The performance of three oncogeriatric screening tools - G8, optimised G8 and CARG - in predicting chemotherapy-related toxicity in older patients with cancer. A prospective clinical study

doi:10.1016/j.jgo.2019.04.004

Journal of Geriatric Oncology

Volume 10, Issue 6, November 2019, Pages 937-943

https://doi.org/10.1016/j.jgo.2019.04.004 Get rights and content

Abstract

Background

Older patients are vulnerable to chemotherapy-related toxicity (CRT). Therefore we evaluated screening tools in their power to predict CRT.

Methods

Patients with cancer aged ≥65 years completed three screening questionnaires (G8, optimised G8 and Cancer and Ageing Research Group (CARG). Additionally, Comprehensive geriatric assessment (CGA) for verification of supportive care needs was undertaken on patients with impaired G8 scores. During chemotherapy treatment patients were assessed, capturing grade 0–5 CRT as defined by NCI CTCAE 4.

Results

104 patients with non-haematological cancers were included at three study sites. Median age was 73 years (range 65–85). Onco-geriatric screening detected 74% as impaired using G8 and optimised G8 questionnaires and 86% using CARG screening. Grade 3–5 toxicity affected 64.4% of all patients. G8 (OR 0.3 95% CI [0.1;1.0]) and optimised G8 (OR 0.4 95% CI [0.1; 1.5]) did not reliably predict CRT, whereas screening with CARG demonstrated a strong prediction of severe CRT: OR 4.2, 95% CI [1.1, 15.9]. CGA was undertaken on 66 patients, revealing deficiencies in nutritional (83%) and functional-status (54%) and occurrence of relevant comorbidity (53%).

Conclusion

The CARG tool could be useful for predicting CRT. CGA showed clinically relevant supportive care needs in patients with a positive G8 screening.

Section snippets

Background

Cancer is a growing public health concern and a leading cause of morbidity and mortality, particularly among older adults. Worldwide, the proportion of people aged 60 years and older will almost double by 2050, rising from 12% to 22% [1]. Approximately 60% of all cancer types and 70% of overall cancer mortality occur in adults aged 65 years and older [2]. Chemotherapy continues to be a key component in cancer therapy, and has been found to benefit older patients with cancer [3,4]. Nevertheless,

Materials and Methods

This prospective observational study was initiated and recruited patients at three study institutions in Leipzig, Germany: University Cancer Center Leipzig (UCCL, central outpatient chemotherapy unit); Department of Radiation Oncology and Radiotherapy, University Hospital Leipzig (inpatients); Department of Haematology and Oncology, St. Georg Hospital Leipzig (inpatients). 116 patients were recruited from August 2016 to June 2017. Eligible patients were 65 years or older, had a diagnosis of

Baseline Characteristics (Table 1)

116 patients were initially eligible for the study. 12 patients did not receive any chemo (radio) therapy after study inclusion. Therefore, analyses were restricted to 104 treated study patients. Baseline characteristics are presented in Table 1. The average age of participants was 73.0 ± 4.82 (range 65–85) years.

72% of participants received polychemotherapy treatment regimens, 81% received standard dose, 69.2% received a platinum-containing chemotherapy and 68% received first-line treatment

Discussion

This study investigated the performance of G8, optimised G8, and CARG questionnaires in predicting CRT in older patients with non-haematological cancers. Additionally, it provided an in-depth analysis of physical, functional, psychological and social factors determining the medical condition of G8-identified frail patients, using the CGA.

When examining the results, we first discovered that CRT was common in the majority of patients, with >90% of participants experiencing at least one ‘grade

Conclusion

The CARG questionnaire yielded strong predictive performance and can be recommended as a supporting tool in the decision making process for or against chemotherapy and the choice of the appropriate regimen. G8 and optimised G8 did not sufficiently predict CRT in our study population. However, they showed good performance in identifying frail patients in a two-step approach and can be used in clinical practice, ideally followed by geriatric interventions where indicated.

Disclosure Statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. I confirm that all authors have made a significant contribution to this manuscript, have seen and approved the final manuscript, and agree to its submission to the Journal of Geriatric Oncology. In addition, I confirm that all authors have provided their disclosures to the corresponding author and that these are recorded.

Acknowledgments

This work was supported by a grant from the German Society of Haematology and Oncology (DGHO e.V.) and Dr. Werner Jackstädt society to D.K. We thank all patients, their families and study teams at all sites for participating and contributing to the study.

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Predictors and effects of toxicity experienced by older adults with cancer receiving systemic therapy in a randomized clinical trial of geriatric assessment
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Older adults represent a large segment of the oncology population, however, they remain underrepresented in clinical research. Treatment of older adults is often extrapolated using data from younger and fitter patients, which may not be appropriate. Furthermore the implications of toxicity from treatment can be greater for this population. Predicting toxicity from treatment and its effect on quality of life and functional status for older adults therefore is important.
We analyzed data from a clinical trial of geriatric assessment and management for Canadian elders with cancer (5C study). We assessed whether the baseline Cancer and Aging Research Group (CARG) toxicity score, G8 score, and Eastern Cooperative Oncology Group (ECOG) performance predicted grade 3–5 toxicity using logistic regression and pattern mixture models. We also assessed the impact of toxicity on quality of life and functional decline. Patients were followed for six months.
Three hundred sixteen patients were included. Mean age was 76 years old and 40% of patients were female. One hundred nineteen patients (38%) experienced at least one grade 3–5 toxicity. Neither the CARG toxicity score, G8, or ECOG were predictive of grade 3–5 toxicity. Patients who experienced grade 3–5 toxicity were more likely to have functional impairments over time (odds ratio 3.71, p = 0.03). However, they maintained their quality of life.
In this secondary analysis of a randomized controlled trial of geriatric assessment and management we did not find any predictors of grade 3–5 toxicity. Patients who did experience toxicity were more likely to report functional decline over time. Older adults who do experience treatment related toxicity may benefit from increased supports.
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Other studies are investigating whether the addition of a perioperative exercise regimen to neoadjuvant chemotherapy (ChT) improves outcomes.41 Geriatric screening and assessment may help to identify patients who need additional support and/or are at increased risk of ChT-associated side-effects.42 Multidisciplinary assessment and planning of treatment are mandatory.
Prospective comparison of the value of CARG, G8, and VES-13 toxicity tools in predicting chemotherapy-related toxicity in older Turkish patients with cancer
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Chan et al. evaluated the performance of G8 and CARG, and concluded that both questionnaires demonstrated a weak prediction of severe CRT in older Chinese patients with cancer [6]. Unlike the Kotzerke et al. and Chan et al. studies, which included patients with gastrointestinal/digestive malignancies rate at 54.8% and 54.1%, respectively, the fact that G8 was predictive for CRT in our study may be attributed to the lower number (28.8%) of patients with gastrointestinal system/digestive malignancy [6,21]. Since many items of the G8 screening tool cover nutritional issues, studying patients with gastrointestinal malignancies may affect the results of studies.
In older patients with cancer, it is very important to choose the appropriate treatment because they are at high risk for chemotherapy toxicity. Our study investigated characteristics of Cancer and Aging Research Group (CARG), Geriatric 8 (G8), and Vulnerable Elders Survey (VES-13) screening tools for predicting chemotherapy-related toxicity (CRT) prospectively.
208 patients aged ≥65 years old for whom chemotherapy was planned to treat non-haematological cancer between February 2021–September 2021 were included in the study. The CARG, G8, and VES-13 toxicity tools were completed by the oncologist through face-to-face interviews before starting the first chemotherapy treatment. CRTs during chemotherapy were evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events v4.03. Logistic regression models, the area under the receiver operating characteristic curve (ROC-AUC), and correlation analyses were used for comparing questionnaires.
Median age was 70.4 (range 65–86) years. Of the participants, 103 (49.5%) participants experienced grade 3–5 CRT (32.2% haematological, 28.4% non-haematological) during chemotherapy. ROC-AUC value of CARG was determined as 0.827 (95% CI [confidence interval]: 0.77–0.88, p < 0.001), it was determined as 0.744 (95% CI: 0.68–0.81, p < 0.001) for G8 and 0.726 (95% CI: 0.66–0.80, p < 0.001) for VES-13. In the univariate regression analysis, CARG (OR [odds ratio] = 13.57, 95% CI: 6.0–30.72, p < 0.001), G8 (OR = 3.19, 95% CI: 1.62–6.29, p = 0.001), and VES-13 (OR = 9.5, 95% CI: 5.01–17.89, p < 0.001) were found to be predictive for CRT. The multivariate analysis (included stage, Eastern Cooperative Oncology Group [ECOG] performance status, presence of comorbid disease, platinum-based treatment regimen, taxane-based treatment regimen, CARG, VES-13, G8) showed that CARG (OR = 12.08, 95% CI: 5.11–28.56, p < 0.001), VES-13 (OR = 10.06, 95% CI: 4.92–22.98, p < 0.001), and G8 (OR = 2.20, 95% CI: 1.04–4.69, p = 0.040) screening tools were strong predictors for CRT. The CARG and VES-13 questionnaires were predictive for reducing the initial treatment dose (p = 0.004, p = 0.004, respectively), interruption of treatment (p < 0.001, p < 0.001, respectively), discontinuing treatment (p = 0.002, p = 0.002, respectively), and unexpected hospitalisation (p = 0.012, p = 0.003, respectively).
We showed that all three CARG, G8, and VES-13 questionnaires are helpful tools in the decision-making process for ideal chemotherapy to predict severe CRT; however, CARG and VES-13 questionnaires appear more useful in daily oncology practice than the G8 questionnaire.
The predictive value of G8 and the Cancer and aging research group chemotherapy toxicity tool in treatment-related toxicity in older Chinese patients with cancer
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One explanation for this could be that 56.3% of the patients in our study had severe TRT. The differences in patient cohort (no hematologic malignancies, more patients received treatment with dose reduction and monotherapies) might explain why overall incidence in our study was lower compared with similar studies with an incidence of 61–81% [18,19]. In our daily practice, the systemic treatment and regimen doses were decided on and modified according to physicians' judgments, and a significant proportion of patients receiving chemotherapy (46.7%) had a dose reduction from the first cycle.
Older patients experience a higher risk of treatment-related toxicity (TRT). The G8 screening tool was developed to separate cancer older patients fit to receive standard treatment from those who are frail and experiencing functional decline due to reduced organ function and multiple comorbidities. The Cancer and Aging Research Group chemotherapy toxicity tool (CARG-tt) questionnaire was developed to predict chemotherapy toxicity in geriatric patients. This prospective observational study evaluated the performance of G8 and CARG-tt in predicting severe TRT in older Chinese cancer patients.
Chinese patients aged ≥65 with a diagnosis of solid malignancy and scheduled to receive anti-cancer treatment (chemotherapy or targeted therapy) were enrolled from March 2016 to July 2017 at the Department of Clinical Oncology at Queen Mary Hospital in Hong Kong. All patients completed the G8 and CARG-tt screening and pre-treatment assessments before starting treatment. Patients were monitored for any severe TRT, which was defined by grades 3–5 using the National Cancer Institute's Common Terminology Criteria for Adverse Events v4.03, treatment discontinuation, or unexpected hospitalization from starting to 30 days after treatment.
A total of 259 patients (male: 154, 59.5%; median age: 73.4, age range: 65–93) were enrolled in the study. Two hundred and ten (81.1%) patients received chemotherapy while the rest (n = 49, 18.9%) received targeted therapy. Overall, 146 patients (56.8%) experienced severe TRT.
The mean G8 score was 12.4 (SD: 2.8). The G8 score had a significant association with unexpected admission (cutoff: 14, 41.3% vs. 26.5%, p = 0.03) but not significant in other types of TRTs. The mean CARG-tt score was 7.67 (SD: 3.7); it was not associated with severe TRTs.
The G8 and CARG-tt demonstrated a weak prediction of severe TRT in older Chinese cancer patients. Future studies need to develop predictive tools for TRT in patients receiving novel antineoplastic therapies, with a focus on subgroup analysis for different populations.
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The performance of three oncogeriatric screening tools - G8, optimised G8 and CARG - in predicting chemotherapy-related toxicity in older patients with cancer. A prospective clinical study

Abstract

Background

Methods

Results

Conclusion

Section snippets

Background

Materials and Methods

Baseline Characteristics (Table 1)

Discussion

Conclusion

Disclosure Statement

Acknowledgments

Ann Oncol

Lancet Oncol [Internet]

J Geriatr Oncol [Internet]

J Geriatr Oncol [Internet]

J Geriatr Oncol [Internet]

Ann Oncol

Ann Oncol

Eur J Cancer

J Chronic Dis

Ageing and health

Media Cent [Internet]

A pooled analysis of adjuvant chemotherapy for resected Colon Cancer in elderly patients

N Engl J Med [Internet]

Toxicity of older and younger patients treated with adjuvant chemotherapy for node-positive breast cancer: the Cancer and Leukemia Group B experience

J Clin Oncol

JR AK. Underrepresentation of patients 65 years of age or older in cancer-treatment trials

N Engl J Med

Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration

J Clin Oncol

Under-representation of older adults in cancer registration trials: known problem, little progress

J Clin Oncol

Role of age and health in treatment recommendations for older adults with breast cancer: the perspective of oncologists and primary care providers

J Clin Oncol

Basic assessment of the older cancer patient

Curr Treat Options Oncol

Screening for a geriatric risk profile in older cancer patients: a comparative study of the predictive validity of three screening tools

Crit Rev Oncol Hematol [Internet]