Abstract
Background:
While radiation therapy (RT) improves function, and quality of life for patients with advanced cancers, patients frequently experience a period of acute toxicity during which functional abilities may decline. Little is understood about changes in functional outcomes after RT in older adults. This study aims to examine changes in daily function at 1 and 6 months following RT.
Methods:
We reviewed the charts of 117 patients who underwent palliative RT on a prospective registry. Activities of daily living (ADL) and instrumental activities of daily living (IADL) scores ranging from 0 to 6 and 0–8, respectively, were collected at baseline, one-month, and six months post-RT. Patients were classified as low deficit for ADL/IADL if they had 0–1 deficits and high deficit if they had 2+ deficits.
Results:
One-hundred seventy RT courses were identified; 99 were evaluable at each time point. The median age was 67 years. At baseline, 29.5 and 29.9% of patients were classified as high-deficit for ADL and IADL functioning, respectively. At one-month, the majority of patients who were low-deficit at baseline remained so for both measures while approximately one quarter of high-deficit patients showed improvement. Most patients identified as low-deficit at one-month remained so at six-months, while no high-deficit patients improved from one- to six-months. Factors associated with high ADL and IADL deficits included: time (six months), increasing age, and Hispanic/other race. Compared to those with ECOG score of 3, patients with lower scores (0–2) had lower odds of high deficit.
Conclusion:
ADL and IADL tools may be useful in describing changes in daily function after palliative RT and in identifying groups of patients who may benefit from additional supportive geriatric care interventions.
Keywords: Palliative RT, ADL, IADL, Radiation oncology
1. Introduction
Radiation therapy (RT) is an integral component of cancer treatment, with up to 60% of cancer patients receiving radiotherapy as part of their oncologic care [1,2]. In over a third of cases, RT is given with palliative intent – meaning, to improve quality of life (QOL) and functional abilities [3–5], as opposed to achieving cure. Palliative RT, which targets patients with advanced cancer who have metastatic lesions in bone, brain, spine, soft tissues or visceral organs causing pain, obstruction, bleeding, or nerve damage [6,7] [ 8–10], may also lead to temporary adverse effects (e.g. fatigue, nausea, diarrhea, and exacerbations of pain) and possibly result in additional burdens negatively impacting QOL or function. Older adults who already harbor an increased risk of functional impairments may be increasingly vulnerable to new or worsened impairments in function and mobility [11–14]. However, little is known of the frequency and magnitude of these impairments during and after RT [25,26].
Activities of daily living (ADL) and instrumental activities of daily living (IADL) are a key measure of daily functioning in older adults, with up to one-third and one-half of patients experiencing deficits in each domain, respectively [27]. Medical oncologists have long recognized that geriatric conditions impact the tolerability of chemotherapy, and validated instruments utilizing these factors are able to predict chemotherapy toxicity better than traditional oncology performance scales. [15–24]. Similar data in radiation oncology is lacking. To further investigate the impact of RT on these functional patient outcomes, we examined changes in ADL and IADL functioning in a cohort of radiation patients with advanced malignancies treated with palliative intent within the Mount Sinai Health System.
2. Materials and Methods
We identified patients >18 years of age with metastatic or advanced/incurable cancer from a prospectively enrolled registry (2018–2020) of palliative radiotherapy at two hospitals in the Mount Sinai Health System, both located in Manhattan (Mount Sinai Hospital and Mount Sinai West). Functional data (ADL and IADL) and demographics were abstracted from electronic health records, as well as detailed information about RT, chemotherapy, toxicities, and other available performance status information. We defined ADL functions as toileting, feeding, dressing, grooming, ambulating, and bathing. Patients received a score of “0” if they had no deficits and a score of “6” if deficits were appreciated in all domains. We defined IADL measures as using the telephone, shopping, preparing foods, housekeeping, washing laundry, managing transportation, managing medications, and managing finances. Patients received a score of “0” if they had no deficits and a score of “8” if deficits were appreciated in all domains. ADL and IADL details were ascertained via the available physical therapy, occupational therapy, social work, physician, and nursing documentation. Data were collected for three time points; prior to beginning RT and one- and six months after completing RT.
Our primary goal was to evaluate ADL and IADL functioning at each time point before and after palliative RT. Patients were classified as low-deficit for ADL/IADL if they had 0–1 deficits and high-deficit if they had 2 or more deficits. Predictors of ADL/IADL outcomes included age, number of RT fractions, sex (male vs. female), race (White vs. Black vs. Hispanic/other), treatment site (bone/spine vs. other), chemotherapy within 2 months (yes vs. no) and European Cooperative Oncology Group Performance Status (ECOG-PS) (good (0–2) vs. 3 vs. 4), a commonly used performance scale in oncology to assess fitness for chemotherapy or radiotherapy [20–28].
Summary statistics including frequencies and percentages for categorical variables and median with range for continuous variables were estimated to examine the distribution of predictors and outcomes. Generalized linear mixed models were fitted to assess the association between high deficits and time and to determine predictors associated with high deficits. Demographics were tabulated for each individual patient while ADL and IADL measures were collected for each individual course of radiation. All analyses were conducted using statistical analysis software (SAS) version 9.4.
3. Results
A total of 117 patients enrolled in the registry who underwent a total of 170 courses of radiation therapy (RT) were included in our analyses. Of these, 99 courses of RT were fully evaluable at all three time points. The remaining RT courses were missing information for at least one time point and were thus excluded. Cohort demographics (n = 117) are listed in Table 1. The median age of the cohort was 67 years. Of these, 57.3% of patients were aged ≤65 years. The most common sites of cancer origin were lung (22.2%) and breast (21.4%). The most common sites of palliative RT treatment were spine (29.9%) and bone (20.5%), and the median RT dose delivered per course was 30 Gray (range: 4–54 Gray). A total of 29 patients received more than one course of radiation (range 1–8 RT courses).
Table 1.
Patient demographics.
| Variable | Total n = 117 |
|---|---|
| Age | Median 67; Range 20–91 |
| 57.26% 65+ years old | |
| Gender | |
| Male | 48.72% (n = 57) |
| Female | 51.28% (n = 60) |
| ECOG PS | |
| 0 | 26.13% (n = 29) |
| 1 | 23.42% (n = 26) |
| 2 | 18.92% (n = 21) |
| 3 | 20.72% (n = 23) |
| 4 | 10.81$ (n = 12) |
| Race | |
| White | 33.62% (n = 39) |
| Black | 25.86% (n = 30) |
| Hispanic/Other | 40.51% (n = 47) |
| Unknown | (n = 1) |
| Treatment Site | |
| Bone/Spine | 50.42% (n = 59) |
| Other | 44.12% (n = 58) |
| Primary Site | |
| Breast | 21.37% (n = 25) |
| Prostate | 12.82% (n = 15) |
| Gastrointestinal Tract | 12.82% (n = 15) |
| Lung | 22.22% (n = 26) |
| Bone Marrow | 10.26% (n = 12) |
| Bladder/Kidney | 7.69% (n = 9) |
| Other | 12.82% (n = 15) |
| RT Dose | Median 29.6 Gray; Range 4–54 Gray |
| Planned RT Dose | Median 30 Gray; Range 4–54 Gray |
| Fractions | Median 6; Range 1–20 |
| Dose/Fraction | Median 3.7 Gray; Range 2–21 Gray |
| RT Courses Received | Median 1; Range 1–8 |
| ADL Functions | |
| Toilet | No Deficit |
| Deficit | |
| Feeding | No Deficit |
| Deficit | |
| Dressing | No Deficit |
| Deficit | |
| Grooming | No Deficit |
| Deficit | |
| Ambulation | No Deficit |
| Deficit | |
| Bathing | No Deficit |
| Deficit | |
| IADL Functions | |
| Telephone Use | No Deficit |
| Deficit | |
| Shopping | No Deficit |
| Deficit | |
| Food Preparation | No Deficit |
| Deficit | |
| Housekeeping | No Deficit |
| Deficit | |
| Laundry | No Deficit |
| Deficit | |
| Transportation | No Deficit |
| Deficit | |
| Medication Management | No Deficit |
| Deficit | |
| Financial Management | No Deficit |
| Deficit | |
ECOG PS- Eastern Cooperative Oncology Group Performance Status.
Tables 2A and B describe how ADL and IADL deficit groupings evolved from baseline to the one- and six-month time points. At baseline, 117 (70.5%) patients were classified as low-deficit based on ADL function, with the remaining 49 (29.5%) patients classified as high deficit. Of 108 patients originally classified as low deficit that were evaluable one month after RT, 98 (90.7%) patients remained low-deficit, while ten (9.3%) became high deficit. Eighty-two patients classified as low-deficit at one-month were evaluable six months after RT. Of these, 65 (79.3%) remained low-deficit, while seventeen (20.7%) became high-deficit. Both patients who became high-deficit at one-month and were evaluable six months after RT remained high-deficit. Of the 30 patients found to be high-deficit at baseline who were evaluable at one-month, 23 (76.7) remained high-deficit at six-months, while seven patients (23.3%) improved to low-deficit. All twelve remaining patients from the high-deficit group at one-month were classified as high-deficit at six-months while two of three (66.7%) remaining patients in the low-deficit group continued to be low-deficit.
Table 2.
|
|
ADL- Activities of daily living; RT- Radiation Therapy; IADL- Instrumental activities of daily living; RT- Radiation Therapy.
Similarly, 115 (70.1%) patients were classified as low-deficit for IADL function at baseline, while 49 (29.9%) were classified as high-deficit. One-hundred and six patients who were low-deficit at baseline remained evaluable at one-month post-RT, with 92 (86.8%) continuing as low-deficit and 14 (13.2%) declining to high-deficit. Of 76 patients who were evaluable and low deficit at 1-month, 66 (86.8%) remained low-deficit at six-months, while ten (13.2%) became high-deficit. Thirty patients who were high-deficit at baseline were analyzed at one-month post-RT, with seven (23.3%) improving to low-deficit and 23 (76.7%) remaining high-deficit. The twelve remaining patients from the high-deficit group at one-month were classified as high-deficit at six-months while two of three (66.7%) patients in the low-deficit group continued to be classified as low-deficit at six months. The results for the subset of patients aged 65 years and older were similar and can be seen in Tables 2C and D for both ADL and IADL outcomes.
The proportion of patients classified as high-deficit at baseline decreased numerically from 29.5% at baseline to 22.6% at one-month (OR: 0.74; 95% CI: 0.41–1.32) but returned to a near-baseline value of 29.3% (OR: 1.43; 95% CI: 0.77–2.67) at six months on univariate analysis. Similar findings were seen for IADL function with 29.9% of patients-classified as high deficit at baseline, 27.0% at one-month (OR: 0.97; 95% CI: 0.54–1.73), and 29.3% at six months (OR: 1.40; 95% CI 0.73–2.68). All odds ratios represent comparisons to baseline values. After adjusting for age, gender, race/ethnicity, treatment site, fractions, ECOG score and completion of chemotherapy, patients evaluated at both baseline and six-months had significantly higher odds of being classified as high-deficit in both ADL (OR: 3.03; 95% CI 1.37, 6.69) and IADL (OR: 3.09, 95% CI: 1.37, 6.97) functions at the six-month time point as compared to baseline. An additional analysis was conducted where low-deficit was defined as having no impairments in ADL/IADL function and high-deficit was defined as having one or more deficits. The results did not differ significantly from the original analysis and are depicted in the supplemental table.
Within the subgroup of patients aged 65 and older, 34.1% and 36.1% were classified as high-deficit in ADLs and IADLs at baseline, respectively. At one-month post-RT, 25.7% of patients were high-deficit in ADLs (OR: 0.74; 95% CI: 0.34–1.59) and 35.7% in IADLs (OR: 1.19; CI: 0.56–2.53) on univariate analysis. At six months, 29.4% were classified as high-deficit in ADLs (OR: 1.23; CI: 0.54–2.82) and 37.3% in IADLs (OR: 1.69; CI: 0.73–3.93). Similar to the analysis for all patients, odds ratios represent comparisons to baseline values. In the multivariate model, patients 65 and older had significantly higher odds of being classified as high deficit at six months as compared to baseline in both ADL (OR: 3.16, 95% CI: 1.10, 9.06) and IADL function (OR: 4.04, 95% CI 1.41, 11.56).
As compared to an ECOG score of 3, an ECOG score of 0–2 was associated with lower odds of being high-deficit (OR: 0.03; 95% CI: 0.01–0.08) in ADL function. This analysis was conducted to determine if there was an association between ECOG PS and ADL/IADL risk groups. Hispanic/other race (OR: 4.19; 95% CI: 1.49–12.13) and increasing age (OR: 1.05; 95% CI: 1.01–1.09) were also associated with being classified as high-deficit in ADLs. Similar findings were appreciated for IADL outcomes (Table 3). These investigations were pursued to help identify subsets of patients at an increased likelihood of ADL/IADL dysfunction.
Table 3.
Linear mixed model regression analysis.
| ADL |
||||||
|---|---|---|---|---|---|---|
| Unadjusted models |
Adjusted models |
|||||
| OR | 95% CI | P-value | OR | 95% CI | P-value | |
| Time | ||||||
| Baseline | Reference | |||||
| 1-month | 0.74 | 0.41, 1.32 | 0.30 | 0.92 | 0.43, 2.00 | 0.84 |
| 6-month | 1.43 | 0.77, 2.67 | 0.26 | 3.03 | 1.37, 6.69 | 0.01 |
| Age | 1.03 | 1.00, 1.06 | 0.24 | 1.05 | 1.01, 1.09 | 0.01 |
| Gender | ||||||
| Male | Reference | |||||
| Female | 1.19 | 0.62, 2.30 | 0.59 | 1.15 | 0.50, 2.64 | 0.75 |
| Race | ||||||
| White | Reference | |||||
| Black | 0.49 | 0.19, 1.25 | 0.13 | 0.80 | 0.24, 2.65 | 0.71 |
| Hispanic/Other | 1.14 | 0.53, 2.45 | 0.74 | 4.19 | 1.45, 12.13 | 0.01 |
| Treatment Site | ||||||
| Two or more sites (e.g. Bone and Spine etc.) | Reference | |||||
| Bone | 0.34 | 0.09, 1.38 | 0.13 | 0.52 | 0.09, 3.04 | 0.46 |
| Spine | 0.54 | 0.14, 2.06 | 0.36 | 0.66 | 0.12, 3.55 | 0.63 |
| Whole brain radiation | 0.73 | 0.13, 4.24 | 0.73 | 0.60 | 0.07, 5.25 | 0.64 |
| Brain stereotactic radiosurgery | 0.31 | 0.07, 1.43 | 0.13 | 1.00 | 0.14, 7.35 | 1.00 |
| Other | 0.72 | 0.16, 3.28 | 0.67 | 1.27 | 0.19, 8.45 | 0.80 |
| Fractions | 1.11 | 1.02, 1.20 | 0.01 | 1.10 | 0.98, 1.24 | 0.11 |
| ECOG | ||||||
| 0–2 | 0.04 | 0.02, 0.10 | <0.01 | 0.03 | 0.01, 0.08 | <0.01 |
| 3 | Reference | |||||
| 4 | 1.53 | 0.31, 7.54 | 0.60 | 1.33 | 0.22, 8.22 | 0.76 |
| Chemotherapy | ||||||
| No | Reference | |||||
| Yes | 0.56 | 0.29, 1.06 | 0.08 | 0.70 | 0.31, 1.58 | 0.39 |
| IADL | ||||||
| Unadjusted Models | Adjusted Models | |||||
| OR | 95% CI | P-value | OR | 95% CI | P-value | |
| Time | ||||||
| Baseline | Reference | |||||
| 1-month | 0.97 | 0.54, 1.73 | 0.91 | 1.58 | 0.74, 3.35 | 0.24 |
| 6-month | 1.40 | 0.73, 2.68 | 0.31 | 3.09 | 1.37, 6.97 | 0.01 |
| Age | 1.05 | 1.02, 1.08 | 0.002 | 1.07 | 1.03, 1.12 | 0.002 |
| Gender | ||||||
| Male | Reference | |||||
| Female | 1.19 | 0.59, 2.38 | 0.63 | 1.49 | 0.61, 3.65 | 0.38 |
| Race | ||||||
| White | Reference | |||||
| Black | 0.52 | 0.19, 1.40 | 0.19 | 1.27 | 0.37, 4.36 | 0.71 |
| Hispanic/Other | 1.01 | 0.44, 2.30 | 0.98 | 3.94 | 1.28, 12.13 | 0.02 |
| Treatment Site | ||||||
| Two or more sites (e.g. Bone and Spine etc.) | Reference | |||||
| Bone | 0.42 | 0.09, 1.93 | 0.26 | 0.54 | 0.08, 3.70 | 0.53 |
| Spine | 0.82 | 0.19, 3.55 | 0.78 | 0.93 | 0.15, 5.86 | 0.94 |
| Whole brain radiation | 0.86 | 0.13, 5.76 | 0.88 | 0.66 | 0.06, 6.99 | 0.73 |
| Brain stereotactic radiosurgery | 0.23 | 0.04, 1.29 | 0.10 | 0.53 | 0.06, 4.87 | 0.57 |
| Other | 0.84 | 0.16, 4.37 | 0.84 | 1.36 | 0.17, 10.62 | 0.77 |
| Fractions | 1.09 | 1.00, 1.19 | 0.05 | 1.05 | 0.93, 1.18 | 0.48 |
| ECOG PS | ||||||
| 0–2 | 0.04 | 0.02, 0.10 | <0.0001 | 0.03 | 0.01, 0.09 | <0.0001 |
| 3 | Reference | |||||
| 4 | 1.36 | 0.24, 7.66 | 0.73 | 1.31 | 0.19, 9.18 | 0.79 |
| Chemotherapy | ||||||
| No | Reference | |||||
| Ye | 0.73 | 0.37, 1.45 | 0.36 | 1.08 | 0.45, 2.63 | 0.86 |
ADL- Activities of daily living; IADL- Instrumental activities of daily living; OR- Odds ratio; CI- Confidence interval; ECOG PS- Eastern Cooperative Oncology Group Performance Status.
RT was generally well-tolerated, with only 7.1% of patients experiencing any treatment-related toxicity. The most common toxicities experienced during a course of RT were nausea (n = 4) and fatigue (n = 3).
4. Discussion
To our knowledge, this study represents the first effort to use ADL and IADL scores as a means to assess functional outcomes in patients after palliative RT. We constructed risk groupings and used them to assess response to palliative RT by evaluating patient functional status at baseline and one- and six-month follow-ups. For both ADL and IADL functioning, the vast majority of patients who were classified as low-deficit at baseline remained low-deficit at one-month. Similar results were appreciated for patients who were classified as low-deficit at the one-month time point and evaluated at six months. These findings suggest that palliative RT may be strongly associated with the preservation of ADL and IADL functions for patients with metastatic disease and good pre-RT functional status.
Additionally, almost a quarter of patients who were classified as high deficit and evaluated at follow-up showed significant improvement in ADL and/or IADL functioning within one month of completing RT. These results could suggest that initial improvements in symptoms immediately after palliative RT may be leading to improvements in the ability to perform daily self-care and functional independence [8–10]. Unfortunately, no patients who were high-deficit in ADL or IADL function at one-month improved at the six-month time point, indicating that the effects of RT are realized quickly after completing treatment and that these patients may require additional interventions to improve ADL and IADL functioning.
While data explaining the reasons for declines in ADL and IADL functioning at six months after RT was not available as part of this study, it has been well documented that continued disease progression and the development of adverse effects from cancer treatments can lead to a decline in overall performance status [29]. Future investigations documenting ADL and IADL functioning at additional time points may provide more robust information on the interactions between palliative RT and ADL/IADL functioning over time and provide opportunities for additional interventions.
This study also identified increasing age as a factor predicting for worse ADL and IADL outcomes in the examined cohort of patients. The subgroup analysis for patients aged 65 and older also suggested significant odds of being classified as high-deficit in both ADLs and IADLs at each time-point. Older adults have historically suffered from worse cancer-related outcomes compared to the general population and this study only further exemplifies the need for persistent efforts to improve outcomes for these patients [14,30]. Additional resources, such as physical therapy and home health aides, may alleviate some of these healthcare disparities and allow for improved functional outcomes. Specific knowledge of the most impacted ADLs and IADLs could provide insight into where resources and interventions should be targeting, in order to make the most impactful difference for older adults.
We also found that patients of Hispanic and other (non-white) race were more likely to experience ADL and IADL deficits, suggesting there were racial and ethnic disparities in this cohort. Future studies to better understand the mechanisms should allow for improved characterization of the etiology of the disparities in these populations with interventions ultimately being tailored to minimize inequities in care.
Our analysis additionally showed that good ECOG performance status (0–2), which is in and of itself a gross assessment of function, was associated with a reduced risk of being classified as high-risk in regards tc ADL and IADL outcomes. However, performance status been shown to be of limited use in geriatric oncology as it lacks specificity, prompting medical oncologists to develop more refined tools to screen for chemotherapy fitness of older patients. Unfortunately, refinement and validation of these chemotherapy fitness tools for the radiation oncology population is limited [15,25,26]. We are hopeful that more specific measures of patient independence and functionality, such as ADL and IADL scores, will further refine our abilities to more optimally assess and care for older patients in the radiation oncology clinic.
Finally, RT was very well tolerated with low rates of overall toxicity and generally mild symptoms. Additionally, these toxicities did not lead to an increased risk of poor ADL or IADL outcomes, suggesting that RI poses a relatively low risk of adverse outcomes in this patient population. However, the overall number of toxicity events was small on this study and it is possible that larger, more comprehensive studies could find a correlation between toxicity and functional outcomes. It is also important to stress the importance of proper patient selection, RT techniques, and consideration of comorbid conditions when designing radiation treatment plans to avoid undue adverse effects.
There were a number of limitations to this study. While the patients included were enrolled on a prospective study evaluating the effects o palliative RT, ADL and IADL outcomes were collected retrospectively, reducing the ability to draw conclusions about the validity of our findings Secondly, ADLs and IADLs were not consistently documented in the patient charts, leading to lost or missing data. Additionally, a significan number of patients were lost to follow-up, likely as a direct or indirect consequence of their advanced cancer diagnoses. While this is to be expected in our population, the loss of available data points impacted our sample size and potentially introduced unknown (and thus unaccounted for) biases into our results. Finally, the retrospective nature o our data collection methods limited our ability to capture important quality of life (QOL) metrics that may help in identifying patients who will derive the largest benefit from palliative RT. We plan to capture and analyze QOL outcomes in future prospectively-designed investigations to address this limitation. Nevertheless, the study provides an important insight into the possibility that ADLs and IADLs may provide a more detailed picture of functional status changes after palliative RT and, as such, deserves further investigation.
5. Conclusion
This study identifies ADLs and IADLs as potential measures for evaluating changes in functional status after palliative radiotherapy. Our results suggest that palliative RT may be effective at preserving ADL and IADL functioning in patients with good functional status and could also be effective at restoring ADL and IADL functioning in a fraction of patients with baseline deficits. Unfortunately, patients who do not benefit within one month of treatment do not show improvement at later time points. Additionally, ADL and IADL functioning significantly worsened for the overall cohort of patients by six-months This decline may be due to disease progression, systemic therapy toxicity, or short durability of response to palliative RT doses. Finally, this study identified Hispanic/other race and increasing age as predictors of poorer ADL and IADL functioning, suggesting that these vulnerable populations may be targets for future interventions, such as home services and physical therapy. While this study has a number of limitations, ADL and IADL function appear to be useful measures of functional status for patients undergoing palliative RT and have the potential to be incorporated into routine practice with the goal of identifying patients, particularly older adults, that would most benefit from palliative RT.
Sponsors Role
This work was supported by a pilot award from the National Institute on Aging Claude D. Pepper Older Americans Independence Center under Grant #5P30AG028741 awarded to Kavita V. Dharmarajan. The authors also wish to acknowledge the support of Biostatics Shared Resource Facility, Icahn School of Medicine, and NCI Cancer Center Support Grant #P30CA196521-01. The authors have no financial disclosures or conflicts to report. The authors do not have any proprietary interests in the materials described in the article.
Footnotes
Presented at the Gerontological Society of America Meeting 2020
IRB Statement
This project was approved by the IRB at the Icahn School of Medicine at Mount Sinai.
Declaration of Competing Interest
The authors wish to declare no conflicts of interest.
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