Materiały źródłowe

• #1 Epithelioid Sarcoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK532911/

  Epithelioid sarcoma is a rare and aggressive soft tissue sarcoma characterized by both epithelial and mesenchymal differentiation. […] The primary treatment for epithelioid sarcoma is complete surgical removal, which is curative in the early stages. Radiation therapy may be used as an adjunct to reduce recurrence risk, and more recently, targeted therapies have been developed for advanced cases. […] Complete surgical resection is curative in early-stage disease. However, local recurrence and late distant metastases may occur, necessitating long-term surveillance. […] Wide excision is the treatment of choice for nonmetastatic epithelioid sarcoma. […] Radiation therapy is often added to mitigate local recurrence; however, the indications for radiation therapy are relatively undefined.

• #1 Epithelioid Sarcoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK532911/

  More recently, an inhibitor of enhancer of zeste homolog 2 (EZH2), Tazemetostat, has been approved for patients with unresectable or metastatic epithelioid sarcoma. […] Local recurrence rates of 40% to 60% have been reported, with a median time to recurrence of 1 to 2 years. However, recurrences have been reported as late as 20 years after the initial operation. As a result, close surveillance with cross-sectional imaging of the primary site and lungs is critical, typically with imaging studies every 6 months to 1 year.

• #2 Epithelioid Sarcoma—From Genetics to Clinical Practice

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7463637/

  Epithelioid sarcoma is a mesenchymal soft tissue sarcoma often arising in the extremities, usually in young adults with a pick of incidence at 35 years of age. […] An optimal long-term management strategy is still to be defined. The best treatment of localized ES is wide surgical resection. Neo-adjuvant or adjuvant radiotherapy may be recommended, as it reduces the local recurrence rate. […] Patients with metastatic ES have a poor prognosis with an expected median overall survival of about a year. Doxorubicin-based regimens are recommended for advanced ES. Tazemetostat, an EZH2 methyltransferase, has shown promising results in ES patients. Novel therapies, including immunotherapy, are still needed. […] The treatment of choice of ES is a radical excision with microscopically radical margins and perioperative radiotherapy after careful assessment in a multidisciplinary team.

• #3 Recommendations from the Epithelioid Sarcoma Collaborative: A White Paper – Journal of Oncology Navigation & Survivorship

  https://www.jons-online.com/issues/2021/september-2021-vol-12-no-9/recommendations-from-the-epithelioid-sarcoma-collaborative-a-white-paper

  Overcoming delays inherent in each interval of the diagnosis journey is recommended. A first step of increasing awareness of STS overall among patients and providers may be to reduce the patient delay in recognizing symptoms of ES. Increased awareness coupled with providing ES resources and educating healthcare providers about the different types of STS may also reduce the GP delay in considering the presentation as a possible cancer and improving the patientcare partnerphysician dialogue. […] Increasing access to expert, experienced sarcoma centers is an essential component of improving outcomes among patients with ES and includes partnerships with advocacy groups to support the cost of patient travel (eg, gas, lodging, air travel). […] Overcoming delays in the diagnosis journey for many ES patients necessitates targeted, curated resources that specifically address the unique needs of AYA patients, including additional sarcoma center AYA programs and information that addresses medical, emotional, social, and financial issues faced by AYA patients.

• #4 Recommendations from the Epithelioid Sarcoma Collaborative: A White Paper – Journal of Oncology Navigation & Survivorship

  https://www.jons-online.com/issues/2021/september-2021-vol-12-no-9/recommendations-from-the-epithelioid-sarcoma-collaborative-a-white-paper

  In conclusion, increasing awareness and understanding of ES is a necessary first step to improve the diagnosis journey by (1) decreasing the time to correct diagnosis; (2) reducing barriers to timely treatment and access to expert, experienced sarcoma centers; and (3) raising awareness among GPs and other care providers who may be the first point of contact for these patients. In addition, establishing a standard for ES diagnosis will create a consistent, reliable clinical evaluation threshold. In a rare disease with significant unmet need, the development of effective new therapies would be a game changer for patients.

• #5 Epithelioid Sarcoma: Symptoms, Treatment & Prognosis

  https://my.clevelandclinic.org/health/diseases/24331-epithelioid-sarcoma

  Epithelioid sarcoma is treatable, especially when detected early. Your healthcare provider will run several tests to determine how big the tumor is and whether it has spread to other areas of your body. Then, theyll design a personalized treatment plan. […] Surgical removal of the tumor is the most common epithelioid sarcoma treatment. If the cancer has spread to nearby lymph nodes, your surgeon may remove those as well. […] This common cancer treatment uses high-powered X-rays to kill cancer cells. Your healthcare provider may use radiation therapy before surgery to shrink the tumor, or after surgery to kill any remaining cancer cells. […] If the cancer has spread to other areas of your body, your healthcare provider may recommend chemotherapy. This treatment uses drugs to kill cancer cells.

• #6 Epithelioid sarcoma | UM Health-Sparrow

  https://www.uofmhealthsparrow.org/departments-conditions/conditions/epithelioid-sarcoma

  Surgery is the most common treatment for epithelioid sarcoma. Sometimes other treatments may be used in addition to surgery. Treatment options may include: […] Surgery involves removing the cancer and some of the healthy tissue around it. Taking some healthy tissue helps make sure that all the cancer cells are removed. Getting all of the cancer cells lowers the risk that the cancer will come back. […] Radiation therapy uses powerful energy beams to kill cancer cells. Radiation therapy is sometimes used before surgery to shrink the tumor. This can make it more likely that all of the cancer will be removed during surgery. Radiation therapy may be used after surgery to kill any cancer cells that might be left. […] Targeted therapy uses medicines that attack specific chemicals in the cancer cells that help them to grow. By blocking these chemicals, targeted treatments can cause cancer cells to die. Targeted therapy might be an option if you can’t have surgery or if other treatments do not work. One targeted therapy used for epithelioid sarcoma is tazemetostat (Tazverik).

• #6 Epithelioid sarcoma | UM Health-Sparrow

  https://www.uofmhealthsparrow.org/departments-conditions/conditions/epithelioid-sarcoma

  Chemotherapy uses strong medicines to kill cancer cells. Chemotherapy may be an option for treating epithelioid sarcoma that spreads to other parts of the body. It also might be used when surgery is not an option. […] Clinical trials are studies of new treatments. These studies provide a chance to try the latest treatment options. The side effects may not be known. Ask your healthcare team whether you might be able to take part in a clinical trial.

• #7 Epithelioid sarcoma | Czarnecka | Nowotwory. Journal of Oncology

  https://journals.viamedica.pl/nowotwory_journal_of_oncology/article/view/94810

  Epithelioid sarcoma (ES) is a very rare sarcoma characterized by loss of INI1. […] The only treatment for ES is radical excision with a microscope-radical margin. In general, the best treatment for ES in extremes is radical resection with a wide margin or amputation with or without lymph node dissection. Surgery may be followed by adjuvant chemotherapy and/or radiation therapy. […] Neoadjuvant chemotherapy with ifosfamide and doxorubicin with / or without radiation therapy must be used after a multidisciplinary team discussion. […] The curative treatment of ES is radical excision with wide R0 margins. In general, the best treatment for ES in the extremities is en bloc excision. In cases with large tumors, amputation must often be performed in order to obtain radical resection with tumor-free margins.

• #7 Epithelioid sarcoma | Czarnecka | Nowotwory. Journal of Oncology

  https://journals.viamedica.pl/nowotwory_journal_of_oncology/article/view/94810

  After MDT adjuvant chemotherapy and/or radiation therapy can also be used in high-risk patients. […] Neodjuvant chemotherapy and radiotherapy (RT) can be considered in patients with ES after multidisciplinary team evaluation (MDT). […] At this point in time, radical surgery with conventionally fractionated perioperative RT is considered the standard of care in ES. […] Patients with large recurrent ES tumors may receive multidisciplinary treatment with chemotherapy with RT with/without hyperthermia after MDT. […] In some cases, after MDT, perioperative chemotherapy can be considered. […] According to the current ESMO-EURACAN-GENTURIS Clinical Practice Guidelines, neoadjuvant treatment of operable localized STS of the extremities and the trunk wall is not yet standard treatment, although it can be proposed for fit patients with high-risk disease.

• #8 Epithelioid Sarcoma | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/449

  Complete surgical resection is curative in early-stage disease. […] However, local recurrence and late distant metastases may occur, necessitating long-term surveillance. […] Radiation therapy may be used as an adjunct treatment and as a palliative measure. […] Recently, treatment options have evolved with the development of targeted therapies, which aim to improve patient outcomes. […] Wide excision is the treatment of choice for nonmetastatic epithelioid sarcoma. […] Although margins of 2 to 5 cm have been described, the extent of resection should be individualized, with every effort made to preserve limb function. […] Despite its propensity for metastasis, sentinel lymph node biopsy is not recommended in clinically node-negative patients. […] Lymph node dissection of the involved basin is indicated in patients with clinically positive lymph nodes.

• #8 Epithelioid Sarcoma | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/449

  The surgical management of solitary in-transit metastases and isolated pulmonary metastases is controversial, and the lack of randomized clinical trials affects the available data. […] Metastasectomy may be indicated in certain situations. […] Radiation therapy is often added to mitigate local recurrence; however, the indications for radiation therapy are relatively undefined. […] Current indications for radiation therapy include patients with narrow margins, microscopically positive margins, local recurrence, and use as a palliative modality in patients with large tumors. […] More recently, an inhibitor of enhancer of zeste homolog 2 (EZH2), Tazemetostat, has been approved for patients with unresectable or metastatic epithelioid sarcoma. […] Local recurrence rates of 40% to 60% have been reported, with a median time to recurrence of 1 to 2 years. […] However, recurrences have been reported as late as 20 years after the initial operation. […] As a result, close surveillance with cross-sectional imaging of the primary site and lungs is critical, typically with imaging studies every 6 months to 1 year.

• #9 Epithelioid Sarcoma: A Review and Update | JCAD – The Journal of Clinical and Aesthetic Dermatology

  https://jcadonline.com/epithelioid-sarcoma-a-review-and-update/

  Epithelioid sarcoma is a rare, high-grade, soft tissue tumor that has a known propensity for local recurrence, regional lymph node involvement, and distant metastases. […] Current treatment modalities, which include radical excision, sentinel lymph node biopsy, and radiation. […] Radical tumor excision is the primary treatment for patients with ES. Negative tumor margins must be obtained, but optimal function, particularly of the upper limb, remains a potential goal. […] Marginal excision is inadequate due to the high rate of local recurrence and distant metastasis. […] Routine sentinel lymph node biopsy (SLNB) does not appear to be supported by data, though it is sometimes advocated due to the high rate of regional recurrence. […] Therapeutic lymph node dissection is indicated when lymph node metastases are present.

• #10 Epithelioid Sarcoma: A Review and Update | JCAD – The Journal of Clinical and Aesthetic Dermatology

  https://jcadonline.com/epithelioid-sarcoma-a-review-and-update/

  While the efficacy of radiation therapy as an adjunct to surgery has been clearly demonstrated in soft tissue sarcomas, studies of ES are limited due to small sample size and limited follow up. […] A decreased risk of local recurrence has been reported with the addition of preoperative or postoperative local radiation therapy when combined with radical surgery. […] Adjuvant chemotherapy appears to be indicated in the case of metastatic disease, but this is less clear in nonmetastatic ES. […] Limited experience with isolated limb perfusion indicates that it may be beneficial for multifocal or large unresectable tumors, allowing for reduction of tumor size with subsequent radical excision. […] Aggressive treatment with preoperative or postoperative radiation therapy combined with wide local excision appears to be indicated once diagnosis is established via histopathological confirmation. […] SLNB and lymphadenectomy may also be helpful in certain subsets of patients.

• #11

  https://www.orthobullets.com/pathology/8076/epithelioid-sarcoma

  Epithelioid Sarcomas are rare, slow-growing, malignant, nodular, soft tissue tumors that most commonly occur in the hand and wrist. […] Treatment is usually wide surgical excision with radiation. […] wide excision with adjuvant radiotherapy […] indication […] all operable tumors […] technique […] perform sentinel node biopsy to evaluate for regional lymph node metastasis […] outcomes […] high rate of multiple recurrences if mistaken for a benign lesion and inadequately excised […] re-excision of the tumor bed is recommended for inadequate initial resection […] amputation […] indications […] may be necessary to prevent spread of disease in cases of multiple recurrences.

• #12 Soft Tissue Sarcoma

  https://www.froedtert.com/sarcoma/conditions/soft-tissue-sarcoma

  Radiation treatment may be recommended to treat your soft tissue sarcoma. […] A combination of conservative surgery and radiotherapy has been shown to achieve excellent local control in sarcoma patients following margin negative surgery. […] One advantage of pre-operative radiation is the delivery of a smaller radiation dose to a smaller target volume when compared with post-operative radiotherapy. […] Brachytherapy is a method for destroying cancer cells by placing a small radioactive source next to the tumor. When combined with surgery, it is a very effective way to treat soft tissue sarcomas. […] External beam radiation therapy is used in several different scenarios. It is often given before or after surgery, or it may be indicated for patients who are not good candidates for surgery because of age or other health problems.

• #13 Soft Tissue Sarcoma Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/soft-tissue-sarcoma/hp/adult-soft-tissue-treatment-pdq

  Adjuvant chemotherapy may be considered but is not known to improve overall survival. […] Doxorubicin has been the standard systemic therapy in managing metastatic soft tissue sarcoma for several decades. […] Other drugs that may have clinical activity as single agents or in combination with doxorubicin are ifosfamide, other anthracyclines (epirubicin, pegylated liposomal doxorubicin), gemcitabine, trabectedin, eribulin, pazopanib, dacarbazine, and taxanes. […] The combination of gemcitabine and docetaxel is used as second-line therapy in treating patients with soft tissue sarcoma. […] Although doxorubicin alone has traditionally been considered the standard when comparing new drugs or regimens in the context of phase III clinical trials, some sarcoma subtypes have shown higher sensitivity to specific agents.

• #13 Soft Tissue Sarcoma Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/soft-tissue-sarcoma/hp/adult-soft-tissue-treatment-pdq

  In the setting of distant metastasis, surgery may be associated with long-term disease-free survival in patients with pulmonary metastasis and optimal underlying disease biology. […] Complete staging and treatment planning by a multidisciplinary team of cancer specialists is required to determine the optimal treatment for patients with soft tissue sarcoma. […] The role of chemotherapy is not well defined. […] There is evidence that favorable clinical outcomes may be associated with referral to a specialized sarcoma treatment center. […] Surgical resection and lymphadenectomy with or without postoperative radiation therapy may be indicated for patients with clinically positive lymph nodes. […] Neoadjuvant chemotherapy with or without radiation therapy or radiation therapy alone may be considered in selected cases where a limb-sparing surgery is advisable and/or there is a high probability of surgical resection with positive margins.

• #13

• #14 Epithelioid Sarcoma—From Genetics to Clinical Practice

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7463637/

  Radical surgery with conventionally fractionated perioperative RT remains a standard of care in ES. […] In some cases, perioperative chemotherapy can be considered. […] The systemic therapy of ES remains challenging and is not supported by high-quality evidence. In the light of available data, anthracycline-based regimens, preferably in combination with ifosfamide, are preferred as a first-line treatment of patients with advanced or metastatic ES. […] Recently, the FDA has approved tazemetostat, an EZH2 inhibitor, for the treatment of adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for radical resection.

• #15 EPITHELIOID SARCOMA

  https://www.seyitaligumustas.com/en/epithelioid-sarcoma

  Epithelioid sarcoma is a very rare (less than 1% of all soft tissue sarcomas) malignant soft tissue tumor. […] The primary treatment for epithelioid sarcoma is removal of the tumor with clean margins (wide resection). The tumor that is not removed cleanly with wide margins has a nearly one hundred percent recurrence rate and is prone to metastasis. For this reason, it is important that the surgeon performing the surgery is an orthopedic oncologist with experience in this area. […] Adding radiotherapy (high dose and large area) to surgical treatment before or after surgery reduces the chance of tumor recurrence. Therefore, surgery with radiotherapy is the standard of care. […] In patients with epithelioid sarcoma, systemic chemotherapy is recommended for locally advanced or metastatic cases. Doxorubicin+ifosfamide, gemcitabine+docetaxel, pazopanib and tazemetostat are among the chemotherapy drugs used for this purpose.

• #16 Epithelioid sarcoma – Wikipedia

  https://en.wikipedia.org/wiki/Epithelioid_sarcoma

  Surgery, radiation, and systemic therapy such as chemotherapy are all used at various times in the treatment of patients who have epitheloid sarcoma. […] Surgical resection of epithelioid sarcoma with wide margins remains the preferred method of treatment, and as of 2023, remains the only curative approach for the cancer, sometimes in concert with radiation or chemotherapy. […] In cases of advanced, recurrent, or metastasized disease, or if the tumor is inoperable, chemotherapy and radiation are the standard of care. […] In January 2020, The U.S. Food and Drug Administration approved the oral medication tazemetostat (trade name Tazverik), a drug that blocks the EZH2 methyltransferase, for the treatment of epithelioid sarcoma in patients aged 16 years and older with either metastatic or locally advanced (unable to be completely removed surgically) disease.

• #17 FDA approves first treatment option specifically for patients with epithelioid sarcoma, a rare soft tissue cancer | FDA

  https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-option-specifically-patients-epithelioid-sarcoma-rare-soft-tissue

  Today, the U.S. Food and Drug Administration granted accelerated approval to Tazverik (tazemetostat) for the treatment of adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection. […] Until today, there were no treatment options specifically for patients with epithelioid sarcoma. The approval of Tazverik provides a treatment option that specifically targets this disease. […] Surgical removal is considered the main treatment when the cancer is localized to one area of the body. Chemotherapy or radiation may also be given. […] Tazverik was granted Accelerated Approval, which enables the FDA to approve drugs for serious conditions to fill an unmet medical need based on a result that is reasonably likely to predict a clinical benefit to patients. Further clinical trials may be required to verify and describe Tazverik’s clinical benefit.

• #18 Two New Soft Tissue Sarcoma Treatments Approved by the FDA | AACR Blog

  https://www.aacr.org/blog/2020/01/28/two-new-soft-tissue-sarcoma-treatments-approved-by-the-fda/

  Tazemetostat (Tazverik) was approved for treating certain patients with epithelioid sarcoma. […] The FDA decision makes tazemetostat the first therapeutic approved specifically for treating this type of cancer. It was approved specifically for treating adults and pediatric patients age 16 and older who have metastatic or locally advanced epithelioid sarcoma that cannot be completely removed with surgery. […] Research has shown that EZH2 fuels the proliferation of cancer cells that lack another protein called INI1 and that more than 90 percent of epithelioid sarcomas lack INI1. These data led to the idea that targeting EZH2 with tazemetostat might benefit patients with epithelioid sarcomas. […] The approval of tazemetostat was based on results from a phase II clinical trial that were presented at a scientific conference in mid-2019. The data showed that nine (15 percent) of the 62 patients with metastatic or locally advanced epithelioid sarcoma who received tazemetostat had partial or complete tumor shrinkage. The response lasted six months or longer for six of the nine patients who had a response. […] Tazemetostat is being tested in several other clinical trials as a treatment for other types of solid tumors lacking INI1 and for several blood cancers, including follicular lymphoma. It is therefore likely that we will hear more about this molecularly targeted therapeutic in the future.

• #19 Targeting epigenetics in sarcomas through EZH2 inhibition | Journal of Hematology & Oncology | Full Text

  https://jhoonline.biomedcentral.com/articles/10.1186/s13045-020-00868-4

  Soft-tissue sarcomas represent a heterogeneous group of diseases with distinct genetic and clinical features accounting for up to 1% of cancer in adults and 15% of cancer in children. Epithelioid sarcoma is an extremely rare and aggressive tumor affecting young adults that is characterized by loss of INI1 expression. […] Tazemetostat, a specific EZH2 inhibitor, has just been approved for patients with advanced epithelioid sarcoma and represents a new therapeutic option in this devastating disease. […] Tazemetostat was well tolerated, with most treatment-related adverse events being grades 1 or 2 (asthenia, anorexia, thrombocytopenia, nausea, and dyspnea). […] Altogether, these results showed that tazemetostat can be associated with substantial clinical benefit in a subset of patients with advanced epithelioid sarcoma. Based on these data, the United States Food and Drug Administration (USFDA) granted accelerated approval to tazemetostat for the treatment of adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection in January 2020. […] A phase Ib investigating the safety of tazemetostat in combination with doxorubicin is ongoing (NCT04204941), and a phase III that will compare doxorubicin versus doxorubicin combined with tazemetostat in the front-line setting for epithelioid sarcoma treatment is planned to open accrual in 2020.

• #20 Targeted Drug Therapy for Soft Tissue Sarcoma | American Cancer Society

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

  Pazopanib can help slow tumor growth and ease side effects in patients with sarcomas that cannot be removed with surgery. […] Tazemetostat can shrink or slow the growth of some of these cancers, although its not yet clear if it can help people live longer. […] Many other targeted drugs might also be helpful in treating certain types of soft tissue tumors.

• #21 New Soft Tissue Sarcoma treatments 2025 | Everyone.org

  https://everyone.org/explore/treatment/?id=18

  Soft tissue sarcoma is a rare type of cancer that originates in the soft tissues of the body, such as muscles, tendons, fat, nerves, and blood vessels. […] Treatment options typically involve surgery, radiation therapy, chemotherapy, targeted therapy, or a combination of these approaches. […] Recently, targeted therapies like pazopanib have been approved for certain types of advanced soft tissue sarcoma, offering additional treatment options. […] Tazverik (Tazemetostat) is a targeted therapy approved by the FDA for patients with metastatic or locally advanced epithelioid sarcoma who are not candidates for surgery. […] Tazverik functions by inhibiting EZH2 (enhancer of zeste homolog 2), an enzyme implicated in tumor growth and progression. […] Fyarro (sirolimus protein-bound particles) is an FDA-approved intravenous medication indicated for the treatment of locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumors (PEComa), a rare subtype of soft tissue sarcoma.

• #21 New Soft Tissue Sarcoma treatments 2025 | Everyone.org

  https://everyone.org/explore/treatment/?id=18

  Ogsiveo (trabectedin), also known commercially as Yondelis, is FDA-approved for the treatment of patients with unresectable or metastatic liposarcoma or leiomyosarcoma who have previously received chemotherapy containing anthracycline. […] Immunotherapy is an emerging treatment option currently being studied in clinical trials for soft tissue sarcoma. […] Several experimental treatments for soft tissue sarcoma are currently under investigation in clinical trials. […] In certain cases, physicians may prescribe medications off-label meaning the medication is FDA-approved for other conditions but not specifically for soft tissue sarcoma. […] Palliative care focuses on symptom management, pain relief, and improving the overall quality of life for patients with advanced or metastatic soft tissue sarcoma.

• #22 Epigenetic Combination Therapy Could Overcome Treatment Resistance in Epithelioid Sarcomas and Rhabdoid Tumors | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/news/epigenetic-combination-therapy-could-overcome-treatment-resistance-in-epithelioid-sarcomas-and-rhabdoid-tumors

  Dr. Kentsis lab will also explore the possibility of combining tazemetostat with immune checkpoint inhibitors, which release a natural brake on the immune system so that immune cells called T cells recognize and attack tumors. A successful combination with immunotherapy might provide a more lasting therapeutic response. […] Our long-term objective is to cure these patients definitively, Dr. Kentsis says.

• #22 Epigenetic Combination Therapy Could Overcome Treatment Resistance in Epithelioid Sarcomas and Rhabdoid Tumors | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/news/epigenetic-combination-therapy-could-overcome-treatment-resistance-in-epithelioid-sarcomas-and-rhabdoid-tumors

  A team led by physician-scientist Dr. Alex Kentsis designed a combination therapy that overcomes resistance to tazemetostat, a drug used to treat epithelioid sarcomas and rhabdoid tumors. […] Based on this discovery, the researchers designed a combination therapy that overcomes the resistance in a lab setting. […] By understanding the mechanisms of resistance, we were able to develop a combination therapy strategy that could improve treatment of not just epithelioid sarcoma but many types of cancer with similar epigenetic defects, Dr. Kentsis says. […] The researchers tested a combination therapy using tazemetostat together with an experimental drug called barasertib, which targets mutations in the relevant pathway. This approach slowed tumor growth in mice, suggesting the treatment approach is promising.

• #23 3 Things You Should Know About Identifying and Treating Epithelioid Sarcoma

  https://www.cancernetwork.com/view/3-things-you-should-know-about-identifying-and-treating-epithelioid-sarcoma

  Disease that recurs, metastasizes, or is diagnosed at an advanced stage is often treated with some form of systemic therapy (eg, traditional chemotherapy or targeted medication). In addition to disease factors, individual patient characteristics must be considered, and shared decision-making is encouraged. Age, comorbidities, personal goals, and lifestyle factors all have the potential to tip the scales of treatment decisions. […] The use of systemic treatment for STS has traditionally been controversial, and it is reserved for advanced cases. Indeed, NCCN guidelines only recommend systemic treatment when the primary tumor is unresectable, the disease is metastatic at diagnosis, or recurrence has occurred following primary treatment. The prognosis for patients who qualify for systemic treatment is generally poor, with a median life expectancy of 8 months for metastatic ES.

• #24 The diagnosis and treatment of the epithelioid sarcomas involving the peripheral nerves | Scientific Reports

  https://www.nature.com/articles/s41598-024-82357-z

  Active functional rehabilitation was accomplished by all these patients after functional reconstruction, and good functional recovery was observed. […] Wide local excision and regional lymph nodes dissection are the first choice of treatment. […] The manners of how to reconstruct the patients function need to be applied flexibly by the doctors. […] Postoperative chemotherapy and radiotherapy are still controversial in the literature. The patients need close follow-up to discovered the local recurrence and/or lymph node metastasis as early as possible.

• #25 Treatment of Soft Tissue Sarcomas, by Stage | American Cancer Society

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

  Radiation may be given after surgery. […] The goal of treatment is to shrink the tumor, making it easier to remove. […] Chemo, radiation, or both might also be given after surgery. These treatments lower the chance of the tumor coming back in or near the same place it started. […] Radiation therapy with or without chemo can be used alone when the tumor’s location or size or the patient’s overall health makes surgery impossible. […] The best success rate is when it has spread only to the lungs. […] For people whose primary tumor and all metastases cannot be removed completely by surgery, radiation therapy and/or chemotherapy are often used. […] For some types of soft tissue sarcomas, treatment with newer targeted drugs or immunotherapy might also be an option. […] If the sarcoma comes back in the same area where it started, it may be treated with surgery. […] If the sarcoma returns in a distant part of the body, chemo, targeted therapy, or immunotherapy drugs may be options.

• #26 UCSF Epithelioid Sarcoma Clinical Trials for 2025 — San Francisco Bay Area

  https://clinicaltrials.ucsf.edu/epithelioid-sarcoma

  Epithelioid sarcoma is a cancer that occurs in the soft tissues of the body. UCSF is conducting research on combining nivolumab and ipilimumab for treatment in children and young adults. […] This clinical trial is studying two immunotherapy drugs (nivolumab and ipilimumab) given together as a possible treatment for INI1-negative tumors. […] This phase I/II trial studies how well tiragolumab and atezolizumab works when given to children and adults with SMARCB1 or SMARCA4 deficient tumors that have either come back (relapsed) or do not respond to therapy (refractory). […] Immunotherapy with monoclonal antibodies, such as tiragolumab and atezolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. […] This randomized phase II/III trial studies how well pazopanib, when combined with chemotherapy and radiation therapy or radiation therapy alone, work in the treatment of patients with newly diagnosed non-rhabdomyosarcoma soft tissue sarcomas that can eventually be removed by surgery. Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as ifosfamide and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Pazopanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

• #27

  https://www.clinicaltrialsregister.eu/ctr-search/search?query=epithelioid+sarcoma

  A Phase 1b/3 Global, Randomized, Double-blind, Placebo-Controlled Trial of Tazemetostat in Combination With Doxorubicin as Frontline Therapy for Advanced Epithelioid Sarcoma […] A PHASE II WINDOW-OF-OPPORTUNITY STUDY OF PREOPERATIVE THERAPY WITH PAZOPANIB (VOTRIENT) IN HIGH-RISK SOFT TISSUE SARCOMA […] A Phase II, Multicenter Study of the EZH2 Inhibitor Tazemetostat in Adult Subjects with INI1-Negative Tumors or Relapsed/Refractory Synovial Sarcoma […] A phase II study of intravenous TZT-1027, administered weekly times two, every three weeks, to patients with advanced or metastatic soft tissue sarcomas (STS) with prior exposure to doxorubicin-based therapy […] A Phase 1 Study of the EZH2 Inhibitor Tazemetostat in Pediatric Subjects with Relapsed or Refractory INI1-Negative Tumors or Synovial Sarcoma

• #28 New strategies in soft tissue sarcoma treatment | Journal of Hematology & Oncology | Full Text

  https://jhoonline.biomedcentral.com/articles/10.1186/s13045-024-01580-3

  The study of NTRK fusions in sarcomas has become increasingly significant due to the therapeutic implications of targeting these genetic abnormalities with TRK inhibitors. […] Tazemetostat stands as a paradigm of effective targeted therapy within a specific sarcoma sub-histotype, leading to an exceptional response and the accelerated approval of an epigenetic drug in January 2020 in the USA, specifically for the treatment of adults and adolescents with locally advanced or metastatic ES not eligible for complete resection. […] This study aims to compare tazemetostat+doxorubicin against the current frontline standard treatment, single-agent doxorubicin+placebo, as a first-line treatment in locally advanced unresectable or metastatic ES.

• #28 New strategies in soft tissue sarcoma treatment | Journal of Hematology & Oncology | Full Text

  https://jhoonline.biomedcentral.com/articles/10.1186/s13045-024-01580-3

  The clinical potential of Mipa was explored in a Phase 1b trial involving patients with advanced sarcomas. […] The development of ADCs has been bolstered by advances in engineering more stable linkers and more potent cytotoxins, which can kill cancer cells at lower doses. […] The rise of immunotherapy, including novel agents like LAG-3 inhibitors and bifunctional proteins that target both TGF- and PD-L1, offers new avenues for treatment, particularly when combined with traditional therapies like chemotherapy. […] In the first biomarker-driven immunotherapy trial conducted in patients with STS, the existence of TLS has been correlated with improved outcomes and heightened responsiveness to immune-checkpoint inhibition. […] These promising findings underscore the potential of immunotherapy as a more effective treatment option for certain sarcoma patients when compared to traditional cytotoxic chemotherapy.

• #29 Epigenetic combination therapy could overcome treatment resistance in epithelioid sarcomas and rhabdoid tumours – ecancer

  https://ecancer.org/en/news/24175-epigenetic-combination-therapy-could-overcome-treatment-resistance-in-epithelioid-sarcomas-and-rhabdoid-tumours

  Epigenetic combination therapy could overcome treatment resistance in epithelioid sarcomas and rhabdoid tumours. […] The outlook for people with these subtypes of soft tissue sarcoma brightened in 2020 when the Food and Drug Administration approved a targeted therapy called tazemetostat for certain patients. […] Unfortunately, tazemetostat has not worked in most people with the mutation, and some patients who initially respond develop resistance to the drug. […] Based on this discovery, the researchers designed a combination therapy that overcomes the resistance in a lab setting. […] The combination therapy uses an epigenetic treatment strategy, which aims at altering the expression of genes. […] By understanding the mechanisms of resistance, we were able to develop a combination therapy strategy that could improve treatment of not just epithelioid sarcoma but many types of cancer with similar epigenetic defects, Dr. Kentsis says.

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