Cancer And Aging Research Group Research Articles

Predictors and effects of toxicity experienced by older adults with cancer receiving systemic therapy in a randomized clinical trial of geriatric assessment

IntroductionOlder adults represent a large segment of the oncology population, however, they remain underrepresented in clinical research. Treatment of older adults is often extrapolated using data from younger and fitter patients, which may not be appropriate. Furthermore the implications of toxicity from treatment can be greater for this population. Predicting toxicity from treatment and its effect on quality of life and functional status for older adults therefore is important. Materials and MethodsWe analyzed data from a clinical trial of geriatric assessment and management for Canadian elders with cancer (5C study). We assessed whether the baseline Cancer and Aging Research Group (CARG) toxicity score, G8 score, and Eastern Cooperative Oncology Group (ECOG) performance predicted grade 3–5 toxicity using logistic regression and pattern mixture models. We also assessed the impact of toxicity on quality of life and functional decline. Patients were followed for six months. ResultsThree hundred sixteen patients were included. Mean age was 76 years old and 40% of patients were female. One hundred nineteen patients (38%) experienced at least one grade 3–5 toxicity. Neither the CARG toxicity score, G8, or ECOG were predictive of grade 3–5 toxicity. Patients who experienced grade 3–5 toxicity were more likely to have functional impairments over time (odds ratio 3.71, p = 0.03). However, they maintained their quality of life. DiscussionIn this secondary analysis of a randomized controlled trial of geriatric assessment and management we did not find any predictors of grade 3–5 toxicity. Patients who did experience toxicity were more likely to report functional decline over time. Older adults who do experience treatment related toxicity may benefit from increased supports.Clinical trial information: NCT0315467.

External Validation of Risk Factors for Unplanned Hospitalization in Older Adults With Advanced Cancer Receiving Chemotherapy.

Older adults (age ≥65 years) receiving chemotherapy are at risk for hospitalization. Predictors of unplanned hospitalization among older adults receiving chemotherapy for cancer were recently published using data from a study conducted by the Cancer and Aging Research Group (CARG). Our study aimed to externally validate these predictors in an independent cohort including older adults with advanced cancer receiving chemotherapy. This validation cohort included patients (n=369) from the GAP70+ trial usual care arm. Enrolled patients were aged ≥70 years with incurable cancer and were starting a new line of chemotherapy. Previously identified risk factors proposed by the CARG study were ≥3 comorbidities, albumin level <3.5 g/dL, creatinine clearance <60 mL/min, gastrointestinal cancer, ≥5 medications, requiring assistance with activities of daily activities (ADLs), and having someone available to take them to the doctor (ie, presence of social support). The primary outcome was unplanned hospitalization within 3 months of treatment initiation. Multivariable logistic regression was applied including the 7 identified risk factors. Discriminative ability of the fitted model was performed by calculating the area under the receiver operating characteristic (AUC) curve. Mean age of the cohort was 77 years, 45% of patients were women, and 29% experienced unplanned hospitalization within the first 3 months of treatment. The proportions of hospitalized patients with 0-3, 4-5, and 6-7 identified risk factors were 24%, 28%, and 47%, respectively (P=.04). Impaired ADLs (odds ratio, 1.76; 95% CI, 1.04-2.99) and albumin level <3.5 g/dL (odds ratio, 2.23; 95% CI, 1.37-3.62) were significantly associated with increased odds of unplanned hospitalization. The AUC of the model, including the 7 identified risk factors, was 0.65 (95% CI, 0.59-0.71). The presence of a higher number of risk factors was associated with increased odds of unplanned hospitalization. This association was largely driven by impairment in ADLs and low albumin level. Validated predictors of unplanned hospitalization can help with counseling and shared decision-making with patients and their caregivers. gov identifier: NCT02054741.

An evaluation of the Index4 tool for chemotherapy toxicity prediction in cancer patients older than 70 years old

Chemotherapy, although beneficial for improving outcomes in both localized and metastatic cancers, may be associated with significant adverse effects, especially for patients with decreased functional reserves. Prediction of patients who will not tolerate well chemotherapy treatment may help in modifying treatment plans and in reallocating resources to vulnerable patients. One hundred seventeen consecutive cancer patients over the age of 70 scheduled for chemotherapy treatment in a single cancer center were included in the study. Prediction of adverse chemotherapy outcomes were calculated using a prediction tool proposed and validated from the Cancer and Aging Research Group (CARG) and a prediction tool proposed by us, called Index4. The 2 tools were compared for their ability to predict grade 3 and 4 toxicities, Emergency Department (ED) and hospital admissions and chemotherapy discontinuation. The accuracy of both predictive tools was suboptimal. A high CARG score had a sensitivity of 46.3% and a specificity of 82% and an Index4 of 1 or above had a sensitivity of 53.7% and a specificity of 60% in predicting grade 3–4 adverse effects. The performance of the 2 tools in predicting ED and hospital admissions and chemotherapy discontinuation was comparable. An Index4 score of 0 was superior in predicting absence of grade 3–4 toxicities than a low CARG score (p = 0.002, McNemar’s test). The CARG tool for chemotherapy adverse effect prediction in geriatric cancer patients and the Index4 were able to predict adverse outcomes with moderate accuracy. Given its ease of calculation Index4 may be an alternative to CARG tool, suitable for a busy oncology practice.

Use of the Cancer and Aging Research Group Predictive Model for Chemotherapy-Related Toxic Effects in a Multiethnic, Older Adult Asian Population

The Cancer and Aging Research Group (CARG) prediction model for chemotherapy-related toxic effects has been developed but not yet validated in older Asian adults. In view of differences in drug metabolism and toxic effect reporting in the Asian population, the ability of this tool to guide the cancer treatment decision-making process in older Asian adults needs to be assessed. To examine the validity of the CARG predictive model in a multiethnic Asian cohort of older adults. In this prognostic study, patients of various Asian ethnicities 70 years or older with a solid tumor diagnosis receiving chemotherapy at the National University Cancer Institute, Singapore, were accrued from June 1, 2017, to January 1, 2019. Their risks of chemotherapy-related toxic effects were calculated using the CARG tool. A geriatric assessment was performed, and the treating oncologist (blinded to the CARG scores) was asked to give an estimated likelihood of toxic effects (low, medium, or high). Chemotherapy-related toxic effects were recorded during each clinic visit. Validation of the prediction model was performed by calculating the area under the receiver operating characteristic curve. Multivariate analyses were performed to identify variables in other domains in the geriatric assessment predicting for severe toxic effects. Grade 3 to 5 toxic effects and hospitalization. The study included 200 patients (median age, 74 years [range, 70-89 years]; 110 [55.0%] male; 177 [88.5%] Chinese, 17 [8.5%] Malay, 4 [2.0%] Indian, and 2 [1.0%] other ethnicities [according to Singapore's national system of race classification]). A total of 137 patients (68.5%) experienced grade 3 to 5 toxic effects, and 131 (65.5%) required hospitalization. The area under the receiver operating characteristic curve for the CARG chemotoxicity prediction model was 0.74 (95% CI, 0.67-0.82), retaining good discrimination in the study population. This prognostic study conducted in a multiethnic Asian cohort of older adults supports the validity of the CARG predictive model in this population, predicting which older adults are at risk of chemotherapy-related toxic effects.

Impact of the Cancer and Aging Research Group (CARG) chemotherapy toxicity (tox) risk score on the benefit of a geriatric assessment–driven intervention (GAIN) among older adults with cancer.

235 Background: The CARG tox score can predict risk of chemotherapy-related tox in older adults with cancer. GAIN can reduce tox vs standard of care (SOC) among these patients (pts); GAIN’s impact across CARG risk groups is unknown. Methods: A secondary analysis of the GAIN randomized clinical trial (NCT02517034) of pts aged ≥65 (solid tumor diagnosis, starting a new chemotherapy) was performed. Pts were randomized 2:1 to receive GAIN vs SOC and were categorized into low (0-5), medium (6-9), and high (10-20) risk groups according to CARG score. The primary outcome was incidence of grade 3-5 tox. Chi-square/Fisher’s exact tests were used to compare outcomes (GAIN vs SOC, stratified by risk groups). Log-rank tests were used to compare 1-year survival across risk groups. Results: This analysis included 600 pts: 26.5% low risk, 45.2% medium risk, 28.3% high risk. Table shows pt/treatment characteristics. For pts with low/medium risk scores, GAIN demonstrated a 14.0% (95% CI 4.1%-23.9%) reduction in tox vs SOC (p = 0.006). No significant reduction in tox was observed among pts with high risk scores (p = 0.86). One-year survival (GAIN vs SOC) for each risk group was 73.6% vs 67.4% (low risk), 68.5% vs 64.5% (medium risk), and 57.3% vs 61.7% (high risk), respectively (log-rank p = 0.10). Conclusions: Older adults with low/medium, but not high, CARG risk scores benefit from GAIN. Additional strategies may be needed to improve outcomes for pts with high CARG risk scores. Clinical trial information: NCT02517034. [Table: see text]

New Advances in Supportive Care: Chemoprotective Agents as Novel Opportunities in Geriatric Oncology.

To explore the effectiveness of trilaciclib and ALRN-6924 in the prevention of cancer chemotherapy-induced toxicity in older patients. New chemoprotective agents are necessary because age is the main risk factor for chemotherapy complications that account largely for the poorer outcome of cancer in the elderly. Trilaciclib and ALRN-6924 cause a reversible block of the proliferation of normal cells through cell cycle arrest (CCA). With this mechanism, they may prevent the toxicity of cycle-active cancer treatment including neutropenia, anemia, thrombocytopenia, lymphopenia, mucositis, and alopecia. Myelopoietic growth factors may prevent neutropenia in the aged, but they may cause severe bone pain, may aggravate thrombocytopenia and anemia, and may cause myelodysplasia and acute leukemia as a late complication. The prevention of thrombocytopenia, anemia, mucositis, and alopecia is unsatisfactory at present. These complications may jeopardize the treatment outcome as they require a reduction of treatment dose/intensity and because many patients find the resulting symptoms intolerable. In three studies of patients with extensive disease small cell lung cancer (ES-SCLC), trilaciclib reduced the severity and duration of neutropenia and thrombocytopenia as well as the need for blood transfusions. In addition, it produced a significant expansion of T-cell clones. Trilaciclib received FDA approval for the prevention of chemotherapy-induced myelosuppression in patients with ES-SCLC. ALRN-6924 is currently studied in phase II study of ES-SCLC. In a phase IB of 38 patients, ALRN-6924 prevented myelosuppression to an extent comparable with trilaciclib. Both drugs proved as effective in patients 65 and older as they were in the younger ones. In an "ex vivo" study, ALRN-6924 protected the epithelial stem cells of hair follicles from taxanes and promised to prevent alopecia. The possibility that CCA of tumor cells may reduce the effectiveness of cycle-active chemotherapy is a major concern. For this reason, the use of trilaciclib, an inhibitor of CDK 4/6, should be limited to tumors with inactivated RB1, and the use of ALRN-6924, an inhibitor of P53, should be limited to tumors with inactivated P53. Chemotherapy-related toxicities limit dose intensity and contribute to significant morbidity and mortality in elderly cancer patients. Trilaciclib and ALRN-6924 are of particular interest to geriatric oncologists because of their novel mechanism of action. Ameliorating chemotherapy-induced toxicities holds the promise of transforming the practice of geriatric oncology by enabling chemotherapeutic regimens that are currently not feasible for this patient population. Specifically, these agents may prevent chemotherapy-induced neutropenia and thrombocytopenia, perhaps the most life-threatening complications of cytotoxic chemotherapy, thereby obviating the need for the use of rescue strategies such as hematopoietic growth factors. In addition, these agents offer the potential for broad tissue protection from other chemotherapy-related toxicities, including mucositis, diarrhea, and alopecia, which historically have been poorly managed. Importantly, by preventing a spectrum of chemotherapy-related toxicities, these agents may permit the administration of chemotherapy at full-dose intensity, prevent functional decline, and grant maintenance of resilience to older cancer patients. As a result, the successful prevention of chemotherapy-induced side effects may not only mitigate the costs of care but also improve patient outcomes and quality of life. Finally, chemoprotective strategies offer the opportunity to apply geriatric principles to clinical trials of cancer treatment. In particular, they may allow the testing of prolongation of "active life expectancy" as a major goal of clinical trials in elderly patients. They may also enable novel and more practical forms of clinical trials. By assessing the risk of chemotherapy-related toxicity with the Chemotherapy Risk Assessment Scale for High Age Patients (CRASH) or the Cancer and Aging Research Group (CARG) instruments, these agents may permit researchers to utilize patients as their own controls and endorse the approval of supportive care drugs based upon the risk profile of individual patients.

Validation of the Cancer and Aging Research Group (CARG) model to identify risks of chemotherapy toxicities in Asian older adults.

12043 Background: Older adults are at an increased risk of chemotherapy related toxicities. Identification of risk factors can facilitate oncologists in tailoring treatment, potentially mitigate the risk of chemotherapy toxicity and improve social economic outcomes. Tools like the Karnofsky Performance Status (KPS) and Geriatric Assessment (GA) are used in clinical practice to guide treatment decisions for older adults with cancer. The CARG model incorporating the GA and clinical variables was developed and validated to predict for grade 3-5 toxicities, although this has not yet been validated in Asians. Methods: Patients ≥70 years old with solid malignancies receiving chemotherapy at the National University Cancer Institute, Singapore were recruited between June 2017 and January 2018. The study aims to verify the application of the CARG model, KPS, GA and oncologists’ estimate of toxicity in a multi-ethnic Asian population. The risks of chemotherapy toxicity were calculated using the CARG model (low risk: 0-5, medium risk: 6-9, high risk: ≥10). A GA including a physician rated KPS score (low risk: 90-100, medium risk:80, high risk: ≤70) and a timed up and go (TUG) test (low risk: ≤12s, high risk: &gt; 12s) were performed for all patients. The attending oncologist (blinded to the CARG score) was asked to give an estimated likelihood (low/medium/high) of chemotoxicity. Chemotherapy related toxicities were captured by chart review based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The area under the receiver operating characteristic (ROC) curve and a univariate analysis of predictors of toxicity were calculated. Results: A total of 200 patients were included. Median age was 74 (range: 70-89). The ethnic makeup of the population consisted of Chinese (N = 177; 88.5%), Malay (N = 17; 8.5%), Indians (N = 4; 2%) and other ethnicities. Majority of patients were males (N = 110; 55%), had metastatic disease at diagnosis (N = 114; 57%) and had gastrointestinal cancers (N = 80; 40%). 75% (N = 150) had polychemotherapy and 55% (N = 110) received full dose chemotherapy. More than half of patients (68.5%) experienced G3-5 toxicities, with 65.5% requiring hospitalization. The CARG model predicted 22.5% of patients as low, 50.5% as medium and 27% as high risk of chemotoxicity. The area under ROC for the CARG model was 0.74 (95% CI, 0.67-0.82). A one-point increase in the CARG score was associated with a 15% increase in the odds of G3-5 toxicities. 84.5% of patients needed &gt; 12s for the TUG test. The TUG score, KPS and oncologist’s prediction of toxicity was predictive of an increased risk of G3-5 toxicities (p &lt; 0.01). Conclusions: This study confirms the validity of the CARG predictive model in Asians and can streamline healthcare delivery in older adults. Development of a more robust predictive model incorporating the KPS and TUG into the CARG model could be considered.

Modified CARG score using data from the electronic health record to predict chemotherapy toxicity in older adults.

12038 Background: Older adults starting chemotherapy are at greater risk of toxicity compared with younger patients. Additional tools are needed to aid in management decisions for this population. The Cancer and Aging Research Group (CARG) chemotherapy toxicity calculator is one such tool, which stratifies older adults into high, intermediate, or low risk for chemotherapy toxicity (Hurria, A., Mohile, S., Tew, W. P., &amp; et al. (2016). Validation of a prediction tool for chemotherapy toxicity in older adults with cancer. Journal of Clinical Oncology, 34(20), 2366–2371. https://doi.org/10.1200/jco.2015.65.4327). This tool relies on a face-to-face encounter to ask questions, e.g. “How is your hearing?” or “Can you take your own medicines?” in addition to lab values such as hemoglobin and creatinine clearance. We modified the CARG chemo toxicity calculator to include data points which could be pulled from the electronic health record (EHR) without the need for a face-to-face encounter to assess for an association with emergency department (ED) visits and hospital admissions. Methods: Retrospective data analysis was conducted using the EHR of patients over age 65 diagnosed with a solid tumor from 1/1/2019 to 12/31/2020 who started chemotherapy. A modified CARG score was calculated using age, cancer type, number of drugs, hemoglobin, creatinine clearance, and falls within the past 6 months. The remaining items needed to calculate the complete CARG score were excluded since they were not accessible in the EHR. We assessed ED visits leading to admission, ED visits leading to discharge, direct admissions, and the total of all 3 visit types for all patients. Results: A modified CARG score was calculated for 763 patients. Multiple models were evaluated and negative binomial distribution was found to be the best fitted for our data. For every one unit increase in our calculated score the number of ED visits which lead to hospital admission increased by 6% (p-value = 0.0156). Additionally, there was a 5% increase in combined ED visits, ED visits leading to admission, and direct admissions for every one unit increase in risk score (p-value = 0.0063). ED visits that did not lead to admission were found not to have an association with the risk score (p-value= 0.1263). (Table) Conclusions: A modified CARG score using data obtained from patients’ EHR had a statistically significant association with increased ER visits that resulted in hospital admission and with the total of ED visits leading to admission, ED visits leading to discharge, direct admissions. Using these outcomes as a surrogate for toxicity, we deduce that a simple tool could be used to predict chemotherapy toxicity in older adults. [Table: see text]

Predicting the Risks of Aggressive-Intent Chemotherapy Toxicity in Older Patients With Lymphoma: A Prospective Observational Pilot Study

IntroductionLymphoma is a disease of older patients and while treatment is subtype specific, curative or aggressive intent combination chemotherapy is often recommended. However, there has been limited evidence on which to base treatment decisions for older adults. Our objectives were to assess the utility of risk stratification measures and serial functional tests in predicting chemotherapy toxicity and as well the feasibility of conducting these in older adults undergoing chemotherapy for lymphoproliferative disorders. Materials and MethodsThis prospective cohort study recruited lymphoma patients 70 years or older planned for systemic chemotherapy. The Cancer and Aging Research Group (CARG) risk stratification tool and Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) were calculated at baseline. The Clinical Frailty Scale (CFS), Charlson Comorbidity Index score, grip strength and gait speed test, and toxicity events, were assessed at baseline and serially throughout treatment. Sarcopenia was calculated on CT scans at baseline, midway through treatment, and 1-month after completion of therapy. The primary endpoint was to assess the feasibility of applying these measures in busy ambulatory clinics. These measures were also correlated with clinical outcomes including ≥grade 3 adverse events (AEs), hospitalizations and emergency department visits, dose changes or delays, and overall survival. ResultsIn total, 30 patients were enrolled (mean age 78.1 ± 6.4 years), of whom 20 were treated with curative intent. A total of 16 patients (53%) experienced grade ≥3 AEs, 9 (56%) of which led to a chemotherapy delay. On univariable analyses, CFS score, a high CARG score, medium to high CRASH score, and the gait speed were associated with grade ≥3 AEs, while only CFS remained significant on multivariable analysis. On univariable analysis, patients with a medium to high risk CRASH score were more likely than low risk patients to have an unplanned emergency department visit or hospitalization. ConclusionsThe CFS seems to predict toxicity in this cohort study, with gait speed, CARG and CRASH scores being potentially additional predictive methods of evaluation.

Validity of the Cancer and Aging Research Group Predictive Tool in Older Japanese Patients.

Simple SummaryThis study aimed to assess the usefulness of the Cancer and Aging Research Group (CARG) predictive tool in predicting chemotherapy-related adverse events (CRAEs) in elderly Japanese patients with cancer. The CARG has developed a very useful tool that can predict CRAEs among patients with solid tumors aged above 65 years. However, considering that this tool is based on data from Europe and the United States, the usefulness of the tool for Japanese people, who have different sensitivities to anticancer drugs and varying life expectancies, is still unknown. This study showed that the CARG tool could help predict CRAEs in elderly Japanese patients with cancer, i.e., this tool has the potential to optimize chemotherapy in elderly Japanese patients with cancer.Background: This study aimed to evaluate the usefulness of the Cancer and Aging Research Group (CARG) predictive tool in older Japanese patients with cancer. Methods: Patients aged 65 years or older with solid tumors treated with new anticancer regimens in Kakogawa Central City Hospital between April 2016 and March 2019 were included. Grade 3 or higher risks of developing chemotherapy-related adverse events (CRAEs) were calculated using the tool (low-, intermediate-, or high-risk scores). The association between grade 3–5 CRAE incidence during the first course of each regimen and the calculated risk or the patient characteristics was evaluated. The difference in the incidences of CRAEs between the groups was evaluated by Fisher’s exact test. Results: This study examined 76 patients (mean age: 71 (65–82) years). The incidence of grade 3–5 CRAE was 38%, 55%, and 76% in patients classified as low, medium, and high CARG risk scores (p = 0.035), and the incidence of severe non-hematological toxicities was 4%, 31%, and 52% (p < 0.01), respectively. Eastern Cooperative Oncology Group performance status and age were not associated with chemotherapy toxicity. Conclusions: The CARG predictive tool was valid, suggesting its usefulness in optimizing chemotherapy outcomes in older patients with cancer.

Prospective comparison of the value of CARG, G8, and VES-13 toxicity tools in predicting chemotherapy-related toxicity in older Turkish patients with cancer

BackgroundIn older patients with cancer, it is very important to choose the appropriate treatment because they are at high risk for chemotherapy toxicity. Our study investigated characteristics of Cancer and Aging Research Group (CARG), Geriatric 8 (G8), and Vulnerable Elders Survey (VES-13) screening tools for predicting chemotherapy-related toxicity (CRT) prospectively. Materials and methods208 patients aged ≥65 years old for whom chemotherapy was planned to treat non-haematological cancer between February 2021–September 2021 were included in the study. The CARG, G8, and VES-13 toxicity tools were completed by the oncologist through face-to-face interviews before starting the first chemotherapy treatment. CRTs during chemotherapy were evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events v4.03. Logistic regression models, the area under the receiver operating characteristic curve (ROC-AUC), and correlation analyses were used for comparing questionnaires. ResultsMedian age was 70.4 (range 65–86) years. Of the participants, 103 (49.5%) participants experienced grade 3–5 CRT (32.2% haematological, 28.4% non-haematological) during chemotherapy. ROC-AUC value of CARG was determined as 0.827 (95% CI [confidence interval]: 0.77–0.88, p < 0.001), it was determined as 0.744 (95% CI: 0.68–0.81, p < 0.001) for G8 and 0.726 (95% CI: 0.66–0.80, p < 0.001) for VES-13. In the univariate regression analysis, CARG (OR [odds ratio] = 13.57, 95% CI: 6.0–30.72, p < 0.001), G8 (OR = 3.19, 95% CI: 1.62–6.29, p = 0.001), and VES-13 (OR = 9.5, 95% CI: 5.01–17.89, p < 0.001) were found to be predictive for CRT. The multivariate analysis (included stage, Eastern Cooperative Oncology Group [ECOG] performance status, presence of comorbid disease, platinum-based treatment regimen, taxane-based treatment regimen, CARG, VES-13, G8) showed that CARG (OR = 12.08, 95% CI: 5.11–28.56, p < 0.001), VES-13 (OR = 10.06, 95% CI: 4.92–22.98, p < 0.001), and G8 (OR = 2.20, 95% CI: 1.04–4.69, p = 0.040) screening tools were strong predictors for CRT. The CARG and VES-13 questionnaires were predictive for reducing the initial treatment dose (p = 0.004, p = 0.004, respectively), interruption of treatment (p < 0.001, p < 0.001, respectively), discontinuing treatment (p = 0.002, p = 0.002, respectively), and unexpected hospitalisation (p = 0.012, p = 0.003, respectively). ConclusionsWe showed that all three CARG, G8, and VES-13 questionnaires are helpful tools in the decision-making process for ideal chemotherapy to predict severe CRT; however, CARG and VES-13 questionnaires appear more useful in daily oncology practice than the G8 questionnaire.

Predicting Chemotherapy-Related Adverse Events in Elderly Cancer Patients with Prior Anticancer Therapy.

To test the usefulness of the Cancer and Aging Research Group (CARG) predictive tool, it was used to assess elderly cancer patients with prior anticancer therapy. Among patients with solid malignancies aged ≥ 65 years receiving second-line chemotherapy who were admitted to the Department of Medical Oncology/Hematology at Kakogawa Central City Hospital between April 2016 and September 2019, the risk ≥ grade 3 of developing chemotherapy-related adverse events (CRAEs) (low, intermediate, or high) was calculated using the tool. Correlations between grades 3 and 5 CRAE incidence rates in the first course of each regimen and CARG risk score, age, and Eastern Cooperative Oncology Group performance status (ECOG PS) were assessed. Included patients (n = 62) had a mean age of 71 years (range, 65–82 years). Severe CRAE incidence in patients with low, medium, or high CARG risk was 27%, 54%, and 71%, respectively (p = 0.026). The incidence of severe non-hematological toxicities was 5%, 35%, and 64%, respectively (p < 0.01). There was no association between age or ECOG PS and chemotherapy toxicity. The results suggest the validity of the CARG predictive tool in elderly cancer patients with prior anticancer therapy. Particularly, the tool showed potential for predicting non-hematological toxicity.

Energy expenditure profiles and the risk of early limiting toxicity in older patients with cancer: The ELCAPA-25 prospective cohort survey

Predicting the risk of early limiting toxicity (ELT) is major challenge for the clinician seeking an effective, safe treatment for older patients with cancer. The Cancer and Aging Research Group (CARG) and CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) toxicity scores were designed to predict chemotherapy-related toxicity. Elevated resting energy expenditure (REE) may predispose to cachexia and increase ELT and mortality in older patients with cancer. The primary objective was to assess the association between elevated REE and ELT in older patients with cancer. The secondary objectives were to assess the discriminant ability of a predictive model including REE (relative to the CARG and CRASH scores) and the prognostic value of elevated REE. We assessed patients aged 70 or over included in the prospective ELCAPA cohort between 2014 and 2018. The inclusion criteria were a solid tumour, a measurement of REE at baseline (mREE, by indirect calorimetry), and a geriatric assessment prior to cancer treatment in a teaching hospital (Paris, France). The mREE was compared with the predicted REE (pREE), as defined by the Harris-Benedict equation. Depending on the mREE/pREE ratio, study participants were classified as hypermetabolic, hypometabolic or normometabolic. The primary endpoint was 3-month ELT, defined as any unplanned hospitalization or any event leading to dose reduction, a treatment delay of more than 7 days, or treatment discontinuation within 3 months of initiation. The secondary endpoint was the 3-month mortality rate. A total of 179 patients were included. The median age was 80 [interquartile range: 76-84] years, 37% of the patients were female, 81.8% had metastatic disease, 67.6% received chemotherapy, 20.7% received hormone therapy, and 11.7% received targeted therapies. According to the mREE/pREE ratio, 85 patients (47%) were hypermetabolic, 63 (35%) were normometabolic, and 31 (18%) were hypometabolic. Sixty patients (33.5%; 95% confidence interval (CI): 26.7-40.9) experienced ELT. The discriminant ability (as assessed by the C-index) of a multivariate model including REE and adjustment factors was 0.82 [95%CI: 0.73-0.91]. In comparison, the discriminant ability of the CARG and CRASH models was 0.57 [0.45-0.68] and 0.51 [0.40-0.62], respectively. In our model, hypermetabolism was an independent risk factor for ELT (adjusted odds ratio=2.44; 95%CI: 1.02-5.80). Other risk factors were the cancer type and stage, the treatment protocol, a clinical diagnosis of depression, the presence of grade 3 or 4 comorbidities, and the serum lactate dehydrogenase level. Hypermetabolism status is an independent predictor of ELT in older patients with cancer, relative to normometabolic status. Baseline REE measurement might improve the ELT risk assessment and decision-making process.

Impact of the Cancer and Aging Research Group score and treatment intensity on survival and toxicity outcomes in older adults with advanced noncolorectal gastrointestinal cancers.

Little is known regarding the predictive value of the Cancer and Aging Research Group (CARG) score, a validated chemotherapy toxicity prediction tool for older adults with cancer, for survival outcomes. This was a prospective observational study of patients ≥65 years old receiving first-line chemotherapy for advanced noncolorectal gastrointestinal cancer for which combination chemotherapy is the standard of care. Overall survival (OS), time to treatment failure (TTF), which was defined as the time from the start of first-line chemotherapy to the discontinuation of first-line chemotherapy for any reason, and toxicity were compared in 4 groups of patients: 1) non-high-risk (nHR) CARG score (<10) and standard-intensity therapy (ST), 2) nHR score and reduced-intensity therapy (RT), 3) high-risk (HR) CARG score (≥10) and ST, and 4) HR score and RT. Fifty patients (median age, 71 years) were enrolled. The median OS in months was 19.7 in nHR/ST (n = 19) group, 12.7 in nHR/RT (n = 9) group, 4.5 in HR/ST (n = 12) group, and 3.9 in HR/RT (n = 10) group (log-rank test, P = .005). The median TTF in months was 9.1 in nHR/ST group, 2.5 in nHR/RT group, 2.3 in HR/ST group, and 3.0 in HR/RT group (log-rank test, P = .04). The CARG-score category was prognostic of OS (HR, 3.04; 95% confidence interval [CI], 1.59-5.83, P = .001) and TTF (HR, 2.60; 95% CI, 1.31-5.20, P = .007). The incidence of grade 3-5 toxicity was 68% in nHR/ST group, 33% in nHR/RT group, 92% in HR/ST group, and 70% in HR/RT group (Fisher exact test, P = .048). Risk-adapted chemotherapy based on the CARG-score may improve treatment outcomes.

Frailty and treatment outcome in advanced gastro-oesophageal cancer: An exploratory analysis of the GO2 trial

IntroductionResearch into the optimal management of frail patients with cancer is limited and treatment decision-making in this cohort can be difficult. A number of measures have been developed to assess frailty, but few studies explore the correlation between frailty measures and cancer treatment outcomes. MethodsThis retrospective cohort study is an exploratory analysis of the GO2 randomised controlled trial. GO2 recruited both older and frail younger patients commencing first-line palliative chemotherapy for advanced gastro-oesophageal (aGO) cancer. This analysis aims to explore the correlation between baseline frailty and treatment outcome. Baseline frailty measures were derived from clinical data and included ECOG Performance Status (PS), the GO2 Frailty Score (GO2FS), Geriatric-8 (G8), Cancer and Aging Research Group (CARG) toxicity score and a ‘modified’ Rockwood Clinical Frailty Scale (mCFS). Novel patient-centred composite measure Overall Treatment Utility (OTU) was the primary endpoint. Ordinal logistic regression was undertaken to give odds ratios for poor vs good/intermediate OTU. Secondary endpoints were progression-free and overall survival. Models were adjusted for age, sex, histology, metastases, Trastuzumab and renal/hepatic function. ResultsIn GO2, 514 patients were randomised between three chemotherapy dose-levels; all of these patients were assessed for OTU and are included in this analysis. Worse GO2FS, mCFS and G8 scores all had a statistically significant association with poor (vs good/intermediate) OTU, progression and death, which persisted after adjustment. Adjusted odds ratios for poor OTU amongst those with the worst GO2FS and mCFS and best G8 scores were as follows: 1.85 (95% confidence interval [CI] 1.20–2.88) for GO2FS ≥3 (‘severely frail’), 1.72 (1.19–2.50) for mCFS 5+ (‘frail’) and 0.57 (0.32–1.00) for G8 > 14 (‘normal’). Worse ECOG PS and CARG scores did not have a statistically significant association with poor OTU/progression/death. ConclusionIn this study, frailty identified via GO2FS, mCFS and G8 conveyed a statistically significant increased risk of worse treatment outcome in older and frail younger patients with aGO cancer. Frailty assessment provides information over and above PS and should be integrated alongside routine assessments in research and clinical practice. In the absence of prospective data, frailty measures can be derived retrospectively to build the evidence base around optimal care of frailer patients.

SIOG2021-0138* - Validation of the Cancer and Aging Research Group (CARG) Toxicity Score in the Community Oncology Setting

SIOG2021-0138* - Validation of the Cancer and Aging Research Group (CARG) Toxicity Score in the Community Oncology Setting

Evaluating the Carg Chemotherapy Toxicity Calculator Among Older Adults Newly Diagnosed with Hematologic Malignancy

Background: Older adults with hematologic malignancy (HM) are a growing demographic and providing effective treatments that balance toxicity and health related quality-of-life (HRQL) is imperative. The well-studied and utilized chemotherapy toxicity tool, the Cancer and Aging Research Group (CARG) chemotherapy toxicity score, has not been validated in hematologic malignancies.Methods: The primary objective of this study was to validate the predictive ability of the CARG score for grade 3-5 toxicity in newly diagnosed (ND) patients >60 years with HM. This was a prospective longitudinal study with 4 study visits: baseline (pre-therapy), visit 2 (Day 90), visit 3 (Day 180), and end-of-study (EOS) which occurred at the earliest of the following events: progression, transplant, or 1-year from baseline. The CARG score was evaluated at baseline. HRQL (PROMIS-GHS) and physical function measured by short physical performance battery (SPPB) were assessed longitudinally at all visits. Treatment toxicity using the NCI CTCAE (version 5.0) were captured monthly, and the worst grade of each type of chemo-related adverse event (AE) was recorded and summarized for each patient. Wilcoxon signed-rank test was used to test if variables changed significantly across visits. Fine and Gray model was used to associate comprehensive geriatric metrics and CARG score with the development of grade 3-5 chemotherapy-related toxicity with death as the competing risk, and Cox model was used to analyze overall survival (OS).Results: Ninety-seven patients with hematologic malignancy (myeloid n=34, lymphoma n=35, plasma cell n=28) were enrolled. The median age was 70 years (range 60-88) with a median 159 days on study (range 1-435). Baseline evaluations: ECOG PS was 0-1 in 69 (85%), median IADL score was 13 (range 5-14), median MOS physical health score was 44.4 (range 0-100), median self-reported KPS was 80% (50-100%), and median comorbidity score was 6 (range 2-12). PROMIS median scores improved from baseline (32, range: 12-49) to EOS (35, range: 16-47, p=0.05). Median SPPB scores improved significantly from baseline (5, range 0-12) to EOS (9, range 0-12, p=0.005). During the study period, 75 patients had 334 grade 1-2 AEs, and 42 patients had 82 grade 3-5 AEs. Hematologic toxicities were more common with 36 (37%) patients having anemia (30 grade 1-2, and 6 grade 3-5) and 11 (11%) patients having febrile neutropenia (all grade 3-5). In multivariable analysis, significant risk factors associated with grade 3-5 toxicity (p<.05) included living alone (HR 3.11, 95%CI: 1.52-6.34) and social activities score (HR 1.21, 95%CI: 1.02-1.42). Risk factors associated with OS in univariable models (p <0.05) were ECOG PS (HR 4.35, 95%CI 2.43-7.79), physical health score (HR 0.86, 95%CI 0.77-0.97), IADL (HR 0.83, 95%CI 0.73-0.95), comorbidities (HR 1.26, 95%CI 1.07-1.48), number of supplements (HR = 0.76, 95% CI 0.60-0.96), memory score (HR 1.08, 95% CI 1.01-1.14), SPPB score (HR 0.87, 95%CI 0.80-0.95) and CARG score (HR 1.12, 95%CI 1.02-1.23). In multivariable analysis, the SPPB score (HR 0.85, 95%CI 0.78-0.93) remained significant for OS.Conclusions: The CARG chemotoxicity score was not predictive of grade 3-5 toxicities in patients ND with HM, but was univariably associated with OS. Higher SPPB scores were strongly associated with OS. Future studies, evaluating modifications of the CARG score are indicated for patients with HM. Objective measures of function, such as the SPPB, may be a reliable method to stratify treatment intensities for older adults with HM. DisclosuresMims: Glycomemetics: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Aptevo: Research Funding; Leukemia and Lymphoma Society's Beat AML clinical study: Consultancy, Research Funding; Xencor: Research Funding; Kartos Pharmaceuticals: Research Funding; Genentech: Consultancy; Abbvie: Consultancy; BMS: Consultancy; Kura Oncology: Consultancy; Syndax Pharmaceuticals: Consultancy; BMS: Consultancy; Jazz Pharmaceuticals: Consultancy; Aptevo: Research Funding. Woyach: AbbVie Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company: Research Funding; AbbVie Inc, ArQule Inc, AstraZeneca Pharmaceuticals LP, Janssen Biotech Inc, Pharmacyclics LLC, an AbbVie Company,: Consultancy; Gilead Sciences Inc: Other: Data & Safety; AbbVie Inc, ArQule Inc, Janssen Biotech Inc, AstraZeneca, Beigene: Other: Advisory Committee.

Implementing the cancer and aging research group (CARG) tool in the ambulatory oncology setting to drive informed treatment selection.

209 Background: Smilow Cancer Hospital is a NCI designated cancer center in Connecticut that has built a network of 15 community-based oncology (CBO) clinics. Older patients present with unique clinical challenges including multiple comorbidities, decreased functional status, and cognitive impairment. ASCO Geriatric Oncology guidelines recommend completing both a comprehensive geriatric assessment and a chemotherapy toxicity risk assessment on all oncology patients ≥65 years old for informed treatment selection. The CARG calculator is a simple, validated tool to assess chemotherapy toxicity risk in older patients with solid tumors. Despite ASCO guidelines, the existence of validated tools, and literature confirming improved patient outcomes, oncologists’ utilization of risk calculators is limited; therefore, we conducted a pilot CARG quality improvement initiative throughout our CBO network. Methods: 36 CBO physicians agreed to complete five CARG tools, document toxicity scores in the EMR, and complete a post-survey between March and June 2021. PDSA cycles included interventions of a hyperlink to the CARG tool incorporated in the EMR and creating a dot phrase built to simplify documentation. Education was provided on both the CARG and the survey. The survey captured perceived clinical value, time commitment, and barriers to implementation. Baseline data was collected during February 2021 and included geriatric patients receiving a new chemotherapy regimen for a solid tumor. Results: 180 consecutive new chemotherapy starts in geriatric patients were monitored. The CARG score utilization in new chemotherapy starts increased from 6.5% of new cases during the first month, to 26.4% in the third month. 82% of providers found the CARG score helpful in discussing chemotherapy risks with patients. In 32% of cases, the CARG score led to a decision to dose attenuate, and in 15% of cases, the CARG score led to a different treatment regimen. Most oncologists (65%) reported spending ≤5 minutes calculating toxicity, and 88% spent ≤10 minutes. 89% of oncologists reported the CARG score was worth the added time. Conclusions: This QI initiative demonstrates feasibility and increased use of the CARG geriatric chemotherapy toxicity tool in accordance with ASCO geriatric guideline-based care. Physician education and EMR workflow modification were utilized. In the CBO setting, oncologists found the CARG tool to be quick and helpful in discussing treatment risks with patients. Use of the CARG tool led to meaningful changes in treatment, including chemotherapy dose attenuation. Further study metrics such as palliative and supportive care referrals, ED visits, and hospitalizations will fuel sustainability.

1701P Impact of the CARG score and treatment intensity on survival and toxicity outcomes in older adults with non-colorectal gastrointestinal (GI) cancers

The Cancer and Aging Research Group (CARG) toxicity score is a validated tool to predict chemotherapy toxicity for older adults with cancer. However, little is known regarding the impact of the CARG-score on survival outcomes.

Geriatric-assessment-identified functional deficits among adults with multiple myeloma with normal performance status

ObjectivesFindings from a brief geriatric assessment (GA) in a cohort of adults with multiple myeloma (MM) are presented, with particular attention to the utility of the GA in identifying important deficits in adults judged to have a normal Karnofsky Performance Status (KPS ≥ 80). Materials and MethodsAdults age 18 and older with MM were recruited into an observational study from 2018 to 2020. A modified Cancer and Aging Research Group (CARG) GA was administered at enrollment. Enrollees also completed the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life of Cancer Patients Core 30 questionnaire (QLQ-C30), with subscales of physical, social, role, and cognitive functioning (range 0–100; higher values indicate better function). Data were analyzed using descriptive statistics for the full cohort and stratified by concurrent KPS (score < 80 vs ≥ 80). ResultsAmong 89 adults, the mean age was 69.1 years, 68% were aged ≥65 years, and 70% were white. In this cohort, 78% had KPS ≥ 80. Among those with KPS ≥ 80, functional impairments (Timed Up and Go ≥14 s and dependence in ≥1 instrumental activity of daily living) were seen in 30% and 21%, respectively, with 11% reporting ≥1 fall in the prior 6 months. At least two GA-identified deficits were detected in 50% of the overall cohort and in 41% of those with KPS ≥ 80. Among those with KPS ≥ 80, self-reported physical impairment on EORTC QLQ-C30 was noted by 34%. ConclusionUsing a modified CARG GA and EORTC questionnaire, functional impairments were identified among adults considered to have a good performance status based on a KPS (≥ 80). Future studies should focus on using GA measures for therapy assignment and identifying opportunities for intervening upon GA-identified deficits.