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Non-Hodgkin's Lymphoma in the Elderly (Part 1: Overview and Treatment of Follicular Lymphoma)

Non-Hodgkin's Lymphoma in the Elderly (Part 1: Overview and Treatment of Follicular Lymphoma)

Non-Hodgkin's lymphoma is one of a few malignancies that have been increasing in incidence over the past several decades. Likewise, these disorders are more common in elderly patients, with a median age of occurrence of 65 years. Therapy in elderly patients may be affected by multiple factors, especially attendant comorbidities. The approaches to management of these patients, with either indolent or aggressive disease processes, have been based on prospective clinical trial results, many of which have included a younger patient population. Fortunately, over the past decade, results of treatment trials that have targeted an older patient population have emerged. The disease incidence and treatment approaches for both follicular (part 1 of this article) and diffuse aggressive (part 2) histologies in elderly patients are reviewed, as well as the impact of aging on the care of these patients.

Non-Hodgkin's lymphoma (NHL) is now the fifth most common malignancy in females, and sixth most common in males.[1] Approximately 59,000 new cases of NHL, and 19,000 deaths due to this disease, are expected in the United States in 2006.[1] Over the past 2 decades, NHL has become one of the few malignancies that is increasing in incidence across all adult age groups, rising by as much as 8% to 10% per year.[2-5] In recent data from the Surveillance, Epidemiology and End Results (SEER) program of the NCI, the incidence of NHL was found to increase exponentially from age 20 to 79 years and then plateau.[6-8] Specifically, the incidence of NHL in US males ranged from 13.1 per 100,000 in people aged 40 to 44 years, to 51.2 per 100,000 in those 60 to 64 years, and 133 per 100,000 in those aged 80 to 84 years.[9]

This increasing incidence is relevant in the elderly population, for although patients aged ≥ 65 years represent 13% of the population, from 25% to 35% of new NHL cases will occur in this group.[10-11] With a median age of 65 years for this disease, about 33% of cases occur in patients who are > 70 years old.[12] With the prediction that the subgroup of the US population > 65 years of age will increase by 12% to 20% over the next several decades, the occurrence of NHL in this older patient population will pose an increasing problem.[13] Incidence rates are higher in males than females across all age groups.[14] In patients older than 60 years of age, incidence rates are slightly higher among whites than blacks. Lastly, the age-specific incidence of small noncleaved cell and lymphoblastic lymphomas increases relatively slowly with age, compared to a more rapid rise in incidence by age for all other histologies.

Part 1 of this two-part article addresses the impact of aging on the treatment of NHL patients, reviews the epidemiology, classification, staging, and prognosis associated with the disease in this setting, and concludes with a discussion of the treatment of follicular NHL. Part 2, which will appear in the September issue of ONCOLOGY, focuses on the treatment of diffuse aggressive lymphomas in the elderly.

Impact of Aging

Clinical care of the older cancer patient is complicated by a variety of factors (Table 1). Clearly, chronologic age alone is not sufficient to categorize these patients.[15] The issue of "ageist stereotyping" may be present among physicians, patients, and family members. Misconceptions with regard to the etiology of cancer, disease course, and treatment may act as barriers to seeking appropriate medical care.[15-17] Specific to elderly NHL patients, a population-based study demonstrated that advanced age was associated with less optimal staging and a greater likelihood of therapy not being administered.[16] Unique social and financial issues related to advanced age also exist in this population.

These issues among others contribute to the paucity of elderly patients in clinical trials. Given a potential referral bias of patients to specialized centers for cancer care, only patients of good performance status (PS) may be entered into many clinical trials. This may not reflect the majority of elderly NHL patients in the general population.[18] There are also issues in evaluating these trials, due to a variable definition of "elderly" (60, 65, or 70 years), small patient numbers, and differing patient characteristics related to PS, comorbidities, and NHL prognostic factors. Quality-of-life assessments assessing both comorbidities and functional status, which are poorly correlated in older cancer patients, are especially important in the elderly population.[17,19-21] Multiple comorbidities have an impact on major organ function and may influence therapy-related toxicities. A correlation has been found between patient function and 2-year mortality.[17] Alterations in host immune function likewise occur in the elderly.[22]

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