Accelerated Sarcopenia in Older Adults with a Cancer Diagnosis –results from the Health ABC Study

Grant R. Williams, Yanjun Chen, Kelly M. Kenzik, Andrew McDonald, Shlomit Shachar, Heidi Klepin, Stephen Kritchevsky, Smita Bhatia for the Health ABC Study

Background

• Loss in muscle mass and muscle strength occur as part of the aging process

- Tzankoff, Norris. J. Appl. Physiol., 1997.- Morley. Family Practice, 2012.

Age (yrs)

Kg

“there is probably no decline in structure and function more dramatic than the decline in lean body mass or muscle mass over the decades of life.”

- Rosenberg, 1997

Multifactorial causes of muscle loss in the older adult with cancer

Williams et al. Journal of Geriatric Oncology. 2018

Sarcopenia in Cancer

• Low muscle mass is common amongst adults diagnosed with cancer, and not just the elderly population

• Associated with increased chemotherapy toxicities, surgical complications, and inferior survival

26,8

44,6

58,3

0

20

40

60

80

<60 60-<70 >70

PER

CEN

TAG

E

AGE

% Sarcopenic

- Caan et al. CEBP. 2017

Research Questions

How does a cancer diagnosis impact the slope of muscle mass and strength decline in adults?•Both before and after a cancer diagnosis

Hypothetical trajectory of muscle loss with time in cancer patients

1) To examine the rate of decline of lean body mass, hand-grip strength, and gait speed (sarcopenia indices) in older adults with cancer pre- and post-cancer diagnosis compared to a non-cancer population.

Objective

Health, Aging and Body Composition Study

• An interdisciplinary study focused on risk factors for the decline of function in older persons, particularly change in body composition with age

• A longitudinal cohort of 3,075 healthy men and women between the ages of 70-79yrs were recruited in 1997-98 from 2 sites (1548 [50.3%] Memphis, 1527 [49.7%] Pittsburgh)

• Lean body mass, hand grip strength and gait speed assessed annually for six years

Methods

Identification of Incident Cancer Cases

• Incident cancer cases were identified within the cohort during annual clinic visits and semi annual telephone interviews

• If cancer reported, a cancer adjudication report was completed

• Pathologic or cytologic reports were obtained, as well as clinic notes, radiologic, and other supportive laboratory data

• Date of diagnosis, cancer type, cancer stage (localized versus metastatic) were obtained

Sarcopenia indices

• Lean body mass (LBM): Assessed using Dual Energy X-ray Absorptiometry (DEXA). Total LBM calculated by summing lean tissue of all extremities and trunk under the assumption that all nonfat and non-bone tissue is skeletal muscle (4500A, version 8.20a; Hologic, Waltham, MA)

• Hand-grip strength: Assessed using the Jamar handheld dynamometer and computed as an average from two trials of each hand

• Gait speed: Assessed over a 20-meter course and examined as a continuous variable 0.1 m/s unit of change

Covariates

•Age at enrollment into the Health ABC study

•Gender

•Race/ ethnicity

•Site of enrollment

Statistical Analyses

Using segmented linear mixed effect models with patient-level random intercept to compare the slopes of change in each of the 3 sarcopenia indices (LBM, HGS and GS) between individuals who did and did not develop cancer, adjusting for age at enrollment, race/ethnicity, gender, and enrollment site for two distinct time periods:• pre-cancer diagnosis• post-cancer diagnosis

Analyses continued

The slopes were examined for the available time period before cancer diagnosis and for the time period after cancer diagnosis

Non-cancer controls matched by mean age at diagnosis (77y) to define ‘pre’ and ‘post’ cancer diagnosis for this group

Results

VariableNon-cancer, n (%)

(n=2560)Cancer, n (%)

(n=515)p

GenderFemale 1392 (54.4) 192 (37.3) <0.001

RaceWhite 1515 (59.2) 279 (54.2) 0.04

SiteMemphisPittsburgh

1284 (50.2)1276 (49.8)

264 (51.3)251 (48.7)

0.7

Lean Body Mass, kg 46.2 49.1 <0.001

Hand-grip strength, kg 29.1 32.4 <0.001

Gait speed, m/s 1.33 1.35 0.20

Patient Characteristics

New-onset cancer types

Prostate23%

Colorectal15%

Lung13%

Breast11%

Other38%

N=515

Lean body mass

p=0.07

p <0.001

Cancer cohort before diagnosis

Cancer cohort after diagnosis

Non-cancer cohort

Cancer Diagnosis

Kg

50

45

40

Time (years) from diagnosis

0 4-4

Hand-grip strength

p=0.115

p=0.69

Cancer cohort before diagnosis

Cancer cohort after diagnosis

Non-cancer cohort

Cancer Diagnosis

Kg

35

30

25

20

Time (years) from diagnosis

0 4-4

Gait Speed

p=0.23

p <0.001

Cancer cohort before diagnosis

Cancer cohort after diagnosis

Non-cancer cohort

Cancer Diagnosis

m/s

1.4

1.2

1.0

0.8

Time (years) from diagnosis

0 4-4

Comparison by cancer types

• Most notable loss of post-diagnosis LBM in prostate and lung cancers compared to control

• Significant pre-diagnosis loss of hand-grip strength for prostate, colorectal, and other cancers only

• Significant pre-diagnosis declines in gait speed for prostate and lung cancers

•Cancer diagnosis results in accelerated decline of lean muscle mass in older adults with cancer compared to non-cancer control• Most notable for prostate and lung cancers

•Declines in hand-grip strength seen pre-cancer diagnosis in certain tumor sub-types, including prostate, colorectal, and other cancers

•Declines in gait-speed notable in pre-diagnosis window, but not post-diagnosis

Discussion

Limitations

•Heterogeneous sample of cancer diagnoses

•A healthy cohort from only two locations with potential for sample bias

•No available cancer treatment information

Strengths

• Large community based cohort followed longitudinally

•Rare opportunity to examine pre-diagnosis time period

•Rich characterization of mass, strength, and function

Future Direction

•Examine the underlying causes of accelerated loses in sarcopenia indices

•Further examine the association of losses in sarcopenia indices with other adverse outcomes in oncology (functional decline, independence, HRQOL)

•Develop intervention strategies to mitigate these loses to minimize adverse outcomes

Acknowledgments

Co-Investigators

Smita Bhatia, MD MPH

Yanjun Chen, MPH

Kelly Kenzik, PhD

Andrew McDonald, MD

Shlomit Shachar, MD

Heidi Klepin, MD MPH

Stephen Kritchevsky, PhD

In Memory of Dr. Arti Hurria

Thank You!