Jeong H, Ko Y, Kim KW, Lee JS, Seo S, Kim SY, Hong YS, Kim JE, Kim TW. Longitudinal changes in body composition during palliative systemic chemotherapy and survival outcomes in metastatic colorectal cancer. World J Gastrointest Oncol 2025; 17(5): 103479 [DOI: 10.4251/wjgo.v17.i5.103479]
Corresponding Author of This Article
Jeong Eun Kim, MD, PhD, Department of Oncology, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea. jeongeunkim@amc.seoul.kr
Research Domain of This Article
Oncology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Hyehyun Jeong, Seyoung Seo, Sun Young Kim, Yong Sang Hong, Jeong Eun Kim, Tae Won Kim, Department of Oncology, Asan Medical Center, Seoul 05505, South Korea
Yousun Ko, Biomedical Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, South Korea
Kyung Won Kim, Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, South Korea
Ji Sung Lee, Clinical Research Center, Asan Medical Center, Asan Medical Center, Seoul 05505, South Korea
Co-corresponding authors: Jeong Eun Kim and Tae Won Kim.
Author contributions: Jeong H performed formal analysis, conducted investigations, prepared the initial draft of the manuscript, and created visualizations for the study; Ko Y and Kim KW developed the software used in this study and analyzed imaging data; Lee JS performed formal analysis; Seo S, Kim SY, and Hong YS curated data; Kim SY, Kim JE and Kim TW obtained the funds for the research project; All authors reviewed and edited the manuscript. Kim JE and Kim TW proposed, conceptualized, and supervised the study, interpreted the data, and managed project administration.
Supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, by the Ministry of Health & Welfare, Republic of Korea, No. RS-2018-KH049509; and the 2022 Cancer Research Support Project from the Korea Foundation for Cancer Research, No. CB-2022-A-3.
Institutional review board statement: This study was approved by the institutional review board of Asan Medical Center and performed in accordance with the ethical standards of the institutional research committee and the Declaration of Helsinki (IRB No. 2021-0078).
Informed consent statement: The requirement for informed consent was waived by the IRB for this retrospective study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request at jeongeunkim@amc.seoul.kr.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jeong Eun Kim, MD, PhD, Department of Oncology, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea. jeongeunkim@amc.seoul.kr
Received: November 21, 2024 Revised: February 22, 2025 Accepted: April 15, 2025 Published online: May 15, 2025 Processing time: 175 Days and 22.3 Hours
Abstract
BACKGROUND
In patients with metastatic colorectal cancer, chemotherapy may lead to changes in body composition, including skeletal muscle quantity and quality, and body fat area and distribution. Longitudinal follow-up data in a homogeneous population are required to understand these changes better.
AIM
To comprehensively evaluate changes in body composition and their prognostic value in patients with metastatic colorectal cancer undergoing palliative chemotherapy.
METHODS
This retrospective study included patients with recurrent or metastatic colorectal cancer who received palliative chemotherapy between 2008 and 2017. Computed tomography scans were analyzed at multiple time points (before each new chemotherapy regimen and after discontinuing all chemotherapy). Body composition was analyzed from each scan using artificial intelligence software (AID-UTM, iAID Inc.), and its association with survival was evaluated through time-dependent Cox regression to adjust for time-varying effects.
RESULTS
This analysis included 1805 patients, with a median age at diagnosis of 57 years, and 62% were male. At first-line chemotherapy initiation, 4.7%, 30.9%, 36.5%, and 37.1% of the patients had sarcopenia, myosteatosis, and visceral and subcutaneous obesity, respectively. During treatment, approximately 54.5% of the patients experienced significant changes in body composition, with 9.1% and 19.2% developing new sarcopenia and myosteatosis, respectively. Sarcopenia and myosteatosis were associated with poorer survival outcomes [hazard ratio (HR) for sarcopenia, 2.55 (95%CI: 2.06-3.16, P < 0.001; HR for myosteatosis, 2.37 (95%CI: 2.00-2.82), P < 0.001]. In contrast, visceral and subcutaneous obesity were associated with improved survival [HR for visceral obesity, 0.69 (95%CI: 0.57-0.82), P < 0.001; HR for subcutaneous obesity, 0.78 (95%CI: 0.64-0.95), P = 0.015], with no negative impacts observed at higher fat levels. These changes correlated with end-of-life survival time.
CONCLUSION
Abnormalities and body composition changes were frequently observed during palliative chemotherapy for advanced colorectal cancer; myosteatosis was common. Comprehensive body composition assessment offers valuable prognostic insights without requiring additional testing.
Core Tip: This retrospective study included a homogeneous group of patients with metastatic colorectal cancer undergoing palliative chemotherapy, monitoring body composition changes through serial computed tomography scans during treatment. The majority of patients experienced changes in body composition, with an increased prevalence of sarcopenia and myosteatosis, both linked to poor survival outcomes. In contrast, visceral and subcutaneous obesity were associated with improved survival. Furthermore, changes in body composition during systemic therapy correlated with end-of-life survival. These findings suggest the prognostic value of monitoring body composition through routine computed tomography scans during chemotherapy.
Citation: Jeong H, Ko Y, Kim KW, Lee JS, Seo S, Kim SY, Hong YS, Kim JE, Kim TW. Longitudinal changes in body composition during palliative systemic chemotherapy and survival outcomes in metastatic colorectal cancer. World J Gastrointest Oncol 2025; 17(5): 103479
Cancer is a systemic disease that is accompanied by alterations in metabolism and body composition[1,2]. Recently, the abnormalities in body composition and their clinical implication in patients with cancer have witnessed growing interest. Numerous studies have consistently linked sarcopenia, characterized by muscle mass loss, to poor prognoses across various cancer types and stages[3]. Moreover, myosteatosis, the infiltration of fat into skeletal muscles, has emerged as a significant factor associated with poor survival in patients with cancer[4].
Recent advancements in imaging techniques have enabled a more comprehensive assessment of body composition. Computed tomography (CT) scans allow for the segmentation of fat and muscle areas, along with the measurement of their attenuations, enabling the detection of sarcopenia[5]. Additionally, muscle attenuation observed in CT images has been correlated with muscle fat content in biopsy studies[6,7], supporting the feasibility of noninvasive myosteatosis assessment using CT scans[8]. Moreover, CT-based analysis can provide insights into obesity-related metabolic changes by reflecting fat distribution rather than solely relying on body weight[9,10].
In colorectal cancer, the presence of sarcopenia at diagnosis has been linked to poorer survival outcomes, higher postoperative morbidity and mortality, and increased chemotherapy toxicity[11]. However, most studies have focused on only baseline values[12]. While some research has included chronological data, the majority of them included patients with operable, nonmetastatic colorectal cancers, or heterogeneous patient populations with various disease stages[13,14]. Limited data exist on comprehensive body composition changes during palliative systemic treatment in metastatic colorectal cancer[4,11]. However, CT-based body composition assessment can address several unmet needs in these patients. Unlike subjective evaluations based on general appearance or body posture, CT imaging provides objective, quantifiable data. Analyzing body composition changes during treatment and evaluating their prognostic value can guide clinical decision-making without requiring additional testing, as CT scans are routinely performed in these patients.
In this study, we analyzed a homogeneous patient cohort with recurrent or metastatic colorectal cancer receiving palliative systemic anti-cancer therapy. Using serial CT scans, we assessed abnormalities in body composition, including sarcopenia, myosteatosis, visceral obesity, and subcutaneous obesity. All measurements were performed using a deep-learning software. Using these methods, we aimed to comprehensively evaluate abnormalities in body composition, their serial changes during systemic chemotherapy, and their prognostic implications in a real-world patient population with advanced colorectal cancer[15].
MATERIALS AND METHODS
Patients
Patients aged ≥ 18 years with recurrent or metastatic colorectal cancer who received palliative systemic chemotherapy between January 2008 and November 2017 at Asan Medical Center, a tertiary referral center in the Republic of Korea, were retrospectively identified.
To evaluate chronological changes in body composition in the metastatic setting, only patients who had at least two abdominal CT scans for measuring body composition markers and were followed up until the discontinuation of palliative systemic chemotherapy were included in the analysis. Specifically, two contrast-enhanced abdominal CT scans were required: (1) A baseline CT scan performed at the initiation of first-line chemotherapy, defined as a CT scan within a 4-week window of the first treatment date; and (2) A follow-up CT scan taken after discontinuation of palliative chemotherapy, defined as the CT scan taken after, but closest to the last treatment date. Patients were excluded if they were still undergoing palliative chemotherapy at the last follow-up date or if they lacked paired baseline and post-therapy CT scans. This study was approved by the Institutional Review Board (IRB) of Asan Medical Center and performed in accordance with the ethical standards of the institutional research committee and the Declaration of Helsinki. The IRB granted a waiver of informed consent for this retrospective study (IRB No. 2021-0078).
CT images acquisition
Abdomen and pelvis CT examinations were performed using Somatom Definition (Siemens Healthineers, Erlangen, Germany), Discovery CT750 HD (GE Healthcare, Milwaukee, WI, United States), or LightSpeed VCT scanner (GE Healthcare). All CT examinations were performed with standardized parameters, including a tube voltage of 120 kVp; automated dose modulation (CareDose 4D, Siemens Healthineers; automA and smartmA, GE Healthcare); a matrix size of 512 × 512; and a collimation width of 0.625 mm. Image data were reconstructed with a slice thickness of 5 mm using the filtered back-projection technique and a soft tissue reconstruction algorithm (B30f kernel; Siemens Healthineers Standard kernel, GE Healthcare). For contrast enhancement, 100-150 mL of iopromide (Ultravist 370 or Ultravist 300; Bayer Schering Pharma, Berlin, Germany) was administered intravenously using an automatic power injector.
Measurements
Sequential abdominal CT images were acquired at the initiation of each line of palliative chemotherapy (within a 4-week window from the start of first-, second-, and third-line systemic therapy) and after the discontinuation of all chemotherapy. Body mass index (BMI) and laboratory markers of nutrition and inflammation, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, absolute lymphocyte counts, serum albumin levels, and total cholesterol levels, were also collected at the time of each CT scan[12,16,17].
Body composition was assessed using artificial intelligence software (AID-UTM, iAID Inc., Seoul, Korea)[18]. Briefly, the convolutional network-based software automatically selected axial CT images at the L3 vertebra level and segmented skeletal muscle, visceral fat, and subcutaneous fat based on predefined thresholds (-29 to +150 HU for abdominal muscles and -190 to -30 HU for fat tissues). The total abdominal muscle area (TAMA) was categorized into three subregions according to the CT density as follows: (1) Intermuscular adipose tissue area (IMAT) (-190 to -30 HU), indicating fat deposits between muscle groups and fibers; (2) Normal attenuation muscle area (NAMA) (+30 to +150 HU), representing healthy muscle with minimal intramuscular fat; and (3) Low attenuation muscle area (LAMA) (-29 to +29 HU), reflecting muscles with high intramuscular lipid pool, indicative of poor muscle health[19]. The fully automated model previously demonstrated a high correlation with manual segmentation performed by board-certified radiologists, achieving mean Dice similarly coefficients of 0.96-0.97[18].
Definition of body composition abnormalities
Body composition abnormalities were classified into four categories as follows, based on T-scores generated in comparison with a young reference group of Koreans[20,21]: (1) Sarcopenia: Defined as a T-score for BMI-adjusted skeletal muscle area (SMA/BMI) below -2.0, translating to absolute cutoff values of 4.97 for men and 3.46 for women; (2) Myosteatosis: Defined as a T-score for the ratio of NAMA/TAMA < -2.0, translating to absolute cutoff values of 66.4 for men and 65.1 for women; (3) Visceral obesity: Defined as a visceral fat area (VFA) of ≥ 100 cm2[22]; and (4) Subcutaneous obesity: Defined as a height-adjusted subcutaneous fat area index (SFAI) of ≥ 50.0 cm2/m2 in men and ≥ 42.0 cm2/m2 in women[23]. Additionally, BMI was categorized according to World Health Organization Asian-Pacific criteria[24].
Statistical analysis
Overall survival (OS) was defined as the time from the initiation of the first palliative chemotherapy to the date of death from any cause. Survival after the last chemotherapy, or end-of-life survival, was assessed from the date of the last CT scan after discontinuation of chemotherapy to the date of death.
Baseline characteristics were analyzed using descriptive statistics. Changes in body composition markers throughout the treatment course were assessed using a linear mixed model. To evaluate the overall prognostic impact of body composition parameters on OS, time-dependent Cox regression was applied. Since body composition parameters were measured at multiple time points for each patient, their time-varying impact on survival should be considered to estimate their effect on OS accurately. Survival after the last systemic therapy was estimated using the Kaplan-Meier method and compared with the log-rank test. A restricted cubic spline model with four knots was used to explore nonlinear associations of body composition markers as continuous values with OS. Pearson’s correlation coefficient (R) was used to assess the correlation among body composition markers, BMI, and laboratory values at each time point. All statistical analyses and visualizations were conducted using R version 4.1.1 (R Foundation for Statistical Computing, Vienna, Austria). The R packages survival[25], rms[26], and corrplot[27] were used for survival analysis, restricted cubic spline modeling, and creating correlation matrices, respectively.
RESULTS
Patient characteristics and body composition at baseline
Figure 1 shows the flow diagram of patient selection for this study. Between January 2008 and November 2017, a total of 2960 patients with recurrent or metastatic colorectal cancer who received palliative systemic therapy were identified. Among them, the following patients were excluded: Those without paired abdominal CT scan at both the initiation and after discontinuation of palliative chemotherapy (n = 1100), those still receiving treatment at the last follow-up (n = 52), and those without survival data (n = 3). Consequently, a total of 1805 patients were included in the final analysis (Supplementary Table 1).
Baseline characteristics of the study participants are summarized in Table 1. All patients received cytotoxic chemotherapy doublets, consisting of fluoropyrimidines combined with irinotecan or oxaliplatin, as first-line treatment. Overall, the median age at diagnosis was 57 years (range: 18-86 years), with men comprising 62.1% (n = 1121) of the cohort. At baseline, 4.7% (n = 85) of patients had sarcopenia, while 30.9% (n = 558) had myosteatosis. Regarding obesity, 36.5% (n = 659) had visceral obesity, while 37.1% (n = 670) had subcutaneous obesity. Notably, the median BMI of patients with sarcopenia at diagnosis was higher than that of the nonsarcopenic group (22.7 vs 24.8, P < 0.001). Patients were further classified by BMI, with 6.9% (n = 125) categorized as underweight and 24.8% (n = 447) as obese (BMI ≥ 25.0 kg/m²). Among the obese patients, 9.4% (n = 42) had a BMI ≥ 30 kg/m².
Duration of palliative systemic therapy, median (95%CI)
11.9 (11.2-12.6)
12.0 (11.3-12.6)
10.2 (6.0-14.4)
0.143
12.5 (11.6-13.6)
10.7 (9.7-11.9)
0.003
11.9 (10.9-12.7)
12.0 (10.6-13.0)
0.631
11.9 (10.8-12.6)
12.1 (10.9-13.1)
0.392
Palliative first-line regimen
0.489
0.895
0.038
0.504
Bevacizumab-containing
433 (24.0)
415 (24.1)
18 (21.2)
297 (23.8)
136 (24.4)
260 (22.7)
173 (26.3)
263 (23.2)
170 (25.4)
Cetuximab-containing
130 (7.2)
126 (7.3)
4 (4.7)
92 (7.4)
38 (6.8)
74 (6.5)
56 (8.5)
80 (7.0)
50 (7.5)
Chemotherapy only
1242 (68.8)
1179 (68.5)
63 (74.1)
858 (68.8)
384 (68.8)
812 (70.9)
430 (65.3)
792 (69.8)
450 (67.2)
Metastasectomy
249 (13.8)
236 (13.7)
13 (15.3)
0.803
175 (14.0)
74 (13.3)
0.715
160 (14.0)
89 (13.5)
0.842
148 (13.0)
101 (15.1)
0.254
Sarcopenia, myosteatosis, and visceral obesity were associated with age. The median age at diagnosis was higher in patients with these conditions compared to those without them (Table 1). The T-scores for sarcopenia and myosteatosis tended to be lower with older age at diagnosis, whereas the VFA was higher. However, SFAI showed no significant association with age (Supplementary Figure 1). The incidence of sarcopenia did not differ significantly between sexes [5.0% (n = 56) vs 4.2% (n = 29) in men and women, respectively; P = 0.535]. However, compared to women, men had higher rates of visceral obesity [44.4% (n = 498) vs 23.5% (n = 161), P < 0.001], but lower rates of myosteatosis [22.1% (n = 248) vs 45.3% (n = 310), P < 0.001] and subcutaneous obesity [15.8% (n = 177) vs 72.1% (n = 493), P < 0.001][15].
Changes in body composition during palliative chemotherapy
Changes in body composition parameters, along with the prevalence of sarcopenia, myosteatosis, visceral obesity, and subcutaneous obesity at each time point, are summarized in Table 2. Figure 2 illustrates the proportions of patients who experienced changes in each body composition marker during treatment. Overall, approximately 54.5% (n = 984) of patients experienced changes in their body composition status during treatment. From baseline to the period after discontinuing systemic therapy, the overall prevalence of sarcopenia increased from 4.7% to 12.0%, while that of myosteatosis rose from 30.9% to 44.8% (Table 2). Notably, 9.1% and 19.2% of patients developed new-onset sarcopenia and myosteatosis, respectively (Figure 2). After the final chemotherapy, myosteatosis emerged as the most common body composition abnormality, affecting 44.8% of patients. Although the overall prevalence of obesity remained relatively stable during treatment, dynamic changes were observed. Specifically, 12.9% and 10.5% of patients developed new visceral and subcutaneous obesity, respectively, while 8.6% and 7.6% of patients saw their pre-existing visceral and subcutaneous obesity resolved during treatment, respectively.
Figure 2 Class changes in body composition during treatment.
Percentage changes in the prevalence of abnormal body composition from baseline to after the last systemic chemotherapy were shown. S: Sarcopenia; ScO: Subcutaneous obesity; M: Myosteatosis; mo: Months; VO: Visceral obesity.
Table 2 Incidence of sarcopenia at baseline, during treatment, and after the last systemic anticancer therapy, n (%).
During a median follow-up period of 40.3 months (95%CI: 37.9-43.9), a total of 983 patients died. The median OS for the entire cohort was 32.0 months (95%CI: 29.8-34.2). Table 3 shows the overall hazard ratios (HRs) estimated through time-dependent Cox regression analyses, which account for time-varying effects by incorporating all CT scans obtained at multiple time points for each patient. The analysis revealed that sarcopenia and myosteatosis were associated with poorer OS, whereas visceral and subcutaneous obesity were linked to better OS. After adjusting for clinical factors, including BMI, age at diagnosis, initial cancer stage, primary tumor location[28], metastasectomy, first-line treatment regimens, and lines of treatment, body composition markers remained independently associated with survival [HR for sarcopenia, 2.55 (95%CI: 2.06-3.16), P < 0.001; for myosteatosis, 2.37 (95%CI: 2.00-2.82) P < 0.001; for visceral obesity, 0.69 (95%CI: 0.57-0.82), P < 0.001; for subcutaneous obesity, 0.78 (95%CI: 0.64-0.95), P = 0.015][15].
Table 3 Univariable and multivariable time-dependent Cox regression analysis.
Univariable
Multivariable
HR (95%CI)
P value
HR (95%CI)
P value
Body composition (categorical)
Sarcopenia
2.64 (2.16-3.23)
< 0.001
2.55 (2.06-3.16)
< 0.001
Myosteatosis
1.91 (1.67-2.18)
< 0.001
2.37 (2.00-2.82)
< 0.001
Visceral obesity
0.74 (0.65-0.85)
< 0.001
0.69 (0.57-0.82)
< 0.001
Subcutaneous obesity
0.75 (0.66-0.86)
< 0.001
0.78 (0.64-0.95)
0.015
BMI (vs normal)
Obese
0.66 (0.57-0.77)
< 0.001
0.68 (0.56-0.83)
< 0.001
Underweight
2.26 (1.74-2.94)
< 0.001
2.26 (1.75-2.91)
< 0.001
Other clinical variables
Age ≥ 60 years
1.20 (1.06-1.36)
0.004
0.80 (0.69-0.93)
0.004
Female sex (vs male)
1.03 (0.91-1.17)
0.650
0.89 (0.74-1.07)
0.229
Initially metastatic (vs recurrent)
1.28 (1.11-1.47)
0.001
1.43 (1.23-1.66)
< 0.001
Primary tumor location (vs left/rectum)
Right
1.25 (1.08-1.45)
0.003
1.40 (1.17-1.67)
< 0.001
Multifocal/unknown
2.25 (1.41-3.59)
0.001
2.26 (1.54-3.31)
< 0.001
Metastasectomy
0.36 (0.29-0.46)
< 0.001
0.35 (0.28-0.45)
< 0.001
First-line chemotherapy with targeted agent (vs chemotherapy only)
0.44 (0.37-0.52)
< 0.001
0.45 (0.37-0.54)
< 0.001
Lines of treatment (vs 1)
2
1.51 (1.28-1.78)
< 0.001
1.50 (1.24-1.82)
< 0.001
≥ 3
1.29 (1.09-1.53)
0.004
1.20 (0.99-1.46)
0.063
Body composition (continuous)
Sarcopenia T-score
0.69 (0.64-0.74)
< 0.001
Myosteatosis T-score
0.80 (0.77-0.84)
< 0.001
Visceral fat area/100
0.76 (0.67-0.86)
< 0.001
Subcutaneous fat index/10
0.89 (0.86-0.92)
< 0.001
BMI/5
0.60 (0.53-0.67)
< 0.001
When body composition markers were analyzed as continuous variables, the findings remained consistent. Figure 3 displays restricted cubic spline curves showing the HRs of each body composition parameter for survival. Higher T-scores for sarcopenia and myosteatosis were linked to better OS (Table 3, Figure 3A and B). Regarding obesity, elevated VFA, SFAI, and BMI were associated with improved OS (Table 3). Moreover, no inverse relationships were observed at the highest levels of VFA, SFAI, or BMI (Figure 3C-E), further supporting the overall protective effect of obesity in survival outcomes.
Figure 3 Restricted cubic spline curve showing the hazard ratios of body composition parameters and survival.
A: Sarcopenia T score; B: Myosteatosis T score; C: Visceral fat area; D: Subcutaneous fat area index; E: Body mass index. P values are for nonlinearity.
Changes in body composition during treatment and their association with end-of-life survival
Survival after the last systemic chemotherapy, or end-of-life survival, was associated with changes in body composition markers during treatment, as shown in Figure 4. Using cutoff values established through sensitivity analyses (Supplementary Figure 2), patients who experienced a significant decrease in T-scores for sarcopenia [T-scores < -0.5 (n = 732, 41.0%)], myosteatosis [T-scores < -0.5 (n = 944, 52.3%)], visceral fat [VFAT < -20% (n = 419, 23.2%)], or subcutaneous fat [SFAI < -15% (n = 447, 24.8%)] during treatment showed shorter survival after the last chemotherapy compared to those who did not, regardless of their baseline status[15].
Figure 4 Baseline status and changes in body composition and their association with survival after the last systemic chemotherapy.
A: Sarcopenia; B: Myosteatosis; C: Visceral obesity; D: Subcutaneous obesity. Decrease in the sarcopenia and myosteatosis indices, visceral fat, and subcutaneous fat were defined as sarcopenia T-scores < -0.5, myosteatosis T-scores < -0.5, visceral fat area < -20%, subcutaneous fat area index < -15%, respectively. ScO: Subcutaneous obesity; mo: Months; VO: Visceral obesity; HR: Hazard ratio.
Correlations with BMI and laboratory tests
Figure 5 shows correlation matrices illustrating relationships among body composition parameters, as well as their correlations with BMI and various laboratory parameters related to nutrition and inflammation (Figure 5A, depicts correlations at the start of palliative chemotherapy, while Figure 5B, shows correlations after discontinuing all chemotherapy). BMI exhibited a weak negative correlation with sarcopenia and myosteatosis (Pearson’s R, -0.34 to -0.19), whereas it showed a moderate positive correlation with VFA or SFAI (Pearson’s R, 0.65-0.72) at both time points. Overall, all laboratory parameters analyzed showed weak correlations with body composition parameters[15].
Figure 5 Correlation matrix at baseline, after the last systemic chemotherapy.
A: Correlation matrix at baseline; B: After the last systemic chemotherapy. The numbers shown are Pearson’s correlation coefficients with P values < 0.05. Negative and positive values indicate negative and positive correlations, respectively. Blanks indicate nonsignificant values. Alb: Albumin; ALC: Absolute lymphocyte count; BMI: Body mass index; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; SFAI: Subcutaneous fat area index; T-chol: Total cholesterol; VFA: Visceral fat area.
DISCUSSION
This study provides a comprehensive evaluation of body composition dynamics during palliative chemotherapy and their impact on metastatic colorectal cancer. Our findings highlight that myosteatosis was the most common body composition abnormality and the most frequent change observed during treatment, surpassing sarcopenia. Survival analysis using serial data acquired at multiple time points demonstrated that sarcopenia and myosteatosis were associated with poorer survival outcomes, whereas obesity, regardless of fat distribution (subcutaneous or visceral), was linked to improved survival. Moreover, dynamic changes in fat and muscle composition during palliative chemotherapy were associated with survival in the last months of life after treatment discontinuation. Despite their strong prognostic value, body composition markers showed only weak correlations with BMI or standard laboratory tests, suggesting the need for dedicated assessments in clinical practice. To the best of our knowledge, this is the largest study to provide a comprehensive, longitudinal analysis of body composition and its prognostic implication in a homogenous cohort of patients with metastatic colorectal cancer undergoing palliative chemotherapy.
Interestingly, the prevalence of sarcopenia at baseline in our cohort (5%) was comparable to that of the healthy Korean population (4%-9%)[21]. Even after the last systemic chemotherapy, the majority of patients remained nonsarcopenic. In contrast, myosteatosis (31%) was more prevalent in our cohort compared to 17%-22% in the healthy population[20], with 19% of patients developing new-onset myosteatosis during treatment. These data suggest that although muscle loss is a significant concern in patients with cancer, qualitative changes in muscle, such as myosteatosis, are more prevalent in colorectal cancer and require clinical attention. Previous studies have reported varying prevalence rates of sarcopenia and myosteatosis among patients with colorectal[11,29], likely due to differences in methodologies and diagnostic cutoffs across studies. We used healthy Koreans as a reference rather than implementing data from Western countries, ensuring that ethnic differences in muscle mass were appropriately accounted for[15,21,30].
We found that sarcopenia and myosteatosis were independently linked to poor survival, with HRs for OS exceeding 2, consistent with previous findings[11,29]. Notably, we incorporated all longitudinal body composition data and utilized a time-dependent approach to assess overall hazards, reflecting the impact of body composition changes during treatment[10]. Moreover, changes in T-scores for sarcopenia and myosteatosis during palliative chemotherapy were significantly associated with end-of-life survival, regardless of baseline body composition status. These findings highlight the importance of monitoring body composition throughout treatment to obtain prognostic insights in the last months of life, which could help in planning appropriate patient care. However, the cutoffs used to define body composition changes in this study remain exploratory and require further validation.
Obesity was found to be associated with favorable survival outcomes, regardless of fat tissue distribution. This contrasts with previous studies that reported poorer survival outcomes in obese patients with colorectal cancer[31-33]. However, those studies primarily included patients who underwent curative resection. Moreover, a protective effect of obesity has been observed in the prospective cohort studies of patients with metastatic colorectal cancer, consistent with our findings[34,35]. Furthermore, patients who experienced a reduction in both visceral and subcutaneous fat during systemic chemotherapy had worse survival outcomes, regardless of their baseline obesity status, further supporting the protective role of obesity in these patients. Besides its association with survival outcomes, we also found that visceral and subcutaneous obesity had only a weak correlation with myosteatosis, suggesting that myosteatosis may serve as a better surrogate of a poor metabolic phenotype than visceral obesity[36,37].
Previous research has highlighted both pro- and antitumoral characteristics of adipose tissue. On the one hand, adipose tissue contributes to cancer development and progression through mechanisms such as chronic inflammation, activation of cancer-related signaling pathways like PI3K/AKT, and increased oxidative stress, which can lead to DNA damage[38-40]. On the other hand, studies have reported enhanced responses to immune checkpoint inhibitors and anti-vascular endothelial growth factor therapies in obese patients. Potential mechanisms include increased expression of programmed cell death protein 1 in T-cells in response to elevated leptin secretion in adipose tissue, as well as the role of peritumoral adipose tissue as a reservoir for immune cells[41-43]. Furthermore, adipose tissue may serve as an energy reserve in patients with advanced-stage cancer and could be linked to reduced protein catabolism[44]. Given these complex interactions, while obesity has been associated with adverse outcomes in some patients with cancer, its impact on survival outcomes varies depending on cancer type and stage. Notably, only a small proportion of patients classified as obese had class II obesity (BMI ≥ 30 kg/m2)[24]. Although we did not observe inverse trends at the highest values of body fat area or BMI, the impact of severe obesity remains challenging to assess with our dataset and should be interpreted with caution.
Lastly, body composition parameters, particularly myosteatosis and sarcopenia, showed only a weak correlation with BMI and other laboratory markers related to nutrition and inflammation. Notably, none of the patients with sarcopenia in our cohort were underweight (BMI < 18.5 kg/m2), and the median BMI was actually higher in patients with sarcopenia than in those without the condition. This is consistent with previous studies indicating that SMA does not correlate with BMI in patients with cancer[45,46]. The prognostic value of abnormal body composition, coupled with its weak correlation with traditional measures, highlights the need for CT-based body composition evaluations in patients with metastatic colorectal cancer. This is particularly beneficial for this category of patients with advanced cancer, as additional testing is not required given that most patients undergo regular CT evaluations. Moreover, our deep-learning-based system facilitated automated body composition assessment, minimizing the need for manual work, extra cost, and additional time[18,47].
This study has some limitations, primarily due to its single-center, retrospective design. Additionally, the study included only Asian patients, and the definitions of sarcopenia and myosteatosis were based on Korean data, which may limit generalizability while minimizing potential confounding effects of ethnicity. However, key strengths of our study include the large, homogeneous patient population and the availability of longitudinal data for each patient. Future studies are needed to determine whether body composition measurements can aid treatment decision-making, such as the timing of chemotherapy administration or patient selection for clinical trials. Further studies are required to explore the effectiveness of therapeutic interventions on body composition and the underlying mechanism driving these changes[48-50]. Although major body composition variables met the proportionality assumption, some clinical variables, such as tumor sidedness, were included in the multivariable model despite breaching this due to their clinical relevance. Lastly, our dataset reflects a real-world population but lacks information on enteral feeding plans and nutritional interventions. Studies controlling for such variables would provide a better understanding of the true prognostic value of body composition.
CONCLUSION
Abnormalities and changes in body composition were frequently observed during palliative chemotherapy in patients with advanced colorectal cancer, with myosteatosis being the most common. While sarcopenia and myosteatosis were associated with poor prognosis, both visceral and subcutaneous obesity had a protective effect on survival. CT-based assessment of these body composition markers during systemic treatment can offer valuable prognostic insight without requiring additional testing.
ACKNOWLEDGEMENTS
This manuscript is based in part on the author's doctoral dissertation.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Oncology
Country of origin: South Korea
Peer-review report’s classification
Scientific Quality: Grade A, Grade A, Grade C
Novelty: Grade B, Grade B, Grade B
Creativity or Innovation: Grade B, Grade B, Grade C
Scientific Significance: Grade B, Grade B, Grade C
P-Reviewer: Li X; Wu HM S-Editor: Li L L-Editor: A P-Editor: Zhao S
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