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Background: Limb salvage surgery in the upper extremity requires additional focus on soft tissue repair and reconstruction to preserve functionality, particularly given the different stability needs of upper extremity reconstructions in terms of range of motion and dexterity.Long-term implant survival data following limb salvage surgery of the upper extremity is heterogenous and largely limited to small series.Purpose: This study assesses the long-term outcomes and causes of failure of endoprosthetic reconstruction for tumors involving the humerus.Methods: 157 consecutive patients who underwent limb salvage surgery via proximal, total, or distal humerus replacement for musculoskeletal tumors at a single institution between 1980 and 2021 were reviewed.Demographic, oncologic, procedural, and functional outcome data were analyzed with average follow-up of 5.6 years.Implant failure was defined as revision surgery and classified by the Henderson classification; failure excluded expected exchange of modular components.Descriptive statistics and 2-sample t-tests were performed on the cohort (Stata, College Station, TX).Patient, implant, and limb salvage survival rates were calculated using implant revision as the endpoint.Kaplan-Meier survivorship analysis was performed on patients based on grade of disease.Results: 125 proximal humerus, 16 total humerus, and 16 distal humerus endoprostheses were included.The mean age of the cohort at surgery was 43.523.9years.58% of patients were treated for primary sarcomas.Average follow-up time was 5.77.1 years (range: 3 months -31.9 years); 73.3% of the cohort followed up for at least 10 years.There was a 19% rate (30 cases) of implant failure.Failure occurred on average 3.94.0years after surgery.The most common reason for implant failure was tumor progression in 13 cases (8.3%); 5 (3.2%) for soft tissue failure; 5 (3.2%) for structural failure; 4 for aseptic loosening (2.5%); and 3 for infection (1.9%).4.8% (8) patients were revised to forequarter amputation, predominantly due to tumor progression.Proximal humeral replacements had an implant-specific survival of 76.0% at 10 years, which exceeded that of DHR and THR.THR has lower forward elevation (P=0.03) and abduction (P=0.03), to PHR. Conclusions:The present study confirms the long-term durability of cemented endoprosthetic reconstructions in setting of oncologic reconstruction for massive bone and soft tissue tumors of the humerus.In this series, the most common cause of implant failure requiring revision of the stemmed component in humerus reconstructions is tumor progression, suggesting that oncologic modality of failure is more likely than mechanical failures in this setting.