Geriatric assessment for oncologists: Rationale and future directions

Critical Reviews in Oncology/Hematology 59 (2006) 211–217

Geriatric assessment for oncologists: Rationale and future directions Arti Hurria a,∗ , Mark S. Lachs b , Harvery J. Cohen c , Hyman B. Muss d , Alice B. Kornblith e a

Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, United States b Weill Medical College of Cornell University, New York, United States c Duke University and VA Medical Center, New York, United States d University of Vermont, New York, United States e Dana-Farber Cancer Institute, New York, United States Accepted 31 March 2006

Contents 1.

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Background, significance, and rationale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1. The oncologist’s evaluation of the older patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2. The geriatrician’s evaluation of the older patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2.1. Functional status . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2.2. Comorbid medical conditions and concomitant medication use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2.3. Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2.4. Cognition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2.5. Psychological state and social support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3. Evaluation of the older patient with cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Development of a cancer-specific geriatric assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Study design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Summary of study results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Future directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Biography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Abstract Sixty percent of all cancer occurrences and seventy percent of cancer mortalities occur in people over the age of 65. As the population ages, there is an emerging need to develop a means for oncologists to characterize the “functional age” of older patients with cancer in order to tailor treatment decisions and stratify outcomes based on factors other than chronological age and to develop interventions to optimize cancer treatment. In this paper, we discuss the formulation of a geriatric assessment for older patients with cancer. The measures included in this assessment were chosen based on their validity, reliability, brevity, adaptability for self-administration, and ability to prognosticate risk for morbidity or mortality in an older patient. The proposed geriatric assessment covers the essential domains of assessment predictive of survival in the geriatric population, is primarily self-administered, and limited personnel time is required. Our eventual goal is to determine if this geriatric assessment measure can identify factors independent of age that predict cancer treatment morbidity and mortality and result in rationale interventions to optimize oncologic care. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Geriatric assessment; Older patient; Geriatric oncology

∗

Corresponding author. Tel.: +1 212 639 3263; fax: +1 212 717 3821. E-mail address: [email protected] (A. Hurria).

1040-8428/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.critrevonc.2006.03.007

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1. Background, significance, and rationale Patients older than age 65, in comparison to those younger than 65 have an 11-fold increased cancer incidence and a 16fold increase in cancer mortality [1]. The population at risk is growing rapidly. By 2030, 20% of the population will be over the age of 65. Unfortunately, oncologists are ill prepared for this demographic shift. Their training is focused on choosing the best treatment intervention for physically fit younger patients. Older patients with cancer are less likely to be offered standard cancer treatments that have been shown to improve survival, in part because of concerns regarding their ability to tolerate treatment [2–11]. However, there is great heterogeneity among older patients of the same chronological age which may distinctively impact their ability to tolerate cancer therapy. Oncologists need an assessment tool that provides information regarding an older individual’s “functional age” in comparison to their “chronological age.” The technology of geriatric assessment could potentially help identify those older adults who are more vulnerable to complications from cancer treatment. This inter-disciplinary assessment provides information regarding the patient’s functional status, comorbid medical conditions, other medications, nutritional status, psychological state, social support, and cognition. Each of these domains is important to consider when formulating a cancer treatment plan. The principles of geriatric assessment are not commonly addressed during oncology or other sub-specialty training. The importance of geriatric assessment in predicting outcomes is being recognized by other sub-specialties [12].

mine a treatment course, assess eligibility for clinical trials, and predict treatment toxicity and survival. KPS and ECOG performance status have been shown to be independent predictors of survival of oncology patients regardless of age [15–19]. Despite the widespread use of KPS and ECOG performance measurements, an older patient would benefit from a more thorough baseline assessment. KPS and ECOG performance status may be misleading for the older patient since clinical trials relying on these scales have largely excluded the frail elderly. For example, it is not uncommon for a healthy older patient to score a 60% on the KPS (“Requires occasional assistance, but is able to care for most of his/her needs.”). This score has been associated with susceptibility to treatment toxicity in younger patients, and is a common exclusion criterion for clinical trials. However, the “need for assistance” may be based on a non-cancer cause, resulting in an underestimate of functional status and overestimate of risk of toxicity. Conversely, KPS and ECOG performance status do not address activities of daily living (ADL) or instrumental activities of daily living (IADL), which are independent predictors of morbidity and mortality in the older patient, nor do they address the other domains usually included in a geriatric assessment, which contribute to the ability to tolerate cancer treatment. For example, in a study by Repetto et al., among older adults with cancer with a good ECOG performance status (rated 0 or 1), 37.7% and 9.3% required assistance with instrumental activities of daily living and activities of daily living, respectively. Hence, KPS or ECOG performance status may overestimate an older patient’s ability to function [20].

1.1. The oncologist’s evaluation of the older patient 1.2. The geriatrician’s evaluation of the older patient Presently, there is no uniform way for oncologists to assess an older patient’s overall health or functional status other than assigning a Karnofsky performance status (KPS) or Eastern Cooperative Oncology Group (ECOG) performance status [13,14] (see Table 1). These generic scales are applied to all adult cancer patients regardless of age. Oncologists use these scales to estimate functional status in order to deter-

The geriatrician’s comprehensive evaluation identifies areas of vulnerability among all geriatric patients, not just those with cancer, and provides valuable information not provided by KPS or ECOG performance status. Below is a description of each domain of geriatric assessment and its relevance to the older patient with cancer.

Table 1 The KPS and ECOG Scales (%)

Karnofsky performance scale (KPS)

Score

ECOG performance scale

100 90 80 70 60 50 40 30 20 10 0

Normal, no complaints, no evidence of disease Able to carry on normal activity; minor signs or symptoms of disease Normal activity with effort; some signs or symptoms of disease Cares for self, unable to carry on normal activity or to do active work Requires occasional assistance, but is able to care for most of his/her needs Requires considerable assistance and frequent medical care Disabled, requires special care and assistance Severely disabled, hospitalization indicated; death not imminent Very sick, hospitalization indicated; death not imminent Moribund, fatal processes, progressing rapidly Dead

0 1

Normal activity; asymptomatic Symptomatic; fully ambulatory

2

Symptomatic; in bed <50% of time

3

Symptomatic; in bed 50% of time; not bedridden

4

100% bedridden

5

Dead

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1.2.1. Functional status In the geriatric population, functional status is an independent predictor for morbidity and mortality. Functional dependence is associated with prolonging hospital stay, worsening of function while in the hospital, need for nursing home placement, and overall mortality [21–24]. Cancer is associated with increased dependence in functional status independent of KPS or ECOG performance status. In a large study of older patients, individuals with cancer had more limitations in activities of daily living (examples include ability to bathe, dress, transfer, maintain continence, and feed one self) and instrumental activities of daily living (examples include ability to telephone, shop, travel, prepare meals, do housework, take medications, and manage one’s finances) than individuals without cancer, and they required more healthcare attention [25]. The oncologist needs an accurate assessment of functional status in order to determine whether the patient receiving chemotherapy can seek medical attention if necessary (i.e., use the telephone, follow instructions, and anticipate and respond to toxicity) [26]. 1.2.2. Comorbid medical conditions and concomitant medication use The number of comorbid medical conditions increases as one ages [27]. Comorbidity has been shown to affect functional recovery following surgical treatment for breast cancer, and correlates with overall survival. In a study by Satariano and Ragland, patients with breast cancer who had three or more comorbid conditions had a 20-fold higher rate of mortality from a comorbid medical condition than from breast cancer. These findings were independent of age, race, treatment, tumor histology, tumor size, social, or behavioral factors, and most importantly, tumor stage. Patients with three or more comorbid conditions had a four-fold increase in mortality compared to those with no comorbid medial conditions [28]. A study of 203 patients with cancer (median age 75; range 63–91) showed little correlation between comorbidity (as measured by the Cumulative Illness Rating Scale-Geriatric and Charlson scale) and functional status (as measured by ECOG performance status, ADL and IADL) [29]. Thus, each is an important domain to measure. An indirect measure of comorbidity is the frequency of medication use. On average, older patients use three-fold more medications than younger patients and are more vulnerable to adverse drug events. A review of a patient’s medication list is needed in order to determine whether prescribed or over-the-counter medications result in a drug interaction [30,31]. 1.2.3. Nutrition Poor nutritional status is an independent predictor of functional dependency and survival in the geriatric population. A low body mass index (<22 kg/m2 ) is associated with increased dependence in activities of daily living and decreased 1 year survival [32]. The prognostic effect of unintentional weight loss in patients with cancer was evaluated

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in a study of 3047 patients enrolled in Eastern Cooperative Oncology Group chemotherapy trials [33]. Weight loss during the 6 months prior to chemotherapy was associated with poorer survival (statistically significant in 9 out of 12 tumor types). In addition, weight loss was associated with lower chemotherapy response rates (significant only in patients with breast cancer). Decreasing weight correlated with decreased performance status in all tumor types except pancreatic and gastric cancer [33]. 1.2.4. Cognition In the geriatric population, the presence of dementia is an independent predictor of mortality [34,35]. An assessment of cognition in an older patient with cancer is essential. New cognitive deficits could imply metastatic disease to the brain. In the era of oral chemotherapy, cognitive assessment is needed to determine if the patient has the decisional capacity to consent and adhere to medication instructions at home. If the patient takes an incorrect number of pills, the treatment could be either fatal (too many) or ineffective (too few). An assessment of cognitive status is also important for the patient who is receiving intravenous chemotherapy. For example, a patient with cognitive impairment will likely need assistance in remembering instructions regarding the use of supportive medications, such as antiemetics. In the presence of cognitive impairment, the involvement of the patient’s family or caregiver is often required to maintain safety. Caregiver education is important in order to identify and report early signs of toxicity, which might warrant medical attention. Caregivers and members of the healthcare team need to be aware that older patients may present with atypical symptoms. For example, for the older patient, delirium might be the first presenting sign of electrolyte imbalance or neutropenic infection. This altered cognitive state may impair the older individual’s ability to communicate toxicity. 1.2.5. Psychological state and social support Social isolation or the lack of social ties is an independent predictor of mortality in the geriatric population [36]. Social support serves as a buffer against the psychological impact of a stressful life event and social support plays an important role in the psychological functioning of the older cancer patient. For example, risk factors for severe psychological distress in women with breast cancer include divorce or separation, and inadequate social support [37]. For older patients with cancer, an assessment of social support is essential to determine if the patient will have the necessary physical and psychological support if they experience a treatment associated complication. 1.3. Evaluation of the older patient with cancer Presently, there is no consensus within the geriatric or oncology community regarding a standard assessment of older patients with cancer. A geriatrician examines all

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Table 2 Findings from a Geriatric Assessment Performed in a Cohort of Older Patients with Cancer [39]

Table 3 Geriatric Assessment Measures Selected Based on Reliability, Validity, Brevity, and Prognostic Value

Domain

Domain

Measures

Functional Status

Activities of Daily Living [Subscale of Medical Outcomes Study Physical Health Scale] [41] Instrumental Activities of Daily Living [Subscale of the OARS] [42] Karnofsky Performance Status (Physician-Rated) [43] Karnofsky Performance Status (Patient-Rated) [44] Timed Up and Go [45] Number of Falls in Last 6 Months [46]

Comorbidity Cognition Psychological Social Functioning

Physical Health Section [Subscale of the OARS] [42] Blessed Orientation–Memory–Concentration Test [47] Hospital Anxiety and Depression Scale [48] Medical Outcomes Study Social Activity Limitations Measure [49] Medical Outcomes Study Social Support Survey: Emotional/Information and Tangible Subscales [49] Seeman and Berkman Social Ties [36]

Functional Status (≥1 deficit) ADL IADL

Percent of Patients with Problems in Each Domain (%) 18 72

Comorbidity (any comorbidity as identified by these scales) Charlson Scale 36 Cumulative Illness Rating Scale 94 Memory Impairment 22 Poor Nutrition 19 Polypharmacy 41

domains of physical, psychological, and social functioning in order to identify all potential areas of vulnerability that can impact on the patient’s ability to maintain functional independence. This multidisciplinary assessment is often performed by direct interview and is time intensive, requiring resources far exceeding the capabilities of the oncology clinic. In contrast, the oncologist looks for a screening tool to identify the seemingly fit older individual whose limited reserve places him/her at risk for life threatening toxicities when physiologically stressed by treatment. The proposed geriatric instrument would not be a substitute for the comprehensive assessment of a geriatrician, but instead, serve to identify the vulnerable older cancer patient who might benefit from a more comprehensive evaluation, specific interventions, and treatment modification. A few investigators have reported on the use of a geriatric oncology assessment tool, each using different assessment tools and administration methods. Ingram et al. reported on the feasibility of a self-reported assessment, which was mailed prior to the oncology visit. Seventy-six percent of patients returned the assessment tool, which included questions regarding demographics, comorbid conditions, functional status, pain, financial well-being, social support, emotional state, spiritual well-being, and quality of life [38]. Balducci and colleagues performed a geriatric assessment, which included questions regarding the patient’s functional status, comorbid medical conditions, memory, nutritional status, and polypharmacy. The assessment uncovered a number of problems, which would not be identified by routine history and physical (see Table 2) [39]. Repetto et al. evaluated the role of geriatric assessment in 363 patients age 65 and older with cancer. The assessment included an evaluation of functional status (ECOG performance status, ADL and IADL), comorbidity (Satariano Index), memory (mini-mental status exam), and depression (geriatric depression scale). In this study, trained interviewers administered the questionnaire [20]. Overcash and colleagues developed an abbreviated comprehensive geriatric assessment consisting of selected items from the ADL and IADL scales, geriatric depression scale, and mini-mental status exam. The goal of this abbreviated assessment is to identify older patients who would benefit from a more comprehensive assessment (51).

Social Support

Nutrition

Body Mass Index [32] Percent Unintentional Weight Loss in the Last 6 Months [33]

2. Development of a cancer-specific geriatric assessment The geriatric and oncology literature were reviewed to choose commonly used, validated measures of geriatric assessment. The development group performed an exhaustive review of available geriatric assessment tools before deciding on the ones proposed in Table 3. Criteria applied to selection included that the measures be validated, reliable, brief, adaptable for self-administration, and able to prognosticate risk for morbidity or mortality in an older patient. A common set of measures was reviewed and approved by oncologists, geriatricians, psychologists, and biostatisticians at several Cancer and Leukemia Group B (CALGB), Cancer in the Elderly Committee and Quality of Life Committee meetings. In comparison to the geriatric instrument proposed by other investigators, this geriatric instrument includes a more comprehensive assessment of: (1) physical functioning (including a performance-based functional status measure and questions regarding the ability to perform rigorous physical activities not measured by traditional activities of daily living and instrumental activities of daily living scales), (2) social functioning, and (3) assessment of cognition. Each domain is critical in assessing older patients with cancer. In particular, our preliminary data demonstrated that a high proportion of older patients with cancer who were receiving chemotherapy were independent in the traditional measures of functional status in the geriatric population, such as activities of daily living and instrumental activities of daily living [40]. This likely reflects the bias to refer a healthier geriatric population for oncologic treatments. Therefore, we included a more comprehensive assessment of physical functioning via the MOS Physical Health Scale and Timed Up and Go in order to obtain an understanding of an individual’s phys-

A. Hurria et al. / Critical Reviews in Oncology/Hematology 59 (2006) 211–217

ical reserve available during the stress of cancer treatment [41,42]. In addition, this geriatric instrument is primarily selfadministered (except for three items that are performed by a healthcare professional), in order to minimize the amount of healthcare personnel time needed. In summary, the proposed geriatric assessment covers the essential domains of assessment predictive of survival in the geriatric population, is primarily self-administered, and limited personnel time is required. We acknowledge that a number of different instruments can be used to perform a geriatric assessment and the proposed assessment is one approach to acquiring this important information. 2.1. Study design A protocol was developed to evaluate the feasibility of this new instrument, as measured by the length of time to complete the assessment, the percent of patients able to complete it without assistance, and the patient’s satisfaction with the assessment. Patients were eligible for this feasibility study if they were age 65 or older, were receiving chemotherapy, and had a diagnosis of breast, lung, colorectal cancer, or lymphoma. All patients were fluent in English because some instruments have not been validated in other languages. Informed consent was obtained prior to participation. The geriatric assessment was primarily self-administered with the exception of three scales which required administration by a healthcare professional: (1) Blessed Orientation-MemoryConcentration Test, (2) Timed Up and Go, and (3) Karnofsky performance status. A trained research interviewer assisted patients who could not complete the self-administered portion of the assessment on their own [50]. 2.2. Summary of study results Forty patients with a mean age of 74 (range 65–87) participated in the study. The sample consisted of patients receiving chemotherapy for breast cancer (25%), colorectal cancer (18%), lung cancer (38%), and lymphoma (20%). The majority of the participants were married (55%), retired (83%), white (90%), and had some college experience or beyond (65%). The geriatric assessment was feasible in this select population, as demonstrated by a mean time to completion of 27 min, with the majority of patients satisfied with the Table 4 Feasibility results (N = 40) Outcome

Result

Time to complete

27 min (S.D. 10); range 8–45 min 78%

Ability to complete self administered portion without assistance Rated the questionnaire as “easy to comprehend” Satisfied with questionnaire length Stated no items were upsetting

83% 90% 100%

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questionnaire length and content and able to complete the self-administered portion of the assessment on their own (Table 4) [50]. 3. Future directions A prospective multicenter feasibility study of incorporating this geriatric instrument as part of the assessment of older patients on clinical trials is planned in the Cancer and Leukemia Group B via the Cancer in the Elderly Committee. This will allow us to determine the feasibility of this instrument in a broader group of patients from varied sociodemographic backgrounds. In order to ensure an adequate representation of patients age 70 and older, accrual to this study will be stratified by age so that a maximum of 25% of patients will be age 65–69 and the remainder will be age 70 and older. If feasibility is confirmed, then subsequent prospective studies will be developed to determine this new tool’s ability to: (1) predict risk of toxicity to cancer treatment, (2) develop interventions to decrease the risk of toxicity, (3) identify those patients who are fit enough to receive standard therapy without modification, and (4) longitudinally evaluate the impact of cancer treatment on these essential geriatric domains. In addition, the geriatric assessment would allow for a comparison of patient characteristics across studies and the ability to control for possible confounding factors contributing to mortality. Future studies are also needed to determine the resource time needed to score the geriatric assessment, and to initiate referrals or interventions as deemed appropriate. Through capturing this information, policy, and practice can be modified to accommodate the increased needs of older patients and allow for appropriate reimbursement for these services. The ultimate goal is to develop an assessment tool that will lead to evidence-based treatment decisions in the older patient based on factors other than chronological age in order to enhance the health, independence, and quality of life of older adults with cancer.

Reviewers Dr. John M. Bennett, University of Rochester Medical Center, Hematology/Oncology Unit, 601 Elmwood Ave., Box 704, Rochester, NY 14642, U.S.A. Dr. Hans Wildiers, Department of Medical Oncology, Multidisciplinary Breast Center, U.H. Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. Dr. Catherine Terret, Geriatric Oncology Program, Department of Medical Oncology, Center Leon Berard, 28, rue Laennec, 69373 Lyon Cedex 08, France. Dr. Arash Naeim, Division of Hematology-Oncology, David Geffen School of Medicine, University of California, Los Angeles, 10945 Le Conte Avenue, Suite 2345, Box 951687, Los Angeles, CA 90095-1687, U.S.A.

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Acknowledgements This work was supported by: (1) K23 AG026749-01 Paul Beeson Career Development Award in Aging Research (recipient: Arti Hurria, MD). (2) American Society of Clinical Oncology-Association of Specialty Professors-Junior Development Award in Geriatric Oncology (recipient: Arti Hurria MD). (3) The Memorial Sloan-Kettering Patrick Byrne Research Fund. (4) Cancer and Leukemia Group B: The Cancer in the Elderly Committee.

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Biography Dr. Arti Hurria is a geriatrician and oncologist, focusing on care of the older patient with cancer. She completed a geriatric fellowship in the Harvard Geriatric Fellowship Program, followed by a hematology–oncology fellowship at Memorial Sloan-Kettering Cancer Center. Dr. Hurria is presently a member of the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center and is a cadre member of the Cancer and Leukemia Group B, Cancer in the Elderly Committee. Dr. Hurria is a recipient of the Paul Beeson Career Development Award in aging research (K23 AG026749-01) and American Society of Clinical Oncology Career Development Award (T. Franklin Williams Scholar).