Additional Insights in Dedifferentiated Liposarcoma With Richard F. Riedel, MD, and Candace L. Haddox, MD
Expert Perspectives
By Keira Smith
Published
As research in dedifferentiated liposarcoma (DDLPS) continues to advance, the importance of multidisciplinary collaboration and access to innovative therapies remains at the forefront of patient care. Recently, Dr. Richard Riedel of Duke Cancer Institute and Dr. Candace Haddox of Dana-Farber Cancer Institute co-chaired i3 Health’s DDLPS Task Force activity, which brought together a panel of experts to address the complexities of this rare and challenging sarcoma subtype. With new clinical trials underway and a growing understanding of the disease’s molecular landscape, Dr. Riedel and Dr. Haddox sat down to highlight promising research directions and insights in honor of Sarcoma Awareness Month in July.
Click the links below for the Task Force activity!
Understanding Dedifferentiated Liposarcoma
Dedifferentiated liposarcoma is a member of the soft tissue sarcoma family—rare cancers that present unique clinical challenges. DDLPS is among the most common subtypes, often coexisting with well-differentiated liposarcoma. Both are adipocytic tumors, typically arising in the retroperitoneum or extremities, and are characterized by MDM2 and CDK4 gene amplifications. These molecular features have become focal points for targeted drug development.
Despite these advances, DDLPS remains a heterogeneous disease. As Dr. Haddox explained, “There’s a lot of variability in how patients present, the location and aggressiveness of disease, and the pace of progression. This heterogeneity complicates clinical management and highlights the need for deeper understanding of treatment resistance, both to chemotherapy and targeted agents.”
Emerging Therapies and Clinical Trials
The landscape of DDLPS research is evolving, with several promising clinical trials underway. Dr. Haddox highlighted the STRASS 2 trial, a global study evaluating perioperative chemotherapy for patients with resectable retroperitoneal liposarcoma. “We’re eager to see whether chemotherapy as part of initial management can delay or prevent recurrence or metastasis,” she noted. Results are anticipated in the coming years, and clinicians are encouraged to refer eligible patients to participating centers.
Targeted therapies remain a major focus, given the prevalence of CDK4 and MDM2 amplifications in DDLPS. The BRIGHTLINE-1 trial, comparing brigimadlin to doxorubicin in advanced DDLPS, is expected to publish results soon. Additionally, combinations such as the programmed cell death protein 1 (PD-1) inhibitor cemiplimab with the CDK4 inhibitor palbociclib are under investigation.
Dr. Riedel pointed to the SARC041 trial, led by Dr. Mark Dickson at Memorial Sloan Kettering, which is evaluating abemaciclib versus placebo in advanced DDLPS. “This study has completed accrual, and we’re optimistic that targeting CDK4 could add a valuable option to our therapeutic arsenal,” he said.
Sarcoma Awareness Month: the Value of Multidisciplinary Care
Both experts emphasized the critical role of multidisciplinary care in DDLPS. “Given the rarity and complexity of these tumors, referral to high-volume centers with sarcoma expertise is essential,” Dr. Riedel advised. “We’re committed to partnering with community oncologists to ensure that patients benefit from the latest advances and collaborative decision making.”
Dr. Haddox echoed this sentiment, noting that individualized treatment planning is especially important when applying limited data from small trials to unique patient scenarios. She also highlighted ongoing research into the immune microenvironment, chromosomal complexity, and novel antibody-drug conjugates, all of which may shape future therapies.
Resources for Clinicians
The task force’s position statement and podcast offer a comprehensive overview of current management strategies and anticipated advances. “It’s a team effort, both in the clinic and in developing these resources,” Dr. Riedel concluded. “We hope they support clinicians in delivering the best possible care for patients with DDLPS.”
Key Takeaways
- Dedifferentiated liposarcoma is a rare, heterogeneous soft tissue sarcoma that poses significant clinical challenges due to its variable presentation and resistance to standard therapies.
- Molecular targets such as MDM2 and CDK4 amplifications are central to ongoing drug development, with several promising clinical trials (including STRASS 2, BRIGHTLINE-1, and SARC041) expected to shape future treatment paradigms.
- Multidisciplinary care at high-volume sarcoma centers is essential for optimal management, and collaboration with community oncologists ensures patients have access to the latest advances.
- Continued research into the tumor microenvironment, chromosomal complexity, and novel therapeutic approaches—including antibody-drug conjugates—offers hope for improved outcomes.
About the Speakers
Richard F. Riedel, MD, is a Professor with tenure in the Division of Medical Oncology at Duke University Medical Center and the Associate Director of Clinical and Translational Research for the Duke Sarcoma Program. His clinical practice is dedicated to the care of patients with bone and soft tissue sarcoma, and his research interests lie in identifying novel therapies for these patients. Dr. Riedel is a member of the National Comprehensive Cancer Network (NCCN) Soft Tissue Sarcoma Guidelines Panel member and the NCCN Gastrointestinal Stromal Tumor (GIST) Guidelines Panel, and he is active in educational initiatives for sarcoma treatment.
Candace L. Haddox, MD, is a Physician at Dana-Farber Cancer Institute and an Instructor in Medicine at Harvard Medical School. She specializes in the treatment of sarcomas, including soft tissue sarcoma, GIST, bone cancers, and uterine sarcoma. Dr. Haddox leads clinical trials in Dana-Farber’s sarcoma group and early phase clinical trials program. Her research focuses on identifying and developing novel targeted therapies and immunotherapies across subtypes of sarcoma and understanding mechanisms of treatment resistance.