Rapid Review

Have We Moved Beyond the Karnofsky Score?

By Jerome W. Yates, MD and William B. Ershler, MD

National Institute on Aging, NIH Drs. Yates and Ershler report no financial relationships relevant to this field of study.

Extensive literature is developing on the role of functional assessment of cancer patients, particularly those who are elderly, in order to provide safer and more effective treatment. The concept of comprehensive assessment, entrenched now in geriatric medicine, finds its roots within medical oncology, as such was the purpose of the performance scale (PS) introduced by Karnofsky and colleagues at Memorial in 1948.1 Since then, and particularly in the last decade, pretreatment assessment has resurfaced within oncology, primarily because of the rapidly expanding population of cancer patients within the geriatric age group. There is no doubt that age-associated comorbidities and functional impairments influence outcomes, both in terms of treatment tolerance and efficacy. Yet, the optimal method for predicting vulnerability remains to be established.2-7 In fact, it remains unclear whether any of the new and more extensive instruments will add values commensurate to the costs involved when compared to the simple assessment provided by the Karnofsky scale, something the practicing oncologist can complete in less than a minute.

The need for such an assessment

Oncologists are unable to practice evidence-based medicine when it comes to the administration of chemotherapy to "typical" older patients because there is little available data on current drugs and drug regimens when administered to elderly patients, particularly those with functional impairments or comorbidities. This is because clinical trials designed to demonstrate efficacy of a particular drug, regimen, or modality typically enroll patients with good performance status and limited comorbidities. Yet, clinical experience has indicated that most oncology modalities, including surgery, radiation, and chemotherapy can be effective in older functionally impaired patients, but this must be balanced by the increased risks of such treatments, notably in those with functional impairments and comorbidities.7 For example, we know that cancer patients with impairment in performing activities of daily living (ADL) or instrumental activities of daily living (IADL) are more likely to experience adverse outcomes,8 and yet approximately half of such patients will present with good or excellent (ECOG) performance status (PS) 0 or 1.9 To the extent that newly derived assessment instruments can identify those elderly patients who present with good to excellent ECOG PS, but who rapidly decompensate upon challenge with aggressive treatment, patients will be more intelligently treated and age bias reduced.10

Components of Assessment

Investigators in geriatric medicine have developed assessment instruments to operationalize research in the area of frailty. Thus, self report, or observed variables, that capture changes such as weight loss, weakness, slow walking speed, and poor endurance have been linked to outcomes such as hospitalization, nursing-home placement, and death.11 As the field has evolved, a number of variables have been introduced into the "comprehensive geriatric assessment" (CGA), including an assessment of ADL, IADL, comorbidity, cognitive status, nutrition, depression, social environment, and the presence or absence of geriatric syndromes, such as falls, delirium, pressure ulcers, and incontinence. A full CGA may take several hours or more, and is likely to be in excess of what is needed in oncology practice to meet the needs as outlined above.

Accordingly, abridged versions have been developed for oncology. For example, Balducci and colleagues have introduced a simpler scheme in which, for the purposes of cancer management in the elderly (i.e., increased vulnerability to adverse outcomes), is defined as one or more of the following: age > 85 years, dependence in one or more ADL, presence of three or more comorbid conditions, and/or presence of one or more geriatric syndromes (pressure sores, incontinence, delirium, falls, and functional dependence).12,13 Using this approach, Tucci and colleagues characterized a series of 84 patients (age 65 years and older) who were treated for diffuse, large B-cell lymphoma at a single institution.14 The majority of patients (74%) received either CHOP or a CHOP-like regimen. A total of 42 patients were characterized by the geriatric assessment as "fit." Response rates (93% vs. 49%; p < .0001) and median survival (not reached vs. 8 months; p < .0001) were found to be superior in the patients characterized as fit, compared with those characterized as unfit. Approximately half of the patients deemed "unfit" were treated with palliative therapy, whereas the remainder were treated with curative intent. For this "unfit" group, there did not appear to be a survival difference using either strategy, raising the possibility that patients characterized as unfit or frail may derive similar benefit from palliative approaches.

What's Next?

There is general agreement that we need better tools to define risks of therapy for elderly patients with cancer. Adopting some features of the CGA is a good first step, but for the purposes of prescribing cancer treatment, it would seem such assessment would benefit from inclusion of laboratory parameters that are relevant both to the patient's general condition and the impact on the disease process. For example, a measure of hemoglobin, albumin, and creatinine could easily be incorporated into an overall "fitness" score. However, most importantly, a prospective clinical trial is needed to confirm the value of pre-treatment assessment in terms of response rate, toxicity, and survival. For example, a trial in which elderly patients were randomly allocated to either pre-treatment assessment, with prescribed treatment based upon assessment, or routine management, in which the Karnofsky or ECOG PS was used to guide treatment. It is not clear yet that we have found the right assessment instrument that will better the Karnofsky PS in such a trial.

References

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6. Molina-Garrido MJ, Guillen-Ponce C. Comparison of two frailty screening tools in older women with early breast cancer. Crit Rev Oncol Hematol. 2010. [Epub ahead of print]

7. Pal SK, Hurria A. Impact of age, sex, and comorbidity on cancer therapy and disease progression. J Clin Oncol. 2010;28:4086-4093.

8. Freyer G, et al. Comprehensive geriatric assessment predicts tolerance to chemotherapy and survival in elderly patients with advanced ovarian carcinoma: A GINECO study. Ann Oncol. 2005;16:1795-1800.

9. Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol. 2007;25:1824-1831.

10. Foster JA, et al. How does older age influence oncologists' cancer management? Oncologist. 2010;15: 584-592.

11. Fried LP, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146-M56.

12. Balducci L, Beghe C. The application of the principles of geriatrics to the management of the older person with cancer. Crit Rev Oncol Hematol. 2000;35:147-154.

13. Balducci L, Extermann M. Management of cancer in the older person: A practical approach. Oncologist. 2000;5:224-237.

14. Tucci A, et al. A comprehensive geriatric assessment is more effective than clinical judgment to identify elderly diffuse large cell lymphoma patients who benefit from aggressive therapy. Cancer. 2009;115:4547-4553.