Severe toxicity free survival: physician-derived definitions of unacceptable long-term toxicities following acute lymphocytic leukaemia
Liv Andrés-Jensen, Andishe Attarbaschi, Edit Bardi, Shlomit Barzilai-Birenboim, Deepa Bhojwani, Melanie M Hagleitner, Christina Halsey, Arja Harila-Saari, Raphaele R L van Litsenburg, Melissa M Hudson, Sima Jeha, Motohiro Kato, Leontien Kremer, Wojciech Mlynarski, Anja Möricke, Rob Pieters, Caroline Piette, Elizabeth Raetz, Leila Ronceray, Claudia Toro, Maria Grazia Valsecchi, Lynda M Vrooman, Sigal Weinreb, Naomi Winick, Kjeld Schmiegelow, Ponte di Legno Severe Toxicity Working Group, Andishe Attarbaschi, Madeline R Adams, Liv Andres-Jensen, Edit Bardi, Shlomit Barzilai-Birenboim, Katja Baust, Deepa Bhojwani, Tineke Boesten, Gabriele Calaminus, Rachel Conyers, Anne-Sophie Darlington, Maëlle de Ville, Gabriele Escherich, Melanie Hagleitner, Christina Halsey, Arja Harila-Saari, Jen-Yin Hou, Ting-Huan Huang, Melissa Hudson, Sima Jeha, Meriel Jenney, Motohiro Kato, Maryna Krawczuk-Rybak, Leontine Kremer, Melchior Lautem, Hse-Che Liu, Elixabet Lopez Lopez, Marion Mateos, Wojciech Mlynarski, Anja Möricke, Katarzyna Muszynska-Roslan, Riitta Niinimaki, Rob Pieters, Caroline Piette, Elizabeth Raetz, Leila Ronceray, Kjeld Schmiegelow, Claudia Toro, Toby Trahair, Maria Grazia Valsecchi, Inge van der Sluis, Raphaële van Litsenburg, Lynda Vrooman, Sigal Weinreb, Andreas Wiener, Naomi Winick, Michihiro Yano, Ting-Chi Yeh, Ester Zapotocka, Liv Andrés-Jensen, Andishe Attarbaschi, Edit Bardi, Shlomit Barzilai-Birenboim, Deepa Bhojwani, Melanie M Hagleitner, Christina Halsey, Arja Harila-Saari, Raphaele R L van Litsenburg, Melissa M Hudson, Sima Jeha, Motohiro Kato, Leontien Kremer, Wojciech Mlynarski, Anja Möricke, Rob Pieters, Caroline Piette, Elizabeth Raetz, Leila Ronceray, Claudia Toro, Maria Grazia Valsecchi, Lynda M Vrooman, Sigal Weinreb, Naomi Winick, Kjeld Schmiegelow, Ponte di Legno Severe Toxicity Working Group, Andishe Attarbaschi, Madeline R Adams, Liv Andres-Jensen, Edit Bardi, Shlomit Barzilai-Birenboim, Katja Baust, Deepa Bhojwani, Tineke Boesten, Gabriele Calaminus, Rachel Conyers, Anne-Sophie Darlington, Maëlle de Ville, Gabriele Escherich, Melanie Hagleitner, Christina Halsey, Arja Harila-Saari, Jen-Yin Hou, Ting-Huan Huang, Melissa Hudson, Sima Jeha, Meriel Jenney, Motohiro Kato, Maryna Krawczuk-Rybak, Leontine Kremer, Melchior Lautem, Hse-Che Liu, Elixabet Lopez Lopez, Marion Mateos, Wojciech Mlynarski, Anja Möricke, Katarzyna Muszynska-Roslan, Riitta Niinimaki, Rob Pieters, Caroline Piette, Elizabeth Raetz, Leila Ronceray, Kjeld Schmiegelow, Claudia Toro, Toby Trahair, Maria Grazia Valsecchi, Inge van der Sluis, Raphaële van Litsenburg, Lynda Vrooman, Sigal Weinreb, Andreas Wiener, Naomi Winick, Michihiro Yano, Ting-Chi Yeh, Ester Zapotocka
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.
Conflict of interest statement
Declaration of interests 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.
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Source: PubMed