Making decisions about radiation
A specialized pathology test may help skull base patients and their doctors decide whether radiation is necessary after surgery
A team of neurosurgeons and colleagues at the University of Pittsburgh Medical Center recently published new research (PDF) showing that newly diagnosed skull base patients whose tumors have a low percentage of certain genetic markers may be able to forego radiation if their entire tumor is removed during surgery.
The research team, led by Georgios Zenonos, MD, used a test called fluorescence in situ hybridization (FISH) to look for the presence of certain genetic markers in the tumor cells of more than 150 adults with skull base chordomas. They started with the hypothesis that identifying the percentage of an individual’s tumor cells with these genetic markers can help determine the need for further treatments such as radiation therapy after surgery.
What is fluorescence in situ hybridization?
Fluorescence in situ hybridization (FISH) is a method for detecting and locating a specific DNA sequence on a chromosome using fluorescent dye. By looking at an individual’s tumor tissue under a microscope, a pathologist can see the presence of DNA sequences — also known as genetic markers — because of the fluorescent dye attached to them. This testing method is available through the pathology labs at most academic medical centers and cancer centers and can be performed on both fresh tumor tissue as well as paraffin-embedded samples.
What genetic markers did they study?
Dr. Zenonos and his team used the FISH method to look for deletions or rearrangements in small stretches of DNA in the tumors of 152 adults with skull base chordoma. Specifically, they tested for deletions of the chromosomes 1p36 and 9p21, which had previously been reported to be deleted, or “lost”, in some chordomas.
What did the researchers determine from the results?
After combining data on the percentage of tumor cells without chromosomes 1p36 and 9p21 and the patients’ outcomes over time, the researchers were able to group patients into three risk groups — low, intermediate, and high. Those with a lower percentage of deletions were placed in the low-risk group, as the researchers determined that these patients usually did better over time than others. As the percentage of deletions gets higher, patients are at increased risk of poor outcomes.
The researchers then analyzed these findings together with data on whether a complete surgical removal of the tumor was achieved (also called gross total resection, or GTR) as well as whether the patients had received radiation after surgery. Their findings led them to conclude that there are some patients who decidedly benefit from treatments like radiation following surgery. This includes all patients in the high risk group as well as patients in the intermediate risk group for whom GTR was not achieved. However, for skull base patients in the low and intermediate risk groups, the researchers determined that if GTR is achieved, radiation may not be necessary and close monitoring following surgery is an option.
There was only one patient in the low risk group who did not have GTR, so there was not enough data to determine an association between radiation and survival. Because of this, the researchers were unable to make any recommendation on radiation treatment for patients in the low risk group when GTR is not achieved. Patients in this category should discuss radiation vs. close monitoring with their treatment team.
Proposed pathway for making decisions about radiation
What do these findings mean for patients?
For skull base patients who are either planning for surgery or have recently had surgery but have not yet had radiation, this new test may help to inform whether radiation is likely to reduce the risk of recurrence or continued tumor growth. Patients should consider talking with their doctors about how this test might help guide a decision about having radiation after surgery.
See the information below about requesting the test.
How can I request this test?
The FISH panel can be done by most pathology labs in academic medical centers and large cancer centers. If you are interested in having this test done, tell your doctors about the recent paper (PDF) by Dr. Zenonos and ask that the FISH testing outlined in the paper be performed on a sample of your tumor. Your doctors can also contact Dr. Zenonos for assistance, at firstname.lastname@example.org. Our Patient Navigators are also available to talk with you about this test and help answer your questions.
What else should I consider about this test?
It is important to keep a few things in mind:
- Regardless of risk group, gross total resection (GTR) is associated with better outcomes. GTR should always be the goal of surgery for skull base chordomas if it can be achieved without unacceptable risk.
- This is a new test that so far has only been studied at one medical center. It is not yet known whether the results can or should be applied to all skull base chordoma patients. In order to validate the utility of the test, additional medical centers are planning their own studies, with additional patients, to confirm the findings of the UPMC team.
- This particular study only included skull base patients. Further studies are needed to determine whether the same biomarkers predict outcomes for patients whose tumors are located in other areas of the spine.
- There are additional factors associated with prognosis. Future research combining these biomarkers with others could potentially provide even greater predictive value.