Hiroshi Kobayashi1, Tomotake Okuma2, Hiroyuki Oka3, Koichi Okajima2, Yuki Ishibashi2, Liuzhe Zhang4, Toshihide Hirai5, Takahiro Ohki2, Yusuke Tsuda5, Masachika Ikegami5, Ryoko Sawada5, Yusuke Shinoda5, Toru Akiyama4, Hirotaka Kawano6, Takahiro Goto2, Sakae Tanaka5. 1. Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. hkobayashi-tky@umin.ac.jp. 2. Department of Musculoskeletal Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan. 3. Department of Medical Research and Management for Musculoskeletal Pain, 22nd Century Medical & Research Center, Faculty of Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. 4. Department of Orthopaedic Surgery, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma, Omiya-ku, Saitama-shi, Saitama, 330-8503, Japan. 5. Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. 6. Department of Orthopaedic Surgery, Faculty of Medicine, University of Teikyo, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8606, Japan.
Abstract
BACKGROUND: Despite the clinical benefits of eribulin on overall survival of advanced soft tissue sarcoma (STS) patients, treatment-related toxicity reduces their QOL. Body composition metrics (BCMs) are associated with poor outcome and drug toxicities in several cancers. This study investigated whether BCMs could predict drug toxicity occurrence in advanced STS patients treated with eribulin. METHODS: This study included 23 advanced STS patients treated with eribulin between March 2016 and April 2018. BCMs were evaluated using a CT scan obtained within 1 month before or after treatment initiation. The relationship of BCMs and other clinical factors was evaluated and CART analysis used to develop classification models for risk groups of drug toxicity. RESULTS: Sixteen patients (69.6%) experienced any grade 3/4 toxicity. Eleven patients (47.8%) developed G4 hematologic toxicity, which was significantly higher in those with low skeletal muscle gauge (SMG) (P = 0.02) and low pretreatment neutrophil count (P = 0.0002). Six patients (26.1%) had grade 3/4 non-hematologic toxicity, and was higher in those with low SMG (P = 0.004), and low serum albumin level (P = 0.02). Five patients with high BMI (P = 0.03) experienced febrile neutropenia (FN) and low pretreatment neutrophil count (P = 0.02). CART analysis classified three risk groups, and area under the receiver operating characteristic curve (AUROCC) was 0.92, 0.88, 0.92 in G4 hematologic AE, G3/4 non-hematologic AE, FN, respectively. CONCLUSIONS: SMG is a significant predictive factor of eribulin drug toxicity in advanced STS patients. Risk classification of drug toxicity through combining predictive factors, could improve the therapeutic strategy used in chemotherapy.
BACKGROUND: Despite the clinical benefits of eribulin on overall survival of advanced soft tissue sarcoma (STS) patients, treatment-related toxicity reduces their QOL. Body composition metrics (BCMs) are associated with poor outcome and drug toxicities in several cancers. This study investigated whether BCMs could predict drug toxicity occurrence in advanced STSpatients treated with eribulin. METHODS: This study included 23 advanced STSpatients treated with eribulin between March 2016 and April 2018. BCMs were evaluated using a CT scan obtained within 1 month before or after treatment initiation. The relationship of BCMs and other clinical factors was evaluated and CART analysis used to develop classification models for risk groups of drug toxicity. RESULTS: Sixteen patients (69.6%) experienced any grade 3/4 toxicity. Eleven patients (47.8%) developed G4 hematologic toxicity, which was significantly higher in those with low skeletal muscle gauge (SMG) (P = 0.02) and low pretreatment neutrophil count (P = 0.0002). Six patients (26.1%) had grade 3/4 non-hematologic toxicity, and was higher in those with low SMG (P = 0.004), and low serum albumin level (P = 0.02). Five patients with high BMI (P = 0.03) experienced febrile neutropenia (FN) and low pretreatment neutrophil count (P = 0.02). CART analysis classified three risk groups, and area under the receiver operating characteristic curve (AUROCC) was 0.92, 0.88, 0.92 in G4 hematologic AE, G3/4 non-hematologic AE, FN, respectively. CONCLUSIONS:SMG is a significant predictive factor of eribulin drug toxicity in advanced STSpatients. Risk classification of drug toxicity through combining predictive factors, could improve the therapeutic strategy used in chemotherapy.
Entities:
Keywords:
Advanced soft tissue sarcoma; Body composition metrics; Eribulin; Toxicity
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