TY - JOUR
T1 - Severe toxicity free survival: physician-derived definitions of unacceptable long-term toxicities following acute lymphocytic leukaemia
AU - Andrés-Jensen, Liv
AU - Ponte di Legno Severe Toxicity Working Group
AU - Attarbaschi, Andishe
AU - Bardi, Edit
AU - Barzilai-Birenboim, Shlomit
AU - Bhojwani, Deepa
AU - Hagleitner, Melanie M.
AU - Halsey, Christina
AU - Harila-Saari, Arja
AU - van Litsenburg, Raphaele R. L.
AU - Hudson, Melissa M.
AU - Jeha, Sima
AU - Kato, Motohiro
AU - Kremer, Leontien
AU - Mlynarski, Wojciech
AU - Möricke, Anja
AU - Pieters, Rob
AU - Piette, Caroline
AU - Raetz, Elizabeth
AU - Ronceray, Leila
AU - Toro, Claudia
AU - Grazia Valsecchi, Maria
AU - Vrooman, Lynda M.
AU - Weinreb, Sigal
AU - Winick, Naomi
AU - Schmiegelow, Kjeld
AU - Adams, Madeline R.
AU - Andres-Jensen, Liv
AU - Baust, Katja
AU - Boesten, Tineke
AU - Calaminus, Gabriele
AU - Conyers, Rachel
AU - Darlington, Anne-Sophie
AU - de Ville, Maëlle
AU - Escherich, Gabriele
AU - Hagleitner, Melanie
AU - Hou, Jen-Yin
AU - Huang, Ting-Huan
AU - Hudson, Melissa
AU - Jenney, Meriel
AU - Krawczuk-Rybak, Maryna
AU - Kremer, Leontine
AU - Lautem, Melchior
AU - Liu, Hse-Che
AU - Lopez Lopez, Elixabet
AU - Mateos, Marion
AU - Muszynska-Roslan, Katarzyna
AU - Niinimaki, Riitta
AU - Trahair, Toby
AU - Valsecchi, Maria Grazia
AU - van der Sluis, Inge
N1 - Funding Information: ER reports grants from Pfizer and has been on a data and safety monitoring board for Celgene, outside the submitted work. KS reports personal fees from Jazz Pharmaceuticals, Servier, Amgen, and Medscape, and personal fees and grants from Servier, outside the submitted work. All other authors declare no competing interests. Funding Information: The study presented in this Review was funded by the Danish Cancer Society and the Danish Childhood Cancer Foundation. The funder of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and final responsibility to submit for publication. We thank all who have contributed to discussions, scrutinising of literature, development of working documents and initial definitions. All contributors are mentioned in the appendix (pp 2–3) . All authors have access to all the data presented in this Review. Publisher Copyright: © 2021 Elsevier Ltd
PY - 2021/7/1
Y1 - 2021/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85108333882&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S2352-3026(21)00136-8
DO - https://doi.org/10.1016/S2352-3026(21)00136-8
M3 - Review article
C2 - 34171282
SN - 2352-3026
VL - 8
SP - e513-e523
JO - Lancet. Haematology
JF - Lancet. Haematology
IS - 7
ER -