Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.

This week’s study is…

Molecular Characterization of Circulating Tumor DNA in Pediatric Rhabdomyosarcoma: A Feasibility Study

We previously published about this research in a story titled “Liquid Biopsies Could Guide Rhabdomyosarcoma Management” which can be found here. The study was originally published in the Journal of Clinical Oncology-Precision Oncology. You can read the full text of the study here. 

This research team was led by scientists at the Institute of Cancer Research, London.

What Happened?

Rhabdomyosarcoma is a rare form of cancer that can be highly aggressive. The majority of patients are children and there is an urgent need to improve outcomes and survival. A significant limitation in the management of rhabdomyosarcoma is a relative lack of disease biomarkers, which can be useful tools to understand treatment response and severity of disease. Plasma circulating tumor DNA (ctDNA) has been a useful biomarker in other cancers but has never been evaluated in this role for rhabdomyosarcoma. This study aimed to explore the feasibility of ctDNA as a biomarker in the disease.

The researchers evaluated blood samples from human patients and a mouse model of the cancer. The study included a total of 28 patients from different centers around Europe. The team hoped to find that measuring ctDNA could serve as a form of liquid biopsy that would allow for a less invasive and faster option in comparison to a conventional tissue biopsy. Before assessing the samples from patients, the scientists focused on the mouse model samples and found that they were able to monitor and detect the cancer tumors and their growth using ctDNA. Furthermore, they found that the mice could be utilized to assess treatment strategies using liquid biopsy.

Before receiving treatment, 18 of the child patients had blood samples taken, as well as samples taken throughout treatment to monitor progression of their rhabdomyosarcoma. 14 of these patients had critical genetic alterations to the tumors. These changes can inform how they should be treated, and certain mutations impacting TP53 and MYOD1 have been linked to faster progression. Patients with such mutations may require a more aggressive regimen.

Levels of ctDNA were higher in patients whose disease had spread to the lymph nodes or other areas. Higher levels of ctDNA were also linked to worse treatment response. From these results, it seems likely that liquid biopsy could help determine if a treatment approach is being useful, as well as which patients may need further therapy. 

About Rhabdomyosarcoma

Rhabdomyosarcoma is a type of soft tissue sarcoma cancer. It is highly aggressive and affects skeletal muscle cells that are not yet fully differentiated. Most people affected by the disease are under age 18. In many cases, the cause of rhabdomyosarcoma remains a mystery, and the cancer often appears sporadically. However, increased risk has been associated with certain genetic disorders, and parental use of cocaine and marijuana may also increase the risk. The symptoms and presentation of this cancer vary widely and often depend on where the tumor appears; often a prominent lump is noticeable. This means that this cancer can, in some cases, be diagnosed early. Treatment approaches include surgery, chemotherapy, radiation, and immunotherapy. Outcomes vary substantially depending on location, but the cure rate for cancer that hasn’t spread is 75 percent. Relapsed or metastatic cancer has much worse survival rates. To learn more about rhabdomyosarcoma, click here.

Why Does it Matter?

This study appears to have identified liquid biopsy, using ctDNA as a biomarker, as an effective tool for monitoring rhabdomyosarcoma and informing treatment approaches on a case-by-case basis. However, the team acknowledges that these findings are from a small-scale pilot study and the results will need to be evaluated on a larger population.

Plans for a larger, international clinical trial are already underway, and the new study is expected to kick off next month.

“Our early pilot findings suggest that liquid biopsies can detect early signs of relapse, assess the severity of disease and help guide choice of drug treatment. We’re excited to be taking these findings into an international clinical trial involving larger numbers of children, and we hope we can realize the potential of using liquid biopsies to make children’s cancer treatment smarter and kinder.” – Janet Shipley, Professor, Study Leader

If these findings can be replicated in the bigger trial, then they have the potential to be a game changer for the treatment of this rare cancer.