Outcome Analysis and Prognostic Factors in Patients of Glioblastoma Multiforme: An Indonesian Single Institution Experience

Sudibio Sudibio; Jellyca Anton; Handoko Handoko; Tiara Bunga Mayang  Permata; Henry  Kodrat; Endang  Nuryadi; Henry Riyanto Sofyan; Rahmad Mulyadi; Renindra Ananda Aman; Soehartati Gondhowiardjo

doi:10.3889/oamjms.2021.7502

Authors

Sudibio Sudibio Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Department of Radiation Oncology, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia https://orcid.org/0000-0003-0538-1167
Jellyca Anton Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Department of Radiation Oncology, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
Handoko Handoko Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Department of Radiation Oncology, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
Tiara Bunga Mayang Permata Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Department of Radiation Oncology, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia https://orcid.org/0000-0002-5890-5545
Henry Kodrat Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Department of Radiation Oncology, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia https://orcid.org/0000-0003-3782-7901
Endang Nuryadi Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Department of Radiation Oncology, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia https://orcid.org/0000-0003-1029-1748
Henry Riyanto Sofyan Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Department of Neurology, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
Rahmad Mulyadi Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Department of Radiology, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
Renindra Ananda Aman Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Department of Neurosurgery, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia https://orcid.org/0000-0002-5135-6256
Soehartati Gondhowiardjo Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Department of Radiation Oncology, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia https://orcid.org/0000-0002-9446-4361

DOI:

https://doi.org/10.3889/oamjms.2021.7502

Keywords:

Glioblastoma multiforme, Prognostic factors, Radiotherapy, Survival

Abstract

Aims: This study was done to assess the survival of patients with glioblastoma multiform and to identify factors that can affect patient survival.

Materials and methods: From January 2015 to December 2019, 55 patients with histopathologically confirmed glioblastoma multiform and received adjuvant radiation/chemoradiation in our department were retrospectively analyzed.

Results: The median overall survival (OS) for entire cohort was 13 months and 1-year OS and 2-year OS rate were 52.7% and 3.6% with the mean follow-up period was 12 months. In univariate analysis, age (≤50 years vs >50 years, p=0.02), performance status (≥90 vs 70-80 vs <70, p<0.001), RTOG RPA classification (class III vs class IV vs class V-VI, p<0.001), parietal lobes tumor site (vs others, p=0.02), residual tumor volume (≤20.4cm³ vs >20.4cm³, p=0.001) and time to initiate adjuvant therapy (<4 weeks vs 4-6 weeks vs >6 weeks, p=0.01) were significantly affect overall survival. In multivariate analysis, RTOG RPA classification and involvement of parietal lobes were independent prognostic factors for overall survival.

Conclusions: RTOG RPA classification that consisted of age and performance status is an independent prognostic factor for the clinical outcome of GBM. Besides this well-known factor, we also identified the involvement of parietal lobe gives a strong negative influence on survival of GBM patients.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, et al. CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the United States in 2012-2016. Neuro Oncol. 2019;21 Suppl 5:v1-100. https://doi.org/10.1093/neuonc/noz150 PMid:31675094

Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathol. 2016;131(6):803-20. https://doi.org/10.1007/s00401-016-1545-1 PMid:27157931

National Comprehensive Cancer Network. Central Nervous System Cancers V3.2019. 2019. p. 123. Available from: https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf [Last accessed on 2021 Feb 24].

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987-96. https://doi.org/10.1056/NEJMoa043330 PMid:15758009

Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, et al. 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. 2009;10(5):459-66. https://doi.org/10.1016/S1470-2045(09)70025-7 PMid:19269895

World Health Organization. Life Expectancy and Healthy life Expectancy Data by Country. Geneva: World Health Organization; 2016. Available from: https://www.apps.who.int/gho/data/view.main.sdg2016lexv?lang=en [Last accessed on 2021 Feb 24].

Ahn S, Park JS, Song JH, Jeun SS, Hong YK. Effect of a time delay for concomitant chemoradiation after surgery for newly diagnosed glioblastoma: A single-institution study with subgroup analysis according to the extent of tumor resection. World Neurosurg. 2020;133:e640-5. https://doi.org/10.1016/j.wneu.2019.09.122 PMid:31568907

Nizamutdinov D, Stock EM, Dandashi JA, Vasquez EA, Mao Y, Dayawansa S, et al. Prognostication of survival outcomes in patients diagnosed with glioblastoma. World Neurosurg. 2018;109:e67-74. https://doi.org/10.1016/j.wneu.2017.09.10 PMid:28951270

Wee CW, Kim E, Kim TM, Park CK, Kim JW, Choi SH, et al. Impact of interim progression during the surgery-to-radiotherapy interval and its predictors in glioblastoma treated with temozolomide-based radiochemotherapy. J Neurooncol. 2017;134(1):169-75. https://doi.org/10.1007/s11060-017-2505-x PMid:28547592

Blumenthal DT, Won M, Mehta MP, Gilbert MR, Brown PD, Bokstein F, et al. Short delay in initiation of radiotherapy for patients with glioblastoma-effect of concurrent chemotherapy: A secondary analysis from the NRG oncology/radiation therapy oncology group database. Neuro Oncol. 2018;20(7):966-74. https://doi.org/10.1093/neuonc/noy017 PMid:29462493

Tian M, Ma W, Chen Y, Yu Y, Zhu D, Shi J, et al. Impact of gender on the survival of patients with glioblastoma. Biosci Rep. 2018;38(6):BSR20180752. https://doi.org/10.1042/BSR20180752 PMid:30305382

Tseng MY, Tseng JH. Survival analysis for adult glioma in England and Wales. J Formos Med Assoc. 2005;104(5):341-8. PMid:15959601

Zhou M, Sareddy GR, Li M, Liu J, Luo Y, Venkata PP, et al. Estrogen receptor beta enhances chemotherapy response of GBM cells by down regulating DNA damage response pathways. Sci Rep. 2019;9(1):6124. https://doi.org/10.1038/s41598-019-42313-8 PMid:30992459

Curran WJ, Scott CB, Horton J, Nelson JS, Weinstein AS, Fischbach AJ, et al. Recursive partitioning analysis of prognostic factors in three radiation therapy oncology group malignant glioma trials. J Natl Cancer Inst. 1993;85(9):704-10. https://doi.org/10.1093/jnci/85.9.704 PMid:8478956

Li J, Wang M, Won M, Shaw EG, Coughlin C, Curran WJ, et al. Validation and Simplification of the radiation therapy oncology group recursive partitioning analysis classification for glioblastoma. Int J Radiat Oncol. 2011;81(3):623-30. https://doi.org/10.1016/j.ijrobp.2010.06.012 PMid:20888136

Kumar N, Kumar P, Angurana S, Khosla D, Mukherjee K, Aggarwal R, et al. Evaluation of outcome and prognostic factors in patients of glioblastoma multiforme: A single institution experience. J Neurosci Rural Pract. 2013;4 Suppl 1:S46-55. https://doi.org/10.4103/0976-3147.116455 PMid:24174800

Lamborn KR, Chang SM, Prados MD. Prognostic factors for survival of patients with glioblastoma: Recursive partitioning analysis. Neuro Oncol. 2004;6(3):227-35. https://doi.org/10.1215/S1152851703000620 PMid:15279715

Kita D, Ciernik IF, Vaccarella S, Franceschi S, Kleihues P, Lütolf UM, et al. Age as a predictive factor in glioblastomas: Population-based study. Neuroepidemiology. 2009;33(1):17-22. https://doi.org/10.1159/000210017 PMid:19325245

Tabchi S, Kassouf E, Florescu M, Tehfe M, Blais N. Factors influencing treatment selection and survival in advanced lung cancer. Curr Oncol. 2017;24(2):e115-22. https://doi.org/10.3747/co.24.3355 PMid:28490934

Bette S, Barz M, Wiestler B, Huber T, Gerhardt J, Buchmann N, et al. Prognostic value of tumor volume in glioblastoma patients: Size also matters for patients with incomplete resection. Ann Surg Oncol. 2018;25(2):558-64. https://doi.org/10.1245/s10434-017-6253-0 PMid:29159745

Chaichana KL, Jusue-Torres I, Navarro-Ramirez R, Raza SM, Pascual-Gallego M, Ibrahim A, et al. Establishing percent resection and residual volume thresholds affecting survival and recurrence for patients with newly diagnosed intracranial glioblastoma. Neuro Oncol. 2014;16(1):113-22. https://doi.org/10.1093/neuonc/not137 PMid:24285550

Grabowski MM, Recinos PF, Nowacki AS, Schroeder JL, Angelov L, Barnett GH, et al. Residual tumor volume versus extent of resection: Predictors of survival after surgery for glioblastoma. J Neurosurg. 2014;121(5):1115-23. https://doi.org/10.3171/2014.7.JNS13244 PMid:25192475

Roelz R, Strohmaier D, Jabbarli R, Kraeutle R, Egger K, Coenen VA, et al. Residual tumor volume as best outcome predictor in low grade glioma-a nine-years near-randomized survey of surgery vs. biopsy. Sci Rep. 2016;6:32286. https://doi.org/10.1038/srep32286 PMid:27574036

Woo PY, Ho JM, Tse TP, Lam SW, Mak CH, Chan DT, et al. Determining a cut-off residual tumor volume threshold for patients with newly diagnosed glioblastoma treated with temozolomide chemoradiotherapy: A multicenter cohort study. J Clin Neurosci. 2019;63:134-41. https://doi.org/10.1016/j.jocn.2019.01.022 PMid:30712777

Ellingson BM, Abrey LE, Nelson SJ, Kaufmann TJ, Garcia J, Chinot O, et al. Validation of postoperative residual contrast-enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma. Neuro Oncol. 2018;20(9):1240-50. https://doi.org/10.1093/neuonc/noy053 PMid:29660006

Yong RL, Wu T, Mihatov N, Shen MJ, Brown MA, Zaghloul KA, et al. Residual tumor volume and patient survival following reoperation for recurrent glioblastoma. J Neurosurg. 2014;121(4):802-9. https://doi.org/10.3171/2014.6.JNS132038 PMid:25061868

Han SJ, Rutledge WC, Molinaro AM, Chang SM, Clarke JL, Prados MD, et al. The effect of timing of concurrent chemoradiation in patients with newly diagnosed glioblastoma. Neurosurgery. 2015;77(2):248-53; discussion 253. https://doi.org/10.1227/NEU.0000000000000766 PMid:25856113

Blumenthal DT, Won M, Mehta MP, Curran WJ, Souhami L, Michalski JM, et al. Short delay in initiation of radiotherapy may not affect outcome of patients with glioblastoma: A secondary analysis from the radiation therapy oncology group database. J Clin Oncol. 2009;27(5):733-9. https://doi.org/10.1200/JCO.2008.18.9035 PMid:19114694

Buszek SM, Al Feghali KA, Elhalawani H, Chevli N, Allen PK, Chung C. Optimal timing of radiotherapy following gross total or subtotal resection of glioblastoma: A real-world assessment using the national cancer database. Sci Rep. 2020;10(1):4926. https://doi.org/10.1038/s41598-020-61701-z PMid:32188907

Lai R, Hershman DL, Doan T, Neugut AI. The timing of cranial radiation in elderly patients with newly diagnosed glioblastoma multiforme. Neuro Oncol. 2010;12(2):190-8. https://doi.org/10.1093/neuonc/nop004 PMid:20150386

Loureiro LV, de Barros Pontes L, Callegaro-Filho D, de Oliveira Koch L, Weltman E, da Silva Victor E, et al. Waiting time to radiotherapy as a prognostic factor for glioblastoma patients in a scenario of medical disparities. Arq Neuropsiquiatr. 2015;73(2):104-10. https://doi.org/10.1590/0004-282X20140202 PMid:25742578

Louvel G, Metellus P, Noel G, Peeters S, Guyotat J, Duntze J, et al. Delaying standard combined chemoradiotherapy after surgical resection does not impact survival in newly diagnosed glioblastoma patients. Radiother Oncol. 2016;118(1):9-15. https://doi.org/10.1016/j.radonc.2016.01.001 PMid:26791930

Randolph DM 2nd, McTyre ER, Paulsson AK, Holmes JA, Hinson WH, Lesser GJ, et al. Impact of timing of radiotherapy in patients with newly diagnosed glioblastoma. Clin Neurol Neurosurg. 2016;151:73-8. https://doi.org/10.1016/j.clineuro.2016.10.012 PMid:27816029

Peker S, Abacioglu U, Sun I, Yuksel M, Pamir MN. Irradiation after surgically induced brain injury in the rat: Timing in relation to severity of radiation damage. J Neurooncol. 2004;70(1):17-21. https://doi.org/10.1023/b:neon.0000040820.78643.0a PMid:15527102

Champ CE, Siglin J, Mishra MV, Shen X, Werner-Wasik M, Andrews DW, et al. Evaluating changes in radiation treatment volumes from post-operative to same-day planning MRI in high-grade gliomas. Radiat Oncol. 2012;7(1):220. https://doi.org/10.1186/1748-717X-7-220 PMid:23259933

Patel DM, Agarwal N, Tomei KL, Hansberry DR, Goldstein IM. Optimal timing of whole-brain radiation therapy following craniotomy for cerebral malignancies. World Neurosurg. 2015;84(2):412-9. https://doi.org/10.1016/j.wneu.2015.03.052 PMid:25839399

Patel RA, Lock D, Helenowski IB, Chandler JP, Sachdev S, Tate MC, et al. Postsurgical cavity evolution after brain metastasis resection: How soon should postoperative radiosurgery follow? World Neurosurg. 2018;110:e310-4. https://doi.org/10.1016/j.wneu.2017.10.159 PMid:29122731

Joo JD, Chang JH, Kim JH, Hong YK, Kim YH, Kim CY. Temozolomide during and after radiotherapy for newly diagnosed glioblastomas: Aprospective multicenter study of Korean patients. J Korean Neurosurg Soc. 2012;52(2):92-7. https://doi.org/10.3340/jkns.2012.52.2.92 PMid:23091665

Karacetin D, Okten B, Yalcin B, Incekara O. Concomitant temozolomide and radiotherapy versus radiotherapy alone for treatment of newly diagnosed glioblastoma multiforme. J BUON. 201116(1):133-7. PMid:21674864

Szczepanek D, Marchel A, Moskał M, Krupa M, Kunert P, Trojanowski T. Efficacy of concomitant and adjuvant temozolomide in glioblastoma treatment. A multicentre randomized study. Neurol Neurochir Pol. 2013;47(2):101-8. https://doi.org/10.5114/ninp.2013.34398 PMid:23649997

Kocher M, Frommolt P, Borberg SK, Rühl U, Steingräber M, Niewald M, et al. Randomized study of postoperative radiotherapy and simultaneous temozolomide without adjuvant chemotherapy for glioblastoma. Strahlenther Onkol. 2008;184(11):572-9. https://doi.org/10.1007/s00066-008-1897-0 PMid:19016015

Gondhowiardjo S, Muthalib A, Khotimah S, Rachman A. Nimotuzumab combined with radiotherapy reduces primary tumor and nodal volume in advanced undifferentiated nasopharyngeal carcinoma. Asia Pac J Clin Oncol. 2009;5(3):175-80. https://doi.org/10.1111/j.1743-7563.2009.01227.x

Du XJ, Li XM, Cai LB, Sun JC, Wang SY, Wang XC, et al. Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: A Phase II multicenter clinical trial. J Cancer. 2019;10(14):3214-23. https://doi.org/10.7150/jca.30123 PMid:31289592

Westphal M, Heese O, Steinbach JP, Schnell O, Schackert G, Mehdorn M, et al. A randomised, open label Phase III trial with nimotuzumab, an anti-epidermal growth factor receptor monoclonal antibody in the treatment of newly diagnosed adult glioblastoma. Eur J Cancer. 2015;51(4):522-32. https://doi.org/10.1016/j.ejca.2014.12.019 PMid:25616647

Wang Y, Pan L, Sheng XF, Chen S, Dai JZ. Nimotuzumab, a humanized monoclonal antibody specific for the EGFR, in combination with temozolomide and radiation therapy for newly diagnosed glioblastoma multiforme: First results in Chinese patients. Asia Pac J Clin Oncol. 2016;12(1):e23-9. https://doi.org/10.1111/ajco.12166 PMid:24571331

Binabaj MM, Bahrami A, ShahidSales S, Joodi M, Joudi Mashhad M, Hassanian SM, et al. The prognostic value of MGMT promoter methylation in glioblastoma: A meta-analysis of clinical trials. J Cell Physiol. 2018;233(1):378-86. https://doi.org/10.1002/jcp.25896 PMid:28266716

Chen Y, Hu F, Zhou Y, Chen W, Shao H, Zhang Y. MGMT promoter methylation and glioblastoma prognosis: A systematic review and meta-analysis. Arch Med Res. 2013;44(4):281-90. https://doi.org/10.1016/j.arcmed.2013.04.004 PMid:23608672

Awad AW, Karsy M, Sanai N, Spetzler R, Zhang Y, Xu Y, et al. Impact of removed tumor volume and location on patient outcome in glioblastoma. J Neurooncol. 2017;135(1):161-71. https://doi.org/10.1007/s11060-017-2562-1 PMid:28685405

Carr MT, Hochheimer CJ, Rock AK, Dincer A, Ravindra L, Zhang FL, et al. Comorbid medical conditions as predictors of overall survival in glioblastoma patients. Sci Rep. 2019;9(1):20018. https://doi.org/10.1038/s41598-019-56574-w PMid:31882968

Carroll KT, Bryant AK, Hirshman B, Alattar AA, Joshi R, Gabel B, et al. Interaction between the contributions of tumor location, tumor grade, and patient age to the survival benefit associated with gross total resection. World Neurosurg. 2018;111:e790-8. https://doi.org/10.1016/j.wneu.2017.12.165 PMid:29309983

Ghosh M, Shubham S, Mandal K, Trivedi V, Chauhan R, Naseera S. Survival and prognostic factors for glioblastoma multiforme: Retrospective single-institutional study. Indian J Cancer. 2017;54(1):362-7. https://doi.org/10.4103/ijc.IJC_157_17 PMid:29199724