Investigating a range of late effects of Hodgkin lymphoma treatments

Dramatic improvement in Hodgkin lymphoma (HL) survival rates over recent decades has come at significant cost: treatment-related late effects which are epitomised in female HL patients treated at young ages. The aims of this PhD were to investigate the clinicopathological features of secondary breast cancers following irradiation, and to explore treatment-related risk factors for a range of less well reported but clinically significant co-morbidities, including: thyroid abnormalities, bone disorders, lympoedema, and neuropathies. A national cohort study of 5,002 female HL patients treated with supradiaphragmatic radiotherapy was extended and updated to include 803 breast cancers after mean follow-up 24.7 years. Histological subtype and hormone receptor status did not differ markedly from sporadic breast cancers, however cases were more commonly diagnosed at young ages, early stage, were higher grade, and bilateral. More aggressive clinical features (oestrogen/progesterone receptor negative, triple negative, high grade) occurred more commonly with shortest follow-up time after HL treatments. I designed and conducted a questionnaire study in 237 HL survivors demonstrating high cumulative burden of a range of conditions at mean 23.5 years since treatment. The most frequently reported disorders were thyroid (33.8%), with significantly raised risks after neck irradiation, and neurological disturbance (36.1%). Increased risk of sensory disturbance was associated with increasing cycles of chemotherapy, particularly vinca-alkaloids. Osteoporosis occurred commonly at young ages and was associated with a significantly increased risk of bone fractures. Lymphoedema and dropped head syndrome were less frequently reported but represent potentially overlooked late effects following high dose irradiation in adulthood. In summary, this work describes and investigates the risks of a range of HL-treatment related late effects, some of which have been scarcely investigated, which contributes to knowledge of late effects in both adult and childhood treated HL patients, with potentially important clinical implications