PUTTING IN PERSPECTIVE
Central question
In older patients with cancer, do the results of a geriatric assessment lead to a change in the cancer-directed systemic therapy plan?
Key findings
Between June 2018 and September 2022, we included 617 patients.
On the geriatric assessment, only 19% of patients were fit.
Following the geriatric assessment, the systemic therapy plan was changed in 239 (38.7%) patients.
Most common treatment change was deintensification in 198 patients (32.1%).
Impact
Ours is the first Indian study to prove that the geriatric assessment alters the cancer-directed therapy plan in a substantial proportion of older patients with cancer.
This underlines the important role of the multidimensional geriatric assessment in the oncologic decision-making process.
INTRODUCTION
In older patients with cancer, deciding the optimal systemic therapy plan is challenging due to the lack of appropriate evidence-based guidelines, the presence of age-related vulnerabilities, the competing risk of death from comorbidities, and diverging treatment goals of older patients and caregivers. Older adults have been traditionally excluded from the majority of oncology clinical trials; thus, most treatment decisions in older persons with cancer are eminence-based rather than evidence-based.[ 1 ] In the absence of clear guidelines regarding the systemic therapy regimen and dose intensity, there is a risk of both overtreatment and undertreatment.[ 2 , 3 ] In a study on 397 persons aged 70 years and over, who were planned for a new cancer chemotherapy regimen, Feliu et al . reported that overall, 43% of patients had received less intensive chemotherapy despite being fit.[ 3 ]
The multidimensional geriatric assessment is a tool that helps in the decision-making process. In the geriatric assessment, an older patient with cancer undergoes various evaluations to detect the presence of non-oncologic vulnerabilities, predicted risk of chemotherapy toxicities, and non-oncologic life expectancy. Additionally, the patient’s and caregiver’s treatment goals and expectations are explored, and a shared treatment decision is made. Guidelines recommend individualizing the treatment plan for each older person with cancer based on the results of the geriatric assessment.[ 4 , 5 ] The American Society of Clinical Oncology and the International Society of Geriatric Oncology recommend that all older persons with cancer planned for therapy should undergo a geriatric assessment.[ 4 , 6 ] However, this is not widely implemented, both globally and in India. In a recent survey of 1277 cancer care providers (70% from North America), Dale et al . found that only 29% of the respondents used validated tools, i.e., conducted a geriatric assessment in their older patients with cancer.[ 7 ] Two predominantly Indian surveys reported that the situation in India was very similar; only 30% of the respondents used validated tools to assess older patients with cancer. Barriers to the widespread implementation of the geriatric assessment include time and space constraints, logistic issues, and the lack of skilled personnel to conduct the geriatric assessment, interpret the results and make recommendations.[ 8 , 9 ]
Global data suggest that the geriatric assessment leads to changes in the oncologic decisions in 17%–39% of the patients, of which two-thirds were recommendations for less intensive therapy. Interventions for non-oncologic vulnerabilities were recommended in over 70% of the patients following the geriatric assessment.[ 10 , 11 ] However, there are no Indian studies that describe the impact of the geriatric assessment on the systemic therapy plan. We, therefore, planned to evaluate this in our older patients with cancer.
MATERIALS AND METHODS
General study details
This was a retrospective and prospective study conducted on patients assessed between June 2018 and September 2021 in the geriatric oncology outpatient clinic of the Department of Medical Oncology at the Tata Memorial Hospital in Mumbai, India.[ 12 ] The Institutional Ethics Committee (IEC)-3 of the Tata Memorial Hospital, India, approved the study in June 2020 (study 900596; protocol provided as Supplementary Appendix 1 ); patients who were evaluated before this date were included as the retrospective cohort, and the IEC waived the requirement to obtain written informed consent from these patients. Patients evaluated after the IEC approval date provided written informed consent and comprised the prospective cohort of the study. These data were analyzed retrospectively. The study was registered with the Clinical Trials Registry of India (CTRI/2020/04/024675). There was no funding for the study. The study was conducted according to the ethical principles established by the Declaration of Helsinki and Good Clinical Practice Guidelines.
Supplementary Appendix 1
Participants
All patients who were 60 years or over with a diagnosis of malignancy and had been assessed in the geriatric oncology clinic were considered for the study. We excluded patients for whom a clear treatment plan was not decided or documented before referral to the geriatric oncology clinic, those who received treatment at a different facility, those for whom the regimen or the doses planned or administered were not clearly documented, those who defaulted after the geriatric assessment, and those who were not planned for systemic therapy.
Objectives
The primary objective was to assess the proportion of patients in whom there was a change in the planned cancer-directed therapy following evaluation in the geriatric oncology clinic. The secondary objectives were to assess the proportion of patients who were recommended interventions for non-oncologic deficits identified through the geriatric assessment, to characterize the types of changes that occurred in the oncologic treatment plan, and to evaluate whether there were any factors that predicted a higher chance of a change in the cancer-directed treatment plan following the geriatric assessment.
Study methodology
The patients’ baseline demographic and clinical parameters and the initial cancer-directed treatment plan were extracted from the geriatric oncology clinic database and the hospital’s electronic medical records. The results of the geriatric assessment, including non-oncologic vulnerabilities (nutrition, comorbidities, function, falls, fatigue, psychological status, social support, polypharmacy, potentially inappropriate medication use, and cognition), chemotherapy toxicity risk assessment (calculated using the Cancer and Ageing Research Group tool), non-oncologic life expectancy (calculated using the ePrognosis Lee Schonberg scale) and the patients’ and caregivers’ goals of therapy were documented both in the geriatric oncology database and in the electronic medical records, which were accessed by the treating physicians. Once the patients were planned or started on therapy, the final treatment plan was extracted from the electronic medical records and compared to the initial pre-geriatric assessment treatment plan.
Statistics
Sample size calculation was not performed for this study; all eligible patients who had undergone a geriatric assessment during the study period were included. Data for all patients evaluated in the geriatric oncology clinic are prospectively entered in a database in the Statistical Package for the Social Sciences (IBM Corp. Released 2015. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp.). This SPSS database was utilized for the current study. Clinicodemographic details and the change in the treatment plan were analyzed using simple descriptive statistics with absolute numbers and percentages. A comparison of various groups of patients was carried out using the Pearson Chi-square test. Logistic regression was used to evaluate whether various clinical factors predicted a change in the cancer-directed treatment plan. The results have been presented as odds ratios (OR) with 95% confidence intervals (CI). The Forest plot was created using the “forestplot” function available in the “forestplot” package version 3.1.0 by Max Gordon and Thomas Lumley available on the R CRAN network https://CRAN.R-project.org/package = forestplot in R Studio.
RESULTS
General study-related and patient-related details
Between June 2018 and September 2021, 688 patients were assessed in the geriatric oncology clinic, of which 617 patients were included [Figure 1 ]. The baseline clinicodemographic features and the results of the geriatric assessment are provided in Table 1 . The median age was 69 years (range, 60–100). The commonest tumors were malignancies originating in the lung in 243 (39.4%) patients and the gastrointestinal tract in 208 (33.7%).
Figure 1: Scheme of the inclusion of participants in the study (GA = geriatric assessment)
Table 1: Baseline clinicodemographic features and the results of the geriatric assessment
Initial systemic therapy plan
Palliative intent therapy was planned in 339 (54.9%) patients. The details of the initial plan of therapy are provided in Table 2 .
Table 2: The initial plan of therapy that was made before the referral of the patients to the geriatric oncology clinic
Results of the geriatric assessment
There were 498 patients (80.7%) who were diagnosed as being either vulnerable (two deranged domains) or frail (three or more deranged domains) on the geriatric assessment. The details of the results of the geriatric assessment are provided in Table 1 . Of the 617 patients, 584 (94.7%) were referred for interventions for non-oncologic vulnerabilities. There were 374 (60.6%) patients who were referred to the physiotherapist and/or occupational therapist; 429 (69.5%) required dietary intervention; and 177 (28.7%) were referred to the psychologist/counselor due to impairment in the psychological or cognition domains.
Final systemic therapy plan
Following the assessment in the geriatric oncology clinic, there was a change in the cancer-directed therapy plan in 239 (38.7%) patients. The commonest change was treatment deintensification in 198 (32.1%) patients [Figure 2 ]. Among patients who were receiving therapy in the curative setting, 91 (32.7%) had de-escalation of therapy, and 21 (7.6%) patients had an escalation of therapy. Among patients who were being treated with palliative intent, 107 (31.6%) had de-escalation of therapy, and 20 (5.9%) patients had an escalation of therapy.
Figure 2: Change in systemic therapy plan following the geriatric assessment (RT = radiation therapy, ChemoRT = chemoradiation, IV = intravenous, TKI = tyrosine kinase inhibitor)
Factors that affected the change in the systemic therapy plan
In 120 (19.4%) patients, systemic therapy was started before referral to the geriatric oncology clinic. There was a change in the oncologic treatment plan following the geriatric assessment in 25 of these 120 patients (20.8%), compared to 214 of the 497 treatment-naïve patients (43.1%), P < 0.001 by Pearson Chi-square test.
Logistic regression revealed that there was a higher chance of a change in the treatment plan following the geriatric assessment in patients between the ages of 70 and 79 years (OR, 1.48; 95% CI, 1.06–2.08) and those over the age of 80 years (OR, 2.20; 95% CI, 1.12–4.34), patients with a performance status of 3 (OR, 2.34; 95% CI, 1.05–5.21), and those with >10% weight loss (OR, 1.48; 95% CI, 1.03–2.11). Patients with higher hemoglobin levels (OR, 0.92; 95% CI, 0.84–0.99) and those who had been started on systemic therapy before undergoing the geriatric assessment (OR, 0.35; 95% CI, 0.22–0.56) had lower odds of a change in the cancer-directed treatment plan [Figure 3 ].
Figure 3: The forest plot shows the odds ratio and the 95% confidence intervals of the association of various factors with a change in the systemic therapy plan following the geriatric assessment (CI = confidence interval, EGOG PS = Eastern Cooperative Oncology Group performance status)
DISCUSSION
In our older Indian patients with cancer, the systemic cancer-directed treatment plan was changed in 38.7% of the patients because of the geriatric assessment. The most common change was treatment deintensification. The factors associated with a higher chance of a change in the cancer treatment plan were increasing age, weight loss ≥10% in the preceding three months, lower hemoglobin, poor performance status, and being treatment-naïve before referral for the geriatric assessment. Thus, the geriatric assessment led to a change in therapy in two out of every five patients, underscoring the critical importance of the information obtained from the geriatric assessment. Performing a pre-treatment geriatric assessment was more likely to lead to a change in therapy, thus making the geriatric assessment mandatory before starting systemic therapy for all patients aged 60 years and over.
Previous studies have reported that 16.7%–38.7% of patients underwent a change in treatment following the geriatric assessment.[ 11 , 13–16 ] The elderly cancer patient (ELCAPA) study conducted in older patients with mainly gastrointestinal, genitourinary, and breast cancers found that the geriatric assessment led to a treatment modification in 78 (20.8%) of 375 patients and that lower scores on the activities of daily living and malnutrition were independent risk factors.[ 13 ] A study that included 105 patients with cancer who were 70 years or older found that the treatment plan was modified for the 93 (88.6%) patients who had an initial treatment decision. However, in this study, only univariate analysis was performed; the body mass index (BMI) and the absence of depressive symptoms were associated with treatment modifications. To screen for depressive symptoms, the mini-geriatric depression scale was used, and an answer of “yes” to any of the five questions was considered a positive response.[ 14 ] A study conducted by Garric et al . among older patients with hematological malignancies reported a change in the treatment plan for 92 (21.7%) patients. Increasing age, functional impairment of the ADL and IADL, mobility impairment, and the presence of comorbidities as assessed by a score >1 on the Charlson comorbidity index were associated factors.[ 15 ]
Similarly, a study that included 384 older patients with solid and hematologic malignancies with an initial cancer treatment plan reported that in 64 (16.7%) patients, the plans were changed following the geriatric assessment. Multivariate analysis revealed that impaired mini-mental status examination, poor scores on the mini-nutritional assessment scale, and low physical performance as assessed on the short physical performance battery were associated with a change in the treatment plan.[ 11 ] A study conducted among 83 older patients with lung cancer reported that a change of oncologic treatment was proposed in 27 (33%) patients and that patients with a greater number of domain impairments were often advised a reduction in the treatment intensity.[ 15 ] In a systematic review of 10 studies, the initial treatment plan was modified in a median of 39% of patients after the geriatric evaluation.[ 10 ] In 2022, Hamaker et al . updated their systematic review to include 61 studies and reported that the oncologic treatment plan was altered in a median of 31% of patients (7%–56%). Studies that included a multidisciplinary team evaluation had a higher change rate.[ 17 ] Similar to the earlier studies reported in the literature, as well as the systematic review by Hamaker et al. , we found that 38.7% of patients had changes made to their initial oncologic treatment plan based on the results of the geriatric assessment.[ 17 ] The commonest change was treatment deintensification in 32.1% of patients; however, it is important to also note that there was an escalation of therapy in 6.7% of the patients; in the absence of the geriatric assessment, these patients would have been overdosed and underdosed, respectively. Our center has a multidisciplinary geriatric oncology evaluation and management team, which may have been one of the reasons for the high rate of change in the systemic treatment plan, as reported by Hamaker et al .[ 17 ]
Compared to previous studies, our patient cohort was younger (median age, 69 years).[ 18 ] The average age of the patients enrolled in previous studies ranged between 79 and 82.8 years.[ 15 , 16 ] Though high-income countries define “older adults” as patients aged 65 years and above, the national policy from India[ 19 ] defines older adults as those aged 60 years and above.[ 20 , 21 ] Earlier studies had enrolled approximately equal numbers of male and female patients, but our study cohort was predominantly male (76.2%). This could be due to the pattern of referral to the geriatric oncology clinic (preferential referrals of patients with lung, gastrointestinal, head-and-neck, and genitourinary cancers, fewer referrals of patients with breast and gynecologic malignancies) and the fact that access to healthcare by Indian women has traditionally been less than that of men.[ 22 , 23 ]
Although previous studies have identified various domains in the geriatric assessment associated with a change in the treatment plan, the results were inconsistent across studies due to the evaluation of dissimilar domains and the difference in the tools used to assess each domain. In our study, we found that increasing age, poor performance status, and significant unintentional weight loss were associated with increased odds of a change in the oncologic treatment plan. Conversely, a higher hemoglobin level and initiation of the treatment before the geriatric assessment were associated with lower odds of a treatment change. These findings are in line with those of prior studies.[ 13–16 ] These factors could be used to select which patients should be prioritized for undergoing a geriatric assessment, especially in resource-constrained settings.
The geriatric assessment is valuable for developing an individualized oncologic care program.[ 24 ] Hamaker et al . found that non-oncologic interventions were recommended in over 70% of the older patients with cancer, especially if the specific expertise for intervening in the identified non-oncologic vulnerabilities was in place.[ 17 ] At our geriatric oncology clinic, approximately 80% of the older patients with cancer were noted to be vulnerable or frail on the geriatric assessment; 95% of the patients were recommended specific interventions for non-oncologic vulnerabilities detected by the geriatric assessment. The results of the geriatric assessment and interventions have increased discussions about the goals of care, improved communication, and lowered chemotherapy-related toxicity rates.[ 16 ]
Several limitations of our study should be borne in mind. This was a single-center observational study, the majority of our patients (76%) were male, and not all malignancies were equally represented due to the pattern of referrals for geriatric assessment at our institution, limiting the generalizability of our study results. As the geriatric oncology clinic evolved, the domains being assessed and the tools used were modified over time (for example, the evaluation of the psychological and social support domains was introduced later). Previous studies have identified various geriatric domains which led to a change in treatment plans, including function, nutrition, etc. As our goal was to identify any factors that could predict a change in the systemic therapy plan before performing the geriatric assessment, we assessed factors like age, sex, BMI, comorbidities, tumor type, metastatic status, hemoglobin, Eastern Cooperative Oncology Group performance status and starting chemotherapy before the geriatric assessment. Our study was a cross-sectional one. The next step will be to assess whether the change in the systemic therapy plan impacted outcomes, including side effects, tolerability, and survival. To assess whether the changes made in the systemic therapy plan as a result of the geriatric assessment were clinically meaningful, it would be imperative to correlate these changes with the oncological outcomes. However, as this was a cross-sectional study, any correlation with the oncological outcomes would be beyond the scope of our current study. We were also unable to evaluate whether there was any difference in the use of growth factors based on the results of the geriatric assessment.
The strengths of our study include the fact that this is the first of its kind study from the Indian subcontinent, it had a large sample size, and we systematically used validated scales to evaluate the various domains of the geriatric assessment.
CONCLUSION
The results of the geriatric assessment led to the identification of a high prevalence of vulnerabilities among older Indian patients with cancer which prompted changes in the initial cancer treatment plan in almost 40% of the patients. Hence, geriatric assessment is an important tool in the oncologic decision-making process for older persons with cancer.
Author contributions
Study concept: VN; design: VN, AR, SG, AR, AK, SK, RC, RD, JK, AP, SM, AD, LS, JD, NS, MV, VG, SB, KP, RB; data collection: VN, AR, SG; analysis and interpretation: VN; manuscript writing: VN, AR; approval of final article: all authors; accountability for all aspects of the work: all authors.
Data sharing statement
Individual de-identified participant data will be made available on reasonable request to the corresponding author, starting from the date of publication until ten years after publication. Requests beyond this timeframe will be considered on a case-by-case basis. In addition, the study protocol, including the statistical data, is already available as part of this article.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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