Effectiveness of the Use of Denosumab When Performing Intralesional Surgery in Patients with Gigant Cell Tumors of the Bones of the Knee Joint

Abstract

In intralesional resection of giant cell tumors, local recurrence rate can be as high as 60–65 %. Some authors attribute recurrences to the presence of an extraosseus component and pathologic fractures, others focus on the effectiveness of bone cavity processing. Currently, denosumab is widely used in treatment of giant cell tumors of the bone. Most frequently, it is used in neoadjuvant regimen at dose 120 mg. This regimen allows to decrease the volume of extraosseous tumor component, form bone margins, and, as a result, make radical resection easier. However, the number of publications on increased risk of local tumor recurrence after neoadjuvant denosumab administration has been growing.Aim. To evaluate the effectiveness of various denosumab administration regimens in intralesional tumor resection in patients with giant cell tumors of the bones forming the knee joint.Materials and methods. The prospective study included outcomes of integrated treatment of 65 patients (34 (52.3 %) women and 31 (47.7 %) men) who underwent surgery at the Division of Bone Oncology of the National Scientific Research Center for Traumatology and Orthopedics named after R.R. Vreden due to giant cell tumors of the knee joint between 2017 and 2023. Mean patient age was 37.5 ± 9.79 years (95 % confidence interval 35.11–39.96; range 19–61 years). Mean follow-up duration was 40.2 ± 13.3 months (95 % confidence interval 36.87–43.46; range 18–68 months). To perform comparative analysis, the patients were divided into 2 groups depending on treatment type. The Group 1 (control) included 32 patients who subcutaneously received 120 mg denosumab prior to surgery (4 injections once a week and then once a month; total number of injections was 6 or more) with subsequent intralesional tumor resection, defect reconstruction with cement in combination with external fixation using a lockable condylar plate. The Group 2 (treatment) included 33 patients who underwent the same surgery as patients of Group 1 and then received subcutaneous injections of 120 mg denosumab (1 injection once a month for 3 months after surgery). Classification and analysis of complications were performed using the International Society of Limb Salvage (ISOLS) 2014 system. Functional outcomes were evaluated using the Musculoskeletal Tumor Society Score (MSTS) at 3, 6, and 12 months.Results. Mean time of recurrence diagnosis in the Group 1 was 9.1 months, in the Group 2 – 14.3 months. Evaluation of the probability of local tumor recurrence depending on treatment type showed statistically significant differences (p = 0.001). Odds of local recurrence in the Group 2 were 10.6 times lower than in the Group 1, and odds of revision surgical intervention in this patient group was 14.5 times higher (with higher probability, this surgery involved oncological endoprosthesis) (p = 0.011). No statistically significant differences in development of distant metastases and probability of death depending on treatment type were found (p = 0.492). According to the obtained data, there are statistically significant differences in functioning of the knee joint per the MSTS scale in the Groups 1 and 2 at 6 and 12 months (p = 0.021 and p = 0.021, respectively). Functional outcomes were better in the Group 2. No significant differences in knee joint functioning per the MSTS scale at 3 months depending on treatment type were found (p = 0.764).Conclusion. Administration of denosumab in the postoperative period allows to improve oncological outcomes due to decreased number of local recurrences (2 (6.1 %) cases), maintenance of excellent local control and good functional results, and to decrease the probability of revision surgical intervention to a minimum. In our study, administration of this drug prior to surgery (intralesional tumor resection) significantly increased the risk of local tumor recurrence (p = 0.001).