World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Original Article

Volume 11, Number 1, February 2020, pages 9-22

Sarcopenia and Visceral Adiposity Did Not Affect Efficacy of Immune-Checkpoint Inhibitor Monotherapy for Pretreated Patients With Advanced Non-Small Cell Lung Cancer

Figure 1. Cross-sectional CT images at the third lumber vertebra level of a 75-year-old male patient. (a) The areas of bilateral psoas muscles (green area), visceral (red) and subcutaneous (blue) adipose tissue area were identified. (b) The multifidus muscle (yellow area) was precisely traced. Four points (yellow dots) were placed on subcutaneous fat away from major vessels. CT: computed tomography.

Figure 2. Kaplan-Meier curves of overall survival according to BMI (a), PMI (b), IMAC (c), VSR (d) and VFA (e). BMI: body mass index; PMI: psoas muscle index; IMAC: intramuscular adipose tissue content; VSR: visceral to subcutaneous adipose tissue area ratio; VFA: visceral fat area.

Figure 3. Kaplan-Meier curves of progression-free survival according to BMI (a), PMI (b), IMAC (c), VSR (d) and VFA (e). BMI: body mass index; PMI: psoas muscle index; IMAC: intramuscular adipose tissue content; VSR: visceral to subcutaneous adipose tissue area ratio; VFA: visceral fat area.

**Table 1.** Baseline Characteristics According to BMI
	BMI	P
^aFisher’s exact test. ^bMann-Whitney U test. Atezo: atezolizumab; BMI: body mass index; CI: confidence interval; CR: complete response; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group performance status; EGFR: epidermal growth factor receptor; Ex: ex-smoker; ICI: immune-checkpoint inhibitors; IQR: interquartile range; NE: not evaluated; Nivo: nivolumab; NLR: neutrophil-to-lymphocyte ratio; NS: non-smoker; ORR: overall response rate; PD: progressive disease; PD-L1: programmed cell death ligand 1; Pem: pembrolizumab; PR: partial response; SD: stable disease; SQ: squamous cell carcinoma; TPS: tumor proportion score.
N	60	14
Backgrounds
Sex (N)
Male/female	40/20	8/6	0.54^a
Age (years)
Median (IQR)	70 (65.3 - 75.0)	69 (61.3 - 71.5)	0.38^b
< 70/≥ 70 years (N)	28/32	9/5	0.37^a
Smoking status
NS/Ex or CS	12/48	3/11	1.00^a
Histology
Non-SQ/SQ	47/13	8/6	0.17^a
EGFR mutation
(+)/(-) or NE	11/49	0/14	0.11^a
PD-L1 TPS
≥ 50%/1-49%/< 1%/NA	11/11/7/31	2/4/1/7	0.86^a
ECOG-PS
0 - 1/2/3	45/12/3	8/4/2	0.21^a
Metastatic sites
< 3/≥ 3	26/34	9/5	0.24^a
BMI
Median (IQR)	23.1 (21.9 - 25.3)	17.0 (15.7 - 17.8)	< 0.01^b
Treatment
ICI regimen (N)
Nivo/Pem/Atezo	45/10/5	12/2/0	0.76^a
Previous treatment (N)
Anti-angiogenic drugs	29	5	0.55^a
Radiotherapy	14	5	0.33^a
Further line treatment (N)	33	4	0.14^a
ICI efficacy
CR/PR/SD/PD/NE	2/7/13/36/2	1/1/2/7/3
ORR (%) (95% CI)	15.0 (7.1 - 26.6)	14.3 (1.8 - 42.8)	1.00^a
DCR (%) (95% CI)	36.7 (24.6 - 50.1)	28.6 (8.4 - 58.1)	0.76^a
Laboratory data
NLR
Median (IQR)	2.81 (1.96 - 4.08)	4.96 (3.69 - 5.97)	< 0.01^b
≤ 5/> 5 (N)	50/10	7/7	0.01^a
Albumin (g/dL)
Median (IQR)	3.6 (3.3 - 3.9)	3.2 (2.8 - 3.2)	< 0.01^b
≥ 3.5/< 3.5 g/dL (N)	42/18	3/11	< 0.01^a

Table 1. Baseline Characteristics According to BMI

BMI

≥ 18.5

< 18.5

^aFisher’s exact test. ^bMann-Whitney U test. Atezo: atezolizumab; BMI: body mass index; CI: confidence interval; CR: complete response; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group performance status; EGFR: epidermal growth factor receptor; Ex: ex-smoker; ICI: immune-checkpoint inhibitors; IQR: interquartile range; NE: not evaluated; Nivo: nivolumab; NLR: neutrophil-to-lymphocyte ratio; NS: non-smoker; ORR: overall response rate; PD: progressive disease; PD-L1: programmed cell death ligand 1; Pem: pembrolizumab; PR: partial response; SD: stable disease; SQ: squamous cell carcinoma; TPS: tumor proportion score.

Backgrounds

Sex (N)

Male/female

40/20

8/6

0.54^a

Age (years)

Median (IQR)

70 (65.3 - 75.0)

69 (61.3 - 71.5)

0.38^b

< 70/≥ 70 years (N)

28/32

9/5

0.37^a

Smoking status

NS/Ex or CS

12/48

3/11

1.00^a

Histology

Non-SQ/SQ

47/13

8/6

0.17^a

EGFR mutation

(+)/(-) or NE

11/49

0/14

0.11^a

PD-L1 TPS

≥ 50%/1-49%/< 1%/NA

11/11/7/31

2/4/1/7

0.86^a

ECOG-PS

0 - 1/2/3

45/12/3

8/4/2

0.21^a

Metastatic sites

< 3/≥ 3

26/34

9/5

0.24^a

BMI

Median (IQR)

23.1 (21.9 - 25.3)

17.0 (15.7 - 17.8)

< 0.01^b

Treatment

ICI regimen (N)

Nivo/Pem/Atezo

45/10/5

12/2/0

0.76^a

Previous treatment (N)

Anti-angiogenic drugs

0.55^a

Radiotherapy

0.33^a

Further line treatment (N)

0.14^a

ICI efficacy

CR/PR/SD/PD/NE

2/7/13/36/2

1/1/2/7/3

ORR (%) (95% CI)

15.0 (7.1 - 26.6)

14.3 (1.8 - 42.8)

1.00^a

DCR (%) (95% CI)

36.7 (24.6 - 50.1)

28.6 (8.4 - 58.1)

0.76^a

Laboratory data

NLR

Median (IQR)

2.81 (1.96 - 4.08)

4.96 (3.69 - 5.97)

< 0.01^b

≤ 5/> 5 (N)

50/10

7/7

0.01^a

Albumin (g/dL)

Median (IQR)

3.6 (3.3 - 3.9)

3.2 (2.8 - 3.2)

< 0.01^b

≥ 3.5/< 3.5 g/dL (N)

42/18

3/11

< 0.01^a

**Table 2.** Baseline Characteristics According to PMI
	PMI	P
^aFisher’s exact test. ^bMann-Whitney U test. Atezo: atezolizumab; BMI: body mass index; CI: confidence interval; CR: complete response; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group performance status; EGFR: epidermal growth factor receptor; Ex: ex-smoker; ICI: immune-checkpoint inhibitors; IQR: interquartile range; NE: not evaluated; Nivo: nivolumab; NLR: neutrophil-to-lymphocyte ratio; NS: non-smoker; ORR: overall response rate; PD: progressive disease; PD-L1: Programmed cell Death ligand 1; Pem: pembrolizumab; PMI: psoas muscle index; PR: partial response; SD: stable disease; SQ: squamous cell carcinoma; TPS: tumor proportion score.
N	21	53
Backgrounds
Sex (N)
Male/female	13/8	35/18	0.79^a
Age (years)
Median (IQR)	70 (61 - 73)	69 (63 - 74)	0.61^b
< 70/≥ 70 years (N)	10/11	27/26	1.00^a
Smoking status
NS/Ex, CS	5/16	10/43	0.75^a
Histology
Non-SQ/SQ	18/3	37/16	0.24^a
EGFR mutation
(+)/(-) or NA	3/18	8/45	1.00^a
PD-L1 status
≥ 50%/1-49%/< 1%/NA	3/5/0/13	10/10/8/25	0.25^a
ECOG-PS
0 - 1/2/3	15/4/2	38/12/3	0.82^a
Metastatic sites
< 3/≥ 3	8/13	27/26	0.44^a
BMI
Median (IQR)	24.5 (21.5 - 27.7)	22.0 (19.8 - 23.8)	0.02^a
PMI
Median (IQR)
Male	7.73 (6.82 - 7.85)	4.29 (3.49 - 5.60)	< 0.01^b
Female	4.61 (4.22 - 4.88)	3.27 (2.99 - 3.49)	< 0.01^b
Treatment
ICI regimen (N)
Nivo/Pem/Atezo	17/3/1	40/9/4	1.00^a
Previous treatment (N)
Anti-angiogenic drug	12	22	0.30^a
Radiotherapy	5	14	1.00^a
Further line treatment (N)	13	24	0.30^a
ICI efficacy
CR/PR/SD/PD/NE	1/0/5/15/0	2/8/10/28/5
ORR (%) (95% CI)	4.8 (0.1 - 23.8)	18.9 (9.4 - 32.0)	0.16^a
DCR (%) (95% CI)	28.6 (11.3 - 52.2)	37.7 (24.8 - 52.1)	0.59^a
Laboratory data
NLR
Median (IQR)	2.79 (2.00 - 3.66)	3.57 (2.10 - 4.88)	0.36^b
≤ 5/> 5 (N)	17/4	40/13	0.76^a
Albumin (g/dL)
Median (IQR)	3.6 (3.2 - 3.9)	3.5 (3.2 - 3.9)	0.67^b
≥ 3.5/< 3.5 g/dL (N)	13/8	32/21	1.00^a

Table 2. Baseline Characteristics According to PMI

PMI

High

Low

^aFisher’s exact test. ^bMann-Whitney U test. Atezo: atezolizumab; BMI: body mass index; CI: confidence interval; CR: complete response; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group performance status; EGFR: epidermal growth factor receptor; Ex: ex-smoker; ICI: immune-checkpoint inhibitors; IQR: interquartile range; NE: not evaluated; Nivo: nivolumab; NLR: neutrophil-to-lymphocyte ratio; NS: non-smoker; ORR: overall response rate; PD: progressive disease; PD-L1: Programmed cell Death ligand 1; Pem: pembrolizumab; PMI: psoas muscle index; PR: partial response; SD: stable disease; SQ: squamous cell carcinoma; TPS: tumor proportion score.

Backgrounds

Sex (N)

Male/female

13/8

35/18

0.79^a

Age (years)

Median (IQR)

70 (61 - 73)

69 (63 - 74)

0.61^b

< 70/≥ 70 years (N)

10/11

27/26

1.00^a

Smoking status

NS/Ex, CS

5/16

10/43

0.75^a

Histology

Non-SQ/SQ

18/3

37/16

0.24^a

EGFR mutation

(+)/(-) or NA

3/18

8/45

1.00^a

PD-L1 status

≥ 50%/1-49%/< 1%/NA

3/5/0/13

10/10/8/25

0.25^a

ECOG-PS

0 - 1/2/3

15/4/2

38/12/3

0.82^a

Metastatic sites

< 3/≥ 3

8/13

27/26

0.44^a

BMI

Median (IQR)

24.5 (21.5 - 27.7)

22.0 (19.8 - 23.8)

0.02^a

PMI

Median (IQR)

Male

7.73 (6.82 - 7.85)

4.29 (3.49 - 5.60)

< 0.01^b

Female

4.61 (4.22 - 4.88)

3.27 (2.99 - 3.49)

< 0.01^b

Treatment

ICI regimen (N)

Nivo/Pem/Atezo

17/3/1

40/9/4

1.00^a

Previous treatment (N)

Anti-angiogenic drug

0.30^a

Radiotherapy

1.00^a

Further line treatment (N)

0.30^a

ICI efficacy

CR/PR/SD/PD/NE

1/0/5/15/0

2/8/10/28/5

ORR (%) (95% CI)

4.8 (0.1 - 23.8)

18.9 (9.4 - 32.0)

0.16^a

DCR (%) (95% CI)

28.6 (11.3 - 52.2)

37.7 (24.8 - 52.1)

0.59^a

Laboratory data

NLR

Median (IQR)

2.79 (2.00 - 3.66)

3.57 (2.10 - 4.88)

0.36^b

≤ 5/> 5 (N)

17/4

40/13

0.76^a

Albumin (g/dL)

Median (IQR)

3.6 (3.2 - 3.9)

3.5 (3.2 - 3.9)

0.67^b

≥ 3.5/< 3.5 g/dL (N)

13/8

32/21

1.00^a

**Table 3.** Baseline Characteristics According to IMAC
	IMAC	P
^aFisher’s exact test. ^bMann-Whitney U test. Atezo: atezolizumab; BMI: body mass index; CI: confidence interval; CR: complete response; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group performance status; EGFR: epidermal growth factor receptor; Ex: ex-smoker; ICI: immune-checkpoint inhibitors; IMAC: intramuscular adipose tissue content; IQR: interquartile range; NE: not evaluated; Nivo: nivolumab; NLR: neutrophil-to-lymphocyte ratio; NS: non-smoker; ORR: overall response rate; PD: progressive disease; PD-L1: Programmed cell Death ligand 1; Pem: pembrolizumab; PR: partial response; SD: stable disease; SQ: squamous cell carcinoma; TPS: tumor proportion score.
N	11	63
Backgrounds
Sex (N)
Male/female	6/5	42/21	0.50^a
Age (years)
Median (IQR)	75 (70.5 - 77.5)	68 (62 - 73)	< 0.01^b
< 70/≥ 70 years (N)	2/9	35/28	0.046^a
Smoking status
NS/Ex, CS	3/8	12/51	0.68^a
Histology
Non-SQ/SQ	7/4	48/15	0.46^a
EGFR mutation
(+)/(-) or NA	2/9	9/54	0.66^a
PD-L1 status
≥ 50%/1-49%/< 1%/NA	1/3/3/4	12/12/5/34	0.21^a
ECOG-PS
0 - 1/2/3	6/3/2	47/13/3	0.17^a
Metastatic sites
< 3/≥3	1/10	34/29	< 0.01^a
BMI
Median (IQR)	23.4 (22.9 - 26.5)	22.0 (19.6 - 24.1)	0.05^b
IMAC
Median (IQR) (minus data)
Male	0.33 (0.34 - 0.29)	0.54 (0.65 - 0.48)	< 0.01^b
emale	0.16 (0.18 - 0.15)	0.41 (0.53 - 0.32)	< 0.01^b
Treatment
ICI regimen (N)
Nivo/Pem/Atezo	9/1/1	48/11/4	0.73^a
Previous treatment (N)
Anti-angiogenic drug	5	29	1.00^a
Radiotherapy	5	14	0.14^a
Further line treatment (N)	4	33	0.52^a
ICI efficacy
CR/PR/SD/PD/NE	0/1/2/6/2	3/7/13/37/3
ORR (%) (95% CI)	9.1 (0.2 - 41.3)	15.9 (7.9 - 27.3)	1.00^a
DCR (%) (95% CI)	27.3 (6.0 - 61.0)	36.5 (24.7 - 49.6)	0.74^a
Laboratory data
NLR
Median (IQR)	3.89 (2.93 - 4.89)	2.98 (2.01 - 4.51)	0.41^b
≤ 5/> 5 (N)	8/3	49/14	0.71^a
Albumin (g/dL)
Median (IQR)	3.5 (3.1 - 4.0)	3.5 (3.2 - 3.9)	0.69^b
≥ 3.5/< 3.5 g/dL (N)	6/5	39/24	0.74^a

Table 3. Baseline Characteristics According to IMAC

IMAC

High

Low

^aFisher’s exact test. ^bMann-Whitney U test. Atezo: atezolizumab; BMI: body mass index; CI: confidence interval; CR: complete response; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group performance status; EGFR: epidermal growth factor receptor; Ex: ex-smoker; ICI: immune-checkpoint inhibitors; IMAC: intramuscular adipose tissue content; IQR: interquartile range; NE: not evaluated; Nivo: nivolumab; NLR: neutrophil-to-lymphocyte ratio; NS: non-smoker; ORR: overall response rate; PD: progressive disease; PD-L1: Programmed cell Death ligand 1; Pem: pembrolizumab; PR: partial response; SD: stable disease; SQ: squamous cell carcinoma; TPS: tumor proportion score.

Backgrounds

Sex (N)

Male/female

6/5

42/21

0.50^a

Age (years)

Median (IQR)

75 (70.5 - 77.5)

68 (62 - 73)

< 0.01^b

< 70/≥ 70 years (N)

2/9

35/28

0.046^a

Smoking status

NS/Ex, CS

3/8

12/51

0.68^a

Histology

Non-SQ/SQ

7/4

48/15

0.46^a

EGFR mutation

(+)/(-) or NA

2/9

9/54

0.66^a

PD-L1 status

≥ 50%/1-49%/< 1%/NA

1/3/3/4

12/12/5/34

0.21^a

ECOG-PS

0 - 1/2/3

6/3/2

47/13/3

0.17^a

Metastatic sites

< 3/≥3

1/10

34/29

< 0.01^a

BMI

Median (IQR)

23.4 (22.9 - 26.5)

22.0 (19.6 - 24.1)

0.05^b

IMAC

Median (IQR) (minus data)

Male

0.33 (0.34 - 0.29)

0.54 (0.65 - 0.48)

< 0.01^b

emale

0.16 (0.18 - 0.15)

0.41 (0.53 - 0.32)

< 0.01^b

Treatment

ICI regimen (N)

Nivo/Pem/Atezo

9/1/1

48/11/4

0.73^a

Previous treatment (N)

Anti-angiogenic drug

1.00^a

Radiotherapy

0.14^a

Further line treatment (N)

0.52^a

ICI efficacy

CR/PR/SD/PD/NE

0/1/2/6/2

3/7/13/37/3

ORR (%) (95% CI)

9.1 (0.2 - 41.3)

15.9 (7.9 - 27.3)

1.00^a

DCR (%) (95% CI)

27.3 (6.0 - 61.0)

36.5 (24.7 - 49.6)

0.74^a

Laboratory data

NLR

Median (IQR)

3.89 (2.93 - 4.89)

2.98 (2.01 - 4.51)

0.41^b

≤ 5/> 5 (N)

8/3

49/14

0.71^a

Albumin (g/dL)

Median (IQR)

3.5 (3.1 - 4.0)

3.5 (3.2 - 3.9)

0.69^b

≥ 3.5/< 3.5 g/dL (N)

6/5

39/24

0.74^a

**Table 4.** Baseline Characteristics According to VSR
	VSR	P
^aFisher’s exact test. ^bMann-Whitney U test. Atezo: atezolizumab; BMI: body mass index; CI: confidence interval; CR: complete response; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group performance status; EGFR: epidermal growth factor receptor; Ex: ex-smoker; ICI: immune-checkpoint inhibitors; IQR: interquartile range; NE: not evaluated; Nivo: nivolumab; NLR: neutrophil-to-lymphocyte ratio; NS: non-smoker; ORR: overall response rate; PD: progressive disease; PD-L1: programmed cell death ligand 1; Pem: pembrolizumab; PR: partial response; SD: stable disease; SQ: squamous cell carcinoma; TPS: tumor proportion score; VSR: visceral to subcutaneous adipose tissue area ratio.
N	20	54
Backgrounds
Sex (N)
Male/female	15/5	33/21	0.41^a
Age (years)
Median (IQR)	74 (69.8 - 77.0)	68 (61.3 - 71.8)	< 0.01^b
< 70/≥ 70 years (N)	5/15	32/22	0.02^a
Smoking status
NS/Ex, CS	3/17	12/42	0.75^a
Histology
Non-SQ/SQ	12/8	43/11	0.13^a
EGFR mutation
(+)/(-) or NA	3/17	8/46	1.00^a
PD-L1 status
≥ 50%/1-49%/< 1%/NA	1/5/2/12	12/10/6/26	0.38^a
ECOG-PS
0 - 1/2/3	11/6/3	42/10/2	0.08^a
Metastatic sites
< 3/≥ 3	11/9	24/30	0.45^a
BMI
Median (IQR)	22.5 (20.4 - 24.0)	22.6 (20.1 - 25.2)	0.84^a
VSR
Median (IQR)
Male	1.87 (1.48 - 3.00)	0.80 (0.52 - 1.07)	< 0.01^b
Female	1.07 (1.01 - 1.15)	0.35 (0.19 - 0.56)	< 0.01^b
Treatment
ICI regimen (N)
Nivo/Pem/Atezo	17/1/2	40/11/3	0.20^a
Previous treatment (N)
Anti-angiogenic drug	9	25	1.00^a
Radiotherapy	7	12	0.37^a
Further line treatment (N)	9	28	0.79^a
ICI efficacy
CR/PR/SD/PD/NE	0/1/3/13/3	3/7/12/30/2
ORR (%) (95% CI)	5.0 (0.1 - 24.9)	18.5 (9.3 - 31.4)	0.27^a
DCR (%) (95% CI)	20.0 (5.7 - 43.7)	40.7 (27.6 - 55.0)	0.11^a
Laboratory data
NLR
Median (IQR)	4.37 (2.39 - 5.93)	3.00 (2.01 - 3.97)	0.13^b
≤ 5/> 5 (N)	12/8	45/9	0.06^a
Albumin (g/dL)
Median (IQR)	3.5 (3.2 - 3.8)	3.6 (3.2 - 4.0)	0.25^b
≥ 3.5/< 3.5 g/dL (N)	11/9	34/20	0.60^a

Table 4. Baseline Characteristics According to VSR

VSR

High

Low

Backgrounds

Sex (N)

Male/female

15/5

33/21

0.41^a

Age (years)

Median (IQR)

74 (69.8 - 77.0)

68 (61.3 - 71.8)

< 0.01^b

< 70/≥ 70 years (N)

5/15

32/22

0.02^a

Smoking status

NS/Ex, CS

3/17

12/42

0.75^a

Histology

Non-SQ/SQ

12/8

43/11

0.13^a

EGFR mutation

(+)/(-) or NA

3/17

8/46

1.00^a

PD-L1 status

≥ 50%/1-49%/< 1%/NA

1/5/2/12

12/10/6/26

0.38^a

ECOG-PS

0 - 1/2/3

11/6/3

42/10/2

0.08^a

Metastatic sites

< 3/≥ 3

11/9

24/30

0.45^a

BMI

Median (IQR)

22.5 (20.4 - 24.0)

22.6 (20.1 - 25.2)

0.84^a

VSR

Median (IQR)

Male

1.87 (1.48 - 3.00)

0.80 (0.52 - 1.07)

< 0.01^b

Female

1.07 (1.01 - 1.15)

0.35 (0.19 - 0.56)

< 0.01^b

Treatment

ICI regimen (N)

Nivo/Pem/Atezo

17/1/2

40/11/3

0.20^a

Previous treatment (N)

Anti-angiogenic drug

1.00^a

Radiotherapy

0.37^a

Further line treatment (N)

0.79^a

ICI efficacy

CR/PR/SD/PD/NE

0/1/3/13/3

3/7/12/30/2

ORR (%) (95% CI)

5.0 (0.1 - 24.9)

18.5 (9.3 - 31.4)

0.27^a

DCR (%) (95% CI)

20.0 (5.7 - 43.7)

40.7 (27.6 - 55.0)

0.11^a

Laboratory data

NLR

Median (IQR)

4.37 (2.39 - 5.93)

3.00 (2.01 - 3.97)

0.13^b

≤ 5/> 5 (N)

12/8

45/9

0.06^a

Albumin (g/dL)

Median (IQR)

3.5 (3.2 - 3.8)

3.6 (3.2 - 4.0)

0.25^b

≥ 3.5/< 3.5 g/dL (N)

11/9

34/20

0.60^a

**Table 5.** Baseline Characteristics According to VFA
	VFA	P
^aFisher’s exact test. ^bMann-Whitney U test. Atezo: atezolizumab; BMI: body mass index; CI: confidence interval; CR: complete response; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group performance status; EGFR: epidermal growth factor receptor; Ex: ex-smoker; ICI: immune-checkpoint inhibitors; IQR: interquartile range; NE: not evaluated; Nivo: nivolumab; NLR: neutrophil-to-lymphocyte ratio; NS: non-smoker; ORR: overall response rate; PD: progressive disease; PD-L1: programmed cell death ligand 1; Pem: pembrolizumab; PR: partial response; SD: stable disease; SQ: squamous cell carcinoma; TPS: tumor proportion score; VSR: visceral to subcutaneous adipose tissue area ratio.
N	44	30
Backgrounds
Sex (N)
Male/female	18/26	8/22	0.23^a
Age (years)
Median (IQR)	68.5 (61.8 - 72.3)	71.0 (66.5 - 76.5)	0.04^b
< 70/≥ 70 years (N)	26/18	11/19	0.10^a
Smoking status
NS/Ex, CS	10/34	5/25	0.57^a
Histology
Non-SQ/SQ	33/11	22/8	1.00^a
EGFR mutation
(+)/(-) or NA	6/38	6/24	0.53^a
PD-L1 status
≥ 50%/1-49%/< 1%/NA	7/9/3/25	6/6/5/13	0.49^a
ECOG-PS
0 - 1/2/3	33/9/2	20/7/3	0.57^a
Metastatic sites
< 3/≥ 3	24/20	11/19	0.16^a
BMI
Median (IQR)	20.8 (18.0 - 22.8)	24.8 (23.0 - 27.3)	< 0.01^a
VFA (cm²)
Median (IQR)	36.4 (18.1 - 57.3)	139.5 (119.5 - 165.9)	< 0.01^a
Treatment
ICI regimen (N)
Nivo/Pem/Atezo	37/7/3	23/5/2	1.00^a
Previous treatment (N)
Anti-angiogenic drug	23	21	0.24^a
Radiotherapy	8	11	0.10^a
Further line treatment (N)	19	18	0.24^a
ICI efficacy
CR/PR/SD/PD/NE	3/6/6/26/3	0/2/9/17/1
ORR (%) (95%CI)	20.5 (9.8 - 35.3)	6.7 (0.8 - 22.1)	0.18^a
DCR (%) (95%CI)	34.1 (20.5 - 49.9)	36.7 (19.9 - 56.1)	0.81^a
Laboratory data
NLR
Median (IQR)	3.13 (2.28 - 4.92)	3.00 (1.88 - 4.42)	0.72^b
≤ 5/> 5 (N)	33/11	24/6	0.78^a
Albumin (g/dL)
Median (IQR)	3.5 (3.2 - 3.9)	3.6 (3.2 - 3.9)	0.68^b
≥ 3.5/< 3.5 g/dL (N)	25/19	20/10	0.47^a

Table 5. Baseline Characteristics According to VFA

VFA

< 100 cm²

≥ 100 cm²

Backgrounds

Sex (N)

Male/female

18/26

8/22

0.23^a

Age (years)

Median (IQR)

68.5 (61.8 - 72.3)

71.0 (66.5 - 76.5)

0.04^b

< 70/≥ 70 years (N)

26/18

11/19

0.10^a

Smoking status

NS/Ex, CS

10/34

5/25

0.57^a

Histology

Non-SQ/SQ

33/11

22/8

1.00^a

EGFR mutation

(+)/(-) or NA

6/38

6/24

0.53^a

PD-L1 status

≥ 50%/1-49%/< 1%/NA

7/9/3/25

6/6/5/13

0.49^a

ECOG-PS

0 - 1/2/3

33/9/2

20/7/3

0.57^a

Metastatic sites

< 3/≥ 3

24/20

11/19

0.16^a

BMI

Median (IQR)

20.8 (18.0 - 22.8)

24.8 (23.0 - 27.3)

< 0.01^a

VFA (cm²)

Median (IQR)

36.4 (18.1 - 57.3)

139.5 (119.5 - 165.9)

< 0.01^a

Treatment

ICI regimen (N)

Nivo/Pem/Atezo

37/7/3

23/5/2

1.00^a

Previous treatment (N)

Anti-angiogenic drug

0.24^a

Radiotherapy

0.10^a

Further line treatment (N)

0.24^a

ICI efficacy

CR/PR/SD/PD/NE

3/6/6/26/3

0/2/9/17/1

ORR (%) (95%CI)

20.5 (9.8 - 35.3)

6.7 (0.8 - 22.1)

0.18^a

DCR (%) (95%CI)

34.1 (20.5 - 49.9)

36.7 (19.9 - 56.1)

0.81^a

Laboratory data

NLR

Median (IQR)

3.13 (2.28 - 4.92)

3.00 (1.88 - 4.42)

0.72^b

≤ 5/> 5 (N)

33/11

24/6

0.78^a

Albumin (g/dL)

Median (IQR)

3.5 (3.2 - 3.9)

3.6 (3.2 - 3.9)

0.68^b

≥ 3.5/< 3.5 g/dL (N)

25/19

20/10

0.47^a

**Table 6.** Adjusted Hazard Ratios of Sarcopenic Factors for Overall Survival and Progression-Free Survival by Multivariate Cox Proportional Hazard Analyses
Variables	Progression-free survival	Overall survival
Multivariate adjustment for serum albumin (< 3.5 vs. ≥ 3.5 g/dL), neutrophil to lymphocyte ratio (< 5 vs. ≥ 5), ECOG-PS (0 - 1 vs. 2 - 4) and driver mutation of EGFR or ALK (wild-type vs. mutated). BMI: body mass index; CI: confidence interval; HR: hazard ratio; IMAC: intramuscular adipose tissue content; PMI: psoas muscle index; VFA: visceral fat area; VSR: visceral to subcutaneous adipose tissue area ratio; ECOG-PS: Eastern Cooperative Oncology Group performance status; EGFR: epidermal growth factor receptor; ALK: anaplastic lymphoma kinase.
BMI (kg/m²)
≥ 18.5	1 (Reference)		1(Reference)
< 18.5	1.11 (0.55 - 2.24)	0.77	1.83 (0.79 - 4.21)	0.16
PMI (cm²/m²)
High	1 (Reference)		1(Reference)
Low	0.84 (0.48 - 1.48)	0.56	1.05 (0.54 - 2.03)	0.88
IMAC
High	1 (Reference)		1(Reference)
Low	0.79 (0.38 - 1.67)	0.54	0.43 (0.18 - 0.998)	0.0496
VSR
High	1 (Reference)		1(Reference)
Low	0.78 (0.42 - 1.46)	0.44	0.72 (0.35 - 1.49)	0.37
VFA
< 100 cm²	1 (Reference)		1 (Reference)
≥ 100 cm²	1.09 (0.64 - 1.84)	0.75	1.22 (0.67 - 2.20)	0.52

Table 6. Adjusted Hazard Ratios of Sarcopenic Factors for Overall Survival and Progression-Free Survival by Multivariate Cox Proportional Hazard Analyses

Variables

Progression-free survival

Overall survival

HR (95% CI)

Multivariate adjustment for serum albumin (< 3.5 vs. ≥ 3.5 g/dL), neutrophil to lymphocyte ratio (< 5 vs. ≥ 5), ECOG-PS (0 - 1 vs. 2 - 4) and driver mutation of EGFR or ALK (wild-type vs. mutated). BMI: body mass index; CI: confidence interval; HR: hazard ratio; IMAC: intramuscular adipose tissue content; PMI: psoas muscle index; VFA: visceral fat area; VSR: visceral to subcutaneous adipose tissue area ratio; ECOG-PS: Eastern Cooperative Oncology Group performance status; EGFR: epidermal growth factor receptor; ALK: anaplastic lymphoma kinase.

BMI (kg/m²)

≥ 18.5

1 (Reference)

1(Reference)

< 18.5

1.11 (0.55 - 2.24)

0.77

1.83 (0.79 - 4.21)

0.16

PMI (cm²/m²)

High

1 (Reference)

1(Reference)

Low

0.84 (0.48 - 1.48)

0.56

1.05 (0.54 - 2.03)

0.88

IMAC

High

1 (Reference)

1(Reference)

Low

0.79 (0.38 - 1.67)

0.54

0.43 (0.18 - 0.998)

0.0496

VSR

High

1 (Reference)

1(Reference)

Low

0.78 (0.42 - 1.46)

0.44

0.72 (0.35 - 1.49)

0.37

VFA

< 100 cm²

1 (Reference)

≥ 100 cm²

1.09 (0.64 - 1.84)

0.75

1.22 (0.67 - 2.20)

0.52