Can Leiomyosarcoma be treated?

From the Guidelines

Leiomyosarcoma can be treated with a multidisciplinary approach, prioritizing surgery, radiation therapy, and chemotherapy, with the goal of improving morbidity, mortality, and quality of life. The treatment approach depends on the stage, location, and individual patient factors.

Treatment Options

• Surgery is often the primary treatment, aiming to remove the tumor completely with negative margins. For localized disease, wide surgical resection may be curative.
• Radiation therapy is frequently used before or after surgery to reduce the risk of local recurrence.
• Chemotherapy medications such as doxorubicin, gemcitabine, docetaxel, trabectedin, and pazopanib may be used, especially for advanced or metastatic disease.

Chemotherapy Regimens

• The typical chemotherapy regimen might include doxorubicin (75 mg/m² every 3 weeks) alone or combined with ifosfamide, as supported by 1.
• For leiomyosarcoma, doxorubicin and dacarbazine could be considered, instead of anthracyclines plus ifosfamide, since this latter could be even detrimental in this specific subtype according to retrospective comparisons 1.
• The combination of gemcitabine plus docetaxel is not recommended as a first-line option for the treatment of advanced STS 1.

Second-Line Options

• High-dose ifosfamide (12–14 g/m2/cycle) can circumvent the tumour resistance to regimens with moderate doses of ifosfamide 1.
• If available, trabectedin can be used for second line in pretreated STS, especially but not exclusively in liposarcoma, leiomyosarcoma and translocation-related sarcomas 1.
• The combination of trabectedin and low dose of radiation therapy has been observed to be feasible and active, and could be taken into account when shrinkage is crucial to palliate symptoms in second line 1.

Prognosis and Follow-Up

• Despite available treatments, leiomyosarcoma can be aggressive with a risk of recurrence, so long-term follow-up is essential.
• Prognosis varies widely depending on tumor size, grade, stage, and the patient's overall health.
• The inclusion of patients with advanced STS in clinical trials should be encouraged whenever available 1.

From the Research

Treatment Options for Leiomyosarcoma

• Leiomyosarcoma is an aggressive mesenchymal malignancy that can be treated with various therapies, including chemotherapy, targeted therapy, and surgery 2, 3, 4, 5, 6.
• First-line therapy for metastatic and/or unresectable leiomyosarcoma includes anthracycline or gemcitabine-based regimens, which provide a median progression-free survival time of about 5 months and overall survival time between 14-16 months 2.
• Effective later-line therapies are limited, but molecular profiling has enhanced our knowledge of the pathophysiology driving leiomyosarcoma, providing potential targets for treatment 2.
• The most promising approaches for advanced leiomyosarcoma include targeting DNA damage repair pathways and aberrant metabolism associated with oncogenesis, as well as novel chemotherapy combinations 2.
• Systemic therapy options for leiomyosarcoma include trabectedin, pazopanib, eribulin, and DTIC, and the location of the primary tumor can help determine the best systemic therapy options 3.
• For patients with disseminated disease, fixed-dose-rate gemcitabine plus docetaxel is an appropriate first-line chemotherapy regimen, and other active cytotoxic agents include doxorubicin, ifosfamide, and dacarbazine 4.
• Targeted therapy, such as antiestrogen therapy with an aromatase inhibitor, may be a reasonable alternative to observation alone in patients with small volume and slowly progressive estrogen receptor/progesterone receptor-positive disease 4.
• Novel targeted agents, such as PARP inhibitors, may usher in a new paradigm of biomarker-driven therapies that will ultimately impact the outcomes of patients with leiomyosarcoma 5.

Factors Influencing Treatment

• The management of leiomyosarcoma is based on the specifics of each individual case, including the location of the disease, whether the disease is metastatic or localized, and whether the tumor is resectable or unresectable 3.
• Factors such as disease-free interval and pattern of spread should be considered within the context of treatment planning 3.
• The increasing use of tumor genomics may ultimately define subsets of patients who may benefit from tailored systemic therapies 3.

Current Research and Developments

• Ongoing progress in the treatment of leiomyosarcoma is contingent upon further development of clinical trials based on molecular findings, with careful consideration for clinical trial design, strong academic collaborations, and prospective correlative analyses 2.
• Recent advances in our understanding of leiomyosarcoma tumor biology and implications for novel therapeutics have highlighted the need for continued research and development of new treatments 2, 5.