Molecular Testing Leads to Personalized Treatment for a Rare Sarcoma: Jason’s Story

Jason Mascolo with his wife, Tricia, and daughter, Maeve

Molecular testing indicated that Jason Mascolo (shown here with wife Tricia and daughter Maeve) was likely to respond to immunotherapy. Five years later, he is still cancer free and no longer needs treatment.

Thirty-four-year-old Jason Mascolo put off getting the nagging pain in his leg checked out for years because he didn’t have health insurance. It wasn’t until he got a job with benefits — as a utility worker with Consolidated Edison — that he went to see a doctor. The news was not good. The doctor told him he had a tumor. “I heard that, and I knew it was bad,” remembers Jason, who’d recently gotten married. His doctor recommended specialists at Memorial Sloan Kettering Cancer Center (MSK).

A biopsy revealed that Jason had a rare cancer called a sarcoma, which had spread (metastasized) to his chest, lungs, and abdomen.

Jason’s diagnosis was very serious, but he was in the right place. MSK’s Sarcoma Center is world-renowned. Recently, MSK researchers published the two largest studies ever on the genetic analysis of sarcoma tumors. These specialized molecular tests can suggest personalized cancer treatments, which are sometimes more effective than standard chemotherapy and may have fewer side effects.

MSK Is a Destination for Sarcoma Treatment

The first step in Jason’s treatment was chemotherapy to shrink the tumor. After some treatment, a surgeon was able to remove the cancer from Jason’s leg. But the other tumors were much more stubborn, despite five different types of chemotherapy over a two-year period. By 2017, Jason and his wife were expecting a baby girl, and he had run out of options for chemotherapy.

The Sarcoma Center at MSK aims to further define the molecular abnormalities that drive the initiation, maintenance, and progression of every sarcoma type and subtype. Learn more.

Then Jason’s MSK medical oncologist, Mrinal Gounder, found something in the molecular testing of Jason’s tumor that suggested a promising avenue for treatment: a gene mutation that triggers the formation of many other cancerous mutations. Dr. Gounder told Jason he was likely to respond to a class of immunotherapy drugs called checkpoint inhibitors. These drugs work best against tumors with a large number of mutations, called a high tumor mutation burden (TMB).

Personalized Drug Treatment Effective Against Jason’s Rare Sarcoma Tumor

Jason received a combination of the drugs ipilimumab (Yervoy®) and nivolumab (Opdivo®) — a treatment originally developed at MSK for melanoma. MSK medical oncologist Sandra D’Angelo later led a clinical trial showing that it also could benefit some people with sarcoma. However, at the time Jason received the treatment, it was not covered by his insurance. Dr. Gounder interceded on Jason’s behalf and convinced the drug company to provide it under a program called compassionate use.

The results were dramatic. The immunotherapy worked. “Shortly after my daughter, Maeve, was born, Dr. Gounder called to tell me my tumors were shrinking,” Jason says. “He called it a miracle.” Today, Jason no longer needs any treatment and remains cancer free.

Molecular Analysis of Sarcoma Tumors Could Revolutionize Treatment

Two recent studies from MSK’s sarcoma team gave insight into how genetic evaluation of tumors can contribute to personalized medicine. The findings have the potential to make fundamental improvements to the way people with sarcoma are treated — both at MSK and beyond.

One study, co-led by MSK medical oncologist Benjamin Nacev, evaluated data from more than 2,100 patients who had molecular analysis of their tumors at MSK, using a test called MSK-IMPACT®. The other study, led by Dr. Gounder, looked at data from an additional 7,400 patients who had their tumors analyzed at other hospitals using a commercial test.

Both papers were published June 15, 2022, in Nature Communications.

Dr. Gounder’s study found that for about 10% of people with sarcoma, next-generation sequencing of tumor tissue actually led to a change in diagnosis. “Sarcoma is a difficult cancer, and it’s challenging to get an accurate diagnosis outside a specialized cancer center,” he says.

Mrinal Gounder

“In this era of precision medicine, it’s important to look at how next-generation sequencing tests like MSK-IMPACT can benefit patients with sarcoma,” says medical oncologist Mrinal Gounder.

The investigators then reviewed their findings with OncoKB®, a database developed at MSK that’s used to match patients with the best personalized therapies based on the mutations found in their tumors. Utilizing OncoKB, Dr. Gounder determined that about one-third of sarcoma patients in his study had mutations that are likely to respond to targeted therapies — either approved drugs or experimental treatments. Another 4% were likely to benefit from immunotherapy because of high TMB.

“Sarcoma is a really rare disease, making up only about 1% of all solid tumors,” Dr. Gounder explains. “Based on how the cancer cells look under the microscope, as well as the molecular changes that we can detect, we know there are more than 100 subtypes.” Jason’s subtype is called perivascular epithelioid cell neoplasm (PEComa).

Helping More Patients Benefit from Personalized Medicine

“In this era of precision medicine, it’s important to look at how next-generation sequencing tests like MSK-IMPACT can benefit patients with sarcoma,” Dr. Gounder adds. “These findings suggested that those with advanced sarcoma should consider having their tumors analyzed.”

“Both of these papers are really striving to provide tools that help the sarcoma community — not just at MSK but also the national and international communities — to do our jobs better,” says Dr. Nacev, who is a fellow of the Jennifer Goodman Linn Laboratory of New Drug Development in Sarcoma and Rare Cancers. “They provide information that not only can potentially guide the development of new treatments for patients but can really help those working on the basic science side of the equation to learn more about the disease,” he adds.

Benjamin Nacev

Medical oncologist Benjamin Nacev says that these kinds of studies “help the sarcoma community — not just at MSK but also the national and international communities — to do our jobs better.”

Drs. Nacev and Gounder and their colleagues are sharing their findings with any doctors and scientists who want to use them. Their data will be available through the cBioPortal for Cancer Genomics, an open-source database launched by MSK computational biologists in 2008. Additionally, OncoKB — which received recognition from the U.S. Food and Drug Administration in 2021 — can be used by doctors anywhere in the world to match their patients with personalized drugs based on the molecular analysis of their tumors.

Jason Is Thankful for Reduced Side Effects and Full Recovery From Immunotherapy Treatment

Jason had a few side effects from the immunotherapy, but he didn’t feel nearly as sick as when he was getting chemotherapy. Checkpoint inhibitors often cause joint pain. In Jason’s case, this pain was successfully treated with steroids.

Jason, who is now 41 and lives in White Plains, New York, is thankful that he was able to work throughout his cancer journey. He says Con Ed was very accommodating, putting him on light duty while he was in active treatment without cutting his hours. He’s now back to his full workload and pursuing all the other things he likes to do, including playing golf and spending time with his family.

“My experience was taxing, but I’ve made it to the other end, which is good,” Jason says. “I feel grateful that I met Dr. Gounder. I also want to thank my wife, Tricia; my mother-in-law; my father-in-law; and my mother, who helped me during this part of my life.”

By using the latest molecular tools to analyze sarcoma tumors, doctors at MSK and around the world will be able to help more patients like Jason.

Dr. Nacev’s study was supported by the National Cancer Institute (NCI) MSK SPORE in Soft Tissue Sarcoma (P50 CA217694), the Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Cycle for Survival®, NCI grants K08 CA245212 and R01 CA228216, Orphan Products Grants Program/U.S. Food and Drug Administration (R01 FD005731), and the Geoffrey Beene Cancer Research Foundation.

Dr. Gounder’s study was funded in part by the National Institutes of Health/NCI Cancer Center Support Grant to MSK (P30CA008748), the Draper Family Fund, and the Gounder Philanthropic Research Fund. Dr. Gounder has received honoraria from Amgen, Bayer, Daiichi-Sankyo, Epizyme, Flatiron Therapeutics, Karyopharm, Medscape, PER, SpringWorks Therapeutics, Tracon, and UpToDate.