PMID- 34916320 OWN - NLM STAT- MEDLINE DCOM- 20220307 LR - 20220307 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 11 IP - 12 DP - 2021 Dec 16 TI - Novel longitudinal Multiple Overall Toxicity (MOTox) score to quantify adverse events experienced by patients during chemotherapy treatment: a retrospective analysis of the MRC BO06 trial in osteosarcoma. PG - e053456 LID - 10.1136/bmjopen-2021-053456 [doi] LID - e053456 AB - OBJECTIVES: This study aims at exploring and quantifying multiple types of adverse events (AEs) experienced by patients during cancer treatment. A novel longitudinal score to evaluate the Multiple Overall Toxicity (MOTox) burden is proposed. The MOTox approach investigates the personalised evolution of high overall toxicity (high-MOTox) during the treatment. DESIGN: Retrospective analysis of the MRC-BO06/EORTC-80931 randomised controlled trial for osteosarcoma. SETTING: International multicentre population-based study. PARTICIPANTS: A total of 377 patients with resectable high-grade osteosarcoma, who completed treatment within 180 days after randomisation without abnormal dosages (+25% higher than planned). INTERVENTIONS: Patients were randomised to six cycles of conventional versus dose-intense regimens of doxorubicin and cisplatin. Non-haematological toxicity data were collected prospectively and graded according to the Common Terminology Criteria for Adverse Events (CTCAE). MAIN OUTCOME MEASURES: The MOTox score described the overall toxicity burden in terms of multiple toxic AEs, maximum-severity episode and cycle time-dimension. Evolution of high-MOTox was assessed through multivariable models, that investigated the impact of personalised characteristics (eg, achieved chemotherapy dose, previous AEs or biochemical factors) cycle-by-cycle. RESULTS: A cycle-by-cycle analysis identifies different evolutions of MOTox levels during treatment, detecting differences in patients' health. Mean MOTox values and percentages of patients with high-MOTox decreased cycle-by-cycle from 2.626 to 1.953 and from 57.8% to 36.6%, respectively. High-MOTox conditions during previous cycles were prognostic risk factors for a new occurrence (ORs range from 1.522 to 4.439), showing that patient's history of toxicities played an important role in the evolution of overall toxicity burden during therapy. Conventional regimen may be preferred to dose-intense in terms of AEs at cycles 2-3 (p<0.05). CONCLUSIONS: The novel longitudinal method developed can be applied to any cancer studies with CTCAE-graded toxicity data. After validation in other studies, the MOTox approach may lead to improvements in healthcare assessment and treatment planning. TRIAL REGISTRATION NUMBER: ISRCTN86294690; Post-results. CI - (c) Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Spreafico, Marta AU - Spreafico M AUID- ORCID: 0000-0002-7773-9976 AD - MOX, Department of Mathematics, Politecnico di Milano, Milan, Italy marta.spreafico@polimi.it. AD - Mathematical Institute, Leiden University, Leiden, Netherlands. AD - CHRP - National Centre for Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy. FAU - Ieva, Francesca AU - Ieva F AUID- ORCID: 0000-0003-0165-1983 AD - MOX, Department of Mathematics, Politecnico di Milano, Milan, Italy. AD - CHRP - National Centre for Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy. AD - CHDS - Centre for Health Data Science, Human Technopole, Milan, Italy. FAU - Arlati, Francesca AU - Arlati F AD - MOX, Department of Mathematics, Politecnico di Milano, Milan, Italy. FAU - Capello, Federico AU - Capello F AD - MOX, Department of Mathematics, Politecnico di Milano, Milan, Italy. FAU - Fatone, Federico AU - Fatone F AD - MOX, Department of Mathematics, Politecnico di Milano, Milan, Italy. FAU - Fedeli, Filippo AU - Fedeli F AUID- ORCID: 0000-0001-5991-2029 AD - MOX, Department of Mathematics, Politecnico di Milano, Milan, Italy. FAU - Genalti, Gianmarco AU - Genalti G AD - MOX, Department of Mathematics, Politecnico di Milano, Milan, Italy. FAU - Anninga, Jakob AU - Anninga J AD - Department of Solid Tumors, Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands. FAU - Gelderblom, Hans AU - Gelderblom H AD - Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands. FAU - Fiocco, Marta AU - Fiocco M AD - Mathematical Institute, Leiden University, Leiden, Netherlands. AD - Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands. AD - Trial and Data Center, Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20211216 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - Q20Q21Q62J (Cisplatin) SB - IM MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - *Bone Neoplasms/drug therapy MH - Cisplatin/therapeutic use MH - Humans MH - *Osteosarcoma/drug therapy MH - Retrospective Studies PMC - PMC8679129 OTO - NOTNLM OT - Chemotherapy OT - Longitudinal data OT - Osteosarcoma OT - Prediction models OT - Toxicity COIS- Competing interests: None declared. EDAT- 2021/12/18 06:00 MHDA- 2022/03/08 06:00 PMCR- 2021/12/16 CRDT- 2021/12/17 06:13 PHST- 2021/12/17 06:13 [entrez] PHST- 2021/12/18 06:00 [pubmed] PHST- 2022/03/08 06:00 [medline] PHST- 2021/12/16 00:00 [pmc-release] AID - bmjopen-2021-053456 [pii] AID - 10.1136/bmjopen-2021-053456 [doi] PST - epublish SO - BMJ Open. 2021 Dec 16;11(12):e053456. doi: 10.1136/bmjopen-2021-053456.