Severe toxicity free survival: physician-derived definitions of unacceptable long-term toxicities following acute lymphocytic leukaemia

Andrés-Jensen, L. et al. (2021) Severe toxicity free survival: physician-derived definitions of unacceptable long-term toxicities following acute lymphocytic leukaemia. Lancet Haematology, 8(7), e513-e523. (doi: 10.1016/S2352-3026(21)00136-8) (PMID:34171282)

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Abstract

5-year overall survival rates have surpassed 90% for childhood acute lymphocytic leukaemia, but survivors are at risk for permanent health sequelae. Although event-free survival appropriately represents the outcome for cancers with poor overall survival, this metric is inadequate when cure rates are high but challenged by serious, persistent complications. Accordingly, a group of experts in paediatric haematology–oncology, representative of 17 international acute lymphocytic leukaemia study groups, launched an initiative to construct a measure, designated severe toxicity-free survival (STFS), to quantify the occurrence of physician-prioritised toxicities to be integrated with standard cancer outcome reporting. Five generic inclusion criteria (not present before cancer diagnosis, symptomatic, objectifiable, of unacceptable severity, permanent, or requiring unacceptable treatments) were used to assess 855 health conditions, which resulted in inclusion of 21 severe toxicities. Consensus definitions were reached through a modified Delphi process supplemented by two additional plenary meetings. The 21 severe toxicities include severe adverse health conditions that substantially affect activities of daily living and are refractory to therapy (eg, refractory seizures), are without therapeutic options (eg, blindness), or require substantially invasive treatment (eg, cardiac transplantation). Incorporation of STFS assessment into clinical trials has the potential to improve and diversify treatment strategies, focusing not only on traditional outcome events and overall survival but also the frequencies of the most severe toxicities. The two major aims of this Review were to: prioritise and define unacceptable long-term toxicity for patients with childhood acute lymphocytic leukaemia, and define how these toxicities should be combined into a composite quantity to be integrated with other reported outcomes. Although STFS quantifies the clinically unacceptable health tradeoff for cure using childhood acute lymphocytic leukaemia as a model disease, the prioritised severe toxicities are based on generic considerations of relevance to any other cancer diagnosis and age group.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Halsey, Professor Chris
Authors: Andrés-Jensen, L., Attarbaschi, A., Bardi, E., Barzilai-Birenboim, S., Bhojwani, D., Hagleitner, M. M., Halsey, C., Harila-Saari, A., van Litsenburg, R. R. L., Hudson, M. M., Jeha, S., Kato, M., Kremer, L., Mlynarski, W., Möricke, A., Pieters, R., Piette, C., Raetz, E., Ronceray, L., Toro, C., Valsecchi, M. G., Vrooman, L. M., Weinreb, S., Winick, N., and Schmiegelow, K.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Lancet Haematology
Publisher:Elsevier
ISSN:2352-3026
ISSN (Online):2352-3026
Published Online:22 June 2021
Copyright Holders:Copyright © 2021 Elsevier Ltd.
First Published:First published in Lancet Haematology 8(7): e513-e523
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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