, Gorlia T, Mason W et al (2006) Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial. J Clin Oncol 24:2563–2569

    Article  CAS  PubMed  Google Scholar 

  19. Matsuo M, Miwa K, Tanaka O et al (2012) Impact of [11C]methionine positron emission tomograpy for target definition of glioblastoma multiforme in radiation therapy planning. Int J Radiat Oncol Biol Phys 82:83–89

    Article  PubMed  Google Scholar 

  20. Iuchi T, Hatano K, Uchino Y et al (2015) Methionine uptake and required dose to control glioblastoma. Int J Radiat Oncol Biol Phys 93:133–140

    Article  CAS  PubMed  Google Scholar 

  21. Bui QC, Lieber M, Withers HR et al (2004) The efficacy of hyperbaric oxygen therapy in the treatment of radiation-induced late side effects. Int J Radiat Oncol Biol Phys 60:871–878

    Article  CAS  PubMed  Google Scholar 

  22. Yonezawa S, Miwa K, Shinoda J et al (2014) Bevacizumab treatment leads to observable morphological and metabolic changes in brain radiation necrosis. J Neurooncol 119:101–109

    Article  CAS  PubMed  Google Scholar 

  23. Lubelski D, Abdullah KG, Weil RJ et al (2013) Bevacizumab for radiation necrosis following treatment of high grade glioma: a systematic review of the literature. J Neurooncol 115:317–322

    Article  CAS  PubMed  Google Scholar 

  24. Furuse M, Nonoguchi N, Kawabata S et al (2013) Bevacizumab treatment for symptomatic radiation necrosis diagnosed by amino acid PET. Jpn J Clin Oncol 43:337–341

    Article  PubMed  Google Scholar 

  25. Matsuda M, Yamamoto T, Ishikawa E et al (2011) Prognostic factors in glioblastoma multiforme patients receiving high-dose particle radiotherapy or conventional radiotherapy. Br J Radiol 84:S54–S60

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was partially supported by grants-in-aid for Scientific Research (B) (15H04901) and Young Scientists (B) (25861064) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Correspondence to Koji Tsuboi.

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Mizumoto, M., Yamamoto, T., Ishikawa, E. et al. Proton beam therapy with concurrent chemotherapy for glioblastoma multiforme: comparison of nimustine hydrochloride and temozolomide. J Neurooncol 130, 165–170 (2016). https://doi.org/10.1007/s11060-016-2228-4

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  • DOI: https://doi.org/10.1007/s11060-016-2228-4

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