Non-Uterine Research Updates-
2022:
- Retroperitoneal LMS Nomogram Model
- Preoperative Differentiation of Uterine Leiomyomas and Leiomyosarcomas: Current Possibilities and Future Directions
Brief Summary of the research update: https://pubmed.ncbi.nlm.nih.gov/35454875/
The complete publication: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9029111/
Here is the conclusion:
Conclusion of the study: The review of current literature led to the conclusion that we still have no reliable method to distinguish leiomyomas and leiomyosarcomas preoperatively. The studies in this field have, in most cases, retrospective design and the number of cases seems to be insufficient to achieve conclusive results. The rarity of malignant myometrial lesions is an obvious reason that explains such a situation.
However, on the horizon, we can identify new game-changing options that have the potential to revolutionize our practice in cases of myometrial lesions.
On one hand, there are many ambitious researchers introducing novel multi-parametric diagnostic scales, having promising performances in differentiating such lesions.
On the other hand, the recent advancement of machine learning and artificial intelligence constitute promising novel tools that give hope that we can solve this problem completely. Nowadays, the biggest challenge for researchers and clinicians is organizing multicenter databases that include numerous cases of both LM and LMS, and using them for the development and validation of these novel tools.
A NOTE: Dr. MITCHELL ACHEE, an LMS survivor and Radiologist, is working closely with several research clinicians at major sarcoma centers of excellence on am imaging project that holds promise to detect malignancies through special imaging which would be very helpful patients. This will be workgroup # 5 within the NLMSF-SPAEN International Research Roundtable. More to follow s this develops further. - Phase II Clinical Trial of Eribulin–Gemcitabine Combination Therapy in Previously Treated Patients With Advanced Liposarcoma or Leiomyosarcoma
- A phase Ib/II study of the combination of lenvatinib (L) and eribulin (E) in advanced liposarcoma (LPS) and leiomyosarcoma (LMS) (LEADER): Efficacy updates.
- Sounding the Alarm on Leiomyosarcoma Recurrence: Role of Circulating Tumor DNA Kasper B, Wilky BA. Researchers of the NLMSF-SPAEN International LMS Research Roundtable – Executive Committee and Workgroup Leadership
- Preclinical modeling of leiomyosarcoma identifies susceptibility to transcriptional CDK inhibitors through antagonism of E2F-driven oncogenic gene expression.
Matthew L Hemming 1, Patrick Bhola 1, Michael A Loycano 1, Justin A Anderson 1, Madeleine L Taddei 1, Leona A Doyle 2, Elizaveta Lavrova 1, Jessica L Andersen 1, Kelly S Klega 1, Morgan R Benson 1, Brian D Crompton 3, Chandrajit P Raut 4, Suzanne George 1, Anthony Letai 5, George D Demetri 1, Ewa Sicinska 1
Note: This research publication update is part of the newly funded NLMSF research project, associated with the NLMSF-SPAEN International LMS Research Roundtable Cell Line Working Group headed by Dr. Hemming.
- What Clinical Trials Are Needed for Treatment of Leiomyosarcoma?
- Large scale multiomic analysis suggests mechanisms of resistance to immunotherapy in leiomyosarcoma.
- Multiomic analysis to reveal distinct molecular profiles of uterine and nonuterine leiomyosarcoma.
- Soft Tissue and Uterine Leiomyosarcoma
Suzanne George, César Serrano, Martee L. Hensley, and Isabelle Ray-Coquard - Proteomic and Metabolomic Profiling in Soft Tissue Sarcomas
Current Treatment Options in Oncology (2022)Cite this article - Surgical resection of leiomyosarcoma of the inferior vena cava: A case series and literature review
- Relationships between highly recurrent tumor suppressor alterations in 489 leiomyosarcomas
2021:
- Prognostic relevance of the hexosamine biosynthesis pathway .
In order to identify metabolic pathways activated in leiomyosarcoma (LMS), we analyzed transcriptomic profiles of distinct subtypes of LMS in several datasets. Primary, recurrent and metastatic tumors in the subtype 2 of LMS showed consistent enrichment of genes involved in hexosamine biosynthesis pathway (HBP). https://pubmed.ncbi.nlm.nih.gov/33941787/ and https://www.nature.com/articles/s41525-021-00193-w - Dr. Matt Hemming’s Presentation
- 2019 Research article publication
- Dr. Brian Crompton and Dr Jonathan Trent’s Presentations
- Dr, Trent’s presentation – references Dr. Junaid Arshad’s 2020 research publication
- Treatment and outcomes of soft tissue sarcoma of groin, hip and thigh: a retrospective review from a tertiary care hospital
- Technical considerations for radical resection of a primary leiomyosarcoma of the vena cava
- Is compartmental surgery always mandatory in retroperitoneal liposarcoma? A case report of multifocal synchronous well-differentiated liposarcoma
- CLINICAL TRIAL ALERT: See video by Dr. Abdul Razak regarding a Phase 2 trial evaluating Olarapib combined with other new drugs through this clinical trial: NCT03851614: This is an active basket trial study including LMS but not recruiting at this time; information to be aware of in this OncLive video presentation.
- Dr. Mattew Ingham – Recorded presentation on recent Uterine LMS research – Video
- Dr. Matthew Ingham – FDA Grants Orphan Drug Status to Sotigalimab for Patients With Soft Tissue Sarcoma
- EPIGENETIC SIGNATURE AND DIFFERENTIATED LEIOJYOSARCOMA SUBTYPES includes ONCOTARGET VIDEO
- PubMed 2018 article: Treatment with epigenetic agents profoundly inhibits tumor growth in leiomyosarcoma
- FRONTIERS – CELL AND DEVELOPMENTAL BIOLOGY Article – June, 2021 Characterizing the Invasive Tumor Front of Aggressive Uterine Adenocarcinoma and Leiomyosarcoma
- Integrative genomic and transcriptomic analysis of leiomyosarcoma
- TP53 Mutation as a Prognostic and Predictive Marker in Sarcoma: Pooled Analysis of MOSCATO and ProfiLER Precision Medicine Trials
- Turning ‘Cold’ tumors ‘Hot’: immunotherapies in sarcoma
- KIF15 upregulation promotes leiomyosarcoma cell growth via promoting USP15-mediated DEK deubiquitylation
- CARIS PRECISION ONCOLOGY LIFE SCIENCE: Leiomyosarcoma (LMS) is a rare group of mesenchymal malignancies found in the uterus, retroperitoneum, skin, or other soft-tissue sites. Treatment for LMS is extrapolated from trials including both uterine (uLMS) and non-uLMS subtypes, although whether they respond similarly and have similar outcomes from treatment is not clear. We examined the molecular composition of LMS by site of origin to better inform future drug development and trial design.
- Cardiac safety of trabectedin monotherapy or in combination with pegylated liposomal doxorubicin in patients with sarcomas and ovarian cancer
- Gastrointestinal leiomyosarcoma demonstrate a predilection for distant recurrence and poor response to systemic treatments
- Primary Pulmonary Artery Sarcoma Confined to the Left Pulmonary Artery
- Management of Soft Tissue Sarcomas in Extremities: Variation in Treatment Recommendations and Surveillance According to Specialty and Continent
- Leiomyosarcoma of the urinary bladder: A SEER database study and comparison to leiomyosarcomas of the uterus and extremities/trunk
- Inflammatory leiomyosarcoma of the head and neck case report
- A randomized phase III trial comparing trabectedin to best supportive care in patients with pre-treated soft tissue sarcoma: T-SAR, a French Sarcoma Group trial
- Containing Cumulative Postoperative Morbidity in Patients with Retroperitoneal Sarcoma May Improve Long-Term Prognosis
- Adult genitourinary sarcoma: The era of optional chemotherapeutic agents for soft tissue sarcoma
- NKX6-1 mediates cancer stem-like properties and regulates sonic hedgehog signaling in l leiomyosarcoma
- What is Hedgehog signaling: The hedgehog signaling pathway is one of many complex cell signaling mechanisms found within multicellular organisms, and has a very important role within developmental tumor biology / tumorigenesis (production of a new growth or growths) It is already known that Sonic hedgehog (Shh) pathway is important for the evolution of radio and chemo-resistance of several types of tumors.
- Next-generation sequencing for the management of sarcomas with no known driver mutations
- Fourteen-Day Gemcitabine-Docetaxel Chemotherapy Is Effective and Safer Compared to 21-Day Regimen in Patients with Advanced Soft Tissue and Bone Sarcoma.
- A preliminary study of deep learning-based treatment response prediction for soft tissue sarcoma using longitudinal diffusion MRI
- Leiomyosarcoma – continuing education research information as of Jan 2021
- A randomized phase III trial comparing trabectedin to best supportive care in patients with pre-treated soft tissue sarcoma: T-SAR, a French Sarcoma Group trial
- Proteomic profiling of soft tissue sarcomas with SWATH mass spectrometry
- PubMed article: Relationships between highly recurrent tumor suppressor alterations in 489 leiomyosarcomas: https://pubmed.ncbi.nlm.nih.gov/33788262/
- Trabectedin for Patients with Advanced Soft Tissue Sarcoma: A Non-Interventional, Retrospective, Multi-center Study of the Italian Sarcoma Group: https://pubmed.ncbi.nlm.nih.gov/33801399/
NBTXR3 Activity in Soft Tissue Sarcoma Could Be Replicated in Other Cancers
Next-Generation sequencing reveals potentially actionable mutations in sarcoma
The role of 18 F-FDG PET/CT in retroperitoneal sarcomas-A multicenter retrospective study
2020:
Sarcoma Experts Elucidate on Combination Chemotherapy Regimens – Sarah Cannon Cancer Institute
Genomic profiling of primary histiocytic sarcoma reveals two molecular subgroups
- A phase II study of pazopanib as front-line therapy in patients with non-resectable or metastatic soft-tissue sarcomas who are not candidates for chemotherapy
- Georgios_Kantidakis_Presentation_ESMO2020
- Guide Patient election for Resection of Sarcoma Lung metastases
- Radiotherapy for Adult Soft Tissue Sarcomas of the Head and Neck
- Genomic Landscape of Uterine Sarcomas Defined Through Prospective Clinical Sequencing
- PharmaMar presents results of trabectedin & doxorubicin for first line treatment of leiomyosarcomas at ASCO 2020
Madrid, June 1st, 2020.- PharmaMar (MSE:PHM) has announced that the final results from the Phase II study of trabectedin in combination with doxorubicin for the treatment of patients with advanced metastatic uterine and soft tissue leiomyosarcoma have been presented in an Oral Abstract Session at the American Society of Clinical Oncology (ASCO) Annual Meeting, that was held on May 29th to 31st, 2020.
Under the title “A single-arm multicenter phase II trial of doxorubicin (Doxo) in combination with trabectedin (Trab) given as first-line treatment to patients with metastatic/advanced uterine (U-LMS) and soft tissue leiomyosarcoma (ST-LMS): Final results of the LMS-02 study” (Abstract 11506), Patricia Pautier, MD, from the Medical Oncology Department, Institut Gustave Roussy, Villejuif, France, has concluded that trabectedin in combination with doxorubicin is an effective first-line treatment for patients with leiomyosarcoma.
The study achieved its primary and secondary endpoints, with a median Progression-Free Survival (PFS) of 10.1 months; a median Overall Survival (OS) of 34.4 months and an acceptable safety profile.
As a reference (not comparable head-to-head studies), the most recent results of other doxorubicin combinations, such as those presented in ASCO 2019 in the “ANNOUNCE” Phase III study (doxorubicin + olaratumumab), reported a median PFS of 6.9 months, and an OS of 21.9 months (ASCO 2019 LBA3)[1].
Patricia Pautier, MD, said: “Combination of doxorubicin and trabectedin constitutes an active first-line therapy for patients with uterine and soft tissue leiomyosarcoma. Results in overall response rate, progression free survival and now in overall survival are very encouraging.” And added: “Results of the LMS04 trial, a randomized phase-III study comparing this combination followed by trabectedin versus doxorubicin alone in 1st-line therapy in metastatic LMS are pending.”
2019:
- BRCA ½ Functional Loss Defines a Targetable Subset in Leiomyosarcoma
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656468/ 
- Dr. Breelyn Wilky at Univ. of Colorado Health Sciences, Denver, CO recently gave a talk on some of the research that being developed in the lab and in clinic on improving outcomes with immunotherapy in sarcomas. It’s long and pretty scientific-focused, but reviews the major immunotherapy trials for sarcomas, and talks about ideas about how to move forward. View the video here.
- CT imaging improves histopathological grading of retroperitoneal leiomyosarcomas
- Overall survival and histology‐specific subgroup analyses from a phase 3, randomized controlled study
- of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma
- Effect of adjuvant therapy on the risk of recurrence in early-stage leiomyosarcoma: A meta-analysis.
2018:
- Cutaneous leiomyosarcoma on the trunk: An unusual presentation with an aggressive course – Case report and review of literature
- Analysis of the CDK4/6 Cell Cycle Pathway in Leiomyosarcomas as a Potential Target for Inhibition by Palbociclib
- Gemcitabine combined with docetaxel precisely regressed a recurrent leiomyosarcoma peritoneal metastasis in a patient-derived orthotopic xenograft (PDOX) model
- Detection of Circulating Tumor DNA in Patients With Leiomyosarcoma With Progressive Disease
- A patient-derived orthotopic xenograft (PDOX) nude-mouse model precisely identifies effective and ineffective therapies for recurrent leiomyosarcoma
- ELSEVIER RESEARCH ARTICLES – UPDATES ON LEIOMYOSARCOMAYou can go to this site directly for information updates on Leiomyosarcoma – There are many articles to see for LMS and ULMS.
- UPDATE FROM THE NATIONAL INSTITUTES OF HEALTH (NIH):
- Diagnostic accuracy of percutaneous biopsy in retroperitoneal sarcoma
- Neoadjuvant Interdigitated Chemoradiotherapy Using Mesna, Doxorubicin, and Ifosfamide for Large, High-grade, Soft Tissue Sarcomas of the Extremity: Improved Efficacy and Reduced Toxicity
Dr. Lara Davis, OHSU physician, researcher shares her research: Discovery and characterization of novel, recurrent, targetable ALK fusions in leiomyosarcoma
The result of this research provides the first validation of a targetable oncogenic kinase fusion as a driver in a subset of leiomyosarcomas. Overall, these findings suggest that some soft tissue sarcomas may harbor previously unknown kinase gene translocations, and their discovery may propel new therapeutic strategies in this treatment-refractory cancer.
- Discovery and characterization of recurrent, targetable ALK fusions in leiomyosarcoma
- Trabectedin, Doxorubicin, and Olaratumab in Patients With Metastatic or Recurrent Leiomyosarcoma
- Cancer research stories from Stanford Medicine and the Stanford Cancer Institute
Read about cancer research from Stanford Medicine’s News & Publications
Twitter updates available @StanfordCancer- In select sarcoma subtypes, researchers determined the disease control rate (DCR) with sorafenib plus dacarbazine. They examined patients with leiomyosarcoma (LMS), synovial sarcoma (SS), or malignant peripheral nerve sheath tumors (MPNST) with up to two previous lines of therapy and adequate hepatic, renal, and marrow function. Treatment regimen for these subjects comprised 3-week cycles of sorafenib at 400 mg oral twice daily and dacarbazine 1,000 mg/m2 intravenously (later reduced to 850 mg/m2). An 18-week DCR of 46% was documented in this study. Modest clinical activity of dacarbazine + sorafenib was evident in patients with these diagnoses. Dacarbazine + sorafenib was feasible and related to favorable disease-control rates; however, this combination also increased the potential for significant toxicity. Read the full article on The Oncologist
- NTRK fusion is associated with several cancers, including infantile fibrosarcoma, which can require amputation or morbid surgery when disease is locally advanced. For this phase 1/2 trial (ClinicalTrials.gov Identifier: NCT02637687), researchers enrolled 11 patients with infantile fibrosarcoma (7 patients) or another sarcoma subtype (4 patients) to receive larotrectinib followed by surgery.“This is very exciting, but only applies to 0.1% of sarcomas. But, it is worth looking into more. I have seen one sarcoma with
one NTRK fusion and it was very exciting.” – from Dr. Neeta Somaiah, MD, Sarcoma Research, Anderson Cancer Center. - A phase II study of tumor ablation in patients with metastatic sarcoma stable on chemotherapy
- A retrospective cohort study of treatment patterns among patients with metastatic soft tissue sarcoma in the US
- A prediction model for treatment decisions in high-grade extremity soft-tissue sarcomas: Personalised sarcoma care (PERSARC).
- A vimentin binding small molecule leads to mitotic disruption in mesenchymal cancers
- Cancer ‘vaccine’ eliminates tumors in mice
- DEFEATING CANCER / PRECISION MEDICINE / PERSONALIZED CARE
- Effect of neoadjuvant chemotherapy plus regional hyperthermia on long-term outcomes among patients with localized high-risk soft tissue sarcoma: The EORTC 62961-ESHO 95 randomized clinical trial
- Expression and role of TYRO3 and AXL as potential therapeutical targets in leiomyosarcoma
- Mocetinostat combined with gemcitabine for the treatment of leiomyosarcoma: Preclinical correlates
- Molecular studies of human carcinomas and sarcomas
Next-generation sequencing for patients with sarcoma: A single center experience
Nivolumab With Ipilimumab Promising for Pretreated Metastatic Sarcoma
Options for Adjuvant Therapy for Uterine Leiomyosarcoma
- Soft Tissue and Uterine Leiomyosarcoma
Leiomyosarcoma Articles by Dr. Alexander Lazar:
Dr. Alexander Lazar (medical advisory council member) is a research pathologist from MD Anderson Cancer Center in Houston, Texas.
Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas
Clinical Observations and Molecular Variables of Primary Vascular Leiomyosarcoma
Mice null for the deubiquitinase USP18 spontaneously develop leiomyosarcomas
Progressive loss of myogenic differentiation in leiomyosarcoma has prognostic value