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

• Published in: BMJ open 2021-12, Vol.11 (12), p.e053456-e053456
• Main Authors: Spreafico, Marta, Ieva, Francesca, Arlati, Francesca, Capello, Federico, Fatone, Federico, Fedeli, Filippo, Genalti, Gianmarco, Anninga, Jakob, Gelderblom, Hans, Fiocco, Marta
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols - adverse effects; Bone cancer; Bone Neoplasms - drug therapy; Cancer therapies; Cardiac arrhythmia; Chemotherapy; Cisplatin - therapeutic use; Cytotoxicity; Drug dosages; Hearing loss; Hematology; Humans; Infections; Longitudinal data; Methods; Mucositis; Nausea; Osteosarcoma; Osteosarcoma - drug therapy; Patients; Prediction models; Research Methods; Retrospective Studies; Sarcoma; Terminology; Toxicity; Ulcers; Vomiting
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2021-053456

ObjectivesThis 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.DesignRetrospective analysis of the MRC-BO06/EORTC-80931 randomised controlled trial for osteosarcoma.SettingInternational multicentre population-based study.ParticipantsA total of 377 patients with resectable high-grade osteosarcoma, who completed treatment within 180 days after randomisation without abnormal dosages (+25% higher than planned).InterventionsPatients 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 measuresThe 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.ResultsA 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