Abstract
Despite recent randomized, prospective evidence supporting use of RT and chemotherapy (CRT) for high-risk low-grade gliomas (LGG), many patients have historically received RT alone, chemotherapy alone or observation postoperatively. The purpose of this study is to evaluate outcomes for historical treatments in comparison to CRT for high-risk diffuse WHO grade II glioma patients. Records from 309 adults with WHO grade II glioma (1997–2008) eligible for RTOG 9802 (incomplete resection/biopsy or age ≥40 years) were retrospectively reviewed. Kaplan–Meier estimates were used for progression-free survival (PFS) and overall survival (OS). The Cox proportional hazards model was used for estimates of risk ratios for univariate and multivariate analyses. Median follow-up was 10.6 years. Adjuvant treatments included radiotherapy (RT) alone (45%), observation (31%), CRT (21%) and chemotherapy alone (3%). Non-astrocytic histology, TERT promoter mutation, 1p/19q codeletion and extensive resections were associated with improved PFS and OS on univariate analysis (all p < 0.05). IDH mutations and adjuvant CRT was associated with improved PFS (all p < 0.05). On multivariate analysis, histology, molecular grouping and extent of resection were significantly associated with PFS and OS. In addition, multivariate analysis revealed that CRT was associated with improved PFS and OS compared with RT alone, and improved PFS compared with observation. This study confirms the benefit of adding chemotherapy to RT compared with RT alone or observation. These findings emphasize the need for aggressive treatment in patients with high-risk LGG.
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Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109
Janny P, Cure H, Mohr M, Heldt N, Kwiatkowski F, Lemaire JJ, Plagne R, Rozan R (1994) Low grade supratentorial astrocytomas. Management and prognostic factors. Cancer 73:1937–1945
Leighton C, Fisher B, Bauman G, Depiero S, Stitt L, MacDonald D, Cairncross G (1997) Supratentorial low-grade glioma in adults: an analysis of prognostic factors and timing of radiation. J Clin Oncol 15:1294–1301
Smith JS, Chang EF, Lamborn KR, Chang SM, Prados MD, Cha S, Tihan T, Vandenberg S, McDermott MW, Berger MS (2008) Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. J Clin Oncol 26:1338–1345
Youland RS, Schomas DA, Brown PD, Parney IF, Laack NNI (2017) Patterns of care and treatment outcomes in older adults with low grade glioma: a 50-year experience. J Neurooncol. doi: 10.1007/s11060-017-2439-3
Shaw EG, Berkey B, Coons SW, Bullard D, Brachman D, Buckner JC, Stelzer KJ, Barger GR, Brown PD, Gilbert MR, Mehta M (2008) Recurrence following neurosurgeon-determined gross-total resection of adult supratentorial low-grade glioma: results of a prospective clinical trial. J Neurosurg 109:835–841
van den Bent MJ, Afra D, de Witte O, Ben Hassel M, Schraub S, Hoang-Xuan K, Malmstrom PO, Collette L, Pierart M, Mirimanoff R, Karim AB (2005) Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial. The Lancet 366:985–990
Buckner JC, Shaw EG, Pugh SL, Chakravarti A, Gilbert MR, Barger GR, Coons S, Ricci P, Bullard D, Brown PD, Stelzer K, Brachman D, Suh JH, Schultz CJ, Bahary JP, Fisher BJ, Kim H, Murtha AD, Bell EH, Won M, Mehta MP, Curran WJ Jr (2016) Radiation plus Procarbazine, CCNU, and Vincristine in low-grade glioma. N Engl J Med 374:1344–1355
Shaw EG, Wang M, Coons SW, Brachman DG, Buckner JC, Stelzer KJ, Barger GR, Brown PD, Gilbert MR, Mehta MP (2012) Randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine chemotherapy for supratentorial adult low-grade glioma: initial results of RTOG 9802. J Clin Oncol 30:3065–3070
Fisher BJ, Hu C, Macdonald DR, Lesser GJ, Coons SW, Brachman DG, Ryu S, Werner-Wasik M, Bahary JP, Liu J, Chakravarti A, Mehta M (2015) Phase 2 study of temozolomide-based chemoradiation therapy for high-risk low-grade gliomas: preliminary results of Radiation Therapy Oncology Group 0424. Int J Radiat Oncol Biol Phys 91:497–504
Baumert BG, Hegi ME, van den Bent MJ, von Deimling A, Gorlia T, Hoang-Xuan K, Brandes AA, Kantor G, Taphoorn MJ, Hassel MB, Hartmann C, Ryan G, Capper D, Kros JM, Kurscheid S, Wick W, Enting R, Reni M, Thiessen B, Dhermain F, Bromberg JE, Feuvret L, Reijneveld JC, Chinot O, Gijtenbeek JM, Rossiter JP, Dif N, Balana C, Bravo-Marques J, Clement PM, Marosi C, Tzuk-Shina T, Nordal RA, Rees J, Lacombe D, Mason WP, Stupp R (2016) Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033–26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol 17:1521–1532
Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, Sicotte H, Pekmezci M, Rice T, Kosel ML, Smirnov IV, Sarkar G, Caron AA, Kollmeyer TM, Praska CE, Chada AR, Halder C, Hansen HM, McCoy LS, Bracci PM, Marshall R, Zheng S, Reis GF, Pico AR, O’Neill BP, Buckner JC, Giannini C, Huse JT, Perry A, Tihan T, Berger MS, Chang SM, Prados MD, Wiemels J, Wiencke JK, Wrensch MR, Jenkins RB (2015) Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med 372:2499–2508
Pafundi DH, Laack NN, Youland RS, Parney IF, Lowe VJ, Giannini C, Kemp BJ, Grams MP, Morris JM, Hoover JM, Hu LS, Sarkaria JN, Brinkmann DH (2013) Biopsy validation of 18F-DOPA PET and biodistribution in gliomas for neurosurgical planning and radiotherapy target delineation: results of a prospective pilot study. Neuro Oncol 15:1058–1067
Youland RS, Brown PD, Giannini C, Parney IF, Uhm JH, Laack NN (2013) Adult low-grade glioma: 19-year experience at a single institution. Am J Clin Oncol 36:612–619
Bauman G, Lote K, Larson D, Stalpers L, Leighton C, Fisher B, Wara W, MacDonald D, Stitt L, Cairncross JG (1999) Pretreatment factors predict overall survival for patients with low-grade glioma: a recursive partitioning analysis. Int J Radiat Oncol Biol Phys 45:923–929
Pignatti F, van den Bent M, Curran D, Debruyne C, Sylvester R, Therasse P, Afra D, Cornu P, Bolla M, Vecht C, Karim AB (2002) Prognostic factors for survival in adult patients with cerebral low-grade glioma. J Clin Oncol 20:2076–2084
Rotta JM, de Oliveira MF, Reis RC, Botelho RV (2017) Malignant transformation of low-grade gliomas in patients undergoing adjuvant therapy. Acta Neurol Belg 117:235–239
Kamasak K, Ekici MA, Gocmez C, Tucer B, Basarslan SK, Kurtsoy A (2012) Malign transformation in the low grade astrocytomas and related factors. Turk Neurosurg 22:566–575
Mehrkens JH, Kreth FW, Muacevic A, Ostertag CB (2004) Long term course of WHO grade II astrocytomas of the Insula of Reil after I-125 interstitial irradiation. J Neurol 251:1455–1464
Sarmiento JM, Venteicher AS, Patil CG (2015) Early versus delayed postoperative radiotherapy for treatment of low-grade gliomas. Cochrane Database Syst Rev. doi:10.1002/14651858.CD009229.pub2
Jung TY, Jung S, Moon JH, Kim IY, Moon KS, Jang WY (2011) Early prognostic factors related to progression and malignant transformation of low-grade gliomas. Clin Neurol Neurosurg 113:752–757
Laack NN, Brown PD, Ivnik RJ, Furth AF, Ballman KV, Hammack JE, Arusell RM, Shaw EG, Buckner JC (2005) Cognitive function after radiotherapy for supratentorial low-grade glioma: a North Central Cancer Treatment Group prospective study. Int J Radiat Oncol Biol Phys 63:1175–1183
Wick W, Roth P, Hartmann C, Hau P, Nakamura M, Stockhammer F, Sabel MC, Wick A, Koeppen S, Ketter R, Vajkoczy P, Eyupoglu I, Kalff R, Pietsch T, Happold C, Galldiks N, Schmidt-Graf F, Bamberg M, Reifenberger G, Platten M, von Deimling A, Meisner C, Wiestler B, Weller M (2016) Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide. Neuro Oncol 18:1529–1537
Johnson BE, Mazor T, Hong C, Barnes M, Aihara K, McLean CY, Fouse SD, Yamamoto S, Ueda H, Tatsuno K, Asthana S, Jalbert LE, Nelson SJ, Bollen AW, Gustafson WC, Charron E, Weiss WA, Smirnov IV, Song JS, Olshen AB, Cha S, Zhao Y, Moore RA, Mungall AJ, Jones SJ, Hirst M, Marra MA, Saito N, Aburatani H, Mukasa A, Berger MS, Chang SM, Taylor BS, Costello JF (2014) Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science 343:189–193
Claus EB, Horlacher A, Hsu L, Schwartz RB, Dello-Iacono D, Talos F, Jolesz FA, Black PM (2005) Survival rates in patients with low-grade glioma after intraoperative magnetic resonance image guidance. Cancer 103:1227–1233
Ius T, Isola M, Budai R, Pauletto G, Tomasino B, Fadiga L, Skrap M (2012) Low-grade glioma surgery in eloquent areas: volumetric analysis of extent of resection and its impact on overall survival. A single-institution experience in 190 patients: clinical article. J Neurosurg 117:1039–1052
Hervey-Jumper SL, Berger MS (2016) Maximizing safe resection of low- and high-grade glioma. J Neurooncol 130:269–282
Beiko J, Suki D, Hess KR, Fox BD, Cheung V, Cabral M, Shonka N, Gilbert MR, Sawaya R, Prabhu SS, Weinberg J, Lang FF, Aldape KD, Sulman EP, Rao G, McCutcheon IE, Cahill DP (2014) IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection. Neuro Oncol 16:81–91
Sonoda Y, Shibahara I, Kawaguchi T, Saito R, Kanamori M, Watanabe M, Suzuki H, Kumabe T, Tominaga T (2015) Association between molecular alterations and tumor location and MRI characteristics in anaplastic gliomas. Brain Tumor Pathol 32:99–104
Qi S, Yu L, Li H, Ou Y, Qiu X, Ding Y, Han H, Zhang X (2014) Isocitrate dehydrogenase mutation is associated with tumor location and magnetic resonance imaging characteristics in astrocytic neoplasms. Oncol Lett 7:1895–1902
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Youland, R.S., Kreofsky, C.R., Schomas, D.A. et al. The impact of adjuvant therapy for patients with high-risk diffuse WHO grade II glioma. J Neurooncol 135, 535–543 (2017). https://doi.org/10.1007/s11060-017-2599-1
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DOI: https://doi.org/10.1007/s11060-017-2599-1