Relationship Between Insulin Resistance And Chemosensitivity Of High Grade Bone Sarcoma

Background: Neoadjuvant chemotherapy with intercalated surgery is the standard of care for resectable high-grade bone sarcoma (BS) but identification of biomarkers for chemosensitivity prediction is still needed. Insulin-like Growth Factor (IGF) pathway was first linked with sarcoma biology approximately 30 years ago (El-Brady OM, 1990). Methods: We recruited 138 pts with newly diagnosed primary localized or metastatic BS. We measured fasting blood glucose and insulin, body mass index (BMI). The HOMA-IR (Homeostasis Model Assessment) score ((Glucose (mmol/l) x Insulin) / 22.5), which has been proven to reliably detect insulin resistance IR was calculated, and patients with HOMA-IR \u003e 2.6 were considered as IR. We collected characteristics usually associated with insulin resistance: age, obesity, diabetes, dyslipidemia and hypertension. Results: Out of 138 pts, 50 (36%) were insulin resistant: HOMA-IR \u003e2.6. Thirty-two IR patients (64%) had no cardiovascular risk factor. In univariate analysis, IR was associated with obesity (BMI \u003e 30 kg/m2)(22% vs 3%, p=0.0015), but not with age (median 36,8 vs 41 years, p=0.19). IR was more prevalent in Ewing sarcoma (14/29; 48%) and chondrosarcoma (7/16; 44%) followed by osteosarcoma (25/67; 37%) and other rare bone sarcomas (4/26; 15.3%), but not significantly (p=0.097). After neoadjuvant chemotherapy and surgery of Ewing tumor and osteosarcoma, pathologic tumor necrosis was higher in IR pts (88.9 vs 75%, p= 0.028). Conclusion: Our results suggest that metabolic profile may help to discriminate best candidates for neoadjuvant chemotherapy in high-grade bone sarcomas. Further studies are needed to confirm and explain these results. Citation Format: Pascaline Boudou-Rouquette, Ithar Gataa, Sixtine De Percin, Camille Tlemsani, David Biau, Valerie Dumaine, Virginie Audard, Frederique Larousserie, Philippe Anract, Anne Jouinot, Francois Goldwasser. Relationship between insulin resistance and chemosensitivity of high grade bone sarcoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3721.