January 11, 2009 — A large European study that followed patients with Hodgkin's lymphoma for nearly 8 years has found that survivors made a good recovery, with health-related quality-of-life scores similar to those of aged-matched controls in the general population. However, high-level fatigue was common, and this needs further study, say the researchers, led by Natacha Huette, PhD, from the University of Caen Basse-Normandie, in France.
"Clearly, persistent fatigue represents one of the great challenges in Hodgkin's lymphoma, and efforts should be undertaken to identify contributing factors and describe better the patterns of recovery," they write.
Their report appears in the December issue of the Lancet Oncology.
The high cure rate for Hodgkin's lymphoma and the fact that most patients are younger than 40 when they are diagnosed means that the quality of survivorship in this disease is an important consideration, notes an accompanying editorial.
Editorialists Andrew Evens, DO, MS, and Lynne Wagner, PhD, both from Northwestern University Feinberg School of Medicine, in Chicago, Illinois, agree with the researchers that this finding that high-level fatigue is common, even 2 years after therapy, needs further study. They suggest that future studies should investigate interventions for fatigue, such as aerobic exercise.
The authors also suggest that, in some patients, physical exercise might improve or even prevent persistent fatigue. However, they add that "at present, our data cannot be used to guide the development of newer treatment approaches, nor do they prove that less intensive treatments with reduced toxicity directly translate to an improved well-being for long-term survivors," they conclude.
Follow-Up of Nearly 8 Years
The analysis reported by Dr. Huette and colleagues was conducted on data collected during a large phase 3 clinical trial that began in 1993. The analysis involved 1577 patients, but analysis of health-related quality of life (HRQoL) was conducted in only 935 patients, and a total of 2666 assessments were carried out. The mean follow-up was 90 months.
Patients had early-stage Hodgkin's lymphoma (stage I or II) and were treated with either a combination of chemotherapy and radiotherapy or radiotherapy alone. The chemotherapy regimen consisted of mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine. A variety of radiotherapy was used: mantle field, subtotal nodal, or involved-field.
Many patients experienced recovery within 18 months of completing treatment.
"It was interesting to note that the therapeutic modality (radiotherapy vs chemotherapy) did not have significant effects on HRQoL, and that many patients experienced recovery within 18 months of completing treatment," note the editorialists.
The researchers report that there was a significant improvement in most HRQoL domains within 18 months of the end of treatment, including fatigue. The 2 domains that did not improve were cognitive functioning and reduced motivation, "suggesting that neither the treatment nor the disease affects these 2 dimensions," they note.
Very few (<10%) patients showed HRQoL impairment, and the scores recorded by these long-term survivors of Hodgkin's lymphoma were similar to those of healthy controls from the general population matched for age and sex, the researchers explain.
Although fatigue improved greatly during the first 18 months after treatment, the levels plateaued and did not fall any further. As a result, "high-level fatigue more than 2 years after therapy was common," the researchers note. The proportion of patients who had persistent fatigue 22 months or more after the end of treatment were 51.7% for general fatigue, 41.5% for physical fatigue, 34.9% for mental fatigue, 32.2% for reduced activity, and 26.3% for reduced motivation.
"Also, of note, emotional domains did not show the same magnitude of improvement after treatment as physical domains," the researchers write. The editorialists also highlight the finding that emotional function might not follow the same trajectory of improvement after treatment as physical functioning. They suggest that future studies should examine cancer-specific psychosocial concerns that are salient among young adults, such as sexual function, fertility, and fear of recurrence. "The survivorship experience among young adults needs to be better understood with regard to psychosocial health needs," they write.
Unknown Cause of Fatigue
Dr. Huette and colleagues note that the only comparable study in this field also found persistent fatigue in survivors. That study, from the Southwest Oncology Group, was published several years ago (J Clin Oncol. 2003;21:3512-3519). This group measured changes in HRQoL over 2 years after randomization in 244 patients with favorable Hodgkin's lymphoma. They reported that patient scores at 1 year were similar to pretreatment scores, without further improvement at the 2-year assessment. However, this group also reported an increased fatigue level, compared with that of the general population (score differences >10 points), and this was more pronounced in men than in women.
In their own study, Dr. Huette and colleagues found that of all the factors they studied (age, sex, treatment), only age had a significant effect on the level of fatigue measured immediately after treatment completion, and this was also true for persistent fatigue. "However, when fatigue level at the end of treatment is added to the model, it substitutes for age," they note.
"Since it is not yet clear what the cause of long-term fatigue in Hodgkin's lymphoma survivors might be, and what the underlying and contributing factors are, it is important that a group at risk of long-term fatigue is identified," they write.
"Conceptually, there is a known and substantial overlap between fatigue and depression," the researchers note. However, in their own study, they cannot exclude depression as one of the underlying causes of high fatigue "because we did not screen for it." But they point out that previous studies have not shown significant effects from antidepressants in fatigued patients.
The researchers and editorialists have disclosed no relevant financial relationships.
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