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Severe Fatigue Affects Survival and Social Reintegration for Hodgkin Lymphoma Survivors

December 30, 2021

Approximately 40 percent of patients with Hodgkin lymphoma (HL) experience persistent fatigue, a chronic symptom that can affect patients years after successful treatment. In a large, prospective study published in the Journal of Clinical Oncology, researchers characterized fatigue and its effects on the daily lives of nearly 4,000 patients with HL, finding that baseline severe fatigue negatively affected survival, employment, and financial status as long as nine years after treatment.

Karolin Behringer, MD, of the University Hospital of Cologne in Germany, and authors analyzed patient-reported, health-related quality-of-life (QOL) data for 4,529 patients with HL (18-60 years) who were enrolled in the German Hodgkin Study Group's fifth generation of clinical trials (HD13, HD14, and HD15) between January 28, 2003, and September 30, 2009.

Patients completed the following questionnaires:

  • Quality of life questionnaire for survivors (QLQ-S): conducted before therapy, after chemotherapy, after radiotherapy, and at follow-up examinations
  • Life-situation questionnaire: conducted at the time of diagnosis and at 2, 5, and 10 years after the end of firstline treatment

A total of 3,759 patients (71% of the entire trial population) had baseline data available and completed all questionnaires, and 37 percent of those patients had severe fatigue at baseline (defined as a score ≥50 [scale of 0-100] on the European Organisation for Research and Treatment of Cancer QOL Questionnaire). Patients with baseline severe fatigue tended to be younger, were mostly female, and had higher-stage disease, compared with those without baseline severe fatigue. During follow-up, the proportion of survivors reporting severe fatigue decreased and remained relatively stable from year one (24%) to year five (20%).

At data cutoff (April 1, 2014), baseline severe fatigue did not significantly affect progression-free survival (PFS; hazard ratio [HR] = 1.19; 95% CI 0.96-1.49; p=0.12). However, when the investigators analyzed the influence of baseline severe fatigue on PFS among different treatment groups, they found that baseline severe fatigue had a greater effect on five-year PFS in patients who were enrolled in the trials' standard treatment groups (n=1,375): 87.1 percent for those with fatigue and 92.1 percent for those without (HR=1.52; 95% CI 1.08-2.12; p=0.02). Baseline severe fatigue had no effect on PFS for patients who received what the trials determined to be the "most effective" treatments (n=1,590; 94.3% vs. 94.0%; HR=0.85; 95% CI 0.56-1.30; p=0.46), which included ABVD plus involved-field radiotherapy and BEACOPPescalated plus radiotherapy.

This relationship was also true for overall survival (OS): Baseline severe fatigue had no significant effect overall (HR=1.07; 95% CI 0.76-1.50; p=0.72), but five-year OS was lower for patients in the standard treatment groups who had baseline severe fatigue (95.1% vs. 97.1%; HR=1.65; 95% CI 0.99-2.75; p=0.05).

Dr. Behringer and authors also tracked employment patterns over time as a function of fatigue's impact on patients' daily lives. They found that survivors with baseline severe fatigue were less likely to be working full- or part-time or attending school, compared with patients who did not report baseline severe fatigue. This was observed at all timepoints (TABLE).

"Especially in young adults with cancer, being uninvolved in school or work is a serious problem, because it contributes to psychological distress at the time of their transition to survivorship," the authors noted.

Severe fatigue was also related to financial problems and more frequent visits to general practitioners among HL survivors. At the five-year follow-up time point, the mean financial impact score was 46.5 (scale of 0-100 on the life-situation questionnaire) for patients with severe fatigue, compared with 17.3 for those without severe fatigue, and the mean number of visits to a general practitioner per year was 7.4 for those with severe fatigue and 4.0 for those without (p values not reported).

"This finding suggests that survivors with severe fatigue often suffer from further somatic distress," the authors wrote. "The detection of severe fatigue in survivors by using standardized questionnaires is essential, and the treatment of severe fatigue in cancer survivors after its detection is necessary."

The study is limited by its reliance on patient-reported outcomes, which could lead to reporting bias. In addition, "because unemployment itself might also cause symptoms of fatigue, it is difficult to clearly distinguish between cancer-induced severe fatigue and symptoms of severe fatigue caused by social conditions," the authors cautioned. Lastly, a high rate of missing patient data may have influenced the findings.


Behringer K, Goergen H, Müller H, et al. Cancer-related fatigue in patients with and survivors of Hodgkin lymphoma: the impact on treatment outcome and social reintegration. J Clin Oncol. 2016;34:4329-37.

TABLE. Employment Patterns for Hodgkin Lymphoma Patients With or Without Baseline Severe Fatigue*
Without Baseline Severe Fatigue With Baseline Severe Fatigue Odds Ratio (95% CI), p Value


Not Working


1,727 (77%)

489 (23%)


916 (69%)

399 (31%)

0.67 (0.57-0.79), <0.001
1 Year


Not Working


1,916 (77%)

572 (23%)


377 (49%)

398 (51%)

0.33 (0.26-0.41), <0.001
2 Years


Not Working


1,919 (83%)

375 (17%)


343 (48%)

252 (52%)

0.32 (0.25-0.42), <0.001
5 Years


Not Working


1,152 (84%)

219 (16%)


192 (57%)

143 (43%)

0.29 (0.21-0.41), <0.001
*Includes patients with available data on fatigue and employment status at the respective time point.


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