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Hypofractionated Stereotactic Reirradiation of Recurrent Glioblastomas

A Beneficial Treatment Option after High-Dose Radiotherapy?

Ist die hypofraktionierte stereotaktische Reradiatio eine sinnvolle Behandlungsoption rezidivierter Glioblastome nach vorheriger hochdosierter Bestrahlung?

Strahlentherapie und Onkologie volume 185, pages 235–240 (2009)Cite this article

Background and Purpose:

Recurrent malignant gliomas have a very poor prognosis. This trial aimed to evaluate the benefits of reirradiation in case of recurrent glioblastoma multiforme (GBM) using hypofractionated stereotactic radiotherapy (hFSRT) after primary high-dose percutaneous irradiation.

Patients and Methods:

Between 1998 and 2008, 53 patients with recurrent GBM were treated by hFSRT based on CT and MR imaging. At the time of recurrence, a median total dose of 30 Gy (20–60 Gy) was delivered in median fractions of 3 Gy/day (2–5Gy).

Results:

The reirradiation was well tolerated (no acute or late toxicity > grade 2), despite the relatively large median tumor volume (35.01 ml). Karnofsky Performance Score was the strongest predictor for survival after reirradiation (p = 0.0159). Tumor volume (p = 0.4690), patient age (p = 0.4301), second operation (p = 0.6930), and chemotherapy (p = 0.1466) at the time of reirradiation did not affect survival. After hFSRT, the median survival was 9 months, and the 1-year progression-free survival (PFS) amounted to 22%.The median overall survival from initial diagnosis was 27 months. 1-year survival from first diagnosis was 83%, 2-year survival 45%. The median time to progression from the end of initial irradiation to recurrence was 12 months. 1-year PFS before reirradiation was 40%.

Conclusion:

hFSRT as a secondary treatment of recurrent GBM is a feasible and effective treatment option. Only minor side effects were observed with prolonged life expectancy of 9 months.

Hintergrund und Ziel:

Die Prognose im Rezidivfall eines malignen Glioms ist schlecht. Diese Studie hatte zum Ziel, den Stellenwert einer hypofraktionierten stereotaktischen Rebestrahlung (hFSRT) bei rezidiviertem Glioblastom (GBM) nach perkutaner hochkonformaler Radiotherapie zu evaluieren.

Patienten und Methodik:

Zwischen 1998 und 2008 wurden 53 Patienten mit einem rezidivierten GBM stereotaktisch rebestrahlt. Die mediane Gesamtherddosis betrug 30 Gy (20–60 Gy), die mediane Einzelherddosis 3 Gy/Tag (2–5 Gy).

Ergebnisse:

Trotz großer Tumorvolumen von median 35,01 ml wurde nach hFSRT keine Akut- oder Spättoxizität > Grad 2 beobachtet. Der Karnofsky-Perfomance-Score war der einzige determinante Faktor hinsichtlich des Gesamtüberlebens nach hFSRT (p = 0,0159). Hingegen beeinflussten Tumorvolumen (p = 0,4690), Patientenalter (p = 0,4301), Zweitoperationen (p = 0,6930) oder Chemotherapie (p = 0,1466) das Gesamtüberleben nach hFSRT nicht. Das mediane Gesamtüberleben nach hFSRT betrug 9 Monate, das progressionsfreie 1-Jahres-Überleben (PFS) 22%. Das mediane Gesamtüberleben nach initialer Diagnosestellung eines GBM lag bei 27 Monaten, das 1- bzw. 2-Jahres-Gesamtüberleben bei 83% bzw. 45%. Der mediane Zeitpunkt bis zum ersten Rezidiv nach initialer Bestrahlung betrug 12 Monate, das 1-Jahres-PFS nach initialer Bestrahlung bis zum ersten Rezidiv 40%.

Schlussfolgerung:

Die hFSRT ist eine geeignete und effektive Behandlungsoption für rezidivierte GBM. Das mediane Gesamtüberleben nach hFSRT konnte bei geringer Nebenwirkungsrate um 9 Monate verlängert werden.

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References

  1. Alexiou GA, Tsiouris S, Voulgaris S, et al. 99mTc-tetrofosmin brain SPECT for target volume delineation in radiotherapy of high-grade gliomas. Letter on Krengli M, Loi G, Sacchetti G, et al. Delineation of target volume for radiotherapy of high-grade gliomas by 99mTc-MIBI SPECT and MRI fusion, in Strahlenther Onkol 2007;183:689-94 (No. 12) (DOI 10.1007/s00066-0071750-x). Strahlenther Onkol 2008;184:332–33.

    PubMed  Article  CAS  Google Scholar 

  2. Chan TA, Weingart JD, Parisi M, et al. Treatment of recurrent glioblastoma multiforme with GliaSite brachytherapy. Int J Radiat Oncol Biol Phys 2005;62:1133–9.

    PubMed  Google Scholar 

  3. Chavaudra J. [Last ICRU recommendations for the prescription, recording and reporting of external bean therapy.] Cancer Radiother 1998;2:607–14.

    PubMed  CAS  Google Scholar 

  4. Cho KH, Hall WA, Gerbi BJ, et al. Single dose versus fractionated stereotactic radiotherapy for recurrent high-grade gliomas. Int J Radiat Oncol Biol Phys 1999;45:1133–41.

    PubMed  Article  CAS  Google Scholar 

  5. Combs SE, Gutwein S, Schulz-Ertner D, et al. Temozolomide combined with irradiation as postoperative treatment of primary glioblastoma multiforme. Phase I/II study. Strahlenther Onkol 2005;181:372–7.

    PubMed  Article  Google Scholar 

  6. Combs SE, Thilmann C, Edler L, et al. Efficacy of fractionated stereotactic reirradiation in recurrent gliomas: long-term results in 172 patients treated in a single institution. J Clin Oncol 2005;23:8863–9.

    PubMed  Article  Google Scholar 

  7. Combs SE, Widmer V, Thilmann C, et al. Stereotactic radiosurgery (SRS): treatment option for recurrent glioblastoma multiforme (GBM). Cancer 2005;104:2168–73.

    PubMed  Article  Google Scholar 

  8. Duchstein S, Gademann G, Peters B. Early and late effects of local high dose radiotherapy of the brain on memory and attention. Strahlenther Onkol 2003;179:441–51.

    PubMed  Google Scholar 

  9. Ernst-Stecken A, Ganslandt O, Lambrecht U, et al. Survival and quality of life after hypofractionated stereotactic radiotherapy for recurrent malignant glioma. J Neurooncol 2007;81:287–94.

    PubMed  Article  Google Scholar 

  10. Geyer P, Blank H, Evers C, et al. Filmless evaluation of the mechanical accuracy of the isocenter in stereotactic radiotherapy. Strahlenther Onkol 2007;183:76–80.

    PubMed  Article  Google Scholar 

  11. Gross MW, Spahn U, Engenhart-Cabillic R. Assessment of the accuracy of a conventional simulation for radiotherapy of head and skull base tumors. Technol Cancer Res Treat 2003;2:345–51.

    PubMed  Google Scholar 

  12. Grosu AL, Weber WA, Franz M, et al. Reirradiation of recurrent high-grade gliomas using amino acid PET (SPECT)/CT/MRI image fusion to determine gross tumor volume for stereotactic fractionated radiotherapy. Int J Radiat Oncol Biol Phys 2005;63:511–9.

    PubMed  CAS  Google Scholar 

  13. Henzel M, Hamm K, Gross MW, et al. Fractionated stereotactic radiotherapy of glomus jugulare tumors. Local control, toxicity, symptomatology, and quality of life. Strahlenther Onkol 2007;183:557–62.

    PubMed  Article  Google Scholar 

  14. Hudes RS, Corn BW, Werner-Wasik M, et al. A phase I dose escalation study of hypofractionated stereotactic radiotherapy as salvage therapy for persistent or recurrent malignant glioma. Int J Radiat Oncol Biol Phys 1999;43:293–8.

    PubMed  CAS  Google Scholar 

  15. Kocher M, Frommolt P, Borberg SK, et al. Randomized study of postoperative radiotherapy and simultaneous temozolomide without adjuvant chemotherapy for glioblastoma. Strahlenther Onkol 2008;184:572–9.

    PubMed  Article  Google Scholar 

  16. Kohshi K, Yamamoto H, Nakahara A, et al. Fractionated stereotactic radiotherapy using gamma unit after hyperbaric oxygenation on recurrent high-grade gliomas. J Neurooncol 2007;82:297–303.

    PubMed  Article  Google Scholar 

  17. Kortmann RD, Jeremic B, Weller M, et al. Radiochemotherapy of malignant glioma in adults. Clinical experiences. Strahlenther Onkol 2003;179:219–32.

    PubMed  Article  Google Scholar 

  18. Larson DA, Prados M, Lamborn KR, et al. Phase II study of high central dose gamma knife radiosurgery and marimastat in patients with recurrent malignant glioma. Int J Radiat Oncol Biol Phys 2002;54:1397–404.

    PubMed  Google Scholar 

  19. Lederman G, Wronski M, Arbit E, et al. Treatment of recurrent glioblastoma multiforme using fractionated stereotactic radiosurgery and concurrent paclitaxel. Am J Clin Oncol 2000;23:155–9.

    PubMed  Article  CAS  Google Scholar 

  20. Lopatta E, Liesenfeld SM, Bank P, et al. Improved patient repositioning accuracy by integrating an additional jaw fixation into a high precision face mask system in stereotactic radiotherapy of the head. Strahlenther Onkol 2003;179:571–5.

    PubMed  Article  Google Scholar 

  21. Nieder C, Adam M, Molls M, et al. Therapeutic options for recurrent high-grade glioma in adult patients: recent advances. Crit Rev Oncol Hematol 2006;60:81–193.

    Article  Google Scholar 

  22. Nieder C, Astner ST, Mehta MP, et al. Improvement, clinical course, and quality of life after palliative radiotherapy for recurrent glioblastoma. Am J Clin Oncol 2008;31:300–5.

    PubMed  Article  Google Scholar 

  23. Shepherd SF, Laing RW, Cosgrove VP, et al. Hypofractionated stereotactic radiotherapy in the management of recurrent glioma. Int J Radiat Oncol Biol Phys 1997;37:393–8.

    PubMed  CAS  Google Scholar 

  24. Shrieve DC, Alexander E 3rd, Wen PY, et al. Comparison of stereotactic radiosurgery and brachytherapy in the treatment of recurrent glioblastoma multiforme. Neurosurgery 1995;36:275–82, discussion 282-4.

    PubMed  Article  CAS  Google Scholar 

  25. Simon JM, Cornu P, Boisserie G, et al. Brachytherapy of glioblastoma recurring in previously irradiated territory: predictive value of tumor volume. Int J Radiat Oncol Biol Phys 2002;53:67–74.

    PubMed  Google Scholar 

  26. Stupp R. Malignant glioma: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 2008;18:Suppl 2:ii69–70.

    Google Scholar 

  27. Stupp R, Hegi ME, Gilbert MR, et al. Chemoradiotherapy in malignant glioma: standard of care and future directions. J Clin Oncol 2007;25:4127–36.

    PubMed  Article  CAS  Google Scholar 

  28. Stupp R, Hottinger AF. Management of malignant glioma - quo vadis? Onkologie 2008;31:300–2.

    PubMed  Article  Google Scholar 

  29. Stupp R, Pica A, Mirimanoff RO, et al. [A practical guide for the management of gliomas.] Bull Cancer 2007;94:817–22.

    PubMed  Google Scholar 

  30. Stupp R, Roila F. Malignant glioma: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 2008;19:Suppl 2:ii83–5.

    PubMed  Article  Google Scholar 

  31. Van Kampen M, Engenhart-Cabillic R, Debus J, et al. The radiosurgery of glioblastoma multiforme in cases of recurrence. The Heidelberg experiences compared to the literature. Strahlenther Onkol 1998;174:19–24.

    PubMed  Article  Google Scholar 

  32. Vordermark D, Kolbl O, Ruprecht K, et al. Hypofractionated stereotactic re-irradiation: treatment option in recurrent malignant glioma. BMC Cancer 2005;5:55.

    PubMed  Article  Google Scholar 

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Affiliations

  1. Department of Radiation Oncology, University Hospital Gießen and Marburg, Marburg, Germany

    Emmanouil Fokas MD, Ulrich Wacker, Markus W. Gross, Martin Henzel, Elitsa Encheva & Rita Engenhart-Cabillic

  2. Department of Radiation Oncology, Medical University of Sofia, Sofia, Bulgaria

    Elitsa Encheva

  3. Department of Radiotherapy and Radiation Oncology, University Hospital Gießen and Marburg, Baldingerstraße, 35043, Marburg, Germany

    Emmanouil Fokas MD

Authors
  1. Emmanouil Fokas MD
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  2. Ulrich Wacker
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  3. Markus W. Gross
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  4. Martin Henzel
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  5. Elitsa Encheva
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  6. Rita Engenhart-Cabillic
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Correspondence to Emmanouil Fokas MD.

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Both authors contributed equally to the study.

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Fokas, E., Wacker, U., Gross, M.W. et al. Hypofractionated Stereotactic Reirradiation of Recurrent Glioblastomas. Strahlenther Onkol 185, 235–240 (2009). https://doi.org/10.1007/s00066-009-1753-x

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  • DOI: https://doi.org/10.1007/s00066-009-1753-x

Key Words:

  • Recurrent glioblastoma
  • Stereotactic radiotherapy
  • Reirradiation
  • Survival

Schlüsselwörter:

  • Rezidiviertes Glioblastom
  • Stereotaktische Bestrahlung
  • Reradiatio
  • Überleben