Longitudinal changes in skeletal muscle and adipose tissue during surgical treatment of oesophagogastric cancer: a prospective study.

doi:10.21203/rs.3.rs-4704469/v1

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Longitudinal changes in skeletal muscle and adipose tissue during surgical treatment of oesophagogastric cancer: a prospective study.

https://doi.org/10.21203/rs.3.rs-4704469/v1

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Background

Low muscle mass, myosteatosis, and excess adiposity are associated with adverse outcomes after oesophagogastric (OG) cancer surgery. There is limited prospective data to evaluate body composition throughout treatment. We aimed to measure longitudinal changes in skeletal muscle and adipose tissue and describe variations according to baseline BMI.

Methods

This prospective longitudinal study included patients having OG cancer surgery at Alfred Health, Melbourne, Australia. CT images and bioimpedance spectroscopy (BIS) were used to assess body composition at multiple time points up to 12 months postoperatively. Low skeletal muscle, myosteatosis and visceral obesity were defined using published thresholds. BMI groups were defined as ≥ 30kg/m² (obese) and < 30kg/m² (non-obese).

Results

There were 50 patients. During neoadjuvant treatment, CT-muscle declined (152.7 vs 142.4cm², p<0.001) and adipose tissue was stable. Postoperatively, total adipose tissue reduced (357.7 vs 224.4cm², p<0.001), but muscle did not (142.4 vs 133.6cm², p=0.064). Low CT-muscle prevalence increased during neoadjuvant treatment (diagnosis 33%, restaging 49%, p=0.02) but not at 12 months (54%, p=0.21). Visceral obesity was common and stable between diagnosis and restaging (58% vs 54%, p=1.00) with a marked reduction at 12 months (19%, p<0.001). BIS-muscle declined rapidly early after surgery and did not recover. The proportion of muscle and adipose tissue loss between BMI groups was comparable.

Conclusion

Weight loss during OG cancer treatment is significant. Skeletal muscle loss occurs during neoadjuvant treatment, while adipose tissue loss is predominant postoperatively. Anticipated changes in body composition should be considered throughout treatment, focusing on early muscle loss.

Health sciences/Health care/Diagnosis/Physical examination

Health sciences/Medical research/Translational research

Significant weight loss is a common consequence of the surgical management of oesophagogastric (OG) cancer and is associated with adverse oncological and surgical outcomes (1–3). A BMI < 18.5kg/m² increases the risk of complications and poorer overall survival after oesophagectomy (4). Obesity (BMI ≥ 30 kg/m²) also negatively impacts surgical outcomes (5), specifically, the association between visceral obesity and anastomotic leaks and pneumonia post-oesophagectomy (6).

Retrospective studies have demonstrated preoperative low muscularity, defined as low skeletal muscle index (SMI), and myosteatosis, a consequence of intramuscular fat infiltration, are associated with pulmonary complications, anastomotic leaks, and poorer survival after OG cancer surgery (7–10). Limited prospective longitudinal studies examine weight and body composition changes during OG cancer treatment, particularly in Western populations where obesity is prevalent. Understanding weight loss patterns and differentiating between skeletal muscle and adipose tissue loss, particularly in patients with obesity, may influence nutrition goals and interventions.

Body composition analysis using computed tomography (CT) segments skeletal muscle and visceral, subcutaneous, and intramuscular adipose tissue. CT analysis is precise, validated against dual-energy x-ray absorptiometry (DXA) to predict total body muscle mass (11), and accessible in oncology settings. However, accessing CT images for body composition analysis is opportunistic, limiting sequential measures. Bioimpedance spectroscopy (BIS) is convenient, has reasonable precision with 2–3% variability between repeated measures, and can be utilised longitudinally (12).

This study aims to a) determine the longitudinal changes in body weight, skeletal muscle, and adipose tissue compartments using CT and BIS body composition assessment techniques in patients undergoing surgical resection of oesophageal and gastric cancer, and b) describe the variation in body composition changes between patients with a preoperative BMI in obese (≥ 30 kg/m²) and non-obese (< 30 kg/m²) categories.

Study design and patient selection

This prospective single-centre longitudinal observational study included adults who had OG cancer surgery with curative intent at The Alfred Hospital, Melbourne, Australia, from 2018 to 2021. Patients with non-cancer resections, benign tumours, and surgery with palliative intent were excluded. Ethics approval was obtained from the Alfred Health Human Research and Ethics Committee (HREC number 104/18).

Clinical management

Patients with primary tumours (T2 or greater) received preoperative chemotherapy (MAGIC protocol (13) pre-2019 and FLOT protocol(14) thereafter for gastric tumours) or concurrent chemoradiotherapy (CROSS protocol (15) for oesophageal and junctional tumours). Surgical resection was a modified radical en bloc oesophagectomy or gastrectomy (D1+). The inpatient nutrition management approach was individualised per standard clinical practice, including feeding jejunostomy tube insertion. A dietitian (LM) provided outpatient dietary counselling.

Data collection

Demographic data were collected at enrolment. Comorbidities, oncological characteristics, and surgical data were sourced from a prospectively maintained database housed by the Department of Oesophago-Gastric and Bariatric Surgery. Disease stage was based on the AJCC Cancer Staging Manual 8th edition (16). Complications were graded according to the Clavien-Dindo Classification (severe ≥ Grade 3) (17).

Study assessments

Enrolment occurred preoperatively, and initial study assessments were conducted within one month before surgery. Study assessments were conducted approximately 2-, 6-, and 12 weeks post-discharge and 6 and 12 months postoperatively. CT images at diagnosis, restaging, and 12 months postoperatively were used for body composition analysis. Anthropometric and BIS measures were taken preoperatively and at each time point postoperatively.

Anthropometric measures

Anthropometric protocols were used to measure body weight and height (12). Patients were classified into BMI categories based on the World Health Organisation BMI scale (18). Loss of weight (LOW) at diagnosis was patient reported. Subsequent LOW was determined from the weight at the previous assessment. Patients were categorised into groups according to their preoperative BMI (non-obese BMI < 30 kg/m², obese BMI ≥ 30 kg/m²).

Computed Tomography (CT) body composition assessment

SliceOmatic Version 5.0 (Tomovision, Montreal, Canada) software measured skeletal muscle quantity and quality and visceral, subcutaneous, and intramuscular adipose tissue from CT images. All skeletal muscles in a single contrast-enhanced axial abdominal slice at L3 were assessed. Tissue quantity was reported as cross-sectional area (CSA) and density as mean attenuation, measured in Hounsfield Units (HU). Body compartments were identified using predefined HU thresholds of -29 to + 150 HU skeletal muscle (SM), -190 to -30 HU subcutaneous adipose tissue (SAT), -50 to -150 HU visceral adipose tissue (VAT), and − 190 to -30 HU intramuscular adipose tissue (IMAT) (11, 19). Two trained assessors (LM and KL) blinded to patient outcomes analysed images; the mean inter-rater coefficient was 0.73%.

Skeletal muscle CSA was normalised for height (m²) to obtain skeletal muscle index (SMI). Low SMI for Caucasians was males < 52.4 cm²/m² and females < 38.5 cm²/m² (20). Low SMI for Asian ethnicity was males < 40.8 cm²/m² and females < 34.9 cm²/m² (21). Muscle attenuation thresholds defining myosteatosis were < 41 HU for BMI ≤ 24.9 kg/m² and < 33 HU for BMI ≥ 25 kg/m² (22). VAT thresholds for visceral obesity were < 163.8 cm² in males and < 80.1 cm2 in females (23). To convert CSA to kg: lean body mass (LBM, kg) = 0.30 x [skeletal muscle cm²] + 6.06 and fat mass (FM, kg) = 0.042 x [total adipose tissue cm²] + 11.2 (11, 24).

Bioimpedance Spectroscopy (BIS) body composition assessment

Impedimed SF-B7 multifrequency bioimpedance spectroscopy device (ImpediMed Limited, Pinkenba, Queensland, Australia) was used to estimate fat-free mass (FFM, kg), fat mass (FM, kg). The fixed frequencies were 5, 10, 50, 100 and 500kHz. BIS assessment protocol was standardised per Earthman et al. (12), and measures were repeated three times. Patients with an electronic implantable device, severe oedema or those using diuretics were excluded from BIS measurements.

Results files were exported to the Impedimed software program (Bioimp, version 5.5.0.1, Impedimed Ltd, Pinkemaba, Queensland, Australia). Reliability was assessed by ensuring frequency limits were 0 to 1000 kHz, half-semi-circular Cole-Cole plots, adjusting the standard error of the estimate (SEE) to < 1, extracellular resistance (Re) was approximately half of intracellular resistance (Ri), and fat-free mass (FFM) was within physiological limits. Exclusion occurred when test conditions were unmet and the extracellular to intracellular body water ratio (ECW: IBW) approached 1. FFM was normalised for height to obtain fat-free mass index (FFMI, kg/m²). Low FFMI was males < 17kg/m² and females < 15kg/m² (25).

Statistics

Statistical analysis was undertaken using SPSS Statistics Version 23 (IBM Corp., New York, USA) or SAS version 9.4 (SAS Institute, Cary, USA). Continuous variables were summarised using means, standard deviations (SD), medians, and interquartile ranges (IQR) according to data type and distribution. Categorical variables were expressed as frequency counts and percentages. Group comparisons were performed using Student’s t-tests or Wilcoxon rank-sum tests as appropriate for continuous variables and chi-square or Fisher’s exact tests (where numbers were small) for categorical variables. Changes in body composition measures over time were assessed using the PROC MIXED procedure in SAS, with each patient treated as a random effect. Models were fitted using main effects for time, group (obese vs non-obese) and an interaction between group and time to ascertain if the groups behaved differently over time. Post-hoc comparisons were performed using Bonferroni adjustment for multiple comparisons. All calculated p values were two-tailed; a p < 0.05 indicated statistical significance. The study was powered to detect a mean difference in CT-derived SMI of 10.5cm/m² (SD 11.9) (26) between low SMI and normal SMI groups with 80% power at a significance level of 0.05.

Baseline characteristics

There were 50 patients; 45 (90%) had accessible measures at diagnosis, and 36 (72%) at 12 months. Patients were predominantly male (n = 31, 62%), mean age of 64 ± 10.3 years, had tumours located at the oesophagogastric junction (n = 30, 60%), and oesophagectomy was most common (n = 34, 68%) (Table 1).

Table 1

Baseline characteristics and postoperative outcomes in oesophagogastric cancer surgery patients (n = 50).
Age (years), mean (SD)	64 (10)	Adjuvant therapy, n (%)
Gender, n (%)		Chemotherapy	11 (22)
Male	31 (62)	No adjuvant therapy	39 (78)
Female	19 (38)	Resection type, n (%)
Comorbidities, n (%)		Distal gastrectomy	1 (2)
History of smoking	33 (66)	Subtotal gastrectomy	5 (10)
Cardiac	11 (22)	Total Gastrectomy	3 (6)
Respiratory	11 (22)	Total extended gastrectomy	7 (14)
Diabetes	8 (16)	3 stage oesophagectomy	7 (14)
Renal	3 (6)	Ivor Lewis oesophagectomy - open	3 (6)
Primary tumour site, n (%)		Ivor Lewis oesophagectomy - hybrid	24 (48)
Gastric	8 (16)	Feeding jejunostomy tube, n (%)	14 (28)
Oesophageal	12 (24)	Postoperative complications, n (%)
Oesophago-gastric junction	30 (60)	Overall	30 (60)
Disease pathology, n (%)		Anastomotic leak	6 (12)
Adenocarcinoma	39 (78)	Atelectasis	0 (0)
Squamous cell carcinoma	6 (12)	Bacteraemia	5 (10)
Signet ring	5 (10)	Cardiac arrythmia	8 (16)
Neoadjuvant therapy, n (%)		Chyle leak	2 (4)
Chemotherapy	13 (26)	Pleural effusion	6 (12)
Chemoradiation	30 (60)	Pneumonia	9 (18)
No neoadjuvant therapy	7 (14)	Pneumothorax	1 (2)
Pathological TNM stage, n (%)		Wound infection	4 (8)
Stage 0	0 (0)	Severe complication	13 (26)
Stage 1	9 (18)	Postoperative outcomes
Stage 2a	5 (10)	LOS (days), median (IQR)	11 (8–16)
Stage 2b	7 (14)	Readmitted ≤ 90 days, n (%)	9 (18)
Stage 3	21 (42)	Disease recurrence at 1 year, n (%)	13 (26)
Stage 4a	8 (16)	Overall survival at 1 year, n (%)	40 (78)
Stage 4b	0 (0)
LOS: length of stay; SD: standard deviation; TNM: tumour, node, metastasis.

Anthropometry

At diagnosis, mean body weight was 85.2kg (± 27.3), BMI 29.0 kg/m² (± 9.2), and 47% (n = 21) were overweight or obese (Table 2). Weight loss was most prominent from surgery to week two post-discharge and continued for 12 months (Fig. 1a). The proportion of underweight patients increased with a marked reduction in obesity, and the incidence of severe weight loss (≥ 10%) increased from 13% (n = 6) at diagnosis to 66% (n = 24) at 12 months (Table 2).

Table 2

Body mass index (BMI) and weight loss from diagnosis to 12 months postoperatively. Percentage weight loss was recorded as total weight lost from premorbid weight.
	Diagnosis n = 45	Preoperative n = 50	Week 2 n = 42	Week 6 n = 36	Week 12 n = 37	6 months n = 36	12 months n = 36	P value
BMI (kg/m²) mean (SE)	29.0 (1.1)	27.9 (1.1)	26.0 (1.1)	25.3 (1.1)	24.9 (1.1)	24.4 (1.1)	24.5 (1.1)	< 0.001*
BMI categories n (%)
Underweight (≤ 18.5 kg/m²)	5 (11)	4 (8)	8 (19)	11 (31)	10 (27)	13 (36)	9 (25)
Healthy weight (18.5–24.9 kg/m²)	19 (43)	23 (46)	19 (45)	13 (36)	13 (35)	12 (33)	16 (44)
Overweight (25-29.9 kg/m²)	8 (17)	9 (18)	12 (29)	9 (18)	10 (27)	8 (23)	8 (22)
Obese (≥ 30 kg/m²)	13 (30)	14 (28)	3 (7)	3 (8)	4 (11)	3 (8)	3 (8)
LOW (%) mean (SE)	3.3 (1.1)	6.0 (0.7)	9.1 (0.7)	10.7 (0.8)	9.8 (0.9)	12.1 (1.1)	13.0 (1.4)	0.002*
Weight loss categories n (%)
< 5%	33 (73)	23 (46)	6 (14)	1 (3)	7 (19)	7 (21)	5 (13)
5-9.9%	6 (13)	16 (32)	24 (57)	18 (50)	13 (35)	6 (18)	7 (20)
10-14.9%	4 (9)	8 (16)	9 (21)	13 (37)	11 (29)	14 (38)	13 (37)
15-19.9%	1 (2)	2 (4)	2 (6)	0 (0)	4 (10)	2 (6)	4 (10)
≥ 20%	1 (2)	1 (2)	1 (3)	4 (10)	2 (6)	6 (18)	7 (20)
BMI: body mass index (kg/m²); LOW: loss of weight; SE: standard error
* p value indicates a significant overall time effect (Linear mixed model)

Body composition assessment

Computed Tomography (CT)

During neoadjuvant treatment, skeletal muscle CSA (p = 0.0004) and skeletal muscle index (SMI) (50.4 ± 1.38 cm/m² diagnosis vs 47.2 ± 1.36 restaging, p = 0.002) reduced significantly without change in total adipose tissue (p = 0.919) (Fig. 2a). Postoperatively, changes in skeletal muscle were not statistically significant (p = 0.064), and SMI (47.2 ± 1.36 cm²/m² vs 45.1 ± 1.44 12 months, p = 0.047) and total adipose tissue (p < 0.0001) reduced with greater VAT loss (-93.5 cm²) compared to SAT (-38.36 cm²). Skeletal muscle attenuation remained stable during neoadjuvant treatment (37.16 ± 1.40 HU at diagnosis vs 36.16 ± 1.38 HU, p = 0.786) and increased at 12 months (40.09 ± 1.48 HU, p = 0.001).

Figure 2b describes the proportion of patients with low SMI, myosteatosis, and visceral obesity. The prevalence of low SMI and obesity was 6.7% (n = 3) at diagnosis, 6% (n = 3) preoperatively, and 3.2% (n = 1) at 12 months.

Females had lower skeletal muscle CSA than males (127.18 ± 8.07 cm² vs 153.36 ± 6.29 cm², p = 0.013) but no difference in SMI (44.68 ± 2.09 cm²/m² females vs 49.31 ± 1.63 cm²/m², p = 0.084). Males and females had similar VAT (p = 0.531), SAT (p = 0.731) and muscle attenuation (p = 0.396). There were no gender differences in skeletal muscle or total adipose tissue CSA change over time (p = 0.892 and p = 0.533, respectively). There were no differences between age groups (< or ≥ 65 years) for skeletal muscle (p = 0.727), total adipose tissue (p = 0.515) and skeletal muscle attenuation (p = 0.625).

Bioimpedance Spectroscopy (BIS)

Fat-free mass (FFM) reduced significantly from surgery to week two (p < 0.0001), with no significant changes after (Fig. 3a). FM loss was not significant until six months postoperatively (p = 0.0004) (Fig. 3b). The proportion with low FFMI increased from surgery to week two (n = 4, 8% vs n = 9, 18% p = 0.031), with no significant change at week 6 (n = 6, 12%), week 12 (n = 8, 16%), six months (n = 7, 14%) or 12 months (n = 6, 12%).

Overall, males had higher FFM than females (59.6 ± 2.5 kg vs 51.2 ± 3.2 kg, p = 0.037) and similar FM (17.7 ± 1.9 kg vs 21.7 ± 2.4 kg, p = 0.195), but there was significant time effect (p = 0.992 and p = 0.083, respectively). Age groups had comparable FFM (p = 0.855) and FM (p = 0.959), with similar postoperative changes.

BMI group differences

There were no differences in baseline, oncological and surgical characteristics of patients with obesity and those without (data not shown). Anthropometric and CT body composition variables are shown in Table 3. Preoperatively, both groups had 5% LOW, whereas patients with obesity had a higher percentage LOW than those without at 12 months (18.4 ± 4.3% vs 11.4 ± 1.3%, p = 0.048).

Table 3

The absolute values for anthropometric and CT body composition variables at diagnosis, preoperatively and 12 months postoperatively, comparing patients who were in obese (BMI ≤ 30kg/m²) and non-obese (BMI < 30kg/m²) groups before surgery. Linear mixed models assessed overall within-group (time effect) and between-group (obese vs non-obese) differences for 32 patients with CT body composition analysis at each time point. Post-hoc analyses compared differences at each time point.
	Diagnosis			Preoperative			Postoperative (12 months)			Overall group effect
	Non-obese n = 24	Obese n = 8	P value	Non-obese n = 24	Obese n = 8	P value	Non-obese n = 24	Obese n = 8	P value	P value
Anthropometrics
Weight (kg)^#	73.7 (2.8)	118.2 (9.5)	< 0.001	72.7 (2.6)	113.1 (9.3)	< 0.001	66.8 (2.9)	92.2 (9.2)	0.003	< 0.001^a,b
% LOW	2.9 (0.9)	0 (0)	0.082	5.2 (1.2)	5.1 (1.7)	0.160	11.4 (1.3)	18.4 (4.3)	0.048	0.069
CT body composition
Skeletal muscle (cm²)^#	135.3 (7.1)	191.8 (18.1)	< 0.001	127.5 (6.8)	178.1 (15.7)	0.002	124.6 (7.0)	160.5 (12.3)	0.016	0.006^a,b
Visceral AT (cm²)*	116.2 (18.5)	415.8 (56.6)	< 0.001	114.5 (18.0)	380.7 (46.9)	< 0.001	63.6 (12.7)	140.8 (32.2)	0.011	< 0.001^b
Subcutaneous AT (cm²)*	145.7 (8.9)	302.8 (57.2)	< 0.001	138.5 (12.3)	301.4 (59.3)	< 0.001	117.4 (12.5)	179.0 (47.3)	0.267	< 0.001^b
Total AT (cm²)*	237.7 (22.2)	808.8 (149.6)	< 0.001	264.2 (26.5)	742.6 (135.4)	< 0.001	192.0 (24.0)	315.0 (91.6)	0.204	< 0.001^b
Muscle density (HU)^#	40.6 (1.6)	27.1 (4.9)	< 0.001	38.7 (1.6)	28.6 (3.9)	< 0.001	41.5 (1.6)	36.0 (3.8)	0.126	0.006^b
Lean muscle mass (kg)^#	46.7 (2.1)	63.6 (5.4)	< 0.001	44.3 (2.0)	59.5 (4.7)	0.002	43.4 (2.21)	54.2 (3.7)	0.016	0.006^a,b
Fat mass (kg)*	22.7 (0.9)	45.2 (6.3)	< 0.001	22.3 (1.1)	42.4 (5.7)	< 0 .001	19.3 (1.0)	24.4 (3.8)	0.204	< 0.001^b
AT: adipose tissue; HU: Hounsfield Units; LOW: loss of weight.
#mean (SE); *median (IQR);
^a p < 0.05 within-group time effect difference between diagnosis and preoperative.
^b p < 0.05 within-group time effect difference between preoperative and postoperative.

At surgery, the absolute change in skeletal muscle CSA (-13.69 ± 6.27 cm² obese vs -7.86 ± 1.63 cm², p = 0.077) and muscle attenuation (-1.84 ± 1.08 HU obese vs 1.50 ± 2.13 HU, p = 0.601) between groups was not significant, but the obese group had lost more TAT than the non-obese group (-66.21 ± 66.43 cm² vs -8.80 ± 10.27 cm², p = 0.045). At 12 months, patients with obesity at diagnosis had greater absolute muscle loss (-31.36 ± 9.95 cm² obese vs 10.71 ± 2.36 cm², p = 0.006), improved muscle attenuation (8.89 ± 2.75 HU obese vs 0.94 ± 1.03 HU, p = 0.002) and higher TAT (-493.80 ± 131.60 cm² obese vs -81.75 ± 20.61 cm², p = 0.001) than patients without obesity. The percentage change in muscle quantity, TAT and muscle attenuation from diagnosis stratified by baseline obesity are shown in Fig. 4.

This prospective longitudinal study found that patients undergoing oesophagogastric cancer surgery experience substantial weight loss, predominantly muscle loss during neoadjuvant treatment and adipose tissue after surgery. Body composition changes were not influenced by the presence of obesity at diagnosis.

Mean weight loss of 13% at 12 months was consistent with studies reporting weight loss rates of 8.8–10.1% one-year post-oesophagectomy (27, 28) and 16% after total gastrectomy (29). Weight loss was rapid in the early postoperative period, with 46% of patients losing ≥ 10% of weight at 12 weeks. Early and severe weight loss, defined as 14–17% LOW within 1.5-3 months, predicts reduced survival after oesophagectomy (1, 30), poorer adjuvant chemotherapy tolerance, and disease-free survival after gastrectomy (3).

Skeletal muscle loss was observed throughout treatment, with the most significant reduction during neoadjuvant treatment. Skeletal muscle loss resulted in almost half of patients having CT-derived low SMI before surgery. Adipose tissue stores remained stable during the same period. Studies have shown muscle atrophy with the preservation of adipose tissue during neoadjuvant chemoradiation (31) and chemotherapy (32). Anecdotally, weight regain may occur after obstructive symptoms subside or neoadjuvant treatment completion. Frequent anthropometric and body composition assessments are required to determine whether weight regain is attributable to increased adipose tissue or skeletal muscle.

Although CT-muscle loss continues, changes from surgery to 12 months were not significant. Contradictory data show a significant decline in skeletal muscle within one year postoperatively (29, 31, 33, 34). Regardless, 36% of patients had low SMI at 12 months, aligning with 35% reported by Elliott et al (31). Boshier et al. demonstrated that one year after oesophagectomy, a greater than 10% decrease in SMI and low SMI was associated with poorer 5-year survival, whereas low SMI at diagnosis was not (33). The marked reduction in total and visceral fat is consistent with retrospective reports (33, 35).

Assessing longitudinal fat and fat-free mass using BIS provides unique insight into body composition variability within one year of surgery. Like weight loss, significant skeletal muscle loss occurred within one month after surgery without subsequent muscle mass recovery. In contrast, ongoing weight loss at 6 and 12 months coincided with a significant reduction in fat mass. There are limited studies utilising prospective bioimpedance measurements. Yoshida et al. showed muscle mass recovered from six months post-oesophagectomy, whereas fat mass was at the lowest point and remained stable (34). Contrasting results may be attributable to fewer patients with BMI ≥ 25 kg/m² (17% vs 46%), the predominance of squamous cell carcinoma, and different preoperative treatments; overall, a vastly different population to OG adenocarcinomas in the present study and Western centres.

Patients with obesity had significantly more weight loss at 12 months compared to the non-obese group (18% vs 11.4%). Although patients with obesity had higher baseline skeletal muscle and adipose tissue compared to patients without obesity, experiencing a greater absolute loss of both, the percentage change in muscle and adipose tissue was comparable between groups. These findings are relevant during neoadjuvant treatment when muscle loss is predominant and fat mass is maintained.

The negative implications of preoperative myosteatosis have been identified (9, 36, 37), but changes in muscle attenuation throughout treatment have not been described. Muscle attenuation was stable at surgery but increased postoperatively, indicating an overall improvement in muscle quality. However, the percentage increase in muscle attenuation after surgery for patients with obesity (55%) was significantly greater than in the non-obese group (3.3%). Muscle attenuation increases with reduced fat infiltration (38), explaining muscle quality improvement with adipose tissue loss.

The mechanisms for body composition changes are likely multifactorial and may differ depending on the phase of treatment. Muscle loss during neoadjuvant treatment and early postoperatively corresponds with inflammatory processes associated with chemotherapy-induced muscle wasting and the surgical stress response driving catabolism (39, 40). Negative energy balance in the absence of inflammation leads to the mobilisation of adipose tissue while preserving skeletal muscle (41) and may explain ongoing weight and fat mass loss observed 6 to 12 months after surgery.

Clinical oncology nutrition guidelines recommend body composition analysis forms part of a comprehensive nutrition assessment to provide individualised interventions (42). Yet, measuring weight alone, without knowledge of body composition changes, remains common. Weight loss experienced by patients with obesity during neoadjuvant treatment may be viewed favourably. Yet, our results demonstrate that weight loss during this period results from muscle wasting rather than fat loss, irrespective of BMI. Conversely, the negative implications of excess central adiposity may not be considered if weight maintenance is the primary focus before surgery.

The preoperative period presents an opportunity to improve body composition. Halliday et al. showed that a multimodal prehabilitation program attenuated skeletal muscle loss and reduced visceral adiposity (43). The marked reduction in weight at 12 months in patients with premorbid obesity, predominantly due to adipose tissue loss, is less concerning if muscle mass is preserved. Interventions to minimise muscle loss after surgery include individualised nutrition counselling for 12 months post-gastrectomy (44) and perioperative multi-disciplinary management (45).

To our knowledge, this is the first study to prospectively measure weight and body composition change, using multiple methods, throughout the curative treatment of oesophagogastric cancer and stratify changes based on premorbid BMI. A key strength is CT body composition analysis, which segments skeletal muscle and adipose tissue, delineating changes between compartments. Less comprehensive techniques that measure muscle circumference may misinterpret changes in muscle size with fluctuations in fat deposition. The study’s generalisability may be limited by challenges in achieving reproducible conditions for valid BIS measures in clinical practice. Finally, obtaining detailed perioperative dietary intake data linked with body composition changes may provide a focus for future nutrition intervention studies.

Weight loss during neoadjuvant treatment is primarily attributable to skeletal muscle loss. Despite continued muscle decline, adipose tissue loss is more substantial postoperatively, an important consideration for patients with obesity. CT body composition analysis provides a precise and validated method accessible to the surgical oncology population. In clinical practice, body composition should be assessed rather than focusing solely on body weight. Future research requires exploring interventions to preserve muscle, particularly during neoadjuvant therapy, and understanding the clinical impact of preoperative adipose tissue loss.

Data availability statement

The datasets generated during and/or analysed during the current study are available from the corresponding author upon reasonable request.

Acknowledgements

The authors would like to acknowledge the support and contributions of Dr Kate Lambell, Senior Dietitian at Alfred Health, Melbourne, Australia, for validating CT image analysis methodology, and Julie Playfair, research nurse at Monash University Department of Surgery, for assistance with study coordination and data collection.

Author contribution statement

Lisa C. Murnane, Paul R. Burton, Audrey C. Tierney, and Adrienne K. Forsyth contributed to the conception and design of the research. Lisa C. Murnane, Kalai Shaw, Paul R. Burton, Wendy A Brown, and Jim Koukounaras contributed to data acquisition. Lisa C. Murnane and Eldho Paul conducted the statistical analysis of data. Lisa C. Murnane, Audrey C. Tierney, and Adrienne K. Forsyth contributed to data interpretation. Lisa C. Murnane drafted the manuscript. All authors provided a critical appraisal of the manuscript and provided approval for publication of the final version.

Funding

No funding was received to conduct this research.

Ethics approval

Full ethics approval was obtained from the Alfred Human Research and Ethics Committee (HREC number 104/18). Informed consent was obtained from all participants.

Competing interests

Lisa Murnane has received a speaker honorarium from Fresenius-Kabi and Nestle Health Science outside of the submitted work. Prof. Wendy Brown has received grants from Johnson and Johnson, Medtronic, GORE and Novo Nordisc, and personal fees from GORE, Novo Nordisc, Merck Sharpe and Dohme, outside of the submitted work. For the remaining authors, no conflicts of interest were declared.

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Longitudinal changes in skeletal muscle and adipose tissue during surgical treatment of oesophagogastric cancer: a prospective study.

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Abstract

Figures

INTRODUCTION

METHODS

Study design and patient selection

Clinical management

Data collection

Study assessments

Anthropometric measures

Computed Tomography (CT) body composition assessment

Bioimpedance Spectroscopy (BIS) body composition assessment

Statistics

RESULTS

Baseline characteristics

Anthropometry

Body composition assessment

Computed Tomography (CT)

Bioimpedance Spectroscopy (BIS)

BMI group differences

DISCUSSION

CONCLUSION

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1