Journal of Geriatric Oncology 10 (2019) 159–163

Contents lists available at ScienceDirect

Journal of Geriatric Oncology

First validation of the G-8 geriatric screening tool in older patients

with glioblastoma
Elise Deluche ⁎, Sophie Leobon, Francois Lamarche, Nicole Tubiana-Mathieu
Department of Medical Oncology, University Hospital, Limoges 87042, France

a r t i c l e i n f o a b s t r a c t

Article history: Introduction: Management of glioblastoma, with a very poor prognosis, remains a challenge in older patients be-
Received 24 April 2018 cause of coexisting comorbidities and the increased risk of toxic treatment effects. The use of screening tools to
Received in revised form 25 June 2018 identify vulnerable patients is essential. This study was performed to establish whether the G8 scale can be
Accepted 9 July 2018 used for screening older patients with glioblastoma.
Available online 20 July 2018
Methods: We retrospectively reviewed the files of patients assessed by the G8 scale and diagnosed with glioblas-
toma at a single center from January 2010 to July 2017. Patients aged 65 years or older were classified into three
Keywords:
G8 screening score
groups (more efficiently than two groups) according to their G8 score to identify those with a poor prognosis:
Glioblastoma high score group, G8 score 14.5–17; intermediate score group, G8 score 10.5–14; and low score group, G8
Older patients score b 10.5.
Prognosis Results: Of 89 patients, 19% were classified into the high score group, 43% into the intermediate score group, and
Adjuvant therapy 38% into the low score group. Median overall survival was four months in the low score group, 15 months in the
intermediate score group, and 42 months in the high score group (p b .0001). On multivariate analysis, G8 score
was a significant independent predictor of overall survival (hazard ratio: 55.46; 99.5% confidence interval:
13.42–229.13; p b .0001).
Conclusions: Here, we highlighted the possibility of using the G8 score, with possibly three cut-offs, in the man-
agement of older patients with glioblastoma and determined the prognostic role of this quick and easy screening
tool.
© 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction According to the National Comprehensive Cancer Network (NCCN)

Glioblastoma (GBM) is the most common primary malignant brain
tumor in adults over 65 years of age and its prognosis is very poor. For
many years, older patients have been under-represented in most ran-
domized studies due to restrictive inclusion criteria. The average age
of the participants in studies on GBM is approximately 55 years, in con-
trast to the population-based median age of 65 years for such pathology
[1]. However, the incidence of GBM in older patients is increasing, and
this has become an important therapeutic challenge in oncology [2]. Re-
cently, temozolomide (TMZ) and radiotherapy (RT), showed a survival
advantage and has now become the standard treatment for GBM pa-
tients older than 70 years [3]. Management of GBM in older patients is
difficult given the poor prognosis, frequent coexisting comorbidities,
and increased risk of toxic effects from the treatment (surgery, RT,
and/or chemotherapy). In general, the treatment options in older pa-
tients can be limited and they are likely to undergo less aggressive treat-
ment rather than receiving the conventional treatment [4, 5].
⁎ Corresponding author at: Medical Oncology, University Hospital, 2 Avenue Martin
Luther King, 87042 Limoges, Cedex, France.
E-mail address: elise.deluche@chu-limoges.fr (E. Deluche).
Guidelines for Senior Adult Oncology and the International Society of
Geriatric Oncology recommendations, the Comprehensive Geriatric As-
sessment (CGA) should be a key part of the treatment approach for all
older patients with cancer [6, 7]. Although the CGA has shown value
in older patients with cancer [8], it is both time- and resource-consum-
ing and is not feasible for all patients. Therefore, several screening tools
have been developed to quickly identify vulnerable older patients. The
scoring system most commonly used by clinicians to predict outcomes
is the Karnofsky Performance Status (KPS) [9–11] or the Eastern Coop-
erative Oncology Group-Performance Status (ECOG-PS) [3] which are
prognostic factors.
The major problem with these scales when applied to GBM concerns
evaluation of the autonomy of patients, which is frequently affected not
by an actual deterioration of their general state, but by an acquired
motor deficit. Moreover, these scales are not specific to older patients.
It is challenging to evaluate older patients with GBM because of the dif-
ficulty in distinguishing neuro-oncology symptoms related to the dis-
ease from age-related symptoms.
Soubeyran et al. designed a new screening tool, with the generic
name G8, specific to older patients with cancer [12]. This tool captures
data on age and includes an additional seven items taken from the

https://doi.org/10.1016/j.jgo.2018.07.002
1879-4068/© 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
160 E. Deluche et al. / Journal of Geriatric Oncology 10 (2019) 159–163

Mini Nutritional Assessment (MNA), i.e., appetite, weight loss, mobility, (75–85 years old), and only two patients belonged to the “oldest old”
cognition and depression, body mass index (BMI), medications, and age group (N85 years). Sixty percent of patients were men, and 40%
self-rated health. This rapid geriatric screening test takes only a few mi- were women. Patient characteristics are listed in Table 1.
nutes to complete and was validated in the ONCODAGE study [13]. The
G8 was validated for predicting survival in various cancers in a large 2.2. G8 Score
prospective multicenter study [14]. If patients with various types of can-
cer were included in this study, G8 score was not evaluated in glioma or All patients were evaluated using the G8 screening tool. The median
glioblastoma [14–19]. G8 score was 11 (range: 4.5–16.0); 19% of patients belonged to the high
Therefore, the present study was performed to establish whether the score group, 43% to the intermediate score group, and 38% to the low
G8 scale can be used in the management of older patients with GBM. score group. The G8 score and patient characteristics are shown in
Table 1.
1.1. Patients and Methods The data for seven items were available for 78 patients, and those as-
sociated with abnormal G8 scores were polypharmacy (except corti-
1.1.1. Patient Population coids and anti-epileptic drugs; p = .002), self-rated health status
The medical records of all patients with GBM referred to our institu- (“Unknown”; p = .015) and mobility (p = .005). Dementia/depression
tion (Limoges University Hospital) from January 2010 to July 2017 were and items taken from the MNA (anorexia, loss of weight, BMI) were not
reviewed in this retrospective study. We collected data on patient char- associated with abnormal G8.
acteristics, type of surgical procedure (biopsy, partial or complete resec- Performance status (PS) was related to G8 score (p = .01) with a
tion), treatments received (chemotherapy, RT), G8 scores, and survival moderate correlation (R: −0.52; 95% confidence interval [CI]: −0.62,
data. −0.17).
Patients were included in the analysis if they fulfilled the following The patients with high G8 score group were younger and had a
criteria: age ≥ 65 years [3], histologically confirmed GBM according to median G8 score of 15.0 (14.0–16.0) and were more likely to be receiv-
the 2007 WHO classification, no chemotherapy and/or RT treatment be- ing radio-chemotherapy, with only one patient receiving no such
fore G8, and availability of G8 score data. treatment.
Patients were excluded if they presented with concomitant cancer or The patients with intermediate G8 score group had a median G8
GBM diagnosed as secondary (grade II–III glioma). score of 12.5 (10.5–14) and 92% of these patients received radio-chemo-
therapy, with only 8% receiving RT treatment alone.
1.1.2. G8 Assessment Patients in the low G8 score group were older and had a median G8
A nurse or physician completed the G8 scale (shown in Table S1). score of 8.0 (4.5–9.0). Forty-four percent of the patients in this group
Total scores range from 0 to 17, with a score ≥ 14 defined as normal were treated with radio-chemotherapy and 27% received palliative care.
and a score b 14 defined as abnormal (according to the conventional
classification system) [13]. For more efficient identification of patients Table 1
with a poor prognosis, they were also divided into three groups by G8 Patient characteristics and G8 score.a
score: 14.5–17, high score group; 10.5–14, intermediate score group;
Demographic, clinical Number High G8 Intermediate Low G8 p
and b10.5, low score group [20]. and tumor of score G8 score score
Clinical data were collected in accordance with French bioethics characteristics patients group group group
laws regarding patient information and consent. The use of retrospec- n = 89 n = 17 n = 38 (43) n = 34
tive and prospective data from the regional solid tumor database was (19) (38)
approved by Limoges Hospital Ethics Committee (President, Dr. Terrier) Age (years)
on 28 April 2016 (approval number 200–2016-14). Patients also pro- Median 74 67 72 77 b0.0001
vided written (signed) informed consent for the collection of biological Range 65–87 65–79 65–84 67–87
materials, and for the use of their data (obtained from biological Age (years)
b80 75 (84) 17 (100) 33 (86) 25 (73) 0.004
materials).
N80 14 (16) 0 (0) 5 (14) 9 (27)
G8 score
1.1.3. Statistical Analysis Median 11.0 15.0 12.5 8.0 b0.0001
All data were collected and analyzed using STATVIEW® software Range 4.5–16.0 14.0–16.0 10.5–13.5 4.5–9.0
(SAS Institute, Inc., Cary, NC). Quantitative results are given as the ECOG-PS scorea
0 0 0 0 0 0.01
median ± SD, qualitative results are shown as percentages, and me- 1 8 1 5 2
dians were compared using the nonparametric Mann–Whitney U test 2 28 10 14 4
for ordinal variables. Overall survival (OS) was calculated from the 3 13 2 4 7
date of initial surgery/biopsy to the date of death from any cause or 4 6 0 1 5
1p19q codeletion
the date of last follow-up. Survival curves were obtained using the
Gender
Kaplan–Meier technique. Relevant variables associated with OS were Male 54 (60) 9 (53) 22 (58) 17 (50) 0.63
examined using univariate and multivariate Cox proportional hazards Female 47 (40) 8 (47) 14 (42) 17 (50)
regression, where applicable. For the multivariate models, a univariate Surgical procedure
inclusion criterion of p ≤ .2 was used. In all analyses, p b .05 was taken (and/or)
Biopsy 54 (60) 9 (53) 16 (42) 29 (85) 0.0007
to indicate statistical significance.
Resection (partial or 41 (46) 10 (58) 25 (72) 6 (17) 0.0001
complete)
2. Results Treatment
Radiotherapy alone 11 (12) 0 (0) 3 (8) 8 (23) 0.01
Radio-chemotherapy 66 (85) 16 (94) 35 (92) 15 (44)
2.1. Characteristics of the Cohort and Treatment
(Stupp)
Chemotherapy alone 2 (2) 0 (0) 0 (0) 2 (6)
A total of 89 patients, aged above 65 years and with a median age of No medical 10 (11) 1 (6) 0 (0) 9 (27)
74.0 years (range: 65–87 years) were included in this study. Based on treatment
the classification of Balducci [21], 49 patients (55%) were classified as ECOG-PS, Eastern Cooperative Oncology Group-Performance Status.
“young old” (65–74 years), 38 (43%) patients were considered “old” a
Missing data: 34 patients.
 E. Deluche et al. / Journal of Geriatric Oncology 10 (2019) 159–163 161

2.3. Patient Outcomes Overall survival

The median OS period was 11.0 months (range: 1.0–43.0 months)
and 65 deaths (73.0%) were reported.
We compared OS between patients with an abnormal G8 score (G8
b 14) and those with a normal G8 score (G8 ≥ 14).
Among the parameters included in the investigation, age, G8 score,
chemotherapy, surgery, and RT were significantly associated with OS
in univariate analysis. In multivariate analysis, only an abnormal G8
score (hazard ratio [HR]: 10.27; 95% CI: 3.12–33.28; p = .0001), absence
of chemotherapy (HR: 2.98; 95% CI: 1.16–7.28; p = .022), and absence
of RT (HR: 4.04; 95% CI: 1.52–10.70; p = .0049) remained significantly
associated with poorer survival (Table 2).
The median OS was 8.0 months in patients with an abnormal G8
score (n = 17) and 42 months in those with a normal G8 score (n =
72) (p b .0001) (Fig. 1).
Next, to define the appropriate cut-off for identification of patients
with a poor prognosis, we adjusted the cut-off value from 14 to 7 points
in 1-point increments, as described previously [20]. The optimal cut-off
was 10.5.
We compared survival between the different groups. Univariate
analysis showed that age b80 years, abnormal G8 score, absence of che-
motherapy, absence of surgery, and absence of RT were significantly as-
sociated with OS (Table 3).
After multivariate analysis, only two parameters remained as inde-
pendent predictors of poorer OS: being in the low G8 score group
(HR: 55.46; 95% CI: 13.42–229.13; p b .0001) and the absence of RT
(HR: 3.11; 95% CI: 1.21–8.00); p = .01) (Table. 3). The Kaplan–Meier
curve of OS according to G8 score, with two cut-offs, is presented in
Fig. 2. The median OS was four months in the low score group (n =
34), 15 months in the intermediate score group (n = 38), and
42 months in the high score group (n = 17) (p b .0001).
3. Discussion
To our knowledge, this is the first study to evaluate the utility of the
G8 screening tool specifically in older patients with GBM, and our re-
sults indicated that the G8 score is an independent prognostic factor
in GBM.
In this study, we showed that dividing patients into three groups ac-
cording to G8 score provided valuable information to better identify pa-
tients with poor prognosis compared to the conventional two-group
classification. The optimal cut-off value for identifying older patient
with cancer requiring a CGA is 14 and 80% of the patients in our study
had a G8 score of b14. These results were similar, albeit in the high
range, compared to previous studies on other cancers (67–80%) [14].
With two cut-off values, 38% of patients were included in the low
score group, 43% in the intermediate score group, and 19% in the high
score group in our study.
In a previous retrospective study, Takahashi et al. showed that the
G8 screening tool adds prognostic value to ECOG-PS in older patient
with cancer, with classification into three groups according to two G8
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
0 5 10 15 20 25 30 35 40 45
Months
Abnormal G8 Normal G8
Fig. 1. Overall survival (OS) according to the G8 score (normal or abnormal) in older
patients with glioblastoma patients: Kaplan–Meier analysis of OS in patients with a
normal G8 score (≥14) or abnormal G8 score (b14).
score cut-off values [20]. Other studies also used two cut-offs to improve
identification of at-risk patients [15, 22].
Moreover, the G8 screening tool seems to be suitable for GBM pa-
tients. In cases of hemiplegia, only one of the eight items (“Mobility”)
is distorted. Even in cases of aphasia, all items can fill. For the item
“Self-rated health” (in comparison with people of the same age), the
physician can select the response option of “Unknown.” All other
items are objective and can be completed by a third party. Thus, the
G8 tool can collect a wide range of information on patients and mitigate
most of the problems related to GBM that distort the classical KPS and
ECOG-PS evaluations.
The G8 is a screening tool that has good sensitivity but lacks specific-
ity (64.4%) [13]. Therefore, a modified G8 screening tool was developed
and validated in a French multicenter prospective cohort (ELCAPA co-
hort) [18]. The modified G8 scale includes six rather than eight items:
weight loss, neurocognitive problems, number of medications, self-re-
ported health, PS, and history of heart failure or coronary artery disease.
As G8 score, modified G8 score was not evaluated in glioma or glioblas-
toma patient.
As discussed previously, the “performance status” in modified G8
score is not necessarily relevant for GBM management, and the item
“history of heart failure or coronary artery disease” does not provide im-
portant information. At present, the modified G8 score does not seem
relevant for the management of GBM. Therefore, a prospective study
should be conducted to evaluate the utility of the modified G8 scale in
the management of GBM.
The definition of “older patients” remains problematic, because it
varied among studies validating the G8 scale, and among different stud-
ies in general (with the cut-off ranging from 65 to 70 years) [14]. Sixty-
five years was used as the threshold in one previous review, taking into
account the epidemiology of cancer [23].

Table 2
Univariate and multivariate analyses of overall survival according to normal or abnormal G8 score: univariate and multivariate Cox regression analysis.

Overall survival

Univariate Multivariate

HR (95% CI) p HR (95% CI) p

Age: b80 years vs. N80 years 0.42 (0.21–0.80) 0.0095 0.97 (0.47–2.00) 0.006
Abnormal G8 vs. normal G8 score 8.81 (3.12–24.8) b 0.0001 10.27(3.12–33.28) 0.0001
Resection: yes vs. no 2.36 (1.40–3.97) 0.0012 1.55 (0.85–2.83) 0.15
Chemotherapy: yes vs. no 7.8 (3.95–15.41) b 0.0001 2.98 (1.16–7.28) 0.022
Radiotherapy: yes vs. no 13.1 (5.8–29.5) b 0.0001 4.04 (1.52–10.70) 0.0049

HR: hazard ratio.

162 E. Deluche et al. / Journal of Geriatric Oncology 10 (2019) 159–163

Table 3 resulted in a sensitivity of 94% and specificity of 55% [14]. Therefore,

Univariate and multivariate analyses of overall survival according to G8 score group with the G8 tool seems to be more suitable for screening GBM patients.
two cut-offs: results of univariate and multivariate Cox analysis.
Our study had some limitations. First, this was a retrospective study
Overall survival performed in a single institution. Second, our study was susceptible to
Univariate Multivariate patient selection bias: we did not include patients with an impaired
general condition because no biopsy was performed to make a patho-
HR (95% CI) p HR (95% CI) p
logic diagnosis of GBM and/or the patients were not seen by an oncolo-
Age: b80 years vs. N80 0.42 (0.21–0.80) 0.0095 1.079 0.83
gist and/or a radiation therapist. This accounts for the size of the study
years (0.52–2.20)
Low
population. Moreover, the G8 score was not always available.
vs. intermediate 51.05 0.0008 55.46 b0.0001 Nevertheless, the median OS and patient characteristics were similar
(15.07–172.85) (13.42–229.13) to those reported previously [29]. We were also unable to investigate
vs. high score group 6.34 (2.15–18.5) b0.0001 8.64 0.0005 prognosis according to molecular markers, such as IDH1 mutation, 1p/
(2.56–29.11)
19q codeletion, and 10p/10q codeletion, because they were not rou-
Resection: yes vs. no 2.36 (1.40–3.97) 0.0012 1.13 (0.59–2.14) 0.70
Chemotherapy: yes vs. 7.8 (3.95–15.41) b0.0001 1.72 (0.74–4.03) 0.20 tinely tested for during the study period.
no
Radiotherapy: yes vs. 13.1 (5.8–29.5) b0.0001 3.11 (1.21–8.00) 0.01
4. Conclusion
no

HR: hazard ratio.

In conclusion, the present study indicated that it is possible to eval-
uate older GBM patients using the G8 scale with two cut-off values. This
Since the publication of the 2005 International Society of Geriatric screening tool can be applied quickly and can effectively distinguish
Oncology guidelines (SIOG) [6], various screening tools have been de- healthy and at-risk patients [14].
vised, among which only five were developed specifically for older can- A large-scale prospective study is warranted to further examine the
cer populations. Among these tools, the G8 scale was in the top two with value of the G8 scale score as a prognostic factor for treatment in older
respect to sensitivity [14]. patients with GBM. The ultimate goal is to develop a management sys-
Although the KPS [24, 25] and ECOG-PS are frequently used to clas- tem for older patients according to the following schema: older patients
sify the PS of GBM patients, and have been validated by SIOG, these with a G8 score ≥ 14 should be considered “fit” and receive the same
scales have limitations. treatment as younger patients, while for patients with a score b 14,
ECOG-PS is usually based on the general impression of the clinician the CGA should be applied in a second step and the treatment limited;
rather than the patients themselves. Clinicians evaluate the patient's patients in the intermediate score group (10.5–14) should not automat-
symptoms and capacity to care for themselves and work, which consti- ically be excluded from standard treatment, and adjuvant chemother-
tutes a subjective evaluation [26, 27]. A previous study comparing the apy and/or radiotherapy may be considered. Finally, patients with a
ECOG-PS recorded by patients, oncologists, and nurses showed signifi- score of b10.5 should be considered “unfit” and palliative care
cant differences between these three groups (p b .001), with oncologists considered.
giving the highest (i.e., healthiest) ECOG-PS assessment score and pa- Supplementary data to this article can be found online at https://doi.
tients the poorest [28]. org/10.1016/j.jgo.2018.07.002.
Moreover, the KPS and ECOG-PS do not adequately describe the
functional status of GBM patients. For example, in the case of hemiplegic
Conflict of Interest Statement
and wheelchair-dependent glioma patients, the KPS score will be low
even if the patient has no symptoms and works full time. In addition,
The authors declare that there are no conflicts of interest.
these instruments are not the optimal screening tools for older patients.
For example, compared to the CGA, the KPS had sensitivity and specific-
ity values of 29% and 44%, respectively, for a cut-off value of b80 years Authorship
used to define older patients [14]; this cut-off varies among studies,
from 50 to 80 years [9–11]. The ECOG-PS cut-off used in one study ED and FL collected clinical data. ED, SL and NTM analyzed the data.
ED wrote the manuscript. All authors contributed to the manuscript,
Overall survival critically revised the manuscript, and approved the final version.
1
0.9 Acknowledgment
0.8
0.7 We thank Textcheck for their assistance with editing the language of
0.6 this manuscript. The English in this document has been checked by at
0.5 least two professional editors, both native speakers of English. For a cer-
0.4 tificate, please see: http://www.textcheck.com/certificate/1RWya6
0.3
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