Kaiser Permanente study finds significant weight loss 3 months after diagnosis can predict future weight loss, creating earlier options for intervention
Most patients with advanced cancer will develop cachexia, a syndrome marked in part by loss of appetite, loss of fat and skeletal muscle, and fatigue. Currently, cancer patients are diagnosed as having cachexia when they have lost 5% or more of their weight in the prior 6 months. But a new Kaiser Permanente study suggests that doctors can identify patients at high risk of cachexia within 3 months of an advanced cancer diagnosis, which could allow for earlier clinical intervention.
“Cancer patients are weighed regularly during their course of care,” said first author Sophia E. Fuller, MA, a data analyst at the Kaiser Permanente Northern California Division of Research. “Our study shows that you can use this weight data collected during routine clinical care to identify patients at high risk of cachexia earlier. This creates the potential to start treating the syndrome much earlier than we currently do.”
The study, published in the Journal of the National Cancer Institute, included 8,338 members of Kaiser Permanente Northern California diagnosed with advanced lung, pancreatic, or colorectal cancer between 2010 and 2021. Patients with these 3 cancer types are at most risk of developing cachexia (pronounced kuh-kek-see-uh.)
Distinct weight trajectories
Electronic health records were used to calculate the patients’ weekly weight changes from 2 months prior to their advanced cancer diagnosis to 6 months after their diagnosis. The researchers identified 4 distinct weight change trajectories — weight stable, minor gains in weight, moderate loss of weight, and severe loss of weight.
The study found that weight trajectories identified at 3 months closely mirrored those identified at 6 months. For example, 99% of the patients in the severe weight loss group at 6 months were in the moderate or severe weight loss group at 3 months. Similarly, 85% of the patients in the moderate loss group at 6 months had moderate or severe weight loss 3 months after their advanced cancer diagnosis.
These findings position us to be able to test new treatments and introduce supportive services much earlier.
— Elizabeth Cespedes Feliciano, ScD
The study also found that the patients who had moderate or severe weight loss after 3 months had a significantly increased risk of death compared to the patients whose weight remained stable. Among the 7,363 patients who survived to 3 months, median survival was 8 months in the severe loss group, 13 months in the moderate loss group, 18 months in the group that gained weight; and 20 months in the stable group.
“These findings position us to be able to test new treatments and introduce supportive services much earlier, which could help improve these patients’ quality of life,” said senior author Elizabeth M. Cespedes Feliciano, ScD, a research scientist at the Division of Research.
The research is one component of a larger coordinated effort by a group of U.S. and U.K. researchers from Cancer Grand Challenges team CANCAN (Cancer Cachexia Action Network). Bette Caan, DrPH, leads the DOR team.
A recent phase II randomized trial of 187 patients, co-led by a CANCAN co-investigator, found that ponsegromab, a monoclonal antibody that targets human growth differentiation factor 15 (GDF-15), improved weight, appetite, and physical activity in patients with elevated levels of GDF-15, better than a placebo.
“The point of the Cancer Grand Challenge is to try to understand from bench to bedside the syndrome of cachexia to help people with cancer live longer with improved quality of life,” said Cespedes Feliciano. “Findings from our new study are especially significant now that we have researchers studying new treatments like ponsegromab that are being developed specifically to treat cachexia.”
This study was supported through Cancer Grand Challenges, a global research initiative co-founded by the National Cancer Institute and Cancer Research U.K.
Co-authors include Stacey Alexeeff, PhD, and Bette Caan, DrPH, of the Division of Research; Marcus DaSilva Goncalves, MD, of NYU Langone Health, Richard F. Dunne, MD, of University of Rochester; Tobias Janowitz, MD, of Cold Spring Harbor Laboratory; Mariam Jamal-Hanjani, MD, of Cancer Research U.K.; and Tilak K. Sundaresan, MD; of Kaiser Permanente San Francisco.
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About the Kaiser Permanente Division of Research
The Kaiser Permanente Division of Research conducts, publishes, and disseminates epidemiologic and health services research to improve the health and medical care of Kaiser Permanente members and society at large. KPDOR seeks to understand the determinants of illness and well-being and to improve the quality and cost-effectiveness of health care. Currently, DOR’s 720-plus staff, including 73 research and staff scientists, are working on nearly 630 epidemiological and health services research projects. For more information, visit divisionofresearch.kp.org or follow us @KPDOR.
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