fnca project of radiotherapy for cervical cancer protocol ... · protocol: cervix-i stage iiib...

FNCA Project of Radiotherapy for Cervical Cancer

Protocol: Cervix-I

Stage IIIB Squamous Cell Carcinoma of the Cervix

Standardized Protocol

Weeks 　　　　 1 2 3 4 5 6 7

External RTWP

30Gy/15-17Fr

CS20Gy/10Fr

Intracavitary RTHDR (5-7 Gy/Fr)

　　　　　　　　　　　　 (either)LDR (30-40 Gy/1-2Fr)

Summary of 210 Registered Cases(Period of patient accrual: Jan. 1995 ~ Dec. 1998)

Country

ChinaIndonesia

JapanKorea

MalaysiaThe Philippines

ThailandVietnam

Total

No. of Pts

3424332012223728

210

Tumor Size at Portio

VNMTHAPHLMYSKORJPNIDNCHN

% o

f C

ases

100

90

80

70

60

50

40

30

20

10

0

Large =>60mm

Medium 40-60mm

Small =<40mm

Cervical tumor size

Tumor Volume at Parametrium


% o

f C

ases

100

90

80

70

60

50

40

30

20

10

0

Heavy(5/5)

Large(4/5)

Medium(3/5)

Small(2/5)

Slight(1/5)

Degree of tumor infiltration into the parametrium

Whole Pelvic Dose in cGy

5500 - 6000

5000 - 5500

4500 - 5000

4000 - 4500

3500 - 4000

3000 - 3500

2500 - 3000

2000 - 2500

1500 - 2000

No. of

Cas

es

140

120

100

80

60

40

20

0

Dose of WP-EBRT(N=210)

ICRT Point-A Dose in cGy (HDR)

3100 - 3300

2700 - 2900

2300 - 2500

1900 - 2100

1500 - 1700

1100 - 1300

No. of

Cas

es

40

30

20

10

0

Point A Dose of HDR-ICBT (N=100)

ICRT Point-A Dose in cGy (LDR/MDR)

5300 - 5500

4900 - 5100

4500 - 4700

4100 - 4300

3700 - 3900

3300 - 3500

2900 - 3100

2500 - 2700

No. of

Cas

es

40

30

20

10

0

Point A Dose of MDR/LDR-ICBT (N=109)

91 -

98

84 -

91

77 -

84

70 -

77

63 -

70

56 -

63

49 -

56

42 -

49

35 -

42

28 -

35

21 -

28

14 -

21

7 - 14

0 -

7

100

80

60

40

20

0

91 -

98

84 -

91

77 -

84

70 -

77

63 -

70

56 -

63

49 -

56

42 -

49

35 -

42

28 -

35

21 -

28

14 -

21

7 - 14

0 -

7

40

30

20

10

0

Overall treatment timeN=190

N=103

Cervix-I

Cervix-II

No.

of p

ts.

No.

of p

ts.

Overall treatment time (days)


Acute Radiation Morbidity

RTOG Grade 0 1 RTOG Grade 0 1 RTOG Grade 0 1 RTOG Grade 0 1 2 3 4 2 3 4 2 3 4 2 3 4

(99.5%)(99.5%)(99.5%)(99.5%)Rectum/Sigmoid colon (%) 75 22.5 2 Rectum/Sigmoid colon (%) 75 22.5 2 Rectum/Sigmoid colon (%) 75 22.5 2 Rectum/Sigmoid colon (%) 75 22.5 2 0 0.50 0.50 0.50 0.5

(98%)(98%)(98%)(98%)Urinary Bladder (%) 81.5 15 1Urinary Bladder (%) 81.5 15 1Urinary Bladder (%) 81.5 15 1Urinary Bladder (%) 81.5 15 1.5 1 1.5 1 1.5 1 1.5 1 1

(98.5%)(98.5%)(98.5%)(98.5%)Small Intestine (%) 76 21 Small Intestine (%) 76 21 Small Intestine (%) 76 21 Small Intestine (%) 76 21 1.5 0.5 11.5 0.5 11.5 0.5 11.5 0.5 1

Late Radiation Morbidity (at 5 years of follow-up)

RTOG/EORTC Grade 0 1 2 RTOG/EORTC Grade 0 1 2 RTOG/EORTC Grade 0 1 2 RTOG/EORTC Grade 0 1 2 3 43 43 43 4

(3%)(3%)(3%)(3%)Rectum/Sigmoid colon (%) 74 18 5 Rectum/Sigmoid colon (%) 74 18 5 Rectum/Sigmoid colon (%) 74 18 5 Rectum/Sigmoid colon (%) 74 18 5 3 03 03 03 0

(4%)(4%)(4%)(4%)Urinary Bladder (%) 78 13 Urinary Bladder (%) 78 13 Urinary Bladder (%) 78 13 Urinary Bladder (%) 78 13 5 2 25 2 25 2 25 2 2

(1%)(1%)(1%)(1%)Small Intestine (%) 94 4 Small Intestine (%) 94 4 Small Intestine (%) 94 4 Small Intestine (%) 94 4 1 1 01 1 01 1 01 1 0

86420

1.0

.8

.6

.4

.2

0.0

Overall survival rates for all cases%

Sur

viva

l

Years after RT

70%

53%

as of Dec. 2003

N=210

86420

1.0

.8

.6

.4

.2

0.0

% S

urvi

val

Years after RT

Overall survival rates by tumor sizeas of Dec. 2003

Large N=30

Small N=71Medium N=10860%

55%

31%

(P<0.05)

86420

1.0

.8

.6

.4

.2

0.0

Overall survival rates by HDR/LDR-ICBT%

Sur

viva

l

Years after RT

LDR N=109

HDR N=100

57.5%

50.7%

as of Dec. 2003

(n.s.)

86420

1.0

.8

.6

.4

.2

0.0

Overall survival rates by OTTas of Dec. 2003

Years after RT

% S

urvi

val

61%

37%

OTT < 50days N=132

OTT > 50days N=58

(P<0.05)

Overall survival rates by country

Country

CHNINDJPNKORMYSPHLTHAVTN

Total

2-y (%)

8242707563646672

69

5-y (%)

50-

525542596360

53

follow-up (%)

8829

10010042967336

73

86420

1.0

.8

.6

.4

.2

0.0

Local control rates for all casesas of Dec. 2003

% S

urvi

val

Years after RT

84%82% N=210

86420

1.0

.8

.6

.4

.2

0.0

Local control rates by tumor sizeas of Dec. 2003

% S

urvi

val

Years after RT

Large N=30

Small N=71

Medium N=10886%

80%

68%

(n.s.)

Summary of the study “Cervix-I”

1. The treatment of the standardized protocol was feasiblein the FNCA countries.

2. The outcome of the treatment was favorable.- acute & late radiation morbidity ： acceptable- 5-year OS： 53%

3. There was a significant difference in OS between patientswith large tumors and those with small or medium-sizedtumors.

4. There was a significant difference in OS between patientstreated within 7 weeks and those treated over 7 weeks.

5. There were wide differences among countries in…- patient characteristics (age，tumor size，etc.)- treatment (rate of protocol deviation)- assessment of the efficacy and toxicity of the treatment - follow-up rate- survival rate

6. This study provided an important opportunity for cross-comparing the present status of RT in Asia.

7. The annual meeting provided the participants witha great deal of information on the current status of radiation oncology.

8. Based on the results, we are conducting some clinical trials, including AHF and ChemoRT for CCand ChemoRT for NPC.

Summary of the study “Cervix-I”


Pat

ient

Age

(M

ean

+/- S

.E.)

80

70

60

50

40

Age distribution by country

WHO Histology


% o

f C

ases

100

90

80

70

60

50

40

30

20

10

0

Sq.C.Ca., NK.Sm

Sq.C.Ca., NK.Lg

Sq.C.Ca., Kerat.

Sq.C.Ca., Diff.Unk.

Sq.C.Ca., Undiff.

Sq.C.Ca., Poor.Diff.

Sq.C.Ca., Mod.Diff.

Sq.C.Ca., Well Diff.

Histological subtype by country

Large =>60mmMedium 40-60mmSmall =<40mm

Whole

Pelv

ic D

ose

in c

Gy

(Mean

+/- S

.E.)

4000

3800

3600

3400

3200

3000

Dose of WP-EBRT according to tumor size

Center Shielded Dose in cGy

3000 - 3500

2500 - 3000

2000 - 2500

1500 - 2000

1000 - 1500

500 - 1000

0 - 500

No. of

Cas

es

120

100

80

60

40

20

0

Dose of CS-EBRT

Large =>60mmMedium 40-60mmSmall =<40mm

Cente

r Shie

lded

Dose

in c

Gy

(Mean

+/- S

.E.)

2000

1800

1600

1400

1200

1000

Dose of CS-EBRT according to tumor size

Summary of 210 Registered Cases

HDR LDRHDR LDRHDR LDRHDR LDR／／／／MDRMDRMDRMDR

No. of patients 100 No. of patients 100 No. of patients 100 No. of patients 100 109109109109

Age 58.8 (31Age 58.8 (31Age 58.8 (31Age 58.8 (31----86) 52.5 (2786) 52.5 (2786) 52.5 (2786) 52.5 (27----79)79)79)79)

Tumor size small 37% Tumor size small 37% Tumor size small 37% Tumor size small 37% 31% 31% 31% 31% medium 52% medium 52% medium 52% medium 52% 52%52%52%52%large 11% large 11% large 11% large 11% 17% 17% 17% 17%

External RT WP 33 (18External RT WP 33 (18External RT WP 33 (18External RT WP 33 (18----60) Gy 36 (3060) Gy 36 (3060) Gy 36 (3060) Gy 36 (30----50) Gy50) Gy50) Gy50) GyCS CS CS CS 17 (017 (017 (017 (0----35) Gy35) Gy35) Gy35) Gy

Brachytherapy (point A) 25 (12Brachytherapy (point A) 25 (12Brachytherapy (point A) 25 (12Brachytherapy (point A) 25 (12----32) Gy 32.5 (2632) Gy 32.5 (2632) Gy 32.5 (2632) Gy 32.5 (26----53) Gy53) Gy53) Gy53) Gy

Whole Pelvic Dose in cGy

6000400020000

ICR

T P

oin

t-A

Dose

in c

Gy

6000

4000

2000

0

HDR

LDR/MDR

Correlation between the dose of WP-EBRT and the point A dose of ICBT

91 -

98

84 -

91

77 -

84

70 -

77

63 -

70

56 -

63

49 -

56

42 -

49

35 -

42

28 -

35

21 -

28

14 -

21

7 - 14

0 -

7

100

80

60

40

20

0

Overall treatment time


No.

of p

ts.

(N=210)

Follow-up status at 5 years

Country

CHN

IDN

JPN

KOR

MYS

PHL

THA

VNM

Total

No. of Pts

34

24

33

20

12

22

37

28

210

No. of Pts followed

30 (88%)

7 (29%)

33 (100%)

20 (100%)

5 (42%)

21 (96%)

27 (73%)

10 (36%)

153 (73%)

Local control rates by country

Country

CHNINDJPNKORMYSPHLTHAVTN

Total

2-y (%)

897186

100100916683

69

5-y (%)

84-

86100100916675

82

follow-up (%)

8829

10010042967336

73

86420

1.0

.8

.6

.4

.2

0.0

OS by degree of infiltration into PM

(n.s.)

86420

1.0

.8

.6

.4

.2

0.0

LC by degree of infiltration into PM

(p<0.05)

86420

1.0

.8

.6

.4

.2

0.0

Local control rates by HDR/LDR-ICBT%

Sur

viva

l

Years after RT

LDRHDR83.0

80.3

(n.s.)

86420

1.0

.8

.6

.4

.2

0.0

LC by OTT (50d)

(n.s.)

86420

1.0

.8

.6

.4

.2

0.0

Overall survival rates by protocol (stage IIIB)

Cervix-II

Cervix-I

Years after RT

% S

urvi

val 62%

73%

(n.s.)

86420

1.0

.8

.6

.4

.2

0.0

Cervix-ICervix-II

Local control rates by protocol (stage IIIB)

Years after RT

% S

urvi

val

86%

82%

(n.s.)

fnca project of radiotherapy for cervical cancer protocol ... · protocol: cervix-i stage iiib...

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