Ourania Nicolatou-Galitis1, Maria Kouri2, Erofili Papadopoulou2, Emmanouil Vardas2, Dimitra Galiti2, Joel B Epstein3, Sharon Elad4, Giuseppina Campisi5, Nikolaos Tsoukalas6, Kivanc Bektas-Kayhan7, Winston Tan8, Jean-Jacques Body9, Cesar Migliorati10, Rajesh V Lalla11. 1. Dental School, National and Kapodistrian University of Athens, Bouboulinas 41, N. Psyhico, 154 51, Athens, Greece. nicolatou.galitis@hotmail.com. 2. Dental School, National and Kapodistrian University of Athens, Bouboulinas 41, N. Psyhico, 154 51, Athens, Greece. 3. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Health System, Los Angeles CA and City of Hope National Medical Center, Duarte, CA, USA. 4. Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA. 5. Sector of Oral Medicine "V. Margiotta", Department Di.Chir.On.S, University of Palermo, Palermo, Italy. 6. Consultant Medical Oncologist, Oncology Department, Veterans Hospital (NIMTS), Athens, Greece. 7. Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Istanbul University, Istanbul, Turkey. 8. Hematology/Oncology, Mayo Clinic Florida, Jacksonville, FL, USA. 9. CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium. 10. Department of Oral and Maxillofacial Diagnostic Sciences, University of Florida College of Dentistry, Gainesville, FL, USA. 11. Section of Oral Medicine, University of Connecticut School of Dental Medicine, Farmington, CT, USA.
Abstract
INTRODUCTION: The reporting of osteonecrosis of the jaw (ONJ) related to anticancer agents without known antiresorptive properties (non-antiresorptives), such as antiangiogenics, tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, immune checkpoint inhibitors, and cytotoxic chemotherapy is increasing. OBJECTIVE: To review characteristics of ONJ in cancer patients receiving non-antiresorptives. METHODS: A systematic review of the literature between 2009 and 2017 was conducted by the Bone Study Group of MASCC/ISOO. RESULTS: Of 6249 articles reviewed and from personal communication, 42 ONJ cases related to non-antiresorptives were identified. No gender predilection was noted. Median age was 60 years and ONJ stage 2 was most common, with predilection for posterior mandible. Exposed bone, pain, and infection were common at diagnosis. In comparison to bone targeting agents (BTAs), radiology, histology, and management were similar, with medication often discontinued. Delayed diagnosis (median 8 weeks) was noted. Important differences included earlier time to ONJ onset (median 20 weeks), absence of trigger event (40%), and greater likelihood of healing and shorter healing time (median 8 weeks) as compared to BTA-related ONJ. Gastrointestinal cancers predominated, followed by renal cell carcinomas compared to breast, followed by prostate cancers in BTA-related ONJ, reflecting different medications. CONCLUSIONS: Data about non-antiresorptive-related ONJ is sparse. This type of ONJ may have better prognosis compared to the BTA-related ONJ, suggested by greater likelihood of healing and shorter healing time. However, the delay in diagnosis highlights the need for more education. This is the first attempt to characterize ONJ associated with different non-antiresorptives, including BRAF and immune checkpoint inhibitors.
INTRODUCTION: The reporting of osteonecrosis of the jaw (ONJ) related to anticancer agents without known antiresorptive properties (non-antiresorptives), such as antiangiogenics, tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, immune checkpoint inhibitors, and cytotoxic chemotherapy is increasing. OBJECTIVE: To review characteristics of ONJ in cancerpatients receiving non-antiresorptives. METHODS: A systematic review of the literature between 2009 and 2017 was conducted by the Bone Study Group of MASCC/ISOO. RESULTS: Of 6249 articles reviewed and from personal communication, 42 ONJ cases related to non-antiresorptives were identified. No gender predilection was noted. Median age was 60 years and ONJ stage 2 was most common, with predilection for posterior mandible. Exposed bone, pain, and infection were common at diagnosis. In comparison to bone targeting agents (BTAs), radiology, histology, and management were similar, with medication often discontinued. Delayed diagnosis (median 8 weeks) was noted. Important differences included earlier time to ONJ onset (median 20 weeks), absence of trigger event (40%), and greater likelihood of healing and shorter healing time (median 8 weeks) as compared to BTA-related ONJ. Gastrointestinal cancers predominated, followed by renal cell carcinomas compared to breast, followed by prostate cancers in BTA-related ONJ, reflecting different medications. CONCLUSIONS: Data about non-antiresorptive-related ONJ is sparse. This type of ONJ may have better prognosis compared to the BTA-related ONJ, suggested by greater likelihood of healing and shorter healing time. However, the delay in diagnosis highlights the need for more education. This is the first attempt to characterize ONJ associated with different non-antiresorptives, including BRAF and immune checkpoint inhibitors.
Entities:
Keywords:
BRAF inhibitors; Bone resorption; Cytotoxic chemotherapy; Immune checkpoint inhibitors; Inhibitors of angiogenesis; Osteonecrosis of the jaw; Tyrosine kinase inhibitors; mTOR inhibitors
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