Sage Journals: Discover world-class research

Abstract

Background

Health-related quality of life (QoL) is a measure that allows us to know the patient’s perception of well-being and how it is affected by their disease and treatments. In cancer patients, sarcopenia has been associated with low scores on various instruments used to assess the QoL; however, little information is available on the effects of sarcopenia and sarcopenic obesity on the QoL of patients with head and neck cancer (H&NC).

Methods

In this cross-sectional study with 71 H&NC patients aged between 40 and 80 years, we describe the scores on the instruments EORTC QLQ C-30 and EORTC QLQ-H&N35 according to the sarcopenia phenotype (NSG, nonsarcopenic group; SG, sarcopenic group; and SOG, sarcopenic obesity group), hand-grip strength, gait speed, total lymphocyte count, albumin, cholesterol and C-reactive protein, and the relationships between these variables.

Results

The prevalence of sarcopenia and sarcopenic obesity was 48% and 28%, respectively. The QoL analysis showed that NSG had higher scores on the physical functioning scale [NSG 93 (83–100); SG 73 (52–88); SOG 83 (53–93), P = .009] and lower scores on the fatigue scale [NSG 11 (0–22); S 39 (30–67); SOG 44 (14–56); P = .004]. The NSG had a higher hand-grip strength (31.1 kg) than SG (24.1 kg, P = .007) and SOG (26.3 kg, P = .001), and a lower C-reactive protein. The SG and SOG showed no differences between them.

Conclusions

Patients with sarcopenia or sarcopenic obesity have lower physical performance and a higher level of fatigue than nonsarcopenic patients. This loss of function can maintain or worsen sarcopenia due to the patient’s self-restraint in physical exertion that encourages an increase in muscle tissue.

Keywords

body composition cachexia muscle strength EORTC QLQ sarcopenia sarcopenic obesity head and neck cancer

Introduction

The estimated prevalence of head and neck cancer (H&NC) in Mexico in the past 5 years is 10 480 cases, with 3882 new cases annually, and the annual mortality rate was 1800 cases, according to Globocan data.¹ These patients experience severe weight loss up to 57% before treatment and up to 85% during treatment.^2
-4 The etiology of weight loss is multifactorial and includes mechanical alterations caused by the tumor, inflammatory phenomena associated with cancer cachexia, and treatment effects.^5,6 Weight loss can induce or perpetuate sarcopenia, affecting overall and disease-free survival, locoregional recurrence, and worsening radiation therapy-related toxicity.^7

-13

Cancer patients with sarcopenic obesity have a disease-free survival rate lower than patients with sarcopenia without obesity.^11,14,15 Excess fat masks muscle mass loss and defies the possibility of an opportune diagnosis of sarcopenia. In addition, it promotes the production of inflammatory mediators—adipocytokines and acute phase reactants—which are involved in different immune and metabolic processes, limits muscle synthesis, and stimulates proteolysis.

Previous research suggests a relationship between sarcopenia and low scores on different instruments used to evaluate the quality of life (QoL) of cancer patients.^16
-18 However, few studies describe the association of sarcopenic obesity with the QoL of cancer patients, and to our knowledge, no study has reported this association in H&NC patients.

Quality of life is a multifactorial construct related to the functioning and perception of well-being,¹⁶ and is influenced by its nutritional status. The objective of this study was to determine the impact of sarcopenia and sarcopenic obesity on QoL scales and several indicators of nutritional status in patients with H&NC.

Patients and Methods

The Institutional Review Board of the Instituto Mexicano del Seguro Social approved this research. It is a cross-sectional study with retrospectively collected laboratory data. All procedures were carried out according to the principles of the Helsinki Declaration; a written declaration of consent was obtained from all participants.

The study consisted of a nonprobability sample of 71 patients between the ages > 40 and < 80 years old confirmed with H&NC. All patients had started their H&NC treatment (surgery, radiation therapy, and/or chemotherapy) in a tertiary facility in Guadalajara, México. Patients with two or more cancers, autoimmune diseases, chronic lung diseases, cardiovascular diseases, renal failure, or contraindications to determining body composition by bioelectrical impedance analysis (pacemaker or metal prostheses, limb amputations, and severe edema) were excluded. The sociodemographic data of the patient, the clinical stage and anatomical location of the tumor, the treatment modality, and the laboratory results were extracted from the medical records.

An experienced dietitian performed the analysis of body composition and classified the patients according to their sarcopenia phenotype. Before the measurement, the patients fasted for 8 hours and wore no jewelry or socks. Height was measured with the Seca 213 height scale (Seca, Germany). The mBCA Seca 514 bioelectric impedance device (Seca, Germany) was used to obtain the patient’s weight, phase angle, total skeletal muscle mass, and percentage of total body fat.

Body mass index (BMI) was calculated as described by the World Health Organization. Skeletal muscle-mass index (SMI) was calculated by dividing the total skeletal muscle mass (kg) by the height squared (m²). Based on SMI and BMI, the patients were divided into 3 groups: (a) nonsarcopenic group (NSG): SMI women ≥ 6.42 kg/m², men ≥ 8.86 kg/m², and BMI < 25 kg/m²; (b) sarcopenic group (SG): SMI women < 6.42 kg/m², men < 8.87 kg/m², and a BMI < 25 kg/m²); and (c) sarcopenic obesity group (SOG): SMI women < 6.42 kg/m², men < 8.87 kg/m², and a BMI ≥ 25 kg/m².^15,19

The ratio of SMI to patient weight was calculated to determine the proportion of total weight that corresponded to muscle mass, which was normalized by dividing by the square of height.

The hand-grip strength was measured using a Jamar Plus+ Digital hand dynamometer (Patterson Medical Supply, Cedarburg, USA). According to the American Association of Hand Therapists, the patient held the device and compressed it with maximum force to achieve maximum contraction. The test was repeated 3 times for each hand, with 1-minute rest intervals between each measurement. The highest result of all tests was recorded.²⁰

The EORTC QLQ-C30 v.3 (validated for the Mexican population) was used to evaluate the QoL.²¹ It consists of 6 multi-item scales (health status/global QoL, physical functioning, role functioning, social functioning, emotional functioning, and cognitive functioning) and 9 single-item scales (fatigue, nausea or vomiting, pain, dyspnea, insomnia, appetite loss, diarrhea, constipation, and financial difficulties). The multi-item scales evaluate constructs related to the patient’s functioning, while the single-item scales describe the severity of cancer-related symptoms.

The EORTC QLQ-H&N35 complementary module for H&NC patients consists of 35 questions, comprises 7 multi-item symptom scales (pain, swallowing, sensory problems, speech problems, trouble with social eating, trouble with social contact, and reduced sexuality), and eleven single-item symptom scales (teeth, open mouth, dry mouth, sticky saliva, coughing, felt ill, painkillers, nutritional supplements, feeding tube, weight loss, and weight gain).

The analysis of both EORTC questionnaire items required the linear transformation of each item or multi-item scale to get a range of scores from 0 to 100. Higher scores on the functioning scales indicate that patients perceive that they have better QoL. On the contrary, higher scores on the symptoms scales indicate a higher frequency of severe symptoms and thus a poorer QoL.²²

Statistical analysis was performed using the IBM® SPSS® Statistics version 26 software package (Armonk, New York). Results are presented as mean ± standard deviation (SD) for variables with normal distributions. Nonparametric variables are represented as medians (interquartile intervals [IQIs]). Categorical variables are expressed as numbers and percentages of the total. We performed Pearson’s chi-square tests to assess differences between 2 groups (Fisher’s tests if the estimated values were < 5); one-way ANOVA and KruskalWallis tests with Bonferroni correction were used to assess differences between the 3 groups. To determine the relationship, we calculated Spearman’s rho. All analyses were two-sided, and a P-value < .05 was considered significant. We used Cronbach’s alpha value for reliability in the multi-item scales in both questionnaires.

Results

We evaluated 71 H&NC patients, 24% in the NSG, 48% in the SG, and 28% in the SOG. We did not find differences in demographic and clinical characteristics between the groups (Table 1).

Table 1.

Comparison of clinical characteristics by sarcopenic phenotype.

	Non-sarcopenia (n = 17)	Sarcopenia (n = 34)	Sarcopenic Obesity (n = 20)	p
Age, mean ± SD	59 ± 8	64 ± 11	68 ± 12	0.1
Sex, n (%)				0.7
Male	14 (82.4)	30 (88.2)	18 (90.0)
Risk factors, n (%)
Family history of cancer	9 (52.9)	12 (35.3)	7 (35.0)	0.5
Tobacco use	13 (76.5)	23 (67.6)	16 (80)	0.6
Alcohol consumption	11 (64.7)	27 (79.4)	17 (85)	0.4
Substance abuse	1 (5.9)	1 (8.8)	1 (5.0)	0.6
Anatomical location of the tumor, n (%)
Oral cavity	5 (29.4)	15 (44.1)	6 (30.0)	0.6
Larynx	8 (47.1)	11 (32.4)	9 (45.0)
Pharynx	1 (5.9)	2 (5.9)	1 (5.0)
Salivary gland	1 (5.9)	0	0
Nasal and sinonasal cancer	1 (5.9)	2 (5.9)	0
Other	1 (5.9)	4 (11.8)	3 (15.0)
Unknown	0 (0)	0 (0)	1 (5.0)
Histology of the tumor, n (%)
Squamous	15 (88.2)	32 (94.1)	20 (100)	0.06
Adenocarcinoma	1 (5.9)	0	0
Melanoma	0	1 (2.9)	0
Not available	1 (5.9)	1 (2.9)	0
Clinical stage, n (%)
I	4 (23.5)	1 (2.9)	2 (10.0)	0.054
II	3 (17.6)	6 (17.6)	2 (10.0)
III	2 (11.8)	6 (17.6)	6 (30.0)
IV	4 (23.5)	20 (58.8)	8 (40.0)
No available	4 (23.5)	1 (2.9)	2 (10.0)
Previous treatment, n (%)
Oncological surgery	6 (35.3)	16 (47.1)	10 (50)	0.8
Radiotherapy	4 (23.5)	9 (26.5)	9 (45)	0.4
Chemotherapy	2 (11.8)	13 (38.2)	6 (30.0)	0.1
Tracheostomy	5 (29.4)	10 (29.4)	2 (10.0)	0.2
Feeding route, n (%)				0.4
Oral	16 (94.1)	29 (85.3)	19 (95)
Enteral	1 (5.9)	5 (14.7)	1 (5.0)
Patient-generated global subjective assessment, n (%)
Well-nourished	4 (23.5)	2 (5.9)	4 (20.0)	0.1
Moderately malnourished or suspected malnutrition	7 (41.2)	13 (38.2)	5 (25.0)
Severely malnourished	0	11 (32.4)	4 (20.0)
Not available	6 (23.9)	8 (23.5)	7 (35.0)

^aDifferences among the 3 groups; statistical test: one-way ANOVA or Kruskal-Wallis test (quantitative data), and X² test or Fisher’s exact test (qualitative data); statistical significance P-value ≤ .05.

The SG had lower albumin values (3.9 g/dL) than SOG (4.3 g/dL) (P = .013) and higher C-reactive protein values than NSG (17.7 vs 4.4, P = .12). Total lymphocyte count and cholesterol values were not different between the 3 groups (Table 2).

Table 2.

Comparisons of the biochemical, anthropometric, and functional parameters by sarcopenic phenotype.

	Non-sarcopenia (n = 17)	Sarcopenia (n = 34)	Sarcopenic Obesity (n = 20)	P*
Albumin (g/dL), Median (IQI)	4.3 (3.9–4.5)	3.9 (3.4–4.3)	4.3 (4.0–4.6)	.008¹
Total lymphocyte count (cells/mm³), mean ± SD	1682.1 ± 692.9	1514.8 ± 789.6	1637.5 ± 726.2	NS
Cholesterol (mg/dL), mean ± SD	186.6 ± 43.7	163.6 ± 33.7	188.6 ± 43.9	NS
C-reactive protein, median (IQI)	4.4 (3.1–19.0)	17.7 (5.1–55.2)	10.0 (3.9–27.0)	.012^&
Body mass index (kg/m²), median (IQI)	29.8 (26.6–30.9)	21.0 (19.3–23.0)	27.7 (26.4–29.6)	.000^&
Body mass index (kg/m²), median (IQI)	29.8 (26.6–30.9)	21.0 (19.3–23.0)	27.7 (26.4–29.6)	.000^ç
Skeletal muscle index (kg/m²), Median (IQI)	9.6 (9.1–10.1)	6.3 (5.1–7.5)	7.8 (7.2–8.4)	.000^&
				.005^
				.004^ç
Body fat percentage (%), mean ± SD	31.7 ± 6.8	25.6 ± 9.2	37.6 ± 8.5	.00 0^ç
Phase angle (°), mean ± SD	4.7 ± .85	3.9 ± 0.9	4.14 ± 0.9	.010^&
Muscle strength (kg)	31.1 (26.3–35.7)	24.1 (19.1–33.7)	26.3 (18.7–30.9)	.005^&
Muscle strength (kg)	31.1 (26.3–35.7)	24.1 (19.1–33.7)	26.3 (18.7–30.9)	.017^
Gait speed 4 m (m/s)	.90 ± .11	.71 ± .22	.88 ± .17	.016^
Gait speed 4 m (m/s)	.90 ± .11	.71 ± .22	.88 ± .17	.010^ç

IQI: interquartile interval, NS: no statistical significance, SD: standard deviation. *Statistical test: one-way ANOVA or Kruskal-Wallis test; significance value corresponds to Bonferroni’s correction. Statistical significance: P-value ≤ .05. ^&Nonsarcopenic group versus sarcopenic group. ^Nonsarcopenic group versus sarcopenic obesity group. ^çSarcopenic group versus sarcopenic obesity group.

Lower BMI values, body fat percentage, and SMI were observed among anthropometric variables in the SG. The phase angle was higher in the NSG (4.7°) than in the SG (3.9°; P =.010), but no differences were found compared to the SOG. The SG had lower albumin values (3.9 g/dL) than SOG (4.3 g/dL) (P = .013) and higher C-reactive protein values than NSG (17.7 vs 4.4, P = .12). The phase angle was higher in the NSG (4.7°) than in the SG (3.9°; P = .010) (Table 2).

The NSG had a higher hand-grip strength (31.1 kg) than SG (24.1 kg, P = .007) and SOG (26.3 kg, P = .001). The NSG (.90 m/s) and SOG (.88 m/s) performed better than SG (.71 m/s) in the 4-m gait speed test (Table 2).

EORTC QLQ-C30

The EORTC QLQ-C30 showed a high level of reliability (Cronbach’s alpha = .804). The NSG had better scores than SG on the physical functioning scale and on the symptoms scales for fatigue, nausea, and vomiting than SG and SOG. No differences were observed between SG and SOG (Table 3).

Table 3.

Comparison of the scores on the EORTC QLQ-C30 and EORTC QLQ-H&N35.

	Non-sarcopenia (n = 17)	Sarcopenia (n = 34)	Sarcopenic Obesity (n = 20)	P*
Scores on the EORTC QLQ-C30 Questionnaire
Global Health status/Quality of life	83 (71–96)	67 (39–83)	71 (52–81)	NS
Physical functioning	93 (83–100)	73 (52–88)	83 (53–93)	.009.010^ç
Fatigue	11 (0–22)	39 (30–67)	44 (14–56)	.000^&
Fatigue	11 (0–22)	39 (30–67)	44 (14–56)	.004^
Nausea and vomiting	0 (0–0)	0 (0–17)	0 (0–33)	.012^&
Nausea and vomiting	0 (0–0)	0 (0–17)	0 (0–33)	.012^
Scores on the EORTC QLQ-H&N35 questionnaire
Swallowing	0 (0-17)	33 (0-52)	33 (2-50)	.004^&
Swallowing	0 (0-17)	33 (0-52)	33 (2-50)	.016^
Senses problems	0 (0-25)	50 (0-71)	0 (0-50)	.012^&
Speech problems	22 (0-56)	44 (11-67)	33 (11-67)	NS
Social eating	0 (0-25)	37 (0-67)	8 (0-42)	.010^&
Sticky saliva	0 (0-16)	67 (33-100)	50 (0-100)	.000^&
Sticky saliva	0 (0-16)	67 (33-100)	50 (0-100)	.006^
Feeding tube	0 (0-0)	0 (0-25)	0 (0-0)	NS
Weight loss	0 (0-100)	100 (0-100)	100 (0-100)	NS
Weight gain	0 (0-100)	0 (0-0)	0 (0-0)	.007^&
Weight gain	0 (0-100)	0 (0-0)	0 (0-0)	.001^

Results are expressed as the median (interquartile interval), NS: no statistical significance. *Statistical test: Kruskal-Wallis test; significance value corresponds to Bonferroni’s correction. Statistically significant P-value ≤ .05. ^&Nonsarcopenic group versus sarcopenic group. ^Nonsarcopenic group versus sarcopenic obesity group. ^çSarcopenic group versus sarcopenic obesity group

The physical functioning scale was positively correlated with SMI, hand-grip strength, gait speed, and the SMI/weight ratio, and negatively correlated with C-reactive protein. On the contrary, the fatigue symptoms scale performed the opposite of the physical functioning scale (Table 4).

Table 4.

Relationships between the scores on EORTC QLQ-C30 and EORTC QLQ-H&N35 questionnaires and the sarcopenia-related parameters.

	Skeletal Muscle-mass Index Rho (p)	Hand-Grip Strength Rho (p)	Gait Speed Rho (p)	Skeletal Muscle-mass Index/Weight Ratio Rho (p)	C-Reactive Protein Rho (p)
Scores on the EORTC QLQ-C30 Questionnaire
Global health status/Quality of life	.167 (.164)	.011 (.927)	.131 (.278)	.040 (.740)	.089 (.462)
Physical functioning	.433 (.000)	.244 (.041)	.401 (.001)	.243 (.041)	−.268 (.024)
Role functioning	.306 (.009)	.248 (.037)	.178 (.138)	.208 (.082)	−.284 (.016)
Fatigue	−.461 (.000)	−.350 (.003)	−.398 (.001)	−.241 (.043)	.248 (.037)
Pain	−.014 (.906)	−.059 (.623)	−.152 (.205)	−.031 (.800)	.354 (.002)
Scores on the EORTC QLQ-H&N35 questionnaire
Pain	−.098 (.414)	.010 (.936)	.061 (.616)	−.064 (.598)	.337 (.004)
Swallowing	−.338 (.004)	−.150 (.213)	−.156 (.0194)	−.073 (.547)	.403 (.000)
Social eating	−.277 (.019)	−.023 (.851)	−.188 (.117)	.034 (.779)	.381 (.001)
Opening mouth	−.253 (.023)	−.003 (.983)	−.108 (.371)	−.142 (.239)	.129 (.285)
Sticky saliva	−.395 (.001)	−.201 (.093)	−.329 (.005)	−.096 (.425)	.366 (.002)
Felt ill	−.101 (.404)	.017 (.889)	−.138 (.250)	−.258 (.030)	.148 (.218)
Pain killers	.088 (.467)	.069 (.569)	−.065 (.589)	.079 (.511)	.409 (.000)
Nutritional supplements	−.325 (.006)	−.056 (.643)	−.221 (.064)	−.199 (.096)	.271 (.022)
Feeding tube	−.233 (.050)	−.115 (.341)	−.329 (.005)	−.022 (.857)	.052 (.665)
Weight loss	−.278 (.019)	−.222 (.063)	−.115 (.339)	.012 (.918)	.287 (.015)

Results are expressed as the correlation coefficient (P-value). Statistical test: Spearman’s rho. Statistical significance P ≤ .05

EORTC QLQ-H&N35 Module

The EORTC QLQ-H&N35 module showed a high level of reliability (Cronbach’s alpha = .911). The NSG had better scores than SG and SOG on the symptom scales, swallowing, sticky saliva, and weight gain. As with the EORTC QLQ-C30, SG and SOG had similar scores (Table 3).

The scales of symptoms pain, swallowing, eating problems, sticky saliva, painkillers, nutritional supplements, and weight loss were positively related to the levels of C-reactive proteins (rho = .375, P = .002). The appetite loss scale was negatively associated with the gait speed test (rho = −.286, P = .016) (Table 4).

The SMI was negatively related to the following symptoms scales: swallowing, trouble with social eating, opening the mouth, sticky saliva, nutritional supplements, and weight loss. The results of the gait speed test were negatively related to sticky saliva and feeding tube scale scores, and the SMI/weight ratio had a negative association with the felt ill symptom scale (Table 5).

Table 5.

Relationships among the indicators of nutritional status, sarcopenia-related parameters, and the scores on EORTC QLQ-C30 and EORTC QLQ-H&N35 questionnaires.

	Albumin Rho (p)	Total Lymphocyte Count Rho (p)	Cholesterol Rho (p)	Body Mass Index Rho (p)	Phase Angle Rho (p)
Sarcopenia-Related Parameters
Skeletal muscle-mass index	.315 (.008)	.168 (.161)	.180 (.133)	.696 (.000)	.608 (.000)
Hand-grip strength	.299 (.011)	.006 (.963)	.108(.371)	.306 (.009)	.561 (.000)
Gait speed	.395 (.001)	.252 (.034)	.357 (.002)	.415 (.000)	.507 (.000)
Skeletal muscle-mass index/Weight ratio	−.090 (.454)	.016 (.895)	−.153 (.202)	−.246 (.039)	.472 (.000)
C-reactive protein	−.537 (.000)	−.062 (.609)	−.383 (.001)	−.329 (.005)	−.322 (.006)
Scores on the EORTC QLQ-C30 questionnaire
Global health status/quality of life	−.088 (0.465)	.279 (.018)	.098 (.416)	.154 (.199)	.080 (.508)
Physical functioning	.163 (.174)	.101 (.401)	.144 (.231)	.320 (.007)	.539 (.000)
Role functioning	.035 (.770)	−.002 (.989)	.058 (.632)	.249 (.037)	.364 (.002)
Fatigue	−.130 (.280)	−.107 (.374)	−.108 (.369)	−.317 (.007)	−.442 (.000)
Nausea and vomiting	.074 (.542)	−.254 (.032)	.060 (.618)	−.127 (.290)	.095 (.429)
Appetite loss	.012 (.921)	−.013 (.916)	−.061 (.611)	−.044 (.717)	−.326 (.006)
Constipation	.256 (.031)	−.041 (.735)	−.107 (.373)	.078 (.521)	.112 (.351)
Scores on the EORTC QLQ-H&N35 questionnaire
Swallowing	−.171 (.155)	−.120 (.317)	−.225 (.059)	−.305 (.010)	−.416 (.000)
Senses	.067 (.578)	−.198 (.098)	−.137 (.253)	−.293 (.013)	−.204 (.088)
Social eating	−.037 (.759)	−.050 (.680)	−.116 (.335)	−.376 (.001)	−.215 (.072)
Sexuality	.045 (.707)	−.266 (.025)	−.048 (.691)	−.245 (.039)	−.056 (.644)
Opening mouth	−.072 (.549)	−.175 (.144)	.083 (.491)	−.169 (.159)	−.253 (.033)
Sticky saliva	−.125 (.298)	−.251 (.035)	−.186 (.120)	−.382 (.001)	−.270 (.023)
Coughing	.138 (.250)	−.090 (.456)	−.083 (.494)	.192 (.109)	−.154 (.201)
Felt ill	.021 (.861)	−.042 (.729)	−.144 (.230)	−.032 (.791)	−.240 (.044)
Pain killers	−.256 (.031)	−.044 (.716)	−.244 (.040)	.013 (.916)	−.168 (.162)
Nutritional supplements	−.257 (.030)	−.157 (.190)	−.132 (.273)	−.291 (.014)	−.424 (.000)
Feeding tube	−.060 (.616)	−.061 (.612)	−.117 (.333)	−.281 (.018)	−.226 (.058)

Results are expressed as the correlation coefficient (P-value). Statistical test: Spearman’s rho. Statistical significance P ≤ .05

Discussion

Sarcopenia and sarcopenic obesity are alterations in body composition that have been associated with a loss of QoL in cancer patients. Although there are many studies, research in H&NC patients remains limited. To fill this literature gap, this article identifies the impact of sarcopenia and sarcopenic obesity on QoL and indicators of nutritional status in patients with H&NC.

This study demonstrates that H&NC patients without sarcopenia have better physical functioning, greater muscle strength, and less fatigue than patients with sarcopenia and sarcopenic obesity. However, no differences were observed between the QoL of patients with sarcopenia and sarcopenic obesity.

Sarcopenia was identified in 50% of our H&NC population, consistent with the prevalence of sarcopenia reported by other authors in H&NC patients.^{7,10,11,23,24} Certain groups of researchers reported lower (7% to 35%)^9,12,25 or higher (71% to 77%) percentages.^26,27 This wide range may be due to differences in how and when the body composition analysis was performed, the method used, and the cutoff points.

We found sarcopenia in 47.5% of overweight or obese patients—overall proportion 26%—consistent with Fattouh, despite his patients being in the pretreatment phase, present in only 30% of our population.¹⁴

In our study, NSG QoL scores were higher than those of patients with sarcopenia, in agreement with Wright et al,¹⁶ who found a positive correlation of skeletal muscle mass with high scores on global QoL (FACT-G questionnaire), physical functioning, and social/family functioning. These observations coincide with data reported by Galvao et al, Van Roekel et al, Caahlin and Cabbage, and Jeffrey et al, with other cancers using instruments such as SF-36¹⁷ or FACT-G.^18,28

-31

In contrast, in our current data, the association analysis of sarcopenic obesity in QoL in H&NC patients showed that the increased QoL values and functional performance were higher in NSG than in SG or SOG, with no differences between SG and SOG.

Although we did not perform survival analysis, other studies comparing overall survival of cancer patients with sarcopenia and sarcopenic obesity found that overall survival in patients with sarcopenic obesity was worse than in patients with sarcopenia only.^8,14

Others have shown that increased skeletal muscle mass in H&NC patients is associated with an increase in physical functioning reported by the patients,¹⁶ consistent with our finding that gait speed is positively related to the physical performance scale. This association is supported by the fact that the gait speed test reflects a person’s level of functionality or ability to perform basic activities.

Similar to the results of the global QoL scale, the physical functioning scale score was higher in the NSG than in SG and SOG, but no differences were found between the last 2. Our correlation analysis showed that a higher ratio of skeletal muscle mass/total weight is associated with lower physical functioning scores. Additionally, anorexia and increased inflammation, as evidenced by elevated serum C-reactive protein values, were also negatively associated with this scale.

For the treatment of sarcopenia, there is strong evidence that resistance exercise increases muscle mass and strength,^32
-34 reduces fatigue degree, and improves patient functionality. Nutritional interventions are recognized as necessary to improve clinical outcomes; a high protein diet or protein supplement (1 to 1.5 g/day) is recommended for the treatment of sarcopenia, and higher protein doses (up to 2 g/day) may be indicated in patients with severe illness or injury, or where there is evidence of proinflammatory disease/catabolic state.^35

-39 Since 1995, Biolo et al⁴⁰ have associated nutritional support and exercise with muscle protein synthesis. Given these facts, the proper planning of interventions that combine exercise and nutritional support is imperative.⁴¹

Serum albumin is a widely used indicator of nutritional status in the general population, but decreased albumin levels in severe pathological conditions such as cancer reflect aggravated inflammation, more so than the nutritional status of patients.^42
-44 Consequently, patients with sarcopenia had the lowest serum albumin levels and the highest C-reactive protein levels in our population. Low albumin production is related to the acute phase response caused by chronic stress caused by cancer and tumor cachexia. Similar values of total lymphocyte count and blood cholesterol between the 3 groups support this hypothesis, since anthropometric differences did not affect these 3 biochemical indicators of nutritional status.^42
-44

When PA values are low, it reflects a decrease in the integrity of the cell membrane. Our results showed lower PA values in SG than in NSG. PA values correlate positively with sarcopenia indicators (SMI, hand-grip strength, and gait speed), in contrast to the description by Garlini et al of healthy subjects.⁴⁵

Some of the limitations of our study need to be acknowledged. One of them is that the report is the result of a cross-sectional study; we cannot establish the causality between the sarcopenia phenotype and the scores on the different scales of the QoL instruments. The lack of homogeneity in clinical characteristics, mainly related to the clinical stage, the anatomical location of the tumor, the treatment phase, and the small sample size, makes it impossible to identify whether these QoL effects are modified by sarcopenic obesity.

The main strength of this study is its originality. As mentioned above, there have been few reports on the association of sarcopenia with QoL in H&NC patients; none of them have described this association in patients who are overweight or obese.

Conclusions

In summary, we demonstrated that patients without sarcopenia have higher physical functioning and less fatigue than patients with sarcopenia or sarcopenic obesity. It should be noted that the QoL of patients with sarcopenia is similar to that of patients with sarcopenic obesity. This information is relevant because being overweight or obese in an oncology patient can mask muscle loss in the absence of appropriate identification tools, thus delaying nutritional interventions. Future research should focus on identifying when H&NC patients begin to lose muscle mass, and suggesting optimal efforts to improve their QoL and functionality.

Footnotes

Acknowledgments

The authors would like to thank the following medical staff for their participation in patient recruitment: Castañeda-Ureña Alejandra, Jiménez-Beltrán Carlos, Jonguitud-Olguín Gregorio, López-Almaráz Luis-Manuel, De-la-Torre-Segura Martha-Karina, and Ramírez-Robles Jorge-Damián.

Authors’ Contributions

Conceptualization, LMABP, BEMH, and DSM; methodology, LMABP; software, BEMH; validation, LMABP, BEMH, BTH, FGB, and ECC; formal analysis, LMABP and BEMH; investigation, ASM, DAOZ, AZA, and JDFC; resources, LMABP, DSM, GAHC, LHBL, REMG, EGS, and CDC; data curation, BEMH; writing—original draft preparation, BEMH; writing—review and editing, LMABP, BEMH, BTH, DSM, FGB, ECC, GAHC, LHBL REMG, EGS, CDC, MSP, AHNZ, and EGS; visualization, LMABP; supervision, BEMH; project administration, LMABP and BEMH; funding acquisition, LMABP.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receiving the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Universidad de Guadalajara ['Convocatoria Apoyo a la Incorporación de Nuevos Profesores de Tiempo Completo PRODEP SEP 2018^′, assigned to Professor number UDG PTC 1388 Luz Ma. Adriana Balderas Peña in document: 511-6/18-9169, date July 31, 2018]. All authors supported the APC.

Ethics Approval

This study was carried out according to the Declaration of Helsinki guidelines and was approved by the Institutional Review Board of the Comité Local de Investigación en Salud 1301, Instituto Mexicano del Seguro Social, México.

Informed Consent

Informed consent was obtained from all subjects involved in the study.

Data Availability

The data sets generated and/or analyzed during the current study are not publicly available because they are the property of the Instituto Mexicano del Seguro Social. Institutional and federal dispositions restrict unlimited access to personal data, but they are available from the corresponding author on reasonable request with prior authorization from the institution.

ORCID iDs

Daniel Sat-Muñoz

Ruben-Eduardo Morán-Galaviz

Eduardo Gómez-Sánchez

Luz-Ma-Adriana Balderas-Peña

References

International Agency for Research on Cancer . Mexico cancer factsheets. 2021. https://gco.iarc.fr/today/data/factsheets/populations/484-mexico-fact-sheets.pdf

Ottosson

Söderström

Kjellén

Nilsson

Zackrisson

Laurell

. Weight and body mass index in relation to irradiated volume and to overall survival in patients with oropharyngeal cancer: a retrospective cohort study. Radiat Oncol. 2014;9:160. doi:10.1186/1748-717X-9-160.

Orell-Kotikangas

Österlund

Saarilahti

Ravasco

Schwab

Mäkitie

. NRS-2002 for pre-treatment nutritional risk screening and nutritional status assessment in head and neck cancer patients. Support Care Cancer. 2015;23(6):1495-1502. doi:10.1007/s00520-014-2500-0.

Lønbro

Petersen

Andersen

Johansen

. Prediction of critical weight loss during radiation treatment in head and neck cancer patients is dependent on BMI. Support Care Cancer. 2016;24(5):2101-2109. doi:10.1007/s00520-015-2999-8.

Ravasco

Monteiro-Grillo

Vidal

Camilo

. Nutritional deterioration in cancer: the role of disease and diet. Clin Oncol. 2003;15(8):443-450. doi:10.1016/s0936-6555(03)00155-9.

Sheth

Sharp

Walters

. Enteral feeding in head and neck cancer patients at a UK cancer centre. J Hum Nutr Diet. 2013;26(5):421-428. doi:10.1111/jhn.12029.

Chargi

Bril

Emmelot-Vonk

De Bree

. Sarcopenia is a prognostic factor for overall survival in elderly patients with head-and-neck cancer. Eur Arch Otorhinolaryngol. 2019;276(5):1475-1486. doi:10.1007/s00405-019-05361-4.

Ganju

Morse

Hoover

TenNapel

Lominska

. The impact of sarcopenia on tolerance of radiation and outcome in patients with head and neck cancer receiving chemoradiation. Radiother Oncol. 2019;137:117-124. doi:10.1016/j.radonc.2019.04.023.

Jung

Roh

Kim

, et al. Prognostic value of body composition on recurrence and survival of advanced-stage head and neck cancer. Eur J Cancer. 2019;116:98-106. doi:10.1016/j.ejca.2019.05.006.

10.

Martin

Gioulbasanis

Senesse

Baracos

. Cancer-associated malnutrition and CT-defined sarcopenia and myosteatosis are endemic in overweight and obese patients. J Parenter Enteral Nutr. 2020;44(2):227-238. doi:10.1002/jpen.1597.

11.

Stone

Olson

Mowery

, et al. Association between sarcopenia and mortality in patients undergoing surgical excision of head and neck cancer. JAMA Otolaryngology-Head & Neck Surgery. 2019;145(7):647-654. doi:10.1001/jamaoto.2019.1185.

12.

Tamaki

Manzoor

Babajanian

Ascha

Rezaee

Zender

. Clinical significance of sarcopenia among patients with advanced oropharyngeal cancer. Otolaryngol-Head Neck Surg (Tokyo). 2019;160(3):480-487. doi:10.1177/0194599818793857.

13.

Swartz

Pothen

Wegner

, et al. Feasibility of using head and neck CT imaging to assess skeletal muscle mass in head and neck cancer patients. Oral Oncol. 2016;62:28-33. doi:10.1016/j.oraloncology.2016.09.006.

14.

Fattouh

Chang

, et al. Association between pretreatment obesity, sarcopenia, and survival in patients with head and neck cancer. Head Neck. 2019;41(3):707-714. doi:10.1002/hed.25420.

15.

Baracos

Arribas

. Sarcopenic obesity: hidden muscle wasting and its impact for survival and complications of cancer therapy. Ann Oncol. 2018;29:ii1-ii9. doi:10.1093/annonc/mdx810.(suppl_2):

16.

Wright

Dillon

Durham

, et al. A randomized trial of adjunct testosterone for cancer-related muscle loss in men and women. J Cachexia, Sarcopenia and Muscle. 2018;9(3):482-496. doi:10.1002/jcsm.12295.

17.

Galvão

Taaffe

Spry

Joseph

Newton

. Combined resistance and aerobic exercise program reverses muscle loss in men undergoing androgen suppression therapy for prostate cancer without bone metastases: a randomized controlled trial. J Clin Oncol. 2010;28(2):340-347. doi:10.1200/JCO.2009.23.2488.

18.

Nipp

Fuchs

El-Jawahri

, et al. Sarcopenia is associated with quality of life and depression in patients with advanced cancer. Oncol. 2018;23(1):97-104. doi:10.1634/theoncologist.2017-0255.

19.

Cruz-Jentoft

Baeyens

Bauer

, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older people. Age Ageing. 2010;39(4):412-423. doi:10.1093/ageing/afq034.

20.

Roberts

Denison

Martin

, et al. A review of the measurement of grip strength in clinical and epidemiological studies: towards a standardised approach. Age Ageing. 2011;40(4):423-429. doi:10.1093/ageing/afr051.

21.

Carrillo

Ortiz-Toledo

MÁ

Salido-Noriega

Romero-Ventura

Ochoa-Carrillo

Oñate-Ocaña

. Validation of the mexican spanish version of the EORTC QLQ-H&N35 instrument to measure health-related quality of life in patients with head and neck cancers. Ann Surg Oncol. 2013;20(5):1417-1426. doi:10.1245/s10434-012-2712-9.

22.

Fayers

and Bottomley

EORTC Quality of Life Group; Quality of Life Unit . Quality of life research within the EORTC-the EORTC QLQ-C30. European Organisation for Research and Treatment of Cancer. Eur J Cancer 2002;38(Suppl 4):S125-S133. doi:10.1016/s0959-8049(01)00448-8. 11858978.

23.

Bril

Pezier

Tijink

Janssen

Braunius

Bree

. Preoperative low skeletal muscle mass as a risk factor for pharyngocutaneous fistula and decreased overall survival in patients undergoing total laryngectomy. Head Neck. 2019;41(6):1745-1755. doi:10.1002/hed.25638.

24.

Cho

Kim

Keum

Lee

Jeung

Lee

. Prognostic significance of sarcopenia with inflammation in patients with head and neck cancer who underwent definitive chemoradiotherapy. Front Oncol. 2018;8:457. doi:10.3389/fonc.2018.00457.

25.

Grossberg

Chamchod

Fuller

, et al. Association of body composition with survival and locoregional control of radiotherapy-treated head and neck squamous cell carcinoma. JAMA Oncol. 2016;2(6):782-789. doi:10.1001/jamaoncol.2015.6339.

26.

Kabarriti

Bontempo

Romano

, et al. The impact of dietary regimen compliance on outcomes for HNSCC patients treated with radiation therapy. Support Care Cancer. 2018;26(9):3307-3313. doi:10.1007/s00520-018-4198-x.

27.

Achim

Bash

Mowery

, et al. Prognostic indication of sarcopenia for wound complication after total laryngectomy. JAMA Otolaryngology-Head & Neck Surgery. 2017;143(12):1159-1165. doi:10.1001/jamaoto.2017.0547.

28.

Jeffery

Lee

YCG

Newton

, et al. Body composition and nutritional status in malignant pleural mesothelioma: implications for activity levels and quality of life. Eur J Clin Nutr. 2019;73(10):1412-1421. doi:10.1038/s41430-019-0418-9.

29.

Aahlin

Tranø

Johns

, et al. Health-related quality of life, cachexia and overall survival after major upper abdominal surgery: a prospective cohort study. Scand J Surg. 2017;106(1):40-46. doi:10.1177/1457496916645962.

30.

Van Roekel

Bours

MJL

Te Molder

MEM

, et al. Associations of adipose and muscle tissue parameters at colorectal cancer diagnosis with long-term health-related quality of life. Qual Life Res. 2017;26(7):1745-1759. doi:10.1007/s11136-017-1539-z.

31.

Adams

Segal

McKenzie

, et al. Impact of resistance and aerobic exercise on sarcopenia and dynapenia in breast cancer patients receiving adjuvant chemotherapy: a multicenter randomized controlled trial. Breast Cancer Res Treat. 2016;158(3):497-507. doi:10.1007/s10549-016-3900-2.

32.

Vlietstra

Hendrickx

Waters

. Exercise interventions in healthy older adults with sarcopenia: a systematic review and meta-analysis. Australas J Ageing. 2018;37(3):169-183. doi:10.1111/ajag.12521.

33.

Csapo

Alegre

. Effects of resistance training with moderate vs heavy loads on muscle mass and strength in the elderly: a meta-analysis. Scand J Med Sci Sports. 2016;26(9):995-1006. doi:10.1111/sms.12536.

34.

Roth

Ferrell

Hurley

. Strength training for the prevention and treatment of sarcopenia. J Nutr Health Aging. 2000;4(3):143-155.

35.

Bauer

Biolo

Cederholm

, et al. Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE study group. J Am Med Dir Assoc. 2013;14(8):542-559. doi:10.1016/j.jamda.2013.05.021.

36.

Bauer

Verlaan

Bautmans

, et al. Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the provide study: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc. 2015;16(9):740-747. doi:10.1016/j.jamda.2015.05.021.

37.

Liao

Tsauo

, et al. Effects of protein supplementation combined with resistance exercise on body composition and physical function in older adults: a systematic review and meta-analysis. Am J Clin Nutr. 2017;106(4):1078-1091. doi:10.3945/ajcn.116.143594.

38.

Geirsdottir

Arnarson

Ramel

Jonsson

Thorsdottir

. Dietary protein intake is associated with lean body mass in community-dwelling older adults. Nutr Res. 2013;33(8):608-612. doi:10.1016/j.nutres.2013.05.014.

39.

Katsanos

Kobayashi

Sheffield-Moore

Aarsland

Wolfe

. A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. Am J Physiol Endocrinol Metab. 2006;291(2):E381-E387. doi:10.1152/ajpendo.00488.2005.

40.

Biolo

Maggi

Williams

Tipton

Wolfe

. Increased rates of muscle protein turnover and amino acid transport after resistance exercise in humans. Am J Physiol. 1995;268(3 Pt 1):E514-E520. doi:10.1152/ajpendo.1995.268.3.E514.

41.

Kuwada

Kuroda

Kikuchi

, et al. Clinical impact of sarcopenia on gastric cancer. Anticancer Res. 2019;39(5):2241-2249. doi:10.21873/anticanres.13340.

42.

Marcason

. Should albumin and prealbumin be used as indicators for malnutrition? J Acad Nutr Diet. 2017;117(7):1144. doi:10.1016/j.jand.2017.04.018.

43.

Almasaudi

Dolan

Edwards

McMillan

. Hypoalbuminemia reflects nutritional risk, body composition and systemic inflammation and is independently associated with survival in patients with colorectal cancer. Cancers. 2020;12(7):1986. doi:10.3390/cancers12071986.

44.

McMillan

. Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care. 2009;12(3):223-226. doi:10.1097/MCO.0b013e32832a7902.

45.

Garlini

Alves

Ceretta

Perry

Souza

Clausell

. Phase angle and mortality: a systematic review. Eur J Clin Nutr. 2019;73(4):495-508. doi:10.1038/s41430-018-0159-1.

Quality of Life and Functionality of Head and Neck Cancer Patients Are Diminished As a Function of Sarcopenia and Obesity

Abstract

Background

Methods

Results

Conclusions

Keywords

Introduction

Patients and Methods

Results

EORTC QLQ-C30

EORTC QLQ-H&N35 Module

Discussion

Conclusions

Footnotes

Acknowledgments

Authors’ Contributions

Declaration of Conflicting Interests

Funding

Ethics Approval

Informed Consent

Data Availability

ORCID iDs

References