PEC-PRO: A new prognostic score from a series of 87 patients with localized perivascular epithelioid cell neoplasms (PEComas) treated with curative intent.
necrosis, perivascular epithelioid cell neoplasms (PEComas)
positive margins
prognostic
sex
vascular invasion
Journal
Cancer
ISSN: 1097-0142
Titre abrégé: Cancer
Pays: United States
ID NLM: 0374236
Informations de publication
Date de publication:
12 Mar 2024
12 Mar 2024
Historique:
revised:
18
12
2023
received:
10
10
2023
accepted:
23
01
2024
medline:
12
3
2024
pubmed:
12
3
2024
entrez:
12
3
2024
Statut:
aheadofprint
Résumé
Perivascular epithelioid cell neoplasms (PEComas) encompass a heterogeneous family of mesenchymal tumors. Previously described clinicopathologic features aimed at distinguishing benign from malignant variants but lacked prognostic value. This retrospective analysis examined clinicopathologic data from patients who had localized PEComa across French Sarcoma Network centers. The authors analyzed 12 clinicopathologic features in a Cox proportional hazard framework to derive a multivariate prognostic risk model for event-free survival (EFS). They built the PEComa prognostic score (PEC-PRO), in which scores ranged from 0 to 5, based on the coefficients of the multivariate model. Three groups were identified: low risk (score = 0), intermediate risk (score = 1), and high risk (score ≥ 2). Analyzing 87 patients who had a median 46-month follow-up (interquartile range, 20-74 months), the median EFS was 96.5 months (95% confidence interval [CI], 47.1 months to not applicable), with 2-year and 5-year EFS rates of 64.7% and 58%, respectively. The median overall survival was unreached, with 2-year and 5-year overall survival rates of 82.3% and 69.3%, respectively. The simplified Folpe classification did not correlate with EFS. Multivariate analysis identified three factors affecting EFS: positive surgical margins (hazard ratio [HR], 5.17; 95% CI, 1.65-16.24; p = .008), necrosis (HR, 3.94; 95% CI, 1.16-13.43; p = .030), and male sex (HR, 3.13; 95% CI, 1.19-8.27; p = 0.023). Four variables were retained in the prognostic model. Patients with low-risk PEC-PRO scores had a 2-year EFS rate of 93.7% (95% CI, 83.8%-100.0%), those with intermediate-risk PEC-PRO scores had a 2-year EFS rate of 67.4% (95% CI, 53.9%-80.9%), and those with high-risk PEC-PRO scores had a 2-year EFS rate of 2.3% (95% CI, 0.0%-18.3%). The PEC-PRO score reliably predicts the risk of postoperative recurrence in patients with localized PEComa. It has the potential to improve follow-up strategies but requires validation in a prospective trial.
Sections du résumé
BACKGROUND
BACKGROUND
Perivascular epithelioid cell neoplasms (PEComas) encompass a heterogeneous family of mesenchymal tumors. Previously described clinicopathologic features aimed at distinguishing benign from malignant variants but lacked prognostic value.
METHODS
METHODS
This retrospective analysis examined clinicopathologic data from patients who had localized PEComa across French Sarcoma Network centers. The authors analyzed 12 clinicopathologic features in a Cox proportional hazard framework to derive a multivariate prognostic risk model for event-free survival (EFS). They built the PEComa prognostic score (PEC-PRO), in which scores ranged from 0 to 5, based on the coefficients of the multivariate model. Three groups were identified: low risk (score = 0), intermediate risk (score = 1), and high risk (score ≥ 2).
RESULTS
RESULTS
Analyzing 87 patients who had a median 46-month follow-up (interquartile range, 20-74 months), the median EFS was 96.5 months (95% confidence interval [CI], 47.1 months to not applicable), with 2-year and 5-year EFS rates of 64.7% and 58%, respectively. The median overall survival was unreached, with 2-year and 5-year overall survival rates of 82.3% and 69.3%, respectively. The simplified Folpe classification did not correlate with EFS. Multivariate analysis identified three factors affecting EFS: positive surgical margins (hazard ratio [HR], 5.17; 95% CI, 1.65-16.24; p = .008), necrosis (HR, 3.94; 95% CI, 1.16-13.43; p = .030), and male sex (HR, 3.13; 95% CI, 1.19-8.27; p = 0.023). Four variables were retained in the prognostic model. Patients with low-risk PEC-PRO scores had a 2-year EFS rate of 93.7% (95% CI, 83.8%-100.0%), those with intermediate-risk PEC-PRO scores had a 2-year EFS rate of 67.4% (95% CI, 53.9%-80.9%), and those with high-risk PEC-PRO scores had a 2-year EFS rate of 2.3% (95% CI, 0.0%-18.3%).
CONCLUSIONS
CONCLUSIONS
The PEC-PRO score reliably predicts the risk of postoperative recurrence in patients with localized PEComa. It has the potential to improve follow-up strategies but requires validation in a prospective trial.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : French Sarcoma Clinical Reference Network
Organisme : Institut National Du Cancer
ID : PRTK-2020-046
Informations de copyright
© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.
Références
Kallen ME, Hornick JL. The 2020 WHO Classification: what’s new in soft tissue tumor pathology? Am J Surg Pathol. 2021;45(1):e1-e23. doi:10.1097/pas.0000000000001552
Sbaraglia M, Bellan E, Dei Tos AP. The 2020 WHO Classification of Soft Tissue Tumours: news and perspectives. Pathologica. 2021;113(2):70-84. doi:10.32074/1591-951x-213
Anderson WJ, Doyle LA. Updates from the 2020 World Health Organization Classification of Soft Tissue and Bone Tumours. Histopathology. 2021;78(5):644-657. doi:10.1111/his.14265
Agaram NP, Sung YS, Zhang L, et al. Dichotomy of genetic abnormalities in PEComas with therapeutic implications. Am J Surg Pathol. 2015;39(6):813-825. doi:10.1097/pas.0000000000000389
Argani P, Aulmann S, Illei PB, et al. A distinctive subset of PEComas harbors TFE3 gene fusions. Am J Surg Pathol. 2010;34(10):1395-1406. doi:10.1097/pas.0b013e3181f17ac0
Akumalla S, Madison R, Lin DI, et al. Characterization of clinical cases of malignant PEComa via comprehensive genomic profiling of DNA and RNA. Oncology. 2020;98(12):905-912. doi:10.1159/000510241
Folpe AL, Mentzel T, Lehr HA, Fisher C, Balzer BL, Weiss SW. Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature. Am J Surg Pathol. 2005;29(12):1558-1575. doi:10.1097/01.pas.0000173232.22117.37
Bleeker JS, Quevedo JF, Folpe AL. “Malignant” perivascular epithelioid cell neoplasm: risk stratification and treatment strategies. Sarcoma. 2012;2012:541626. doi:10.1155/2012/541626
Bennett JA, Braga AC, Pinto A, et al. Uterine PEComas: a morphologic, immunohistochemical, and molecular analysis of 32 tumors. Am J Surg Pathol. 2018;42(10):1370-1383. doi:10.1097/pas.0000000000001119
Schoolmeester JK, Howitt BE, Hirsch MS, Dal Cin P, Quade BJ, Nucci MR. Perivascular epithelioid cell neoplasm (PEComa) of the gynecologic tract: clinicopathologic and immunohistochemical characterization of 16 cases. Am J Surg Pathol. 2014;38(2):176-188. doi:10.1097/pas.0000000000000133
Tirumani SH, Shinagare AB, Hargreaves J, et al. Imaging features of primary and metastatic malignant perivascular epithelioid cell tumors. AJR Am J Roentgenol. 2014;202(2):252-258. doi:10.2214/ajr.13.10909
Lin Y, Liu X, Zhang X, et al. Clinicopathological features and treatment of perivascular epithelioid cell tumor [abstract]. J Clin Oncol. 2021;39(15 suppl):e23538. doi:10.1200/jco.2021.39.15_suppl.e23538
Benson C, Vitfell-Rasmussen J, Maruzzo M, et al. A retrospective study of patients with malignant PEComa receiving treatment with sirolimus or temsirolimus: the Royal Marsden Hospital experience. Anticancer Res. 2014;34(7):3663-3668.
Sanfilippo R, Jones RL, Blay JY, et al. Role of chemotherapy, VEGFR inhibitors, and mTOR inhibitors in advanced perivascular epithelioid cell tumors (PEComas). Clin Cancer Res. 2019;25(17):5295-5300. doi:10.1158/1078-0432.ccr-19-0288
Sanfilippo R, Fabbroni C, Fucà G, et al. Addition of antiestrogen treatment in patients with malignant PEComa progressing to mTOR inhibitors. Clin Cancer Res. 2020;26(20):5534-5538. doi:10.1158/1078-0432.ccr-20-1191
Wagner AJ, Ravi V, Riedel RF, et al. Nab-sirolimus for patients with malignant perivascular epithelioid cell tumors. J Clin Oncol. 2021;39(33):3660-3670. doi:10.1200/jco.21.01728
Bourgmayer A, Nannini S, Bonjean P, Kurtz JE, Malouf GG, Gantzer J. Natural history and treatment strategies of advanced PEComas: a systematic review. Cancers (Basel). 2021;13(20):5227. doi:10.3390/cancers13205227
Hermanek P, Wittekind C. The pathologist and the residual tumor (R) classification. Pathol Res Pract. 1994;190(2):115-123. doi:10.1016/s0344-0338(11)80700-4
Van Buuren S. Flexible Imputation of Missing Data. 2nd ed. Chapman & Hall/CRC; 2018. Accessed December 18, 2023. https://www.routledge.com/Flexible-Imputation-of-Missing-Data-Second-Edition/Buuren/p/book/9781032178639
Van Buuren S, Groothuis-Oudshoorn K. mice: multivariate imputation by chained equations in R. J Stat Softw. 2011;45(3):1-67. doi:10.18637/jss.v045.i03
Rubin DB. Multiple Imputation for Nonresponse in Surveys. Wiley Series in Probability and Statistics. John Wiley & Sons, Inc.; 1987. Accessed January 6, 2023. http://doi.wiley.com/10.1002/9780470316696
Armah HB, Parwani AV. Malignant perivascular epithelioid cell tumor (PEComa) of the uterus with late renal and pulmonary metastases: a case report with review of the literature. Diagn Pathol. 2007;2(1):45. doi:10.1186/1746-1596-2-45
Hsu LH, Chu NM, Liu CC, et al. Sex-associated differences in non-small cell lung cancer in the new era: is gender an independent prognostic factor? Lung Cancer. 2009;66(2):262-267. doi:10.1016/j.lungcan.2009.01.020
Liu C, Chen T, Zeng W, et al. Reevaluating the prognostic significance of male gender for papillary thyroid carcinoma and microcarcinoma: a SEER database analysis. Sci Rep. 2017;7(1):11412. doi:10.1038/s41598-017-11788-8
Toulmonde M, Bonvalot S, Méeus P, et al. Retroperitoneal sarcomas: patterns of care at diagnosis, prognostic factors and focus on main histological subtypes: a multicenter analysis of the French Sarcoma Group. Ann Oncol. 2014;25(3):735-742. doi:10.1093/annonc/mdt577
Callegaro D, Miceli R, Bonvalot S, et al. Development and external validation of two nomograms to predict overall survival and occurrence of distant metastases in adults after surgical resection of localised soft-tissue sarcomas of the extremities: a retrospective analysis. Lancet Oncol. 2016;17(5):671-680. doi:10.1016/s1470-2045(16)00010-3
Gronchi A, Miceli R, Shurell E, et al. Outcome prediction in primary resected retroperitoneal soft tissue sarcoma: histology-specific overall survival and disease-free survival nomograms built on major sarcoma center data sets. J Clin Oncol. 2013;31(13):1649-1655. doi:10.1200/jco.2012.44.3747
Callegaro D, Miceli R, Bonvalot S, et al. Development and external validation of a dynamic prognostic nomogram for primary extremity soft tissue sarcoma survivors. EClinicalMedicine. 2019;17:100215. doi:10.1016/j.eclinm.2019.11.008
Tanaka K, Ozaki T. New TNM classification (AJCC eighth edition) of bone and soft tissue sarcomas: JCOG Bone and Soft Tissue Tumor Study Group. Jpn J Clin Oncol. 2019;49(2):103-107. doi:10.1093/jjco/hyy157
Voss RK, Callegaro D, Chiang YJ, et al. Sarculator is a good model to predict survival in resected extremity and trunk sarcomas in US patients. Ann Surg Oncol. 2022;29(7):4376-4385. doi:10.1245/s10434-022-11442-2
Stacchiotti S, Frezza AM, Blay JY, et al. Ultra-rare sarcomas: a consensus paper from the Connective Tissue Oncology Society community of experts on the incidence threshold and the list of entities. Cancer. 2021;127(16):2934-2942. doi:10.1002/cncr.33618