Comparison of mood disorder screening scales in geriatric oncology: THYMOG study results CURRENT STATUS: POSTED

Background: Early and systematic depression screening is recommended for older patients with cancer. The objective of this study is to evaluate the performance of three different mood disorder screening scales for detection of Major Depressive Disorder (MDD) in older patients with cancer. Methods: A prospective multicentric study was conducted in patients with cancer over 70 years of age, comparing three self-administered questionnaires: the 15-item Geriatric Depression Scale (GDS-15), the Hospital Anxiety and Depression Scale - Depression (HADS-D) and the Distress Thermometer (DT). Three weeks after initial assessment, in case of score above the standard cut-off, a reassessment of the patient’s mood was performed by the primary care physician, using the DSM-V MDD diagnostic criteria and the DT. Potential differences between an abnormal mood screening test and a confirmed MDD was assessed using variance analysis for each screening scale. Results: 93 patients with an average age of 81 years [70 - 95 years] were included. 66 patients had at least one abnormal score on one of the screening scales. A MDD was confirmed for 10 of the 36 reassessed patients (28%). Abnormal screening by the GDS-15 (p=0.021), the HADS-D (p=0.018) and the DT (p=0.045) was significantly associated with MDD diagnosis. Conclusions: The three screening scales enabled detection of MDD in older patients with cancer. Among the tested scales, the HADS-D could perform best in detecting MDD. However, these screening scales may not be sufficiently reliable for MDD screening in this population. Further studies are needed to confirm the results.

with ageing [1]. Approximately 30% of all cancers occur in patients aged 75 years and older and nearly 7% in patients aged 85 years and older [2][3][4]. Considering the actual ageing of the population [5][6], estimations show that by 2050, one in two cancers will occur in people over the age of 75 [1,3,7].
Depression is the most commonly encountered psychiatric pathology in geriatric and cancer patient populations [8,11]. The estimated depression prevalence in older patients with cancer is approximately between 3% to 31% depending on the depression criteria and the cancer type [12][13][14][15]. However, depression is often under-diagnosed in older patients since the clinical presentation can differ from the younger population (more physical symptoms, fewer psychological symptoms) [16][17][18][19][20]. Clinicians can also attribute somatic signs of depression to usual ageing or miss nonspecific symptoms such as asthenia, weight loss, sleep disorders or sexual desire disorders [16][17][18][19][20]. It is estimated that 60 to 70% of depressive disorders in older patients are underdiagnosed or undertreated [9,18].
Yet, this geriatric syndrome has a significant impact on patient survival, risk of suicide, morbidity, quality of life, therapeutic management and health care costs [9,15,19,21]. have not been specifically validated among older patients with cancer [15]. Despite the existing screening recommendations from health authorities and clinical practice guidelines, there is no consensus on the choice of a specific mood disorder screening scale to use in this population. Consequently, there is a heterogeneity of practice and a risk of under diagnosis depression in this older population.
The objective of this study is to evaluate the performance of three mood disorder screening scales frequently used in geriatric oncology (GDS-15, HADS-D and DT) by comparing their level of agreement with the Diagnostic Statistical Manual of Mental Disorders -version V (DSM-V) [24] for major depressive disorder (MDD) diagnostic criteria in older patients with cancer or haematological malignancy. The relationships between the presence of mood disorders and various medical, psychological and socio-environmental factors were also studied.

Study Protocol
A prospective, multicentric, non-randomized and observational study was conducted in France between January 2016 and August 2017 in a University Hospital Center, a Regional Cancer Center and a General Hospital.
Patients who were at least 70 years of age, were fluent in French, hospitalized or outpatients, who had a confirmed diagnosis (new diagnosis, relapse or progression) of cancer or haematological malignancy which had been detected within the last month were eligible. Patients who were unable to answer questionnaires were not eligible for the study.
Before inclusion, each patient received an information note and their consent for participation was collected.
The study protocol was approved by institutional review boards and ethics committees (clinical trials: RCB 2015-A00836-43).
Data Collection of medical, psychological and socio-environmental factors After obtaining consent, the following data was collected from patient and medical record:

Mood Disorder Screening
During the initial assessment, each patient included completed three self-administered questionnaires: the GDS-15, the HADS-D and the DT.
When patients obtained a score above the standard cut-off on one of the scales (GDS-15: score 5/15 [25,26], HADS-D: score 11/21 (cut-off indicated by Zigmond as to be used for research) [27], DT: score 4/10 [28]), a psychological consultation was suggested. Patients were also informed that they needed to consult their primary care physician within the next three weeks so their mood could be reassessed.

Diagnostic Reassessment
In the event of a score above the standard cut-off on one of the scales, the patient's primary care physician was contacted both by telephone and mail. He was informed of the need to reassess the patient's mood within three weeks to confirm or refute the diagnosis of a MDD (symptoms must be present for at least two weeks according to DSM-V diagnostic criteria [24]).
Mood reassessment consisted of MDD screening according to the DSM-V diagnostic criteria and completion of a DT. The DT score was chosen for the reassessment because of its fast completion for the primary care physician unlike the other tests.
Documents sent by mail to the primary care physician included the study synopsis, a table compiling the DSM-V diagnostic criteria for MDD, a DT and a pre-stamped envelope so the reassessment could be easily sent.
Four weeks after inclusion, if no postal response was returned, the primary care physician was contacted again by the investigator. Primary care physician or patient refusal to participate or patient death was recorded.

Statistical analysis
The study protocol was validated by a statistical methodologist from the Biostatistics and The relationships between medical, psychological and socio-environmental factors and the presence of a MDD and a positive screening for mood disorders, were analyzed by a Chisquared test or a Fischer exact test.
Pearson correlation coefficient was used to assess links between the DT scores obtained during initial assessment and during the primary care physician's reassessment.
Patients with missing data were not included in the statistical analysis.
The results were considered statistically significant if p value was < 0.05.  The data for each measurement for the different screening scales are shown in Table 2 prospective studies carried out in geriatric oncology [29][30][31]. Indeed, the sociodemographic characteristics of the population in our study, such as average age, living place and marital status are comparable to those found in studies by Kenis et al [29], Soubeyran et al. [30]and in the ELCAPA study [31]. Moreover, it is worth highlighting the fact that the functional status for basic daily living activities among our population is similar to that of the ELCAPA cohort (ADL ≤ 5: 29% as against31.5%) [31]. The general health status of the two populations was also comparable (PS ≥ 2: 52.7% as against49.9%) [31] in contrast to that in studies by Kenis

GDS-15 is currently the most widely-used screening tool for detecting depression in older
patients. According to a meta-analysis carried out by Wancata et al. [32] it is 80% sensitive and 75% specific. In 2017, Saracino et al. [33]  HADS is a scale designed to exclude any items relating to somatic aspects [27]. Among the general population it is reportedly 50% sensitive and 97% specific [27]. In two studies carried out among older patients with cancer, Rhondali et al. [20]and Saracino et al. [33]found for the HADS-D respectively sensitivities of 50% and 17% and specificities of 67% and 93%. In Saracino's study [33] These results show an important heterogeneity regarding to the properties of the two scales. The absence of consensus regarding clinical cut-off for diagnosis may partly explain these discrepancies. Furthermore, the statistical performance of these two selfadministered questionnaires appears disappointing. Indeed, a sensitivity of at least 80% and a specificity of at least 70% are considered necessary for depression screening in geriatric oncology [33]. This lack of sensitivity could expose older patients with cancer to a significant risk of under-diagnosis which could lead to an increase in the risk of suicide and morbidity/mortality. On the other hand, the lack of specificity could expose patients to over-diagnosis and a consequent risk of emotional breakdown and inappropriate medication prescriptions [33].
Beyond these statistical considerations, some of the questions included in these screening scales may seem inappropriate for older patients with cancer and could be misinterpreted in the context of a recent cancer diagnosis. For examples "Do you feel that your situation is hopeless?" or "Do you feel full of energy?" in the GDS-15 [25][26] or the statement "I get a sort of frightened feeling as if something awful is about to happen" in the HADS-D [27]. Such statements could draw the newly diagnosed cancer patient to focus on potentially negative experiences to come, as well as exacerbate anxiety or depression.
Nevertheless, Rhondali et al. highlighted the potential usefulness of these screening tools in older patients with cancer [20]. Despite wide variations in performance, the different self-administered questionnaires in this study (specifically the GDS, the HADS and the DT) identified several MDD undiagnosed during the standard clinical oncological consultation.
In our study, analysis of ROC curves and positive likelihood ratios underlined that the HADS-D was the most effective screening tool for detecting a MDD.
DT was designed for quick identification of individuals at risk of mood disorders (the time required for the test is less than one minute) [34]. Its use in patients with cancer is currently recommended by The National Comprehensive Cancer Network (NCCN) [35] [37][38][39][40]. In contrast to these studies, we did not find any statistically significant association between the medical, Beyond the specific use of these screening tools, it seems of critical importance to call for depression in older patients with cancer to be recognized using a global, multidimensional and multidisciplinary approach, in which psychologists also play a role. Moreover, the fact that a majority of patients refuse the proposed psychological consultation should question us about our non-drug management methods in this particular population.

Ethics approval
The study protocol was approved by institutional review boards (