Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1 (5-Year IF – 2.0)
Journal Citation Indicator (JCI) (2023) – 0.4
Scopus CiteScore – 3.7 (CiteScore Tracker – 4.0)
Index Copernicus  – 171.00; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2015, vol. 24, nr 2, March-April, p. 279–287

doi: 10.17219/acem/40456

Publication type: original article

Language: English

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The Impact of Surgery on the Efficacy of Adjuvant Therapy in Glioblastoma Multiforme

Anna Brzozowska1,2,A,B,C,D, Anna Toruń3,G, Maria Mazurkiewicz1,2,E,F

1 Chair and Department of Oncology, Medical University of Lublin, Poland

2 St. John’s Cancer Center, Lublin, Poland

3 Department of Mathematics and Medical Biostatistics, Medical University of Lublin, Pola

Abstract

Background. Glioblastoma multiforme (GBM) is the most malignant brain tumor. Surgery still remains a fundamental part of treatment in GBM, followed by radiotherapy and chemotherapy.
Objectives. The aim of the study was to assess the impact of surgery on the efficacy of adjuvant therapy in patients with glioblastoma multiforme.
Material and Methods. The study involved 181 patients: 50 treated with adjuvant radiotherapy (RTH) only (60 Gy in daily 2Gy fractions) and 131 treated with postoperative radiochemotherapy (RTH-CHT) (60 Gy, 2Gy/d) + 75 mg/m2 temozolomide for 42 days of radiotherapy, followed by 6 courses every 28 days; the first course was 150 mg/m2 for 1–5 days, and the subsequent courses were 200 mg/m2 for 1–5 days). Overall survival (OS) and disease-free survival (DFS) were assessed. The statistical analysis entailed the log-rank test, Kaplan-Meier curves and Cox proportional hazards regression; the threshold of statistical significance was set at p = 0.05.
Results. Median OS and DFS were significantly increased (p = 0.001) in the RTH-CHT group compared with the RTH group: 9.77 months vs 6.38 months for OS, and 8.4 months vs 4.33 months for DFS. After radical surgery, RTH-CHT extended OS by 5.3 months and DFS by 4.5 months in comparison to RTH. In patients who underwent non-radical surgery, the type of adjuvant therapy made no difference in either OS or DFS. In the RTH-CHT group, OS and DFS depended on the extent of the surgery, and were significantly longer in patients who underwent radical surgery (OS: p = 0.03128; DFS: p = 0.01206). In the RTH group, the type of surgery had no effect on survival.
Conclusion. Radiochemotherapy significantly prolongs OS and DFS compared with radiotherapy alone in GBM patients who have undergone radical removal of the tumor. Among patients who had non-radical surgery, the type of adjuvant treatment has no effect on OS or DFS.

Key words

glioblastoma multiforme, adjuvant treatment, surgery.

References (30)

  1. Stupp R, Gander M, Leyvraz S: Current and future developments in the use of temozolomide for the treatment of brain tumours. Lancet Oncol 2001, 2, 552–560.
  2. Ohgaki H, Kleihues P: Epidemiology and etiology of gliomas. Acta Neuropathol 2005, 109, 93–108.
  3. Laws ER, Parney IF, Huang W: Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the glioma outcomes project. J Neurosurg 2003, 99, 467–473.
  4. Buckner JC: Factors influencing survival in high-grade gliomas. Semin Oncol 2003, 30, Suppl 19, 10–14.
  5. Curran WJ, Scott CB, Horton J: Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. J Natl Cancer Inst 1993, 85, 704–710.
  6. DeAngelis LM: Brain tumors. N Engl J Med 2001, 344, 114–123.
  7. Tolcher AW, Gerson SL, Denis L: Marked inactivation of O6-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules. Br J Cancer 2003, 88, 1004–1011.
  8. Stupp R, Mason WP, Bent MJ: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005, 352, 987–996.
  9. Athanassiou H, Synodinou M, Maragoudakis E: Randomized phase II study of temozolomide and radiotherapy compared with radiotherapy alone in newly diagnosed glioblastoma multiforme. J Clin Oncol 2005, 23, 2372–2377.
  10. Van Genugten J, Leffers P, Baumert B: Effectiveness of temozolomide for primary glioblastoma multiforme in routine clinical practice. J Neurooncol 2010, 96, 249–257.
  11. Helseth R, Helseth E, Johannesen TB: Overall survival, prognostic factors, and repeated surgery in a consecutive series of 516 patients with glioblastoma multiforme. Acta Neurol Scand 2010, 122, 159–167.
  12. Laws ER, Parney IF, Huang W: Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the glioma outcomes project. J Neurosurg 2003, 99, 467–473.
  13. Lacroix M, Abi-Said D, Fourney DR: A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 2001, 95, 190–198.
  14. Stummer W, Reulen HJ, Meinel T: Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias. Neurosurgery 2008, 62, 564–576.
  15. Gorlia T, Bent MJ, Hegi ME: Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981–22981/CE.3. Lancet Oncol 2008, 9, 29–38.
  16. Irwin C, Hunn M, Purdie G: Delay in radiotherapy shortens survival in patients with high grade glioma. J Neurooncol 2007, 5, 339–343.
  17. Do V, Gebski V, Barton MB: The effect of waiting for radiotherapy for grade III/IV gliomas. Radiother Oncol 2000, 57, 131–136.
  18. Burnet NG, Jena R, Jefferies SJ: Mathematical modelling of survival of glioblastoma patients suggests a role for radiotherapy (R Coll Radiol) dose escalation and predicts poorer outcome after delay to start treatment. Clin Oncol 2006, 18, 93–103.
  19. Lutterbach J: Live fast, die early? The deleterious effects of waiting time in patients with glioblastoma. Anticancer Drugs 2003, 14, 447–448.
  20. Rock K, McArdle O, Forde P: A clinical review of treatment outcomes in glioblastoma multiforme – the validation in a non-trial population of the results of a randomised Phase III clinical trial: has a more radical approach improved survival? Br J Radiol 2012, 85, 729–733.
  21. Caloglu M, Yurut-Caloglu V, Karagol Het: Prognostic factors other than the performance status and age for glioblastoma multiforme: a single-institution experience. J BUON 2009, 14, 211–218.
  22. Westphal M, Hilt D.C, Bortey E: A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro Oncol 2003, 5, 79–88.
  23. Steltzer KJ, Sauvé KI, Spence AM: Corpus callosum involvement as a prognostic factor for patients with highgrade astrocytoma. Int J Radiat Oncol Biol Phys 1997, 38, 27–30.
  24. Van den Bent MJ, Stupp R, Mason W: Impact of extent of resection on overall survival in newly-diagnosed glioblastoma after chemo-irradiation with temozolomide: further analysis of EORTC study 26981. Eur J Cancer 2005, Suppl. 2, 134.
  25. Stummer W, Meinel T, Ewelt C: Prospective cohort study of radiotherapy with concomitant and adjuvant temozolomide chemotherapy for glioblastoma patients with no or minimal residual enhancing tumor load after surgery. J Neurooncol 2012, 108, 89–97.
  26. Stummer W, Van den Bent M, Westphal M: Cytoreductive surgery of glioblastoma as the key to successful adjuvant therapies: new arguments in an old discussion. Acta Neurochir 2011, 153, 1211–1218.
  27. Koritzinsky M, Seigneuric R, Magagnin MG: The hypoxic proteome is influenced by gene-specific changes in mRNA translation. Radiother Oncol 2005, 76, 177–186.
  28. Holash J, Maisonpierre PC, Compton D: Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. Science 1999, 284, 1994–1998.
  29. Giese A, Bjerkvig R, Berens ME: Cost of migration: invasion of malignant gliomas and implications for treatment. J Clin Oncol 2003, 21, 1624–1636.
  30. Navalitloha Y, Schwartz ES, Groothuis EN: Therapeutic implications of tumor interstitial fluid pressure in subcutaneous RG-2 tumors. Neuro Oncol 2006, 8, 227–233.
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