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Depressive symptoms and health-related quality of life in older women with gynecologic Cancers
JGO-00828; No. of pages: 8; 4C: Journal of Geriatric Oncology xxx (2019) xxx
Contents lists available at ScienceDirect
Journal of Geriatric Oncology
Depressive symptoms and health-related quality of life in older women with gynecologic Cancers Amy K. Klapheke a,b,⁎, Theresa H.M. Keegan b,c, Rachel Ruskin d, Rosemary D. Cress a,b a
Public Health Institute, Cancer Registry of Greater California, 1750 Howe Ave, Ste 550, Sacramento, CA 95825, USA Department of Public Health Sciences, University of California Davis, One Shields Ave., Medical Sciences 1-C, Davis, CA 95616, USA Division of Hematology and Oncology, University of California Davis Comprehensive Cancer Center, 2279 45th St., Sacramento, CA 95817, USA d Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California Davis Comprehensive Cancer Center, 2279 45th St., Sacramento, CA 95817, USA b c
a r t i c l e
i n f o
Article history: Received 21 June 2019 Received in revised form 22 August 2019 Accepted 10 October 2019 Available online xxxx Keywords: Gynecologic cancer Quality of life Depression Cancer survivor
a b s t r a c t Objectives: This study aims to assess factors associated with depressive symptoms in older women with gynecologic cancers and to examine the association of depression with health-related quality of life (HRQOL). Materials and methods: Women aged 65 and older previously diagnosed with cervical, ovarian, or uterine cancer (n=1977) were identified from the Surveillance, Epidemiology, and End Results – Medicare Health Outcomes Survey database and compared to propensity-matched cancer-free controls (n=9885). Women with and without depressive symptoms were compared by cancer status. Logistic regression was used to identify factors associated with depressive symptoms, and linear regression was used to determine the association of depressive symptoms with HRQOL measures. Results: The prevalence of depressive symptoms was higher among older women with gynecologic cancer (31.9%, 32.2%, and 25.3% for cervical, ovarian, and uterine cancer, respectively) than cancer-free older women (24.9%) (p=0.05). Adjusting for demographic and clinical factors, older women with ovarian cancer were significantly more likely to have depressive symptoms than controls (Prevalence Odds Ratio = 1.74, 95% CI: 1.31, 2.32, p b 0.01). Among older women with gynecologic cancer, comorbid conditions and functional limitations were strongly associated with depressive symptoms. Women with depressive symptoms showed significant decrements in both physical and mental measures of HRQOL. Conclusion: This study gives insight into correlates of depressive symptoms that may be used to better identify women with gynecologic cancers who are at risk of depression. The relatively high prevalence of depressive symptoms and significant deficits in HRQOL underscore the need for effective screening and treatment of depression in older women with gynecologic cancers. © 2019 Elsevier Ltd. All rights reserved.
1. Introduction In 2019, it is estimated that nearly 100,000 American women will be diagnosed with cancer of the cervix, ovary, or uterus, and about 30,000 will die from these diseases [1]. This burden is especially high in older women; of the approximately 1.2 million American survivors of one of these cancers [2], over half are currently over the age of 65 [3]. While this age group accounts for more than half of the deaths due to these malignancies [4], improvements in early detection and treatment have led to increased survivorship [5,6]. This has pushed many providers and researchers to focus efforts not just on extending quantity of life, but on improving quality of life among women with these cancers. Older women with gynecologic cancer experience a number of physical and mental problems that may negatively impact their
health-related quality of life (HRQOL). In addition to disease-related symptoms and adverse effects of treatment [7], women with gynecologic cancers commonly present with anxiety [8], anger [9], fear [9], and sexual dysfunction [10], and women with these cancers are at high risk of depression [11]. Studies of patients with a variety of cancers found that depression is correlated with worse HRQOL [12,13] and may exacerbate cancer-related distress, hinder the ability to effectively cope with a cancer diagnosis [14,15], increase anxiety and pain [16], and even elevate mortality risk [17]. Despite depression being the most common psychiatric disorder among older patients with cancer [18], depression is often unrecognized and untreated in this population [19]. The timely diagnosis and treatment of depression is vital to ameliorating its impact on the HRQOL of older patients with cancer [20], who are already susceptible to worsening HRQOL.
⁎ Corresponding author at: Public Health Institute, Cancer Registry of Greater California, 1750 Howe Ave, Ste 550, Sacramento, CA 95825, USA. E-mail address: [email protected] (A.K. Klapheke).
https://doi.org/10.1016/j.jgo.2019.10.001 1879-4068/© 2019 Elsevier Ltd. All rights reserved.
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Depressive symptoms and health-related quality of life in older women with gynecologic Cancers, J Geriatr Oncol, https://doi.org/10.1016/j.jgo.2019.10.001
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A.K. Klapheke et al. / Journal of Geriatric Oncology xxx (2019) xxx
While estimates of depression in people with cancer vary [21], some studies reported that prevalence of depression is higher among women with gynecologic cancers than among women and men without cancer or with other cancers [22,23]. Yet, factors associated with depressive symptoms and the impacts on HRQOL are largely understudied among older women with these cancers. Research specific to these women is necessary, as the unique experiences of patients with gynecologic cancer make generalizations from other populations difficult [24,25]. Therefore, this study aimed 1) to compare the risk of depressive symptoms among older women with cervical, ovarian, and uterine cancers with matched cancer-free controls, 2) to identify factors associated with positive depression screen among older women diagnosed with a gynecologic cancer, and 3) to examine the relationship between depressive symptoms and HRQOL in this population. The findings from this study may be useful in identifying women with gynecologic cancers who are at high risk of depression and in determining the most appropriate psychosocial or clinical supportive services. 2. Materials and Methods 2.1. Data Source and Study Population This study analyzed data from the Surveillance, Epidemiology, and End-Results – Medicare Health Outcomes Survey (SEER-MHOS) linked database. Extensive details of the SEER-MHOS linkage have been published elsewhere [26,27]. Briefly, SEER-MHOS links cancer data from the SEER program of population-based registries with MHOS data of Medicare Advantage (MA) enrollees. SEER-MHOS includes data on MA beneficiaries in the SEER regions of Connecticut, Hawaii, Iowa, New Mexico, Utah, Kentucky, Louisiana, New Jersey, California, Detroit, Atlanta, Seattle-Puget Sound, and greater Georgia. Each year, a baseline MHOS is administered to a cohort of 1000 to 1200 randomly selected MA beneficiaries from each managed care plan, and respondents are then asked to take a follow-up survey two years later. This study utilizes data from survey years 1998-2012. The Public Health Institute institutional review board granted this research exempt from review. This analysis included female MHOS participants who were at least 65 years old and resided in a SEER region at the time of the survey. A case was defined as a woman who was diagnosed with a first primary invasive cervical, ovarian, or uterine cancer and who completed at least one MHOS within ten years after diagnosis. Women who were diagnosed with another type of cancer before the survey were excluded. For cases who completed more than one survey, the first survey postcancer diagnosis was used; for women without cancer, the first survey was used. Individuals with missing MHOS data on depressive symptoms were excluded (nb11 [b6.4%], n = 14 [3.3%], n = 61 [3.6%], and n = 2297 [1.1%] of eligible women with cervical, ovarian, uterine, and no cancer, respectively). 2.2. Measures Positive depression screen was defined using an algorithm by Rost et al. [28] and was based on responses to questions from the Diagnostic Interview Schedule in the MHOS. As demonstrated in previous SEERMHOS studies [13,29,30], there were two ways to determine a positive screen. The first requires an affirmative response to the question, “In the past year, have you had 2 weeks or more during which you felt sad, blue, or depressed; or when you lost interest or pleasure in things that you usually cared about or enjoyed? (yes/no).” The second screening method includes an affirmative response to both of the following questions: (1) “In the past year, have you felt depressed or sad much of the time? (yes/no)” and (2) “Have you ever had 2 years or more in your life when you felt depressed or sad most days, even if you felt okay sometimes? (yes/no),” as well as responding at least “some of the time” to the question, “How much of the time during the past 4 weeks have you felt downhearted and blue? (none of the time/some
of the time/most of the time/all of the time).” Participants who fit either of the two criteria were classified as having depressive symptoms. HRQOL was measured using the Medical Outcomes Study Short Form-36 (SF-36) and the Veterans RAND 12-Item Health Survey (VR12) for survey years 1998-2005 and 2006-2012, respectively. The two instruments have been linked using a published algorithm [31]. The items on the questionnaires correspond to eight health domains and are summarized by physical component summary (PCS) and mental component summary (MCS) scores. Both summary scores are derived from a weighted combination of all eight scales, with PCS scores reflecting higher weights for general health, physical functioning, role limitations due to physical problems, and bodily pain subscales. MCS scores have higher weights for mental health, social functioning, role limitations due to emotional problems, and vitality. Scores range from 0-100 and were normed with a mean of 50 and standard deviation of 10 in the U.S. general population. Higher scores reflect better HRQOL. A difference of two points or greater was considered a minimally important difference (MID) for each score, which has been deemed clinically meaningful [32–34]. MCS and mental health scores were not assessed in this study, as they both incorporate one question that was also used to screen for depression. Functional limitations were measured using an activity of daily living (ADL) index [35], which asked: “Because of a health or physical problem, do you have any difficulty doing the following activities without special equipment or help from another person? (I am unable to do this activity/Yes, I have difficulty/No, I do not have difficulty).” Six activities were assessed: bathing, dressing, eating, getting in/out of chairs, walking, and using the toilet. A binary variable (yes/no) was created for each ADL to indicate whether the respondent had no difficulty or had at least some difficulty performing the activity. The number of limitations was summed to create an ADL index score, with higher scores indicating more disability. Limitations were summarized individually, but because of significant correlation between impairments, the index score was used in regression analyses. Other key variables included age at time of survey, race/ethnicity, educational attainment, marital status at survey, household income, SEER geographic region, survey completer, and survey administration. Self-reported comorbid conditions (yes/no) included hypertension, cardiovascular disease, stroke, lung disease, gastrointestinal disorders, arthritis, sciatica, and diabetes. For women with cancer, additional variables were SEER summary stage at diagnosis and time since diagnosis. 2.3. Statistical Analysis Using propensity scores and a greedy matching algorithm [36], five women without cancer were matched to each woman with cancer on propensity score to balance the distribution of and minimize potential bias related to baseline characteristics (age at survey, race/ethnicity, education level, marital status, household income, SEER region, survey administration, survey completer, comorbid conditions, and ADL index). Study participant characteristics were summarized by cancer type and by positive depression screen. Women with and without depressive symptoms were compared by cancer status using chi-square and ttests for categorical and continuous variables, respectively. Logistic regression models were used to calculate prevalence odds ratios (PORs) and 95% confidence intervals (CIs) for positive depression screen. The first model compared women with and without cancer, adjusting for cancer type and all covariates in Table 1, except stage at diagnosis and time since diagnosis. To identify factors associated with depressive symptoms in women with cancer, an analysis was performed restricted to patients with cancer, which included variables for cancer site, stage at diagnosis, and time since diagnosis. Interactions between cancer site and each variable were examined and indicated that a combined cancer model was warranted. Finally, linear regression was used to estimate adjusted mean HRQOL subscale scores for women with and without depressive
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Depressive symptoms and health-related quality of life in older women with gynecologic Cancers, J Geriatr Oncol, https://doi.org/10.1016/j.jgo.2019.10.001
A.K. Klapheke et al. / Journal of Geriatric Oncology xxx (2019) xxx
symptoms. The differences in least squares means associated with depressive symptoms were adjusted for the same covariates used in the logistic regression analyses. Because HRQOL scores varied significantly by cancer type, mean HRQOL scores were calculated separately for each cancer site as well as for controls. All statistical tests were twosided and considered significant at p b 0.05 All analysis was performed using SAS version 9.4 (Cary, NC). 3. Results A total of 1977 women with cancer (144, 354, and 1479 with cervical, ovarian, and uterine cancer, respectively) and 9885 women without cancer were identified for analysis. The characteristics of the study population stratified by cancer site are shown in Table 1. The prevalence of depressive symptoms was higher among gynecologic patients with
3
cancer (31.9%, 32.2%, and 25.3% for cervical, ovarian, and uterine cancer, respectively) than cancer-free women (24.9%) (p = 0.05). Women with and without depressive symptoms are compared by cancer status in Table 2. Among women with and without cancer, non-white persons, women with less education, and women with lower household income were significantly more likely to have positive depression screen (p b 0.01). Those who were unmarried were more likely to have depressive symptoms, but this was only significant for controls. The proportion of women with comorbidities was higher among those with positive depression screen (p b 0.01). Similarly, women with positive depression screen were significantly more likely to have greater impairments in ADLs (p b 0.01). Among cases, women with regional/distant diagnosis were more likely to have depressive symptoms (p b 0.01). After adjusting for demographic and clinical factors, women with ovarian cancer were about 74% more likely to have
Table 1 Characteristics of older women with gynecologic cancer and matched cancer-free controls (N = 11,862). Cervix
Positive depression screen Age at survey, mean (SD) Race/ethnicity White Asian or Pacific Islander Black or African American Hispanic Other Education level Less than high school High school graduate Some college or 2-year degree College graduate or more Unknown Marital status Married Unmarried Unknown Household income b$20,000 $20,000 - $39,999 N $40,000 Unknown Region West Midwest/Northeast South Completed survey by mail Self-completed survey Comorbid conditions Hypertension Cardiovascular disease Stroke Lung disease Gastrointestinal disorders Arthritis Sciatica Diabetes Activities of daily living (ADL) Difficulty bathing Difficulty dressing Difficulty eating Difficulty getting in/out of chairs Difficulty walking Difficulty using the toilet ADL index (SD) Months since diagnosis, mean (SD) Stage at diagnosis Localized Regional/distant Unstaged/unknown
Ovary
Uterus
All cancer
No cancer
N = 144
N = 354
N = 1479
N = 1977
N = 9885
N (%)
N (%)
N (%)
N (%)
N (%)
46 (31.9) 74.0 (6.4)
114 (32.2) 74.2 (6.2)
374 (25.3) 75.1 (6.6)
534 (27.0) 74.8 (6.5)
2464 (24.9) 75.3 (7.0)
71 (49.3) 14 (9.7) 27 (18.8) 27 (18.8) ^
270 (76.3) 18 (5.1) 27 (7.6) 32 (9.0) ^
1157 (78.2) 86 (5.8) 103 (7.0) 93 (6.3) 40 (2.7)
1498 (75.8) 118 (6.0) 157 (7.9) 152 (7.7) 52 (2.6)
7494 (75.8) 588 (5.9) 785 (7.9) 762 (7.7) 256 (2.6)
66 (45.8) 47 (32.6) 23 (16.0) ^ ^
85 (24.0) 118 (33.3) 89 (25.1) 60 (16.9) ^
325 (22.0) 546 (36.9) 355 (24.0) 224 (15.1) 29 (2.0)
476 (24.1) 711 (36.0) 467 (23.6) 290 (14.7) 33 (1.7)
2591 (26.2) 3564 (36.1) 2378 (24.1) 1210 (12.2) 142 (1.4)
48 (33.3) 91 (63.2) ^
164 (46.3) 186 (52.5) ^
617 (41.7) 846 (57.2) 16 (1.1)
829 (41.9) 1123 (56.8) 25 (1.3)
4145 (41.9) 5654 (57.2) 86 (0.9)
80 (55.6) 23 (16.0) 15 (10.4) 26 (18.1)
110 (31.1) 110 (31.1) 60 (16.9) 74 (20.9)
537 (36.3) 366 (24.7) 246 (16.6) 330 (22.3)
727 (36.8) 499 (25.2) 321 (16.2) 430 (21.8)
3820 (38.6) 2433 (24.6) 1524 (15.4) 2108 (21.3)
75 (52.1) 34 (23.6) 35 (24.3) 114 (79.2) 119 (82.6)
228 (64.4) 66 (18.6) 60 (16.9) 297 (83.9) 313 (88.4)
906 (61.3) 371 (25.1) 202 (13.7) 1225 (82.8) 1331 (90.0)
1209 (61.2) 471 (23.8) 297 (15.0) 1636 (82.8) 1763 (89.2)
6049 (61.2) 2338 (23.7) 1498 (15.2) 8121 (82.2) 8823 (89.3)
96 (66.7) 33 (22.9) 15 (10.4) 17 (11.8) ^ 76 (52.8) 38 (26.4) 32 (22.2)
210 (59.3) 109 (30.8) 17 (4.8) 45 (12.7) 23 (6.5) 188 (53.1) 89 (25.1) 63 (17.8)
998 (67.5) 433 (29.3) 106 (7.2) 191 (12.9) 74 (5.0) 876 (59.2) 358 (24.2) 381 (25.8)
1304 (66.0) 575 (29.1) 138 (7.0) 253 (12.8) 106 (5.4) 1140 (57.7) 485 (24.5) 476 (24.1)
6527 (66.0) 3001 (30.4) 837 (8.5) 1486 (15.0) 604 (6.1) 5879 (59.5) 2556 (25.9) 2367 (23.9)
33 (22.9) 27 (18.8) 19 (13.2) 40 (27.8) 63 (43.8) 21 (14.6) 1.4 (1.9) 54.4 (38.0)
68 (19.2) 45 (12.7) 36 (10.2) 88 (24.9) 130 (36.7) 38 (10.7) 1.1 (1.7) 41.8 (34.3)
247 (16.7) 177 (12.0) 78 (5.3) 460 (31.1) 609 (41.2) 150 (10.1) 1.2 (1.6) 52.7 (36.3)
348 (17.6) 249 (12.6) 133 (6.7) 588 (29.7) 802 (40.6) 209 (10.6) 1.2 (1.7) 50.9 (36.3)
1732 (17.5) 1337 (13.5) 600 (6.1) 2988 (30.2) 4004 (40.5) 1023 (10.3) 1.2 (1.7) -
55 (38.2) 66 (45.8) 23 (16.0)
91 (25.7) 233 (65.8) 30 (8.5)
1058 (71.5) 250 (16.9) 171 (11.6)
1204 (60.9) 549 (27.8) 224 (11.3)
-
^In compliance with Surveillance, Epidemiology, and End Results-Medicare guidelines, cell counts less than 11 are not shown.
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Depressive symptoms and health-related quality of life in older women with gynecologic Cancers, J Geriatr Oncol, https://doi.org/10.1016/j.jgo.2019.10.001
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A.K. Klapheke et al. / Journal of Geriatric Oncology xxx (2019) xxx
depressive symptoms than controls (POR = 1.74, 95% CI: 1.31, 2.32, p b 0.01). The risk of positive screen was slightly elevated among women with cervical (POR = 1.17, 95% CI: 0.74 1.84, p = 0.51) and uterine cancers (POR = 1.08, 95% CI: 0.92, 1.26, p = 0.37) compared to controls, though these findings were not statistically significant. The estimates for factors associated with depressive symptoms in women with cancer are displayed in Table 3. Older age was associated with a small decrease in odds of depressive symptoms (POR = 0.98, 95% CI: 0.96, 1.00. pb 0.05). Demographic and surveyrelated factors were not significantly associated with odds of depressive symptoms. However, cardiovascular disease (POR = 1.59, 95% CI: 1.18, 2.14, pb 0.01), stroke (POR = 1.81, 95% CI: 1.10, 2.98, p b 0.05), and sciatica (POR = 1.53, 95% CI: 1.12, 2.09, p b 0.01) significantly increased
the odds of screening positively for depression. For every additional impairment in ADL, the odds of depressive symptoms increased by 27% (POR = 1.27, 95% CI: 1.16, 1.39, p b 0.01). There was no change in odds with time since diagnosis. Later stage at diagnosis was significantly associated with greater odds of positive depression screen (POR = 1.62, 95% CI: 1.17, 2.24, p b 0.01). Adjusted mean scores for HRQOL subscales stratified by cancer type and positive depression screen are shown in Table 4, and the mean differences in scores between those with and without depressive symptoms are illustrated in Fig. 1. HRQOL scores were generally higher among women without cancer or depressive symptoms. Women with positive depression screen had lower scores for all subscales and all cancer types, though some comparisons were not statistically significant.
Table 2 Characteristics of older women with gynecologic cancer and cancer-free controls by depression screen. All cancer
Age at survey, mean (SD) Race/ethnicity White Asian or Pacific Islander Black or African American Hispanic Other Education level Less than high school High school graduate Some college or 2-year degree College graduate or more Unknown Marital status Married Unmarried Unknown Household income b$20,000 $20,000 - $39,999 N $40,000 Unknown Region West Midwest/Northeast South Completed survey by mail Self-completed survey Comorbid conditions Hypertension Cardiovascular disease Stroke Lung disease Gastrointestinal disorders Arthritis Sciatica Diabetes Activities of daily living (ADL) Difficulty bathing Difficulty dressing Difficulty eating Difficulty getting in/out of chairs Difficulty walking Difficulty using the toilet ADL index (SD) Months since diagnosis, mean (SD) Stage at diagnosis Localized Regional/distant Unstaged/unknown
No cancer
Depression
No depression
Depression
No depression
(N = 534)
(N = 1443)
(N = 2464)
(N = 7421)
N (%)
N (%)
N (%)
N (%)
75.2 (7.0)
74.7 (6.4)
75.4 (7.3)
75.3 (7.0)
372 (69.7) 23 (4.3) 56 (10.5) 58 (10.9) 25 (4.7)
1126 (78.0) 95 (6.6) 101 (7.0) 94 (6.5) 27 (1.9)
1725 (70.0) 126 (5.1) 236 (9.6) 278 (11.3) 99 (4.0)
5769 (77.7) 462 (6.2) 549 (7.4) 484 (6.5) 157 (2.1)
171 (32.0) 174 (32.6) 109 (20.4) 70 (13.1) 10 (1.9)
305 (21.1) 537 (37.2) 358 (24.8) 220 (15.2) 23 (1.6)
841 (34.1) 831 (33.7) 527 (21.4) 228 (9.3) 37 (1.5)
1750 (23.6) 2733 (36.8) 1851 (24.9) 982 (13.2) 105 (1.4)
204 (38.2) 323 (60.5) ^
625 (43.3) 800 (55.4) 18 (1.2)
891 (36.2) 1541 (62.5) 32 (1.3)
3254 (43.8) 4113 (55.4) 54 (0.7)
235 (44.0) 121 (22.7) 72 (13.5) 106 (19.9)
492 (34.1) 378 (26.2) 249 (17.3) 324 (22.5)
1163 (47.2) 547 (22.2) 252 (10.2) 502 (20.4)
2657 (35.8) 1886 (25.4) 1272 (17.1) 1606 (21.6)
316 (59.2) 116 (21.7) 102 (19.1) 426 (79.8) 434 (81.3)
893 (61.9) 355 (24.6) 195 (13.5) 1210 (83.9) 1329 (92.1)
⁎ ⁎⁎
1523 (61.8) 523 (21.2) 418 (17.0) 1971 (80.0) 2007 (81.5)
4526 (61.0) 1815 (24.5) 1080 (14.6) 6150 (82.9) 6816 (91.8)
378 (70.8) 206 (38.6) 72 (13.5) 79 (14.8) 43 (8.1) 361 (67.6) 180 (33.7) 169 (31.6)
926 (64.2) 369 (25.6) 66 (4.6) 174 (12.1) 63 (4.4) 779 (54.0) 305 (21.1) 307 (21.3)
⁎⁎ ⁎⁎ ⁎⁎ ⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎
1784 (72.4) 1003 (40.7) 319 (12.9) 549 (22.3) 241 (9.8) 1755 (71.2) 939 (38.1) 768 (31.2)
4743 (63.9) 1998 (26.9) 518 (7.0) 937 (12.6) 363 (4.9) 4124 (55.6) 1617 (21.8) 1599 (21.5)
⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎
176 (33.0) 133 (24.9) 76 (14.2) 252 (47.2) 308 (57.7) 118 (22.1) 2.0 (2.0) 48.3 (36.6)
172 (11.9) 116 (8.0) 57 (4.0) 336 (23.3) 494 (34.2) 91 (6.3) 0.9 (1.4) 51.8 (36.2)
⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎
838 (34.0) 697 (28.3) 347 (14.1) 1211 (49.1) 1548 (62.8) 528 (21.4) 2.1 (2.0) -
894 (12.0) 640 (8.6) 253 (3.4) 1777 (23.9) 2456 (33.1) 495 (6.7) 0.9 (1.4) -
⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎
294 (55.1) 190 (35.6) 50 (9.4)
910 (63.1) 359 (24.9) 174 (12.1)
-
-
⁎⁎
⁎⁎
⁎⁎
⁎⁎
⁎⁎
⁎⁎
⁎⁎
⁎⁎
⁎⁎
⁎⁎
^In compliance with Surveillance, Epidemiology, and End Results-Medicare guidelines, cell counts less than 11 are not shown. ⁎ Significantly different at p b0.05. ⁎⁎ Significantly different at p b0.01.
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Depressive symptoms and health-related quality of life in older women with gynecologic Cancers, J Geriatr Oncol, https://doi.org/10.1016/j.jgo.2019.10.001
A.K. Klapheke et al. / Journal of Geriatric Oncology xxx (2019) xxx
Except for PCS scores, the differences in scores between those with and without depression exceeded the MID threshold for women with any cancer. The greatest decrements were observed for social functioning, with mean differences of -13.2, -8.9, and -10.1 points for patients with cervical, ovarian, and uterine cancer, respectively. 4. Discussion To our knowledge, this is one of the first studies to assess depressive symptoms and the association with HRQOL in managed care beneficiaries with gynecologic cancers. While the true prevalence of major depressive disorder is not available in this study cohort, we determined that the prevalence of depressive symptoms was higher in women with gynecologic cancers than in matched controls. This finding is consistent with previous reports that older people with cancer are more likely to screen positively for depression than persons without cancer [37]. After adjusting for other factors, we found that women with cervical or uterine cancers had similar risk of positive depression screen as women without cancer, while patients with ovarian cancer were significantly more likely to have depressive symptoms. This finding may relate to most women with ovarian cancer being diagnosed with latestage disease, which is associated with a rapid decline in quality of life that can be further exacerbated by aggressive treatment [7]. Some studies suggest that depression rates may decrease with time since diagnosis [13,38,39]. However, our results showed no difference over time in the prevalence of depressive symptoms for women diagnosed with cancer, which may reflect the idea that long-term cancer Table 3 Logistic regression results for association with positive depression screen among older women with gynecologic cancers. POR Cancer site (vs. Uterus) Cervix Ovary Age at survey, per year Race/ethnicity (vs. white) Asian or Pacific Islander Black or African American Hispanic Other Education level (vs. college graduate or more) Less than high school High school graduate Some college or 2-year degree Unmarried vs. married Household income (vs. N $40,000) b$20,000 $20,000 - $39,999 Region (vs. West) Midwest and Northeast vs. West South vs. West Survey completed by phone vs. by mail Proxy completed survey vs. self Comorbid conditions (vs. not having each condition) Hypertension Cardiovascular disease Stroke Lung disease Gastrointestinal disorders Arthritis Sciatica Diabetes ADL index Time since diagnosis, per month Regional/distant vs. localized disease at diagnosis
95% CI
P-value
0.90 (0.52, 1.56) 0.71 1.23 (0.84, 1.79) 0.30 0.98 (0.96, 1.00) b0.05⁎ 0.64 1.39 1.25 2.16
(0.34, 1.23) (0.81, 2.38) (0.75, 2.09) (0.98, 4.75)
0.18 0.23 0.40 0.06
1.06 0.76 0.68 1.07
(0.66, 1.71) (0.50, 1.16) (0.44, 1.04) (0.79, 1.44)
0.82 0.21 0.08 0.68
1.20 (0.80, 1.81) 0.38 1.03 (0.69, 1.54) 0.89 0.81 1.23 0.92 1.54
(0.56, 1.17) (0.83, 1.83) (0.63, 1.35) (0.99, 2.39)
0.26 0.31 0.67 0.06
1.02 1.59 1.81 0.86 1.70 1.18 1.53 1.12 1.27 1.00 1.62
(0.76, 1.38) (1.18, 2.14) (1.10, 2.98) (0.59, 1.27) (1.00, 2.90) (0.88, 1.58) (1.12, 2.09) (0.81, 1.54) (1.16, 1.39) (1.00, 1.00) (1.17, 2.24)
0.89 b0.01⁎ b0.05⁎ 0.46 0.05 0.27 b0.01⁎ 0.51 b0.01⁎ 0.87 b0.01⁎
Abbreviations: POR = Prevalence Odds Ratio; CI = Confidence Interval; ADL = Activities of Daily Living. +Adjusted for age, race/ethnicity, education, marital status, household income, SEER region, survey administration, survey completer, comorbid conditions, ADL index, time since diagnosis, and stage at diagnosis. ⁎ Statistically significant.
5
survivors can develop anxiety and depression as they worry about recurrence [40,41]. Given that the median time since diagnosis was more than four years in this study, our results underscore the idea that patients with gynecologic cancer may continue to experience psychological distress long after completion of initial treatment. Indeed, another study of managed care enrollees who were alive at least five years post-diagnosis found that survivors of various cancers were more likely than individuals who were cancer-free to have a mental health problem [42], and a study of long-term survivors of cancer found a persistently increased risk of psychological distress [20]. As such, screening for depression should be routinely conducted throughout the trajectory of cancer treatment and survival. We found that demographic factors were not generally predictive of positive depression screen in women with gynecologic cancer. Rather, depressive symptoms were most strongly associated with comorbid conditions, namely cardiovascular disease, stroke, and sciatica, as well as functional limitations. This finding is consistent with studies of mental health problems in patients with other cancers [43] and is also supported by studies of functional status and gynecologic cancer in younger patient populations [11,44,45]. Our findings show that these issues are important in older women, especially since cancer often coexists with other physical ailments in older patients [3]. Physical conditions, including stroke and cardiovascular disease, have been shown to be associated with depression independently of cancer [46]. The negative effects of cancer may be compounded further by disability associated with aging and physical comorbidities, which can further increase emotional distress, decrease mobility, and limit social interaction. Additionally, cancer and physical problems cause biological changes, including tissue damage and chronic stress, that can lead to depression [47]. The relatively high prevalence of positive depression screen observed in this study is concerning, as depression is often underdiagnosed and untreated in older persons [48]. Compared to younger persons, older adults with depression are more likely to present with social withdrawal, cognitive changes, and somatic complaints than affective symptoms [14,49]. This complicates the recognition of depression in older adults with cancer, as many cancer- and treatment-related effects overlap with symptoms of depression [14]. Furthermore, studies have demonstrated that older age is associated with a lower likelihood of referral to specialized psychosocial oncology care [50], and that women with cancer are unlikely to receive treatment for depression or supportive counseling [11]. This lack of diagnosis and treatment of depression represents an important health issue in need of intervention, as our results provide striking evidence that depressive symptoms are associated with substantial detriments in HRQOL. The largest deficits in HRQOL associated with positive depression screen were observed for social functioning, role limitations due to emotional problems, and vitality, which exceeded the MID threshold by three to more than six times in women with gynecologic cancer. These constructs have been found to be closely related to depression in older adulthood [49]. While depression can negatively impact HRQOL, it is also likely that the declines in HRQOL associated with cancer and aging lead to depressive symptoms. A gynecologic cancer diagnosis can cause significant role changes and disruption of daily activities, which are important risk factors for depression in older adults [49]. After treatment, women with gynecologic cancer often report social stigma, isolation, and altered relationships with significant others, family members, and friends [51,52], which can increase feelings of anxiety, loneliness, and despair. Additionally, fatigue, the most commonly reported symptom in women with gynecologic cancer [51], can significantly worsen depressive symptoms. Loss of vitality may limit social activity, increase emotional distress, and contribute to psychological problems. Taken together, these findings may help providers better address and manage depression and HRQOL in their patients with cancer. Understanding how depression manifests may help providers determine which psychosocial or clinical services are most appropriate [49].
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Depressive symptoms and health-related quality of life in older women with gynecologic Cancers, J Geriatr Oncol, https://doi.org/10.1016/j.jgo.2019.10.001
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A.K. Klapheke et al. / Journal of Geriatric Oncology xxx (2019) xxx
Table 4 Adjusted+ mean scores for health-related quality of life among older women with gynecologic cancer and matched cancer-free controls by depression screen. Scale
Physical component summary General Health Physical functioning Role limitations - physical Bodily pain Social functioning Role limitations - emotional Vitality
Cervix
Ovary
Uterus
No cancer
Depression
No depression
Depression
No depression
Depression
No depression
Depression
No depression
Mean (95% CI)
Mean (95% CI)
Mean (95% CI)
Mean (95% CI)
Mean (95% CI)
Mean (95% CI)
Mean (95% CI)
Mean (95% CI)
32.2 (24.5, 39.9) 33.6 (25.6, 41.6) 27.2 (19.3, 35.1) 37.2 (28.3, 46.0) 36.3 (27.5, 45.0) 31.2 (23.9, 38.5) 40.6 (32.9, 48.2) 39.4 (32.6, 46.2)
33.8 (27.2, 40.4) 39.8 (32.9, 46.8) 31.9 (25.0, 38.7) 44.6 (37.0, 52.3) 39.2 (31.7, 46.7) 44.4 (38.1, 50.6) 52.2 (45.6, 58.8) 48.2 (42.4, 54.1)
30.2 (25.9, 34.4) 33.5 (29.1, 37.9) 30.0 (25.6, 34.4) 34.2 (29.4, 38.9) 36.1 (31.9, 40.2) 36.2 (31.7, 40.8) 40.9 (36.6, 45.1) 37.7 (33.7, 41.7)
32.3 (28.3, 36.2) 36.8 (32.7, 40.9) 31.9 (27.8, 36.1) 37.8 (33.3, 42.2) 40.8 (36.9, 44.6) 45.1 (40.9, 49.4) 49.0 (45.0, 53.0) 43.7 (40.0, 47.5)
37.0 (35.3, 38.7) 37.4 (35.7, 39.1) 35.4 (33.4, 37.3) 40.4 (38.3, 42.4) 41.6 (39.8, 43.3) 37.4 (35.6, 39.3) 41.0 (39.1, 42.9) 41.9 (40.1, 43.6)
37.7 (36.1, 39.2) 42.1 (40.6, 43.7) 38.1 (36.3, 39.9) 43.9 (42.1, 45.8) 44.2 (42.6, 45.8) 47.6 (45.9, 49.2) 51.9 (50.1, 53.6) 48.4 (46.8, 50.0)
38.1 (37.5, 38.8) 40.1 (39.4, 40.7) 37.1 (36.3, 37.8) 40.7 (39.9, 41.4) 41.0 (40.3, 41.7) 38.7 (38.0, 39.4) 40.8 (40.1, 41.6) 43.6 (42.9, 44.3)
38.5 (37.9, 39.0) 43.9 (43.4, 44.5) 38.9 (38.2, 39.5) 44.1 (43.5, 44.8) 44.0 (43.4, 44.5) 47.0 (46.4, 47.6) 51.0 (50.4, 51.7) 49.2 (48.6, 49.8)
⁎
⁎
⁎⁎ ⁎⁎ ⁎⁎
⁎
⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎
⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎
⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎
+Means were adjusted for age, race/ethnicity, education, marital status, household income, SEER region, survey administration, survey completer, comorbid conditions, and Activities of Daily Living score. Models for women with cervical, ovarian, and uterine cancers were also adjusted for stage at diagnosis and time since diagnosis. ⁎ Significant different at p b0.05. ⁎⁎ Significantly different at p b0.01.
In addition to the mental health subscales, we found that depressive symptoms were associated with significant decreases in scores for general health and role limitations due to physical problems among all women with cancer in this study. These data highlight how depression not only relates to psychological health, but that there are also important links between depressive symptoms and physical disability [53,54]. Such issues are particularly important in older adults, who are more likely to be impacted by comorbid conditions, functional limitations, and deficits in self-care than younger persons [55]. There are several notable limitations of this study. Diagnosis with clinical depression was not captured in the MHOS over the study period. This study assessed depressive symptoms at one point in time after cancer diagnosis, and we did not have data on prior history of or
treatment for depression. We were unable to adjust for disease status at the time of survey completion and did not account for cancer treatment. Comorbidities were based on self-report, and the relative severity of each and sequence with respect to cancer was not known. This study population included MA enrollees from SEER regions only, and data on Medicare fee-for-service beneficiaries was not available. It has been hypothesized that managed care enrollees are healthier than the general Medicare population [56]; thus, our findings may underestimate the prevalence of depressive symptoms and its association with HRQOL. Finally, as this was a cross-sectional analysis, no conclusions can be made about temporality between cancer, depression, or HRQOL. Despite these limitations, this study adds important contributions to existing literature. Previous studies seeking to investigate depression
Fig. 1. Adjusted+ mean deficits in health-related quality of life scores associated with positive depression screen among older women with gynecologic cancer and matched cancer-free controls. +Means were adjusted for age, race/ethnicity, education, marital status, household income, SEER region, survey administration, survey completer, comorbid conditions, and Activities of Daily Living score. Models for women with cervical, ovarian, and uterine cancers were also adjusted for stage at diagnosis and time since diagnosis.
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Depressive symptoms and health-related quality of life in older women with gynecologic Cancers, J Geriatr Oncol, https://doi.org/10.1016/j.jgo.2019.10.001
A.K. Klapheke et al. / Journal of Geriatric Oncology xxx (2019) xxx
and HRQOL in women with gynecologic cancers have been limited by a lack of age-matched comparison groups and highly selective patient populations. Using the extensive information available in SEER-MHOS, we were able to adjust for important confounders, including demographics, comorbid conditions, and functional impairments. We were also able to compare women with cancer to a matched group of women who were cancer-free, which allowed us to distinguish the associations of cancer and older age with depressive symptoms. The results of this study give insight into important correlates of depressive symptoms that may be used to better recognize older women with cancer who are at risk of depression. Identifying those who are at increased risk of depression is an important first step to providing needed clinical and psychosocial support. In addition, these findings shed light on aspects of life that are strongly associated with depressive symptoms in older women with gynecologic cancer. Understanding these issues can help clinicians prioritize their patients’ needs, determine the most appropriate supportive services, and facilitate referrals to mental health care. Author contributions Conceptualization: AK, TK, RR, RC; Data curation: AK, RC; Methodology: AK, TK, RR, RC; Project administration: AK, TK, RR, RC; Formal analysis: AK; Writing- original draft: AK; Writing- review and editing: AK, TK, RR, RC; Supervision: TK, RR, RC Declaration of Competing Interest The authors have no conflicts of interest to disclose. Acknowledgments None. References [1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69(1): 7–34. https://doi.org/10.3322/caac.21551. [2] Howlader N, Noone A, Krapcho M, et al. SEER cancer statistics review; April 2017; 1975–2014. https://seer.cancer.gov/csr/1975_2014/. [3] Parry C, Kent EE, Mariotto AB, Alfano CM, Rowland JH. Cancer survivors: a booming population. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol 2011;20(10):1996–2005. https://doi.org/10.1158/1055-9965. EPI-11-0729. [4] Mirhashemi R, Nieves-Neira W, Averette H. Gynecologic malignancies in older women | cancer network. Oncology 2001;15(5):580–98. [5] Malvezzi M, Carioli G, Rodriguez T, Negri E, La Vecchia C. Global trends and predictions in ovarian cancer mortality. Ann Oncol 2016;27(11):2017–25. https://doi.org/ 10.1093/annonc/mdw306. [6] Hashim D, Boffetta P, La Vecchia C, et al. The global decrease in cancer mortality: trends and disparities. Ann Oncol 2016;27(5):926–33. https://doi.org/10.1093/ annonc/mdw027. [7] Chase DM, Watanabe T, Monk BJ. Assessment and significance of quality of life in women with gynecologic cancer. Future Oncol Lond Engl 2010;6(8):1279–87. https://doi.org/10.2217/fon.10.96. [8] Hipkins J, Whitworth M, Tarrier N, Jayson G. Social support, anxiety and depression after chemotherapy for ovarian cancer: a prospective study. Br J Health Psychol 2004;9(Pt 4):569–81. https://doi.org/10.1348/1359107042304542. [9] Ferrell B, Smith SL, Cullinane CA, Melancon C. Psychological well being and quality of life in ovarian cancer survivors. Cancer 2003;98(5):1061–71. https://doi.org/10. 1002/cncr.11291. [10] Shankar A, Prasad N, Roy S, et al. Sexual dysfunction in females after cancer treatment: an unresolved issue. Asian Pac J Cancer Prev APJCP 2017;18(5):1177–82. https://doi.org/10.22034/APJCP.2017.18.5.1177. [11] Ell K, Sanchez K, Vourlekis B, et al. Depression, correlates of depression, and receipt of depression care among low-income women with breast or gynecologic cancer. J Clin Oncol 2005;23(13):3052–60. https://doi.org/10.1200/JCO.2005.08.041. [12] Brown LF, Kroenke K, Theobald DE, Wu J, Tu W. The association of depression and anxiety with health-related quality of life in cancer patients with depression and/ or pain. Psychooncology 2010;19(7):734–41. https://doi.org/10.1002/pon.1627. [13] White AJ, Reeve BB, Chen RC, Stover AM, Irwin DE. Coexistence of urinary incontinence and major depressive disorder with health-related quality of life in older Americans with and without cancer. J Cancer Surviv Res Pract 2014;8(3):497–507. https://doi.org/10.1007/s11764-014-0360-8.
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Contents lists available at ScienceDirect
Journal of Geriatric Oncology
Depressive symptoms and health-related quality of life in older women with gynecologic Cancers Amy K. Klapheke a,b,⁎, Theresa H.M. Keegan b,c, Rachel Ruskin d, Rosemary D. Cress a,b a
Public Health Institute, Cancer Registry of Greater California, 1750 Howe Ave, Ste 550, Sacramento, CA 95825, USA Department of Public Health Sciences, University of California Davis, One Shields Ave., Medical Sciences 1-C, Davis, CA 95616, USA Division of Hematology and Oncology, University of California Davis Comprehensive Cancer Center, 2279 45th St., Sacramento, CA 95817, USA d Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California Davis Comprehensive Cancer Center, 2279 45th St., Sacramento, CA 95817, USA b c
a r t i c l e
i n f o
Article history: Received 21 June 2019 Received in revised form 22 August 2019 Accepted 10 October 2019 Available online xxxx Keywords: Gynecologic cancer Quality of life Depression Cancer survivor
a b s t r a c t Objectives: This study aims to assess factors associated with depressive symptoms in older women with gynecologic cancers and to examine the association of depression with health-related quality of life (HRQOL). Materials and methods: Women aged 65 and older previously diagnosed with cervical, ovarian, or uterine cancer (n=1977) were identified from the Surveillance, Epidemiology, and End Results – Medicare Health Outcomes Survey database and compared to propensity-matched cancer-free controls (n=9885). Women with and without depressive symptoms were compared by cancer status. Logistic regression was used to identify factors associated with depressive symptoms, and linear regression was used to determine the association of depressive symptoms with HRQOL measures. Results: The prevalence of depressive symptoms was higher among older women with gynecologic cancer (31.9%, 32.2%, and 25.3% for cervical, ovarian, and uterine cancer, respectively) than cancer-free older women (24.9%) (p=0.05). Adjusting for demographic and clinical factors, older women with ovarian cancer were significantly more likely to have depressive symptoms than controls (Prevalence Odds Ratio = 1.74, 95% CI: 1.31, 2.32, p b 0.01). Among older women with gynecologic cancer, comorbid conditions and functional limitations were strongly associated with depressive symptoms. Women with depressive symptoms showed significant decrements in both physical and mental measures of HRQOL. Conclusion: This study gives insight into correlates of depressive symptoms that may be used to better identify women with gynecologic cancers who are at risk of depression. The relatively high prevalence of depressive symptoms and significant deficits in HRQOL underscore the need for effective screening and treatment of depression in older women with gynecologic cancers. © 2019 Elsevier Ltd. All rights reserved.
1. Introduction In 2019, it is estimated that nearly 100,000 American women will be diagnosed with cancer of the cervix, ovary, or uterus, and about 30,000 will die from these diseases [1]. This burden is especially high in older women; of the approximately 1.2 million American survivors of one of these cancers [2], over half are currently over the age of 65 [3]. While this age group accounts for more than half of the deaths due to these malignancies [4], improvements in early detection and treatment have led to increased survivorship [5,6]. This has pushed many providers and researchers to focus efforts not just on extending quantity of life, but on improving quality of life among women with these cancers. Older women with gynecologic cancer experience a number of physical and mental problems that may negatively impact their
health-related quality of life (HRQOL). In addition to disease-related symptoms and adverse effects of treatment [7], women with gynecologic cancers commonly present with anxiety [8], anger [9], fear [9], and sexual dysfunction [10], and women with these cancers are at high risk of depression [11]. Studies of patients with a variety of cancers found that depression is correlated with worse HRQOL [12,13] and may exacerbate cancer-related distress, hinder the ability to effectively cope with a cancer diagnosis [14,15], increase anxiety and pain [16], and even elevate mortality risk [17]. Despite depression being the most common psychiatric disorder among older patients with cancer [18], depression is often unrecognized and untreated in this population [19]. The timely diagnosis and treatment of depression is vital to ameliorating its impact on the HRQOL of older patients with cancer [20], who are already susceptible to worsening HRQOL.
⁎ Corresponding author at: Public Health Institute, Cancer Registry of Greater California, 1750 Howe Ave, Ste 550, Sacramento, CA 95825, USA. E-mail address: [email protected] (A.K. Klapheke).
https://doi.org/10.1016/j.jgo.2019.10.001 1879-4068/© 2019 Elsevier Ltd. All rights reserved.
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Depressive symptoms and health-related quality of life in older women with gynecologic Cancers, J Geriatr Oncol, https://doi.org/10.1016/j.jgo.2019.10.001
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A.K. Klapheke et al. / Journal of Geriatric Oncology xxx (2019) xxx
While estimates of depression in people with cancer vary [21], some studies reported that prevalence of depression is higher among women with gynecologic cancers than among women and men without cancer or with other cancers [22,23]. Yet, factors associated with depressive symptoms and the impacts on HRQOL are largely understudied among older women with these cancers. Research specific to these women is necessary, as the unique experiences of patients with gynecologic cancer make generalizations from other populations difficult [24,25]. Therefore, this study aimed 1) to compare the risk of depressive symptoms among older women with cervical, ovarian, and uterine cancers with matched cancer-free controls, 2) to identify factors associated with positive depression screen among older women diagnosed with a gynecologic cancer, and 3) to examine the relationship between depressive symptoms and HRQOL in this population. The findings from this study may be useful in identifying women with gynecologic cancers who are at high risk of depression and in determining the most appropriate psychosocial or clinical supportive services. 2. Materials and Methods 2.1. Data Source and Study Population This study analyzed data from the Surveillance, Epidemiology, and End-Results – Medicare Health Outcomes Survey (SEER-MHOS) linked database. Extensive details of the SEER-MHOS linkage have been published elsewhere [26,27]. Briefly, SEER-MHOS links cancer data from the SEER program of population-based registries with MHOS data of Medicare Advantage (MA) enrollees. SEER-MHOS includes data on MA beneficiaries in the SEER regions of Connecticut, Hawaii, Iowa, New Mexico, Utah, Kentucky, Louisiana, New Jersey, California, Detroit, Atlanta, Seattle-Puget Sound, and greater Georgia. Each year, a baseline MHOS is administered to a cohort of 1000 to 1200 randomly selected MA beneficiaries from each managed care plan, and respondents are then asked to take a follow-up survey two years later. This study utilizes data from survey years 1998-2012. The Public Health Institute institutional review board granted this research exempt from review. This analysis included female MHOS participants who were at least 65 years old and resided in a SEER region at the time of the survey. A case was defined as a woman who was diagnosed with a first primary invasive cervical, ovarian, or uterine cancer and who completed at least one MHOS within ten years after diagnosis. Women who were diagnosed with another type of cancer before the survey were excluded. For cases who completed more than one survey, the first survey postcancer diagnosis was used; for women without cancer, the first survey was used. Individuals with missing MHOS data on depressive symptoms were excluded (nb11 [b6.4%], n = 14 [3.3%], n = 61 [3.6%], and n = 2297 [1.1%] of eligible women with cervical, ovarian, uterine, and no cancer, respectively). 2.2. Measures Positive depression screen was defined using an algorithm by Rost et al. [28] and was based on responses to questions from the Diagnostic Interview Schedule in the MHOS. As demonstrated in previous SEERMHOS studies [13,29,30], there were two ways to determine a positive screen. The first requires an affirmative response to the question, “In the past year, have you had 2 weeks or more during which you felt sad, blue, or depressed; or when you lost interest or pleasure in things that you usually cared about or enjoyed? (yes/no).” The second screening method includes an affirmative response to both of the following questions: (1) “In the past year, have you felt depressed or sad much of the time? (yes/no)” and (2) “Have you ever had 2 years or more in your life when you felt depressed or sad most days, even if you felt okay sometimes? (yes/no),” as well as responding at least “some of the time” to the question, “How much of the time during the past 4 weeks have you felt downhearted and blue? (none of the time/some
of the time/most of the time/all of the time).” Participants who fit either of the two criteria were classified as having depressive symptoms. HRQOL was measured using the Medical Outcomes Study Short Form-36 (SF-36) and the Veterans RAND 12-Item Health Survey (VR12) for survey years 1998-2005 and 2006-2012, respectively. The two instruments have been linked using a published algorithm [31]. The items on the questionnaires correspond to eight health domains and are summarized by physical component summary (PCS) and mental component summary (MCS) scores. Both summary scores are derived from a weighted combination of all eight scales, with PCS scores reflecting higher weights for general health, physical functioning, role limitations due to physical problems, and bodily pain subscales. MCS scores have higher weights for mental health, social functioning, role limitations due to emotional problems, and vitality. Scores range from 0-100 and were normed with a mean of 50 and standard deviation of 10 in the U.S. general population. Higher scores reflect better HRQOL. A difference of two points or greater was considered a minimally important difference (MID) for each score, which has been deemed clinically meaningful [32–34]. MCS and mental health scores were not assessed in this study, as they both incorporate one question that was also used to screen for depression. Functional limitations were measured using an activity of daily living (ADL) index [35], which asked: “Because of a health or physical problem, do you have any difficulty doing the following activities without special equipment or help from another person? (I am unable to do this activity/Yes, I have difficulty/No, I do not have difficulty).” Six activities were assessed: bathing, dressing, eating, getting in/out of chairs, walking, and using the toilet. A binary variable (yes/no) was created for each ADL to indicate whether the respondent had no difficulty or had at least some difficulty performing the activity. The number of limitations was summed to create an ADL index score, with higher scores indicating more disability. Limitations were summarized individually, but because of significant correlation between impairments, the index score was used in regression analyses. Other key variables included age at time of survey, race/ethnicity, educational attainment, marital status at survey, household income, SEER geographic region, survey completer, and survey administration. Self-reported comorbid conditions (yes/no) included hypertension, cardiovascular disease, stroke, lung disease, gastrointestinal disorders, arthritis, sciatica, and diabetes. For women with cancer, additional variables were SEER summary stage at diagnosis and time since diagnosis. 2.3. Statistical Analysis Using propensity scores and a greedy matching algorithm [36], five women without cancer were matched to each woman with cancer on propensity score to balance the distribution of and minimize potential bias related to baseline characteristics (age at survey, race/ethnicity, education level, marital status, household income, SEER region, survey administration, survey completer, comorbid conditions, and ADL index). Study participant characteristics were summarized by cancer type and by positive depression screen. Women with and without depressive symptoms were compared by cancer status using chi-square and ttests for categorical and continuous variables, respectively. Logistic regression models were used to calculate prevalence odds ratios (PORs) and 95% confidence intervals (CIs) for positive depression screen. The first model compared women with and without cancer, adjusting for cancer type and all covariates in Table 1, except stage at diagnosis and time since diagnosis. To identify factors associated with depressive symptoms in women with cancer, an analysis was performed restricted to patients with cancer, which included variables for cancer site, stage at diagnosis, and time since diagnosis. Interactions between cancer site and each variable were examined and indicated that a combined cancer model was warranted. Finally, linear regression was used to estimate adjusted mean HRQOL subscale scores for women with and without depressive
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Depressive symptoms and health-related quality of life in older women with gynecologic Cancers, J Geriatr Oncol, https://doi.org/10.1016/j.jgo.2019.10.001
A.K. Klapheke et al. / Journal of Geriatric Oncology xxx (2019) xxx
symptoms. The differences in least squares means associated with depressive symptoms were adjusted for the same covariates used in the logistic regression analyses. Because HRQOL scores varied significantly by cancer type, mean HRQOL scores were calculated separately for each cancer site as well as for controls. All statistical tests were twosided and considered significant at p b 0.05 All analysis was performed using SAS version 9.4 (Cary, NC). 3. Results A total of 1977 women with cancer (144, 354, and 1479 with cervical, ovarian, and uterine cancer, respectively) and 9885 women without cancer were identified for analysis. The characteristics of the study population stratified by cancer site are shown in Table 1. The prevalence of depressive symptoms was higher among gynecologic patients with
3
cancer (31.9%, 32.2%, and 25.3% for cervical, ovarian, and uterine cancer, respectively) than cancer-free women (24.9%) (p = 0.05). Women with and without depressive symptoms are compared by cancer status in Table 2. Among women with and without cancer, non-white persons, women with less education, and women with lower household income were significantly more likely to have positive depression screen (p b 0.01). Those who were unmarried were more likely to have depressive symptoms, but this was only significant for controls. The proportion of women with comorbidities was higher among those with positive depression screen (p b 0.01). Similarly, women with positive depression screen were significantly more likely to have greater impairments in ADLs (p b 0.01). Among cases, women with regional/distant diagnosis were more likely to have depressive symptoms (p b 0.01). After adjusting for demographic and clinical factors, women with ovarian cancer were about 74% more likely to have
Table 1 Characteristics of older women with gynecologic cancer and matched cancer-free controls (N = 11,862). Cervix
Positive depression screen Age at survey, mean (SD) Race/ethnicity White Asian or Pacific Islander Black or African American Hispanic Other Education level Less than high school High school graduate Some college or 2-year degree College graduate or more Unknown Marital status Married Unmarried Unknown Household income b$20,000 $20,000 - $39,999 N $40,000 Unknown Region West Midwest/Northeast South Completed survey by mail Self-completed survey Comorbid conditions Hypertension Cardiovascular disease Stroke Lung disease Gastrointestinal disorders Arthritis Sciatica Diabetes Activities of daily living (ADL) Difficulty bathing Difficulty dressing Difficulty eating Difficulty getting in/out of chairs Difficulty walking Difficulty using the toilet ADL index (SD) Months since diagnosis, mean (SD) Stage at diagnosis Localized Regional/distant Unstaged/unknown
Ovary
Uterus
All cancer
No cancer
N = 144
N = 354
N = 1479
N = 1977
N = 9885
N (%)
N (%)
N (%)
N (%)
N (%)
46 (31.9) 74.0 (6.4)
114 (32.2) 74.2 (6.2)
374 (25.3) 75.1 (6.6)
534 (27.0) 74.8 (6.5)
2464 (24.9) 75.3 (7.0)
71 (49.3) 14 (9.7) 27 (18.8) 27 (18.8) ^
270 (76.3) 18 (5.1) 27 (7.6) 32 (9.0) ^
1157 (78.2) 86 (5.8) 103 (7.0) 93 (6.3) 40 (2.7)
1498 (75.8) 118 (6.0) 157 (7.9) 152 (7.7) 52 (2.6)
7494 (75.8) 588 (5.9) 785 (7.9) 762 (7.7) 256 (2.6)
66 (45.8) 47 (32.6) 23 (16.0) ^ ^
85 (24.0) 118 (33.3) 89 (25.1) 60 (16.9) ^
325 (22.0) 546 (36.9) 355 (24.0) 224 (15.1) 29 (2.0)
476 (24.1) 711 (36.0) 467 (23.6) 290 (14.7) 33 (1.7)
2591 (26.2) 3564 (36.1) 2378 (24.1) 1210 (12.2) 142 (1.4)
48 (33.3) 91 (63.2) ^
164 (46.3) 186 (52.5) ^
617 (41.7) 846 (57.2) 16 (1.1)
829 (41.9) 1123 (56.8) 25 (1.3)
4145 (41.9) 5654 (57.2) 86 (0.9)
80 (55.6) 23 (16.0) 15 (10.4) 26 (18.1)
110 (31.1) 110 (31.1) 60 (16.9) 74 (20.9)
537 (36.3) 366 (24.7) 246 (16.6) 330 (22.3)
727 (36.8) 499 (25.2) 321 (16.2) 430 (21.8)
3820 (38.6) 2433 (24.6) 1524 (15.4) 2108 (21.3)
75 (52.1) 34 (23.6) 35 (24.3) 114 (79.2) 119 (82.6)
228 (64.4) 66 (18.6) 60 (16.9) 297 (83.9) 313 (88.4)
906 (61.3) 371 (25.1) 202 (13.7) 1225 (82.8) 1331 (90.0)
1209 (61.2) 471 (23.8) 297 (15.0) 1636 (82.8) 1763 (89.2)
6049 (61.2) 2338 (23.7) 1498 (15.2) 8121 (82.2) 8823 (89.3)
96 (66.7) 33 (22.9) 15 (10.4) 17 (11.8) ^ 76 (52.8) 38 (26.4) 32 (22.2)
210 (59.3) 109 (30.8) 17 (4.8) 45 (12.7) 23 (6.5) 188 (53.1) 89 (25.1) 63 (17.8)
998 (67.5) 433 (29.3) 106 (7.2) 191 (12.9) 74 (5.0) 876 (59.2) 358 (24.2) 381 (25.8)
1304 (66.0) 575 (29.1) 138 (7.0) 253 (12.8) 106 (5.4) 1140 (57.7) 485 (24.5) 476 (24.1)
6527 (66.0) 3001 (30.4) 837 (8.5) 1486 (15.0) 604 (6.1) 5879 (59.5) 2556 (25.9) 2367 (23.9)
33 (22.9) 27 (18.8) 19 (13.2) 40 (27.8) 63 (43.8) 21 (14.6) 1.4 (1.9) 54.4 (38.0)
68 (19.2) 45 (12.7) 36 (10.2) 88 (24.9) 130 (36.7) 38 (10.7) 1.1 (1.7) 41.8 (34.3)
247 (16.7) 177 (12.0) 78 (5.3) 460 (31.1) 609 (41.2) 150 (10.1) 1.2 (1.6) 52.7 (36.3)
348 (17.6) 249 (12.6) 133 (6.7) 588 (29.7) 802 (40.6) 209 (10.6) 1.2 (1.7) 50.9 (36.3)
1732 (17.5) 1337 (13.5) 600 (6.1) 2988 (30.2) 4004 (40.5) 1023 (10.3) 1.2 (1.7) -
55 (38.2) 66 (45.8) 23 (16.0)
91 (25.7) 233 (65.8) 30 (8.5)
1058 (71.5) 250 (16.9) 171 (11.6)
1204 (60.9) 549 (27.8) 224 (11.3)
-
^In compliance with Surveillance, Epidemiology, and End Results-Medicare guidelines, cell counts less than 11 are not shown.
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Depressive symptoms and health-related quality of life in older women with gynecologic Cancers, J Geriatr Oncol, https://doi.org/10.1016/j.jgo.2019.10.001
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A.K. Klapheke et al. / Journal of Geriatric Oncology xxx (2019) xxx
depressive symptoms than controls (POR = 1.74, 95% CI: 1.31, 2.32, p b 0.01). The risk of positive screen was slightly elevated among women with cervical (POR = 1.17, 95% CI: 0.74 1.84, p = 0.51) and uterine cancers (POR = 1.08, 95% CI: 0.92, 1.26, p = 0.37) compared to controls, though these findings were not statistically significant. The estimates for factors associated with depressive symptoms in women with cancer are displayed in Table 3. Older age was associated with a small decrease in odds of depressive symptoms (POR = 0.98, 95% CI: 0.96, 1.00. pb 0.05). Demographic and surveyrelated factors were not significantly associated with odds of depressive symptoms. However, cardiovascular disease (POR = 1.59, 95% CI: 1.18, 2.14, pb 0.01), stroke (POR = 1.81, 95% CI: 1.10, 2.98, p b 0.05), and sciatica (POR = 1.53, 95% CI: 1.12, 2.09, p b 0.01) significantly increased
the odds of screening positively for depression. For every additional impairment in ADL, the odds of depressive symptoms increased by 27% (POR = 1.27, 95% CI: 1.16, 1.39, p b 0.01). There was no change in odds with time since diagnosis. Later stage at diagnosis was significantly associated with greater odds of positive depression screen (POR = 1.62, 95% CI: 1.17, 2.24, p b 0.01). Adjusted mean scores for HRQOL subscales stratified by cancer type and positive depression screen are shown in Table 4, and the mean differences in scores between those with and without depressive symptoms are illustrated in Fig. 1. HRQOL scores were generally higher among women without cancer or depressive symptoms. Women with positive depression screen had lower scores for all subscales and all cancer types, though some comparisons were not statistically significant.
Table 2 Characteristics of older women with gynecologic cancer and cancer-free controls by depression screen. All cancer
Age at survey, mean (SD) Race/ethnicity White Asian or Pacific Islander Black or African American Hispanic Other Education level Less than high school High school graduate Some college or 2-year degree College graduate or more Unknown Marital status Married Unmarried Unknown Household income b$20,000 $20,000 - $39,999 N $40,000 Unknown Region West Midwest/Northeast South Completed survey by mail Self-completed survey Comorbid conditions Hypertension Cardiovascular disease Stroke Lung disease Gastrointestinal disorders Arthritis Sciatica Diabetes Activities of daily living (ADL) Difficulty bathing Difficulty dressing Difficulty eating Difficulty getting in/out of chairs Difficulty walking Difficulty using the toilet ADL index (SD) Months since diagnosis, mean (SD) Stage at diagnosis Localized Regional/distant Unstaged/unknown
No cancer
Depression
No depression
Depression
No depression
(N = 534)
(N = 1443)
(N = 2464)
(N = 7421)
N (%)
N (%)
N (%)
N (%)
75.2 (7.0)
74.7 (6.4)
75.4 (7.3)
75.3 (7.0)
372 (69.7) 23 (4.3) 56 (10.5) 58 (10.9) 25 (4.7)
1126 (78.0) 95 (6.6) 101 (7.0) 94 (6.5) 27 (1.9)
1725 (70.0) 126 (5.1) 236 (9.6) 278 (11.3) 99 (4.0)
5769 (77.7) 462 (6.2) 549 (7.4) 484 (6.5) 157 (2.1)
171 (32.0) 174 (32.6) 109 (20.4) 70 (13.1) 10 (1.9)
305 (21.1) 537 (37.2) 358 (24.8) 220 (15.2) 23 (1.6)
841 (34.1) 831 (33.7) 527 (21.4) 228 (9.3) 37 (1.5)
1750 (23.6) 2733 (36.8) 1851 (24.9) 982 (13.2) 105 (1.4)
204 (38.2) 323 (60.5) ^
625 (43.3) 800 (55.4) 18 (1.2)
891 (36.2) 1541 (62.5) 32 (1.3)
3254 (43.8) 4113 (55.4) 54 (0.7)
235 (44.0) 121 (22.7) 72 (13.5) 106 (19.9)
492 (34.1) 378 (26.2) 249 (17.3) 324 (22.5)
1163 (47.2) 547 (22.2) 252 (10.2) 502 (20.4)
2657 (35.8) 1886 (25.4) 1272 (17.1) 1606 (21.6)
316 (59.2) 116 (21.7) 102 (19.1) 426 (79.8) 434 (81.3)
893 (61.9) 355 (24.6) 195 (13.5) 1210 (83.9) 1329 (92.1)
⁎ ⁎⁎
1523 (61.8) 523 (21.2) 418 (17.0) 1971 (80.0) 2007 (81.5)
4526 (61.0) 1815 (24.5) 1080 (14.6) 6150 (82.9) 6816 (91.8)
378 (70.8) 206 (38.6) 72 (13.5) 79 (14.8) 43 (8.1) 361 (67.6) 180 (33.7) 169 (31.6)
926 (64.2) 369 (25.6) 66 (4.6) 174 (12.1) 63 (4.4) 779 (54.0) 305 (21.1) 307 (21.3)
⁎⁎ ⁎⁎ ⁎⁎ ⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎
1784 (72.4) 1003 (40.7) 319 (12.9) 549 (22.3) 241 (9.8) 1755 (71.2) 939 (38.1) 768 (31.2)
4743 (63.9) 1998 (26.9) 518 (7.0) 937 (12.6) 363 (4.9) 4124 (55.6) 1617 (21.8) 1599 (21.5)
⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎
176 (33.0) 133 (24.9) 76 (14.2) 252 (47.2) 308 (57.7) 118 (22.1) 2.0 (2.0) 48.3 (36.6)
172 (11.9) 116 (8.0) 57 (4.0) 336 (23.3) 494 (34.2) 91 (6.3) 0.9 (1.4) 51.8 (36.2)
⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎
838 (34.0) 697 (28.3) 347 (14.1) 1211 (49.1) 1548 (62.8) 528 (21.4) 2.1 (2.0) -
894 (12.0) 640 (8.6) 253 (3.4) 1777 (23.9) 2456 (33.1) 495 (6.7) 0.9 (1.4) -
⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎
294 (55.1) 190 (35.6) 50 (9.4)
910 (63.1) 359 (24.9) 174 (12.1)
-
-
⁎⁎
⁎⁎
⁎⁎
⁎⁎
⁎⁎
⁎⁎
⁎⁎
⁎⁎
⁎⁎
⁎⁎
^In compliance with Surveillance, Epidemiology, and End Results-Medicare guidelines, cell counts less than 11 are not shown. ⁎ Significantly different at p b0.05. ⁎⁎ Significantly different at p b0.01.
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Depressive symptoms and health-related quality of life in older women with gynecologic Cancers, J Geriatr Oncol, https://doi.org/10.1016/j.jgo.2019.10.001
A.K. Klapheke et al. / Journal of Geriatric Oncology xxx (2019) xxx
Except for PCS scores, the differences in scores between those with and without depression exceeded the MID threshold for women with any cancer. The greatest decrements were observed for social functioning, with mean differences of -13.2, -8.9, and -10.1 points for patients with cervical, ovarian, and uterine cancer, respectively. 4. Discussion To our knowledge, this is one of the first studies to assess depressive symptoms and the association with HRQOL in managed care beneficiaries with gynecologic cancers. While the true prevalence of major depressive disorder is not available in this study cohort, we determined that the prevalence of depressive symptoms was higher in women with gynecologic cancers than in matched controls. This finding is consistent with previous reports that older people with cancer are more likely to screen positively for depression than persons without cancer [37]. After adjusting for other factors, we found that women with cervical or uterine cancers had similar risk of positive depression screen as women without cancer, while patients with ovarian cancer were significantly more likely to have depressive symptoms. This finding may relate to most women with ovarian cancer being diagnosed with latestage disease, which is associated with a rapid decline in quality of life that can be further exacerbated by aggressive treatment [7]. Some studies suggest that depression rates may decrease with time since diagnosis [13,38,39]. However, our results showed no difference over time in the prevalence of depressive symptoms for women diagnosed with cancer, which may reflect the idea that long-term cancer Table 3 Logistic regression results for association with positive depression screen among older women with gynecologic cancers. POR Cancer site (vs. Uterus) Cervix Ovary Age at survey, per year Race/ethnicity (vs. white) Asian or Pacific Islander Black or African American Hispanic Other Education level (vs. college graduate or more) Less than high school High school graduate Some college or 2-year degree Unmarried vs. married Household income (vs. N $40,000) b$20,000 $20,000 - $39,999 Region (vs. West) Midwest and Northeast vs. West South vs. West Survey completed by phone vs. by mail Proxy completed survey vs. self Comorbid conditions (vs. not having each condition) Hypertension Cardiovascular disease Stroke Lung disease Gastrointestinal disorders Arthritis Sciatica Diabetes ADL index Time since diagnosis, per month Regional/distant vs. localized disease at diagnosis
95% CI
P-value
0.90 (0.52, 1.56) 0.71 1.23 (0.84, 1.79) 0.30 0.98 (0.96, 1.00) b0.05⁎ 0.64 1.39 1.25 2.16
(0.34, 1.23) (0.81, 2.38) (0.75, 2.09) (0.98, 4.75)
0.18 0.23 0.40 0.06
1.06 0.76 0.68 1.07
(0.66, 1.71) (0.50, 1.16) (0.44, 1.04) (0.79, 1.44)
0.82 0.21 0.08 0.68
1.20 (0.80, 1.81) 0.38 1.03 (0.69, 1.54) 0.89 0.81 1.23 0.92 1.54
(0.56, 1.17) (0.83, 1.83) (0.63, 1.35) (0.99, 2.39)
0.26 0.31 0.67 0.06
1.02 1.59 1.81 0.86 1.70 1.18 1.53 1.12 1.27 1.00 1.62
(0.76, 1.38) (1.18, 2.14) (1.10, 2.98) (0.59, 1.27) (1.00, 2.90) (0.88, 1.58) (1.12, 2.09) (0.81, 1.54) (1.16, 1.39) (1.00, 1.00) (1.17, 2.24)
0.89 b0.01⁎ b0.05⁎ 0.46 0.05 0.27 b0.01⁎ 0.51 b0.01⁎ 0.87 b0.01⁎
Abbreviations: POR = Prevalence Odds Ratio; CI = Confidence Interval; ADL = Activities of Daily Living. +Adjusted for age, race/ethnicity, education, marital status, household income, SEER region, survey administration, survey completer, comorbid conditions, ADL index, time since diagnosis, and stage at diagnosis. ⁎ Statistically significant.
5
survivors can develop anxiety and depression as they worry about recurrence [40,41]. Given that the median time since diagnosis was more than four years in this study, our results underscore the idea that patients with gynecologic cancer may continue to experience psychological distress long after completion of initial treatment. Indeed, another study of managed care enrollees who were alive at least five years post-diagnosis found that survivors of various cancers were more likely than individuals who were cancer-free to have a mental health problem [42], and a study of long-term survivors of cancer found a persistently increased risk of psychological distress [20]. As such, screening for depression should be routinely conducted throughout the trajectory of cancer treatment and survival. We found that demographic factors were not generally predictive of positive depression screen in women with gynecologic cancer. Rather, depressive symptoms were most strongly associated with comorbid conditions, namely cardiovascular disease, stroke, and sciatica, as well as functional limitations. This finding is consistent with studies of mental health problems in patients with other cancers [43] and is also supported by studies of functional status and gynecologic cancer in younger patient populations [11,44,45]. Our findings show that these issues are important in older women, especially since cancer often coexists with other physical ailments in older patients [3]. Physical conditions, including stroke and cardiovascular disease, have been shown to be associated with depression independently of cancer [46]. The negative effects of cancer may be compounded further by disability associated with aging and physical comorbidities, which can further increase emotional distress, decrease mobility, and limit social interaction. Additionally, cancer and physical problems cause biological changes, including tissue damage and chronic stress, that can lead to depression [47]. The relatively high prevalence of positive depression screen observed in this study is concerning, as depression is often underdiagnosed and untreated in older persons [48]. Compared to younger persons, older adults with depression are more likely to present with social withdrawal, cognitive changes, and somatic complaints than affective symptoms [14,49]. This complicates the recognition of depression in older adults with cancer, as many cancer- and treatment-related effects overlap with symptoms of depression [14]. Furthermore, studies have demonstrated that older age is associated with a lower likelihood of referral to specialized psychosocial oncology care [50], and that women with cancer are unlikely to receive treatment for depression or supportive counseling [11]. This lack of diagnosis and treatment of depression represents an important health issue in need of intervention, as our results provide striking evidence that depressive symptoms are associated with substantial detriments in HRQOL. The largest deficits in HRQOL associated with positive depression screen were observed for social functioning, role limitations due to emotional problems, and vitality, which exceeded the MID threshold by three to more than six times in women with gynecologic cancer. These constructs have been found to be closely related to depression in older adulthood [49]. While depression can negatively impact HRQOL, it is also likely that the declines in HRQOL associated with cancer and aging lead to depressive symptoms. A gynecologic cancer diagnosis can cause significant role changes and disruption of daily activities, which are important risk factors for depression in older adults [49]. After treatment, women with gynecologic cancer often report social stigma, isolation, and altered relationships with significant others, family members, and friends [51,52], which can increase feelings of anxiety, loneliness, and despair. Additionally, fatigue, the most commonly reported symptom in women with gynecologic cancer [51], can significantly worsen depressive symptoms. Loss of vitality may limit social activity, increase emotional distress, and contribute to psychological problems. Taken together, these findings may help providers better address and manage depression and HRQOL in their patients with cancer. Understanding how depression manifests may help providers determine which psychosocial or clinical services are most appropriate [49].
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Depressive symptoms and health-related quality of life in older women with gynecologic Cancers, J Geriatr Oncol, https://doi.org/10.1016/j.jgo.2019.10.001
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A.K. Klapheke et al. / Journal of Geriatric Oncology xxx (2019) xxx
Table 4 Adjusted+ mean scores for health-related quality of life among older women with gynecologic cancer and matched cancer-free controls by depression screen. Scale
Physical component summary General Health Physical functioning Role limitations - physical Bodily pain Social functioning Role limitations - emotional Vitality
Cervix
Ovary
Uterus
No cancer
Depression
No depression
Depression
No depression
Depression
No depression
Depression
No depression
Mean (95% CI)
Mean (95% CI)
Mean (95% CI)
Mean (95% CI)
Mean (95% CI)
Mean (95% CI)
Mean (95% CI)
Mean (95% CI)
32.2 (24.5, 39.9) 33.6 (25.6, 41.6) 27.2 (19.3, 35.1) 37.2 (28.3, 46.0) 36.3 (27.5, 45.0) 31.2 (23.9, 38.5) 40.6 (32.9, 48.2) 39.4 (32.6, 46.2)
33.8 (27.2, 40.4) 39.8 (32.9, 46.8) 31.9 (25.0, 38.7) 44.6 (37.0, 52.3) 39.2 (31.7, 46.7) 44.4 (38.1, 50.6) 52.2 (45.6, 58.8) 48.2 (42.4, 54.1)
30.2 (25.9, 34.4) 33.5 (29.1, 37.9) 30.0 (25.6, 34.4) 34.2 (29.4, 38.9) 36.1 (31.9, 40.2) 36.2 (31.7, 40.8) 40.9 (36.6, 45.1) 37.7 (33.7, 41.7)
32.3 (28.3, 36.2) 36.8 (32.7, 40.9) 31.9 (27.8, 36.1) 37.8 (33.3, 42.2) 40.8 (36.9, 44.6) 45.1 (40.9, 49.4) 49.0 (45.0, 53.0) 43.7 (40.0, 47.5)
37.0 (35.3, 38.7) 37.4 (35.7, 39.1) 35.4 (33.4, 37.3) 40.4 (38.3, 42.4) 41.6 (39.8, 43.3) 37.4 (35.6, 39.3) 41.0 (39.1, 42.9) 41.9 (40.1, 43.6)
37.7 (36.1, 39.2) 42.1 (40.6, 43.7) 38.1 (36.3, 39.9) 43.9 (42.1, 45.8) 44.2 (42.6, 45.8) 47.6 (45.9, 49.2) 51.9 (50.1, 53.6) 48.4 (46.8, 50.0)
38.1 (37.5, 38.8) 40.1 (39.4, 40.7) 37.1 (36.3, 37.8) 40.7 (39.9, 41.4) 41.0 (40.3, 41.7) 38.7 (38.0, 39.4) 40.8 (40.1, 41.6) 43.6 (42.9, 44.3)
38.5 (37.9, 39.0) 43.9 (43.4, 44.5) 38.9 (38.2, 39.5) 44.1 (43.5, 44.8) 44.0 (43.4, 44.5) 47.0 (46.4, 47.6) 51.0 (50.4, 51.7) 49.2 (48.6, 49.8)
⁎
⁎
⁎⁎ ⁎⁎ ⁎⁎
⁎
⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎
⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎
⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎ ⁎⁎
+Means were adjusted for age, race/ethnicity, education, marital status, household income, SEER region, survey administration, survey completer, comorbid conditions, and Activities of Daily Living score. Models for women with cervical, ovarian, and uterine cancers were also adjusted for stage at diagnosis and time since diagnosis. ⁎ Significant different at p b0.05. ⁎⁎ Significantly different at p b0.01.
In addition to the mental health subscales, we found that depressive symptoms were associated with significant decreases in scores for general health and role limitations due to physical problems among all women with cancer in this study. These data highlight how depression not only relates to psychological health, but that there are also important links between depressive symptoms and physical disability [53,54]. Such issues are particularly important in older adults, who are more likely to be impacted by comorbid conditions, functional limitations, and deficits in self-care than younger persons [55]. There are several notable limitations of this study. Diagnosis with clinical depression was not captured in the MHOS over the study period. This study assessed depressive symptoms at one point in time after cancer diagnosis, and we did not have data on prior history of or
treatment for depression. We were unable to adjust for disease status at the time of survey completion and did not account for cancer treatment. Comorbidities were based on self-report, and the relative severity of each and sequence with respect to cancer was not known. This study population included MA enrollees from SEER regions only, and data on Medicare fee-for-service beneficiaries was not available. It has been hypothesized that managed care enrollees are healthier than the general Medicare population [56]; thus, our findings may underestimate the prevalence of depressive symptoms and its association with HRQOL. Finally, as this was a cross-sectional analysis, no conclusions can be made about temporality between cancer, depression, or HRQOL. Despite these limitations, this study adds important contributions to existing literature. Previous studies seeking to investigate depression
Fig. 1. Adjusted+ mean deficits in health-related quality of life scores associated with positive depression screen among older women with gynecologic cancer and matched cancer-free controls. +Means were adjusted for age, race/ethnicity, education, marital status, household income, SEER region, survey administration, survey completer, comorbid conditions, and Activities of Daily Living score. Models for women with cervical, ovarian, and uterine cancers were also adjusted for stage at diagnosis and time since diagnosis.
Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Depressive symptoms and health-related quality of life in older women with gynecologic Cancers, J Geriatr Oncol, https://doi.org/10.1016/j.jgo.2019.10.001
A.K. Klapheke et al. / Journal of Geriatric Oncology xxx (2019) xxx
and HRQOL in women with gynecologic cancers have been limited by a lack of age-matched comparison groups and highly selective patient populations. Using the extensive information available in SEER-MHOS, we were able to adjust for important confounders, including demographics, comorbid conditions, and functional impairments. We were also able to compare women with cancer to a matched group of women who were cancer-free, which allowed us to distinguish the associations of cancer and older age with depressive symptoms. The results of this study give insight into important correlates of depressive symptoms that may be used to better recognize older women with cancer who are at risk of depression. Identifying those who are at increased risk of depression is an important first step to providing needed clinical and psychosocial support. In addition, these findings shed light on aspects of life that are strongly associated with depressive symptoms in older women with gynecologic cancer. Understanding these issues can help clinicians prioritize their patients’ needs, determine the most appropriate supportive services, and facilitate referrals to mental health care. Author contributions Conceptualization: AK, TK, RR, RC; Data curation: AK, RC; Methodology: AK, TK, RR, RC; Project administration: AK, TK, RR, RC; Formal analysis: AK; Writing- original draft: AK; Writing- review and editing: AK, TK, RR, RC; Supervision: TK, RR, RC Declaration of Competing Interest The authors have no conflicts of interest to disclose. Acknowledgments None. References [1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69(1): 7–34. https://doi.org/10.3322/caac.21551. [2] Howlader N, Noone A, Krapcho M, et al. SEER cancer statistics review; April 2017; 1975–2014. https://seer.cancer.gov/csr/1975_2014/. [3] Parry C, Kent EE, Mariotto AB, Alfano CM, Rowland JH. Cancer survivors: a booming population. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol 2011;20(10):1996–2005. https://doi.org/10.1158/1055-9965. EPI-11-0729. [4] Mirhashemi R, Nieves-Neira W, Averette H. Gynecologic malignancies in older women | cancer network. Oncology 2001;15(5):580–98. [5] Malvezzi M, Carioli G, Rodriguez T, Negri E, La Vecchia C. Global trends and predictions in ovarian cancer mortality. Ann Oncol 2016;27(11):2017–25. https://doi.org/ 10.1093/annonc/mdw306. [6] Hashim D, Boffetta P, La Vecchia C, et al. The global decrease in cancer mortality: trends and disparities. Ann Oncol 2016;27(5):926–33. https://doi.org/10.1093/ annonc/mdw027. [7] Chase DM, Watanabe T, Monk BJ. Assessment and significance of quality of life in women with gynecologic cancer. Future Oncol Lond Engl 2010;6(8):1279–87. https://doi.org/10.2217/fon.10.96. [8] Hipkins J, Whitworth M, Tarrier N, Jayson G. Social support, anxiety and depression after chemotherapy for ovarian cancer: a prospective study. Br J Health Psychol 2004;9(Pt 4):569–81. https://doi.org/10.1348/1359107042304542. [9] Ferrell B, Smith SL, Cullinane CA, Melancon C. Psychological well being and quality of life in ovarian cancer survivors. Cancer 2003;98(5):1061–71. https://doi.org/10. 1002/cncr.11291. [10] Shankar A, Prasad N, Roy S, et al. Sexual dysfunction in females after cancer treatment: an unresolved issue. Asian Pac J Cancer Prev APJCP 2017;18(5):1177–82. https://doi.org/10.22034/APJCP.2017.18.5.1177. [11] Ell K, Sanchez K, Vourlekis B, et al. Depression, correlates of depression, and receipt of depression care among low-income women with breast or gynecologic cancer. J Clin Oncol 2005;23(13):3052–60. https://doi.org/10.1200/JCO.2005.08.041. [12] Brown LF, Kroenke K, Theobald DE, Wu J, Tu W. The association of depression and anxiety with health-related quality of life in cancer patients with depression and/ or pain. Psychooncology 2010;19(7):734–41. https://doi.org/10.1002/pon.1627. [13] White AJ, Reeve BB, Chen RC, Stover AM, Irwin DE. Coexistence of urinary incontinence and major depressive disorder with health-related quality of life in older Americans with and without cancer. J Cancer Surviv Res Pract 2014;8(3):497–507. https://doi.org/10.1007/s11764-014-0360-8.
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Please cite this article as: A.K. Klapheke, T.H.M. Keegan, R. Ruskin, et al., Depressive symptoms and health-related quality of life in older women with gynecologic Cancers, J Geriatr Oncol, https://doi.org/10.1016/j.jgo.2019.10.001