. 2022 May 27;12:892935. doi: 10.3389/fonc.2022.892935

Table 2.

Main characteristics of included studies (n = 19).

1st Author Year Country	Study design, Aim	Cancer type, stage¹	Sample size (number of males), age²	Treatment³	Measuring tool, component⁴	Pre-NAT	Post-NAT	Findings
Yip 2014 UK (39)	Retrospective, To evaluate changes in body composition after NAC and the association with outcomes.	EC	35 (30)	NAC:	CT FFM (kg/m²)	18.47 ± 2.24	17.57 ± 2.14	Muscle change:
		0-III	63 (34-78)	100%				FFM ↓ significantly after NAC, change rate was -4.6 ± 6.8%. Prevalence of sarcopenia: increased, from 16% to 43%.
								Association with outcomes:
								• Skeletal muscle loss (SML) was associated with risk of circumferential resection margin positivity, but not related to survival.
Ida 2014 Japan (38)	Prospective, To determine the influence of NAC on the body composition and to evaluate the association with postoperative complications.	EC	30 (25)	NAC: 100%	BIA SMM (kg)	24.9 ± 0.8	25.2 ± 0.7	Muscle change:
		I-IV	65 (53-75)					No significant decrease showed in SMM after NAC. 36.7% patients had SML.
								Association with outcomes:
								• Change in skeletal muscle was associated with postoperative complications.
Reisinger 2015 Netherlands (40)	Prospective, To investigate whether the degree of muscle mass lost during NCRT predicts postoperative mortality.	EC	96 (80)	NCRT: 100%	CT	50.9 ± 8.5	48.4 ± 8.5	Muscle change:
		I-IV	NS		SMI (cm²/m²)			SMM ↓ significantly after NCRT. Prevalence of sarcopenia: increased, from 56% to 67%.
								Association with outcomes:
								No significant association between muscle loss and mortality was found in the complete cohort. For advanced stage (III-IV), SML may predict postoperative mortality.
Liu 2016 Japan (41)	Retrospective, To determine whether changes in skeletal muscle after NAT predict prognosis.	EC	84 (72)	NAC: 23%	CT SM (PMI) (cm²/m²)	4.63 (1.77-6.89) ^a	4.54 (1.59-6.89) ^a	Muscle change:
		I-III	NS	NCRT: 77%				SMM ↓ significantly after NAT. 64% patients had SML. Cut-off value for severe SML: >-0.28; 50% patients had severe SML.
								Association with outcomes:
								• Severe SML during NAT was associated with poor overall survival (OS).
Miyata 2017 Japan (24)	Retrospective, To investigate changes in body composition during NAC and assess whether chemotherapy-related toxicities affect body composition.	EC	94 (76)	NAC: 100%	BIA SMM (kg)	25.0 ± 4.8	24.9 ± 4.8	Muscle change:
		I-IV	64.2 ± 8.8					No significant decrease showed in SMM after NAC. Prevalence of sarcopenia: increased, from 47% to 53%.
								Association with outcomes:
								• The incidence of serious adverse events (e.g., febrile neutropenia) was associated with severe SML.
Guinan 2017 Ireland (42)	Prospective, To investigate SMM and physical performance from diagnosis to post-NAT.	EC	28 (23)	NAC: 21%	CT SMI (cm²/m²)	60.3 ± 8.1	54.7 ± 7.5	Muscle change:
Guinan 2017 Ireland (42)		NS	62.8 ± 8.2	NCRT: 79%	CT SMI (cm²/m²)	60.3 ± 8.1	54.7 ± 7.5	SMM ↓ significantly after NAT. Prevalence of sarcopenia: increased, from 7% to 22%. Association with outcomes: NS
Motoori 2018 Japan (18)	Retrospective, To evaluate the influence of sarcopenia, changes in body composition, and adverse events during NCRT on postoperative infectious complications.	EC	83 (66)	NCRT: 100%	BIA SMI (kg/m²)	NS	NS	Muscle change:
		I-IV	65 (45-81)					SMM ↓ significantly after NCRT in patients with postoperative infectious complications. 53% patients had SML. Cut-off value for severe SML: >5%; 18.0% patients had severe SML.
								Association with outcomes:
								• SML during NCRT was a significant risk factor for postoperative infectious complications.
Jarvinen 2018 Finland (43)	Retrospective,	EC	115 (86)	NAC: 76%	CT SMI (cm²/m²)	NS	NS	Muscle change:
	To assess the effect of sarcopenia and skeletal muscle loss during NAT.	NS	NS	NCRT: 24%				Prevalence of sarcopenia: not significant increased, from 79% to 80%. Cut-off value for severe SML: >3%; 50% patients had severe SML.
								Association with outcomes:
								• Severe SML during NAT was associated with poor OS.
Ozawa 2019 Japan (29)	Retrospective, To investigate the impact of skeletal muscle loss on patients with ES after NAT.	EC	82 (71)	NAC: 46%	CT SM (PMI) (cm²/m²)	5.08 (2.74-9.93) ^a	4.87 (2.59-9.61) ^a	Muscle change:
		NS	63.5 ± 7.5	NCRT: 54%				Mean reduction in PMI value: 0.2 cm²/m². 75.6% patients had SML.
								Association with outcomes:
								• Low muscle mass before surgery was related to higher risk of recurrence and poorer disease-free survival (DFS).
Yassaie 2019 New Zealand (30)	Retrospective, To assess whether the change in muscle mass with neoadjuvant treatment can predict postoperative outcomes.	EC	53 (49)	NAC: 89%	CT SM (TPA) (cm²)	NS	NS	Muscle change:
		0-IV	SML ≤4%: 62.6 ± 6.7	NCRT: 11%				Loss rate in TPA after NAT: 7.3 ± 6.8%. Cut-off value for severe SML: >4%; 62.3% had severe SML.
			SML >4%: 65.8 ± 8.0
								Association with outcomes:
								• Severe SML was associated with higher risk of postoperative mortality.
Yoon 2020 Korea (37)	Retrospective, To assess whether sarcopenia and skeletal muscle loss affected survival outcomes of esophageal cancer patients who received NCRT followed by surgery.	EC	248 (NS)	NCRT: 100%	CT SMI (cm²/m²)	49.72 ± 7.92	45.10 ± 7.57	Muscle change:
		NS	63.5 ± 7.6					Change rate in SMM: -6.6 ± 6.1% Prevalence of sarcopenia: increased, from 63% to 84%. Cut-off value for severe SML: >10%; 28.2% patients had severe SML.
								Association with outcomes:
								• Severe SML was associated with poorer OS and DFS.
Kawakita 2020 Japan (26)	Retrospective, To investigate the effect of the severity and timing of changes in PMI on the survival of patients under NCRT plus esophagectomy and the association between PMI and other prognostic markers in these patients.	EC	113 (96)	NCRT: 100%	CT SM (PMI)	SML≥20% after surgery (n=27): 4.80 (3.38-5.81) ^a	SML ≥20% after surgery (n=27): 4.52 (3.16-5.03) ^a	Muscle change:
		IIb-IIIc	SML <20%: 64 (59-68)	NCRT: 100%	CT SM (PMI)	SML≥20% after surgery (n=27): 4.80 (3.38-5.81) ^a	SML ≥20% after surgery (n=27): 4.52 (3.16-5.03) ^a	Median (range) rate loss in PMI: 5.3 (1.5-12.7) % Cut-off value for severe SML: ≥13%; 25.0% patients had severe SML.
			SML ≥20%: 65 (56-68)		(cm²/m²)	SML<20% after surgery (n=86): 4.26 (3.72-5.41) ^a	SML <20% after surgery (n=86): 4.22 (3.55-4.95) ^a	Association with outcomes:
			SML ≥20%: 65 (56-68)		(cm²/m²)	SML<20% after surgery (n=86): 4.26 (3.72-5.41) ^a	SML <20% after surgery (n=86): 4.22 (3.55-4.95) ^a	• No significant association between muscle loss during NACT and OS or DFS was found
Hagens 2020 Netherlands (44)	Retrospective, To evaluate the change in body composition, sarcopenia, and muscle strength during NCRT, and the impact of body composition and muscle strength on postoperative morbidity and survival.	EC	322 (244)	NCRT: 100%	CT SMI (cm²/m²)	No complication (n=86): 46.2 ± 9.3	No complication (n=94): 46.3 ± 8.7	Muscle change:
		NS	63.7 ± 8.7			No complication (n=86): 46.2 ± 9.3	No complication (n=94): 46.3 ± 8.7	• Prevalence of sarcopenia: not significant increased, from 56% to 58%.
						Minor complication (n=95): 46.1 ± 8.6	Minor complication (n=107): 45.0 ± 8.5	Association with outcomes:
						Minor complication (n=95): 46.1 ± 8.6	Minor complication (n=107): 45.0 ± 8.5	• No significant association between muscle loss during NACT and postoperative morbidity was found.
						major complication (n=44): 46.9 ± 10.1	major complication (n=66): 46.3 ± 9.2
Boer 2020 UK (27)	Retrospective, To assess changes in body composition during NAC and to determine its predictive value for postoperative complications.	EC	199 (158)	NAC: 100%	CT SMI (cm²/m²) SMA (m²)	51.87 ± 10.31	49.19 ± 9.71	Muscle change:
		AEGJ	66 (28-80)			150.41 ± 33.61	142.60 ± 31.94	SMM ↓ significantly after NAC. Prevalence of sarcopenia: increased, from 42% to 54%. Cut-off value for severe SML: >5%; 45.7% patients had severe SML.
		GC
		NS
								Association with outcomes:
								• No significant association between severe SML and postoperative complications was found.
Matsuura 2019 Japan (26)	Retrospective, To clarify whether low pre-treatment SMM could be a predictor of adverse events during NAC and explore the relationship between SMM and adverse events during NAC.	GC	41 (28)	NAC: 100%	CT SM (PMI) (cm²/m²)	4.77 ± 1.11	4.50 ± 1.20	Muscle change:
		II-IV	72 (48-82)					• SMM ↓ significantly after NAC: -5.95 ± 7.69%
								Association with outcomes:
								• Severe diarrhea was associated with SML during NAT.
Zhang 2021 China (25)	Retrospective, To explore the association between body composition changes during NAT and survival in patients with GC.	GC	157 (115)	NAC: 82%	CT SMA (cm²)	137.96 (111.87-154.41) ^a	137.97 (112.03-156.41) ^a	Muscle change:
		0-III	61 (53-67)	NCRT: 18%				No significant change showed in SMM after NAT. Cut-off value for severe SML: >2%; 42.7% patients had severe SML.
								Association with outcomes:
								• No significant association between skeletal muscle mass change and survival was found.
Levolger 2017 Netherlands (17)	Retrospective, To assess body composition changes during NCRT and its impact on outcome.	RC	122 (71)	NCRT: 100%	CT SMI (cm²/m²)	46.6 (41.2-53.4) ^b	46.9 (40.2-53.1) ^b	Muscle change:
		III, IV	61(53-66)					• No significant change showed in mean SMI after NCRT, while a wide distribution in muscle change was observed.
								Association with outcomes:
								• SML during NCRT was associated with DFS and distant metastasis-free survival.
Nardi 2019 Italy (23)	Retrospective, To establish the correlation between body composition changes after NCRT and postoperative outcomes.	RC	52 (34)	NCRT: 100%	CT SMA (cm²)	133.87 ± 31.6	133.39 ± 31.5	Muscle change:
		NS	63 (32-79)					No significant change showed in SMM after NCRT. Prevalence of sarcopenia: not significant increased, from 58% to 60%. 36.5% patients had SML >2%, and 30.7% >5%.
								Association with outcomes:
								• Severe SML during NCRT was associated with shorter DFS.
Fukuoka 2019 Japan (16)	Retrospective,	RC	47 (35)	NAC: 43%	CT SM (PMI) (cm²/m²)	325.4 (146.7-696.1) ^c	313.0 (110.5-722.3) ^c	Muscle change:
	To explore the relationship between skeletal muscle changes during NAT and prognosis.	I-III	66 (27-88)	NCRT: 57%				Mean change rate was -4.3%, and the range was -25.2-24.8%. Cut-off value for severe SML: >10%; 31.9% patients had severe SML.
								Association with outcomes:
								• Severe SML during NAT was associated with shorter DFS and OS.

¹EC, esophageal cancer; GC, gastric cancer; CRC, colorectal cancer; AEGJ, adenocarcinoma of esophagogastric junction; NS, not specified.

²Age was presented as mean ± sd OR median (range).

³Treatment: NAC, neoadjuvant chemotherapy; NCRT, neoadjuvant chemoradiotherapy.

⁴FFM, fat free mass (calculated based on SMM); SMM, skeletal muscle mass; SMI, skeletal muscle index; SMA, skeletal muscle area; SML, skeletal muscle loss.

SM (PMI) = skeletal muscle which was evaluated as psoas muscle index; SM (TPA) = skeletal muscle which was evaluated as total psoas muscle area.

Data was presented as median (range).

Data was presented as median (IQR).

Data was presented as mean (range).

The symbol ↓ means “muscle mass decreased after neoadjuvant therapy”.