Quality of Life in Long-term Survivors of Hodgkin's Lymphoma

Abstract & Commentary

By William B. Ershler, MD

Synopsis: A long-term longitudinal assessment of quality of life among patients treated for early-stage Hodgkin's lymphoma reveals that, with the exception of fatigue, there is general improvement over time. Factors that influence the rate of improvement include age and sex, but do not include the type of treatment received (radiation vs. chemotherapy).

Source: Heutte N, et al. Quality of life after successful treatment of early-stage Hodgkin's lymphoma: 10 year follow-up of the EORTC-GELA H8 randomized controlled trial. Lancet Oncol. 2009;10:1160-1170.

Currently, more than 80% of newly diagnosed patients with Hodgkin's lymphoma will be long-term survivors.1 Yet, little is known about the changes over time in health-related quality-of-life (HRQoL) measures for patients during their post-treatment follow-up and re-adaptation to normal life. To address this, Heutte et al from Europe report on the HRQoL of patients treated in the randomized H8 trial of the European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Group and the Groupe d'Etudes des Lymphomes de l'Adulte (GELA). Their goal was to assess HRQoL and fatigue following treatment, to analyze relations with treatment, and to identify factors that predict persistent fatigue.

Patients received HRQoL questionnaires at the end of primary therapy and several times during follow-up. The EORTC QLQ-C30 was used to assess HRQoL, and the Multidimensional Fatigue Inventory (MFI-20) was used to assess fatigue. Changes of mean HRQoL scores over time were analyzed with mixed models.

In all, there were 2,666 assessments from 935 patients. Mean follow-up was 90 months (range 52-118 months). Age affected all functioning and symptom scores except emotional functioning, with younger age associated with higher functioning and lower severity of symptoms. Furthermore, improvement with time showed similar patterns between age groups. Women reported lower HRQoL and higher symptom scores than did men. Overall, 3.2% (14/439 for role functioning) to 9.7% (43/442 for social functioning) and 5.8% (29/498 for reduced motivation) to 9.9% (49/498 for general fatigue) of patients reported impairments of 10 points or more (on a 0-100 scale) in QLQ-C30 and MFI-20 scores, respectively, independent of age and sex. Emotional domains were more affected than physical ones. There was no relation between HRQoL outcome and type of treatment. Fatigue (MFI-20 scores) at the end of treatment was the only predictive variable for persistent fatigue, with odds ratios varying from 2.58 (95% CI 1.00-6.67) to 41.51 (12.02-143.33; p £ 0.0001). Sensitivity analyses adjusting for missing data were much the same as the main results.

Commentary

HRQoL data after treatment for early-stage Hodgkin's lymphoma show that patients experience strain and limitations in all subdomains, apart from cognitive functioning, and also have reduced motivation. However, in most domains, there was gradual improvement and, although there was no survey prior to treatment, overall HRQoL 18 months or so after treatment was comparable to published data of the general European population.2-4 Curiously, fatigue status at the end of treatment seemed to predict subsequent HRQoL and general fatigue; reduced motivation persisted throughout the follow-up. What it is about Hodgkin's lymphoma and persistent fatigue that remains incompletely understood? Certainly early on, fatigue figures prominently in the symptom complex and often can be related to anemia or other "B" symptoms. However, why fatigue should persist over the long term remains unclear, but perhaps is somehow related to depression. Unfortunately, this parameter was not assessed in the current report. It is notable that in another study performed within the Southwest Oncology Group on 244 patients with early Hodgkin's disease, persistent fatigue was observed two years after treatment, at a point when other QoL indicators had returned to pre-treatment levels.5

In the current study, while differences in HRQoL improvement with time were linked to age and sex, there was no association with type of treatment (i.e., radiation vs. chemotherapy). On the surface, this runs counter to findings from the SWOG study, in which patients receiving combined modality treatment were found at six months after treatment to have significantly more symptom distress than those who had received radiation alone. However, by one year, there was no difference, a finding consistent with the current report.

Thus, the findings from this report can be considered good news. For the most part, those qualities of life that are impaired with the diagnosis and treatment of Hodgkin's lymphoma gradually return to baseline levels. Yet, the persistence of fatigue remains to be explained.

References

1. Ansell SM, Armitage JO. Management of Hodgkin lymphoma. Mayo Clin Proc. 2006;81:419-426.

2. Hjermstad MJ, et al. Using reference data on quality of life — the importance of adjusting for age and gender, exemplified by the EORTC QLQ-C30 (+3). Eur J Cancer. 1998;34:1381-1389.

3. Michelson H, et al. Health-related quality of life measured by the EORTC QLQ-C30 — reference values from a large sample of Swedish population. Acta Oncol. 2000;39:477-484.

4. Watt T, et al. Fatigue in the Danish general population. Influence of socio-demographic factors and disease. J Epidemiol Community Health. 2000;54: 827-833.

5. Ganz PA, et al. Health status and quality of life in patients with early-stage Hodgkin's disease treated on Southwest Oncology Group Study 9133. J Clin Oncol. 2003;21:3512-3519.