Thursday, June 18, 2015
In this Q&A, medical oncologist Mark Dickson discusses how people with liposarcoma are cared for at Memorial Sloan Kettering, what’s new in diagnosis and treatment, and the research he and his colleagues are conducting to improve patients’ treatment options.
- Liposarcoma is a rare cancer of the fat tissue.
- MSK doctors have a lot of experience diagnosing and treating it.
- They are conducting several clinical trials of new treatments.
- Genomic testing is now making personalized treatment possible.
Liposarcomas are tumors that arise in the body’s fat tissue. They are relatively rare, affecting only about 2,000 people each year in the United States. But it’s not an unusual disease at Memorial Sloan Kettering: Our doctors and researchers specialize in this and about 50 other types of soft tissue sarcoma.
Mark Dickson is a medical oncologist who specializes in liposarcoma as well as other sarcomas of the soft tissue and bone and Kaposi sarcoma. In a recent interview, Dr. Dickson discussed the challenges of treating liposarcoma and the research he is doing to improve the lives of people living with the disease by finding treatments that are more effective and less toxic.
How are liposarcomas detected and diagnosed?
Symptoms vary depending on the location of the tumor. For patient with a tumor in the abdomen, a common symptom is weight gain. A patient can gain ten to 20 pounds because some tumors can be very large [between 30 and 50 centimeters in diameter]. Patients who have tumors on their thighs or arms usually notice them right away. But a tumor in the abdomen might not be diagnosed as quickly since people often think their bellies have grown bigger due to normal weight gain.
Doctors use imaging tests, typically MRIs, to determine how far the disease has spread and to aid in assessing the stage of the tumor. The next step is a biopsy. Since sarcomas are rare, it is important that a surgeon or radiologist who is highly experienced with sarcomas does the biopsy.Back to top
Why are liposarcomas so difficult to treat?
Sarcomas are rare, and liposarcomas even rarer. The average oncologist might see one sarcoma in a year. That’s why patients are best off coming to a center such as MSK, where sarcomas are routine, not exceptional.
There are four types of liposarcoma. The most common is well-differentiated liposarcoma, low-grade tumors whose cells look like normal fat cells and grow slowly. Myxoid/round cell liposarcomas are intermediate to high-grade tumors, with the round cell being the high-grade form. Pleomorphic liposarcoma is the rarest but sometimes is a very aggressive disease type. And a dedifferentiated liposarcoma is a high-grade tumor that occurs when a lower-grade tumor changes and creates new high-grade cells.
Patients with well-differentiated liposarcoma can survive for decades, but recurrence is a problem. Simple well-differentiated tumors can be removed surgically and the prognosis is often good, but recurrent tumors are more challenging because the cancer can spread to other parts of the body and surgery may not be an option. Radiation has to be used sparingly to avoid side effects, and chemotherapy does not work well for many liposarcomas.
The five-year survival rate for patients with a high-grade liposarcoma is less than 50 percent. That’s why we’re seeking better treatments.Back to top
What follow-up do patients need after they’re done with active treatment?
Because recurrence can occur from months to decades after the initial diagnosis, people who have been treated for liposarcoma need to be monitored for the rest of their lives. Patients will have follow-up testing — which typically consists of a physical exam and imaging tests to detect metastasis — on a schedule determined by their physician.
Are there any clinical trials for liposarcoma drugs taking place?
There are several clinical trials being conducted at MSK that are centered on well-differentiated and dedifferentiated liposarcomas.
We are testing drugs that will turn off certain genes that become overexpressed in liposarcomas, including the genes CDK4 and MDM2. Ideally we will find a drug as effective as imatinib (Gleevec™), which was developed to target the cancer cells that cause chronic myelogenous leukemia and blocks the production of the abnormal protein that causes cancer. Gleevec is also very effective against some gastrointestinal stromal tumors.
We are seeing particularly promising results with the CDK4-targeting drug PD0332991 (palbociclib). To date, 90 patients have taken part in a phase II trial that looks at the drug’s efficacy. In 2013, we published a preliminary study in the Journal of Clinical Oncology that found that 70 percent of the 30 patients given PD0332991 for 12 weeks did not have their disease progress during that time. This was a higher percentage than expected. In addition, some patients had significant shrinking of their tumors.
Trials for drugs that can inhibit the overexpression of MDM2 are just under way. We are doing phase I trials with the goal of seeing whether a drug is safe to use — and hopefully showing some efficacy. One of the trials involves SAR405838, an investigational anticancer drug. The purpose of this study is to find the highest dose of SAR405838 that can be given safely in patients with liposarcoma and other advanced cancers that have either continued to grow despite standard therapy or for which no standard treatments exist.Back to top
What other research efforts aimed at liposarcoma are happening at MSK?
Among the challenges of treating sarcomas is that they are not one disease but have different subtypes, so there is a lot of variety between different people’s tumors. For comparison, in melanoma, you’ll find a common type of mutations in the gene BRAF that can be targeted with a drug in approximately 60 percent of patients. We will not find these high percentages in sarcomas. However, even finding a clinically relevant mutation present in a smaller number of patients is helpful. I believe that genomic research will be key in helping patients with liposarcomas.
We are utilizing a test known as MSK-IMPACT™, a targeted tumor-sequencing test that can detect gene mutations and other critical genetic aberrations in both rare and common cancers. The goal is to find aberrations that make cancers vulnerable to particular drugs and to match individual patients with available therapies or clinical trials that will most benefit them. To date, we have done sequencing on about 300 soft tissue sarcomas.Back to top