Evaluation of the efficacy of systemic therapy for advanced uterine leiomyosarcoma: A systematic review, meta‐analysis, and meta‐regression analysis

Ijaz, Iqra; Shahzad, Muhammad Naveed; Hosseinifard, Hossein; Liu, Shuya; Sefidan, Masoud Ostadi; Kahloon, Lubna Ejaz; Imani, Saber; Hua, Zhong; Zhang, Yu Qin

doi:10.1002/cam4.5930

Cited by 3 publications

(3 citation statements)

References 79 publications

(225 reference statements)

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“…In other studies [ 13 , 14 ], adjuvant therapy was reported to not affect disease-free and overall survival. However, in a recently published meta-analysis, it was reported that a history of neoadjuvant chemotherapy and local radiotherapy in earlier stages of the disease have an improvement in the outcome of recurrent uterine LMS receiving current therapy [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical Features and Prognostic Factors in Patients With Uterine Leiomyosarcoma: A Single-Center Experience

Yalciner,

Bölek,

Berna Köksoy

2023

Cureus

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Background Uterine leiomyosarcomas (LMS) are associated with more recurrence and higher mortality compared to other uterine cancers. Considering the limited number of case series in the literature, the limited effectiveness of standard treatment methods, and the inadequacy of molecular biomarkers, we planned to investigate the effects of treatment methods and survival outcomes in these patients. Methodology The study was designed retrospectively, and the records of patients who were followed up and treated at Ankara University Faculty of Medicine, Medical Oncology Clinic, between January 1, 2011, and December 31, 2021, were reviewed. Patients over 18 years of age with a pathological diagnosis of uterine LMS were included. Demographic, clinical, and pathological data were recorded using the hospital database. The International Federation of Gynecology and Obstetrics (FIGO) staging was reassessed for each patient in accordance with the AJCC Cancer Staging Manual, Eighth Edition (2017). Tumor size, location, and grade were also evaluated. Types of treatments, protocols, and adverse effects were recorded. Relapsed patients, relapse localization, and treatments given at relapse were recorded and compared. Results Twenty-eight patients were included. The mean age of the patients was 53.7 years. The median follow-up time was 39.3 months. The localization of LMS could be detected in 22 (78.57%) patients, among them 20 (90.9%) patients had intramural, 1 (4.5%) had submucosal, and 1 (4.5%) had subserosal LMS. All patients (26, 92.8%) underwent primary surgery, except for 2 (7.14%) patients who were metastatic at the time of diagnosis. Adjuvant treatment suggestion was made for 7 (25%) patients with a high risk of recurrence in the multidisciplinary tumor council. Partial response was observed in 1 (3.5%) of the 2 (7.1%) metastatic patients, and stable disease was observed in the other. Recurrence was detected in 22 (84.6%) patients . Fifteen (53.6%) patients died during the follow-up period. Survival was better in premenopausal patients (99.2 versus 51.6 months, P = 0.056). No significant difference was found when the survival of patients who received and did not receive adjuvant treatment were compared. In relapsed patients, there was no significant difference in survival between patients who underwent and did not undergo surgical treatment. Conclusions Uterine LMS is a rare and aggressive malignancy with limited diagnostic methods, frequent recurrences, high mortality, and limited use of nonsurgical treatments. The positive effect of adjuvant treatment on survival has not been demonstrated. Further studies are needed to investigate the effect of hormone receptor status on prognosis and new biomarkers.

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Section: Discussionmentioning

confidence: 99%

Clinical Features and Prognostic Factors in Patients With Uterine Leiomyosarcoma: A Single-Center Experience

Yalciner,

Bölek,

Berna Köksoy

2023

Cureus

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“…In clinical application, tyrosine kinase inhibitor pazopanib in a retrospective analysis showed a promising effect for sarcoma patients. Most patients with sarcoma had uLMS with a median overall survival (OS) of 17.5 months compared to 11.1 months for the nonuterine population [105,106].…”

Section: Protein Kinases and Intracellular Signaling Pathwaysmentioning

confidence: 99%

“…The management of uLMS remains challenging due to its aggressive behavior. Although targeted treatments have increased the options for treatment for subpopulations, the overall risk for recurrence and mortality is high for women with this disease [106,178,179]. Surgery is an important aspect of treatment as primary surgical resection is the standard of care for patients with resectable disease.…”

Section: Treatment Of Uterine Leiomyosarcomamentioning

confidence: 99%

Comprehensive Review of Uterine Leiomyosarcoma: Pathogenesis, Diagnosis, Prognosis, and Targeted Therapy

Yang,

Madueke-Laveaux,

Cun

et al. 2024

Cells

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Uterine leiomyosarcoma (uLMS) is the most common subtype of uterine sarcomas. They have a poor prognosis with high rates of recurrence and metastasis. The five-year survival for uLMS patients is between 25 and 76%, with survival rates approaching 10–15% for patients with metastatic disease at the initial diagnosis. Accumulating evidence suggests that several biological pathways are involved in uLMS pathogenesis. Notably, drugs that block abnormal functions of these pathways remarkably improve survival in uLMS patients. However, due to chemotherapy resistance, there remains a need for novel drugs that can target these pathways effectively. In this review article, we provide an overview of the recent progress in ascertaining the biological functions and regulatory mechanisms in uLMS from the perspective of aberrant biological pathways, including DNA repair, immune checkpoint blockade, protein kinase and intracellular signaling pathways, and the hedgehog pathway. We review the emerging role of epigenetics and epitranscriptome in the pathogenesis of uLMS. In addition, we discuss serum markers, artificial intelligence (AI) combined with machine learning, shear wave elastography, current management and medical treatment options, and ongoing clinical trials for patients with uLMS. Comprehensive, integrated, and deeper insights into the pathobiology and underlying molecular mechanisms of uLMS will help develop novel strategies to treat patients with this aggressive tumor.

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Evaluation of the efficacy of systemic therapy for advanced uterine leiomyosarcoma: A systematic review, meta‐analysis, and meta‐regression analysis

et al. 2023

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Uterine leiomyosarcoma (uLMS) is an aggressive mesenchymal neoplasm associated with a poor prognosis. Systemic chemotherapy is the standard therapy for patients with uLMS. However, it is unclear which treatment regimen results in the most favorable clinical outcome. We performed a meta‐analysis and meta‐regression analysis to assess the efficiency of different treatments received by patients with advanced, metastatic, and relapsing uLMS by evaluating the objective response rate (ORR) and disease control rate (DCR) as primary endpoints. The frequentist random effects meta‐analysis model was used to compare the outcomes of different treatment regimens for advanced uLMS. A meta‐regression analysis was performed to estimate the association between the study‐specific hazard ratios and specific demographic variables. A meta‐analysis of 51 reports including 1664 patients was conducted. Among patients who received adjuvant chemotherapy (916 patients; 55%), gemcitabine and docetaxel were the most frequently used drugs. First‐line monotherapy with alkylating agents (pooled ORR = 0.48; 95% confidence interval [CI]: 0.44–0.52) and second‐line monotherapy with protein kinase inhibitors (pooled ORR = 0.45; 95% CI: 0.39–0.52) resulted in favorable prognoses. The combinations of anthracycline plus alkylating therapy (pooled DCR = 0.74; 95% CI: 0.67–0.79) and of gemcitabine plus docetaxel (pooled DCR = 0.70; 95% CI: 0.63–0.75) showed the greatest benefits when used as first‐line and second‐line chemotherapies, respectively. Subgroup meta‐analysis results revealed that dual‐regimen therapies comprising anthracycline plus alkylating therapy and gemcitabine plus docetaxel are practical therapeutic choices for International Federation of Gynecology and Obstetrics stages III–IVb with distant metastases when assessed by computed tomography (p = 0.001). Furthermore, neoadjuvant chemotherapy and local radiotherapy resulted in favorable outcomes for patients with earlier stages of distant relapsed uLMS (p < 0.001). Our findings provide a basis for designing new therapeutic strategies and can potentially guide clinical practice toward better prognoses for uLMS patients with advanced, metastatic, and relapsing disease.

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Evaluation of the efficacy of systemic therapy for advanced uterine leiomyosarcoma: A systematic review, meta‐analysis, and meta‐regression analysis

Cited by 3 publications

References 79 publications

Clinical Features and Prognostic Factors in Patients With Uterine Leiomyosarcoma: A Single-Center Experience

Clinical Features and Prognostic Factors in Patients With Uterine Leiomyosarcoma: A Single-Center Experience

Comprehensive Review of Uterine Leiomyosarcoma: Pathogenesis, Diagnosis, Prognosis, and Targeted Therapy

Evaluation of the efficacy of systemic therapy for advanced uterine leiomyosarcoma: A systematic review, meta‐analysis, and meta‐regression analysis

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