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Table 1 Patient characteristics

Characteristic

PDT (n = 30)

Age, years

Median (range)

60.5 (23–85)

Sex, n (%)

Male

16 (53)

Female

14 (47)

Preoperative Karnofsky Performance Status score

Median (range)

80 (30–100)

Tumor locations, n (%)

Frontal

14 (47)

Temporal

9 (30)

Parietal

4 (13)

Occipital

1 (3)

Insular

1 (3)

Basal ganglia

1 (3)

Laterality, n (%)

Right

20 (67)

Left

10 (33)

Preoperative tumor volume, cm3

Median (range)

32.9 (2.2–140.0)

PDT

Median (range)

14 (2–31)

Extent of resection, n (%)

Gross total

23 (77)

Subtotal

5 (17)

Partial

2 (7)

Histopathology, n (%)

Glioblastoma

26 (87)

Anaplastic astrocytoma

2 (7)

Anaplastic oligodendroglioma

2 (7)

Isocitrate dehydrogenase mutation status, n (%)

Wild-type

25 (83)

17

Mutant

5 (17)

MGMT promoter methylation status, n (%)

Methylated

15 (50)

Unmethylated

9 (30)

Unknown

6 (20)

MIB-1 index, %

Median (range)

460

20 (10–80)

PDT, photodynamic therapy; MGMT, O6-methylguanine-DNA methyltransferase

18

461

Table 2 Tumor characteristics based on recurrence pattern after PDT

Local

(n = 10)

Distant

(n = 1)

Dissemination

(n = 8)

None

(n = 11)

Frontal

3 (30)

1 (100)

4 (50)

6 (55)

Temporal

4 (40)

0 (0)

1 (13)

4 (36)

Parietal

2 (20)

0 (0)

1 (13)

1 (9)

Occipital

0 (0)

0 (0)

1 (13)

0 (0)

Insular

1 (10)

0 (0)

0 (0)

0 (0)

Basal ganglia

0 (0)

0 (0)

1 (13)

0 (0)

Right

6 (60)

1 (100)

5 (63)

8 (73)

Left

4 (40)

0 (0)

3 (38)

3 (27)

32.9 (10.9–108.7)

8.7

34.6 (2.2–102.9)

37.7 (3.6–140.0)

12 (2–31)

15 (8–22)

15 (5–31)

Gross total

9 (90)

1 (100)

5 (63)

8 (73)

Subtotal

1 (10)

0 (0)

3 (38)

1 (9)

Partial

0 (0)

0 (0)

0 (0)

2 (18)

10 (100)

1 (100)

7 (88)

8 (73)

Anaplastic astrocytoma

0 (0)

0 (0)

0 (0)

2 (18)

Anaplastic oligodendroglioma

0 (0)

0 (0)

1 (13)

1 (9)

10 (100)

1 (100)

6 (75)

8 (73)

0 (0)

0 (0)

2 (25)

3 (27)

Methylated

6 (60)

1 (100)

3 (38)

5 (45)

Unmethylated

3 (30)

0 (0)

2 (25)

4 (36)

Unknown

1 (10)

0 (0)

3 (38)

2 (18)

Characteristic

Tumor locations, n (%)

Laterality, n (%)

Preoperative tumor volume, cm3

Median (range)

PDT

Median (range)

Extent of resection, n (%)

Histopathology, n (%)

Glioblastoma

Isocitrate dehydrogenase mutation status, n (%)

Wild-type

Mutant

MGMT promoter methylation status, n (%)

MIB-1 index, %

19

Median (range)

462

25 (10–70)

30

PDT, photodynamic therapy; MGMT, O -methylguanine-DNA methyltransferase

20

40 (10–80)

20 (10–25)

463

Figure Legends

464

Fig. 1 Axial diffusion-weighted imaging (DWI), T2-weighted FLAIR, and contrast-enhanced T1-weighted

465

imaging (CE-T1WI) of a 49-year-old woman showing a contrast-enhancing tumor in the left frontal lobe (upper

466

row of a). Post-PDT magnetic resonance (MR) images obtained on day 1 show complete resection of the

467

contrast-enhancing lesion and hyperintense signal on DWI adjacent to the resection cavity wall (middle row of

468

a). Follow-up MR images show local recurrence in the resection cavity wall of the primary tumor 22.5 months

469

after surgery (lower row of a). DWI (left of b) and CE-T1WI (right of b) show the relationship between the

470

hyperintense signal as the acute response and the recurrence site after PDT. The circle with the dotted line

471

indicates the area without hyperintense signal on DWI as the acute response (left of b). The white arrow

472

indicates the local recurrence site (right of b). The recurrence site is the area that does not show a hyperintense

473

signal on DWI obtained on day 1 after PDT (b). The histopathological diagnosis was WHO grade IV

474

glioblastoma, IDH wild-type. PDT, photodynamic therapy

475

476

Fig. 2 Axial diffusion-weighted imaging (DWI), T2-weighted FLAIR, and contrast-enhanced T1-weighted

477

imaging (CE-T1WI) of a 67-year-old woman showing a contrast-enhancing tumor in the right temporal lobe

478

(upper row of a). Post-PDT magnetic resonance (MR) images obtained on day 1 show complete resection of the

479

contrast-enhancing lesion and hyperintense signal on DWI adjacent to the resection cavity wall (middle row of

480

a). Follow-up MR images show local recurrence in the resection cavity wall of the primary tumor 7.7 months

481

after surgery (lower row of a). DWI (left of b) and CE-T1WI (right of b) show the relationship of the

482

hyperintense signal as the acute response with the recurrence site after PDT. The circle with the dotted line

483

indicates the area without hyperintense signal on DWI as the acute response (left of b). The white arrow

484

indicates the local recurrence site (right of b). The recurrence site is the area that does not show a hyperintense

485

signal on DWI obtained on day 1 after PDT (b). The histopathological diagnosis was WHO grade IV

486

glioblastoma, IDH wild-type. PDT, photodynamic therapy

487

488

Fig. 3 Axial diffusion-weighted imaging (DWI), T2-weighted FLAIR, and contrast-enhanced T1-weighted

489

imaging (CE-T1WI) of a 40-year-old man showing a ring-enhancing tumor in the left frontal lobe (a–c). Post-

490

PDT magnetic resonance (MR) images obtained on day 1 show complete resection of the contrast-enhancing

491

lesion and hyperintense signal on DWI adjacent to the resection cavity wall (d–f). Follow-up MR images at 32.7

492

months after surgery show intact tumor tissue in the primary tumor bed (g–i) and distant recurrence in the left

21

493

frontal lobe (j–l). The histopathological diagnosis was WHO grade IV glioblastoma, IDH wild-type. PDT,

494

photodynamic therapy

495

496

Fig. 4 Axial diffusion-weighted imaging (DWI), T2-weighted FLAIR, and contrast-enhanced T1-weighted

497

imaging (CE-T1WI) of a 76-year-old man showing a ring-enhancing tumor in the left parietal lobe (a–c). Post-

498

PDT magnetic resonance (MR) images obtained on day 1 show complete resection of the contrast-enhancing

499

lesion and hyperintense signal on DWI adjacent to the resection cavity wall (d–f). Follow-up MR images at 1.4

500

months after surgery show intact tumor tissue in the primary tumor bed (g–i) and dissemination (j–l). The

501

histopathological diagnosis was WHO grade IV glioblastoma, IDH wild-type. PDT, photodynamic therapy

22

(Day 1)

Local recurrence

Post-PDT

Before surgery

DWI

FLAIR

CE-T1WI

Post-PDT (Day 1)

Recurrence

DWI

CE-T1WI

(Day 1)

Local recurrence

Post-PDT

Before surgery

DWI

FLAIR

CE-T1WI

Post-PDT (Day 1)

Recurrence

DWI

CE-T1WI

Primary tumor bed

Recurrence

Distant recurrence

(Day 1)

Post-PDT

Before surgery

DWI

FLAIR

CE-T1WI

Primary tumor bed

Recurrence

Dissemination

(Day 1)

Post-PDT

Before surgery

DWI

FLAIR

CE-T1WI

Journal of Neuro-Oncology

Supplementary Information for

Hyperintense signal on diffusion-weighted imaging for monitoring the acute response and local

recurrence after photodynamic therapy in malignant gliomas

Yuichi Fujita*, Hiroaki Nagashima, Kazuhiro Tanaka, Mitsuru Hashiguchi, Tomoo Itoh, Takashi Sasayama

Supplementary Fig. 1 Intraoperative microscopic images during PDT. The resection cavity was irradiated with

a semiconductor laser (a). The cross-hair indicates the focal point of the laser. The large blood vessel is

protected by aluminum foil to avoid direct irradiation (b). PDT, photodynamic therapy

Supplementary Fig 2 Preoperative axial DWI of a representative case showing a mass lesion in the right frontal

lobe (a). Postoperative DWI shows time-dependent changes after PDT (b–e). On day 1 after PDT, linear

hyperintense signals were detected at the surface of the resected cavity (b). The hyperintense signals on DWI

disappeared in about 30 days (c–e). DWI, diffusion-weighted imaging; PDT, photodynamic therapy

Journal of Neuro-Oncology

Supplementary Table 1 Characteristics of recurrent and non-recurrent patients

Recurrence

(n = 19)

Characteristic

Non-recurrence

(n = 11)

Age, years

Median (range)

62.0 (35–85)

48.0 (23–69)

Sex, n (%)

Male

9 (47)

7 (64)

Female

10 (53)

4 (36)

Preoperative Karnofsky Performance Status score

Median (range)

70 (30–100)

90 (50–100)

Tumor locations, n (%)

Frontal

8 (42)

6 (55)

Temporal

5 (26)

4 (36)

Parietal

3 (16)

1 (9)

Occipital

1 (5)

0 (0)

Insular

1 (5)

0 (0)

Basal ganglia

1 (5)

0 (0)

Laterality, n (%)

Right

12 (63)

8 (73)

Left

7 (33)

3 (27)

Preoperative tumor volume, cm3

Median (range)

31.5 (2.2–108.7)

37.7 (3.6–140.0)

PDT

Median (range)

12 (2–31)

15 (5–31)

Extent of resection, n (%)

Gross total

15 (79)

8 (73)

Subtotal

4 (21)

1 (9)

Partial

0 (0)

2 (18)

Histopathology, n (%)

Glioblastoma

18 (95)

8 (73)

Anaplastic astrocytoma

0 (0)

2 (18)

Anaplastic oligodendroglioma

1 (5)

1 (9)

Isocitrate dehydrogenase mutation status, n (%)

Wild-type

17 (89)

8 (73)

Mutant

2 (11)

3 (27)

MGMT promoter methylation status, n (%)

Methylated

10 (53)

5 (45)

Unmethylated

5 (26)

4 (36)

Unknown

4 (21)

2 (18)

MIB-1 index, %

Median (range)

30 (10–80)

20 (10–25)

PDT, photodynamic therapy; MGMT, O6-methylguanine-DNA methyltransferase

P Value

0.12

0.47

0.09

1.00

0.70

0.80

0.62

0.24

0.13

0.33

0.68

0.01

Journal of Neuro-Oncology

Supplementary Table 2 Characteristics of patients based on recurrence patterns

Local

(n = 10)

Characteristic

Distant

(n = 1)

Dissemination

(n = 8)

P value

Age, years

Median (range)

61.0 (43–73)

40

68.0 (35–85)

Sex, n (%)

Male

3 (30)

1 (100)

5 (63)

Female

7 (70)

0 (0)

3 (38)

Preoperative Karnofsky Performance Status score

Median (range)

70 (50–100)

90

70 (30–100)

Tumor locations, n (%)

Frontal

3 (30)

1 (100)

4 (50)

Temporal

4 (40)

0 (0)

1 (13)

Parietal

2 (20)

0 (0)

1 (13)

Occipital

0 (0)

0 (0)

1 (13)

Insular

1 (10)

0 (0)

0 (0)

Basal ganglia

0 (0)

0 (0)

1 (13)

Laterality, n (%)

Right

6 (60)

1 (100)

5 (63)

Left

4 (40)

0 (0)

3 (38)

Preoperative tumor volume, cm3

Median (range)

32.9 (10.9–108.7)

8.7

34.6 (2.2–102.9)

PDT

Median (range)

12 (2–31)

15 (8–22)

Extent of resection, n (%)

Gross total

9 (90)

1 (100)

5 (63)

Subtotal

1 (10)

0 (0)

3 (38)

Partial

0 (0)

0 (0)

0 (0)

Histopathology, n (%)

Glioblastoma

10 (100)

1 (100)

7 (88)

Anaplastic astrocytoma

0 (0)

0 (0)

0 (0)

Anaplastic oligodendroglioma

0 (0)

0 (0)

1 (13)

Isocitrate dehydrogenase mutation status, n (%)

Wild-type

10 (100)

1 (100)

6 (75)

Mutant

0 (0)

0 (0)

2 (25)

MGMT promoter methylation status, n (%)

Methylated

6 (60)

1 (100)

3 (38)

Unmethylated

3 (30)

0 (0)

2 (25)

Unknown

1 (10)

0 (0)

3 (38)

MIB-1 index, %

Median (range)

25 (10–70)

30

40 (10–80)

PDT, photodynamic therapy; MGMT, O6-methylguanine-DNA methyltransferase; NaN, not a number

---------------------------------------------∗Corresponding

author. Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1

Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan; Email: fyuichi@med.kobe-u.ac.jp

0.22

0.24

0.59

0.74

0.34

0.54

0.34

0.50

0.23

0.76

0.65

...