Does the Addition of Mutations of CTNNB1 S45F to Clinical Factors Allow Prediction of Local Recurrence in Patients With a Desmoid Tumor? A Local Recurrence Risk Model.

Autor:	Pinto FFE; Department of Pelvic Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil., Mello CAL; Department of Clinical Oncology, A. C. Camargo Cancer Center, São Paulo, Brazil., Nakagawa SA; Department of Pelvic Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil., Chung WT; Department of Pelvic Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil., Torrezan GT; Clinical and Functional Genomics Group, International Research Center/CIPE, A. C. Camargo Cancer Center, São Paulo, Brazil.; National Institute of Science and Technology in Oncogenomics and Therapeutic Innovation, São Paulo, Brazil., Barros BDF; Clinical and Functional Genomics Group, International Research Center/CIPE, A. C. Camargo Cancer Center, São Paulo, Brazil., Cunha IW; Department of Anatomic Pathology, A. C. Camargo Cancer Center, São Paulo, SP, Brazil., Calsavara VF; Cedars Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA., Carraro DM; Clinical and Functional Genomics Group, International Research Center/CIPE, A. C. Camargo Cancer Center, São Paulo, Brazil.; National Institute of Science and Technology in Oncogenomics and Therapeutic Innovation, São Paulo, Brazil., Lopes A; Department of Pelvic Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	Clinical orthopaedics and related research [Clin Orthop Relat Res] 2023 Oct 01; Vol. 481 (10), pp. 1978-1989. Date of Electronic Publication: 2023 Apr 27.
DOI:	10.1097/CORR.0000000000002627
Abstrakt:	Background: The initial approach to the treatment of desmoid tumors has changed from surgical resection to watchful waiting. However, surgery is still sometimes considered for some patients, and it is likely that a few patients would benefit from tumor removal if the likelihood of local recurrence could be predicted. However, to our knowledge, there is no tool that can provide guidance on this for clinicians at the point of care. Question/purpose: We sought to explore whether a combined molecular and clinical prognostic model for relapse in patients with desmoid tumors treated with surgery would allow us to identify patients who might do well with surgical excision. Methods: This was a retrospective, single-center study of 107 patients with desmoid tumors who were surgically treated between January 1980 and December 2015, with a median follow-up of 106 months (range 7 to 337 months). We correlated clinical variables (age, tumor size, and localization) and CTNNB1 gene mutations with recurrence-free survival. Recurrence-free survival was estimated using a Kaplan-Meier curve. Univariate and multivariable analyses of time to local recurrence were performed using Cox regression models. A final nomogram model was constructed according to the final fitted Cox model. The predictive performance of the model was evaluated using measures of calibration and discrimination: calibration plot and the Harrell C-statistic, also known as the concordance index, in which values near 0.5 represent a random prediction and values near 1 represent the best model predictions. Results: The multivariable analysis showed that S45F mutations (hazard ratio 5.25 [95% confidence interval 2.27 to 12.15]; p < 0.001) and tumor in the extremities (HR 3.15 [95% CI 1.35 to 7.33]; p = 0.008) were associated with a higher risk of local recurrence. Based on these risk factors, we created a model; we observed that patients considered to be at high risk of local recurrence as defined by having one or two factors associated with recurrence (extremity tumors and S45F mutation) had an HR of 8.4 compared with patients who had no such factors (95% CI 2.84 to 24.6; p < 0.001). From these data and based on the multivariable Cox models, we also developed a nomogram to estimate the individual risk of relapse after surgical resection. The model had a concordance index of 0.75, or moderate discrimination. Conclusion: CTNNB1 S45F mutations combined with other clinical variables are a potential prognostic biomarker associated with the risk of relapse in patients with desmoid tumors. The developed nomogram is simple to use and, if validated, could be incorporated into clinical practice to identify patients at high risk of relapse among patients opting for surgical excision and thus help clinicians and patients in decision-making. A large multicenter study is necessary to validate our model and explore its applicability. Level of Evidence: Level III, therapeutic study. Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Association of Bone and Joint Surgeons.)
Databáze:	MEDLINE
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