Melanoma incidence has been rapidly increasing worldwide, with fewer than 10% of people whose melanoma tumours have spread or metastasized surviving longer than a decade after detection. Despite the considerable progress that has been made in the clinical treatment of melanoma, reliable markers to predict treatment response or to measure early recurrent disease are still not available. Now, a study from researchers at NYU Langone Medical Center shows that a blood test that monitors blood levels of DNA fragments from dead cancer cells does a better job than the current standard test at tracking the severity and potential spread of metastatic melanoma. The team state such a test would help to determine as early as possible when switching to an alternative therapy is warranted.
Previous studies show that the standardised test, in widespread use for decades to inform treatment decisions, measures blood levels of the enzyme lactate dehydrogenase, or LDH. LDH is the only blood-based biomarker that has been incorporated in the staging system, as elevated levels of LDH are associated with higher disease burden and significantly decreased survival. LDH also plays an important role as a stratification parameter in many clinical trials. However, LDH is non-specific and increases with many other conditions and malignancies other than melanoma. The current study shows that the newer test looks at levels of circulating tumour DNA, or ctDNA, released into the blood when tumour cells die and break apart to spill their contents.
The current study followed thirty-one patients with inoperable metastatic melanoma over three years to show that circulating tumour DNA is a superior blood test for evaluating and tracking progression of metastatic melanoma. Results show that ctDNA levels in blood were elevated in 12 of 15 patients (80%) who were about to undergo treatment for their metastatic melanoma; by contrast, blood levels of LDH were elevated before therapy in seven of 23 patients (30%). Data findings also show that ctDNA could detect cancer recurrence, as confirmed by X-ray or CT scan, in 22 of 26 patients (85%) tested and undergoing therapy, while LDH was elevated in only 14 patients (54%).
The lab note that all participants had one of the two most common genetic mutations linked to the frequently fatal skin cancer, BRAF or NRAS. They go on to add that all had ctDNA and LDH blood tests performed after therapy, and most before treatment, with normal blood levels of ctDNA statistically determined by averaging results from 30 people who did not have melanoma. Among the study’s other key findings was that the ctDNA test was helpful in patients with small tumours whose melanoma had nevertheless spread; specifically, ctDNA blood levels were elevated in five of seven such cases (71%), while LDH levels were elevated in only one of 13 (8%).
The team surmise that recent studies have suggested that ctDNA blood testing may be useful in monitoring progression of breast and colon cancers as well. They go on to add that an accurate blood test is preferred by doctors and many patients because it avoids the risk of infection and pain that accompany invasive needle biopsy and the radiation exposure that comes with X-ray or CT scans. For the future, the researchers state that a reliable blood test for tracking potential disease progression is preferred because blood tests offer feedback on what is happening throughout the body, while scans may not always visualize all parts of the body.
Source: NYU Hospitals Center
