NATIONAL LEIOMYOSARCOMA FOUNDATION

                            2026-2027 RESEARCH GRANT ANNOUNCEMENT

NLMSF Empowering patients through information / education / support

LOI deadline: April 15th, 2025

Please submit to Matthew Hemming, M.D., PhD.: matthew.hemming@umassmemorial.org  and 
Alessandra Maleddu M.D.:  alessandra.maleddu@cuanschutz.edu

Introduction: The National Leiomyosarcoma Foundation (NLMSF) is dedicated to meeting the needs of leiomyosarcoma (LMS) patients, caregivers and families through education and research. In order to facilitate advances in the treatment of LMS through research, the NLMSF is accepting research proposals for pilot studies that will launch “out of the box” ideas and new research trajectories to move the field forward.

Scope of the award/ areas of interest: All direct funds must be used to support LMS research. Proposals involving any scientific discipline are allowed including those related to biomarkers and imaging. This award was created to support basic and translational research. Other highly translational projects that are not based in a traditional wet lab may be considered (for example: in silico computational biology, radiomics, etc.); however, investigators who are considering submitting a non-traditional research project are highly encouraged to discuss the appropriateness of their project ahead of time. Clinical research (interventional trials) will not be supported by this award; however, work studying human samples and annotated data sets obtained from clinical trials is allowed. Studies requiring human samples must show documentation of IRB approval prior to awarding of funds (or document waivers if applicable).

Letter of Intent (LOI) Overview: The NLMSF seeks LOIs for research grant funding. The total award will be $50,000 per year for 2 years.  Indirect costs should not exceed 10% of the total budget.
The LOI should consist of:
1) Proposed research (2 page maximum)
2) Applicant NIH Biosketch

 Key Dates:
LOI due: April 15th, 2025
Invitations for full proposal sent: May 30th, 2025
Full proposal due: August 31st, 2025
Announcement: November 2025
Funding start date: January 2026

_____________________________________________________________________________________________________________________

2025

Clinical outcomes following stereotactic radiosurgery for brain metastases from sarcoma primaries: An international multicenter analysis (Cancer 2025 Jul 1;131(13):e35931.  doi: 10.1002/cncr.35931.)


Leiomyosarcoma Therapeutic Approaches and Future Directions (7 April 2025) available on-line in the Hematology/Onc0logy Clinics of North America (22 May 2025)
https://www.sciencedirect.com/science/article/abs/pii/S0889858825000450?via%3Dihub

Emerging Role of Blood-based Biomarkers in Sarcomas (2 April 2025) available on-line in the Hematology/Onc0logy Clinics of North America (22 May 2025)
https://www.sciencedirect.com/science/article/abs/pii/S0889858825000401?via%3Dihub

A Phase II Multi-Center Trial of Trabectedin in Combination with Olaparib in Patients with Advanced Unresectable or Metastatic Sarcoma.

Siontis BL, Rice JD, Schuetze SM, Rottmann D, Angeles CV, Fox AK, Zyczynski LE, Hayek S, Robinson SI, Okuno SH, Ho TP, Chugh R.  (13 May 2025)
Clin Cancer Res. 2025 May 13. doi: 10.1158/1078-0432.CCR-25-0298. Online ahead of print.

PMID: 40358615

Histology-driven tailoring of surgical approaches in retroperitoneal soft tissue sarcoma: retrospective cohort study.

Musa J, Willis F, Rompen IF, Harnoss JC, Grünewald TGP, Al-Saeedi M, Büchler MW, Schneider M. (7 May2025)
BJS Open. 2025 May 7;9(3):zraf050. doi: 10.1093/bjsopen/zraf050.

PMID: 40357995

Myxoid Leiomyosarcoma of the Uterus – A Case Report (2 Apr 2025) in Oncology Letters

 
Comprehensive mutational profiling identifies new driver events in cutaneous leiomyosarcoma  https://academic.oup.com/bjd/article-abstract/192/2/335/7818451?redirectedFrom=fulltext&login=false

Plain language summary

Cutaneous leiomyosarcoma (or ‘cLMS’ for short) is a type of skin tumour. It commonly appears as a painful nodule on the trunk, legs or arms. Surgery to remove it is recommended, but it can grow back and may spread to other organs. For this reason, we need to understand more about cLMS to try to find other treatments. Analysing the genetic material in tumour cells lets us know which genes have been mutated or altered. This is important as these mutations or alterations can play a role in the development of a tumour or its progression. Recording all the mutations and alterations found in a tumour is crucial to understanding the biology of the disease. It is also important in finding ways to diagnose the disease, predicting how it will progress and finding treatments for it. Up to now, only two studies have analysed the genetic material in cLMS tumours. Samples were only available from small groups of people and fewer than 100 genes were investigated. To study the genetic changes in cLMS and identify the key events that cause them, we analysed all the genes in the DNA of a large number of people with cLMS. We confirmed that two genes (called ‘TP53’ and ‘RB1’) could be key to the development of cLMS. We also found new possible causes of cLMS, including exposure to sunlight, changes in chromosomes and some gene fusions. These findings give us a better understanding of the biology of cLMS.

Exploration of the mutational landscape of cutaneous leiomyoma confirms FH as a driver gene and identifies targeting purine metabolism as a potential therapeutic strategy | British Journal of Dermatology | Oxford Academic       https://doi.org/10.1093/bjd/ljae432

 

2024

Dr. Patricia Pautier- a research update in the New England Journal of Medicine

Published November 27, 2024
N Engl J Med 2024;391:2057-2058 
DOI: 10.1056/NEJMc2412479

VOL. 391 NO. 21

Doxorubicin–Trabectedin in Leiomyosarcoma | New England Journal of Medicine

The results of the LMS04 trial reported by Pautier et al. (Sept. 5 issue)1 are unprecedented in terms of the median progression-free and overall survival. The French Sarcoma Group should be lauded for conducting this large trial in patients with a specific sarcoma subset. However, we would like to raise a few issues. Trabectedin was administered over a period of 3 hours instead of 24 hours, which is standard practice. Robust data indicate that 24-hour administration yields superior tumor control and progression-free survival.2 Unlike other drugs, trabectedin does not have cumulative toxic effects. 

CLINICAL TRIALS:

Randomized controlled, open-label, phase IIb/III study of lurbinectedin in combination with doxorubicin versus doxorubicin alone as first-line treatment in patients with metastatic leiomyosarcoma.  Clinical trial information: NCT06088290.

AuthorsGregory Michael CoteSant P. ChawlaGeorge DemetriBernd KasperRobin Lewis JonesJavier Martin BrotoJoseph WooleyMia C. WeissSalvatore TafutoGiuseppe BadalamentiIrene Carrasco-GarciaPaloma PeinadoJean-Yves BlayGaston BoggioCristian Marcelo FernandezAntonio NietoCarmen Maria KahattAli Hassan Zeaiter, and Axel Le Cesne  Click this title for research update:

Randomized controlled, open-label, phase IIb/III study of lurbinectedin in combination with doxorubicin versus doxorubicin alone as first-line treatment in patients with metastatic leiomyosarcoma. | Journal of Clinical Oncology

  Study of ADI-PEG 20 or Placebo Plus Gem and Doc in Previously Treated Subjects With Leiomyosarcoma (ARGSARC)

July 25, 2024 updated by: Polaris Group

ADI-PEG 20 or Placebo Plus Gemcitabine and Docetaxel in Previously Treated Subjects With Leiomyosarcoma (ARGSARC): A Randomized, Double Blind, Multi-Center Phase 3 Trial

To compare the efficacy and safety in subjects with advanced or metastatic LMS previously treated with an anthracycline.

Study Overview

This is a global, multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 3 trial that will compare the efficacy and safety in subjects with advanced or metastatic LMS previously treated with an anthracycline.

A Phase 3 Study of ADI-PEG 20 or Placebo Plus Gemcitabine and …

www.mskcc.org/cancer-care/clinical-trials/24-147

Full Title ADI-PEG 20 or Placebo Plus Gemcitabine and Docetaxel in Previously Treated Subjects with Leiomyosarcoma (ARGSARC): A Randomized, Double-Blind, Multi-Center Phase 3 Trial (WIRB) Purpose Leiomyosarcoma is a type of cancer that forms in smooth muscle. Researchers want to see if adding ADI-PEG 20 to the usual chemotherapy for leiomyosarcoma works better than chemotherapy alone 

Investigator                        Co investigator

Viswatej (Vishu) Avutu        Robert Maki

Frontiers | Leiomyosarcoma of the abdomen and retroperitoneum; a systematic
review (frontiersin.org)
  

doi: 10.1200/JCO.24.00358
Phase Ib Study for the Combination of Doxorubicin, Dacarbazine, and Nivolumab as the Upfront Treatment in Patients With Advanced Leiomyosarcoma: A Study by the Spanish Sarcoma Group (GEIS)  


Principle investigator:  Dr. Javier Martin – Broto,  esteemed member of the National LMS Foundation’s International LMS Research Roundtable
 and recent speaker at the Roundtable meeting – the 6th year of a successful meeting bringing researchers from around the world to discuss and collaborate on new focus areas to address the unmet needs in research and treatment.
https://pubmed.ncbi.nlm.nih.gov/39356980

Purpose: Doxorubicin, alongside a select group of cytotoxic agents, is capable of inducing an adaptive immune response via a well-established peculiar type of tumor cell death called immunogenic cell death (ICD). We hypothesize that combining doxorubicin and dacarbazine with nivolumab may enhance therapeutic efficacy by exerting synergy in the ICD circuit. We hereby present a phase Ib trial with this combination.   Conclusion: This scheme of doxorubicin, dacarbazine, and nivolumab is feasible and well tolerated. Clinical activity is encouraging and the prognostic impact of HMGB1 supports the relevance of ICD activation. Further clinical research is already underway with this concept in leiomyosarcoma.

Immunotherapy in Sarcoma: Current Data and Promising Strategies

AuthorsGeorgina E. Wood, MD, PhDChristian Meyer, MDFlorent Petitprez, PhD, and Sandra P. D’Angelo, MD dangelos@mskcc.orgAUTHORS INFO & AFFILIATIONS

Immunotherapy in Sarcoma: Current Data and Promising Strategies | American Society of Clinical Oncology Educational Book (ascopubs.org)   (May 2024)

TRANSLATIONAL CANCER MECHANISMS AND THERAPY| MAY 15 2024
Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma 

Josephine K. Dermawan  Clin Cancer Res (2024) 30 (10): 2260–2271.  

https://doi.org/10.1158/1078-0432.CCR-24-0148

 
Leiomyosarcoma – Continuing Education Activity (28 Feb 2024)
 

2023

New Therapeutics for Soft TissueSarcomas – Overview of current Immunotherapy for future direction of STS 14 May 2023
Gyuhee Seong   and   Sandra D’Angelo

High Grade Sarcomas with Myogenic Differentiation Harboring Hotspot PDGFRB Mutations  (May 2023)
https://www.sciencedirect.com/science/article/abs/pii/S089339522300008X
NOTE:   LMS discussed in this article

The Biology and Treatment of LMS Apr 2023

Targeting the Molecular and Immunologic Features of Leiomyosarcoma (31 Mar 2023)
https://www.mdpi.com/2072-6694/15/7/2099

Sequential Targeting of Retinoblastoma and DNA Synthesis Pathways Is aTherapeutic Strategy for Sarcomas That Can Be Monitoredin Real Time (15 Mar 2023) This research done at MD Anderson Cancer Center was supported by the NLMSF https://pubmed.ncbi.nlm.nih.gov/36603130/

Not All Leiomyosarcomas Are the Same: How to Best Classify LMS (8 Mar 2023) https://link.springer.com/article/10.1007/s11864-023-01067-2

Therapeutic advances in leiomyosarcoma Kristine Lacuna; Sminu Bose, Mathew Ingham, Gary Schwartz (8 Mar 2023) 2023)https://www.frontiersin.org/articles/10.3389/fonc.2023.1149106/full

Clinical characteristics of sarcoma cases in which long-term disease control was achieved with trabectedin treatment: A retrospective study:(1 Mar 2023)
https://pubmed.ncbi.nlm.nih.gov/36857355/

Emerging Trends in Immunotherapy for Adult Sarcomas
Marium HusainLuxi ChenDavid LiebnerJoal BeaneMark RubinsteinRaphael PollockClaire VerschraegenGabriel Tinoco

The Oncologist, oyad052, https://doi.org/10.1093/oncolo/oyad052
Published: 1 March 2023
 
Jonathan Trent, MD, PhD. Sylvester Comprehensive Cancer Center, Sarcoma Center, Miami, FL

Presentation to the Patient – Family Advocacy Network:  Use of Trabectedin in the Treatment of LMS (29 Jan 2023) Hosted by the NLMSF. 
Video recording: https://youtu.be/efuZXkaRncQ

 

2022

Molecular subtypes of leiomyosarcoma: Moving toward a consensus (2 Nov 2022)
https://onlinelibrary.wiley.com/doi/full/10.1002/ctd2.149

Landmark Series: A Review of Landmark Studies in the Treatment of Primary Localized Retroperitoneal Sarcoma 
(2 Nov 2022)  https://link.springer.com/article/10.1245/s10434-022-12517-w

CLINICAL TRIALS: TARGETED THERAPY (2 Aug 2022)
Phase II Clinical Trial of Eribulin–Gemcitabine Combination Therapy in Previously Treated Patients With Advanced Liposarcoma or Leiomyosarcoma
https://aacrjournals.org/clincancerres/article-abstract/28/15/3225/707113/Phase-II-Clinical-Trial-of-Eribulin-Gemcitabine?redirectedFrom=fulltext

Phase II Clinical Trial of Eribulin–Gemcitabine Combination Therapy in Previously Treated Patients With Advanced Liposarcoma or Leiomyosarcoma (2 Aug 2022)

A phase Ib/II study of the combination of lenvatinib (L) and eribulin (E) in advanced liposarcoma (LPS) and leiomyosarcoma (LMS) (LEADER): Efficacy updates. (2 Aug 2023)

 Retroperitoneal LMS Nomogram Model (3 Jul 2022)

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 (13 Jun 2022)

PRESS RELEASE NEWS  from Dr. Brian Van Tine about UNESBULIN: for LMS:  (3 Jun 2022)
https://ir.ptcbio.com/…/preliminary-results-presented…Preliminary Results Presented at ASCO Demonstrated Promising Clinical Efficacy with Unesbulin in Leiomyosarcoma Study

Surgical management strategy for leiomyosarcoma of Zone I-II inferior vena cava: A case series  (3 Jun 2022)   https://pubmed.ncbi.nlm.nih.gov/35665732/

Article by Dr. Matthew Hemming in the Journal of TRANSLATIONAL CANCER MECHANISMS AND THERAPY| 
Preclinical Modeling of Leiomyosarcoma Identifies Susceptibility to Transcriptional CDK Inhibitors through Antagonism of E2F-Driven Oncogenic Gene Expression (1 Jun 2022)
https://aacrjournals.org/clincancerres/article-abstract/28/11/2397/698931/Preclinical-Modeling-of-Leiomyosarcoma-Identifies?redirectedFrom=fulltextz
Note:  This research publication update relates to a research project being funded by the NLMSF being done by Dr. Matt Hemming 

Preoperative Differentiation of Uterine Leiomyomas and Leiomyosarcomas: Current Possibilities and Future Directions (13 Apr 2022)
Brief Summary of the research update: https://pubmed.ncbi.nlm.nih.gov/35454875/
The complete publication (1 Apr 2022): 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.

What Clinical Trials Are Needed for Treatment of Leiomyosarcoma? (11 Mar 2022)

Proteomic and Metabolomic Profiling in Soft Tissue Sarcomas
Current Treatment Options in Oncology (2022)Cite this article (16 Feb 2022)

Surgical resection of leiomyosarcoma of the inferior vena cava: A case series and literature review (Dec 2021)

Relationships between highly recurrent tumor suppressor alterations in 489 leiomyosarcomas ( 1 Aug 2021)

2021:

Large scale multiomic analysis suggests mechanisms of resistance to immunotherapy in leiomyosarcoma.(ASCO Abstract 2021)

Multiomic analysis to reveal distinct molecular profiles of uterine and nonuterine leiomyosarcoma. (ASCO Abstract 2021)

2020:

2019: 

Epub 2019 Jun 4.

Genomic Evolutionary Patterns of Leiomyosarcoma and Liposarcoma

Ali Amin-Mansour 1Suzanne George 2Stefano Sioletic 3Scott L Carter 1Mara Rosenberg 1Amaro Taylor-Weiner 1Chip Stewart 1Aaron Chevalier 1Sara Seepo 1Adam Tracy 1Gad Getz 1Jason L Hornick 3Marisa R Nucci 3Bradley Quade 3George D Demetri 2 4Chandrajit P Raut 5Levi A Garraway 1 2 6Eliezer M Van Allen 7 2 6Andrew J Wagner 8

Genomic Evolutionary Patterns of Leiomyosarcoma and Liposarcoma – PubMed (nih.gov)

Full Journal article:   Genomic Evolutionary Patterns of Leiomyosarcoma and Liposarcoma | Clinical Cancer Research | American Association for Cancer Research (aacrjournals.org)

2018:

Soft Tissue and Uterine Leiomyosarcoma
Suzanne George,  César Serrano, Martee L. Hensley, and Isabelle Ray-Coquard (10 Jan 2018)

Non-Uterine Research Updates-

Soft Tissue Sarcoma