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New Approaches to Managing Difficult-to-Treat Sarcomas

July 2017

A malignant tumor of mesenchymal origin, myxoid liposarcoma usually occurs in the extremities and is the second most common type of liposarcoma, accounting for about 30% to 35% of these cancers.1 Liposarcoma, among the most common soft tissue tumor subtypes of sarcoma, represents about 15% of sarcomas, or about 2,000 cases per year.2 Myxoid liposarcoma is 1 among several categories of the disease, which are classified based on histology, molecular characteristics, and growth patterns.1, 3 Liposarcomas can also rarely manifest as a combination of morphologies (mixed liposarcomas).1 The American Cancer Society estimates that in 2017 about 12,390 patients in the United States will be diagnosed with and about 4,990 will die from soft tissue sarcomas.4 When gastrointestinal stromal tumors, the most common sarcoma of the GI tract, are included, the total yearly incidence rises by about another 5,000 to 7,000 cases.

Myxoid liposarcoma have round to oval mesenchymal cells, small signet ring lipoblasts, and a rich network of capillaries in the myxoid stroma. These tumors normally grow slowly and present as a painless, nonulcerating enlarging mass deep in the soft tissue of the extremities. They can also spread to serosal surfaces, bones, abdominal cavity, and other soft tissues.1 The round cell component determines their aggressiveness. Myxoid liposarcomas possessing 5% or more round cells have an unfavorable prognosis. More than 90% of myxoid liposarcomas contain a particular chromosomal translocation, t(12;16) (q13:p11), that generates a FUS-DDITR (TLS-CHOP) fusion gene. TLS-CHOP produces a hybrid protein believed to induce malignant transformation.1, 2, 5 Myxoid liposarcomas can also harbor mutations in the catalytic subunit of phosphatidylinositol 3-kinase (PI3K), a growth regulatory protein. Patients with PI3K subunit mutations have shorter disease-specific rates of survival than do those with the normal catalytic subunit.1

July-2017-Cancer-Care-Consult-Feature-Article-Main-Image-CSC
— A University of Minnesota Health staff member reviews team scheduling. Sarcomas, like many cancers, are best managed through a team-oriented, multimodal approach.

Myxoid liposarcoma is best managed with a team-oriented, multimodal treatment approach.2, 5 Surgery with or without radiation therapy is the standard treatment. Presurgical radiation therapy can improve outcomes, as a recent small study revealed. Among 11 patients treated at University of Minnesota Health locations, those who received a preoperative regimen of radiation therapy (50 Gy per week for 5 weeks) followed by surgery had good responses.6 The approach illuminates the differences observed between imaging and histological analyses and allows for more effective surgery.

Even with surgery, however, about 40% of patients relapse and require additional treatment, with chemotherapy becoming another option. Determining the best chemotherapeutic agent to use in patients who relapse can be difficult. First-line chemotherapies include but are not limited to doxorubicin (with or without ifosfamide), gemcitabine, or trabectedin.1, 5 As a recent study suggests, it may be possible to predict long-term outcomes of soft tissue sarcomas as early as after a single cycle of chemotherapy by evaluating changes in PET-CT scan activity. This may allow changes in therapy earlier than would otherwise be possible.7

Recent studies of gene expression patterns in other types of soft tissue tumors suggest that expression patterns may correlate better with tumor biological behavior than histology and allow targeting of specific genes for more effective chemotherapy.8,9 Different treatment regimens for soft tissue sarcomas are also being explored in clinical trials. Trials of new agents for sarcomas, including liposarcoma, are underway for patients with newly diagnosed and recurrent disease. (See Specialty Updates)

References

  1. Manji GA, Schwartz GK. Managing Liposarcomas: Cutting through the fat. J Oncol Pract. March 2016;13(3):221-227.
  2. De Vita A, Mercatali L, Pieri F, , et al. Current classification, treatment options, and new perspectives in the management of adipocytic sarcomas. Onco Targets Ther. Oct 11, 2016;9:6233-6246.
  3. Abbas Manji G, Singer S, Koff A, et al. Application of molecular biology to individualize therapy for patients with liposarcoma. Am Soc Clin Oncol Ed Book. 2015;213-218.
  4. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. Jan. 2017;67(1):7-30.
  5. Crago AM, Yee AY. Multimodality Management of Soft Tissue Tumors in the Extremity.Surg Clin N Am. 2016;96:977-992.
  6. Wilke C, Wilson J, Ogilvie C, et al. Radiologic and pathologic response after neoadjuvant radiotherapy for myxoid liposarcomas of the extremities. Poster presented at: 59th Annual Meeting of the American Society Therapeutic Radiation Oncology. September 24-27, 2016; San Diego, CA.
  7. Cheng, E.Y., Manivel, J.C., Froelich, J.W., Weigel, B., Ho, Y.Y., and Skubitz, K.M. FDG-PET-CT response after neoadjuvant chemotherapy continues to predict progression free survival at mid-term in prospective trial for soft tissue sarcomas. Paper presented at: CTOS 20th Annual Meeting; 2014; Berlin.
  8. Skubitz KM, Skubitz APN, Xu WW, et al. Gene expression identifies heterogeneity of metastatic behavior among high-grade non-translocation associated soft tissue sarcomas. J Transl Medd. 2014;12:176-185.
  9. Skubitz KM, Geschwind K, Xu WW, Koopmeiners JS, Skubitz AP. Gene expression identifies heterogeneity of metastatic behavior among gastrointestinal stromal tumors. J Transl Med. 2016;14:51. doi: 10.1186/s12967- 016-0802-3.

When to refer

University of Minnesota Health Cancer Care radiation, oncology, and surgical teams offer comprehensive diagnosis and treatment of patients who have soft tissue tumors, including liposarcoma, osteosarcoma, and fibrosarcoma. Treatment regimens are tailored to the individual patient and include radiation therapy, surgery, and chemotherapy. We offer patients access to clinical trials continue efforts to determine the effectiveness of chemotherapeutic agents and regimens for patients with advanced or recurrent sarcomas.

Our teams work hard to keep physicians informed of patients’ care. Our staffs provide detailed reports, from diagnosis to treatment and follow-up.

To schedule a consultation or referral: 855-486-7226

Collaborative Care

Many of our patients do not live within the Twin Cities metropolitan area. To minimize travel difficulties and lost time from school or work for our patients, we are committed to partnering with the patient’s referring provider and other local providers. Some patients can be initially discussed over the phone in collaboration with the referring provider. We aim to expedite the process so that, in one trip to the Twin Cities, patients can be assessed and also complete surgery, if required. In many cases, care after discharge can also be provided locally.

Physician Outreach Program

To schedule a physician meeting or to visit our facility, contact Melinda Tuma, System Manager, Outreach Services. Phone: 612-273-9947; email: marvold1@fairview.org.

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