Neurology India
menu-bar5 Open access journal indexed with Index Medicus
  Users online: 4555  
 Home | Login 
About Editorial board Articlesmenu-bullet NSI Publicationsmenu-bullet Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
 Resource Links
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Article in PDF (392 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this Article

 Article Access Statistics
    PDF Downloaded38    
    Comments [Add]    

Recommend this journal


Table of Contents    
Year : 2019  |  Volume : 67  |  Issue : 2  |  Page : 410-411

Shifting goal posts and paradigm shifts: Trends in outcome evaluation in glioma management

Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India

Date of Web Publication13-May-2019

Correspondence Address:
Dr. A Arivazhagan
Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.258012

Rights and Permissions

How to cite this article:
Arivazhagan A. Shifting goal posts and paradigm shifts: Trends in outcome evaluation in glioma management. Neurol India 2019;67:410-1

How to cite this URL:
Arivazhagan A. Shifting goal posts and paradigm shifts: Trends in outcome evaluation in glioma management. Neurol India [serial online] 2019 [cited 2020 Sep 27];67:410-1. Available from:

The outcome in cancer has always been quantified in terms of survival. Survival would be further subcategorized as overall survival and disease-free/progression free survival. As modern medicine developed, so did treatments, which can control cancer and can induce remission or cure in a few cancers. Thus, the medical community started looking beyond survival in these patients. For example, radical surgery was replaced by conservative surgery and breast reconstruction in breast cancer, with the addition of effective chemotherapy and targeted therapy.

Cure for brain tumors, especially the malignant ones, is still elusive in almost all histological subtypes. Glioma, the most common primary malignant tumor in the brain, has been a subject of intense research for novel therapies, with some improvements obtained in the survival parameters. The addition of temozolomide (TMZ) has been the last game-changing therapy, which evolved into the standard of care. Nevertheless, recent outcome evaluation studies and trials have begun to shift the goals of treatment beyond prolonging survival.

As the survival of patients with brain tumor improves, the clinician and the patient together start looking forward towards a meaningful quality of living rather than being merely alive. The effects of the treatment for disease should provide a better life and not become a burden. This change in perspective occurred early in medulloblastoma, which was nicely elucidated by Gudrunardottir et al., in their review of literature on childhood medulloblastomas from 1920 to 2014. They noted that the quality-of-life outcomes in medulloblastoma gained importance as these children achieved excellent 5- and 10-year survival rates.[1]

With the advent of the realization that holistic improvement in patient health is more important than mere survival, quality of life is being regarded as an important endpoint in glioma care. Such evolution is evident in two realms, namely, patient care and research. Many recent landmark trials which evaluate the outcome of newer treatments include health-related quality of life (HRQoL) and cognitive assessment as a part of the study.[2],[3],[4] The EF-14 trial, which is a randomized phase III trial evaluating the utility of tumor-treating fields (TTF) in glioblastoma, noted that, initially, HRQoL improved in patients treated with TTF/TMZ (change from baseline [CFB] at 3 months: 24% and CFB at 6 months: 13%) versus TMZ (CFB3: −7% and CFB6: −17%), although this difference was no longer evident at the 9-month point.

Similarly, a number of clinical studies now include functional and QoL assessment as a part of the standard of care.[5],[6],[7] Duffau et al., stressed the importance of maintaining the onco-functional balance in treatment, wherein the goal should be to achieve maximal tumor resection while preserving QoL.[6] Minniti et al., used the European Organization for Research and Treatment of Cancer quality-of-life questionnaire version 3 (QLQ-C30) and QLQ-(brain cancer module) BN20 questionnaire to evaluate elderly patients with a glioblastoma (GBM) treated with shorter course radiotherapy and TMZ, and reported that this abbreviated course was associated with survival benefit with no adverse effect on HRQoL until the time of disease progression.[5]

Khatri et al., have addressed the QoL outcomes in patients with glioma and reported improvements in QoL following surgical resection, which are sustained on longitudinal assessment.[8] Very few studies on QoL in glioma have been reported from India.[9],[10],[11] Region-specific evaluation is extremely relevant since the functional outcomes are often influenced by sociocultural and economic factors, which vary across regions. The previous studies have performed a cross-sectional assessment at some time point of the treatment. Mahalakshmi et al., reported QoL measures preoperatively,[9] while Budrukkar et al., evaluated the status after surgery and before starting adjuvant therapy.[10] Solanki et al., reported QoL at follow-up in long-term survivors of GBM.[11] The present study by Khatri et al., has prospectively assessed the functional status using both patient-reported outcome (PRO) and clinician-reported outcome scores before surgery and at various time period of follow-up, thereby providing strong evidence of functional improvement following treatment. HRQoL was assessed using the short form-36 questionnaire, and they utilized effect size, relative efficiency, and minimal clinically important differences for assessing responsiveness.[8] A subset analysis of the different histological subgroups, namely, Grade II and Grade III/IV gliomas, may be pertinent. Many factors, such as adjuvant treatment, steroid effect, sociocultural, and financial-educational status, can influence the QoL and need to be considered while interpreting the QoL data.

QoL outcome measures can be varied, which comprise PROs, performance outcomes, clinician-reported outcomes, and observer-reported outcomes. A number of scores and scales are available, which address diverse components of health and function.[12],[13] Blakeley et al., lucidly reported that the selection of the specific tool should be based on the outcome/component of QoL, which is addressed by a study, the strength and limitations of the tool, and the ability of the tool to identify the meaningful change.[14] In the same direction, the Response Assessment in Neuro-Oncology-Patient-Reported Outcome working group has recently deliberated on the issue and recommended the application of appropriate PRO tools, with defined outcomes both for research trials and clinical practice.[15] The era for defining the management outcome more comprehensively to provide a meaningful better life to patients has arrived and we, the clinicians, should start looking beyond overall survival and disease-free survival.

  References Top

1 Gudrunardottir T, Lannering B, Remke M, Taylor MD, Wells EM, Keating RF, et al. Treatment developments and the unfolding of the quality of life discussion in childhood medulloblastoma: A review. Childs Nerv Sys 2014;30:979-90.  Back to cited text no. 1
Herrlinger U, Schafer N, Steinbach JP, Weyerbrock A, Hau P, Goldbrunner R, et al. Bevacizumab plus irinotecan versus temozolomide in newly diagnosed O6-methylguanine-DNA methyltransferase nonmethylated glioblastoma: The randomized GLARIUS trial. J Clin Oncol 2016;34:1611-9.  Back to cited text no. 2
Reijneveld JC, Taphoorn MJB, Coens C, Bromberg JEC, Mason WP, Hoang-Xuan K, et al. Health-related quality of life in patients with high-risk low-grade glioma (EORTC 22033-26033): A randomised, open-label, phase 3 intergroup study. Lancet Oncol 2016;17:1533-42.  Back to cited text no. 3
Zhu JJ, Demireva P, Kanner AA, Pannullo S, Mehdorn M, Avgeropoulos N, et al., on behalf of the EFTI. Health-related quality of life, cognitive screening, and functional status in a randomized phase III trial (EF-14) of TTF with temozolomide compared to temozolomide alone in newly diagnosed glioblastoma. J Neuro-oncol 2017;135:545-52.  Back to cited text no. 4
Minniti G, Scaringi C, Baldoni A, Lanzetta G, De Sanctis V, Esposito V, et al. Health-related quality of life in elderly patients with newly diagnosed glioblastoma treated with short-course radiation therapy plus concomitant and adjuvant temozolomide. Int J Radiat Oncol Biol Phys 2013;86:285-91.  Back to cited text no. 5
Duffau H, Mandonnet E. The “onco-functional balance” in surgery for diffuse low-grade glioma: Integrating the extent of resection with quality of life. Acta Neurochir (Wien) 2013;155:951-7.  Back to cited text no. 6
Henriksson R, Asklund T, Poulsen HS. Impact of therapy on quality of life, neurocognitive function and their correlates in glioblastoma multiforme: A review. J Neurooncol 2011;104:639-46.  Back to cited text no. 7
Khatri D, Jaiwal AK, Das KK, Pandey S, Bhaisora K, Kumar R. Health-related quality of life after surgery in supratentorial glioma. Neurol India 2019;67:467-75.  Back to cited text no. 8
  [Full text]  
Mahalakshmi P, Vanisree AJ. Quality of life measures in glioma patients with different grades: A preliminary study. Indian J Cancer 2015;52:580-5.  Back to cited text no. 9
[PUBMED]  [Full text]  
Budrukkar A, Jalali R, Dutta D, Sarin R, Devlekar R, Parab S, et al. Prospective assessment of quality of life in adult patients with primary brain tumors in routine neurooncology practice. J Neurooncol 2009;95:413-9.  Back to cited text no. 10
Solanki C, Sadana D, Arimappamagan A, Rao K, Rajeswaran J, Subbakrishna DK, et al. Impairments in quality of life and cognitive functions in long-term survivors of glioblastoma. J Neuroscienc Rural Prac 2017;8:228-35.  Back to cited text no. 11
Gabel N, Altshuler DB, Brezzell A, Briceno EM, Boileau NR, Miklja Z, et al. Health related quality of life in adult low and high-grade glioma patients using the National Institutes of Health patient reported outcomes measurement information system (PROMIS) and Neuro-QOL assessments. Front Neurol 2019;10:212.  Back to cited text no. 12
Bergo E, Lombardi G, Guglieri I, Capovilla E, Pambuku A, Zagone V. Neurocognitive functions and health-related quality of life in glioblastoma patients: A concise review of the literature. Eur J Cancer Care (Engl) 2019;28:e12410.  Back to cited text no. 13
Blakeley JO, Coons SJ, Corboy JR, Kline Leidy N, Mendoza TR, Wefel JS. Clinical outcome assessment in malignant glioma trials: Measuring signs, symptoms, and functional limitations. Neurooncol 2016;18(Suppl 2):ii13-20.  Back to cited text no. 14
Dirven L, Armstrong TS, Blakeley JO, Brown PD, Grant R, Jalali R, et al. Working plan for the use of patient-reported outcome measures in adults with brain tumours: A Response Assessment in Neuro-oncology (RANO) initiative. Lancet Oncol 2018;19:e173-80.  Back to cited text no. 15


Print this article  Email this article
Online since 20th March '04
Published by Wolters Kluwer - Medknow