Quality of Life in a 2-Year Follow-up: Signs of PNP Predicting Cognitive Functioning in Survivors Treated in the HD10–12 Trials of the German Hodgkin Study Group (GHSG).
Authors: Halbsguth Teresa , Mueller Horst , Flechtner Hans-Henning , Brillant Corinne , Behringer Karolin , Schober Thomas , Nisters-Backes Hiltrud , Engert Andreas , Borchmann Peter 
Published: April 2020

Abstract
Purpose: Hodgkin Lymphoma (HL) is one of the best curable cancers in adults. Thus, current research is focusing on the increasing proportion of HL survivors with respect to the long-term consequences of therapy. Especially health related quality of life (QoL) needs thorough investigation since this is relevant for HL patients, complex and so far there is limited knowledge. QoL incorporates different aspects such as general QoL, fatigue, emotional, physical, role, social, sexual and cognitive functions. This analysis is focusing on QoL in the HD10–12 trials of the GHSG with special emphasis on cognitive functions (CF) and possible predictors in a 2 year follow-up.
Methods: Patients of the GHSG trials HD10–12 completed the QLQ-C30, the MFI20 and some additional items at the time of diagnosis, after chemotherapy, after radiotherapy and at follow-up examinations. We describe the courses of the QLQ-C30 scales with means and 95%-confidence intervals for each measurement point and in relation to the respective norm values. In accordance with well established criteria, we used a cut off point of 10 points below the expected value to define self reported cognitive deficits (CD). In multiple regressions we analysed the role of the following predictors for cognitive functions 2 years after treatment: age, sex, disease stage, treatment modality, baseline score of cognitive functioning and symptoms of peripheral neuropathy (PNP) before and after chemotherapy application.
Results: In the sample of 3608 patients all scales showed abnormal values from the beginning, further deterioration to the end of chemotherapy and continuous recovery from the end of radiotherapy on. Most scales improved clearly beyond their pre-treatment values but only physical functioning finally approached normal values. The CF scale showed a remarkable flat long term course and, opposed to the other scales, reached no improvement beyond the pre-treatment level. In 1044 patients with baseline and 2 year results, 439 met the criteria of relevant CD at baseline. Of these, 60.4% still felt handicapped after 2 years and 39.6% were in the range of normal values. 605 patients reported no CD at baseline and 69.6 % of them remained unaffected after 2 years (30.4% had developed CD). After adjustment for age, sex, disease stage, treatment modality and CF baseline scores, the regression analyses showed significant impact of symptoms of PNP before (p&lt;.001) and after (p=.002) chemotherapy on CF after 2 years.
Conclusion: In this large prospective study most QoL domains are remarkably improved after recovery from HL. In contrast CD occur frequently and show virtually no improvement. Symptoms of PNP as well as baseline values of CF are specifically predictive of future cognitive complaints. Further studies are necessary to investigate whether these results could be used for treatment modification or the development of intervention strategies.