Interpretation of Central Shielding External Beam ... · 2/16/2014 · (BED at Point A = 90 Gy...

Interpretation of Central Shielding

External Beam Radiation Therapy

Saitama Medical University International Medical Center

Department of Radiation Oncology

Shingo Kato, MD, PhD

1

2

1. Japanese standardized protocol of RT

2. Treatment results of Japanese protocol

3. Cumulative dose-volume relationship of CTV in

combined radiotherapy (experimental study)

4. Cumulative dose-volume relationships of HR-CTV

and OARs in combined radiotherapy (clinical)

Interpretation of CS-EBRT

3








Whole Pelvis

Intracavitary Brachytherapy:

HDR

once/week, 3-4 fractions

Concurrently with CS-EBRT

Composite dose distributions

of EBRT and ICBT

Radiation Therapy for Cervical Cancer in Japan

Central Shielding

External Beam RT:

WP: 4 Field box

20-40 Gy

+CS: AP/PA

30-10 Gy

+

RT schedule for early disease in Japan & the USA

HDR-ICBT (Point A dose)

EBRT (central shielding)

EBRT (whole pelvis)

Weeks 1 2 3 4 5 6 7 8

JapanWP 20 Gy CS 30 Gy

ICBT 24 Gy/4Fr

ICBT 30 Gy/5Fr

USA WP 45 Gy

5

(BED at Point A = 84 GyEQD2)

(BED at Point A = 52 GyEQD2?)

RT schedule for advanced disease in Japan & USA

Weeks 1 2 3 4 5 6 7 8

WP 50.4 Gy

(BED at Point A = 90 GyEQD2)

WP 30-(40) Gy CS (10)-20 Gy

ICBT 24 Gy/4Fr

Japan

USA

HDR-ICBT (Point A dose)

EBRT (central shielding)

EBRT (whole pelvis)

(BED at Point A = 62-72 GyEQD2?)

6

ICBT 30 Gy/5Fr

7

Stage

HDR-ICBT

Point A dose

(Gy/Fr)

Total dose to

Point A

(Gy(EQD2))

IB1-IIA

(< 4 cm)

IB2-IVA

(> 4 cm)

45

45-50

25/5-30/5

30/5

76-84

84-90

Doses of EBRT & HDR-ICBT

WP

EBRT (Gy)

CS

20 24/4 52 (?)30

0

30-40

0

10-20 24/4 62-72 (?)

USA

USA

Japan

Japan

Country

Optimum dose and fractionation schedule of HDR-ICBT are still controversial.

8

Central shielding (CS) EBRT

Spatial proximity of applicators to rectum & bladder at BT.

Relatively high doses delivered to rectum & bladder at BT.

CS in EBRT enables to reduce dose to rectum & bladder.

Although dose to central tumor is decreased by CS,

high dose can be delivered to central tumor at BT.

Small pelvic cavity & narrow vagina in Japanese women.

9








0

20

40

60

80

100

Years after RT

% s

urv

iva

l

5 10 15 20

Stage I n=146

Stage II n=305

Stage III n=554

Stage IV n=143

46.9

24.1

22.7

3.1

88.4

74.069.1

51.956.3

42.1

15.410.5

Follow-up rate at 20 y : 98%

(Nakano T, Kato S, et al. Cancer 103: 92-101, 2005)

Overall survival rates by stage (RT alone NIRS 1968~1986)

(Japanese standard protocol)

0

20

40

60

80

100

Years after RT

% s

urv

ival

5 10 15 20

Stage I n=146

Stage II n=305

Stage III n=554

Stage IV n=143

94.388.8

80.1

74.1

65.7

59.4

21.617.6

86.1

66.8

56.0

17.6



Cause-specific survival rates by stage(RT alone NIRS 1968~1986) (Japanese standard protocol)

3 cm>

95%

87%

87%

3-5 cm

89%

81%

77%

5 cm<

-

71%

62%

Tumor size

Stage

IB

II

III

P-value

* 0.11

* 0.15

** 0.15

*** 0.02

* 0.06

** 0.04

***0.004

* **

***

*

* *****

10-year Pelvic Control Rates by Tumor Size(RT alone NIRS 1968~1986) (Japanese standard protocol)


Author

(year)

Perez et al.

(IJROBP 1998)

Horiot et al.

(IJROBP 1988)

Eifel et al.

(IJROBP 1994)

Petereit et al.

(IJROBP 1999)

Nakano et al.

(Cancer 2005)

JAROG0401

(IJROBP 2011)

5y overall

survival (%)

82 (10y DFS)

89

90 (DSS)

86 (3y)

88

95 (3y)

Treatment

RT (LDR)

RT (LDR)

RT (LDR)

RT (HDR)

RT (HDR)

RT(HDR)

No. of

cases

493

(Stage IB)

229

(Stage I)

701

(Stage IB1)

59

(Stage IB)

146

(Stage IB)

60

(Stage I-II)

5y pelvic

control (%)

88 (10y)

93

97

85 (3y)

93

96 (3y)

13

Results of RT alone for Stage I-II (non-bulky) Cervical Cancer

Treatment Results (RT alone) for Stage IIB Cervical Cancer

Author

(year)

Perez et al.

(1992)

Horiot et al.

(1988)

Hopkins et al.

(1991)

Eifel et al.

(unpublished data)

Nakano et al.

(2005)

Teshima et al.

(1993)

Kapp et al.

(1998)

5y overall

survival (%)

77

70

62

54

69

61

63 (DSS)

Dose

rate

LDR

LDR

LDR

LDR

HDR

HDR

HDR

No. of

cases

353

314

163

211

261

80

65

5y pelvic

control (%)

83

78

NA

81

86

NA

66

Treatment Results (RT alone) for Stage III Cervical Cancer

Author

(year)

Perez et al.

(1992)

Horiot et al.

(1988)

Hopkins et al.

(1991)

Eifel et al.

(unpublished data)

Nakano et al.

(2005)

Teshima et al.

(1993)

Kapp et al.

(1998)

5y overall

survival (%)

59

50

36

47

56

47

49 (DSS)

Dose

rate

LDR

LDR

LDR

LDR

HDR

HDR

HDR

No. of

cases

293

482

117

328

554

147

78

5y pelvic

control (%)

64

57

NA

70

76

NA

59

0

10

20

30

Years after RT

% P

rob

ab

ilit

y

5 10 15 20

Rectum/Sigmoid

Bladder

Small intestine

14.3

20.9

5.7

21.6

18.3

8.6

16.1

24.3

23.0


(Nakano T, Kato S. et al. Cancer 103: 92-101, 2005) 16

Late radiation complications (all grades)RT alone using Japanese standard protocol (NIRS 1968~1986)

0

5

10

15

% P

rob

ab

ilit

y

Years after RT5 10 15 20

Rectum/Sigmoid

Bladder

Small intestine

2.6

3.8

0.8

4.4

3.3

0.9

8.3

5.3

1.3


(Nakano T, Kato S. et al. Cancer 103: 92-101, 2005)17

Late radiation complications (grade 3-5)RT alone using Japanese standard protocol (NIRS 1968~1986)

Investigator

(Journal, year)

Eifel et al.

(IJROBP 1995)

Komaki et al.

(IJROBP 1995)

Eifel et al

(JCO 2004)

Teshima et al.

(Cancer 1993)

Nakano et al

(Cancer 2005)

Institution

M. D. Anderson

P.C.S. in USA

RTOG 90-01

Osaka Univ.

NIRS

5-year MC

2.9%

(Stage IB)

10%

8.9%

9.3%

4%

3.8%

RT / CCRT

(LDR / HDR)

RT

(LDR)

RT

(LDR)

CCRT (LDR)

RT (LDR)

RT

(LDR/HDR)

RT (HDR)

18

Incidence of major (Grade 3-5) rectal complications

19

Summary 1

Japanese standardized protocol for cervical cancer consists

of WP-EBRT, CS-EBRT, and HDR-ICBT.

In spite of the favorable results, it has been controversial

whether the dose to the cervical tumor in Japanese protocol

is optimal.

Especially, it is difficult to estimate the contribution of CS-

EBRT to the cervical tumor with conventional method.

Long-term follow-up study demonstrated that Japanese

treatment protocol produced favorable treatment outcomes

with lower incidence of late radiation complications.

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21

Conventional method

WP-EBRT ICBTCS-EBRT

Simple DVH parameter additionCumulative DVH parameters

HR-CTV D90, D2cc of OARs

DVH DVHDVH DVH DVH DVH

Composite dose distributions method

Cumulative DVH parameters

HR-CTV D90, D2cc of OARs

WP-EBRT ICBTCS-EBRT

Accumulation of each dose

distributions (with DIR)

• EBRT

– WP-EBRT: 4 Field box (18x18x14 cm)

– CS-EBRT: AP-PA (18x18 cm) , CS width 3 cm

– WP+CS: 20+30, 30+20, 40+10 Gy

• HDR-ICBT

– Tandem (6 cm) & Ovoids (3 cm gap), Standard loading pattern

– 24 Gy/4fr to point A

• CTV

– Cylindrical volume: Height 4 cm, above tandem ring

– Diameter: 3, 4, or 5 cm

• Accumulation of dose distributions

– Rigid Accumulation

– Conversion into BED, LQ model, α/β=10, display by EQD2

• Dose-volume histogram analysis

– HR-CTV D90 (EQD2) 22

Experimental study using water-equivalent phantom

EBRT

(WP + CS)

ICBT Cumulative dose

distributions

23

Cumulative dose distributions

+

DVH: WP 30Gy/15Fr + CS 20Gy/10Fr + ICBT 24 Gy/4Fr(CS 3 cm width)

Target ⏀ 3cmTarget ⏀ 4cmTarget ⏀ 5cm

WP + CSICBTComposition

0 50 100 150 200 250 (EQD2, Gy) 24

Point A dose

• Point A locates at the place of steep dose gradient in CS-EBRT.

(also in the composite dose distributions of EBRT + ICBT.)

• Point A dose is a fluctuating dose and is not an appropriate

parameter to assess the dose to the tumor.

ー 35 Gy (EQD2)

ー 40 Gy (EQD2)

ー 45 Gy (EQD2)

CS 3 cm

Point A

ー ⏀3 cm Target

ー ⏀4 cm Target

ー ⏀5 cm Target

26

ー ⏀3 cm Target ー 80 Gy (EQD2)



Cumulative dose distributions(WP 30 Gy + CS 20 Gy + ICBT 24 Gy/4Fr to point A)

CS 3 cm 51 Gy

62 Gy

80 Gy

Point A dose (cervical tumor

dose) was reported to be

52 Gy (stage I/II non-bulky

tumor, JROSG 04-2) ,

62-65 Gy (stage III-IVA, JGOG

1066),

with simple addition of numbers

while omitting CS doses.

The doses to the tumor may

be underestimated in the

literature.

WP CS Target

diameter

at BT

WP+CS

(GyEQD2)

ICBT

(GyEQD2)

Cumulative

CTV D90

(GyEQD2)

Point A dose

(Literature)

(GyEQD2)

20 Gy 30 Gy 52 1)

3 cm 22.65 54.00 80.42

30 Gy 20 Gy 62 2)

3 cm 31.79 54.00 88.22

4 cm 31.86 33.86 70.27

5 cm 31.95 23.38 60.46

40 Gy 10 Gy 72

4 cm 40.97 33.86 77.45

5 cm 41.04 23.38 68.05

27

CTV D90 (GyEQD2) in Japanese protocol (CS width 3cm, Point A dose 24 Gy/4Fr)

The doses to cervical tumor in the literatures may be underestimated.

1) IJROBP: 82, e49-e56, 2012. 2) Gynecol Oncol: 126, 211-216, 2012.

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Cumulative dose distributions(WP 30 Gy + CS 20 Gy + ICBT 24 Gy/4Fr to point A)

CS 3 cm 51 Gy

62 Gy

80 Gy

CS-EBRT can reduce the dose

to the rectum and bladder.

Small tumor (⏀3 cm) at BT is

covered with > 87 Gy (CTV D90).

Medium-sized tumor (⏀ 4 cm) at

BT is covered with > 70 Gy (CTV

D90).

If the antero-posterior diameter

of the CTV < 4 cm, the CTV is

covered with higher dose.

Large tumor (⏀ 5 cm) at BT is

not covered with high dose in

this setting.

CTV D90 (GyEQD2) in Japanese protocol (CS width 3 cm, Point A dose at BT 24 Gy/4Fr)

CTV

diameter

at BT

WP

(Gy)

CS

(Gy)

WP+CS

CTV D90

(GyEQD2)

ICBT

CTV D90

(GyEQD2)

Cumulative

CTV D90

(GyEQD2)

3 cm 20 30 22.65 54.00 80.42

30 20 31.79 54.00 88.22

4 cm 30 20 31.86 33.86 70.27

40 10 40.97 33.86 77.45

5 cm 30 20 31.95 23.38 60.46

40 10 41.04 23.38 68.05

29

30

Composite dose distributions consisting of

WP- & CS-EBRT and ICBTs can be created

using image registration software.

Cumulative DVHs can be calculated from the

composite dose distributions.

This method may be effective to estimate

cumulative DVH parameters of combined RT.

Summary 2

31








Treatment

1. Treatment: CCRT with w-CDDP

2. EBRT: WP 30-40 Gy + CS 10-20 Gy

3. EBRT boost: 6-10 Gy to PM invasion/bulky LN meta. is allowed.

4. BT: CT-based 3D IGBT for all sessions

ICBT + ISBT is allowed

HR-CTV D90 > 6 Gy/Fr

Total EQD2 to the rectum < 75 GyEQD2

If both dose constraints are not realized simultaneously,

1st priority is dose constraint of rectum

Treatment

RT30-40 Gy 10-20 Gy

> 24 Gy/4Fr to HR-CTV D90

Weeks 1 2 3 4 5 6 7 8

CT

CDDP 40mg/m2 weekly

EBRT

BT

Image CT/MRI MRI CT CT CT CT

34

Patients (SMU 2013.8-10)

Stage

IIIB

IIB

IIB

IIIB

IIB

Case

1

2

3

4

5

Cumulative

HR-CTV D90

(GyEQD2)

73.3

79.8

77.3

72.3

78.6

D90

Rectum

(GyEQD2)

66.0

50.6

55.9

64.7

51.1

D90

Bladder

(GyEQD2)

68.2

85.2

79.2

106.8

71.1

35

Cumulative dose distributions(WP 30 Gy + CS 20 Gy + ICBT > 24 Gy/4Fr to HR-CTV D90)

70 Gy

60 Gy

50 Gy

Bladder

Rectum

HR-CTV

36

70 Gy

60 Gy

50 Gy

Cumulative dose distributions(WP 30 Gy + CS 20 Gy + ICBT > 24 Gy/4Fr to HR-CTV D90)

Bladder

Rectum

HR-CTV

37

Summary 3

In a patient with a small pelvis & narrow vagina, applicators are

close proximity to the rectum, sigmoid, and bladder.

A high dose may be irradiated to the OARs at BT.

CS in EBRT can effectively reduce the dose to the OARs.

For small tumor (⏀3 cm) at BT, Japanese protocol can deliver

> 80 Gy to CTV.

For medium-sized tumor (⏀ 4 cm) at BT, Japanese protocol

can deliver > 70 Gy to CTV.

CTV in the 2nd, 3rd, or 4th BT may be smaller than that of the

1st BT. The cumulative dose to CTV may be greater than 70 Gy

and closer to 80 Gy.

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Summary 3

Favorable local control has been obtained with Japanese

protocol in the patients with small or medium-sized tumor.

There may be some radiobiological advantages in Japanese

protocol.

- short OTT

- high dose delivered to CTV with BT in the early time of RT

course (large oxic cell component)

- reoxygenation of tumor cells during BT course

For large tumor (⏀ 5 cm) at BT, it is difficult to cover CTV with

high dose in Japanese protocol.

Special techniques may be needed to deliver higher dose to CTV

(combined IC and IS-BT, EBRT boost etc.)

Interpretation of Central Shielding External Beam ... · 2/16/2014 · (BED at Point A = 90 Gy...

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