Late Endocrine and Metabolic Sequelae and Long‐Term Monitoring of Classical Hodgkin Lymphoma and Diffuse Large B‐Cell Lymphoma Survivors: A Systematic Review by the Fondazione Italiana Linfomi

Background: Overall survival after lymphoma has improved in recent years, but the high prevalence of late treatment‐related sequelae has been observed as a counterpart. Method: In this systematic review, FIL researchers aimed to: (i) estimate the incidence or prevalence of late endocrine‐metabolic sequelae, (ii) evaluate the effects of modern therapeutic approaches on incidence or prevalence of late endocrine‐metabolic sequelae, and (iii) determine whether there is evidence of follow‐up schemes for their screening/early diagnosis in the subset of long‐term classical Hodgkin lymphoma (cHL) and diffuse large B‐cell lymphoma (DLBCL) survivors treated at adult age. The MEDLINE, Embase and the Cochrane Library databases were searched for relevant articles published up to October, 2020. The study selection process was conducted by three independent reviewers and was reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. A risk of bias assessment was performed using the Cochrane tool for randomized trials and the Newcastle‐Ottawa Scale for observational studies. Results: In the final analysis, eight studies were included, four of which focused on thyroid disease, two on gonadal dysfunction, one on bone disease and one on metabolic syndrome. Hypothyroidism was reported in up to 60% of adult cHL survivors and was frequently recorded even with modern radiotherapy approaches. Menopause occurred in 52–72% of women after chemotherapy. An 86% reduction in vertebral density was reported following R‐CHOP‐like chemotherapy. Sarcopenia and metabolic syndrome were reported in 37.9% and 60% of patients, respectively. No validated screening protocols were found for the early diagnosis of long‐term treatment‐related endocrine and metabolic sequelae, thus the authors finally suggest the execution of screening exams according to the risk category which were identified in the epidemiologic studies.