Prognostic value of health-related quality of life for overall survival in elderly non-small-cell lung cancer patients

doi:10.1016/j.ejca.2015.10.004

European Journal of Cancer

Volume 52, January 2016, Pages 120-128

https://doi.org/10.1016/j.ejca.2015.10.004 Get rights and content

Highlights

•
We investigated whether the health-related quality of life score is a prognostic factor for overall survival (OS) in elderly patients with advanced NSCLC.
•
Global health status (GH) dimension score at baseline was associated with favourable OS when adjusted for clinical, functional, and histological factors.
•
We distinguished three groups according to GH score: high (GH <46), intermediate (46 ≤GH ≤67), and low (GH >67) mortality risk.
•
Subgroup analyses suggested the baseline GH score to be a predictor of treatment effect.

Abstract

Background

We investigated whether the health-related quality of life (HRQoL) score is a prognostic factor for overall survival (OS) in elderly patients with advanced non-small-cell lung cancer (NSCLC).

Methods

We included 451 NSCLC patients aged 70–89 years enrolled in the Intergroupe Francophone de Cancérologie Thoracique 0501 trial, using scores of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 at baseline to investigate the prognostic value of HRQoL for OS, in addition to conventional factors. Cox regression model was used for both univariate and multivariate analyses of OS.

Results

Global health status (GH) dimension score at baseline was associated with favourable OS when adjusted for clinical, functional, and histological factors (hazard ratio [HR]: 0.986; 95% confidence interval [CI]: 0.980–0.992).

We distinguished three groups according to GH score: high (GH <46), intermediate (46 ≤GH ≤67), and low (GH >67) mortality risk. The median OS values were 14.5, 8.2, and 5.3 months in the low-, intermediate-, and high-risk categories, respectively (log-rank P <0.0001).

In the high-risk group, doublet chemotherapy was not associated with favourable OS (HR: 0.70; 95% CI: 0.49–1.003; P=0.052), whereas in the intermediate- and low-risk groups, doublet chemotherapy was associated with favourable OS (HR: 0.72; 95% CI: 0.54–0.96; P=0.023 and HR: 0.50; 95% CI: 0.30–0.84; P=0.0089, respectively).

Conclusion

This study supports the additional prognostic value of HRQoL data at diagnosis to identify vulnerable subpopulations in elderly NSCLC patients. HRQoL could thus be valuable in selecting patients who will benefit from doublet chemotherapy.

Section snippets

Background

The number of studies using health-related quality of life (HRQoL) assessment has been growing over the last decade. The Food and Drug Administration considers HRQoL to be an end-point for assessing direct clinical benefits for the patient [1], [2], [3]. Moreover, there has been evidence to suggest that assessing baseline HRQoL dimension scores in cancer patients improves the prediction of overall survival (OS) [4], [5], [6], [7], [8], [9]. Quinten et al. carried out a meta-analysis involving

Sample

The IFCT 0501 study design has been previously described [14]. Patients aged 70–89 years with stage IV NSCLC or stage III unsuitable for radical radiation therapy and performance status (PS) ≤2 were eligible for this phase III trial. They were randomly assigned 1:1 to four 28-day cycles of monthly carboplatin plus weekly paclitaxel or five 21-day cycles of single agent vinorelbine or gemcitabine, on days 1 and 8 of each cycle. Patients were stratified by centre, World Health Organization (WHO)

Study population

Between April 2006 and December 2009, 451 patients were enrolled. The number of patients who completed the entire questionnaire at baseline was 361 (80.04%), the number of available questionnaires (i.e. with at least one QoL score that could be calculated) being 421 (93.3%). At baseline, the patients who completed the entire QoL questionnaire and those who did not were found to display similar clinical characteristics (Table 1). The baseline HRQoL scores for each dimension have been presented

Discussion

To our knowledge, this is the first analysis of HRQoL data derived from the EORTC QLQ-C30 questionnaire as prognostic markers of OS in elderly advanced NSCLC patients. Based on our data, the GH dimension score provided significant value in addition to PS, treatment type, smoking status, histology, and both ADL and MMS scores.

This is in line with other studies investigating HRQoL in NSCLC patients [6], [14], [15], [16]. Sloan et al. [12] and Jacot et al. [13] demonstrated that overall HRQoL

Conflict of interest statement

Frédéric Fiteni declares no conflict of interest. Dewi Vernerey declares no conflict of interest. Franck Bonnetain reports grants and personal fees from ROCHE, grants, personal fees and non-financial support from NOVARTIS, personal fees from MERCK SERONO, and personal fees from NESTLE. Fabien Vaylet declares no conflict of interest. Hélène Sennelart declares no conflict of interest. Jean Tredaniel declares no conflict of interest. Denis Moro-Sibilot declares participation to Roche, Eli Lilly,

Funding

Funding was received from Ligue Contre Le Cancer and Intergroupe Francophone de Cancérologie Thoracique.

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This study aimed to describe quality of life (QoL) five years after diagnosis, in a representative sample of lung cancer (LC) survivors, to compare the QoL of survivors aged 70 years or older with that of younger ones, and to identify factors associated with poorer long-term QoL in both age groups.
Our study sample consists of all individuals with a LC diagnosed between January 2010 and December 2011, who participated in the French national survey VICAN 5.
A total of 371 participants had LC. At the time of the survey, 21.3% of the participants were 70 years or older. In this older age group, feeling self-conscious about appearance and suspected neuropathic pain were independently associated with physical QoL impairment and lower Post-Traumatic Growth Inventory score, and suspected neuropathic pain was associated with impaired mental QoL. In younger patients, impaired physical QoL was independently associated with male gender, metastatic cancer, suspected neuropathic pain, report of severe after-effects of LC and difficulty breathing at rest in the past 7 days, and impaired mental QoL was independently associated with male gender, impaired ECOG-PS, and anxiety.
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It is worth noting that the characterisation of symptom clusters often focuses on patient symptoms and seldom incorporates other aspects of HRQoL that cover patients' functioning abilities, which are equally important in managing patients with cancer [15]. HRQoL indicators, such as physical, emotional, social, cognitive and role functioning, have also been shown to be inter-related and to be correlated with various symptom scales (e.g. physical-functioning vs pain), as well as being predictive of survival in cancer clinical trials [13,14]. This reiterates the need to have a more holistic picture of the interrelationships among the various HRQoL indicators, which will better inform our choices on effective patient management strategies.
The European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) measures 15 health-related quality of life (HRQoL) scales relevant to the disease and treatment of patients with cancer. A study by Martinelli (2011) demonstrated that these scales could be grouped into three main clusters: physical, psychological and gastrointestinal. This study aims to validate Martinelli's findings in an independent dataset and evaluate whether these clusters are consistent across cancer types and patient characteristics.
Pre-defined criteria for successful validation were three main clusters should emerge with a minimum R-squared value of 0.51 using pooled baseline-data. A cluster analysis was performed on the 15 QLQ-C30 HRQoL-scales in the overall dataset, as well as by cancer type and selected patient characteristics to examine the robustness of the results.
The dataset consisted of 20,066 patients pooled across 17 cancer types. Overall, three main clusters were identified (R² = 0.61); physical-cluster included role-functioning, physical-functioning, social-functioning, fatigue, pain, and global-health status; psychological-cluster included emotional-functioning, cognitive-functioning, and insomnia; gastro-intestinal-cluster included nausea/vomiting and appetite loss. The results were consistent across different levels of disease severity, socio-demographic and clinical characteristics with minor variations by cancer type. Global-health status was found to be strongly linked to the scales included in the physical-functioning-related cluster.
This study successfully validated prior findings by Martinelli (2011): the QLQ-C30 scales are interrelated and can be grouped into three main clusters. Knowing how these multidimensional HRQoL scales are related to each other can help clinicians and patients with cancer in managing symptom burden, guide policymakers in defining social-support plans and inform selection of HRQoL scales in future clinical trials.
Clinimetrics: The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire
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Modifiable factors associated with health-related quality of life among lung cancer survivors following curative intent therapy
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Rehabilitation services may also need to be remotely-delivered to overcome barriers in access, uptake, and completion [102], particularly during global viral (e.g., COVID-19) pandemics that require social distancing. Additional novel and important contributions of our study are: 1) inclusion of patients who underwent radio/-ablation therapy for stage I lung cancer, a growing patient population given advances in radio/-ablation techniques and often excluded from studies that examined posttreatment lung cancer survivorship issues; 2) focus on individual functional impairments and symptoms that are potentially modifiable with identified effect sizes that have been suggested to be clinically meaningful in patients with lung cancer [80], met multiple statistical significance thresholds, and therefore should be targeted in interventions to improve the HRQL of lung cancer survivors following curative intent therapy; 3) comorbidities defined individually (and not combined as a total sum), which has important implications in the clinical setting to improve control of specific comorbidities (e.g., OSA); 4) HRQL defined with a highly prognostic measure [55–58]; and 5) being (to the best of our knowledge) among the first study to identify factors that explain most (>50%) of the variance in HRQL, enhancing clinical translation. Despite a thorough list of factors examined, we did not have information on spirituality [103] or stigma [104], important factors associated with HRQL in patients with lung cancer; or disease-/progression-free survival, an important patient-relevant (and clinical) endpoint [105].
The number of lung cancer survivors is increasing along with advances in screening, diagnosis, and treatment. Following curative intent therapy, many lung cancer survivors experience significant health-related quality of life (HRQL) impairments. We sought to identify potentially modifiable factors that contribute to the HRQL of these patients.
In this cross-sectional observational study of disease-free, stage I-IIIA lung cancer survivors following curative intent therapy, we used a conceptual model to examine factors that included behavioral, objective functional and physiologic, self-rated function and symptom burden, specific comorbidities, and non-modifiable demographic and clinical lung cancer-related characteristics. We assessed HRQL using the valid and prognostic European Organization for Research and Treatment of Cancer Quality of Life (QoL) Core 30 global health/QoL subscale. We used univariable and multivariable linear regression modeling with backward elimination of potentially modifiable and non-modifiable factors, and interpreted clinically and statistically significant, consistent, and independent modifiable factors as meaningful.
Among 75 participants at a median of 12 months since treatment completion, the mean (standard deviation) C30 global health/QoL score was 62.7 (23.3) points (0–100 scale range). In multivariable analysis, with and without non-modifiable factors, we identified three clinically and statistically significant, consistent, and independent factors (unstandardized β range) associated with global health/QoL: 1) abnormal exercise-induced dyspnea (−9.23 to −10.0 points); 2) impaired self-rated role function (or inability to perform work or daily activities and pursuing leisure-time activities) (−12.6 to −16.4 points); and 3) abnormal insomnia (or trouble sleeping) (−12.6 to −16.4 points).
We identified meaningful modifiable factors associated with the HRQL of disease-free, stage I-IIIA lung cancer survivors following curative intent therapy. Interventions to improve the HRQL of these patients should aim to reduce exercise-induced dyspnea, improve role function – the ability to perform work and other daily including leisure-time activities, and control insomnia.
Impact of health-related quality of life (HRQoL) on short-term mortality in patients with recurrent ovarian, fallopian or peritoneal carcinoma (the NOGGO-AGO QoL Prognosis-Score-Study): results of a meta-analysis in 2209 patients
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Social epidemiological studies in the 1980s showed that self-reported health or health-related quality of life (HRQoL) variables have independent prognostic power for survival.6,7 This could also be shown for several groups of patients including cancer patients.8-11 In a review, almost all studies of different cancer types showed a significant relation of HRQoL variables with survival.
Recurrent ovarian cancer is an incurable disease with variable but poor prognosis. Health-related quality of life (HRQoL) is a patient-reported outcome measure generally applied to measure effects of therapies. Our aim was the development and validation of a risk score for the prediction of short-term mortality using the combination of sociodemographic and clinical factors and HRQoL.
For exploratory and validation analysis, the North-Eastern German Society of Gynecological Oncology (NOGGO) and Working Group Gynecological Oncology (AGO) study databases were screened for trials. Only trials which obtained defined HRQoL measurements were included in the final analysis. Multivariable logistic regression analyses were used to identify risk factors and their weighting for the risk score. Modulation with cubic regression analyses revealed median survival and short-term mortality defined as 1-year mortality for each value.
For exploration, 974 patients from three clinical studies of the NOGGO and for validation, 1235 patients from several clinical studies of the AGO were eligible. The risk score included platinum-free interval, performance status, age, global QoL and nausea/vomiting. Receiver operating characteristic analysis showed a good predictive value with an area under the curve of 0.81 for model 1 in the exploration and 0.74 in the validation. Short-term mortality in model 1 was 8.2%, 23.5% and 58.4% in the exploration sample, and 19.7%, 38.1% and 63.4% in the validation sample for patients under low, medium and high risk, respectively.
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We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement when reporting our study.20 Of the 1724 records screened, 138 studies including 158 127 patients with cancer met the inclusion criteria.21-156 The identification and selection of the studies included in this review is reported in a Preferred Reporting Items for Systematic Reviews and Meta-Analysis flowchart (see Appendix 2 in Supplemental Materials found at https://doi.org/10.1016/j.jval.2020.10.017).
Assessment of patient-reported outcomes (PROs) in oncology is of critical importance because it provides unique information that may also predict clinical outcomes.
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Eligibility criteria selected 138 studies including 158 127 patients, of which 43 studies were randomized, controlled trials. Overall, 120 (87%) studies reported at least 1 PRO to be statistically significantly prognostic for overall survival. Lung (n = 41, 29.7%) and genitourinary (n = 27, 19.6%) cancers were most commonly investigated. The prognostic value of PROs was investigated in secondary data analyses in 101 (73.2%) studies. The EORTC QLQ-C30 questionnaire was the most frequently used measure, and its physical functioning scale (range 0-100) the most frequent independent prognostic PRO, with a pooled hazard ratio estimate of 0.88 per 10-point increase (95% CI 0.84-0.92).
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¹: Shared authorship.

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Original ResearchPrognostic value of health-related quality of life for overall survival in elderly non-small-cell lung cancer patients

Highlights

Abstract

Background

Methods

Results

Conclusion

Section snippets

Background

Sample

Study population

Discussion

Conflict of interest statement

Funding

J Visc Surg

Eur J Cancer

Eur J Cancer

Lancet Oncol

Ann Oncol

Ann Oncol

Lancet

Quality-of-life end points in cancer clinical trials: the U.S. food and drug administration perspective

J Natl Cancer Inst Monogr

Food and drug administration requirements for approval of new anticancer drugs

Cancer Treat Rep

Quality of life data as prognostic indicators of survival in cancer patients: an overview of the literature from 1982 to 2008

Health Qual Life Outcomes

Early change in patient-reported health during lung cancer chemotherapy predicts clinical outcomes beyond those predicted by baseline report: results from Eastern Cooperative Oncology Group Study 5592

J Clin Oncol

Original Research
Prognostic value of health-related quality of life for overall survival in elderly non-small-cell lung cancer patients