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Whats New in Leiomyosarcoma Research?

 

Leiomyosarcoma Research Articles and News- Updates:

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Adjuvant gemcitabine-docetaxel chemotherapy for stage I uterine leiomyosarcoma: Trends and survival outcomes

The link to the information update:

Johns Hopkins researchers say they’ve unlocked key to cancer metastasis and how to slow it: http://www.baltimoresun.com/health/bs-hs-cancer-trigger-20170625-story.html

Phase 3 results trabectedin or dacarbazine in ULMS-

Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial.

Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study.

https://www.ncbi.nlm.nih.gov/pubmed/28654633#

Over – expressed  P R A M E  is a potential immunotherapy target in sarcoma subtypes, including LMS –  please read on . . .

http://www.researchtopractice.com/STSU117/Video/3

ASCO 2017 Sarcoma/LMS Related Research Presentations
The meeting slides through the ASCO Meeting Library

Pembrolizumab Active in Few Soft Tissue, Bone Sarcoma SubtypesPembrolizumab shows antitumor activity in osteosarcoma and undifferentiated pleomorphic sarcoma, but not other types of soft tissue sarcomas.

Systemic Therapy for Soft Tissue Sarcoma: Proposals for the Optimal Use of Pazopanib, Trabectedin, and Eribulin: https://www.ncbi.nlm.nih.gov/pubmed/28547734

The management of soft tissue tumours of the abdominal wall

European Journal of Surgical Oncology   ||   Review Article

Small, superficial, indeterminate soft-tissue lesions as suspected sarcomas: Is primary excision biopsy suitable

Skeletal Radiology

Here is an interesting article to discuss with your oncologist.Some of the medical terminology definitions are provided to help you with the information provided in the article.

Multinuclear NMR and MRI reveal an early metabolic response to mTOR inhibition in sarcoma

Link: https://www.ncbi.nlm.nih.gov/pubmed/28386017

Definitions:  Rapalog: Analogs of rapamycin (MTOR inhibitor) Immunosupressant/ anti-cancer properties of rapamycin
Glycosis –  the enzymatic breakdown of clucose or other carbohydrate by wan of phosphate derivatives
Phenotypic –  detectable expression of the genotype and environment constituting visible characteristics . .  .
Let me know if you need more information to better understand this article and I will try to help you.

May 19, 2017:

A recent article by Dr. George Demetri and Dr. J. Verweij on Latruvo and Soft Tissue Sarcoma: https://connection.asco.org/magazine/current-controversies-oncology/providing-olaratumab-patients-soft-tissue-sarcoma-practice?j=39242036&sfmc_sub=976772672&l=18416124_HTML&u=667352132&mid=10831468&jb=49&et_cid=39242036&et_rid=976772672&linkid=Providing+Olaratumab+to+Patients+With+Soft+Tissue+Sarcoma%3a+A+Practice+Dilemma

Here is an interesting article for possible further discussion with your oncologist/ medical care team: “Histotype” – defined:  Any of a range of tissue types that arise during the growth of a tumor origin.

Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas

Current and ongoing immunotherapy treatments hold promise  for sarcomas – in particular these studies are looking at Leiomyosarcomas and pleomorphic sarcoma:http://www.news-medical.net/news/20170503/Study-suggests-how-existing-and-emerging-immunotherapy-treatments-could-be-successful-for-sarcomas.aspx

A Phase II Study of T-VEC plus Pembrolizumab Immunotherapy in Patients with Sarcoma- Currently recruiting participants- Read more at: https://www.mskcc.org/cancer-care/clinical-trials/16-1534

Axitinib and Pembrolizumab in Subjects With Advanced Alveolar Soft Part Sarcoma and Other Soft Tissue Sarcomas: This study is currently recruiting participants – to learn more, visit  https://www.clinicaltrials.gov/ct2/show/NCT02636725?term=axitinib+%28Inlyta%29+and+pembrolizumab&rank=1

Immunotherapy with single agent nivolumab for advanced leiomyosarcoma of the uterus: Results of a phase 2 study-Learn more at https://www.ncbi.nlm.nih.gov/pubmed/28440953

Exceptional Responder to Pembrolizumab Guides Immunotherapy Progress in Leiomyosarcoma – See more at: http://www.onclive.com/web-exclusives/exceptional-responder-to-pembrolizumab-guides-immunotherapy-progress-in-leiomyosarcoma#sthash.5EC09Foa.dpuf

Further clarification of the “rare cancer cell line project” announced on a previous E-Bulletin. The cancer cell line project is a collaborative effort of the Broad Institute of MIT/Harvard and the Rare Cancer Research Foundation, a non-for profit foundation.  This project was created because both parties felt that there were not enough “living” cancer cell lines of rare cancer in existence and the lack of sufficient cell line was hindering the advancement of research on these rare tumors. The Project does receive some funding from the NIHA little more background information would be helpful.  The Broad Institute of MIT and Harvard was launched in 2004 to improve human health by using genomics to advance our understanding of the biology and treatment of human disease, and to help lay the groundwork for a new generation of therapies.  If you wish you can learn more about the Broad Institute of MIT and Harvard on their official website https://www.broadinstitute.org.  More information about the Rare Cancer Research Foundation can be obtained on their website.The Cancer Cell line Project is not a new project.  However, inclusion of Leiomyosarcoma into the small group (8 previous rare cancers in the project) is NEW.  The Cancer Cell line Project was looking to add a few more rare cancers to those already in the project.  The NLMSF working with the RCRF was able to get LMS accepted as one of the new rare cancers in the project.  Our application had to be accepted by both the RCRF and the Broad Institute.The Cancer Cell Line Project is under the purview of the Institutional Review Board (IRB) of the Broad institute.  In accordance with FDA regulations, and IRB which is an independent entity, had the authority to approve, require modifications in (to secure approval) or disapprove research.  This group review serves an important role in the protection of the rights and welfare of human research subjects.  The IRB provides ongoing oversight of the research to ensure compliance.The Cancer Cell Line Project is not in the in a strict definition a specific research project.  Its goal to develop “living” rare cancer lines (tissue cell cultures) that they can then genomically characterize and then share with other researchers throughout the world for use in their research endeavors.  Those researchers if they have the means to do so can also continue to “grow” the tumor cell lines in their labs for future research.  A created tumor cell line is truly remarkable thing.  The gift to patients that keeps on giving.As most of you probably already know, there is an LMS Tissue Bank at Dr. Matt Van de Rijn’s lab at Stanford.  This is one of if not the largest collections of  LMS patient tumor samples in the world.  It is a tremendous resource for LMS researchers.  The NLMSF strongly supports this tissue bank and encourages all LMS patients to have paraffin block samples of their tumors sent to this tissue bank for use in current and future research projects.  Our foundation has helped to fund research in Dr. van de Rijn’s lab for many years and he recently graciously accept to become a member of the Medical Advisory Committee of our Foundation.The Broad Institute Cell Line Project does not conflict or compete with the LMS Tissue Bank at Stanford.  These are complementary projects that in different ways will help to advance LMS research.  The Cancer Cell Lines developed at the Broad Institute require fresh tumor tissue samples for their creation.  Living cancer cell lines cannot be created from tissue stored in paraffin block.  That is why tumor cell line creation  is not only difficult and costly,  but also requires coordination at many levels.  That is why so few tumor cell lines exist.The beauty of the collaborative project of the RCRF and the Broad Institute is that do to funding that they have been able to attain they have made the acquisition of a sample fresh of a patient’s tumor tissue obtained at the time of surgery or biopsy at any hospital in the United States as easy as possible.
Other than giving consent to donate a small portion of their tumor tissue sample,  a portion not needed for their treatment, the process proceeds without any involvement or effort by the patient.  The patient’s tumor tissue sample is de-identified before it is sent to the Broad Institute.  The researchers creating the tumor cell line will know no personal information about the patient who donated the tissue.  The patient will not receive any information back about their tumor or any future research done on their tumor.The choice to donate a sample of their tumor tissue to the Cancer Cell Line Project is solely and completely up to the patient.  It is an on-line process.  The NLMSF’s involvement is only to inform you that the project exists.  We will have no knowledge of who chooses to participate.  The NLMSF will receive no financial gain or other compensation from the RCRF  or the Broad institute.

RESEARCH ALERT: BROUGHT TO YOU BY IGNYTA PHARMACEUTICALS:

STARTRK-2 Clinical Trial Currently Recriting Participants

2 hrs · 
This Phase 2 clinical trial of entrectinib, IGNYTA’s oral tyrosine kinase inhibitor targeting solid tumors that possess activating alterations to the NTRK1, NTRK2, NTRK3, ROS1 or ALK genes. The trial is currently recuriting recruiting participants with fusions of the ROS1, ALK, andNTRK genes. For more information, visit the STARTRK-2 website:

STARTRK-2 Facebook Page:

The National Leiomyosarcoma Foundation announces an exciting new collaborative partnership with the Rare Cancer Research Foundation (RCRF), which will allow Leiomyosarcoma (LMS) patients to DIRECTLY DONATE their FRESH TUMOR TISSUE to be used for the creation of new LMS TUMOR CELL LINES, which can be used for future LMS research by researchers throughout the world.The RCRF has created a program with the Broad Institute of MIT and Harvard dedicated to the creation of new tumor cell lines of rare cancers called  The Cancer Cell Line Project”. Only a limited number of rare cancers are and will be included in this project. Cell Lines mean:  tumor tissue in vitro (Petri dish) for analysis and testing to continue to grow more tumor tissue/cells for further research study initiatives. For more information: http://eepurl.com/cKoS0z

VIDEO BY DR. SETH POLLACK: A special video presentation by Dr. Seth Pollack on a small clinical  trial:  Deploying An Ancient Defense to Kill Cancer.”    Registration for Sarcoma/LMS Patient-Family Education Program at the Fred Hutchinson Cancer Center
with Dr. Pollack is through www.nlmsf.org – under Patient Education.
The link to watch the video:

Community Healthcare Systems Seeking To Incorporate Genetic Testing Into Cancer Care They Offer:

The Wall Street Journal (3/6, Kincaid, Subscription Publication, 6.37M) reports community healthcare systems are seeking to incorporate genetic testing into the cancer care they provide. Richard Schilsky, chief medical officer of the American Society of Clinical Oncology, points out that most patients with cancer receive care in a community setting, though testing tumors for multiple genetic mutations has been more prevalent in academic settings where oncologists have the resources to interpret complicated results.
CHECK WITH YOUR OWN ONCOLOGIST IF YOU ARE INTERESTED IN PURSUING THIS.

Identification of microRNA biomarkers for response of advanced soft tissue sarcomas to eribulin: Translational results of the EORTC 62052 trial-The expression level of specific microRNAs in soft tissue sarcoma tissue samples might predict response to eribulin. Click here for the full study

Optimizing Local Control in High-Grade Uterine Sarcoma: Adjuvant Vaginal Vault Brachytherapy as Part of a Multimodal Treatment:https://www.ncbi.nlm.nih.gov/pubmed/28174295

The Value of Adaptive Preoperative Radiotherapy in Management of Soft Tissue Sarcoma: https://www.ncbi.nlm.nih.gov/pubmed/28169043

Central venous access related adverse events after trabectedin infusions in soft tissue sarcoma patients; experience and management in a nationwide multi-center study: https://www.ncbi.nlm.nih.gov/pubmed/28163887

OncLive Insights Videos from three research oncologists
http://www.onclive.com/insights/sts-monoclonal-antibodies/final-thoughts-on-sts

Seth M. Pollack, assistant professor, Division of Oncology, University of Washington, and attending physician, Seattle Cancer Care Alliance, discusses the role of radiomics in the treatment landscape of sarcoma. Radiomics, which is a fairly new field of study, quantifies complex aspects of tumor images related to tumor biology. Prior research has validated its use in predicting patient outcomes in lung and head and neck cancers. According to Pollack, sarcoma may be an ideal treatment landscape in which to study radiomics because so many patients with this disease already undergo MRIs as part of their overall treatment. This essentially provided the rationale for examining radiomics in this particular patient population. In his research, Pollack found that, after patients’ tumor images were analyzed through a list of radiomic features, the model that was made to predict outcomes was extremely accurate. In fact, it was found to be more accurately predictive than other standard factors, such as those based on tumor grade, tumor size, and other clinical features. – See more at: http://www.onclive.com/onclive-tv/dr-pollack-on-the-role-of-radiomics-in-sarcoma#sthash.XFZMhYEU.dpuf

Response to anti-PD1 therapy with nivolumab in metastatic sarcomas: https://www.ncbi.nlm.nih.gov/pubmed/28169043

2016 CTOS Annual Meeting in Libson, Portugal: The National Leiomyosarcoma Foundation represented the LMS Community  at the 2016 Connective Tissue Oncology Conference in Lisbon, Portugal. Dr. Achee and I traveled to Portugal on our own to represent LMS patients and their families, as is the case for all conferences as well as patient programs hosted in cities across the United States and abroad by the Foundation. The landmark $1 million dollar Collaborative International LMS Research Project, initiated by the Liddy Shriver Initiative, was discussed at a special session hosted by the Liddy Shriver Initiative, who brought together the esteemed researchers for such a large scale research project, which launched in August. This session was to brief other researchers at the conference who also have an interest in LMS research efforts and  perhaps already involved in research projects of their own. This  is truly  a “gift of hope” on a global scale for the LMS community. We are so thankful for the opportunity, and grateful to Bruce and Beverly Shriver  – the Liddy Shriver Initiative – for bringing us all together for such a promising research breakthrough potential and ultimately to make a difference for hopeful acceleration of treatment advancements for the future. We salute all who could come together to support the vision and mission of this particular Liddy Shriver initiative.  The Shriver family has for so many years,  contributed so much to the Sarcoma Community in tribute to their daughter who was lost to Ewings Sarcoma.  Their tireless work promoting research ideas and endeavors, and bringing together key researchers for each project for various sarcoma subtypes has been truly the definition of “proactive passion.” It goes without saying that they are highly respected by the medical research community. The National Leiomyosarcoma Foundation will receive updates on the inroads made from this recently co-funded LMS research project as well as other continuous updates on medical research efforts,  clinical trials, and related youtube presentations through www.nlmsf.org.  Additionally,  your contribution to the website through your voice – adds hope for patients and families everywhere –  your voice matters! We thank you all for you continued interest, support, and contribution to the efforts being made by foundations that honor you, represent you, and work tirelessly on behalf of the LMS Community.The link below is a briefing of the LMS research project  – a brief summary of the initial  ACOR announcement of this project in August and Sept. powerpoint Lisbon Portugal Briefing on the LMS Collaborative International LMS Research Project:  updated-maximizing-therapeutic-response-in-leiomyosarcoma

Scientists develop cancer therapy that reduces toxic chemotherapy effects. https://www.mdlinx.com/oncology/article/670?utm_source=in-house&utm_medium=message&utm_campaign=lf-onc-nov16

FDA Approves Merck’s KEYTRUDA (pembrolizumab) in metastatic non-small cell lung cancer (NSCLC) for First-Line treatment of patients whose tumors have high programmed death-ligand 1 (PD-L1) expression with no genomic tumor aberrations (EGFR or ALK ). http://www.mercknewsroom.com/news-release/prescription-medicine-news/fda-approves-mercks-keytruda-pembrolizumab-metastatic-nsclc-

FDA Approves Lartruvo for adults with a subtype of STS for which an anthracycline-containing regimen is pertinent, and which cannot be cured with radiotherapy or surgery. Approval was granted based on safety and effectiveness data from the Phase 2 JGDG trial of 133 patients. https://www.drugs.com/history/lartruvo.html

The FDA has approved olaratumab (Lartruvo) for soft-tissue sarcoma when used with doxorubicin (Adriamycin) as first-line treatment. (In other words, you don’t have to do other drugs first.) This is the first “first-line” treatment approved for sarcoma in 40 years. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm525878.htm

Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomized, double-blind, placebo-controlled, phase 2 trial. Patients and Families- Click the Link “The Lancet Oncology”   to read the rest of the article.  This is important information to discuss with your oncologist /oncology medical team. http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30507-1/abstract

Neoadjuvant anthracycline plus ifosfamide chemotherapy was linked to significantly increased survival rates in patients with soft tissue sarcomas located in the torso or extremities who were at high risk of recurrence. Click here for more information.

Short, full-dose adjuvant chemotherapy (CT) in high-risk adult soft tissue sarcomas (STS): long-term follow-up of a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. Click here for the abstract.

Trabectedin Improves PFS vs Best Supportive Care in Sarcoma

Trabectedin significantly improves progression-free survival in patients with pretreated advanced soft tissue sarcomas.

Click here for more information.

High expression of proteasome activator complex subunit 1 (PSME1) is associated with poor survival in soft tissue leiomyosarcoma patients and might be used to predict the likely course of the disease.

Definitions of a few of the terms in order of their appearance in this article:
Spectrometry –  a measuring instrument for the study of the interaction of matter involving molecules or other material related to the study (and involving wavelength or frequency).
Proteasome –  cellular protein – damaged/degraded
immunoproteasome –  a proteasome assembled in response to pro-inflammatory signals.
Microarrays – molecules (or fragments), usually of DNA or protein, attached in a pattern for use in biochemical or genetic analysis.
Covariates –   known, controlled variables that may affect the outcome of a clinical trial.
Immunohistochemistry –  demonstration of specific antigens (harmful antibodies) in tissues by the use of dyes or fluorescent markers.
Histological –  study of microscopic tissue structures
Biomarker –  a distinctive biological indicator of a disease process –  biochemical, genetic, or molecular characteristic.

Click here for more information on the study.

The BMC ( British Journal of Cancer) features an article on molecular classification of uterine leiomyosarcomas. Their data supports the existence of distinct leiomyosarcoma subgroups which are clinically associated with tumor grades. These findings will help advance the classification of leiomyosarcomas and promote more individualized treatments. Click here for the abstract.

The Liddy Shriver Sarcoma Initiative is funding a $1 million international collaborative grant for leiomyosarcoma (LMS) research. The two-year project will enlist investigators from France, Germany, and the United States with the aim of identifying new therapies and starting clinical trials for the most prevalent and clinically challenging types of LMS.

The Grant Announcement  – “$1 Million Study on Leiomyosarcoma Set to Begin” –http://bit.ly/2bcT1iq

The Experimental Plan Article – Maximizing Therapeutic Response in Leiomyosarcoma –http://bit.ly/2aSLxR2

For more information, visit the website http://sarcomahelp.org/leiomyosarcoma-collaborative-research.htm

A study exploring chromosomal abnormalities in uterine smooth muscle tumors found that uterine leiomyomas with abnormal nuclei and leiomyosarcomas are closely related. Click here for the abstract.

A study published by the BJC found that antiapoptotic (anti-cell death) Bc1-2 family proteins are highly expressed in soft tissue leiomyosarcomas and inhibition of these proteins increases tumor sensitivity to chemotherapy. Click here for the abstract.

The journal BMC Cancer features an article about Trabectedin and inoperable or recurrent soft tissue sarcomas. Their data suggest there may be some benefit in using trabectedin, particularly in patients with leiomyo- or liposarcoma who failed standard of care agents.Click here to view abstract or click here to link to free full text article.

Dr. Hussein Tawbi, formerly of the Pittsburgh Cancer Research Center and currently at MD Anderson, has pioneered two important treatment advancements not only in Sarcoma but also in Melanoma. Tawbi is leading a three-year study on the effectiveness of pembrolizumab. Dr. Tawbi spoke in 2013 at the National Leiomyosarcoma Foundation’s conference for patients and families.  Click to read full article at the Pittsburgh Business Times.

Eli Lilly and Company Clinical Trial for soft tissue sarcoma involving their developing of Olaratumab in combination with Doxorubicin for patients with advanced metastatic disease can be viewed here: https://clinicaltrials.gov/ct2/show/NCT02451943

Doctors discuss liver problems with Trabectedin (Yondelis), which may be the second or third drug tried in leiomyosarcoma patients. This interview was done before the drug got  FDA approval. http://www.onclive.com/peer-exchange/soft-tissue-sarcoma/trabectedin-in-soft-tissue-sarcoma

There’s excitement that palbociclib, approved by the FDA for some types of breast cancer, may be useful in other cancers. It inhibits CDK4 & 6, which also are present in LMS. The following article says we need more research before we get too excited: http://www.healthnewsreview.org/news-release-review/new-breast-cancer-drug-may-effective-types-cancer/

Promising results from early investigation of a new injectable agent was developed at MIT that creates a “fluorescent probe” to image cancer cells to aid in surgical removal of all cancerous tissue on the first attempt. More on Lumicell’s product: http://www.medicalnewstoday.com/articles/304776.php