A simple blood test may one day help doctors decide how best to treat people with advanced melanoma.
New research suggests that a substance in the blood can provide clues about how quickly the cancer is growing and how well a patient may respond to different treatment strategies.
Melanoma is a type of skin cancer that begins in cells that make skin pigment. It is less common than some other skin cancers, but it can be much more dangerous when it spreads to organs or other parts of the body.
Once melanoma has spread, doctors have several powerful treatments available. These include medicines that help the immune system attack cancer and drugs designed to block specific changes inside tumor cells.
About half of people with metastatic melanoma have a change in a gene called BRAF. This change can act like a stuck accelerator, sending signals that encourage cancer cells to grow.
Patients with this BRAF change can receive targeted medicines that interfere with the cancer’s growth signals. They can also receive immunotherapy, which helps the body’s immune defenses recognize and attack cancer cells.
One difficult question is which treatment should come first. Starting with immunotherapy may provide long-lasting control for some patients, while rapidly growing cancers may need a different approach.
Researchers from Karolinska Institutet and international partners investigated whether a blood measurement could help answer this question. Their study focused on a marker known as TKa.
TKa reflects the activity of an enzyme involved when cells make new DNA before dividing. Higher levels in the blood can therefore provide a sign that cancer cells are multiplying rapidly.
The study included 81 people with metastatic melanoma whose tumors carried a BRAF mutation. All had participated in the international SECOMBIT clinical trial.
SECOMBIT compared three different ways of ordering immunotherapy and targeted treatment. This gave researchers an opportunity to examine whether TKa levels were linked not only with survival but also with which treatment sequence worked best.
Before treatment began, the researchers measured TKa in blood samples. They then compared the results with how long patients lived and how long their cancer remained under control.
The differences were substantial. Patients who started with high TKa levels tended to have their cancer worsen sooner and had shorter survival than those with low levels.
Five years after treatment began, about 71% of patients in the low-TKa group were still alive. In comparison, approximately 37% of those with high TKa levels were alive.
This suggests that TKa may provide doctors with information about how aggressive a patient’s cancer is. A high result could identify people whose tumors are growing particularly quickly and who may need a carefully chosen treatment plan.
The researchers also saw an interesting difference in treatment sequence. Patients with high TKa appeared to do better when they received a short period of targeted treatment before moving to immunotherapy.
For people with low TKa, starting with immunotherapy appeared to produce better results. If confirmed, this could eventually help doctors choose treatment based on the biological behavior of each person’s cancer rather than using the same order for everyone.
Targeted therapy can often shrink BRAF-mutated melanoma quickly. Immunotherapy may take longer to work, but in some patients it can produce cancer control that lasts for years.
This may help explain why treatment order could matter. Someone with a rapidly growing cancer may benefit from bringing the disease under control quickly before beginning a treatment designed to produce a longer-lasting immune response.
TKa may also have another possible use. The researchers found that levels often increased when melanoma began getting worse, suggesting that repeated blood tests might help doctors monitor disease during treatment.
At present, doctors usually follow metastatic melanoma using a combination of scans, physical examinations, symptoms and laboratory tests. A useful blood marker could potentially provide another way to detect changes between scans.
The research was published in the journal Clinical Cancer Research. Hildur Helgadottir of Karolinska Institutet was the study’s first author, and the analysis involved researchers from several European hospitals and universities.
However, the findings are not yet strong enough to change routine melanoma care. Only 81 patients were included in this analysis, and smaller groups were created when researchers compared different TKa levels and treatment sequences.
That makes the treatment-order results particularly important to confirm in larger studies. An apparent benefit in a small group can sometimes disappear when the same question is tested in many more patients.
The study also does not show that TKa should replace scans or established clinical information. Its most likely future role would be as an additional tool that helps doctors understand tumor growth and make more personalized decisions.
Overall, the results are promising because the test is based on blood, which is relatively easy to collect repeatedly. If larger trials confirm the findings, TKa could eventually help doctors estimate prognosis, monitor treatment and choose which therapy to use first for some patients with advanced melanoma.
Source: Karolinska Institutet.
