interpretation of central shielding external beam ... · 2/16/2014 · (bed at point a = 90 gy...
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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
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
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
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
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
Follow-up rate at 20 y : 98%
(Nakano T, Kato S, et al. Cancer 103: 92-101, 2005)
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)
(Nakano T, Kato S, et al. Cancer 103: 92-101, 2005)
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
Follow-up rate at 20 y : 98%
(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
Follow-up rate at 20 y : 98%
(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.
20
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
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)
ー ⏀4 cm Target ー 62 Gy (EQD2)
ー ⏀5 cm Target ー 51 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.
28
ー ⏀3 cm Target ー 80 Gy (EQD2)
ー ⏀4 cm Target ー 62 Gy (EQD2)
ー ⏀5 cm Target ー 51 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
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
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
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.
38
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.)