Giant cell tumor of bone: Epidemiological profile (fifth version) – A study protocol

The giant cell tumor of bone (GCTB) represents approximately 5% of primary bone tumors, and more than half of cases affect individuals between 20 and 50 years of age. Despite being a benign neoplasm, 3 to 5% of cases may show pulmonary metastases, besides it has high potential for bone destruction at the main site of the lesion, often in the epiphyses of long bones, which may lead to serious functional problems in affected patients. Multidisciplinary treatment of GCTB has been a cause for discussion in the last decade due to the discovery of drugs such as denosumab that prevent tumor progression and may be useful in cases of patients with local recurrences and unresectable tumors. The therapeutic basis of GCTB remains the isolated surgical treatment by intralesional (with adjuvants), marginal or wide resection. Intralesional treatment presents higher rates of recurrence, however it preserves the adjacent joint function and much of the individual bone stock. Resection with aspects of patients with GCTB of wrist and hand, and to analyze the clinical and surgical aspects of patients with knee GCTB. These findings may help in the maintenance or change of national guidelines for the treatment of GCTB. This study protocol was submitted to ethical assessment under the CAAE (Ethical Appreciation Presentation Certificate) registry No. 94280918.0.0000.5327 (5th version), evaluated through the substantiated opinion No. 4.770.705, and approved by the Institutional Research Ethics Committee on June 12, 2022.

aspects of patients with GCTB of wrist and hand, and to analyze the clinical and surgical aspects of patients with knee GCTB. These findings may help in the maintenance or change of national guidelines for the treatment of GCTB. This study protocol was submitted to ethical assessment under the CAAE (Ethical Appreciation Presentation Certificate) registry No. 94280918.0.0000.5327 (5th version), evaluated through the substantiated opinion No. 4.770.705, and approved by the Institutional Research Ethics Committee on June 12, 2022. Keywords: Brazil; Denosumab; Epidemiology; Giant cell tumor of bone; Margins of excision; Surgical procedures, Operative.

Introduction
The giant cell tumor of bone (GCTB) was first described in 1818 by Cooper. Years later, Nelaton and Virchow described, respectively, the local aggressiveness pattern and the potential for malignancy of this lesion. GCTB represents approximately 5% of primary bone tumors, and more than half of the cases affect individuals between 20 and 50 years of age; 3 to 5% of cases may present with pulmonary metastases and, despite being a benign neoplasm, it has high potential for bone destruction at the primary site of the lesion. The characteristic local aggressiveness of GCTB may be responsible for serious functional issues in affected patients. This is due to the frequent location in the long bones epiphyses, that is, in periarticular regions such as knee, wrist, hip, shoulder, among others (Bertoni, et al., 1985;Eckardt & Grogan, 1986;Siebenrock et al., 1988;Turcotte, 2006).
Multidisciplinary treatment of GCTB has been a cause for discussion in the last decade due to the discovery of drugs Current knowledge of GCTB surgical outcomes has been based on major world series (Deheshi et al., 2007;Balke et al., 2009;Ferraz et al., 2016). On the other hand, there is a lack of Brazilian epidemiological and surgical data on this specific type of neoplasm, except for a few series of cases (Camargo et al., 2001;Baptista et al., 2001;Catalan et al., 2006;Rigollino et al., 2017).
The primary objective of this paper is to identify the epidemiological profile of GCTB. The secondary objectives are to describe the surgical aspects of treatment in the main diagnostic centers and treatment of bone tumors, to analyze the clinical and surgical aspects of patients with wrist and hand GCTB, and to analyze the clinical and surgical aspects of patients with knee GCTB. These findings may help in the maintenance or change of guidelines within the country for the treatment of GCTB.

Type of Study
A retrospective, multicenter national cohort study based on the data analysis from medical records of patients diagnosed with GCTB from co-participating centers.

Data Collection
Data collection will be performed locally from the printed clinical form (Figure 1) to all patients included in the study. Source: Authors.

Data Analysis
Data will be collected and sent to the coordinating center -Hospital de Clínicas de Porto Alegre (HCPA) -and then, it will be analyzed. Research, Society and Development, v. 11, n. 10, e536111033230, 2022 (CC BY 4.

Sample Size
Considering a confidence level of 95% and error of 5%, we estimate a sample of 385 Patients. About 20 collaborating centers will be contacted and invited to participate, contributing approximately 20 cases each. Sampling will be for convenience. The calculation sample size was performed in the WinPEPI (Programs for Epidemiologists) version 11.65.
The sample size calculated at the beginning of the project will be maintained.

Statistical Analyses
Descriptive variables will be represented by absolute and relative frequency. Quantitative variables will be represented by mean and standard deviation.
Analyses of Kaplan-Meier curves will be used to describe and compare the groups.
Representations of this analysis will be made with mean and confidence interval.
To compare the groups (tumor site, gender, age group, etc.) the analysis of uni/multivariate Cox regression, being calculated the hazard ratio (HR).
Bivariate analyses will have their significance determined by chi-square, Student's t-test, according to the type of data involved.
The level of significance adopted will be 5% (p≤.05) and the analyses will be carried out in the SPSS program, version 18.0.

Study Co-Participants Centers
The Study Co-Participants Centers are described in the Table 1.

Ethical Aspects
This research will begin after approval of the project by the Research Ethics Committee of HCPA, which will be the coordinating center of this study. The present study design was developed as recommended by the Resolution No. 466/2012 of the National Health Department. The researchers request waiver of a free and informed consent form and an assent term, since only the data contained in the patient's medical records will be accessed.
The researchers will sign a term of commitment for data use.
There are no known risks to this research, except those related to the possible confidentiality. However, the researchers involved are committed to ensuring the confidentiality of the data collected and published.
As for the benefits of this research, we can say that there is no direct benefit to participants of this research, as they have already undergone clinical treatment. However, future research participants will therefore benefit from education through a more complete possible will have an impact on reliable and safe results.
The new researchers involved in the project are committed to maintaining the confidentiality of information of the research participants already inserted in this project.

Budget
Financial resources will be requested for the implementation of this research through the Children's Cancer and Research and Events Incentive Fund and national research funding agencies, according to a budget spreadsheet.
Additional figures with statistical analyses, papers preparation and translation will be responsibility of the researchers.

Schedule
Due to the new objectives included in the project, it was necessary to adjust its schedule, as described in the Table 2.

Basic Infrastructure and Technical Support
The proposed trials have an adequate physical area and computers with statistical and biostatistical programs provided by the HCPA (Orthopedics and Traumatology Service, Research and Graduate Group, Clinical Pathology Service, Multi-tissue Bank). Proponent and team have experience in conducting projects and publishing results using the methodology specified above.