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416

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418

18

419

FIGURE LEGENDS

420

Fig. 1

421

Flowchart of the participants

422

423

Fig. 2

424

Histogram of normalized total psoas muscle area among patients with borderline resectable

425

pancreatic cancer.

426

Gray bar, patients who could undergo resection; black bar, patients who could not undergo

427

resection due to an advanced tumor.

428

429

Fig. 3

430

Kaplan–Meier curves for overall survival in patients with (A) resectable pancreatic cancer

431

and (B) borderline resectable pancreatic cancer.

432

433

Supplementary Fig. 1

434

Abdominal computed tomography image at the level of the third lumbar vertebra. The right

435

and left psoas muscle areas, which comprise the total psoas muscle area (TPA), were traced

436

(dotted line). Normalized TPA = measured TPA [mm2]/height [m]2.

437

438

Supplementary Fig. 2

439

Kaplan–Meier curves for recurrence free survival in patients with (A) resectable pancreatic

440

cancer and (B) borderline resectable pancreatic cancer.

441

19

Table 1 Baseline characteristics of patients with resectable pancreatic cancer

Variables

Normal-TPA

Low-TPA

(n = 29)

(n = 15)

p Value

Baseline characteristics of the patients before neoadjuvant chemotherapy

Age (years)

72 (63–76)

73 (71–74)

0.691

18 (62)

9 (60)

0.894

1.62 (1.54–1.68)

1.61 (1.53–1.69)

0.941

58.0 (48.9–65.2)

50.9 (46.7–55.5)

0.095

21.9 (20.2–23.5)

19.3 (18.1–20.6)

0.015

Male

9.00 (8.26–10.41)

7.11 (6.25–7.67)

<0.001

Female

6.75 (6.30–7.05)

5.52 (5.25–5.60)

<0.001

Male gender [n (%)]

Height (m)

Body weight (kg)

Body mass index (kg/m )

Total psoas muscle area (cm2/m2)

Tumor location [n (%)]

0.464

Head

24 (83)

11 (73)

Body, tail

5 (17)

4 (27)

10/8/11

3/5/7

0.719

43 (42–45)

44 (41–46)

0.803

14/11/4

7/7/1

0.824

C-reactive protein to albumin ratio

0.11 (0.01–0.37)

0.03 (0.01–0.15)

0.488

Neutrophil to lymphocyte ratio

2.36 (1.81–3.64)

2 (1.51–2.68)

0.173

166 (114–227)

153 (124–209)

0.720

25.0 (21.0–30.0)

18.0 (17.5–23.5)

0.002

145 (57–580)

54 (26–348)

0.287

Charlson comorbidity index (0/1/>1)

Prognostic score

Prognostic nutritional index

modified glasgow prognostic score (0/1/2)

Platelet-to-lymphocyte ratio

Tumor size (mm)

CA 19-9 serum level (U/mL)

Treatment details and treatment response

Chemotherapy regimen [n (%)]

0.376

FOLFIRINOX

1 (3)

0 (0)

Gemcitabine + nab-paclitaxel

3 (10)

0 (0)

Gemcitabine + S-1

25 (86)

14 (93)

0 (0)

1 (7)

49 (41–55)

35 (20–41)

0.016

1.00 (1.00–1.00)

0.96 (0.50‒1.00)

0.010

23 (79)

7 (47)

0.042

-5 (-8–-2)

0 (-2–0)

0.008

S-1

Duration of chemotherapy (days)

Relative dose intensity

Rate of chemotherapy completion [n (%)]

Change of tumor size (mm)

RECIST criteria [n (%)]

0.452

Complete response / Partial response

8 (28)

2 (13)

Stable disease / Progressive disease

21 (72)

13 (87)

15 (52)

11 (73)

0.208

Leukopenia

5 (17)

7 (47)

0.071

Neutropenia

15 (52)

10 (67)

0.522

0 (0)

1 (7)

0.341

29 (100)

15 (100)

NA

Adverse events Grade ≥3 [n (%)]

Any hematotoxicity

Platelets

Resection [n (%)]

Type of operation [n (%)]

0.468

Pancreaticoduodenectomy

23 (79)

10 (67)

Distal or total pancreatectomy

6 (21)

5 (33)

Portal vein

5 (17)

6 (40)

0.144

Artery

0 (0)

0 (0)

NA

Operation time (min)

402 (347–449)

368 (316–483)

0.569

Blood loss (ml)

660 (365–915)

440 (243–1179)

0.683

Combined resection [n (%)]

Evans grading [n (%)]

0.647

Grade IIb, III, IV

5 (17)

1 (7)

Grade I, IIa

24 (83)

14 (93)

R0 resection [n (%)]

26 (90)

14 (93)

1.000

Clavien-Dindo grade ³3 [n (%)]

11 (28)

2 (13)

0.162

24 (17–33)

21 (19–23)

0.511

23 (79)

13 (87)

0.695

Postoperative hospital stays (days)

Adjuvant chemotherapy [n (%)]

Data are presented as median (interquartile range [IQR]) or n (%). CA 19-9 serum level carbohydrate antigen 19-9 serum level,

FOLFIRINOX combination of fluorouracil, leucovorin, oxaliplatin, and irinotecan, RECIST criteria, Response Evaluation Criteria in

Solid Tumors criteria. NA not applicable.

Table 2 Baseline characteristics of patients with borderline resectable pancreatic cancer

Variables

Normal-TPA

Low-TPA

(n = 48)

(n = 23)

p Value

Baseline characteristics of the patients before neoadjuvant chemotherapy

Age (years)

68 (60–72)

66 (59–72)

1.000

28 (58)

14 (61)

0.839

1.61 (1.55–1.66)

1.61 (1.53–1.69)

0.658

56.7 (48.6–63.1)

52.6 (44.4–59.4)

0.078

22.1 (20.4–23.5)

19.7 (18.7–20.7)

0.001

Male

8.35 (7.55–9.53)

6.20 (5.63–6.88)

<0.001

Female

7.30 (7.02–8.15)

5.36 (4.99–6.10)

<0.001

Male gender [n (%)]

Height (m)

Body weight (kg)

Body mass index (kg/m )

Total psoas muscle area (cm2/m2)

Tumor location [n (%)]

0.234

Head

14 (29)

3 (13)

Body, tail

34 (71)

20 (87)

27/15/6

9/11/3

0.359

44.5 (42–47)

43 (37–46)

0.158

34/11/3

13/7/3

0.369

C-reactive protein to albumin ratio

0.06 (0.01–0.13)

0.04 (0.01–0.07)

0.535

Neutrophil to lymphocyte ratio

2.29 (1.74–3.87)

2.33 (1.49–3.2)

0.606

167 (126–208)

172 (116–210)

0.768

27.5 (22.0–32.0)

30.0 (25.0–36.0)

0.108

279 (45–943)

67 (20–456)

0.231

Charlson comorbidity index (0/1/>1)

Prognostic score

Prognostic nutritional index

modified glasgow prognostic score (0/1/2)

Platelet-to-lymphocyte ratio

Tumor size (mm)

CA 19-9 serum level (U/mL)

Treatment details and treatment response

Chemotherapy regimen [n (%)]

<0.001

FOLFIRINOX

22 (46)

1 (4)

Gemcitabine + nab-paclitaxel

24 (50)

22 (96)

Gemcitabine + S-1

2 (4)

0 (0)

S-1

0 (0)

0 (0)

60 (49–77)

59 (49–128)

0.610

1.00 (1.00–1.00)

1.00 (0.89–1.00)

0.007

39 (81)

9 (39)

0.001

-4 (-7–-1)

-1 (-8–0)

0.274

Duration of chemotherapy (days)

Relative dose intensity

Rate of chemotherapy completion [n (%)]

Change of tumor size (mm)

RECIST criteria [n (%)]

0.359

Complete response / Partial response

8 (17)

6 (26)

Stable disease / Progressive disease

40 (83)

17 (74)

27 (56)

16 (70)

0.313

Leukopenia

13 (27)

8 (35)

0.582

Neutropenia

27 (56)

16 (70)

0.313

4 (8)

2 (9)

1.000

46 (96)

16 (70)

0.004

Adverse events Grade ≥3 [n (%)]

Any hematotoxicity

Platelets

Resection [n (%)]

Type of operation [n (%)]*

0.582

Pancreaticoduodenectomy

34 (74)

13 (81)

Distal or total pancreatectomy

12 (26)

3 (19)

Portal vein

37 (80)

13 (81)

1.000

Artery

9 (20)

4 (25)

0.725

487 (439–536)

506 (416–590)

0.797

1075 (668–1532)

888 (652–1613)

0.541

Combined resection [n (%)]*

Operation time (min)*

Blood loss (ml)*

Evans grading [n (%)]*

0.713

Grade IIb, III, IV

9 (20)

2 (13)

Grade I, IIa

37 (80)

14 (88)

R0 resection [n (%)]*

38 (79)

9 (39)

0.046

Clavien-Dindo grade ³3 [n (%)]

5 (11)

3 (19)

0.414

23 (19–28)

23 (19–24)

0.735

41 (89)

14 (88)

1.000

Postoperative hospital stays (days)*

Adjuvant chemotherapy [n (%)]*

Data are presented as median (interquartile range [IQR]) or n (%). CA 19-9 serum level carbohydrate antigen 19-9 serum level,

FOLFIRINOX, combination of fluorouracil, leucovorin, oxaliplatin, and irinotecan, RECIST criteria, Response Evaluation Criteria in

Solid Tumors criteria. *n = 62

Table 3 Unadjusted and adjusted Cox regression analyses for overall survival and recurrence-free survival

Univariate analysis

Multivariate analysis

Variables

HR

95%CI

Normal-TPA

1.00

[Reference]

Low-TPA

1.71

0.38–7.68

Age, per SD increase

0.92

Male

Body mass index, SD decrease

p Value

HR

95%CI

p Value

1.00

[Reference]

0.482

1.43

0.27–7.53

0.670

0.44–1.91

0.823

1.26

0.54–2.94

0.586

6.18

0.77–49.57

0.086

8.10

0.81–81.18

0.075

1.04

0.5–2.16

0.915

1.33

0.44–4.02

0.616

Normal-TPA

1.00

[Reference]

1.00

[Reference]

Low-TPA

2.98

1.33–6.70

0.008

2.57

1.06–6.24

0.037

Age, per SD increase

1.11

0.75–1.65

0.612

1.05

0.68–1.62

0.818

Male

1.49

0.66–3.39

0.336

1.92

0.82–4.47

0.133

Body mass index, SD decrease

1.53

0.99–2.35

0.055

1.38

0.86–2.22

0.182

Normal-TPA

1.00

[Reference]

1.00

[Reference]

Low-TPA

0.38

0.13–1.11

0.075

0.37

0.12–1.13

0.080

Age, per SD increase

1.33

0.87–2.03

0.185

1.32

0.86–2.02

0.203

Male

0.98

0.43–2.22

0.965

1.20

0.49–2.91

0.694

Body mass index, SD decrease

0.91

0.60–1.39

0.672

1.09

0.67–1.77

0.740

Normal-TPA

1.00

[Reference]

1.00

[Reference]

Low-TPA

1.60

0.84–3.06

0.151

1.65

0.8–3.38

0.173

Age, per SD increase

1.19

0.88–1.60

0.268

1.19

0.85–1.65

0.310

Male

0.88

0.49–1.57

0.667

0.99

0.54–1.80

0.961

Body mass index, SD decrease

1.06

0.80–1.40

0.705

0.94

0.69–1.28

0.700

Overall survival

Resectable pancreatic cancer (n = 44)

Indicator

Borderline resectable pancreatic cancer (n = 71)

Indicator

Recurrence-free survival

Resectable pancreatic cancer (n = 44)

Indicator

Borderline resectable pancreatic cancer (n = 62)

Indicator

TPA total psoas area, CI confidence interval, HR hazard ratio, SD standard deviation.

Survival analysis was performed using a univariate Cox proportional hazards model. Variables of baseline characteristics of the

patients before neoadjuvant chemotherapy (TPA, age, sex, and body mass index) were incorporated into multivariate analysis.

Patients treated with neoadjuvant chemotherapy for pancreatic

cancer from January 2015 and September 2020 (n = 187)

Patients treated with

combined radiation

therapy (n = 61)

Patients previously treated

with chemotherapy in

another hospital (n = 11)

Resectable pancreatic

cancer (n = 44)

Borderline resectable

pancreatic cancer (n = 71)

Fig. 1

30

Number of patients

25

No Resection

20

Resection

15

10

3.0

4.0

5.0

6.0

7.0

8.0

9.0

10.0

11.0

12.0

13.0

Total psoas muscle area (cm2/m2)

Fig. 2

A. Resectable pancreatic cancer

Normal-TPA

1.0

Low-TPA

Survival

0.8

0.6

0.4

0.2

0.0

Log-rank: p = 0.477

0.0

Normal-TPA

Low-TPA

0.5

Number at risk

29

27

15

15

1.0

1.5

2.0

Follow-up (Years)

27

10

19

10

2.5

3.0

B. Borderline resectable pancreatic cancer

1.0

Survival

0.8

0.6

0.4

0.2

0.0

Log-rank: p = 0.006

0.0

Normal-TPA

Low-TPA

0.5

1.0

Number at risk

48

47

45

23

20

17

1.5

2.0

2.5

Follow-up (Years)

41

13

34

28

3.0

18

Fig. 3

Supplementary Fig. 1

A. Resectable pancreatic cancer

Normal-TPA

1.0

Low-TPA

Survival

0.8

0.6

0.4

0.2

0.0

Log-rank: p = 0.064

0.0

0.5

1.0

Number at risk

Normal-TPA

Low-TPA

29

15

23

10

1.5

2.0

2.5

Follow-up (Years)

17

3.0

B. Borderline resectable pancreatic cancer

1.0

Survival

0.8

0.6

0.4

0.2

0.0

Log-rank: p = 0.147

0.0

0.5

1.0

Number at risk

Normal-TPA 46

40

35

Low-TPA 16

10

10

1.5

2.0

2.5

Follow-up (Years)

24

15

13

3.0

10

Supplementary Fig. 2

...