Abstract
Background
Cancer patients’ symptom burden is commonly attributed to their cancer and its treatment. Increasingly, cancer patients have many other chronic comorbid conditions. However the degree to which these comorbid conditions may contribute to patient-reported symptom burden is unclear.
Methods
We explored the relationship between the presence of comorbid conditions, symptom experience and burden, and perceived bother from cancer or comorbid conditions in 3106 cancer patients. We examined the associations between number of comorbidities (identified based on current medications), patient-reported symptom burden (the number of symptoms scored ≥7 on the 13-item MDASI physical scale), patient-reported bother from comorbid conditions and from cancer (‘not at all’ to ‘extremely’) along with clinician-reported difficulty in caring for patient’s symptoms.
Results
Based on medication lists, 19% patients had at least 5 of 12 comorbid conditions. About 39% rated at least 1 symptom ≥7, and this proportion increased with increasing number of comorbid conditions (48% v 36% for patients with ≥5 v 1 comorbid conditions). One-third of patients reported moderate or worse bother, and this was significantly associated with increased number of comorbid conditions (OR=2.4) and increased symptom burden (OR=1.22). Clinicians ratings of difficulty in managing patients’ symptoms was significantly associated with bother from cancer (OR=2.0), comorbid conditions (OR=1.6), and symptom burden (OR=1.1).
Conclusions
Comorbidity is common in cancer patients and is associated with greater symptom burden and clinician reports of difficulty in managing patients’ symptoms. Greater attention to comorbid conditions is needed to optimize the symptom management of cancer patients with multimorbidity.
Keywords: comorbidity, cancer, symptom burden, outpatient cancer patients with solid tumor, SOAPP study
The number of Americans with more than one chronic condition is expected to rise from 60 million in 2000 to 81 million in 2020.1 While the increase in multimorbidity is seen among middle-aged adults, growth is greatest in those 65 and older.2 Based on self-report data from the 2009–10 National Health Interview Survey, 45% of adults ≥65 years reported at least 2 of 9 chronic conditions (hypertension, heart disease, diabetes, cancer, stroke, chronic bronchitis, emphysema, current asthma, and kidney disease), a 37% increase compared to the 1999–2000 Survey.2 Multimorbidity is associated with decrements in quality of life and functional status, and increased healthcare utilization.3–6
Cancer affects 40.8% of adults during their lifetime.7 The incidence of cancer in those over 65 is 10 times greater than in those younger than 65.8 With increasing age, those diagnosed with cancer are much more likely to have one or more pre-existing chronic conditions. Cancer patients with comorbidity have poorer survival and often do not receive various standard cancer and supportive care therapies.9–11 The impact of cancer and pre-existing comorbidity on patients’ symptom burden is only beginning to be appreciated. Whereas a few studies have highlighted the impact of multimorbidity on receipt of cancer treatment,12 fatigue and pain symptoms,13 and mortality,14 data on how comorbidity influences the patient illness experience, and overall symptom burden are sparse. To address this gap, we conducted a secondary analysis using the E2Z02 Symptom Outcomes and Practice Patterns (SOAPP) study data, which is a large-scale multicenter prospective observational study to describe the prevalence and severity of common symptoms in oncology outpatients over a 1-month period. The aims of the present analysis were to examine the associations between (1) number of comorbidities, (2) patient-reported symptom burden, (3) patient-reported bother from comorbid conditions, and (4) patient-reported bother from cancer. We also examined the association between these variables and clinician-reported difficulty in caring for the patient’s symptoms.
METHODS
Patients
All patients included in this report were enrolled in the SOAPP study. A full description of the methods has been published elsewhere.15 In total, 3,123 oncology outpatients at any point in the trajectory of their care for invasive breast, lung, prostate, or colorectal cancer were enrolled to the SOAPP study between March 2006 and May 2008. Eligible patients had to be at least 18 years of age, receiving care at an Eastern Cooperative Oncology Group (ECOG)-affiliated institution, willing to complete the follow-up survey, and judged by the study screener to have cognitive function adequate for completing study surveys. Patients were registered at 38 institutions, including 6 academic sites and 32 community clinics. Patients treated in academic centers were enrolled from disease site-specific clinics. In contrast, patients treated in community clinics were enrolled from general oncology clinics. Patients were recruited when they checked in for their clinic appointments, and patient information was collected before their visit with a clinician. Patients and their treating oncology clinicians were surveyed at the initial visit and at follow-up 28–35 days later. Further details about the study cohort have been published.16 The protocol was approved by the institutional review boards at each registering institution. All patients provided written informed consent.
Measures
Patients’ clinical and demographic information, including cancer treatment history and current therapies, were collected at baseline via patient-specific and provider-specific surveys. The protocol and case report forms are accessible on the study web site (www.ecogsoapp.org).
Symptom burden
Patients completed the modified 19-item M.D. Anderson Symptom Inventory (MDASI), a validated patient symptom assessment.17–19 Thirteen items measure physical symptoms: pain, nausea, shortness of breath, lack of appetite, dry mouth, vomiting, numbness/tingling, diarrhea, constipation, sore mouth, skin rash, hair loss and coughing. Patients rated each symptom “at its worst” in the previous 24 hours, regardless of its causes, using an 11-point numeric scale ranging from 0 (“not present”) to 10 (“as bad as you can imagine”). We defined symptom burden as the number of severe symptoms rated ≥7 on the MDASI’s 0–10 scale, on the basis of results from various studies.18, 20
Number of comorbidities
The presence of comorbid conditions was not collected in the original study. However, the use of chronic medications was collected. We therefore used medication data to identify chronic comorbid conditions using RxRisk. RxRisk is an adaptation of the Chronic Disease Score (CDS) which uses pharmacy dispensing data to identify classes of medication that are taken as proxies for the existence of chronic disease. The CDS has shown anticipated relationships with functional status, health services use, and mortality.21–23 In the SOAPP study, clinicians reported patients’ specific medications at baseline via the Medication Form, including those that were newly prescribed. In the present report, using RxRisk, we identified the presence of chronic comorbid conditions requiring ongoing management by the report of specific medications linked to those conditions. Patients were considered to have a specific disease if the patient was initiating/continuing the medications commonly used for the treatment of the disease at study entry (Supplementary Material Table A1). A total of 12 comorbid conditions were identified for this analysis: anxiety/depression/psychotic illness, cardiac disease, coronary/peripheral vascular disease, diabetes, hypertension, asthma/chronic obstructive pulmonary disease, gastric acid disorder, Parkinson disease, thyroid disorder, gout, human immunodeficiency virus (HIV), and history of transplant requiring chronic anti-rejection therapy.21
Patient-reported bother by comorbid conditions and cancer
In the study, general patient perceptions about cancer and comorbidity were assessed with exploratory items asking patients about their level of “bother” from these areas. General health perception is part of the health-related quality of life model described by Wilson and Cleary which links biological and physiological factors, symptoms, functioning, and general health perceptions to overall quality of life.24 Patients rated how bothered they were by “difficulties related to health problems other than cancer” using a 5-point scale from ‘not at all’ to ‘extremely’. Patients rated their bother due to cancer in a similar way.
Clinician-reported difficulty in managing patient’s symptoms
For each enrolled patient, his/her oncology clinician was asked “Relative to other patients with same stage of disease, how would you categorize the degree of difficulty in caring for this patient’s physical/psychological symptoms?”. Potential responses included “very difficult”, “difficult”, “average”, “easier than average”, and “much easier than average”.
Statistical analysis
The association between categorical and binary variables was examined using the Chi-square test. Linear regression models were constructed to examine how the number of comorbid conditions affected symptom burden. Logistic regression models were used to examine the association between the numbers of comorbidities, symptom burden and bother due to cancer and due to comorbidities, and to explore factors associated with clinician-reported difficulty in caring for patients’ symptoms. Adjusted covariates were the same in all models and included age, years since diagnosis, race/ethnicity, disease status, disease stage, ECOG performance status (PS), weight loss in the past 6 months, prior systemic therapy, prior radiotherapy, current therapy, total number of current medicines, individual counseling, and participation in support group. The Variance Inflation Factor (VIF) was used to check multicollinearity among covariates in the multivariable regression models (VIF<3 for all variables). Major model assumptions (independence, equal variance, normality, linearity) were checked for linear models, and Hosmer-Lemeshow tests were used to check model fit for logistic models. A few variables had some modest missing data, and a separate category for missing data was generated for categorical covariates if the proportion of missingness was greater than 5 percent. Otherwise, patients with missing data were excluded from the regression models. Clustered sandwich estimators of standard errors were used in all regression models to account for the clustering effect of institutions. All P values were two-sided and P < 0.05 was considered statistically significant. No adjustment was made for multiple comparisons. STATA 13.1 software (2009; StataCorp, College Station, TX) was used for all data analysis.
RESULTS
Patient characteristics and comorbidity prevalence
Table 1 summarizes the sample’s clinical and demographic characteristics, as well as the prevalence and type of comorbidities. Of 3123 patients total, 3106 patients were analyzed. Of those 50% had breast cancer, 23% had colorectal cancer, 17% had lung cancer and 10% had prostate cancer. The median age was 61 years. Overall, 2,432 (78%) patients reported initiating or continuing medications for at least one of the 12 comorbid conditions; 18% had 1 comorbid condition, and 19% had 5 or more comorbid conditions. The most common comorbid condition was hypertension (45%), followed by anxiety/tension/psychotic illness (35%). In multivariable linear regression models, lung cancer, increased age, minority status, increased time since cancer diagnosis, poor performance status, taking more medications and receiving counseling were associated with more comorbid conditions (data not shown). Patients with metastatic cancer, currently receiving cancer treatment or participating in a support group were likely to report fewer comorbid conditions (data not shown).
Table 1.
Patient Characteristics and comorbidity at baseline (N=3106)
| Variable | No. of pts | % |
|---|---|---|
| Demographic characteristics | ||
| Age (median, range) | 61 | 18–93 |
| Sex | ||
| Women | 2170 | 69.9 |
| Men | 936 | 30.1 |
| Race (n=37 missing) | ||
| White | 2648 | 86.3 |
| Black | 364 | 11.9 |
| Others | 57 | 1.8 |
| Ethnicity (n=249 missing) | ||
| Hispanic | 285 | 10.0 |
| Non-Hispanic | 2572 | 90.0 |
| ECOG PS (n=15 missing) | ||
| 0 | 1755 | 56.8 |
| 1 | 1105 | 35.8 |
| 2–4 | 231 | 7.5 |
| Type of institution | ||
| Academic | 303 | 9.8 |
| Community | 2803 | 90.3 |
| Disease characteristics and treatment | ||
| Years since cancer diagnosis (median, range) (n=51 missing) | 1.2 | 0.0–52.3 |
| Disease site | ||
| Breast | 1544 | 49.7 |
| Colorectal | 718 | 23.1 |
| Prostate | 320 | 10.3 |
| Lung | 524 | 16.9 |
| Disease status (n=20 missing) | ||
| Complete remission | 1157 | 37.5 |
| Partial remission | 147 | 4.8 |
| Stable disease | 1336 | 43.3 |
| Progressive disease | 446 | 14.5 |
| Disease stage (n=11 missing) | ||
| No evidence of disease | 1332 | 43.0 |
| Locoregional | 589 | 19.0 |
| Metastatic | 959 | 31.0 |
| Locoregional + metastatic | 215 | 7.0 |
| Patient currently receive therapy | ||
| No | 807 | 26.0 |
| Yes | 2299 | 74.0 |
| Prior systemic therapy (n=1 missing) | ||
| No | 1195 | 38.5 |
| Yes | 1910 | 61.5 |
| Prior radiation therapy (n=27 missing) | ||
| No | 1782 | 57.9 |
| Yes | 1297 | 42.1 |
| Total number of different medications currently taking (n=311 missing) | ||
| 0–4 | 900 | 32.2 |
| 5–9 | 1,208 | 43.2 |
| 10 or more | 687 | 24.6 |
| Individual counseling (n=12 missing) | ||
| No | 2795 | 90.3 |
| Yes | 299 | 9.7 |
| Participation in support group (n=12 missing) | ||
| No | 2890 | 93.4 |
| Yes | 204 | 6.6 |
| Comorbidity conditions (n=3106) | ||
| No comorbidity | 674 | 21.7 |
| Any comorbidity | 2432 | 78.3 |
| Median (range) | 3 (1–12) | |
| 1 comorbid condition | 560 | 18.0 |
| 2 comorbid conditions | 525 | 16.9 |
| 3 comorbid conditions | 425 | 13.7 |
| 4 comorbid conditions | 327 | 10.5 |
| ≥5 comorbid conditions | 595 | 19.2 |
| Type of comorbidity (n=3106) | ||
| Hypertension | 1411 | 45.4 |
| Anxiety/depression | 1088 | 35.0 |
| Gastric acid disorder | 806 | 25.9 |
| Coronary/peripheral vascular disease | 791 | 25.5 |
| Cardiac disease | 723 | 23.3 |
| Diabetes | 360 | 11.6 |
| Thyroid disorder | 295 | 9.5 |
| Asthma/chronic obstructive pulmonary disease | 291 | 9.4 |
| Gout | 34 | 1.1 |
| Parkinson’s disease | 29 | 0.9 |
| Rejection | 5 | 0.2 |
| Human immunodeficiency virus | 1 | 0.03 |
Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status.
Symptom burden and its association with comorbidity
Approximately 39% of patients reported having at least 1 severe symptom (i.e., rated the severity of at least 1 symptom ≥7) (Table 2). The proportion increased with increasing number of comorbid conditions (48% v 36% for patients with ≥5 v 1 comorbid conditions). With the exception of skin rash and hair loss, the percent of severe symptoms (≥7) was highest among those with the highest number of comorbid conditions (Supplementary Material Table A2). The multivariable linear regression analysis showed a positive linear association between number of comorbid conditions and patient-reported symptom burden (p<0.001), adjusting for cancer-related factors and other variables (Table 3, Model 1). Cancer-related factors (no response to cancer therapy, prior systemic therapy, and current cancer treatment) were significantly associated with increased symptom burden as well (data not shown). Other characteristics associated with increased symptom burden included younger age, minority status, poor PS, and >5% weight loss in the past 6 months (data not shown).
Table 2.
Prevalence of patient-reported symptom burden, bother from comorbid conditions, and bother from cancer (N=3106)
| Variable | Total | Number of comorbidity (Col%) | ||||||
|---|---|---|---|---|---|---|---|---|
| N | Col% | 0 (n=668) | 1 (n=558) | 2 (n=521) | 3 (n=425) | 4 (n=326) | 5–12 (n=593) | |
| Total number of symptoms scored ≥7 (n=15 missing) | ||||||||
| 0 | 1,882 | 60.9 | 66.5 | 64.3 | 62.8 | 58.4 | 60.1 | 51.9 |
| 1–3 | 967 | 31.3 | 28.4 | 30.1 | 30.1 | 32.9 | 30.7 | 35.8 |
| 4–6 | 192 | 6.2 | 3.7 | 4.3 | 6.0 | 6.6 | 8.0 | 9.8 |
| 7–9 | 39 | 1.3 | 0.9 | 1.3 | 1.0 | 1.7 | 0.9 | 1.9 |
| 10–13 | 11 | 0.4 | 0.5 | 0.0 | 0.2 | 0.5 | 0.3 | 0.7 |
| ≥1 | 1,209 | 39.1 | 33.5 | 35.7 | 37.2 | 41.6 | 39.9 | 48.1 |
| ≥2 | 673 | 21.8 | 16.3 | 17.2 | 20.9 | 23.1 | 24.5 | 30.5 |
| ≥3 | 394 | 12.7 | 10.0 | 9.0 | 12.1 | 14.1 | 13.8 | 18.4 |
| ≥5 | 140 | 4.5 | 3.4 | 3.0 | 4.0 | 5.2 | 4.3 | 7.3 |
| Bother from comorbidities (n=15 missing) | ||||||||
| Not at all | 1,083 | 35.0 | 49.5 | 44.4 | 36.3 | 27.6 | 26.7 | 18.8 |
| A little bit | 996 | 32.2 | 27.5 | 31.8 | 32.6 | 35.9 | 37.1 | 32.3 |
| Moderately | 638 | 20.6 | 14.8 | 16.1 | 20.9 | 22.2 | 25.2 | 27.7 |
| Quite a bit | 315 | 10.2 | 6.6 | 6.1 | 9.2 | 11.3 | 9.8 | 18.4 |
| Extremely | 59 | 1.9 | 1.6 | 1.6 | 1.0 | 3.1 | 1.2 | 2.9 |
| Moderate/quite a bit/extremely | 1,012 | 32.7 | 23.0 | 23.8 | 31.1 | 36.6 | 36.2 | 49.0 |
| Bother from cancer (n=23 missing) | ||||||||
| Not at all | 655 | 21.3 | 23.2 | 23.1 | 19.9 | 20.0 | 26.2 | 16.8 |
| A little bit | 926 | 30.0 | 33.5 | 30.8 | 30.6 | 29.2 | 24.9 | 28.3 |
| Moderately | 803 | 26.1 | 20.9 | 26.3 | 26.0 | 27.6 | 25.2 | 31.0 |
| Quite a bit | 557 | 18.1 | 17.2 | 15.6 | 19.3 | 18.8 | 20.0 | 18.8 |
| Extremely | 142 | 4.6 | 5.2 | 4.1 | 4.2 | 4.5 | 3.7 | 5.3 |
| Moderate/quite a bit/extremely | 1,502 | 48.8 | 43.4 | 46.1 | 49.5 | 50.8 | 48.9 | 55.0 |
Table 3.
Multivariable regression analyses for symptom burden, bother from comorbid conditions, bother from cancer, and clinician-reported difficulty in caring for patients’ symptoms
| Model* | Dependent variable | Independent variable | Coef† | 95% CI | P value | |
|---|---|---|---|---|---|---|
|
| ||||||
| Model 1: Association between comorbidity and symptom burden (linear regression) | Symptom burden (continuous) | Number of comorbidities (continuous) | 0.10 | 0.06 | 0.14 | <0.001 |
|
| ||||||
| Model 2: Association of comorbidity and symptom burden with bother from comorbidity (logistic regression) | Bother from comorbidity (moderately or more bothered=1) | Number of comorbidities (ref=0) | ||||
|
| ||||||
| 1 | 1.06 | 0.85 | 1.32 | 0.586 | ||
|
| ||||||
| 2 | 1.48 | 1.18 | 1.85 | 0.01 | ||
|
| ||||||
| 3 | 1.65 | 1.16 | 2.34 | 0.05 | ||
|
| ||||||
| 4 | 1.64 | 1.16 | 2.31 | 0.05 | ||
|
| ||||||
| ≥5 | 2.41 | 1.83 | 3.17 | <0.001 | ||
|
| ||||||
| Symptom burden (continuous) | 1.22 | 1.16 | 1.28 | <0.001 | ||
|
| ||||||
| Model 3: Association of comorbidity and symptom burden with bother from cancer (logistic regression) | Bother from cancer (moderately or more bothered=1) | Number of comorbidities (ref=0) | ||||
|
| ||||||
| 1 | 0.99 | 0.74 | 1.33 | 0.952 | ||
|
| ||||||
| 2 | 1.19 | 0.88 | 1.60 | 0.259 | ||
|
| ||||||
| 3 | 1.20 | 0.90 | 1.60 | 0.205 | ||
|
| ||||||
| 4 | 0.98 | 0.63 | 1.52 | 0.935 | ||
|
| ||||||
| ≥5 | 1.13 | 0.74 | 1.75 | 0.569 | ||
|
| ||||||
| Symptom burden (continuous) | 1.52 | 1.38 | 1.66 | <0.001 | ||
|
| ||||||
| Model 4: Factors associated with clinician’s difficulty in caring for patients’ symptoms (logistic regression) | Difficulty in caring for patients’ symptoms (more difficult=1) | Bother from comorbidity(moderate or more vs. other) | 1.58 | 1.17 | 2.13 | 0.003 |
|
| ||||||
| Bother from cancer(moderate or more vs. other) | 1.99 | 1.42 | 2.80 | <0.001 | ||
|
| ||||||
| Number of comorbidities (continuous) | 1.01 | 0.93 | 1.08 | 0.939 | ||
|
| ||||||
| Symptom burden (continuous) | 1.14 | 1.06 | 1.22 | <0.001 | ||
Adjusted covariates were the same in all models and included age, years since diagnosis, race/ethnicity, disease status, disease stage, ECOG PS, weight loss in the past 6 months, prior systemic therapy, prior radiotherapy, current therapy, total number of current medicines, individual counseling, and participation in support group.
Coef is odds ratio (OR) in the logistic regression analysis (models 2–4), and it is the expected change in number of symptoms with rating ≥7 associated with 1 more comorbid condition in the linear regression analysis (model 1).
Patient-reported bother from comorbidity and from cancer
One-third of patients were bothered moderately or worse due to comorbidity, and the proportion increased with increasing number of comorbid conditions (23.8%, 31.1%, 36.6%, 36.2%, 49.0% for 1, 2, 3, 4, ≥5 comorbid conditions, respectively, Ptrend<0.001, Table 2). There was also a strong positive association between patient-reported symptom burden and patient-reported bother due to comorbidity. Among those not or slightly bothered by comorbidity, ≥1 symptom was rated 7 or worse by 33% of patients, compared to 52% in patients at least moderately bothered by comorbidity (Fisher’s exact p<0.001). In addition, the proportion of patients rating ≥7 for each symptom (except for hair loss) was higher among patients reporting moderate or worse bother from comorbidity (data not shown). These associations remained significant in the multiple logistic regression analysis adjusting for other covariates (Table 3, Model 2). Patients had 2.4 times higher odds (95% CI: 1.8, 3.2) of being moderately or more severely bothered by comorbidity if they had 5 or more comorbid conditions compared to no comorbidity. The odds of being bothered by comorbidity increased by 22% with every additional symptom rated as severe (i.e., ≥7). Patients with breast cancer, longer period since cancer diagnosis, poor PS, and receiving counseling services were more likely to be bothered by comorbidity (data not shown).
About half of patients reported moderate or worse bother from cancer, and it was significantly associated with cancer characteristics (lung cancer, shorter period since cancer diagnosis, advanced disease, no response to cancer treatment) and symptom burden, and did not change with increasing number of comorbid conditions (Table 3, Model 3).
Clinician-reported difficulty in managing patients’ symptoms
Compared to patients with the same stage of disease, clinicians reported greater difficulty caring for patients’ physical /psychological symptoms if the patient reported greater symptom burden (odds ratio {OR} =1.1, 95% CI: 1.1, 1.2), greater bother from comorbidity (OR=1.6, 95% CI: 1.2, 2.1), or greater bother from cancer (OR=2.0, 95% CI: 1.4, 2.8) (Table 3, Model 4). It was not associated with the number of comorbidities. Breast cancer, non-complete response status, no current cancer treatment, older age, and poor PS were associated with the provider’s perception of increased difficulty in providing care (data not shown).
DISCUSSION
To our knowledge, the SOAPP study is the largest prospective evaluation of comorbidity and symptom burden in outpatient oncology patients with solid tumors in the United States to date. This secondary analysis of the SOAPP study shows that the presence of multiple chronic comorbid conditions is quite common in cancer patients and the number of comorbid conditions is positively associated with patient-reported symptom burden, adjusting for cancer-related factors. Few other studies have examined this relationship. In Hung’s relatively small study of 134 colorectal cancer patients, the presence of comorbidity was associated with increased pain but not with increased overall physical symptoms.19 In a systemic review limited to breast cancer, the number of comorbid conditions increased with age, was associated with symptom burden, functional decline, and low adherence to surveillance, and also with decreased quality of life; however this study did not describe patient-reported bother and symptom severity.25, 26 In a systematic review of cancer-related fatigue, comorbidity was associated with increased levels of fatigue; however, no other symptoms were evaluated nor was patient-reported bother.27 In the CanCORS study, lung or colorectal cancer patients with limited financial reserves were more likely to have higher symptom burden and decreased quality of life; however, financial reserve was the main focus of the study and comorbidity or bother due to other symptoms was not examined.28 None of the previous studies looked for clinician reported difficulty in patient management and how it related to patients’ experience of comorbidity or symptom burden. It is not uncommon to attribute patients’ symptoms to cancer,29 but the results of this analysis suggest that comorbidity should be adequately acknowledged and thoroughly considered as a contributor to symptom burden in managing cancer patients.
Our study also suggests that patients with advanced cancer, those receiving active cancer treatment or support group participants had fewer comorbid conditions. This finding is consistent with previous studies which have reported that compared to patients without comorbidity, those with more comorbidities may be less likely to receive standard cancer treatment.9, 12 Thus, decisions related to cancer treatment may depend not only on the type and stage of cancer, but also on type and severity of comorbidity rather than number of comorbidities. It should be noted, however, that the relationship between comorbidity and metastatic cancer may be confounded by the methodology by which comorbidity was ascertained. Our study identified comorbidity through the patients’ exposure to active medications for a chronic condition. It is possible that for a subset of patients with advanced cancer, medications for some chronic conditions were discontinued or did not appear on their medication list, decreasing our ability to capture these comorbid conditions.
Overall, we found that about one-third of cancer patients are at least moderately bothered by comorbidity. Mental health comorbidity was common. The number of comorbid conditions, symptom burden, duration of cancer, age and performance status were all associated with bother from comorbidities. Bother from comorbidity may be an indicator of treatment burden, a concept only recently being appreciated in the multimorbidity literature.30 Patient-reported bother from comorbid health problems and from cancer was positively associated with clinician-reported difficulty in caring for a patient’s physical /psychological symptoms compared to patients with the same stage of disease. Because treatment burden is influenced by the particular treatment a condition requires (e.g. diabetes requires more interventions than hypertension), it is not altogether surprising that the degree to which patients were bothered by their comorbid conditions was of greater importance than the number of comorbidities.
Bother due to both cancer and to comorbid conditions plays an important role in patient experience and also appears to serve as an indicator for complexity in patient care. Careful exploration of the determinants of bother and symptom burden, focusing not only on the patient’s underlying cancer but also their comorbid conditions, may improve overall quality of life. With aging and the increasing prevalence of chronic co-occurring conditions, clinical challenges associated with comorbidity will increase. Because comorbidity is associated with symptom burden and perceived care complexity, clinicians and health systems will have to attend to the interplay between comorbid conditions, solid tumor treatment, and symptom management.
There are several important limitations in the study. First, the analyses presented in this paper represent a secondary data analysis from the large prospective multicenter SOAPP study. Second, although not an uncommon practice for comorbidity assessment, the measurement of comorbidity was derived from medication data. In this cancer population, 12 comorbid conditions were definitively identified based on medication data. While this list may not have included every condition, it provided a list of actively treated conditions most likely to contribute to disease burden. Third, symptom burden is measured using the MDASI physical scale and only considers the severity of the symptom in the previous 24 hours, and does not capture chronicity. Fourth, the term “bother”, while common and understandable in everyday life, may represent more than one domain including general health perception and illness or treatment-related burden. This exploratory item from the SOAPP study is worthy of further study. That the number of comorbidities was not associated with patient-reported bother from cancer (but was associated with patient-reported bother from comorbidities) supports that patients were effective in distinguishing between the cancer and comorbid conditions. Lastly, these findings can be generalized only to patients with common solid tumors who receive care at academic and community sites associated with the US National Cancer Institute clinical trials network.
In conclusion, comorbidity is common in cancer patients, and symptom burden varies significantly according to the number of comorbid conditions. Clinicians may enhance the care of patients with cancer by taking into account the role of comorbidities in symptom burden. Future research should focus prospectively and longitudinally on the role of multiple co-occurring conditions on symptom burden, treatment complexity, patient experience, and overall illness burden, with the goal of reducing suffering and improving quality of life for patients with solid tumors.
Supplementary Material
Acknowledgments
Funding: This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, MD) and supported in part by Public Health Service Grants CA34604 and CA27525, and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Drs. Fisch and Zhao had full access to the data. Dr. Ritchie made the decision to submit them for publication.
Footnotes
Disclosures: The authors made no disclosures.
Author contributions: Conception and design: Christine S. Ritchie, Fengmin Zhao, Michael J. Fisch
Data analysis and interpretation: Fengmin Zhao and Judith Manola
Manuscript writing: All authors
Final approval of manuscript: All authors
Previous presentation: Presented as a poster (abstr # 6080) at the American Society of Clinical Oncology Annual Meeting, Chicago, Illinois, June 1-5, 2012.
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