Glioblastoma management in the temozolomide era: have we improved outcome?
Tóm tắt
Temozolomide (TMZ) during and after radiotherapy (RT) is recommended for patients with newly diagnosed glioblastoma (GBM). We analyzed the adoption of this new standard of care for GBM in an academic cancer centre in Canada and assessed its impact on survival. GBM patients registered with Cancer Care Ontario between 2004 and 2008 were identified. Those ≥16 years age, newly diagnosed, treated at our institution, had confirmed pathology and complete records were included. Demographics, treatments, toxicity and outcome were captured. For survival analysis patients were stratified by age, ECOG, and treatment modalities including total cycles of TMZ. Descriptive statistics were used for early progressors and long term survivors. Kaplan–Meier curves, log-rank test and Cox proportional hazards model were used for survival analyses. At a median follow-up of 28 months, we compared our outcome to updated EORTC-NCIC CE 3 results. Of 517 patients 433 were included for analysis. Majority were male (63 %), ECOG 0–1 (66 %), and ≤65 years (55 %). 44 % received CRT followed by TMZ, 13 % had CRT only, 30 % had RT only and 13 % had best supportive care. 10 % were early progressors and 9 % survived beyond 2 years. Comparison of our results to NCIC CTG CE.3 study data showed median survival was 15.8 versus 14.6 months, 2 year survival rate for CRT plus TMZ was 35 versus 26 %, and for RT alone 0 versus 10 %, respectively. <50 % of GBM patients complete CRT with TMZ in the real-world setting. Prognosis for most patients with GBM remains dismal particularly if they are not suitable for RT and CRT.
Tài liệu tham khảo
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 (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996
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 (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 10:459–466
Shahar T, Nossek E, Steinberg DM, Rozovski U, Blumenthal DT, Bokstein F, Sitt R, Freedman S, Corn BW, Kanner AA, Ram Z (2012) Trial to survive: the impact of enrollment in clinical trials on survival of patients with glioblastoma. J Clin Neurosci 19:1530–1534
Paszat L, Laperriere N, Groome P, Schulze K, Mackillop W, Holowaty E (2001) A population-based study of glioblastoma multiforme. Int J Radiat Oncol Biol Phys 51:100–107
Booth CM, Mackillop WJ (2008) Translating new medical therapies into societal benefit. JAMA 300:2177–2179
Ronning PA, Helseth E, Meling TR, Johannesen TB (2012) A population-based study on the effect of temozolomide in the treatment of glioblastoma multiforme. Neuro Oncol 14:1178–1184
Scoccianti S, Magrini SM, Ricardi U, Detti B, Buglione M, Sotti G, Krengli M, Maluta S, Parisi S, Bertoni F, Mantovani C, Tombolini V, De Renzis C, Lioce M, Fatigante L, Fusco V, Muto P, Berti F, Rubino G, Cipressi S, Fariselli L, Lupattelli M, Santoni R, Pirtoli L, Biti G (2010) Patterns of care and survival in a retrospective analysis of 1059 patients with glioblastoma multiforme treated between 2002 and 2007: a multicenter study by the central nervous system study group of Airo (Italian Association of Radiation Oncology). Neurosurgery 67:446–458
Conway PH, Clancy C (2009) Comparative-effectiveness research—implications of the federal coordinating council’s report. N Engl J Med 361:328–330
Robles SC, Marrett LD, Clarke EA, Risch HA (1988) An application of capture-recapture methods to the estimation of completeness of cancer registration. J Clin Epidemiol 41:495–501
Booth CM, Shepherd FA, Peng Y, Darling GE, Li G, Kong W, Mackillop WJ (2010) Adoption of adjuvant chemotherapy for non-small-cell lung cancer: a population-based outcomes study. J Clin Oncol 28:3472–3478
Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280
Malmstrom A, Gronberg BH, Marosi C, Stupp R, Frappaz D, Schultz H, Abacioglu U, Tavelin B, Lhermitte B, Hegi ME, Rosell J, Henriksson R (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 13:916–926
Wick W, Platten M, Meisner C, Felsberg Jr, Tabatabai G, Simon M, Nikkhah G, Papsdorf K, Steinbach JP, Sabel M, Combs SE, Vesper J, Braun C, Meixensberger Jr, Ketter R, Mayer-Steinacker R, Reifenberger G, Weller M (2012) Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial. Lancet Oncol 13:707–715
Laperriere N, Weller M, Stupp R, Perry JR, Brandes AA, Wick W, van den Bent MJ (2013) Optimal management of elderly patients with glioblastoma. Cancer Treat Rev 39:350–357
Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones Sn, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD (2009) IDH1 and IDH2 mutations in gliomas. Engl J Med 360:765–773
Turcan S, Rohle D, Goenka A, Walsh LA, Fang F, Yilmaz E, Campos C, Fabius AWM, Lu C, Ward PS, Thompson CB, Kaufman A, Guryanova O, Levine R, Heguy A, Viale A, Morris LGT, Huse JT, Mellinghoff IK, Chan TA (2012) IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 483:479–483
Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ (2006) ALA-Glioma Study Group: fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7:392–401
Sanai N, Berger MS (2008) Glioma extent of resection and its impact on patient outcome. Neurosurgery 62:753–764 (discussion 264–756)
Pichlmeier U, Bink A, Schackert G, Stummer W (2008) Resection and survival in glioblastoma multiforme: an RTOG recursive partitioning analysis of ALA study patients. Neuro Oncol 10:1025–1034
Hentschel SJ, Sawaya R (2003) Optimizing outcomes with maximal surgical resection of malignant gliomas. Cancer Control 10:109–114
Figueroa ME, Abdel-Wahab O, Lu C, Ward PS, Patel J, Shih A, Li Y, Bhagwat N, Vasanthakumar A, Fernandez HF, Tallman MS, Sun Z, Wolniak K, Peeters JK, Liu W, Choe SE, Fantin VR, Paietta E, Löwenberg B, Licht JD, Godley LA, Delwel R, Valk PJM, Thompson CB, Levine RL, Melnick A (2010) Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 18:553–567
Lu C, Ward PS, Kapoor GS, Rohle D, Turcan S, Abdel-Wahab O, Edwards CR, Khanin R, Figueroa ME, Melnick A, Wellen KE, O’Rourke DM, Berger SL, Chan TA, Levine RL, Mellinghoff IK, Thompson CB (2012) IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature 483:474–478
Laffaire J, Everhard S, Idbaih A, Criniere E, Marie Y, de Reynies A, Schiappa R, Mokhtari K, Hoang-Xuan K, Sanson M, Delattre JY, Thillet J, Ducray F (2011) Methylation profiling identifies 2 groups of gliomas according to their tumorigenesis. Neuro Oncol 13:84–98
Hegi ME, Diserens A-C, Gorlia T, Hamou M-F, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JEC, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003