Physician-defined severe toxicities occurring during and after cancer treatment: Modified consensus definitions and clinical applicability in the evaluation of cancer treatment

Camilla Grud Nielsen; Birthe Lykke Thomsen; Bodil Als-Nielsen; Rachel Conyers; Sima Jeha; Marion K Mateos; Wojciech Mlynarski; Rob Pieters; Mathias Rathe; Kjeld Schmiegelow; Liv Andrés-Jensen

doi:10.3389/fped.2023.1155449

Physician-defined severe toxicities occurring during and after cancer treatment: Modified consensus definitions and clinical applicability in the evaluation of cancer treatment

Front Pediatr. 2023 Apr 26:11:1155449. doi: 10.3389/fped.2023.1155449. eCollection 2023.

Authors

Camilla Grud Nielsen¹, Birthe Lykke Thomsen^{1

2}, Bodil Als-Nielsen¹, Rachel Conyers^{3

4

5}, Sima Jeha⁶, Marion K Mateos^{7

8

9}, Wojciech Mlynarski¹⁰, Rob Pieters¹¹, Mathias Rathe^{12

13}, Kjeld Schmiegelow¹, Liv Andrés-Jensen¹

Affiliations

¹ Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital, Copenhagen, Denmark.
² Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
³ Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia.
⁴ Pharmacogenomics, Stem Cell Biology, Murdoch Children's Research Institute, Melbourne, VIC, Australia.
⁵ Children's Cancer Centre, The Royal Children's Hospital, Melbourne, VIC, Australia.
⁶ Department of Oncology, St Jude Children's Research Hospital, Memphis, TN, United States.
⁷ Kids Cancer Centre, Sydney Children's Hospital Randwick, Sydney, NSW, Australia.
⁸ Discipline of Paediatrics and Child Health, School of Clinical Medicine, UNSW Medicine & Health, UNSW, Sydney, NSW, Australia.
⁹ Children's Cancer Institute, Lowy Cancer Research Centre, UNSW, Sydney, NSW, Australia.
¹⁰ Department of Pediatrics, Oncology & Hematology, Medical University of Lodz, Lodz, Poland.
¹¹ Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands.
¹² Department of Pediatric Hematology and Oncology, Hans Christian Andersen's Children's Hospital, Odense University Hospital, Odense, Denmark.
¹³ Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

Abstract

Overall survival after cancer is increasing for the majority of cancer types, but survivors can be burdened lifelong by treatment-related severe toxicities. Integration of long-term toxicities in treatment evaluation is not least important for children and young adults with cancers with high survival probability. We present modified consensus definitions of 21 previously published physician-defined Severe Toxicities (STs), each reflecting the most serious long-term treatment-related toxicities and representing an unacceptable price for cure. Applying the Severe Toxicity (ST) concept to real-world data required careful adjustments of the original consensus definitions, translating them into standardized endpoints for evaluating treatment-related outcomes to ensure that (1) the STs can be classified uniformly and prospectively across different cohorts, and (2) the ST definitions allow for valid statistical analyses. The current paper presents the resulting modified consensus definitions of the 21 STs proposed to be included in outcome reporting of cancer treatment.

Keywords: cancer treatment; childhood cancer; long-term; severe-toxicity-free-survival; toxicities.

Grants and funding

The study was funded by the Danish Childhood Cancer Foundation (Grant number: 2021–7377). The funder had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The fellowship of Marion Mateos is funded by Cancer Institute NSW Early Career Fellowship funding (ECF181430).