Not all advanced melanomas behave in the same way. Some grow quickly and become difficult to control, while others respond to treatment for years, and a new study suggests a blood test may help doctors tell the difference.
Researchers have found that high levels of a blood marker called TKa were linked with worse outcomes in people with metastatic melanoma carrying a BRAF gene mutation. The same marker may also offer clues about which cancer treatment should be given first.
Melanoma begins in melanocytes, the cells that produce the pigment that gives skin much of its color. When found early, melanoma can often be removed successfully with surgery.
The situation becomes more serious when cancer cells spread beyond the original tumor. Metastatic melanoma can reach the lymph nodes, lungs, liver, brain and other organs.
Treatment has improved dramatically over the past decade. Many patients now live much longer because of immunotherapy and medicines that target particular weaknesses in melanoma cells.
A common weakness involves the BRAF gene. Around half of metastatic melanomas contain a BRAF mutation that encourages cancer cells to keep growing and dividing.
Targeted drugs can block signals produced by this altered gene pathway. These medicines can work quickly, sometimes causing tumors to shrink within a relatively short period.
Immunotherapy works differently. Instead of attacking the BRAF pathway directly, it removes some of the brakes that stop immune cells from recognizing and attacking cancer.
Both approaches can be valuable, but doctors still face an important decision when a patient can receive either one. Should immunotherapy be used first, or should targeted treatment come before it?
The international SECOMBIT trial was designed to explore different treatment sequences. Researchers involved in the new analysis asked whether a blood marker could help identify the best strategy for different patients.
They studied samples from 81 participants with BRAF-mutated metastatic melanoma. The marker they measured was circulating thymidine kinase activity, shortened to TKa.
Thymidine kinase is connected with the process cells use to copy DNA before dividing. When many cancer cells are actively multiplying, TKa activity in the blood can rise.
This makes TKa potentially useful as a window into the speed of tumor growth. Unlike a scan, which shows the size and location of visible tumors, the blood test may provide information about how actively cancer cells are dividing.
Patients with low TKa before treatment had much better long-term outcomes in the study. After five years, around 71% were still alive.
Among patients who began with high TKa, about 37% were alive after five years. Their cancer also tended to progress sooner despite treatment.
The finding suggests that TKa could help doctors estimate prognosis before therapy begins. High levels may signal a more aggressive disease that needs especially close attention.
But the researchers went a step further. They examined whether the marker was related to the success of different treatment orders.
People with high TKa appeared to benefit from receiving targeted therapy for a short period before immunotherapy. This strategy may offer rapid control of a fast-growing tumor before the immune-based treatment takes over.
Patients with low TKa showed a different pattern. Their outcomes appeared better when immunotherapy was used from the beginning.
This distinction could be important because there is rarely a perfect treatment sequence for every patient. A useful marker could help doctors match the order of medicines to how aggressively an individual’s cancer is behaving.
The study also followed TKa during treatment. Levels often increased when melanoma progressed, raising the possibility that the blood test could act as an early warning that treatment is losing control of the disease.
Repeated blood testing is generally easier than repeated tissue biopsies. If TKa proves reliable, it might eventually complement scans and other tests used to follow patients with advanced cancer.
The study was published in Clinical Cancer Research. It was led by Hildur Helgadottir at Karolinska Institutet, with Mattias Bergqvist of Biovica involved in the biomarker analysis and Paolo Ascierto leading the international SECOMBIT study.
The findings are encouraging, but they need careful interpretation. The analysis involved only 81 patients, which is a modest number for deciding how a major cancer treatment should be selected.
Once patients were divided according to their TKa level and treatment sequence, the groups became even smaller. This means the apparent differences in the best treatment order should be treated as an important clue rather than final proof.
Researchers will need larger studies to determine useful TKa cutoffs and show that choosing treatment based on the test actually helps patients live longer. They will also need to establish how often the test should be repeated and how changes should influence care.
Even so, the study demonstrates the growing potential of blood markers in cancer medicine. Instead of relying only on where tumors are and how large they appear, doctors may increasingly be able to measure what the cancer is doing biologically.
If future trials confirm these results, TKa could become one more piece of information used to personalize melanoma care. Its greatest value may be in helping doctors recognize fast-moving disease early and choose a treatment strategy suited to that urgency.
Source: Karolinska Institutet.
