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 https://www.wjon.org

Original Article

Volume 11, Number 4, August 2020, pages 139-149

Sarcopenia and Visceral Adiposity Are Not Independent Prognostic Markers for Extensive Disease of Small-Cell Lung Cancer: A Single-Centered Retrospective Cohort Study

Figure 1. Kaplan-Meier curves of overall survival according to BMI (a), PMI (b), IMAC (c) and VSR (d). BMI: body mass index; PMI: psoas muscle index; IMAC: intramuscular adipose tissue content; VSR: visceral-to-subcutaneous fat ratio.

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

**Table 1.** Baseline Characteristics According to BMI
	BMI	P
^aFisher’s exact test; ^bMann-Whitney U test. BMI: body mass index; CR: complete response; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group-performance status; Ex: ex-smoker; IQR: interquartile range; NE: not evaluated; NS: non-smoker; ORR: overall response rate; PD: progressive disease; PR: partial response; SD: stable disease; ULN: upper limit of normal range; LDH: lactate dehydrogenase.
N	16	112
Backgrounds
Sex (N), men/women	10/6	91/21	0.10^a
Age (years)
Median (IQR)	72.5 (67.8 - 76)	71.5 (64.8 - 78)	0.33^b
< 75/≥ 75 years (N)	9/7	70/42	0.78^a
Smoking status, NS/Ex/CS/unknown	1/4/11/0	2/37/72/1	0.45^a
ECOG-PS, 0 - 1/2/3	7/7/2	70/24/18	0.21^a
c-stage, IIIB/IV	1/15	18/94	0.46^a
Metastatic sites
Brain	2	22	0.74^a
Liver	6	31	0.56^a
Bone	3	15	0.70^a
BMI, median (IQR)	16.9 (16.1 - 17.3)	23.1 (20.6 - 25.8)	< 0.01^b
Treatment
Platinum-based, cisplatin/carboplatin	2/14	29/83	0.35^a
Partner drugs, etoposide/irinotecan	0/16	15/97	0.21^a
Efficacy
CR/PR/SD/PD/NE	0/7/2/4/3	2/69/15/17/9
ORR (%)	43.8	63.4	0.17^a
DCR (%)	56.2	76.8	0.12^a
Second or later line (N)	7	62	0.43^a
Amrubicin (N)	5	44	0.60^a
Topotecan (N)	0	13	0.37^a
Irinotecan (N)	0	7	0.60^a
Pretreatment laboratory data
Albumin (g/dL)
Median (IQR)	3.1 (2.8 - 3.9)	3.7 (3.2 - 3.9)	0.13^b
≥ 3.5/< 3.5 g/dL (N)	6/10	68/44	0.11^a
LDH (IU/L)
Median (IQR)	266 (201 - 492)	286 (217 - 402)	0.94^b
< ULN/≥ ULN	6/10	31/81	0.56^a

Table 1. Baseline Characteristics According to BMI

BMI

< 18.5

≥ 18.5

^aFisher’s exact test; ^bMann-Whitney U test. BMI: body mass index; CR: complete response; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group-performance status; Ex: ex-smoker; IQR: interquartile range; NE: not evaluated; NS: non-smoker; ORR: overall response rate; PD: progressive disease; PR: partial response; SD: stable disease; ULN: upper limit of normal range; LDH: lactate dehydrogenase.

112

Backgrounds

Sex (N), men/women

10/6

91/21

0.10^a

Age (years)

Median (IQR)

72.5 (67.8 - 76)

71.5 (64.8 - 78)

0.33^b

< 75/≥ 75 years (N)

9/7

70/42

0.78^a

Smoking status, NS/Ex/CS/unknown

1/4/11/0

2/37/72/1

0.45^a

ECOG-PS, 0 - 1/2/3

7/7/2

70/24/18

0.21^a

c-stage, IIIB/IV

1/15

18/94

0.46^a

Metastatic sites

Brain

0.74^a

Liver

0.56^a

Bone

0.70^a

BMI, median (IQR)

16.9 (16.1 - 17.3)

23.1 (20.6 - 25.8)

< 0.01^b

Treatment

Platinum-based, cisplatin/carboplatin

2/14

29/83

0.35^a

Partner drugs, etoposide/irinotecan

0/16

15/97

0.21^a

Efficacy

CR/PR/SD/PD/NE

0/7/2/4/3

2/69/15/17/9

ORR (%)

43.8

63.4

0.17^a

DCR (%)

56.2

76.8

0.12^a

Second or later line (N)

0.43^a

Amrubicin (N)

0.60^a

Topotecan (N)

0.37^a

Irinotecan (N)

0.60^a

Pretreatment laboratory data

Albumin (g/dL)

Median (IQR)

3.1 (2.8 - 3.9)

3.7 (3.2 - 3.9)

0.13^b

≥ 3.5/< 3.5 g/dL (N)

6/10

68/44

0.11^a

LDH (IU/L)

Median (IQR)

266 (201 - 492)

286 (217 - 402)

0.94^b

< ULN/≥ ULN

6/10

31/81

0.56^a

**Table 2.** Baseline Characteristics According to PMI
	PMI	P
^aFisher’s exact test; ^bMann-Whitney U test. BMI: body mass index; PMI: psoas muscle index; CR: complete response; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group-performance status; Ex: ex-smoker; IQR: interquartile range; NE: not evaluated; NS: non-smoker; ORR: overall response rate; PD: progressive disease; PR: partial response; SD: stable disease; ULN: upper limit of normal range; LDH: lactate dehydrogenase.
N	93	35
Backgrounds
Sex (N), men/women	75/18	26/9	0.47^a
Age (years)
Median (IQR)	71 (66 - 76)	72 (63.5 - 79)	0.79^b
< 75/≥ 75 years (N)	59/34	20/15	0.55^a
Smoking status, NS/Ex/CS/unknown	1/29/62/1	2/12/21/0	0.43^a
ECOG-PS, 0 - 1/2/3	51/25/17	26/6/3	0.15^a
c-stage, IIIB/IV	14/79	5/30	1.00^a
Metastatic sites
Brain	17	7	0.80^a
Liver	29	8	0.39^a
Bone	14	4	0.79^a
BMI
Median (IQR)	21.0 (19.1 - 24.0)	24.6 (23.2 - 27.1)	< 0.01^b
≥ 18.5/< 18.5	78/15	34/1	0.07^a
Treatment
Platinum-based, cisplatin/carboplatin	22/71	9/26	0.82^a
Partner drugs, etoposide/irinotecan	81/12	32/3	0.76^a
Efficacy
CR/PR/SD/PD/NE	0/57/10/16/10	2/19/7/5/2
ORR (%)	61.3	60.0	1.00^a
DCR (%)	72.0	80.0	0.50^a
Second or later line (N)	46	23	0.12^a
Amrubicin (N)	34	15	0.55^a
Topotecan (N)	9	4	0.75^a
Irinotecan (N)	5	2	1.00^a
Pretreatment laboratory data
Albumin (g/dL)
Median (IQR)	3.6 (3.0 - 3.9)	3.7 (3.3 - 3.9)	0.57^b
≥ 3.5/< 3.5 g/dL (N)	49/44	25/10	0.07^a
LDH (IU/L)
Median (IQR)	282 (218 - 410)	323 (205 - 410)	0.69^b
< ULN/≥ ULN	26/67	11/24	0.83^a

Table 2. Baseline Characteristics According to PMI

PMI

Low

High

^aFisher’s exact test; ^bMann-Whitney U test. BMI: body mass index; PMI: psoas muscle index; CR: complete response; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group-performance status; Ex: ex-smoker; IQR: interquartile range; NE: not evaluated; NS: non-smoker; ORR: overall response rate; PD: progressive disease; PR: partial response; SD: stable disease; ULN: upper limit of normal range; LDH: lactate dehydrogenase.

Backgrounds

Sex (N), men/women

75/18

26/9

0.47^a

Age (years)

Median (IQR)

71 (66 - 76)

72 (63.5 - 79)

0.79^b

< 75/≥ 75 years (N)

59/34

20/15

0.55^a

Smoking status, NS/Ex/CS/unknown

1/29/62/1

2/12/21/0

0.43^a

ECOG-PS, 0 - 1/2/3

51/25/17

26/6/3

0.15^a

c-stage, IIIB/IV

14/79

5/30

1.00^a

Metastatic sites

Brain

0.80^a

Liver

0.39^a

Bone

0.79^a

BMI

Median (IQR)

21.0 (19.1 - 24.0)

24.6 (23.2 - 27.1)

< 0.01^b

≥ 18.5/< 18.5

78/15

34/1

0.07^a

Treatment

Platinum-based, cisplatin/carboplatin

22/71

9/26

0.82^a

Partner drugs, etoposide/irinotecan

81/12

32/3

0.76^a

Efficacy

CR/PR/SD/PD/NE

0/57/10/16/10

2/19/7/5/2

ORR (%)

61.3

60.0

1.00^a

DCR (%)

72.0

80.0

0.50^a

Second or later line (N)

0.12^a

Amrubicin (N)

0.55^a

Topotecan (N)

0.75^a

Irinotecan (N)

1.00^a

Pretreatment laboratory data

Albumin (g/dL)

Median (IQR)

3.6 (3.0 - 3.9)

3.7 (3.3 - 3.9)

0.57^b

≥ 3.5/< 3.5 g/dL (N)

49/44

25/10

0.07^a

LDH (IU/L)

Median (IQR)

282 (218 - 410)

323 (205 - 410)

0.69^b

< ULN/≥ ULN

26/67

11/24

0.83^a

**Table 3.** Baseline Characteristics According to IMAC
	IMAC	P
^aFisher’s exact test; ^bMann-Whitney U test. IMAC: intramuscular adipose tissue content; BMI: body mass index; CR: complete response; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group-performance status; Ex: ex-smoker; IQR: interquartile range; NE: not evaluated; NS: non-smoker; ORR: overall response rate; PD: progressive disease; PR: partial response; SD: stable disease; ULN: upper limit of normal range.
N	114	14
Backgrounds
Sex (N), men/women	89/25	12/2	0.73^a
Age (years)
Median (IQR)	71.5 (66 - 76)	76.5 (66.5 - 81.8)	0.15^b
< 75/≥ 75 years (N)	72/42	7/7	0.39^a
Smoking status, NS/Ex/CS	2/36/75/1	1/5/8/0	0.41^a
ECOG-PS, 0 - 1/2/3	71/27/16	6/4/4	0.27^a
c-stage, IIIB/IV	17/97	2/12	1.00^a
Metastatic sites
Brain	24	0	0.07^a
Liver	31	6	0.23^a
Bone	17	1	0.69^a
BMI
Median (IQR)	21.8 (19.5 - 24.5)	24.1 (22.9 - 25.7)	0.06^b
≥ 18.5/< 18.5	98/16	14/0	0.21^a
Treatment
Platinum-based, cisplatin/carboplatin	29/85	2/12	0.52^a
Partner drugs, etoposide/irinotecan	99/15	14/0	0.37^a
Efficacy
CR/PR/SD/PD/NE	2/69/14/18/11	0/7/3/3/1
ORR (%)	62.3	50.0	0.40^a
DCR (%)	74.6	71.4	0.76^a
Second or later line (N)	62	7	0.78^a
Amrubicin (N)	43	6	0.77^a
Topotecan (N)	12	1	1.00^a
Irinotecan (N)	7	0	1.00^a
Pretreatment laboratory data
Albumin (g/dL)
Median (IQR)	3.7 (3.1 - 3.9)	3.4 (2.9 - 3.8)	0.21^b
≥ 3.5/< 3.5 g/dL (N)	68/46	6/8	0.26^a
LDH (IU/L)
Median (IQR)	285 (210 - 428)	292 (225 - 388)	0.79^b
< ULN/≥ ULN	33/81	4/10	1.00^a

Table 3. Baseline Characteristics According to IMAC

IMAC

Low

High

^aFisher’s exact test; ^bMann-Whitney U test. IMAC: intramuscular adipose tissue content; BMI: body mass index; CR: complete response; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group-performance status; Ex: ex-smoker; IQR: interquartile range; NE: not evaluated; NS: non-smoker; ORR: overall response rate; PD: progressive disease; PR: partial response; SD: stable disease; ULN: upper limit of normal range.

114

Backgrounds

Sex (N), men/women

89/25

12/2

0.73^a

Age (years)

Median (IQR)

71.5 (66 - 76)

76.5 (66.5 - 81.8)

0.15^b

< 75/≥ 75 years (N)

72/42

7/7

0.39^a

Smoking status, NS/Ex/CS

2/36/75/1

1/5/8/0

0.41^a

ECOG-PS, 0 - 1/2/3

71/27/16

6/4/4

0.27^a

c-stage, IIIB/IV

17/97

2/12

1.00^a

Metastatic sites

Brain

0.07^a

Liver

0.23^a

Bone

0.69^a

BMI

Median (IQR)

21.8 (19.5 - 24.5)

24.1 (22.9 - 25.7)

0.06^b

≥ 18.5/< 18.5

98/16

14/0

0.21^a

Treatment

Platinum-based, cisplatin/carboplatin

29/85

2/12

0.52^a

Partner drugs, etoposide/irinotecan

99/15

14/0

0.37^a

Efficacy

CR/PR/SD/PD/NE

2/69/14/18/11

0/7/3/3/1

ORR (%)

62.3

50.0

0.40^a

DCR (%)

74.6

71.4

0.76^a

Second or later line (N)

0.78^a

Amrubicin (N)

0.77^a

Topotecan (N)

1.00^a

Irinotecan (N)

1.00^a

Pretreatment laboratory data

Albumin (g/dL)

Median (IQR)

3.7 (3.1 - 3.9)

3.4 (2.9 - 3.8)

0.21^b

≥ 3.5/< 3.5 g/dL (N)

68/46

6/8

0.26^a

LDH (IU/L)

Median (IQR)

285 (210 - 428)

292 (225 - 388)

0.79^b

< ULN/≥ ULN

33/81

4/10

1.00^a

**Table 4.** Baseline Characteristics According to VSR
	VSR	P
^aFisher’s exact test; ^bMann-Whitney U test. VSR: visceral-to-subcutaneous fat ratio; BMI: body mass index; CR: complete response; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group-performance status; Ex: ex-smoker; IQR: interquartile range; NE: not evaluated; NS: non-smoker; ORR: overall response rate; PD: progressive disease; PR: partial response; SD: stable disease; ULN: upper limit of normal range; LDH: lactate dehydrogenase.
N	72	56
Backgrounds
Sex (N), men/women	52/20	49/7	0.049^a
Age (years)
Median (IQR)	69 (64.8 - 76)	73.5 (67.8 - 78.3)	0.04^b
< 75/≥ 75 years (N)	50/22	29/27	0.046^a
Smoking status, NS/Ex/CS	1/22/49/0	2/19/34/1	0.54^a
ECOG-PS, 0 - 1/2/3	40/19/13	37/12/7	0.47^a
c-stage, IIIB/IV	10/62	9/47	0.80^a
Metastatic sites
Brain	15	9	0.65^a
Liver	20	17	0.85^a
Bone	10	8	1.00^a
BMI
Median (IQR)	21.1 (19.1 - 24.3)	23.3 (20.9 - 26.2)	0.02^b
≥ 18.5/< 18.5	60/12	52/4	0.18^a
Treatment
Platinum-based, cisplatin/carboplatin	17/55	14/42	1.00^a
Partner drugs, etoposide/irinotecan	65/7	48/8	0.58a
Efficacy
CR/PR/SD/PD/NE	1/44/6/14/7	1/32/11/7/5
ORR (%)	62.5	58.9	0.72^a
DCR (%)	70.8	78.6	0.42^a
Second or later line (N)	37	32	0.59^a
Amrubicin (N)	25	24	0.37^a
Topotecan (N)	7	6	1.00^a
Irinotecan (N)	5	2	0.47^a
Pretreatment Laboratory data
Albumin (g/dL)
Median (IQR)	3.4 (3.1 - 3.9)	3.8 (3.2 - 4.0)	0.15^b
≥ 3.5/< 3.5 g/dL (N)	35/37	39/17	0.02^a
LDH (IU/L)
Median (IQR)	270 (217 - 430)	304 (209 - 402)	0.63^b
< ULN/≥ ULN	21/51	16/40	1.00^a

Table 4. Baseline Characteristics According to VSR

VSR

Low

High

^aFisher’s exact test; ^bMann-Whitney U test. VSR: visceral-to-subcutaneous fat ratio; BMI: body mass index; CR: complete response; CS: current smoker; DCR: disease control rate; ECOG-PS: Eastern Cooperative Oncology Group-performance status; Ex: ex-smoker; IQR: interquartile range; NE: not evaluated; NS: non-smoker; ORR: overall response rate; PD: progressive disease; PR: partial response; SD: stable disease; ULN: upper limit of normal range; LDH: lactate dehydrogenase.

Backgrounds

Sex (N), men/women

52/20

49/7

0.049^a

Age (years)

Median (IQR)

69 (64.8 - 76)

73.5 (67.8 - 78.3)

0.04^b

< 75/≥ 75 years (N)

50/22

29/27

0.046^a

Smoking status, NS/Ex/CS

1/22/49/0

2/19/34/1

0.54^a

ECOG-PS, 0 - 1/2/3

40/19/13

37/12/7

0.47^a

c-stage, IIIB/IV

10/62

9/47

0.80^a

Metastatic sites

Brain

0.65^a

Liver

0.85^a

Bone

1.00^a

BMI

Median (IQR)

21.1 (19.1 - 24.3)

23.3 (20.9 - 26.2)

0.02^b

≥ 18.5/< 18.5

60/12

52/4

0.18^a

Treatment

Platinum-based, cisplatin/carboplatin

17/55

14/42

1.00^a

Partner drugs, etoposide/irinotecan

65/7

48/8

0.58a

Efficacy

CR/PR/SD/PD/NE

1/44/6/14/7

1/32/11/7/5

ORR (%)

62.5

58.9

0.72^a

DCR (%)

70.8

78.6

0.42^a

Second or later line (N)

0.59^a

Amrubicin (N)

0.37^a

Topotecan (N)

1.00^a

Irinotecan (N)

0.47^a

Pretreatment Laboratory data

Albumin (g/dL)

Median (IQR)

3.4 (3.1 - 3.9)

3.8 (3.2 - 4.0)

0.15^b

≥ 3.5/< 3.5 g/dL (N)

35/37

39/17

0.02^a

LDH (IU/L)

Median (IQR)

270 (217 - 430)

304 (209 - 402)

0.63^b

< ULN/≥ ULN

21/51

16/40

1.00^a

**Table 5.** Adjusted Hazard Ratios of Indexes of Sarcopenia and Visceral Obesity for Overall Survival and Progression-Free Survival
Variables	PFS, HR (95% CI)	P	OS, HR (95% CI)	P
Multivariate adjustment for age (< 75 vs. 5 75 years), serum albumin (≥ 3.5 vs. < 3.5 g/dL), LDH (≤ UNL vs. > UNL), c-stage (IIIB vs. IV) and ECOG-PS (0 - 1 vs. 2 - 4). BMI: body mass index; CI: confidence interval; ECOG-PS: Eastern Cooperative Oncology Group-performance status; HR: hazard ratio; IMAC: intramuscular adipose tissue content; LDH: lactate dehydrogenase; PMI: psoas muscle index; UNL: upper limit of normal range; VSR: visceral-to-subcutaneous fat ratio; PFS: progression-free survival; OS: overall survival.
BMI
≥ 18.5	1 (reference)		1 (reference)
< 18.5	1.36 (0.79 - 2.34)	0.27	1.47 (0.83 - 2.57)	0.18
PMI (cm²/m²)
High	1 (reference)		1 (reference)
Low	1.44 (0.94 - 2.19)	0.09	1.32 (0.84 - 2.07)	0.23
IMAC
Low	1 (reference)		1 (reference)
High	0.97 (0.51 - 1.84)	0.93	0.87 (0.45 - 1.69)	0.68
VSR
Low	1 (reference)		1 (reference)
High	1.08 (0.73 - 1.59)	0.71	0.96 (0.63 - 1.47)	0.86

Table 5. Adjusted Hazard Ratios of Indexes of Sarcopenia and Visceral Obesity for Overall Survival and Progression-Free Survival

Variables

PFS, HR (95% CI)

OS, HR (95% CI)

Multivariate adjustment for age (< 75 vs. 5 75 years), serum albumin (≥ 3.5 vs. < 3.5 g/dL), LDH (≤ UNL vs. > UNL), c-stage (IIIB vs. IV) and ECOG-PS (0 - 1 vs. 2 - 4). BMI: body mass index; CI: confidence interval; ECOG-PS: Eastern Cooperative Oncology Group-performance status; HR: hazard ratio; IMAC: intramuscular adipose tissue content; LDH: lactate dehydrogenase; PMI: psoas muscle index; UNL: upper limit of normal range; VSR: visceral-to-subcutaneous fat ratio; PFS: progression-free survival; OS: overall survival.

BMI

≥ 18.5

1 (reference)

< 18.5

1.36 (0.79 - 2.34)

0.27

1.47 (0.83 - 2.57)

0.18

PMI (cm²/m²)

High

1 (reference)

Low

1.44 (0.94 - 2.19)

0.09

1.32 (0.84 - 2.07)

0.23

IMAC

Low

1 (reference)

High

0.97 (0.51 - 1.84)

0.93

0.87 (0.45 - 1.69)

0.68

VSR

Low

1 (reference)

High

1.08 (0.73 - 1.59)

0.71

0.96 (0.63 - 1.47)

0.86

**Table 6.** Review of Studies That Evaluated CT-Determined Sarcopenia in SCLC
Author (year)	Patients	Sarcopenia definitions	Survival comparison; sarcopenia vs. non-sarcopenia	Multivariate analyses
BSC: best supportive care; chemo: chemotherapy; CI: confidence interval; CRT: chemo-radiotherapy; CS: cachexia score; ED: extensive disease; FI: fat index; HR: hazard ratio; LD: limited disease; MI: muscle index; NLR: neutrophil-to-lymphocyte ratio; OS: overall survival; PFS: progression-free survival; PMI: psoas muscle index; SCLC: small-cell lung cancer; SMI: skeletal muscle index; CT: computed tomography.
Kim et al (2015) [7]	149 SCLC; male (85.2%), ED (67.8%), chemo alone (48.3%), CRT (29.5%), BSC alone (20.8%)	L3MI, sarcopenia (79.2%)	OS, 8.6 vs. 16.8 months, P = 0.031	Non-sarcopenia vs. sarcopenia; OS, HR 1.68, 95% CI 1.04 - 2.72, P = 0.034
Go et al (2016) [8]	117 male SCLC; ED (54.7%), CRT (45.3%)	SMI of pectoralis muscles, sarcopenia (24.8%)	PFS, 6.0 vs. 7.5 months, P = 0.009; OS, 10.5 vs. 13.5 months, P = 0.052	Sarcopenia with low NLR + non-sarcopenia vs. sarcopenic with high NLR; PFS, HR 3.805, 95% CI 1.774 - 8.158, P = 0.001; OS, HR 2.230, 95% CI 1.048 - 4.743, P = 0.037
Kim et al (2017) [9]	127 male SCLC; ED (69.3%), chemo alone (48.0%), CRT (29.1%), BSC alone (21.3%)	CS defined by L3MI and L3FI; CS0 (13.4%), CS1 (74.8%), CS2 (11.8%)	OS, 5.0 (CS2) vs. 8.9 (CS1) vs. 18.3 months (CS0), P = 0.007	CS0 vs. CS1, OS, HR 1.99, 95% CI 1.05 - 3.78, P = 0.036; CS0 vs. CS2, OS, HR 2.59, 95% CI 1.14 - 5.89, P = 0.023
Ours (2020)	128 ED-SCLC; male (78.9%), chemo alone (100%)	PMI; low PMI (72.7%)	PFS, 4.5 vs. 5.2 months, P = 0.17; OS, 8.8 vs. 11.4 months, P = 0.17	High PMI vs. low PMI; PFS, HR 1.44, 95% CI 0.94 - 2.19, P = 0.09; OS, HR 1.32, 95% CI 0.84 - 2.07, P = 0.23

Table 6. Review of Studies That Evaluated CT-Determined Sarcopenia in SCLC

Author (year)

Patients

Sarcopenia definitions

Survival comparison; sarcopenia vs. non-sarcopenia

Multivariate analyses

BSC: best supportive care; chemo: chemotherapy; CI: confidence interval; CRT: chemo-radiotherapy; CS: cachexia score; ED: extensive disease; FI: fat index; HR: hazard ratio; LD: limited disease; MI: muscle index; NLR: neutrophil-to-lymphocyte ratio; OS: overall survival; PFS: progression-free survival; PMI: psoas muscle index; SCLC: small-cell lung cancer; SMI: skeletal muscle index; CT: computed tomography.

Kim et al (2015) [7]

149 SCLC; male (85.2%), ED (67.8%), chemo alone (48.3%), CRT (29.5%), BSC alone (20.8%)

L3MI, sarcopenia (79.2%)

OS, 8.6 vs. 16.8 months, P = 0.031

Non-sarcopenia vs. sarcopenia; OS, HR 1.68, 95% CI 1.04 - 2.72, P = 0.034

Go et al (2016) [8]

117 male SCLC; ED (54.7%), CRT (45.3%)

SMI of pectoralis muscles, sarcopenia (24.8%)

PFS, 6.0 vs. 7.5 months, P = 0.009; OS, 10.5 vs. 13.5 months, P = 0.052

Sarcopenia with low NLR + non-sarcopenia vs. sarcopenic with high NLR; PFS, HR 3.805, 95% CI 1.774 - 8.158, P = 0.001; OS, HR 2.230, 95% CI 1.048 - 4.743, P = 0.037

Kim et al (2017) [9]

127 male SCLC; ED (69.3%), chemo alone (48.0%), CRT (29.1%), BSC alone (21.3%)

CS defined by L3MI and L3FI; CS0 (13.4%), CS1 (74.8%), CS2 (11.8%)

OS, 5.0 (CS2) vs. 8.9 (CS1) vs. 18.3 months (CS0), P = 0.007

CS0 vs. CS1, OS, HR 1.99, 95% CI 1.05 - 3.78, P = 0.036; CS0 vs. CS2, OS, HR 2.59, 95% CI 1.14 - 5.89, P = 0.023

Ours (2020)

128 ED-SCLC; male (78.9%), chemo alone (100%)

PMI; low PMI (72.7%)

PFS, 4.5 vs. 5.2 months, P = 0.17; OS, 8.8 vs. 11.4 months, P = 0.17

High PMI vs. low PMI; PFS, HR 1.44, 95% CI 0.94 - 2.19, P = 0.09; OS, HR 1.32, 95% CI 0.84 - 2.07, P = 0.23

**Table 7.** Review of Studies That Evaluated BMI in Untreated SCLC
Author (year)	Patients	BMI	Survival comparison	Univariate analyses	Multivariate analyses
BSC: best supportive care; CBDCA: carboplatin; Chemo: chemotherapy; CI: confidence interval; CRT: chemo-radiotherapy; ED: extensive disease; LD: limited disease; HR: hazard ratio; NA: not accessed; OS: overall survival; PFS: progression-free survival; SCLC: small-cell lung cancer; VP-16: etoposide; BMI: body mass index.
Georgiadis et al (1995) [29]	262 SCLC; male (63%), ED (44%), chemo alone (61%), CRT (39%)	Obese (27.1%), men ≥ 27.8, women ≥ 27.3; severely obese (10.7%), men ≥ 31.1, women ≥ 32.3	Not described in details, but insignificant	NA	NA
Kim et al (2015) [7]	149 SCLC; male (85.2%), ED (67.8%), chemo alone (48.3%), CRT (29.5%), BSC alone (20.8%)	≥ 23 vs. < 23 (59.1%)	NA	OS; HR 1.19 (95% CI 0.83 - 1.72), P = 0.340	NA
Go et al (2016) [8]	117 male SCLC; ED (54.7%), CRT (45.3%)	≥ 18.5 vs. < 18.5 (10.3%)	NA	PFS, HR 1.749 (95% CI 0.930 - 3.291), P = 0.083; OS, HR 1.077 (95% CI 0.554 - 2.096), P = 0.827	PFS, 1.001 (0.500 - 2.006), P = 0.998; OS, not assessed
Kim et al (2017) [9]	127 male SCLC; ED (69.3%), chemo alone (48.0%), CRT (29.1%), BSC alone (21.3%)	≥ 18.5 vs. < 18.5 (15.0%)	NA	OS, HR 2.32 (95% CI 1.38 - 3.89), P < 0.001	NA
Abdel-Rahman (2018) [28]	455 ED-SCLC in a phase III trial; male (72.5%), CBDCA + VP-16 (100%)	< 25 (48.1%) vs. ≥ 25	NA	PFS, HR 0.891 (95% CI 0.644 - 1.234), P = 0.487; OS, HR 0.856 (95% CI 0.678 - 1.082), P = 0.194	PFS, OS; NA
Shen et al (2019) [30]	178 SCLC; male (79.78%), ED (71.91%), VP-16 containing chemo alone	18.5 - 24 (56.74%) vs. < 18.5 (6.74%) vs. ≥ 24	P = 0.4107	PFS, 18.5 - 24 vs. < 18.5, P = 0.851; 18.5 - 24 vs. ≥ 24, P = 0.212	NA
Shepshelovich et al (2019) [31]	2,787 SCLC from 16 studies; male (56%), ED (59%),	< 18.5 vs. normal	OS (ED), P < 0.001; OS (LD), P = 0.002	HR 1.16 (95% CI 0.89 - 1.51), P = 0.28	HR 1.20 (95% CI 0.92 - 1.6), P = 0.18
	25 - 30 vs. normal		HR 0.97 (95% CI 0.87 - 1.07), P = 0.51	HR 0.93 (95% CI 0.84 - 1.0), P = 0.20
	> 30 vs. normal		HR 1.05 (95% CI 0.94 - 1.19), P = 0.39	HR 1.07 (95% CI 0.95 - 1.2), P = 0.24
Ours (2020)	128 ED-SCLC; male (78.9%), chemo alone (100%)	≥ 18.5 vs. < 18.5 (12.5%)	PFS, P = 0.39; OS, P = 0.07	NA	PFS, 1.36 (0.79 - 2.34), P = 0.27; OS, 1.47 (0.83 - 2.57), P = 0.18

Table 7. Review of Studies That Evaluated BMI in Untreated SCLC

Author (year)

Patients

BMI

Survival comparison

Univariate analyses

Multivariate analyses

BSC: best supportive care; CBDCA: carboplatin; Chemo: chemotherapy; CI: confidence interval; CRT: chemo-radiotherapy; ED: extensive disease; LD: limited disease; HR: hazard ratio; NA: not accessed; OS: overall survival; PFS: progression-free survival; SCLC: small-cell lung cancer; VP-16: etoposide; BMI: body mass index.

Georgiadis et al (1995) [29]

262 SCLC; male (63%), ED (44%), chemo alone (61%), CRT (39%)

Obese (27.1%), men ≥ 27.8, women ≥ 27.3; severely obese (10.7%), men ≥ 31.1, women ≥ 32.3

Not described in details, but insignificant

Kim et al (2015) [7]

149 SCLC; male (85.2%), ED (67.8%), chemo alone (48.3%), CRT (29.5%), BSC alone (20.8%)

≥ 23 vs. < 23 (59.1%)

OS; HR 1.19 (95% CI 0.83 - 1.72), P = 0.340

Go et al (2016) [8]

117 male SCLC; ED (54.7%), CRT (45.3%)

≥ 18.5 vs. < 18.5 (10.3%)

PFS, HR 1.749 (95% CI 0.930 - 3.291), P = 0.083; OS, HR 1.077 (95% CI 0.554 - 2.096), P = 0.827

PFS, 1.001 (0.500 - 2.006), P = 0.998; OS, not assessed

Kim et al (2017) [9]

127 male SCLC; ED (69.3%), chemo alone (48.0%), CRT (29.1%), BSC alone (21.3%)

≥ 18.5 vs. < 18.5 (15.0%)

OS, HR 2.32 (95% CI 1.38 - 3.89), P < 0.001

Abdel-Rahman (2018) [28]

455 ED-SCLC in a phase III trial; male (72.5%), CBDCA + VP-16 (100%)

< 25 (48.1%) vs. ≥ 25

PFS, HR 0.891 (95% CI 0.644 - 1.234), P = 0.487; OS, HR 0.856 (95% CI 0.678 - 1.082), P = 0.194

PFS, OS; NA

Shen et al (2019) [30]

178 SCLC; male (79.78%), ED (71.91%), VP-16 containing chemo alone

18.5 - 24 (56.74%) vs. < 18.5 (6.74%) vs. ≥ 24

P = 0.4107

PFS, 18.5 - 24 vs. < 18.5, P = 0.851; 18.5 - 24 vs. ≥ 24, P = 0.212

Shepshelovich et al (2019) [31]

2,787 SCLC from 16 studies; male (56%), ED (59%),

< 18.5 vs. normal

OS (ED), P < 0.001;
OS (LD), P = 0.002

HR 1.16 (95% CI 0.89 - 1.51), P = 0.28

HR 1.20 (95% CI 0.92 - 1.6), P = 0.18

25 - 30 vs. normal

HR 0.97 (95% CI 0.87 - 1.07), P = 0.51

HR 0.93 (95% CI 0.84 - 1.0), P = 0.20

> 30 vs. normal

HR 1.05 (95% CI 0.94 - 1.19), P = 0.39

HR 1.07 (95% CI 0.95 - 1.2), P = 0.24

Ours (2020)

128 ED-SCLC; male (78.9%), chemo alone (100%)

≥ 18.5 vs. < 18.5 (12.5%)

PFS, P = 0.39; OS, P = 0.07

PFS, 1.36 (0.79 - 2.34), P = 0.27; OS, 1.47 (0.83 - 2.57), P = 0.18