Anemia and Brain Function in Elderly Lung Cancer Patients

Abstract & Commentary

By Stuart M. Lichtman, MD, FACP, Associate Attending, Memorial Sloan-Kettering Cancer Center, Commack, NY. Dr. Lichtman reports no financial relationship to this field of study.

Synopsis: Chemotherapy-related anemia is associated with impairment of functional status and cognitive functions. In elderly cancer patients anemia correction or maintenance could be useful to preserve functional independency and protect from mental decay. However, the study results need to be confirmed on a larger series of patients within a controlled clinical trial.

Source: Mancuso A, et al. Correlation between anemia and functional/cognitive capacity in elderly lung cancer patients treated with chemotherapy. Ann Oncol. 2006;17:146-150.

The older population is undergoing a continuous growth and currently 60% of all cancers occur in persons older than 65 years of age. Cancer in older individuals is expected to become progressively more common, with 80% of all cancers occurring in this population by the year 2050. Among the common age-related cancers non-small-cell lung cancer (NSCLC) must be considered a disease of older adults: the median age of newly diagnosed lung cancer patients in developed countries is approximately 68 years, and as many as 40% of patients may be older than 70 years at diagnosis. Evidence from earlier clinical trials suggests that platinum-based chemotherapy regimens offer patients with advanced NSCLC modest quality of life (QoL) and survival advantages compared with best supportive care. Subgroup analyses of these trials and retrospective studies suggest that the relative survival benefits of chemotherapy are maintained in older age groups.

One of the major issues in the management of NSCLC in elderly patients is the high prevalence of comorbidity that may affect the function, the functional reserve, the QoL, the life expectancy and the tolerance of treatment by older individuals.1 Anemia is a common finding in cancer patients and its prevalence increases after 65 years.2 Anemia has a negative impact on most patients, but in an elderly cancer population the consequences can be even more significant.3 Anemia and fatigue might precipitate functional dependence in the elderly considering that higher mobility difficulties have been reported in women older than 70 years with lower Hb level.4 The prevention of fatigue and anemia may reduce the risk of functional dependence and its correction in this setting of patients results in improved QoL. A large number of cognitive and emotional complications of anemia, including headaches, loss of concentration and depression, have been reported in cancer patients.

A direct correlation between hemoglobin levels and cognition was established by Pickett et al and they reported that increasing the hematocrit of chronic dialysis patients above 33%-36% with blood transfusions improved attention span, learning ability and memory.5

With the aim of systematizing all these data, using CGA variables, the authors have investigated in this prospective study whether any association exists between Hb levels and functional capacity, cognitive impairment and comorbidities in elderly lung cancer patient treated with chemotherapy. This prospective observational study was conducted in the department of respiratory diseases, San Camillo-Forlanini Hospital, Rome, Italy. Patients enrolled in the study were required to be older than 70 years and to have a confirmed diagnosis of lung cancer and were undergoing chemotherapy. All patients were evaluated before the initiation of chemotherapy (baseline) and before each subsequent cycle (after 21 days) for QoL, mental capacity, functional status, depression and comorbidities. Evaluation scales were taken from the Comprehensive Geriatric Assessment (CGA), a multidimensional, interdisciplinary diagnostic process to determine the medical, psychological and functional capabilities of a frail elderly person. Cognitive function was measured with the Mini-Mental State Examination (MMSE), a widely used brief screening test for cognitive deficit.

Forty two lung cancer patients age older than 70 were enrolled in the study. After the baseline evaluation, patients were visited before each therapy cycle (21 days). The analysis showed that higher Hb values were associated with higher (better) values of the upward scales ADL, IADL and MMSE (ie, a positive correlation) and with lower (better) values of the downward scales VAS, CIRS and GDS (ie, a negative correlation). For all indexes, statistical significance was attained at one or more of the time points. The results were in the direction showing that Hb increase was associated with improvement of the indexes. In 14 patients given erythropoietin mean Hb increased by 1.6 g/dL (95% CI, 0.8-2.3) and all indexes were improved. On the contrary, in 18 patients not given erythropoietin where mean Hb decreased by -1.8 g/dL, a parallel worsening was observed for all indexes.

Commentary

Anemia may adversely influence the management of older cancer patients receiving chemotherapy with or without radiotherapy by limiting the dose intensity and the dose density of the treatment, and thus preventing adequate cancer control. This prospective survey analyzed correlations between anemia and CGA principal parameters, revealing functional decline, cardiovascular and central nervous comorbidity, and risk of therapeutic complications as well as QoL. In these elderly cancer patients Hb level was associated to QoL, functional capacity, mental decline, presence of comorbidities and depression. Moreover, the change in Hb level was associated with the change in all the above parameters although not significantly for IADL. This suggests that the treatment of anemia or maintenance of adequate Hb levels could be useful to preserve or improve QoL and overall health status in elderly cancer patients undergoing chemotherapy. These results are one of the clinical evidences of guidelines (ASCO-ASH, NCCN, EORTC) that recommend the treatment of mild anemia level (Hb 10-12 g/dL) in an elderly population with comorbidities.6 In interpreting the results of this study, however, one should be aware that other factors, such as patient’s performance status, chemotherapy regimen and response to chemotherapy, may have interacted with the Hb level and the other variables examined. This studies importance lies in the fact the prospective intervention studies have not been in elderly patients to determine whether there is a correlation between correction of anemia and improvement in cognitive parameters.

References

1. Extermann M. Measurement and impact of comorbidity in older cancer patients. Crit Rev Oncol Hematol. 2000;35:181-200.

2. Ania BJ, et al. Prevalence of anemia in medical practice: community versus referral patients. Mayo Clin Proc. 1994;69:730-735.

3. Balducci L, Hardy CL. Anemia of Aging: A Model of Erythropoiesis in Cancer Patients. Cancer Control. 1998;5(2 Suppl 1):17-21.

4. Chaves PH, et al. Looking at the relationship between hemoglobin concentration and prevalent mobility difficulty in older women. Should the criteria currently used to define anemia in older people be reevaluated? J Am Geriatr Soc. 2002;50:1257-1264.

5. Pickett JL, et al. Normalizing hematocrit in dialysis patients improves brain function. Am J Kidney Dis. 1999;33:1122-1130.

6. Lichtin A. The ASH/ASCO clinical guidelines on the use of erythropoietin. Best Pract Res Clin Haematol. 2005;18:433-438.