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      Therapeutic approaches in patients with bone metastasis due to endometrial carcinoma – A systematic review

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          Graphical abstract

          Highlights

          • Systematic review of 1566 patients with bone metastasis in endometrial carcinoma.

          • Median survival after bone metastasis ranged from 10 to 16 months.

          • Treatment approaches are heterogeneous.

          Abstract

          Background

          Bone metastases (BM) are uncommon in endometrial carcinoma (EC), without information on the optimal oncologic management of patients with BM in EC. Here, we systematically review clinical characteristics, treatment approaches and prognosis in patients with BM in EC.

          Methods

          We conducted a systematic literature search until 27th March 2022 on PubMed, MEDLINE, Embase and clinicaltrials.gov. Outcomes included treatment frequency and survival after BM with comparators being treatment approaches (local cytoreductive bone surgery, systemic therapy, and local radiotherapy). Risk of bias was assessed using the NIH Quality Assessment Tool and Navigation Guide methodology.

          Results

          We retrieved 1096 records of which 112 retrospective studies (12 cohort studies, 12/12 fair quality; 100 case studies, 100/100 low quality) with a total of 1566 patients were included. The majority had a primary diagnosis of FIGO stage IV, grade 3 endometrioid EC. Singular BM were present in a median of 39.2%, multiple BM in 60.8% and synchronous additional distant metastases in 48.1% of patients respectively. In patients with secondary BM median time to bone recurrence was 14 months. Median survival after BM was 12 months. Local cytoreductive bone surgery was assessed in 7/13 cohorts and performed in a median of 15.8% (interquartile range [IQR] 10.3–43.0) of patients. Chemotherapy was assessed in 11/13 cohorts and administered in a median of 55.5% (IQR 41.0–63.9), hormonal therapy (7/13 cohorts) in 24.7% (IQR 16.3–36.0), and osteooncologic therapy (4/13 cohorts) in 2.7% (IQR 0.0–7.5) of patients respectively. Local radiotherapy was assessed in 9/13 cohorts and performed in a median of 66.7% (IQR 55.6–70.0) of patients. Survival benefits were seen in 2/3 cohorts after local cytoreductive bone surgery, and in 2/7 cohorts after chemotherapy without survival benefits in the remaining cohorts and investigated therapies. Limitations include the lack of controlled intervention studies, the heterogeneity and retrospective nature of the investigated populations.

          Conclusions

          This systematic review shows heterogenous therapeutic approaches in clinical practice without clear evidence for optimal oncologic management for patients with BM in EC.

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          Most cited references106

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Integrated Genomic Characterization of Endometrial Carcinoma

            Summary We performed an integrated genomic, transcriptomic, and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumors and ~25% of high-grade endometrioid tumors have extensive copy number alterations, few DNA methylation changes, low ER/PR levels, and frequent TP53 mutations. Most endometrioid tumors have few copy number alterations or TP53 mutations but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A, KRAS and novel mutations in the SWI/SNF gene ARID5B. A subset of endometrioid tumors we identified had a dramatically increased transversion mutation frequency, and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy number low, and copy number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may impact post-surgical adjuvant treatment for women with aggressive tumors.
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              Oligometastases.

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                Author and article information

                Contributors
                Journal
                J Bone Oncol
                J Bone Oncol
                Journal of Bone Oncology
                Elsevier
                2212-1366
                2212-1374
                15 May 2023
                August 2023
                15 May 2023
                : 41
                : 100485
                Affiliations
                [a ]Women’s Clinic, Cantonal Hospital Baselland, Rheinstrasse 26, 4410 Liestal, Switzerland
                [b ]University of Basel, Petersplatz 1, 4001 Basel, Switzerland
                [c ]Breast Center, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland
                [d ]Medical Oncology, Cantonal Hospital Baselland, Medical University Clinic, Muehlemattstrasse 13, 4410 Liestal, Switzerland
                Author notes
                [* ]Corresponding author at: University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland. martin.heidinger@ 123456usb.ch
                Article
                S2212-1374(23)00018-0 100485
                10.1016/j.jbo.2023.100485
                10213377
                d847f815-5ecd-41b5-bff7-895028a5263d
                © 2023 The Author(s)

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 24 April 2023
                : 7 May 2023
                : 11 May 2023
                Categories
                Review Article

                bone metastasis,endometrial neoplasms,cytoreduction surgical procedures,chemotherapy,radiotherapy,systematic review

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