Systemic Treatment of Metastatic/Recurrent Uterine Leiomyosarcoma: A Changing Paradigm

Arend, Rebecca C.; Toboni, Michael D.; Montgomery, Allison M.; Burger, Robert A.; Olawaiye, Alexander; Monk, Bradley J.; Herzog, Thomas J.

doi:10.1634/theoncologist.2018-0095

Cited by 24 publications

(28 citation statements)

References 86 publications

(77 reference statements)

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“…Many cytotoxic regimens have been tested, and the majority of studies have used doxorubicin, ifosfamide, gemcitabine, docetaxel, trabectedin, dacarbazine and pazopanib as single agents or in combination. The response rate by chemotherapy ranges approximatively from 10 to 50%, better especially for combination regimes, but the prognosis of this disease still remains poor [ 13 ]. Therefore, the discovery of novel, more effective targeted treatments on the basis of molecular profiling together with the identification of prognostic molecular markers remains an unmet clinical need.…”

Section: Introductionmentioning

confidence: 99%

Genomic Database Analysis of Uterine Leiomyosarcoma Mutational Profile

Astolfi

Nannini

Indio

et al. 2020

Cancers

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Uterine Leiomyosarcoma (uLMS) is by far the most common type of uterine sarcoma, characterized by an aggressive clinical course, a heterogeneous genetic profile and a very scarce response to cytotoxic chemotherapy. The genetic make-up of uLMS is an area of active study that could provide essential cues for the development of new therapeutic approaches. A total of 216 patients with uLMS from cBioPortal and AACR-GENIE databases were included in the study. The vast majority of patients (81%) carried at least one mutation in either TP53, RB1, ATRX or PTEN. The most frequently mutated gene was TP53, with 61% of the patients harboring at least one mutation, followed by RB1 at 48%. PTEN alteration was more frequent in metastases than in primary lesions, consistent with a later acquisition during tumor progression. There was a significant trend for TP53 and RB1 mutations to occur together, while both TP53 and RB1 were mutually exclusive with respect to CDKN2A/B inactivation. Overall survival did not show significant correlation with the mutational status, even if RB1 mutation emerged as a favorable prognostic factor in the TP53-mutant subgroup. This comprehensive analysis shows that uLMS is driven almost exclusively by the inactivation of tumor suppressor genes and suggests that future therapeutic strategies should be directed at targeting the main genetic drivers of uLMS oncogenesis.

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Section: Introductionmentioning

confidence: 99%

Genomic Database Analysis of Uterine Leiomyosarcoma Mutational Profile

Astolfi

Nannini

Indio

et al. 2020

Cancers

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“…We identified 19 reviews and systematic reviews discussing the treatment of uLMS. [ 6 , 7 , 15 , 18 – 33 ] Six guidelines and consensus papers dealing with the optimal approach of uLMS patients were found. [ 4 , 5 , 14 , 34 – 36 ] Retrospective studies including real world data or studies from institutional databases were 18.…”

Section: Results-discussionmentioning

confidence: 99%

“…Recently, other treatment modalities such as chemotherapy, radiotherapy, and targeted therapies have been used in different settings. [ 6 , 7 ]…”

Section: Introductionmentioning

confidence: 99%

The systemic treatment of uterine leiomyosarcomas

Kyriazoglou¹,

Liontos²,

Ntanasis‐Stathopoulos³

et al. 2021

Medicine

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Background: Uterine leiomyosarcomas are rare malignant mesenchymal tumors. The systemic treatment of these tumors includes chemotherapy and radiotherapy. However, there are still a lot of unanswered questions regarding the ideal therapeutic approach. Methods: We have conducted a systematic review of the treatment strategies of uterine leiomyosarcomas for the last ten years. Results: Adjuvant chemotherapy is still a matter of dilemma. Doxorubicin based chemotherapy or the combination of Gemcitabine-Docetaxel are the regimens of choice for the first line setting. Beyond the first line, there are several options;, including chemotherapy, targeted therapy, and recently efforts of introducing immunotherapy to the therapeutic armamentarium of clinicians treating uterine leiomyosarcomas. Conclusions: Despite the efforts of the clinicians dealing with uterine leiomyosarcomas, the optimal therapeutic algorithm is yet to be described.

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Section: Introductionmentioning

confidence: 99%

“…LMS is the most common uterine sarcoma [16,17], composed of malignant smooth muscle cells with significant cellularity, nuclear atypia, necrosis, high mitotic index, invasion, and metastasis [18]. This tumor is extremely aggressive, exhibits resistance to standard therapy, and has high rates of progression and relapse [16,18]. Signaling pathways and their molecular mechanisms are responsible for malignant LMS transformation processes are still unknown, but some evidence suggests that tumor instability is a result of multiple genetic and epigenetic errors [4,19,20].…”

Section: Introductionmentioning

confidence: 99%

Let-7 miRNA’s Expression Profile and Its Potential Prognostic Role in Uterine Leiomyosarcoma

Almeida

Anjos

Uno

et al. 2019

Cells

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The lethal-7 (let-7) family is an important microRNA (miRNA) group that usually exerts functions as a tumor suppressor. We aimed to evaluate the expression profile of let-7a, let-7b, let-7c, let-7d, let-7e, let-7f, let-7g, and let-7i and to assess their value as prognostic markers in uterine leiomyosarcoma (LMS) patients. The miRNAs expression profile was assessed in 34 LMS and 13 normal myometrium (MM) paraffin-embedded samples. All let-7 family members showed downregulation in LMS. Our findings showed that patients with let-7e downregulation had worse overall survival (OS) and is an independent prognostic factor (hazard ratio [HR] = 2.24). In addition, almost half the patients had distant metastasis. LMS patients with downregulated let-7b and let-7d had worse disease-free survival (DFS); they are not independent prognostic factors (HR = 2.65). Patients’ ages were associated with let-7d, let-7e and let-7f (p = 0.0160) downregulation. In conclusion, all the let-7 family members were downregulated in LMS patients, and the greater the loss of expression of these molecules, the greater their relationship with worse prognosis of patients. Let-7e expression might influence the OS, while let-7b and le-7d might influence the DFS. The lowest expression levels of let-7d, let-7e, and let-7f were associated with the oldest patients. Our findings indicate strong evidence of let-7’s role as a potential prognostic biomarker in LMS.

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Systemic Treatment of Metastatic/Recurrent Uterine Leiomyosarcoma: A Changing Paradigm

Cited by 24 publications

References 86 publications

Genomic Database Analysis of Uterine Leiomyosarcoma Mutational Profile

Genomic Database Analysis of Uterine Leiomyosarcoma Mutational Profile

The systemic treatment of uterine leiomyosarcomas

Let-7 miRNA’s Expression Profile and Its Potential Prognostic Role in Uterine Leiomyosarcoma

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