The research team found that many of those with detectable levels of circulating tumor DNA before treatment went on to experience melanoma recurrence, as did those with detectable levels at certain points during treatment.
Credit: Getty/Westend61
Monitoring blood levels of DNA fragments shed by dying tumor cells may accurately predict skin cancer recurrence, a new study shows.
Led by researchers at NYU Langone Health and its Perlmutter 麻豆视频app Center, the study showed that approximately 80 percent of stage 3 melanoma patients who had detectable levels of circulating tumor DNA (ctDNA) before they started treatment to suppress their tumors went on to experience recurrence.
The researchers also found that the disease returned more than four times faster in this group than in those with no detectable levels of the biomarker, and the higher their levels, the faster the cancer returned.
鈥淥ur findings suggest that circulating tumor DNA tests could help oncologists identify which melanoma patients are most likely to respond well to therapy,鈥 said study lead author Mahrukh Syeda, MS. 鈥淚n the future, such assessments may be used routinely in the clinic to help guide treatment decisions,鈥 added Syeda, a research scientist in the at NYU Grossman School of Medicine.
The research team also found that nearly all of those with detectable levels of ctDNA at 3, 6, 9, or 12 months into treatment experienced melanoma recurrence. As a result, the authors say, if the gene fragments are not observable prior to therapy but appear later on, this could indicate that the disease might be worsening.
In stage 3 melanoma, which is one of the most aggressive forms of skin cancer, tumor cells have spread from the skin to nearby lymph nodes. After those lymph nodes are surgically removed, say the study authors, recurrence can be hard to spot using common imaging methods like X-rays and CT scans, which has fueled the search for other ways to detect cancer activity early on.
According to Syeda, swiftly tracking treatment progress and being able to spot signs of cancer growth could be helpful in a disease as dangerous as melanoma, which is notoriously difficult to treat once it spreads to other body parts. Early feedback from a ctDNA analysis might save lives, she says.
This ctDNA method works by focusing on the most common mutations in the genetic code in melanoma cells. The mutated DNA spills into surrounding blood as the cells break down.
Previous research has shown that ctDNA tests accurately trace the progression of colorectal and breast cancers, among others. In addition, in 2021, the authors of the current report found that higher levels of ctDNA in those with stage 4 melanoma, which has spread throughout the body, were linked to lower chances of survival. They also found that changes in ctDNA measurements during treatment could be used to identify patients with better or worse chances of survival.
Their latest investigation, , is the largest to date to assess ctDNA as a predictor for recurrence in patients with stage 3 melanoma, says Syeda.
The results were in nearly 600 men and women who had participated in an earlier clinical trial for stage 3 melanoma. The research team used blood samples from people in a clinical trial from Europe, North America, and Australia. They compared ctDNA measurements to clinical evidence of cancer recurrence. Their statistical analysis accounted for factors other than tumor shedding that could affect recurrence, such as sex, age, and type of therapy.
Among the findings, the results showed that assessing ctDNA levels was as good or better at predicting recurrence than other experimental tests that examine a tumor itself, such as those that measure immune activity within a group of cancer cells.
鈥淯nlike standard tissue-based analyses of tumor cells, which can only suggest the likelihood of recurrence, circulating tumor DNA tests provide a clear, direct measure of the disease itself and can tell us outright that melanoma has returned,鈥 said study senior author and dermatologist David Polsky, MD, PhD.
Dr. Polsky, the Alfred W. Kopf, MD, Professor of Dermatologic Oncology in the Ronald O. Perelman Department of Dermatology, cautions that in some cases, cancer still recurred even though the patient had received a negative ctDNA test before starting therapy.
To address this, the authors next plan to improve the sensitivity of their test, adds Dr. Polsky, also a professor in the . They also intend to explore, in a clinical setting, whether using the biomarker to make treatment decisions can indeed improve patients鈥 chances of survival and quality of life.
Funding support for the study was provided by Novartis Pharmaceuticals Corporation in East Hanover, New Jersey.
Dr. Polsky was an advisory board member for the pharmaceutical companies Novartis and Merck. He has also received honoraria from WebMD, Physicians鈥 Education Resource, and Oncology Specialty Group (OncLive), as well as laboratory research contracts from Novartis and Bristol-Myers Squibb, and laboratory support from Bio-Rad, a developer of life science and diagnostic technologies. The terms and conditions of all these relationships are being managed in accordance with the policies and procedures of NYU Langone Health.
In addition to Syeda and Dr. Polsky, other NYU Langone Health investigators involved in the study are Jennifer Wiggins, PhD, and Saim Ali, BA. Other study authors include Georgina Long, MD, PhD, at the University of Sydney in Australia; James Garrett, PhD, at Novartis Pharmaceuticals Corporation in Cambridge, Massachusetts; Victoria Atkinson, MD, at the University of Queensland in Woolloongabba, Australia; Mario Santinami, MD, at the National 麻豆视频app Institute of Milan, in Italy; Dirk Schadendorf, MD, at the University of Duisburg-Essen in Germany; Axel Hauschild, MD, at the University Hospital, Campus Kiel, in Germany; Michael Millward, MD, at the University of Western Australia in Nedlands; Mario Mandala, MD, at the University of Perugia in Italy; Vanna Chiarion-Sileni, MD, at the Veneto Institute of Oncology in Padua, Italy; Michael Smylie, MD, at the Cross 麻豆视频app Institute in Edmonton, Canada; Georgy Manikhas, MD, at St. Petersburg Oncology Hospital in Russia; Reinhard Dummer, MD, at the University Hospital Zurich Skin 麻豆视频app Center in Switzerland; Sachin Bajirao Adnaik, PhD, at Novartis Healthcare Pvt. Ltd. in Hyderabad, India; and Monique Tan, MD, MPH, and Maya Dajee, PhD, at Novartis Pharmaceuticals in East Hanover, New Jersey.
About NYU Langone Health
NYU Langone Health is a fully integrated health system that consistently achieves the best patient outcomes through a rigorous focus on quality that has resulted in some of the lowest mortality rates in the nation. Vizient Inc. has ranked NYU Langone No. 1 out of 115 comprehensive academic medical centers across the nation for three years in a row, and U.S. News & World Report recently placed nine of its clinical specialties among the top five in the nation. NYU Langone offers a comprehensive range of medical services with one high standard of care across 7 inpatient locations, its Perlmutter 麻豆视频app Center, and more than 320 outpatient locations in the New York area and Florida. With $14.2 billion in revenue this year, the system also includes two tuition-free medical schools, in Manhattan and on Long Island, and a vast research enterprise.
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