Accelerated losses in sarcopenia measures exist pre- and post-diagnosis

Accelerated losses in sarcopenia measures were seen before and after a cancer diagnosis, possibly representing opportunities for targeted interventions to boost outcomes, researchers reported.

In a matched cohort study, patients with a cancer diagnosis had a more pronounced decline in gait speed (β = −0.02, 95% CI −0.03 to −0.01, P<0.001) versus controls without cancer, according to Grant R. Williams, MD, of the University of Alabama at Birmingham, and co-authors.

However, prior to cancer diagnosis, there was no significant decline in appendicular lean mass (ALM, β = −0.02, 95% CI −0.07 to 0.04, P=0.49) or hand grip strength (β = −0.21; 95% CI −0.43 to 0, P=0.05), they wrote in JAMA Network Open.

And after cancer diagnosis, there was a decline in ALM, but not hand grip strength or gait speed, the authors added, noting that “Accelerated loses in gait speed prior to cancer diagnosis, along with accelerated loses in ALM post-diagnosis suggest that a cancer diagnosis does affect age-related losses in some sarcopenia indices.”

Finally, slow gait speed was associated with an increase in mortality and an increase in disability, they stated.

Williams and co-authors pointed out that age-related loss in muscle mass and strength can be seen as early in people in their 40s, and it may be further complicated by the development of cancer and its related treatments.

“Low skeletal muscle mass is highly prevalent in older adults with cancer and strongly associated with a higher risk of adverse events, such as chemotherapy-related toxic effects, surgical complications, and poorer overall survival,” they said.

One of the hallmarks of sarcopenia is cancer cachexia, and the latter “is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass, along with adipose tissue wasting, systemic inflammation and other metabolic abnormalities leading to functional impairment,” explained researchers in Portugal in a review article.

A meta-analysis and systematic review by researchers in China and Hong Kong found that “sarcopenia is a risk factor for mortality among female early breast cancer patients,” while a review from Mexican investigators noted that “The prevalence of sarcopenia in patients with [colorectal cancer] ranges between 12%-60%.” Another study from China reported that radiologically-determined sarcopenia was tied to poor overall survival and cancer-specific survival in urologic cancer patients.

The current study population came from the Health, Aging, and Body Composition (Health ABC) study that included 3,075 community-dwelling older adults who were recruited from a random sample of white Medicare beneficiaries and all eligible black residents in and around Pittsburgh, and Memphis, Tennessee (mean age 74.1; 48.5% male; 41.7% black). Participants were recruited in January 1997 and observed until December 2013.

Data for the current study were analyzed from May 2018 to February 2020. Annual assessments of ALM, hand grip strength, and gait speed were the primary outcome measures. Among the participants, 16.7% developed cancer within the first 7 years of the study, most commonly prostate (23.2%), followed by colorectal cancer (12.5%). Of these, 32.0% were diagnosed with metastatic disease.

The authors reported that slow gait speed was associated with a 44% increase in mortality (hazard ratio 1.44, 95% CI 1.05-1.98, P=0.02) and a 70% increase in disability (HR 1.70, 95% CI 1.08 to 2.68, P =0.02).

But low ALM (HR 1.02, 95% CI 0.80 to 1.30, P=0.90) and low hand grip strength (HR 1.18, 95% CI 0.91 to 1.54, P=0.22) were not tied to increased mortality or increased disability (HR 0.91, 95% CI 0.71-1.17, P= 0.47 and HR 1.29, 95% CI 0.98-1.69, P=0.07).

Williams’ group also found that declines in gait speed pre-cancer diagnosis were observed in patients with prostate cancer (β= −0.02, 95% CI −0.04 to −0.01, P=0.002) and metastatic disease (β = −0.03, 95% CI −0.04 to −0.02, P<0.001). Also, declines in ALM after post-cancer diagnosis were “most striking in patients with metastatic disease,” they wrote (β = −0.32, 95% CI −0.53 to −0.10, P<0.001).

The authors suggested that “Accelerated declines in gait speed leading up to cancer diagnosis may be caused by symptoms, hospitalizations, and/or surgery associated with a cancer diagnosis.” But they also noted that “it was surprising to find significant declines in gait speed before cancer diagnosis specifically within individuals with prostate cancers, as many of these individuals likely had asymptomatic and localized disease.”

The finding highlights the “importance of gait speed as a potential marker of frailty and as a critical tool in risk prediction in older adults with cancer,” they stated.

As for the lack of an association between ALM and mortality, “our findings suggest potential discrepancies in the accelerated losses in sarcopenia measures… the relationship between muscle mass, muscle strength, and physical performance is not linear, and prior research has shown only modest correlation… Muscle strength and physical performance do not depend solely on muscle mass, and many other factors complicate this relationship, including muscle composition.”

Study limitations included the fact that only a small number of the Health ABC participants developed cancer. Also, the main study did not have information on cancer treatment so Williams’ group could not “examine the association of specific treatments with trajectories of specific sarcopenia indices.”

The authors posed several questions that need to be answered on this topic, including “Are these losses the result of cancer cachexia or cancer treatment?” and “What are the best interventions to mitigate the decline in sarcopenia indices?”

Other studies have taken up the last question, such as the planned ChemoFit that will evaluate a home-based exercise intervention in esophago-gastric cancer. Previously, a U.S.-based systematic review looked at the cost-effectiveness of pharmacological management (Anamorelin and Enobosarm) of cachexia in cancer patients. Also, the European Society for Clinical Nutrition and Metabolism has put forth recommendations for optimizing perioperative nutrition for better outcomes, while researchers in Canada assessed a nutritional intervention to reverse the severe loss of muscle mass in cancer patients.

  1. A steeper decline in gait speed prior to a cancer diagnosis, and accelerated declines in appendicular lean mass after cancer diagnosis, were found in a matched cohort study of 515 older adults.

  2. Accelerated losses in differing sarcopenia measures were seen before and after a cancer diagnosis and may present opportunities for targeted interventions to improve outcomes.

Shalmali Pal, Contributing Writer, BreakingMED™

The study was supported by the Walter B. Frommeyer Fellowship in Investigative Medicine at the University of Alabama at Birmingham, the National Institutes on Aging (NIA), the Wake Forest University Claude D. Pepper Older Americans Independence Center, and the Intramural Research Program of the NIA.

Williams and co-authors reported no relationships relevant to the contents of this paper to disclose.

Cat ID: 120

Topic ID: 78,120,282,494,730,120,255,925