Materiały źródłowe

• #1 Therapeutic advances in leiomyosarcoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10031121/

  Leiomyosarcoma is an aggressive mesenchymal malignancy and represents one of the most common subtypes of soft tissue sarcomas. […] As a result, the treatment of advanced leiomyosarcoma is challenging. 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. […] Effective later-line therapies are limited. […] To date, 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. This review highlights the recent progress made in the treatment of advanced leiomyosarcoma.

• #2 Leiomyosarcoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK551667/

  Leiomyosarcoma is an aggressive tumor of smooth muscle origin and one of the most common subtypes of sarcoma. […] Treatment depends on the size, grade, and location of the lesion, as well as patient-related factors such as age and the ability to tolerate aggressive therapy. Surgery is the cornerstone of curative therapy, with radiation and chemotherapy being important adjuncts. […] The current standard of care involves upfront surgery for resectable tumors, with chemotherapy and radiation typically serving as adjuncts. […] The management of leiomyosarcoma depends on the disease site, tumor size, grade, and patient-dependent factors. The potential options include surgical resection, radiation, and chemotherapy. A multidisciplinary approach at high-volume sarcoma centers is highly recommended.

• #3 Soft Tissue Sarcoma: Leiomyosarcoma | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/cancer-care/types/soft-tissue-sarcoma/types/leiomyosarcoma

  Leiomyosarcoma is a form of soft tissue sarcoma, which is a cancer that begins in the connective tissues of the body. […] The main treatment for leiomyosarcoma is surgery to remove the tumor. Leiomyosarcoma can begin in many different parts of the body. The surgery thats right for you depends on the exact size and location of the tumor. […] Radiation and chemotherapy are less beneficial for people with leiomyosarcoma than they are for people with other forms of soft tissue sarcoma. Some people with leiomyosarcoma that has spread to other parts of the body may benefit from chemotherapy. If an operation is successful, often no extra treatment is necessary.

• #3 Leiomyosarcoma: Symptoms, Treatment & Prognosis

  https://my.clevelandclinic.org/health/diseases/22059-leiomyosarcoma

  Leiomyosarcoma treatment depends on the location and size of the tumor. Options include: […] When surgery is possible, its the go-to treatment option for leiomyosarcoma. The goal is to remove the entire tumor so that the cancer doesnt come back. […] Providers recommend chemotherapy when the tumor is large, or when cancer cells have spread to other parts of your body. […] Providers might use radiation therapy before surgery (neoadjuvant therapy) to shrink the tumor, or after surgery (adjuvant therapy) to kill any remaining cancer cells. […] Your healthcare team may recommend targeted therapy as a stand-alone therapy or in combination with other treatments. […] Recovery times can vary drastically depending on several factors, including: […] It could take several weeks or months to fully recover. Even after youre feeling better, youll still need regular checkups to monitor your health and reduce the risk of cancer recurrence (return).

• #4 Leiomyosarcoma – NCI

  https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-soft-tissue-tumors/leiomyosarcoma

  Treatment for each patient will be unique and depends on the size and location of the tumor. You should go to an expert in LMS treatment to decide the best approach for treating your tumor. […] The best option for LMS treatment is surgery. If all of the tumor is removed, there is a good chance of LMS being cured. If some cancer cells are left behind, there is a greater chance of the cancer coming back in the same spot, or a different part of the body. […] Radiation therapy can be used around the time of surgery. The radiation is aimed at the tumor area to prevent it from growing back after it is removed. […] When the LMS tumors are large, or the cancer cells have spread to other parts of the body, then chemotherapy is used in combination with surgery.

• #5 Leiomyosarcoma – Diagnosis & Disease Information for HCPs

  https://www.cancertherapyadvisor.com/ddi/leiomyosarcoma/

  Leiomyosarcoma Treatment Leiomyosarcoma Treatment Adverse Effects and Drug Interactions Complications of Leiomyosarcoma Educating Patients About Leiomyosarcoma […] Treatment usually consists of surgical resection with clean margins, often complemented by adjuvant radiation and systemic chemotherapy. […] Optimal patient care requires an integrated approach that combines surgical, medical, and radiation oncology specialists to plan and administer individualized treatment. […] The first-line treatment of leiomyosarcoma is surgical resection, the most effective treatment for localized disease. […] Most patients with uterine leiomyosarcoma will undergo total hysterectomy with bilateral salpingo-oophorectomy and may be subjected to pelvic lymphadenectomy if there is clinical suspicion of nodal involvement.

• #6 Treatment for Uterine Sarcoma, by Type and Stage | American Cancer Society

  https://www.cancer.org/cancer/types/uterine-sarcoma/treating/by-stage.html

  The main treatment for early-stage uterine sarcoma is surgery to remove the uterus, sometimes along with the fallopian tubes and ovaries. In certain cases the lymph nodes might be removed and checked. Surgery might be followed by treatment with radiation, chemotherapy (chemo), or hormone therapy. Targeted drug therapy and immunotherapy might also be used in advanced cancers. […] Women who can’t have surgery because they have other health problems or because their cancer has spread are treated with radiation, chemo, or hormone therapy. Often some combination of these treatments is used. […] Most women have surgery to remove the uterus (hysterectomy), as well as the fallopian tubes and ovaries (bilateral salpingo-oophorectomy). […] Some stage I cancers might not need more treatment after surgery. Observation (being watched closely after surgery) is an option. In other cases, treatment with radiation, with or without chemo, might be needed after surgery if there’s a high chance the cancer will come back. This is called adjuvant treatment.

• #7

  https://link.springer.com/article/10.1007/s11864-021-00928-y

  Leiomyosarcoma is one of the most common subtypes of soft tissue sarcomas accounting for approximately 20% of sarcomas. As leiomyosarcoma patients frequently develop metastatic disease, effective systemic therapies are needed to improve clinical outcomes. The overall activity of the currently available conventional systemic therapies and the prognosis of patients with advanced and/or metastatic disease are poor. As such, the treatment of this patient population remains challenging. […] Therefore, the aim of this review is to briefly summarize state-of-the-art treatments for leiomyosarcoma patients and to describe trial characteristics needed for informative clinical studies. […] Surgery remains the cornerstone in the management of patients with localized LMS and the standard surgical procedure is a wide excision with negative margins (R0). In the case of R1 or R2 resections, re-operation in experienced centers is considered following possible preoperative treatments. […] In patients with extremity high-risk LMS (G2-3, deep 5 cm lesions), adjuvant or neoadjuvant radiation therapy is administered in addition to surgery. […] Adjuvant chemotherapy is not globally accepted as the standard treatment strategy for the postoperative therapy of adult patients with LMS but can be considered in high-risk patients to reduce the risk of local recurrence and increase survival rates. […] Neoadjuvant chemotherapy may have the same potential benefits as adjuvant chemotherapy, but similarly universal consensus does not exist. […] The efficacy of neoadjuvant chemotherapy in retroperitoneal LMS (and liposarcomas) is currently being evaluated in the EORTC/Soft Tissue and Bone Sarcoma Group (STBSG) STRASS-2 trial in patients with resectable retroperitoneal sarcomas (NCT04031677), which hopefully may settle the long-lasting controversial debate about this topic.

• #8 General Approach to Treatment of Leiomyosarcoma

  https://www.leiomyosarcoma.info/general.htm

  Use A Sarcoma Oncologist. All LMS patients should be treated, or have their treatment overseen, by a sarcoma oncologist. […] LMS is a chemotherapy and radiation resistant cancer. Surgical or ablative methods are the treatments of choice. Therefore be very thoughtful if offered chemotherapy or radiation for treatment. […] For primary tumors on many sites, adjuvant treatment has not proven to be of benefit if the surgical excision had wide, clear margins. The adjuvant treatments recommended are usually either radiation or chemotherapy, sometimes both. […] If there are very few metastases, and they are operable, usually the solution is surgical resection or ablation. This may or may not be followed by chemotherapy. […] If the tumor is inoperable, then judicious use of chemotherapy or radiation sometimes actually downgrades the situation and makes it operable. The attempt to downgrade an inoperable situation into an operable one by means of radiation and/or chemotherapy is called neoadjuvant treatment.

• #9 Leiomyosarcoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK551667/

  The primary goals of treatment with curative intent include achieving surgical resection with negative margins, reducing local recurrence, improving functional outcomes, and reducing the risk of distant metastasis. […] Radiotherapy (RT) in STS improves local control, preserves function, and reduces local recurrence but does not improve survival. […] The timing of radiotherapy also remains a topic of debate for both retroperitoneal and extremity or trunk leiomyosarcoma as major trials continue to accrue patients. […] The general principles of radiotherapy for any STS also apply to patients diagnosed with non-uterine leiomyosarcoma. […] Patients diagnosed with leiomyosarcoma should be treated at centers that experience a high volume of such patients. […] Surgical resection with a negative margin leads to the best outcomes in terms of overall survival.

• #10 Leiomyosarcoma – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/leiomyosarcoma/diagnosis-treatment/drc-20577224

  Treatment of leiomyosarcoma depends on where the cancer is, how big it is and whether it has spread to other areas of the body. Your overall health and what you want also are part of the treatment plan. […] The goal of surgery is to remove all the leiomyosarcoma. But that might not be possible if the cancer is large or involves nearby organs. Then your surgeon may remove as much of the cancer as possible. […] Radiation therapy treats cancer with powerful energy beams. The energy can come from X-rays, protons or other sources. […] Radiation therapy can be used before, after or during surgery. It can treat cancer cells that can’t be removed during surgery. Radiation therapy also might be used when surgery isn’t an option. […] Chemotherapy treats cancer with strong medicines. Most chemotherapy medicines are given through a vein.

• #11 Leiomyosarcoma | Sarcoma UK

  https://sarcoma.org.uk/about-sarcoma/what-is-sarcoma/types-of-sarcoma/leiomyosarcoma/

  Surgery is the most common treatment method for patients with leiomyosarcoma, regardless of subtype, and especially if the cancer has not spread. For uterine leiomyosarcoma, a hysterectomy (which is a surgical procedure to remove the uterus) is often recommended if the cancer is limited to the uterus and has not spread. […] Radiotherapy may also be offered if the leiomyosarcoma is located in either a limb or in the trunk. It can be offered either before or after surgery to reduce the risk of your cancer recurring. Radiotherapy can also be offered if surgery is not possible or if the tumour cannot be completely removed. […] There is limited data on the role of chemotherapy in treating soft tissue and uterine leiomyosarcoma. This means that the effectiveness of chemotherapy on leiomyosarcoma that has not spread is yet to be fully understood. There is potentially a role for chemotherapy if the cancer has spread, if surgery is not possible or if the tumour cannot be completely removed.

• #12 Leiomyosarcoma | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/24180

  Radiotherapy (RT) in STS improves local control, preserves function, and reduces local recurrence but does not improve survival. […] The timing of radiotherapy also remains a topic of debate for both retroperitoneal and extremity or trunk leiomyosarcoma as major trials continue to accrue patients. […] The current National Comprehensive Cancer Network (NCCN) guidelines recommend pulmonary metastasectomy for oligometastatic disease in highly selected patients with no other sites of distant disease. Local recurrences should be managed with surgical resection if amenable to complete tumor extirpation. […] The general principles of radiotherapy for any STS also apply to patients diagnosed with non-uterine leiomyosarcoma. […] Patients with superficial or contained STS up to a size of 5 cm who undergo complete excision of the tumor with wide margins (more than 1 cm clean margin) can be monitored clinically without the need for postoperative radiotherapy.

• #13 Treatment for Uterine Sarcoma, by Type and Stage | American Cancer Society

  https://www.cancer.org/cancer/types/uterine-sarcoma/treating/by-stage.html

  For leiomyosarcoma (LMS) of the uterus, adjuvant radiation may lower the chance of the cancer growing back in the pelvis (called local recurrence), but it doesn’t seem to help people live longer. […] Since the cancer can still come back in the lungs or other distant organs, some experts recommend giving chemo after surgery (adjuvant chemotherapy) for stage II cancers. […] Surgery is done when the surgeon feels they can remove all of the cancer. This includes removing the uterus (a hysterectomy), removing both fallopian tubes and ovaries (bilateral salpingo-oophorectomy), other organs that are involved with the tumor, and lymph node dissection or sampling. […] After surgery, treatment with radiation or chemo might be offered to lower the chance that the cancer will come back. […] Stage IVA cancers have spread to nearby organs and tissues, such as the bladder or rectum, and maybe to nearby lymph nodes. These cancers might be able to be completely removed with surgery, and this is usually done if possible.

• #14 The Future of Targeted Therapy for Leiomyosarcoma

  https://www.mdpi.com/2072-6694/16/5/938

  As mentioned, the treatment of recurrent or metastatic LMS typically involves cytotoxic chemotherapy. However, there are no existing biomarkers readily available in clinical practice that predict the response to chemotherapy in LMS. Given the modest response rates with combination chemotherapy (20–30%) relative to the toxicity, it would be ideal to have a predictive biomarker to avoid unnecessary toxicity in patients unlikely to benefit from chemotherapy.

• #15 Therapeutic advances in leiomyosarcoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10031121/

  Patients with advanced LMS are typically treated with chemotherapy, either with gemcitabine or doxorubicin based regimens in the first-line setting. Beyond first-line chemotherapy, which provides a median progression-free survival (PFS) of only about 5 months, there are limited treatment options for advanced disease. […] Molecular profiling has aided in understanding the biology of LMS, providing implications for novel targeted therapies. […] In the first-line setting, doxorubicin or gemcitabine based regimens are commonly used. […] Although subgroup analysis performed within the GeDDiS trial demonstrated no evidence of differential treatment effect by histologic subtype, other studies in uterine LMS have suggested unique sensitivity to gemcitabine and docetaxel. […] Other gemcitabine-based regimens may be considered for early-line treatment of LMS, such as gemcitabine plus vinorelbine and gemcitabine plus dacarbazine.

• #16 Treatment and prognosis of uterine leiomyosarcoma – UpToDate

  https://www.uptodate.com/contents/treatment-and-prognosis-of-uterine-leiomyosarcoma

  Treatment and prognosis of uterine leiomyosarcoma […] Whenever possible, patients with uterine sarcomas should be referred to specialty centers with expertise in their diagnosis and management. […] This topic will cover the treatment approach to high-grade uterine LMS. […] Early-stage disease […] Chemotherapy […] Doxorubicin […] Docetaxel and gemcitabine […] Docetaxel and gemcitabine followed by doxorubicin […] Radiation therapy […] Advanced disease […] Choice of agents […] Preferred option for first-line therapy […] Doxorubicin plus trabectedin followed by trabectedin maintenance […] Alternative initial or subsequent line treatment options […] Gemcitabine plus docetaxel […] Doxorubicin […] Single-agent gemcitabine […] Later-line options […] Pegylated liposomal doxorubicin […] Ifosfamide […] Trabectedin (as a single agent) […] Dacarbazine or temozolomide […] Pazopanib […] Eribulin […] Endocrine therapy.

• #17

  https://link.springer.com/article/10.1007/s11864-021-00928-y

  Standard first-line chemotherapy for STS consists of anthracycline-based regimens, and doxorubicin is the first-line chemotherapy of choice in patients with advanced LMS. […] Doxorubicin plus ifosfamide demonstrated a significantly higher response rate and longer progression-free survival (PFS) compared to single-agent doxorubicin, but no significant difference in overall survival (OS) in a trial including all STS subtypes. […] In patients with LMS, the combination of doxorubicin plus dacarbazine is another option for multi-agent first-line chemotherapy. […] In second line or later, trabectedin is a standard option for the treatment of advanced STS (including LMS) after failure of doxorubicin with or without ifosfamide, or for patients unsuited to receive these agents. […] Pazopanib is recommended for selected subtypes of advanced STS including LMS after prior chemotherapy for advanced and/or metastatic disease.

• #18 Trabectedin and Doxorubicin Effective for Leiomyosarcoma – NCI

  https://www.cancer.gov/news-events/cancer-currents-blog/2024/leiomyosarcoma-yondelis-doxorubicin-improve-survival

  Treating people with advanced leiomyosarcoma with the combination of the chemotherapy drugs trabectedin (Yondelis) and doxorubicin can help them live longer, a clinical trial has found. […] The trial showed that adding trabectedin (Yondelis) to doxorubicin as an initial treatment for people with a type of sarcoma called leiomyosarcoma helped them live longer than people initially treated with doxorubicin alone: a median of 33 months versus 24 months. […] People initially treated with the combination, which was given for about four and a half months, could continue taking trabectedin by itself for up to almost a year, a strategy called maintenance therapy. […] But people in the trabectedin plus doxorubicin group lived almost a year longer, she continued, which argues that the initial response to combination treatment and maintenance was helpful in a way that sequential therapy is not she said.

• #19 The Future of Targeted Therapy for Leiomyosarcoma

  https://www.mdpi.com/2072-6694/16/5/938

  Leiomyosarcoma is a subtype of soft tissue sarcoma with poor outcomes and response to currently available treatments. The goal of this review is to assess the current landscape of targeted therapies and explore how our current understanding of the biology of leiomyosarcoma may inform the development of new targeted therapies to improve the treatment of leiomyosarcoma. […] Surgery is the mainstay of treatment for localized LMS, with the addition of radiation and chemotherapy depending on the clinical characteristics and associated local and distant recurrence risks. Treatment of recurrent or metastatic LMS typically involves cytotoxic chemotherapy. The LMS-04 trial demonstrated the efficacy of doxorubicin plus trabectedin over doxorubicin alone with a response rate of 36% compared to 13%, respectively, and a disease control rate (response or stable disease) of 91.9% versus 78.9%. This represents the most efficacious chemotherapy regimen prospectively validated to date for LMS and the first trial to demonstrate an overall survival (OS) benefit with an anthracycline-based chemotherapy combination in the first line setting for advanced LMS.

• #20 Therapeutic advances in leiomyosarcoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10031121/

  Early-line therapy for LMS also includes the combination of doxorubicin plus dacarbazine. […] Later-line treatment of LMS includes trabectedin, pazopanib, and other chemotherapy agents. […] Trabectedin is approved in patients with advanced liposarcoma (LPS) or LMS who received prior treatment with anthracyclines. […] Pazopanib is another approved treatment for patients with advanced STS who have previously received chemotherapy, with activity in LMS. […] Other chemotherapy agents are also considered for later-line treatment of LMS. […] Early-line treatment options for LMS provide a median PFS of approximately 5 months with a median OS of 14-16 months. […] There is an urgent need for improved treatment options for patients with LMS. […] Based on a greater understanding of LMS tumor biology, novel approaches to LMS have evolved and are currently being explored in ongoing clinical trials.

• #21 Leiomyosarcoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK551667/

  Neoadjuvant chemotherapy has proven effective in high-risk STS or leiomyosarcoma of the extremity or trunk; however, the evidence is limited. […] Trabectedin is an effective treatment for leiomyosarcoma. Clinicians should not discontinue the drug in patients who respond to trabectedin unless the patient develops toxicity or progression of the tumor.

• #22 The Future of Targeted Therapy for Leiomyosarcoma

  https://www.mdpi.com/2072-6694/16/5/938

  There are no FDA-approved targeted therapies specifically for LMS. Pazopanib, a tyrosine kinase inhibitor with high affinity for VEGFR, PDGFR, KIT, and FGFR, is FDA-approved for advanced soft tissue sarcomas, including LMS, that have received prior chemotherapy. This is based on the results of the PALETTE trial, which showed that pazopanib significantly prolonged median progression-free survival (PFS, 4.6 vs. 1.6 months for placebo), and a clinical benefit was seen in 73% (6% partial response and 67% stable disease) with pazopanib versus 38% (stable disease only) with placebo. […] Hormone therapy targeting the estrogen and progesterone receptors (ER and PR) was also utilized to treat LMS, particularly ULMS. These were based on findings that 25–60% and 35–65% of ULMS express ER and PR, respectively. Higher ER and PR expression were associated with better survival. A single-arm phase 2 trial of the aromatase inhibitor letrozole treated 27 patients with advanced ULMS and demonstrated a 12-week PFS of 50%. The best response was the stable disease in 54%, and the median duration of treatment was 2.2 months. However, most other evidence comes from retrospective analyses or case reports.

• #23 Leiomyosarcoma – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/leiomyosarcoma/diagnosis-treatment/drc-20577224

  Healthcare professionals might suggest chemotherapy to prevent the leiomyosarcoma from returning after surgery. It also might be used to control cancer that spreads to other areas of the body. […] Targeted therapy for cancer is a treatment that uses medicines that attack specific chemicals in the cancer cells. By blocking these chemicals, targeted treatments can cause cancer cells to die. […] Targeted therapy may be an option for leiomyosarcoma that grows large or spreads to other parts of the body. Your healthcare professional may test your cancer cells to see if targeted medicines might help you.

• #24 Targeted Drug Therapy for Uterine Sarcomas | American Cancer Society

  https://www.cancer.org/cancer/types/uterine-sarcoma/treating/targeted-therapy.html

  Pazopanib (Votrient) is a targeted drug that might be used to treat a leiomyosarcoma that has spread or come back after treatment. […] Olaparib (Lynparza), rucaparib (Rubraca), and niraparib (Zejula) might be used to treat advanced uterine leiomyosarcomas, typically after chemotherapy has been tried.

• #25 Leiomyosarcoma – Diagnosis & Disease Information for HCPs

  https://www.cancertherapyadvisor.com/ddi/leiomyosarcoma/

  Pazopanib, a tyrosine kinase inhibitor, has shown modest efficacy in leiomyosarcoma. […] Although pazopanib has been FDA-approved as a second-line treatment for treating advanced soft tissue sarcomas, its overall impact in leiomyosarcoma is still being evaluated, and it is generally reserved for metastatic or refractory cases. […] Investigational medications such as immune checkpoint inhibitors and targeted molecular agents for treating leiomyosarcoma are being evaluated in clinical trials, but their clinical impact has not yet been fully defined. […] The therapeutic landscape of leiomyosarcoma continues to evolve with discovery-driven research in pursuit of better systemic therapy options and improved patient outcomes.

• #26 Targeted Therapy Shows Promise for Aggressive Form of Uterine Sarcoma | Herbert Irving Comprehensive Cancer Center (HICCC) – New York

  https://www.cancer.columbia.edu/news/targeted-therapy-shows-promise-aggressive-form-uterine-sarcoma

  Results of a new phase 2 clinical trial demonstrate the potential of targeted therapy in combination with chemotherapy to treat patients with uterine leiomyosarcoma. […] The trial aimed to test a novel therapy for uterine leiomyosarcoma called olaparib, a PARP inhibitor originally developed for individuals with BRCA1 or BRCA2 mutations. […] Based on these promising initial results, the team is now working on the development of a large, randomized phase 3 clinical trial to test this drug combination against the current standard of care. […] We think that this will eventually become a new standard of care for patients with uterine leiomyosarcoma and will have a profound effect for women with the disease for which there are no available therapies, adds Dr. Schwartz. […] Preclinical research from HICCC and other institutions confirmed the existence of BRCAness in uterine leiomyosarcoma, as well as the potential efficacy of combining PARP inhibitors with chemotherapy. […] The team also analyzed the tumor biopsy data for genomic signatures of BRCAness that may predict which patients would benefit from taking olaparib. Early findings suggest that such a predictive biomarker does exist, although studies remain ongoing in this area.

• #27 PARP Inhibitors May Be a Promising Treatment Strategy in Advanced Uterine Leiomyosarcoma

  https://www.oncnursingnews.com/view/parp-inhibitors-may-be-a-promising-treatment-strategy-in-advanced-uterine-leiomyosarcoma

  Findings from a phase 2 clinical trial (NCT03880019) recently published in the Journal of Clinical Oncology demonstrated that combined treatment with olaparib (Lynparza) and temozolomide led to a 27% objective response rate in patients with advanced, pretreated uterine leiomyosarcoma. The trial met its primary end point. […] According to Kjersten Dosumu, DNP, MS, AGPCNP-BC, these results are exciting for sarcoma specialists. […] Dosumu: This combination of these two drugs, olaparib and temozolomide, had been studied kind of individually in other types of diseases. Olaparib is a PARP, or a poly adenosine diphosphate-ribose polymerase, inhibitor. PARP helps to mediate DNA repair when it has been damaged. PARP inhibitors stop the DNA from repairing, basically. […] Temozolomide was added in because it is an alkylating agent, so it helps to increase the activity of the olaparib, or the PARP inhibitor.

• #28 Treatment of hormone positive uterine leiomyosarcoma with aromatase inhibitors | Clinical Sarcoma Research | Full Text

  https://clinicalsarcomaresearch.biomedcentral.com/articles/10.1186/2045-3329-4-5

  Aromatase inhibitors (AIs) have not been used consistently as part of the management of hormone receptor positive uterine leiomyosarcomas (ULMS). As a result, the published data regarding the efficacy of AIs in this subtype of ULMS are sparse. […] In this population of patients with hormone positive ULMS, AIs achieved a significant CBR (62.5%) in 1st line, which was retained in 2nd line (CBR: 50%). The relatively prolonged median PFS (14 months), along with the favourable toxicity profile could place AIs among the first choices of systemic treatment in hormone positive ULMS, preferably in strongly positive (90%), and/ or low grade and low volume disease. […] AIs could be considered active agents for 1st line treatment in hormone positive advanced ULMS, preferably for these highly selected ULMS patients with strongly ER and/or PgR positive status (90%) and/or low grade and/or low volume disease, as it appears to be more limited in unselected cohorts. Moreover, in such highly selected patients with advanced ULMS, it could also be considered 2nd line treatment with exemestane (steroidal AI), in view of the positive outcomes in our small cohort (CBR: 50%). As expected, AIs were well tolerated.

• #29 Leiomyosarcoma | Macmillan Cancer Support

  https://www.macmillan.org.uk/cancer-information-and-support/soft-tissue-sarcoma/leiomyosarcoma

  A team of specialists meet to discuss the best possible treatment plan for you. This is called a multidisciplinary team (MDT). Because sarcomas are rare cancers, you should be referred to a specialist unit for treatment. This may mean you need to travel further to have your treatment. […] The treatment you have depends on a number of things, including: where the leiomyosarcoma started, the size of the tumour, the grade of the leiomyosarcoma, your general health. […] The main treatments for leiomyosarcoma are surgery and radiotherapy. Sometimes chemotherapy is used as well. […] Surgery is the main treatment for leiomyosarcoma. The aim is to remove all of the cancer and an area of healthy tissue around it. This area is called a margin. The type of operation you have will depend on where the leiomyosarcoma started.

• #30 FAQ – Leiomyosarcoma Prognosis, Causes & Treatment | LMSDR

  https://www.lmsdr.org/leiomyosarcoma-faq

  Consult a sarcoma specialist before deciding on a treatment. […] Surgery with wide margins is the gold standard treatment for leiomyosarcoma. We say, When in doubt, cut it out! Make an appointment and discuss your options with the surgeon, who knows best if surgery is an option. When surgery is not possible, discuss chemotherapy and immunotherapy options with your oncologist. You can also consult the interventional radiologist for targeted radiation methods which can also be very effective. […] Stage IV sarcomas are rarely curable. But some patients may be cured if the main tumor and all of the areas of cancer spread (metastases) can be removed by surgery. Your chances of survival are higher if you seek the advice of a sarcoma specialist at a high volume sarcoma center. […] Please get a second opinion with a high volume sarcoma center and specialist. Research shows that those who see sarcoma specialists live longer than those who dont.

• #31 Clinical characteristics and treatment outcomes of women with recurrent uterine leiomyosarcoma | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-024-03415-3

  To determine the clinical characteristics and treatment outcomes of women with recurrent uterine leiomyosarcoma (uLMS). […] Overall, 71 patients with first recurrence of uLMS were included in our study. 19 patients (26.8%) received systemic therapy and 52 patients (73.2%) received secondary cytoreductive surgery (SCS). […] SCS is an important treatment choice for recurrent uLMS and seems to have benefited patients. […] Optimal surgical resection for recurrent uLMS may provide an opportunity for long-term survival in a select patient population. […] Secondary cytoreduction to no residual disease is an option that may be proposed in recurrent uLMS. […] Modern multimodal therapy or combining chemotherapy with aggressive surgery in selected patients may be significant in prolonging survival of women with this fatal disease.

• #32 General Approach to Treatment of Leiomyosarcoma

  https://www.leiomyosarcoma.info/general.htm

  Chemotherapy and radiation do not cure LMS, but sometimes they work well enough for long enough to allow a surgical solution or control where none existed before. […] Participation in clinical trials for inoperable LMS stage IV is often urged because of the scarcity of effective nonsurgical treatments. […] There are other treatments becoming available that might be used in addition to chemotherapy, or in an adjuvant situation. Among these are Gleevec for PDGFr positive tumors, anti-hormone treatment for tumors with hormone receptors, antibody targeted viruses for tumors, replacement p53 gene therapy, vaccines, monoclonal antibodies, anti-angiogenesis treatment with targeted molecules or copper-lowering agents or metronomic dosing, targeted molecular tumoristatic agents.

• #33 Leiomyosarcoma Treatments: Surgery, Radiation, Chemotherapy

  https://www.webmd.com/cancer/treat-leiomyosarcoma

  Treatments that you might get with other types of cancer, such as chemotherapy and radiation therapy, arent usually used to treat early-stage leiomyosarcoma. But if leiomyosarcoma has spread to other areas of your body, like your lymph nodes or other organs, your medical team may recommend chemotherapy, radiation, or targeted therapy. […] Chemotherapy uses medications to treat cancer. These drugs may be pills or injections. Because chemotherapy enters your bloodstream and travels throughout your body to destroy cancer cells, they’re especially helpful for cancer that has spread. […] Radiation therapy uses radiation to kill cancer cells. The type of radiation you get depends on the location of your tumor. […] Targeted therapy is the use of drugs that target and change cancer cells. While doctors can use these medications along with chemotherapy, they arent the same because they dont affect healthy cells. Targeted therapy is often used to treat cancers that are more advanced and may be particularly helpful when other treatments dont work. […] If you have late-stage leiomyosarcoma that hasnt responded to other treatments, your doctor may recommend you participate in a clinical trial to test new treatments.

• #34 Therapeutic advances in leiomyosarcoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10031121/

  The combination of olaparib plus trabectedin was studied in a phase 1b trial by Dr. Grignani and colleagues, where this combination was deemed safe and well-tolerated. […] This led to a phase 2 study of trabectedin in combination with olaparib for advanced unresectable or metastatic sarcoma, which included a cohort of patients with LPS and LMS. […] Another potential therapy targeting DNA damage repair pathways in LMS includes the cell-penetrating peptide, ATX-101. […] Newer approaches to LMS involve directly targeting the cells main DNA damage response machinery, which is comprised of ataxia telangiectasia and Rad3-related protein (ATR), ataxia telangiectasia mutated (ATM) protein kinase and the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). […] As a result, strategies have been aimed to deplete tumor-associated macrophages and inhibit CSF1 signaling in sarcoma.

• #35 Targeted Therapy Shows Promise for Aggressive Uterine Sarcoma – Advances in Oncology | NewYork-Presbyterian

  https://www.nyp.org/advances/article/cancer/targeted-therapy-shows-promise-for-aggressive-uterine-sarcoma

  Results of a phase 2 clinical trial demonstrate the potential of targeted therapy in combination with chemotherapy to treat patients with uterine leiomyosarcoma, a rare, aggressive form of cancer that affects some 2,500 women every year in the United States. […] The clinical trial aimed to test a novel therapy for uterine leiomyosarcoma olaparib a PARP inhibitor originally developed for individuals with BRCA1 or BRCA2 mutations. […] Chemotherapy has been tried with only a very modest effect on improving survival. So our idea was to use precision medicine to define a subset of women who would benefit from a PARP inhibitor. […] The study involved 22 patients who received olaparib along with a low dose of temozolomide, a chemotherapy drug. […] Based on these promising initial results, the team received support from the National Cancer Institute to launch a large, randomized phase 3 clinical trial to test this novel drug combination against the current standard of care.

• #36 Therapeutic advances in leiomyosarcoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC10031121/

  Novel immunotherapy agents are also being tested in LMS. […] A phase 2 trial of APX005M in combination with doxorubicin in STS is actively recruiting patients. […] In LMS, aberrant PI3K/AKT/mTOR signaling has been seen due to PTEN loss and amplifications of IGF1R, AKT, RICTOR, and mTOR. […] Currently approved chemotherapy regimens for LMS demonstrate modest efficacy therefore studies have investigated novel chemotherapy combinations in order to improve benefit. […] This led to a phase 3 trial of doxorubicin plus trabectedin versus doxorubicin as first-line treatment for patients with advanced LMS. […] A randomized, placebo-controlled phase 2/3 trial has been developed and is actively recruiting patients.

• #37 Treatment with epigenetic agents profoundly inhibits tumor growth in leiomyosarcoma | Oncotarget

  https://www.oncotarget.com/article/25056/text/

  Leiomyosarcomas are rare mesenchymal neoplasms characterized by a smooth muscle differentiation pattern. Due to the extremely poor prognosis in patients, the development of novel chemotherapeutic regimens remains critically important. […] Treatment with guadecitabine led to a decrease in growth across the spectrum of sensitivity in LMS cell lines, both in a delayed in vitro and in vivo model; in parallel experiments, apoptotic pathways were activated in sensitive and less sensitive lines. Additional studies are required to explore potential therapeutic applications and mechanisms for leiomyosarcoma treatment. […] Guadecitabine was the most effective at decreasing cell survival in LMS cell lines. […] As per the above results, guadecitabine was the more effective DNMTi at inhibiting growth in cell lines with varying sensitivity, while also inducing apoptotic pathways.

• #38 Treatment with epigenetic agents profoundly inhibits tumor growth in leiomyosarcoma | Oncotarget

  https://www.oncotarget.com/article/25056/text/

  Given the remarkable in vitro anti-proliferative responses seen in LMS cell lines with low doses of epigenetic modulators, we explored if these effects could be seen in vivo. Guadecitabine was used for in vivo testing since it appeared to have increased potency as compared to Aza and DAC from in vitro models. […] The prognosis for sarcoma patients remains very poor, in spite of progress that has been made in other types of cancer. […] Guadecitabine, of the three DNMTi, was the most effective at slowing cellular viability in the cell line with the highest responsivity (SK-UT1), and the only drug to accomplish this at a clinically relevant concentration. […] Our results show that the hypomethylating agent guadecitabine appears to have greater efficacy in treatment of LMS cell lines in vitro than its counterparts. These anti-tumor effects were also replicated with in vivo models. Further studies are needed to elucidate the mechanism of this finding.

• #39

  https://link.springer.com/article/10.1007/s11864-021-00928-y

  The overall effectiveness of the currently available systemic treatment options for patients with LMS in the advanced and/or metastatic setting is limited; thus, patients overall prognosis remains poor. Therefore, designing and performing clinically meaningful and promising studies are of utmost importance to improve the prognosis of this patient population. […] Studies should be LMS-specific: Evidence-based data for LMS mainly comes from clinical trials open for the recruitment of a variety of heterogeneous STS subtypes; there are few prospective trials exclusively designed for the inclusion of LMS or even uterine LMS patients. […] Studies should focus on certain clinical settings: The majority of clinical studies are currently being conducted in the metastatic disease setting, mainly in later treatment lines (3rd/4th/5th line) potentially prolonging patients lives for only a few months. […] Studies should explore new therapeutic avenues: Besides the evaluation of the activity of conventional chemotherapeutic agents for LMS, new treatment avenues need to be explored. […] Studies should evaluate the role of biomarkers: Circulating tumor DNA (ctDNA) offers a rapid and noninvasive method of next-generation sequencing (NGS) that could be used for diagnosis, prognostic assessment, disease-response assessment to therapy, and detection of recurrence. […] In summary, there is a clear need for large international randomized or single-arm LMS-specific clinical trials, with an underlying biological rationale.

• #40 New Genomic Models for Leiomyosarcoma Treatment | Cleveland Clinic

  https://my.clevelandclinic.org/podcasts/cancer-advances/new-genomic-models-for-leiomyosarcoma-treatment

  We try to look at what kind of genetic changes correlate with worse overall and progression free survival, and we’re able to identify some changes that can help potentially propose a risk stratification that is based on genomics. […] The purpose of this is to develop a risk stratification model that is relatively readily accessible by most oncologists. […] If we have a leiomyosarcoma that was called low grade just by pure morphology. However, if we sequence it and we see things like ovoid mutation, ATRX mutation for example, we know that the presence of those mutations are significantly associated with worse survival in at least two large cohorts. […] The more information we share, the easier it is to validate this kind of study and the better informed we’ll be.

• #41 Sarcoma Treatment Centers | Leiomyosarcoma Information – LMSDR

  https://www.lmsdr.org/sarcoma-treatment-centers

  LMSDR highly recommends that you make every effort to be treated at, or at least get a second opinion from, a recognized high volume sarcoma center. […] Overall survival rates are better for those treated at a sarcoma center. […] SARC – Sarcoma Alliance Through Research Collaboration, offers an expert virtual tumor board to oncologists globally each month. Your doctor presents your case and they give their treatment recommendations. […] Sarcoma Alliances Hand-in-Hand Program offers reimbursement for up to $1,000 for first time visits at a sarcoma center. […] NORTHWEST SARCOMA provides grants of $500 to sarcoma patients currently undergoing treatment in AK, ID, MT, OR, or WA. […] Finish Sarcoma Foundation travel funds for John Hopkins sarcoma patients from MD, PA, VA, OH, or WV.

• #42 Follow-Up Care After Leiomyosarcoma Treatment

  https://www.webmd.com/cancer/leiomyosarcoma-aftercare

  Once your treatment is done, your oncologist may tell you that your leiomyosarcoma is in remission. This means that signs of your cancer have faded or disappeared. But that doesnt mean youre through with doctors appointments. Follow-up care is very important. […] You’ll need regular checkups and tests to make sure that the leiomyosarcoma doesn’t return. Your health care team can also ease any remaining side effects of your treatment. […] Your cancer doctor (they are called „oncologists”) will tell you how often you’ll need follow-up visits. During these visits, your doctor will look for signs of cancer. […] It’s common for leiomyosarcoma to come back, or recur. One study suggests that it returns nearly 40% of the time. The chances are highest in the first 5 years after treatment, so you’ll need the most follow-up then.

• #43 Leiomyosarcoma | Sarcoma UK

  https://sarcoma.org.uk/about-sarcoma/what-is-sarcoma/types-of-sarcoma/leiomyosarcoma/

  You may be offered an opportunity to take part in a study to investigate new diagnosis methods or treatments. Some studies also look at the care and wellbeing of patients. Your doctor or nurse can give you more information on opportunities for you to take part in a clinical trial. […] After treatment, you will have regular follow-up appointments for several years. You should receive a follow-up schedule from your sarcoma clinical nurse specialist. The usual practice will include: A chance to discuss symptoms, An examination to look for any signs of the sarcoma returning. This may include an MRI or ultrasound if required after examination, A chest x-ray to rule out any secondary cancers occurring in the lungs. […] Leiomyosarcoma can reappear in the same area after the treatment of a previous tumour; this is called a local recurrence. If the cancer does reappear, it is important to get treated as quickly as possible. This could involve further surgery and/or radiotherapy; your treatment will be assessed on an individual basis. Your multidisciplinary team will work closely with each other and with you to provide support and involve you in discussing all the possible treatment options.

• #44 Follow-Up Care After Leiomyosarcoma Treatment

  https://www.webmd.com/cancer/leiomyosarcoma-aftercare

  During your follow-up visits, your doctor will ask you how you’re feeling and do a physical exam. […] Your doctor may also order tests to check for cancer. They can depend on where your leiomyosarcoma was in your body and how serious the disease was. […] Having leiomyosarcoma can also raise your risk for getting another cancer down the road. […] You may have side effects of your leiomyosarcoma treatments. They may happen months or years after you’re finished. As part of your follow-up care, your health care team will treat these side effects. […] If you didn’t get a survivorship care plan during your treatment, ask your doctor about one. This plan includes: Details about your cancer and its treatment, A schedule for your follow-up exams and tests, A list of possible side effects of your treatment, Ways you can stay healthy through diet and physical activity.

• #45 FAQ – Leiomyosarcoma Prognosis, Causes & Treatment | LMSDR

  https://www.lmsdr.org/leiomyosarcoma-faq

  Sarcoma specialists recommend CT or MRI scans of the chest, pelvis and abdomen: every 3-4 months until one is NED (no evidence of disease) for 2 years. […] If your tumor started in tissue that is estrogen sensitive (female reproductive organs and breasts) your tumor may be estrogen sensitive. Ask your doctor to order the pathology tests for estrogen and progesterone receptors. If positive, you might be a candidate to take estrogen blockers for post-menopausal women.

• #46 Treatment for Uterine Sarcoma, by Type and Stage | American Cancer Society

  https://www.cancer.org/cancer/types/uterine-sarcoma/treating/by-stage.html

  If uterine sarcoma recurs, it often comes back in the first few years after treatment. […] Treatment options for recurrent uterine sarcoma are the same as those for stage IV (4) cancers. If the cancer can be removed, surgery might be done. If not already given, radiation might be used to reduce the size of the tumor and relieve the symptoms of large pelvic tumors. Chemotherapy, targeted drug therapy, immunotherapy, or hormone therapy are often needed when uterine sarcoma recurs.

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