Circulating DNA Analysis for Soft Tissue Sarcoma

Overseen By Albiruni Razak, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Prior malignancy, Metastases, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 14

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study will collect blood and tumor tissue samples from patients with soft tissue sarcoma to look at circulating tumor deoxyribonucleic acid (DNA). When tumor cells are damaged or die, DNA from the tumor cells are released into the blood stream as the cells break down. This is called circulating tumor DNA. Circulating tumor DNA is an important biomarker that may be used in cancer detection, prediction of treatment response, and disease monitoring.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the idea that Circulating DNA Analysis for Soft Tissue Sarcoma is an effective treatment?

The available research shows that Circulating DNA Analysis can help monitor soft tissue sarcoma by detecting changes in tumor DNA found in the blood. This method allows doctors to track the disease without invasive procedures. For example, one study found that when patients were in full remission, no tumor DNA was detected, but it was present when the disease was active. This suggests that the treatment can help in early detection of recurrence and in monitoring how well a patient is responding to treatment. However, the research also indicates that this method is not yet perfect, as it did not detect tumor DNA in all cases. Compared to traditional methods, Circulating DNA Analysis offers a less invasive way to gather information about the tumor, which could lead to quicker treatment decisions and potentially better outcomes for patients. ^{1 2 3 4 5}

What safety data exists for circulating DNA analysis in soft tissue sarcoma treatment?

The research does not directly address safety data for circulating DNA analysis in soft tissue sarcoma treatment. However, it highlights the potential of liquid biopsy as a minimally invasive method to monitor tumor genetics and disease state, which could reduce the need for invasive tissue biopsies. The studies suggest that while liquid biopsy methods, including circulating tumor DNA analysis, are promising, there are technical challenges and limitations, such as poor concordance with solid tumor genomic profiling, that need to be addressed before widespread clinical implementation. No specific safety concerns are mentioned in the provided abstracts. ^{1 3 4 6 7}

Is circulating DNA analysis a promising treatment for soft tissue sarcoma?

Yes, circulating DNA analysis is promising for soft tissue sarcoma because it can help detect tumors early, monitor treatment response, and identify recurrences before they are visible on scans. This could lead to earlier and more effective treatment decisions, potentially improving patient survival. ^{1 2 5 8 9}

Research Team

Albiruni Razak, MD

Principal Investigator

Princess Margaret Cancer Centre

Eligibility Criteria

This trial is for adults over 18 with high-risk soft tissue sarcoma who are suitable for surgery and radiotherapy. They must have a performance status indicating they can care for themselves, have tumor tissue from a biopsy, and be able to consent to the study. Those with other recent cancers, metastases, serious illnesses affecting compliance or planned chemotherapy are excluded.

Inclusion Criteria

Patients must have archival tissue from the diagnostic biopsy available.

Ability to understand and willing to sign a written informed consent document and comply with study requirements.

I have a confirmed diagnosis of a high-risk sarcoma in my limbs or abdomen.

Exclusion Criteria

My cancer has spread to nearby lymph nodes or other parts of my body.

I have not had cancer in the last 5 years, except for skin or early cervical cancer.

I do not have any serious illnesses that would stop me from following the study's requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Sample Collection

Blood and tumor tissue samples are collected for DNA testing

Prior to planned radiation treatment

1 visit (in-person)

Post-Surgery Monitoring

Blood samples are collected 2-4 weeks after cancer surgery

2-4 weeks

1 visit (in-person)

Long-term Follow-up

Blood samples are collected every 12 weeks after surgery for up to 2 years to monitor ctDNA levels

2 years

Every 12 weeks (in-person)

Treatment Details

Interventions

• Archival tumor tissue collection and blood draws

Trial Overview The study is collecting blood samples and archival tumor tissues from patients to analyze circulating tumor DNA (ctDNA). This ctDNA may help in detecting cancer, predicting how well treatments might work, and monitoring the disease's progression during treatment.

Participant Groups

Group I: Soft Tissue Sarcoma Experimental Treatment 1 Intervention

A sample of archival tumor tissue will be collected. Blood samples (about 20-30 mL or 1-2 tablespoons each sample) will be taken: * Prior to planned radiation treatment * 2-4 weeks after cancer surgery * Every 12 weeks after surgery for up to 2 years

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Mount Sinai Hospital, Canada

Collaborator

Trials

210

Recruited

70,700+

The Hospital for Sick Children

Collaborator

Trials

724

Recruited

6,969,000+

Findings from Research

In a study of 64 patients with soft tissue sarcomas (STS), circulating free DNA (cfDNA) levels were significantly higher and more fragmented compared to patients in remission and healthy controls, indicating its potential as a diagnostic biomarker.

The study established sensitive assays to detect specific genetic alterations in circulating tumor DNA (ctDNA) for certain types of liposarcomas, which correlated with clinical outcomes and could help in monitoring tumor activity and detecting recurrences, suggesting a need for closer follow-up in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genotyping of circulating cell-free DNA enables noninvasive tumor detection in myxoid liposarcomas. Braig, D., Becherer, C., Bickert, C., et al.[2019]

In a study involving 25 plasma samples from 3 patients with soft tissue sarcomas (STS), circulating tumor DNA (ctDNA) levels were found to correlate with tumor burden, allowing for early detection of recurrences and monitoring of treatment response.

The quantification of ctDNA showed that it could indicate minimal residual disease during remission and significantly decline after effective treatments, suggesting that it may help guide timely therapeutic decisions and potentially improve patient survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individualized Mini-Panel Sequencing of ctDNA Allows Tumor Monitoring in Complex Karyotype Sarcomas. Braig, D., Runkel, A., Eisenhardt, AE., et al.[2022]

Liquid biopsy presents a promising, minimally invasive alternative to traditional tissue biopsies for monitoring sarcomas, which are diverse and complex tumors, allowing for more accurate and dynamic assessment of the disease.

Recent advancements in liquid biopsy technologies have identified various blood-based tumor components, such as circulating tumor cells and cell-free nucleic acids, which could enhance precision medicine approaches in treating sarcoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of liquid biopsy in bone and soft tissue sarcomas: Present and future. Li, X., Seebacher, NA., Hornicek, FJ., et al.[2020]

In a study of 24 advanced soft tissue sarcoma patients, circulating tumor DNA (ctDNA) was detected in 18, but the concordance between ctDNA and solid tumor genomic profiling was low, particularly for copy number alterations.

The highest concordance rates were observed in leiomyosarcoma patients, with a 76% agreement for short variant alterations when tumor fractions were detectable, suggesting that ctDNA profiling may not be broadly applicable for all sarcoma types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Evaluation of the Concordance of Commercial Circulating Tumor DNA Alterations with Tumor-Based Sequencing across Multiple Soft Tissue Sarcoma Subtypes. Demoret, B., Gregg, J., Liebner, DA., et al.[2020]

In a study of 29 patients with various subtypes of soft tissue sarcomas (STS), circulating tumor DNA (ctDNA) was detected in only 17% of cases, indicating that while it may help track some patients, it is not consistently reliable for monitoring STS progression.

The analysis showed that perioperative cell-free DNA (cfDNA) levels were elevated but did not correlate with important clinical factors like tumor size or recurrence, suggesting limited diagnostic value for cfDNA in STS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Circulating Nucleic Acid Characteristics of Non-Metastatic Soft Tissue Sarcoma Patients. Eastley, N., Sommer, A., Ottolini, B., et al.[2021]

Liquid biopsies, which analyze circulating tumor cells and circulating tumor DNA in blood, offer a promising alternative to traditional tissue biopsies for diagnosing and monitoring sarcomas, a rare and heterogeneous group of tumors.

While initial results for using liquid biopsies in sarcomas are encouraging, there are still technical challenges that need to be overcome before they can be widely implemented in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liquid Biopsies in Sarcoma Clinical Practice: Where Do We Stand? van der Laan, P., van Houdt, WJ., van den Broek, D., et al.[2023]

The tumor biobank at the University of Siena has been crucial for cancer research since 1985, collecting a diverse range of biological samples such as DNA, RNA, tissues, and blood to enhance patient care.

This extensive collection of samples and clinical data supports the development of new strategies for cancer treatment, highlighting the importance of biobanks in advancing oncological research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of a tumor bank: a thirty years experience of the University of Siena (Italy). Corso, G., Garosi, L., Marrelli, D., et al.[2015]

The study utilized the CellSieve™ microfiltration system to detect circulating tumor cells (CTCs) in both mouse models and human patients with high-grade sarcomas, showing that CTC presence correlates with disease burden and can indicate clinically silent metastases.

In human patients, CTCs were found at diagnosis and decreased with effective treatment, suggesting that monitoring CTC levels could help predict metastatic relapse even before visible symptoms appear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Size-based detection of sarcoma circulating tumor cells and cell clusters. Hayashi, M., Zhu, P., McCarty, G., et al.[2019]

In a study of 12 soft tissue sarcoma patients, structural variants were successfully detected in 91.6% of tissue samples and 50% of matched plasma samples using a sarcoma-specific targeted next generation sequencing (NGS) panel.

The findings suggest that circulating tumor DNA (ctDNA) analysis can be a valuable tool for diagnosing and monitoring sarcomas, indicating a need for further research in larger patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of Structural Variants in Circulating Cell-Free DNA from Sarcoma Patients Using Next Generation Sequencing. Mc Connell, L., Gazdova, J., Beck, K., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Genotyping of circulating cell-free DNA enables noninvasive tumor detection in myxoid liposarcomas. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Individualized Mini-Panel Sequencing of ctDNA Allows Tumor Monitoring in Complex Karyotype Sarcomas. [2022]

3. Ireland pubmed.ncbi.nlm.nih.gov

Application of liquid biopsy in bone and soft tissue sarcomas: Present and future. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Prospective Evaluation of the Concordance of Commercial Circulating Tumor DNA Alterations with Tumor-Based Sequencing across Multiple Soft Tissue Sarcoma Subtypes. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The Circulating Nucleic Acid Characteristics of Non-Metastatic Soft Tissue Sarcoma Patients. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Liquid Biopsies in Sarcoma Clinical Practice: Where Do We Stand? [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Assessment of a tumor bank: a thirty years experience of the University of Siena (Italy). [2015]

8. United States pubmed.ncbi.nlm.nih.gov

Size-based detection of sarcoma circulating tumor cells and cell clusters. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Detection of Structural Variants in Circulating Cell-Free DNA from Sarcoma Patients Using Next Generation Sequencing. [2020]