The associations between nutritional factors and chemotherapy toxicity in older adults with solid tumors.

Abstract

Introduction:

Nutritional status can directly affect morbidity and mortality in older adults with cancer. We evaluated the association between pre-treatment body mass index (BMI), albumin level, and unintentional weight loss (UWL) in the prior 6 months and chemotherapy toxicity among older adults with solid tumors.

Methods:

This is a secondary analysis of a prospective multi-center study involving chemotherapy treated patients ≥65 years old. Geriatric assessment, BMI, albumin level, and UWL data were collected pretreatment. Multivariable logistic regression models evaluated the associations between nutritional factors and risk of ≥grade 3 chemotherapy toxicity (3+ChemTox).

Results:

750 patients with a median age of 72 (range: 65-94) and mostly stage IV disease were enrolled. Pretreatment median BMI and albumin were 26 kg/m² (range: 15.1-52.1) and 3.9 mg/dL (range 1.0-5.0) respectively. Nearly 50% of patients reported UWL, 17.6% reporting >10% UWL. Multivariable analysis (MVA) revealed no association between >10% UWL and risk for 3+ChemTox (adjusted odd ratio [AOR]=0.87, p=0.58). MVA showed a trend towards association between BMI ≥30 kg/m² and decreased risk of 3+ChemTox (AOR = 0.65, p = 0.06), while low albumin (≤3.6 mg/dL) was associated with higher risk of 3+ChemTox (AOR = 1.50, p = 0.03). Analysis of the joint effect of BMI and albumin demonstrated the lowest risk of 3+ChemTox among patients with high BMI (≥30 kg/m²) and normal albumin (AOR = 0.41, p = 0.008).

Conclusion:

Among older adults with solid tumors higher BMI and normal albumin are associated with lower risk of 3+ChemTox. Additional research is warranted to define the clinical significance of nutritional markers and inform future interventions.

Precis:

This study evaluated the association between nutritional factors and the risk of chemotherapy toxicity among older adults with solid tumors. Body mass index (BMI) and Albumin were identified as the strongest predictors for chemotherapy tolerance in this patient population.

Introduction:

As a result of modern medical advances, better management of chronic medical conditions, and the aging of the baby boomer population, the number of older adults in the US is on the rise. Currently, there are 46 million people age 65 and older within the US, and this number is expected to grow to 98 million by the year 2060 ¹. Life expectancy in the US has risen to 79 years, and currently an 85 year old individual is projected to live an additional six to seven years ². Cancer is a disease of older adults, with almost 60% of cancers diagnosed in people age 65 and older ³. Despite these statistics, clinical trials carry a dearth of older patients which results in limited data to shared decision making for cancer treatment ^4-7. Oncologists are tasked with treating older patients while balancing patient preferences and quality of life ^8,9.

Geriatric assessment (GA) including a nutritional evaluation is recommended for evaluating older adults with cancer prior to initiation of cancer therapy, as nutritional concerns are commonly identified among older patients^10-15. Under-nutrition, which is defined as insufficient intake of nutrients to meet the patient’s energy needs, is commonly seen among patients with cancer and has been shown to be a risk factor for morbidity, mortality, and treatment intolerance ^16-18. Studies have reported under-nutrition in >70% of hospitalized patients with cancer and >40% of patients seen in outpatient clinics ^19-21.

Historically Body Mass Index (BMI), albumin level, and unintentional weight loss (UWL) have been used as clinical indicators of nutritional status and are recommended by the European Society for Clinical Nutrition and Metabolism (ESPEN) and by the recently published nutritional guidelines by Global Leadership Initiative on Malnutrition (GLIM) ^22,23. However, in recent years the use of BMI has become more challenging in the face of the obesity epidemic. There are limited data that provide an understanding of the associations between nutritional factors (BMI, Albumin, UWL) and chemotherapy tolerance in older adults with cancer in order to guide appropriate treatment selection and nutritional interventions in this population. To address this knowledge gap, we assessed the associations between these nutritional factors and grade 3 or higher (grade 3+) chemotherapy related toxicity, and sought to identify specific combinations of these factors as predictors of toxicity risk in a large cohort of older adults with solid tumors.

Methods:

Study Population and Data Collection

This is a secondary data analysis of a prospective longitudinal study of 750 patients age ≥65 years with solid tumors recruited from 10 institutions across the US ^24,25. All participating site institutional review boards approved the study. Patients were eligible if they were beginning a new chemotherapy regimen for any solid tumor malignancy, spoke English, and were ≥65 years of age. They completed a GA prior to initiation of chemotherapy which included measures of nutritional status, functional status, comorbidity, psychological state, social support, comorbidity and cognition ²⁵ (Table 1). GA was completed primarily by patient self-report; however, assistance was provided for patients who needed help in completing the questionnaires. Three items were completed by a member of the healthcare team: Blessed Orientation-Memory-Concentration test ²⁶, Timed Up and Go ²⁷, and Karnofsky Performance Status (KPS) ²⁸.

Table 1:

Patients demographics, disease, treatment and nutritional characteristics

Characteristics	Patients ( n=750)
Age: Median age (range), years	72 (65-94)
65-69	261 (34.8%)
70-74	194 (25.9%)
75-79	166 (22.1%)
≥80	129 (17.2%)
Gender:
Female	419 (55.9%)
Male	331 (44.1%)
Cancer type:
Breast	116 (15.5%)
GI	203 (27.1%)
GU	80 (10.7%)
GYN	105 (14%)
Lung	207 (27.6%)
Other	39 (5.2%)
Cancer stage:
I	33 (4.4%)
II	99 (13.2%)
III	175 (23.3%)
IV	436 (58.6%)
Missing	7 (0.9%)
Chemotherapy
First line	531 (70.8%)
≥ Second line	219 (29.2%)
Chemotherapy regimen:
Multi-agent	527 (70.3%)
Single agent	223 (29.7%)
Standard dose:
No	177 (23.6%)
Yes	548 (73.1%)
Missing	25 (3.3%)
Median (range) KPS-physician reported:	90 (40-100)
≤70	50 (6.7%)
70-90	283 (37.7%)
≥90	405 (54%)
Missing	12 (1.6%)
Median number of co-morbidities:	2 (0-12)
0-1	232 (30.9%)
≥2	518 (69.1%)
CARG Toxicity Risk Group
Low	188 (25.1%)
Medium	360 (48.0%)
High	166 (22.1%)
Missing	36 (4.8%)
Unintentional Weight Loss (%)
No	375 (50.0%)
Yes	369 (49.2%)
≤5%	97 (12.9%)
5.1-10%	140 (18.7%)
>10%	132 (17.6%)
Missing	6 (0.8%)
Median UWL (range) among patients with UWL	7.4% (1.1%-33.5%)
Median BMI (range) at treatment initiation (kg/m2) (N=748):	26.0 (15.1-52.1)
<18.5	17 (2.3%)
18.5-24.9	291 (38.8%)
25-29.9	286 (38.1%)
≥30	154 (20.5%)
Missing	2 (0.3%)
Median albumin level (range) at treatment initiation (mg/dL) (N=722)	3.9 (1.0-5.0)
Normal (>3.6)	475 (63.3%)
Low (≤3.6)	247 (32.9%)
Missing	28 (3.7%)

Abbreviation: KPS = Karnofsky Performance Status, GI = gastro-intestinal, GU = genitourinary, GYN = gynecologic, BMI-Body Mass Index; UWL – Unintentional Weight Loss; CARG- Cancer and Aging Research Group.

The primary objective of the study was to develop a chemotherapy toxicity prediction model. The Cancer and Aging Research Group (CARG) score was developed and validated utilizing the best subset method which identifies the combination of variables that best predicts the risk of chemotherapy toxicity ^24,25. This CARG score is comprised of the 11 variables including patient age, tumor type and treatment variables, laboratory values (hemoglobin and creatinine clearance), and GA questions (falls, ability to walk one block, ability to take medications without assistance, decrease in social activities, and hearing). The score ranges from 0 to 19 and can define a low (score 0-5), intermediate (score 6-9), and high risk (score 10-19) for grade 3+ chemotherapy toxicity.

Our secondary analysis focused on three traditional measures of nutritional status which were captured in the pre-chemotherapy geriatric assessment: UWL in the past 6 months before treatment initiation, BMI and albumin level at treatment initiation. At the time of enrollment, patients reported whether they had involuntary weight loss, their current weight and weight 6-month earlier, which were used to calculate the percentage of weight loss. These measures have been validated as markers of nutritional status in prior studies ^22,31,32. In addition, sociodemographics, tumor and treatment variables, and laboratory test results were captured. Grade 3+ chemotherapy toxicities were captured using the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE, version 3.0). Two physicians reviewed toxicities and concurred that they were attributable to chemotherapy. Our analysis focused on the associations between nutritional factors captured in GA and grade 3+ chemotherapy toxicity. Since patients were enrolled at time of new chemotherapy regimen initiation and may have received prior chemotherapy, these nutritional variables were not assessed at time of diagnosis.

Statistical Analyses

Descriptive statistics were calculated to summarize patient demographic and clinical characteristics. Univariate and multivariable unconditional logistic regression models ³³ were used to assess odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for grade 3+ chemotherapy toxicity associated with nutritional factors, including UWL over the 6 months prior to treatment initiation, BMI, and albumin level at treatment initiation. In our analysis, previously published categories for UWL (≤5% loss, 5.1-≤10.0% loss, >10% loss) were used ²⁹. Based on the Center for Disease Control (CDC) guideline, four categories of BMI were created: <18.5, 18.5-24.9, 25-29.9, ≥30kg/m^{2 30}. We used Youden Index ³⁴ to identify albumin 3.6 mg/dL with the highest sensitivity and specificity in classifying the presence or absence of grade 3+ chemotherapy toxicity, based on which, albumin level at treatment initiation was classified into: normal (>3.6 mg/dL) and low (≤3.6 mg/dL). For a nutritional factor (e.g., UWL, BMI) with ordered categories, we conducted a test for trend to assess whether the risk of grade 3+ chemotherapy toxicity increased or decreased in a monotonic manner across the levels of the ordinal variable.

In the univariate unconditional logistic regression analyses, patients with missing value for the specific nutritional factor in the model were excluded (UWL: n = 6, BMI: n = 2, albumin: n = 28). The multivariable model was adjusted for the CARG Toxicity Risk Group (low, medium, high) and mutually adjusted for the three nutritional factors. We thus excluded patients with missing value for any of these three nutritional factors (n = 36) and those with missing data for CARG Toxicity Risk Group (n = 26).

Univariate and multivariable unconditional logistic regression models ³³ were also used to examine the joint effects of BMI and albumin level at treatment initiation. In the analysis for joint effect, seventeen patients with BMI <18.5 kg/m² were excluded since the number was sparse for further stratification by albumin level and not appropriate to be combined with any other BMI categories. Based on the levels of BMI (18.5-24.9, 25.0-29.9, ≥30.0 kg/m²) and albumin (low, normal), we generated a six-category variable (Table 3).

Table 3:

Joint effects of BMI and albumin at treatment initiation on risk of grade 3+ chemotherapy toxicity

BMI at treatment initiation/Albumin	Univariate analysis				Multivariate analysis*
	Grade 3+ toxicity N (%)		UOR (95% CI)	p value	Grade 3+ toxicity N (%)		AOR (95% CI)	p value
	No	Yes			No	Yes
Low albumin
BMI 18.5-24.9 kg/m2	32 (31.7)	69 (68.3)	1.00 (Referent)		30 (31.6)	65 (68.4)	1.00 (Referent)
BMI 25.0-29.9 kg/m2	30 (35.7)	54 (64.3)	0.84 (0.45-1.54)	0.56	28 (34.2)	54 (65.8)	0.96 (0.49-1.87)	0.91
BMI ≥30.0 kg/m2	28 (50.9)	27 (49.1)	0.45 (0.23-0.88)	0.02	26 (51.0)	25 (49.0)	0.43 (0.20-0.90)	0.03
Normal albumin†
BMI 18.5-24.9 kg/m2	88 (50.0)	88 (50.0)	0.46 (0.28-0.78)	0.003	87 (50.9)	84 (49.1)	0.50 (0.28-0.88)	0.02
BMI 25.0-29.9 kg/m2	90 (46.9)	102 (53.1)	0.53 (0.32-0.87)	0.01	87 (46.3)	101 (53.7)	0.68 (0.39-1.21)	0.19
BMI ≥30.0	57 (60.0)	38 (40.0)	0.31 (0.17-0.56)	<0.0001	52 (58.4)	37 (41.6)	0.41 (0.21-0.79)	0.008

Abbreviations: BMI = body mass index, UOR = unadjusted odds ratio, CI = confidence interval, AOR= adjusted odds ratio.

^*Models adjusted for unintended weight loss over the past 6 months and CARG Toxicity Risk Group in the overall analysis.

^†Above 3.6 mg/dL.

All statistical tests were two‐sided and p values less than 0.05 were considered statistically significant. Data were analyzed using SAS 9.4 analytic software (SAS Institute, Cary, NC).

Results:

Patients’ characteristics

The study cohort included 750 patients over the age 65 with solid tumors who were starting a new chemotherapy regimen (Table 1). The majority of patients were at least 70 years old (65.2%) with a median age of 72 (range 65-94) with slight predominance of females (55.9%). The four most common cancers in this cohort included lung (27.6%), gastrointestinal (27.1%), breast (15.5%) and gynecologic (14%) cancers, with more than half of the patients receiving therapy for metastatic disease (58.6%). Most patients received treatment in the first line setting (70.8%), the majority of times with multi-agent chemotherapy (70.3%) and at standard dosing (73.1%). The median KPS as reported by the treating oncologist was 90 (range 40-100). Nearly 70 percent of patients (69.1%) had at least two comorbid conditions in addition to their cancer.

Nearly half of the patients (49.2%) reported UWL in the 6 months prior to treatment initiation, with 132 patients (17.6%) reporting loss of >10% of their body weight. Among those with UWL, the median percentage weight loss was 7.4% (Range: 1.1-33.5%). The median BMI in this cohort was 26 (range 15.1-52.1). Median albumin level at treatment initiation was 3.9 mg/dL (range: 1.0-5.0), with 32.9% of patients having low albumin (≤3.6 mg/dL).

Associations between nutritional factors and risk of grade 3+ chemotherapy toxicity

Grade 3+ chemotherapy toxicity occurred in approximately half (54.7%; N= 410) of the patients. Univariate analysis showed that compared to patients with UWL ≤5% over 6 months prior to treatment, those with >10% UWL had 52% increased risk of grade 3+ chemotherapy toxicity (Unadjusted OR [UOR] = 1.52, p = 0.04, Table 2). However, multivariable analysis (MVA) showed that this association was not sustained after adjustment for CARG Toxicity Risk Group, BMI, and albumin level at treatment initiation (Adjusted OR [AOR] = 0.87, p = 0.58) (Table 2).

Table 2.

Associations between nutritional factors and risk of grade 3+ chemotherapy toxicity

	Univariate analysis				Multivariate analysis*
	Grade 3+ toxicity N (%)		UOR (95% CI)	p value	Grade 3+ toxicity N (%)		AOR (95% CI)	p value
	No	Yes			No	Yes
Unintended weight loss over the past 6 months
≤5.0% loss	223 (47.3)	249 (52.8)	1.00 (Referent)		209 (47.1)	235 (52.9)	1.00 (Referent)
5.1-≤10.0% loss	65 (46.4)	75 (53.6)	1.03 (0.71-1.51)	0.86	60 (46.9)	68 (53.1)	0.82 (0.54-1.26)	0.37
>10.0% loss	49 (37.1)	83 (62.9)	1.52 (1.02-2.26)	0.04	46 (38.0)	75 (62.0)	0.87 (0.55-1.40)	0.58
Test for trend				0.06				0.44
BMI at treatment initiation (kg/m2)
<18.5	5 (29.4)	12 (70.6)	1.81 (0.62-5.26)	0.28	5 (29.4)	12 (70.6)	2.55 (0.80-8.14)	0.11
18.5-24.9	125 (43.0)	166 (57.0)	1.00 (Referent)		117 (44.0)	149 (56.0)	1.00 (Referent)
25-29.9	123 (43.0)	163 (57.0)	1.00 (0.72-1.39)	0.99	115 (42.6)	155 (57.4)	1.22 (0.84-1.76)	0.30
≥30	86 (55.8)	68 (44.2)	0.60 (0.40-0.88)	0.01	78 (55.7)	62 (44.3)	0.65 (0.42-1.01)	0.06
Test for trend				0.009				0.06
Albumin level at treatment initiation (mg/dL)
Normal (>3.6)	239 (50.3)	236 (49.7)	1.00 (Referent)		230 (50.0)	230 (50.0)	1.00 (Referent)
Low (≤3.6)	93 (37.3)	155 (62.8)	1.71 (1.25-2.34)	0.0009	85 (36.5)	148 (63.5)	1.50 (1.05-2.14)	0.03

Abbreviations: BMI = body mass index; UOR = unadjusted odds ratio; AOR= adjusted odds ratio; CI = confidence interval.

^*Models with adjustment for CARG Toxicity Risk Group (low, medium, high) and mutual adjustment of the three nutritional factors listed in the table.

Higher BMI at treatment initiation appeared to be associated with a lower risk of grade 3+ chemotherapy toxicity (Figure 1). Risk of grade 3+ chemotherapy toxicity decreased with BMI level increase, but this negative association was marginally statistically significant in MVA (univariate p for trend = 0.009, multivariable p for trend = 0.06, Table 2). Compared to patients with BMI 18.5-24.9 kg/m², those with BMI ≥30 kg/m² had approximately 40% lower risk of grade 3+ chemotherapy toxicity (AOR = 0.65, p = 0.06). The association between albumin level and risk of grade 3+ chemotherapy toxicity was outlined in Figure 2. Compared to patients with normal albumin level (>3.6 mg/dL), those with low albumin level (≤3.6 mg/dL) had higher risk of grade 3+ chemotherapy toxicity (AOR=1.50, p=0.03) Table 2.

Figure 1:

The distribution of patients with vs. without grade 3+ chemotherapy toxicity by body mass index (BMI) level

Figure 2:

The distribution of patients with vs. without grade 3+ chemotherapy toxicity by albumin (Alb) decile.

Additional analyses of the association of these three nutritional factors with risk of grade 3+ chemotherapy toxicity, including adjustment for each of the other variables listed in Table 1, analysis by stage (1-3 vs. 4), and analysis restricted to patients with GI or lung cancer showed similar results (data not shown).

Joint effects of BMI and albumin on risk of grade 3+ chemotherapy toxicity

Given the observed high risk of grade 3+ chemotherapy toxicity associated with low BMI and low albumin level, we analyzed the potential joint protective effect of high BMI and normal albumin on chemotherapy toxicity. The protective effect of high BMI (≥30 kg/m²) was noted especially for patients with low albumin (AOR = 0.43, p = 0.03) Table 3. Normal albumin compared to low albumin was associated with a decreased risk of toxicity particularly among those with BMI 18.5-24.9 kg/m² (AOR= 0.50, p = 0.02). The lowest risk of grade 3+ chemotherapy toxicity was observed among patients with BMI ≥30 kg/m² and normal albumin when compared to those with BMI 18.5-24.9 kg/m² and low albumin ( AOR = 0.41, p = 0.008).

Furthermore, joint effect of BMI and albumin level was assessed in two subgroups of low vs. medium/high CARG toxicity risk group. In both these subgroups, the lowest risk of grade 3+ chemotherapy toxicity was among patients with BMI ≥30 kg/m² and normal albumin (low risk group: AOR = 0.12, p = 0.007; medium/High risk group: AOR = 0.49, p = 0.06) (data not shown).

Discussion:

Our study demonstrates an increased risk of grade 3+ chemotherapy toxicity in the setting of low BMI and low albumin among patient over the age of 65 who treated with chemotherapy. Under-nutrition is highly prevalent among older adults with cancer and associated with morbidity, hospitalization, decreased quality of life, functional decline and mortality ^18,35,36-38. In addition, oncology studies have demonstrated an increase in risk of treatment related toxicity in the setting of poor nutritional status ^39-43.

Unintentional weight loss is a clinical factor that has been shown to predict for poor outcomes and suggested as nutritional status assessment tool for cancer patients in the clinical setting ^44,45. Accurate determination of self-reported unintentional weight loss is challenging. Vierboom et al. evaluated the patterns of weight change among 30,000 adults in the National Health and Nutrition Examination Survey (NHANES) 1999-2014 ⁴⁶. The probability of ≥10% weight loss in the year prior to diagnosis was the highest for cancer patients (OR 3.1, 95% CI: 1.9-4.84). Within our cohort most patients reported some level of UWL prior to initiation of therapy, 17.6% had >10% of UWL. Since our patient cohort consisted of patients at various time points of their disease course, UWL 6 months prior to treatment initiation does not reflect the true incidence of weight loss prior to diagnosis. In our analysis, UWL was associated with higher risk of grade 3+ toxicity without the adjustment for any other factors, which was lost after adjustment for CARG toxicity risk group, BMI and albumin. This may be related to the inaccuracy associated with a patient’s self-reported measure such as UWL. As BMI and albumin are more objectives measures, their increased ability to predict outcome is not surprising, and raises the concern regarding the use of UWL as the main factor for nutrition evaluation of older adults with cancer.

The CDC recommendations outline normal BMI as 18.5-24.9, BMI >25 is considered overweight and >30 is considered Obese ³⁰. With the obesity epidemic, recent data shows that 41% of adults over the age of 60 are obese, which is in line with the BMI of our patients which was in the overweight category (median BMI 26) ^47,19. Our data demonstrates the association between high BMI (≥30 kg/m²) and decreased risk of grade 3+ chemotherapy toxicity. The meta-analysis conducted by Winter et al. of 32 studies with 197,940 older patients evaluated the association between BMI and all-cause mortality ⁴⁸. This analysis reported an increased risk of all-cause mortality in individuals with BMI <23.0, with a U-shaped association and the lowest risk seen among patients with BMI of 27-27.9. The possible protective effect of higher BMI among older patients has been suggested by other studies as well ^49,50. Our study provided additional evidence that warrant re-consideration of the current CDC BMI criteria, and discussion regarding adjustment of the recommended BMI for older patients specifically in the setting of anti-cancer therapy.

Among this patient cohort 33% had low albumin at time of treatment initiation. Low albumin level was associated with 50% increased risk of chemotherapy toxicity after adjustment for the CARG model and the other two nutritional factors (BMI and UWL). Assessment of serum albumin is a way to estimate the visceral protein function which is commonly suppressed by under-nutrition and inflammation in cancer patients ³². A recent systematic review demonstrated a clear association between hypoalbuminemia at treatment initiation and poor survival among patients various cancers ⁵¹. Similar to our data, a recent small study demonstrated a strong association between low albumin and early termination of chemotherapy in older patients with lung cancer ⁵². Although the association between albumin level and chemotherapy toxicity is less well studied, as a whole, the published data as well as our findings indicate that normal albumin plays an important role in treatment tolerance and outcomes of cancer patients.

In our analysis a protective effect of high BMI (≥30 kg/m²) was observed for patients with low albumin, and the protective effect of normal albumin was observed among patients with low BMI (18.5-24.9 kg/m²). Our findings suggest that combining these two nutritional factors may provide better prediction of treatment tolerance of older adults with cancer. These data are in line with other reports highlighting challenges with the use of a single nutritional marker, and the importance of body composition as predictor of treatment and disease related outcomes. Lung cancer studies reported a poorly understood reverse association between BMI and mortality, known as the obesity paradox ⁵³. Similar findings were reported in other cancers including colon cancer and melanoma ^54-57. Research in this area raised the suggestion of a sub-group of obese individuals that are considered “metabolically healthy obese” ^58,59. These patients present with favorable fat distribution, reduced adipose tissue inflammation and cardiorespiratory fitness ⁶⁰. On the other end of the spectrum, sarcopenia is a strong predictor for chemotherapy toxicity, and although most commonly reported among patients with low BMI, it has also been reported in patients with high BMI ⁶¹. Recent studies defined the condition of sarcopenic obesity in cancer patients, who present with obesity and low muscle mass ⁶². Hence, BMI alone cannot depict the true body composition and may be suboptimal for evaluation of the nutritional status ⁶³. In this setting, albumin level may assist in defining the nutritional status of the patient. Our work supports this theory with evidence of improved prediction of outcome with the use of both markers, which warrants further investigation.

To the best of our knowledge this is the first study to document protective effect of high BMI with regards to chemotherapy related toxicities in older adults with cancer. The strength of our data comes from evaluating a large cohort of older patients with cancer treated at 10 centers in the United States. The study included extensive follow up and well annotated information on these patients. However, this report carries some limitation as an ad hoc analysis with significant heterogeneity in the type of cancers included. Nutritional issues may be more prevalent and carry a stronger effect on outcomes among patients with gastrointestinal malignancies as compared to other cancers ²⁰. However, our analyses by stage (1-3 vs. 4) and among GI/lung cancer patients showed similar results. In addition, precise dosing information was not collected on this study, thus it is difficult to know if the patient’s BMI affected the dose calculation of the chemotherapy and therefore incidence of adverse events. Given the high median BMI of our patient population, it is possible that some of these patients had treatment dose calculated based on ideal rather than actual body weight, thus affecting tolerance. In this study patients were evaluated at the start of their treatment course, whereas nutritional changes occur through the disease course and may have a different impact at later stages of the disease. A longitudinal evaluation of nutritional factors was not collected in this study and should be the focus of future clinical trials. Finally, since the study was conducted in centers in the United States and primarily in patients with solid tumors, validations of these results is required in other countries and in different patient populations.

In conclusion, among older adults with solid tumors who were undergoing chemotherapy treatment, albumin level was found to be strongly associated with grade 3+ chemotherapy toxicity. Conversely, high BMI was found to have a protective effect and associated with a lower risk of chemotherapy toxicity. Our study provides additional support to the important impact of BMI and albumin level on the tolerance of chemotherapy. Oncologist should carefully consider these factors as part of a comprehensive geriatric assessment prior to recommended chemotherapy for older adults with cancer ^10,12. Additional studies are needed to validate these results, and evaluate interventions to improve nutritional status of older adults with cancer undergoing therapy.