Pretreatment Comprehensive Assessment for Elderly Lymphoma Patients
Pretreatment Comprehensive Assessment for Elderly Lymphoma Patients
Abstract & Commentary
By William B. Ershler, MD
Synopsis: Elderly patients with diffuse large cell lymphomas were assessed for the presence of various factors that might influence clinical outcomes from aggressive therapy. Of 84 patients, 50% were assessed as "fit" and 50% "unfit." Patients who were determined to be "fit" had a very satisfactory response to chemotherapy, comparable to younger patients, whereas those who were "unfit" fared poorly, whether they received aggressive or palliative chemotherapy. Further investigation is warranted to confirm the value of this instrument for patients with lymphoma and on a broader scale for older cancer patients for whom aggressive therapy is under consideration.
Source: Tucci A, et al. A comprehensive 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.
Over the past two decades there has been an increased awareness of a multitude of issues relating to cancer in the elderly.1,2 Questions such as why older people get more cancer, are the cancers inherently different in young vs. old patients, and should older patients be treated differently remain to be completely addressed, let alone resolved. The issue has been brought to a front burner with the recognition that cancer is primarily a disease of the elderly and that this segment of the population is rapidly and globally expanding. Evidence-based management of older cancer patients remains nearly impossible because elderly patients are rarely included in pivotal clinical research trials, and when they are, the selected elderly subjects are usually not typical geriatric patients, but represent a subset of otherwise healthy, functionally completely intact older patients.
One feature of geriatric medicine is the great heterogeneity amongst older patients. Clinical oncologists are familiar with this concept. Whereas some 75-year-olds appear suitable candidates for chemotherapy and tolerate treatment without problems others who also appear suitable experience rapid and progressive toxicity shortly after drug is administered. Karnofsky and Eastern Cooperative Oncology Group (ECOG) Performance Scales have proven extremely useful in younger patients in predicting the tolerability of aggressive treatment, but are not sufficiently discriminatory to identify those elderly patients who appear capable of receiving such treatment only to rapidly decompensate once treated.
Thus, a central domain of geriatric oncology has been the development of an assessment tool that could be practically administered in a busy oncology setting.3 In the current report, Tucci et al in Brescia, Italy, report of their rendition of a simple comprehensive geriatric assessment (CGA) developed to identify elderly patients with diffuse large cell lymphoma (DLCL) who were suitable candidates for anthracycline-containing immunochemotherapy.
Their CGA included an assessment of four parameters: 1) age ≥ 80 years; 2) activity of daily living (ADL), that is, loss of any activity, including bathing, dressing, toileting, transferring, feeding, and continence; 3) comorbidity score according to the Cumulative Illness Rating Score for Geriatrics (CIRS-G); and, 4) the presence of a "geriatric syndrome," defined as the occurrence of dementia, delirium, depression, incontinence, falls, osteoporosis, neglect and abuse, or failure to thrive. After written informed consent, patients were classified in the category of "fit" patients if they were aged < 80 years, were able to perform all ADLs, had fewer than three grade 3 CIRS-G comorbidities and no grade 4 comorbidities (hematological comorbidities were not investigated), and were without any of the geriatric syndromes. All other patients were classified as "unfit."
The CGA was performed in 84 consecutive patients, aged 65 years and older, with DLCL over a four-year span (January 2003 through December 2006). Treatment with curative versus palliative intent was chosen according to clinical judgment. Cyclophosphamide, hydroxydaunomycin, Oncovin® (vincristine), and prednisone (CHOP) or CHOP-like regimens were given to 62 (74%) patients. The outcome of patients was analyzed according to both the treatment received and the results of CGA.
According to CGA, 42 (50%) patients were classified as "fit." They were younger (p < .0001) and had less frequent systemic symptoms (p = .03). All 42 of these patients were prescribed curative treatment on the basis of clinical judgment. Their response rate (92.5% vs. 48.8%; p < .0001) and median survival (not reached vs. 8 months; p < .0001) were significantly better than those of 42 patients considered "unfit" by CGA. Among unfit patients, 20 had actually received curative and 22 palliative therapy on the basis of clinical judgment. These subgroups did not differ in any geriatric or lymphoma-related characteristic. The clinical outcome for the 42 "unfit" patients was similar and independent of the type of treatment received (median survival, 8 vs. 7 months). Progressive lymphoma rather than drug toxicity was the main cause of failure/death for both of these subgroups.
Commentary
The concept of performing a comprehensive assessment of geriatric cancer patients prior to treatment is intuitively reasonable. The problem has been developing an instrument that includes the right components to sufficiently discriminate those elderly who are likely to do well with aggressive therapy from those who probably won't. Experts in geriatric medicine might question the four parameters used in this CGA. For example, it would exclude all 80-year-old patients from receiving CHOP, and it seems to weigh heavily on the appearance of geriatric syndromes, the diagnosis of which is often based on rather subjective criteria. Parameters that might be relevant and easily incorporated, such as certain measures obtained by routine blood work and notably important in prognosis, such as hemoglobin level, serum lactate dehydrogenase (LDH) or serum albumin, might find their way onto a geriatric oncology assessment. Yet, it's hard to find fault with their results. Patients classified as fit by the CGA had a very satisfactory clinical outcome, comparable to younger patients with the same treatment. On the other hand, patients who were found to be "unfit" had a poorer outcome, whether they were treated with aggressive or palliative chemotherapy regimens. Furthermore, the subgroup of unfit patients who were clinically considered able to benefit from full-dose treatment (n = 20) had the same outcomes as patients given palliation (n = 22).
For any form of CGA to be of practical benefit, it must be simple, rapidly administered, and scored. In this regard, the authors report that administration of their instrument took approximately 15 minutes - significantly longer than assessing an ECOG PS, but certainly acceptable, considering the overall importance of their findings.
Thus, the CGA reported by Tucci et al has met the first test. It is an efficient method to identify elderly DLCL patients who can benefit from a curative approach with anthracycline-containing immunochemotherapy. Additional work from other institutions is needed to confirm the value of this instrument for older patients with DLCL and to assess whether it will be of comparable value for patients with other malignancies.
References
1. Ershler WB, Balducci L. Treatment considerations for older patients with cancer. In Vivo. 1994;8:737-744.
2. Balducci L, Ershler WB. Cancer and ageing: a nexus at several levels. Nat Rev Cancer. 2005;5:655-662.
3. Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol. 2007;25:1824-1831.
Elderly patients with diffuse large cell lymphomas were assessed for the presence of various factors that might influence clinical outcomes from aggressive therapy.Subscribe Now for Access
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