Hodgkin Lymphoma Patients Have High Fatigue Levels Regardless of Tumor Stage

Patients with Hodgkin lymphoma have a high incidence of severe acute and persistent fatigue, regardless of their tumor stage or the treatment method chosen for their disease, according to a study published in Lancet Oncology.

Instead, researchers led by Stefanie Kreissl, MD, of the University Hospital of Cologne in Germany, noted that long-term fatigue resulted mainly from fatigue levels seen at baseline.

The researchers wrote that participants with severe baseline fatigue (fatigue score ≥ 50) tended to remain at high fatigue levels during the 5-year follow-up, while participants with more advanced-stage disease with moderate fatigue at baseline (fatigue score < 50) had significant improvement in fatigue after successful treatment.

Fatigue is a commonly reported symptom associated with Hodgkin lymphoma. In this study, Kreissl and colleagues used fatigue data from three trials, HD13, HD14, and HD15, which looked at early-stage favorable disease, early-stage unfavorable disease, and advanced-stage disease, respectively, and compared them with fatigue in the German population. Fatigue was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 self-administered questionnaire at baseline, during chemotherapy, at the end of treatment, and every year for 5 years. They estimated the effect of different disease and patient characteristics on fatigue with multiple regression analyses and identified fatigue trajectories with growth mixture models.

Results showed that those patients with a higher tumor burden at baseline had higher fatigue score at baseline, but the researchers noted that “even early-stage patients with typically low tumor burden had clinically relevant fatigue.” Patients in the HD15 study, those with advanced-stage disease, had a mean baseline fatigue score of 49.0 compared with 30.8 in HD13 and 39.8 in HD14.

“Surprisingly, the large effect of disease stage on the extent of baseline fatigue did not translate into different fatigue levels during treatment, because all the different treatment intensities used in our trials induced very severe fatigue symptoms,” the researchers wrote. “This finding is surprising because the intensity of treatment with only two cycles ABVD [doxorubicin, bleomycin, vinblastine, and dacarbazine] for early-stage disease is very different from six to eight cycles of escalated BEACOPP [bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone].”

Scores were similar among the three studies in the second year after the end of treatment (HD13: 28.5; HD14: 28.8; HD15: 30.7), and in the fifth year after treatment (HD13: 30.8; HD14: 27.1; HD15: 28.2).

The only factors found to be significantly associated with fatigue at the second and fifth year after treatment were baseline fatigue (P < .0001) and age (P < .0001).

The researchers identified three to four fatigue trajectories in their analysis. First, those patients with higher levels of baseline fatigue had higher levels of persistent fatigue. Second, 36% of patients with early-stage unfavorable disease and 46% of patients with advanced-stage disease spontaneously returned to a fatigue level similar to that of the general population. Third, about one-third of patients had their fatigue level improve, but it remained higher than the general population. Finally, the patients in each disease category with the highest baseline fatigue scores had no change in their fatigue scores.

In a comment that accompanied the study, Michel Henry-Amar, MD, PhD, and Raphaël Busson, MD, of Centre de Traitement des Données du Cancéropôle Nord-Ouest, pointed out that a limitation to the method used by Kreissl and colleagues is that it “cannot provide any information about which patients will belong to which category because it is based on a posteriori data.”

In addition, Henry-Amar and Busson noted that fatigue is a multidimensional entity and was assessed with a one-dimensional method in this analysis.

“Before tertiary prevention interventions are undertaken to manage or prevent the development of persistent fatigue, among which exercise-programs and cognitive behavioral therapy have been proposed, there is a need to understand the mechanisms by which individuals who develop a cancer are also susceptible to develop abnormal fatigue,” they concluded.