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Standard dose and dose-escalated radiation therapy are associated with favorable survival in select elderly patients with newly diagnosed glioblastoma

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Abstract

We hypothesized elderly patients with good Karnofsky Performance Status (KPS) treated with standard dose or dose-escalated radiation therapy (SDRT/DERT) and concurrent temozolomide (TMZ) would have favorable overall survival (OS) compared to historical elderly patients treated with hypofractionated RT (HFRT). From 2004 to 2015, 66 patients age ≥ 60 with newly diagnosed, pathologically proven glioblastoma were treated with SDRT/DERT over 30 fractions with concurrent/adjuvant TMZ at a single institution. Kaplan–Meier methods and the log-rank test were used to assess OS and progression-free survival (PFS). Multivariate analysis (MVA) was performed using Cox Proportional-Hazards. Median follow-up was 12.6 months. Doses ranged from 60 to 81 Gy (median 66). Median KPS was 90 (range 60–100) and median age was 67 years (range 60–81), with 29 patients ≥ 70 years old. 32% underwent gross total resection (GTR). MGMT status was known in 28%, 42% of whom were methylated. Median PFS was 8.3 months (95% CI 6.9–11.0) and OS was 12.7 months (95% CI 9.7–14.1). Patients age ≥ 70 with KPS ≥ 90 had a median OS of 12.4 months. Median OS was 27.1 months for MGMT methylated patients. On MVA controlling for age, dose, KPS, MGMT, GTR, and adjuvant TMZ, younger age (HR 0.9, 95% CI 0.8–0.9, p < 0.01), MGMT methylation (HR:0.2, 95% CI 0.1–0.7, p = 0.01), and GTR (HR:0.5, 95% CI 0.3–0.9, p = 0.01) were associated with improved OS. Our findings do not support routine use of a standard 6-week course of radiation therapy in elderly patients with glioblastoma. However, a select group of elderly patients with excellent performance status and MGMT methylation or GTR may experience favorable survival with a standard 6-week course of treatment.

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References

  1. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups, National Cancer Institute of Canada Clinical Trials Group (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10(5):459–466. https://doi.org/10.1016/S1470-2045(09)70025-7

    Article  CAS  PubMed  Google Scholar 

  2. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, National Cancer Institute of Canada Clinical Trials Group (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996. https://doi.org/10.1056/NEJMoa043330

    Article  CAS  PubMed  Google Scholar 

  3. Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS (2015) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro-oncology 17(Suppl 4):iv1–iv62. https://doi.org/10.1093/neuonc/nov189

    Article  Google Scholar 

  4. Curran WJ Jr, Scott CB, Horton J, Nelson JS, Weinstein AS, Fischbach AJ, Chang CH, Rotman M, Asbell SO, Krisch RE et al (1993) Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials. J Natl Cancer Inst 85(9):704–710

    Article  PubMed  Google Scholar 

  5. Bell EH, Pugh SL, McElroy JP, Gilbert MR, Mehta M, Klimowicz AC, Magliocco A, Bredel M, Robe P, Grosu AL, Stupp R, Curran W Jr, Becker AP, Salavaggione AL, Barnholtz-Sloan JS, Aldape K, Blumenthal DT, Brown PD, Glass J, Souhami L, Lee RJ, Brachman D, Flickinger J, Won M, Chakravarti A (2017) Molecular-based recursive partitioning analysis model for glioblastoma in the temozolomide era: a correlative analysis based on NRG oncology RTOG 0525. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2016.6020

    PubMed  Google Scholar 

  6. Gaspar LE, Scott C, Murray K, Curran W (2000) Validation of the RTOG recursive partitioning analysis (RPA) classification for brain metastases. Int J Radiat Oncol Biol Phys 47(4):1001–1006

    Article  CAS  PubMed  Google Scholar 

  7. Scott CB, Scarantino C, Urtasun R, Movsas B, Jones CU, Simpson JR, Fischbach AJ, Curran WJ Jr (1998) Validation and predictive power of Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis classes for malignant glioma patients: a report using RTOG 90-06. Int J Radiat Oncol Biol Phys 40(1):51–55

    Article  CAS  PubMed  Google Scholar 

  8. Mirimanoff RO, Gorlia T, Mason W, Van den Bent MJ, Kortmann RD, Fisher B, Reni M, Brandes AA, Curschmann J, Villa S, Cairncross G, Allgeier A, Lacombe D, Stupp R (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(16):2563–2569. https://doi.org/10.1200/JCO.2005.04.5963

    Article  CAS  PubMed  Google Scholar 

  9. Li J, Wang M, Won M, Shaw EG, Coughlin C, Curran WJ Jr, Mehta MP (2011) Validation and simplification of the Radiation Therapy Oncology Group recursive partitioning analysis classification for glioblastoma. Int J Radiat Oncol Biol Phys 81(3):623–630. https://doi.org/10.1016/j.ijrobp.2010.06.012

    Article  PubMed  Google Scholar 

  10. Keime-Guibert F, Chinot O, Taillandier L, Cartalat-Carel S, Frenay M, Kantor G, Guillamo JS, Jadaud E, Colin P, Bondiau PY, Menei P, Loiseau H, Bernier V, Honnorat J, Barrie M, Mokhtari K, Mazeron JJ, Bissery A, Delattre JY, Association of French-Speaking N-O (2007) Radiotherapy for glioblastoma in the elderly. New Engl J Med 356 (15):1527–1535. https://doi.org/10.1056/NEJMoa065901

  11. Perry JR, Laperriere N, O’Callaghan CJ, Brandes AA, Menten J, Phillips C, Fay M, Nishikawa R, Cairncross JG, Roa W, Osoba D, Rossiter JP, Sahgal A, Hirte H, Laigle-Donadey F, Franceschi E, Chinot O, Golfinopoulos V, Fariselli L, Wick A, Feuvret L, Back M, Tills M, Winch C, Baumert BG, Wick W, Ding K, Mason WP, Trial I (2017) Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med 376(11):1027–1037. https://doi.org/10.1056/NEJMoa1611977

    Article  CAS  PubMed  Google Scholar 

  12. Roa W, Brasher PM, Bauman G, Anthes M, Bruera E, Chan A, Fisher B, Fulton D, Gulavita S, Hao C, Husain S, Murtha A, Petruk K, Stewart D, Tai P, Urtasun R, Cairncross JG, Forsyth P (2004) Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial. J Clin Oncol 22(9):1583–1588. https://doi.org/10.1200/JCO.2004.06.082

    Article  CAS  PubMed  Google Scholar 

  13. Roa W, Kepka L, Kumar N, Sinaika V, Matiello J, Lomidze D, Hentati D, Guedes de Castro D, Dyttus-Cebulok K, Drodge S, Ghosh S, Jeremic B, Rosenblatt E, Fidarova E (2015) International Atomic Energy Agency Randomized Phase III Study of radiation therapy in elderly and/or frail patients with newly diagnosed glioblastoma multiforme. J Clin Oncol 33(35):4145–4150. https://doi.org/10.1200/JCO.2015.62.6606

    Article  PubMed  Google Scholar 

  14. Malmstrom A, Gronberg BH, Marosi C, Stupp R, Frappaz D, Schultz H, Abacioglu U, Tavelin B, Lhermitte B, Hegi ME, Rosell J, Henriksson R, Nordic Clinical Brain Tumour Study Group (NCBTSG) (2012) Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial. Lancet Oncol 13(9):916–926. https://doi.org/10.1016/S1470-2045(12)70265-6

    Article  PubMed  Google Scholar 

  15. Tsien CI, Brown D, Normolle D, Schipper M, Piert M, Junck L, Heth J, Gomez-Hassan D, Ten Haken RK, Chenevert T, Cao Y, Lawrence T (2012) Concurrent temozolomide and dose-escalated intensity-modulated radiation therapy in newly diagnosed glioblastoma. Clin Cancer Res 18(1):273–279. https://doi.org/10.1158/1078-0432.CCR-11-2073

    Article  CAS  PubMed  Google Scholar 

  16. Burton E, Ugiliweneza B, Woo S, Skirboll S, Boakye M (2014) A seer-medicare data analysis of elderly glioblastoma patients: treatment patterns, outcomes and cost. Neuro-oncology. https://doi.org/10.1093/neuonc/nou253.2

    PubMed Central  Google Scholar 

  17. Darefsky AS, King JT, Dubrow R (2012) Adult glioblastoma multiforme survival in the temozolomide era: a population-based analysis of surveillance, epidemiology, and end results registries. Cancer 118(8):2163–2172. https://doi.org/10.1002/cncr.26494

    Article  PubMed  Google Scholar 

  18. Batchelor TT, Betensky RA, Esposito JM, Pham LDD, Dorfman MV, Piscatelli N, Jhung S, Rhee D, Louis DN (2004) Age-dependent prognostic effects of genetic alterations in glioblastoma. Clin Cancer Res 10(1):228–233. doi:https://doi.org/10.1158/1078-0432.Ccr-0841-3

    Article  CAS  PubMed  Google Scholar 

  19. Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M, Nikkhah G, Papsdorf K, Steinbach JP, Sabel M, Combs SE, Vesper J, Braun C, Meixensberger J, Ketter R, Mayer-Steinacker R, Reifenberger G, Weller M, NOA-08 Study Group of Neuro-oncology Working Group (NOA) of German Cancer Society (2012) Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol 13(7):707–715. https://doi.org/10.1016/S1470-2045(12)70164-X

    Article  CAS  PubMed  Google Scholar 

  20. Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, Taylor LP, Lieberman F, Silvani A, Fink KL, Barnett GH, Zhu JJ, Henson JW, Engelhard HH, Chen TC, Tran DD, Sroubek J, Tran ND, Hottinger AF, Landolfi J, Desai R, Caroli M, Kew Y, Honnorat J, Idbaih A, Kirson ED, Weinberg U, Palti Y, Hegi ME, Ram Z (2015) Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial. JAMA 314(23):2535–2543. https://doi.org/10.1001/jama.2015.16669

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Michelle M. Kim.

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This article does not contain any studies with human participants or animals performed by any of the authors. This retrospective analysis was approved through the local institutional review board.

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Jackson, W.C., Tsien, C.I., Junck, L. et al. Standard dose and dose-escalated radiation therapy are associated with favorable survival in select elderly patients with newly diagnosed glioblastoma. J Neurooncol 138, 155–162 (2018). https://doi.org/10.1007/s11060-018-2782-z

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