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CLINICAL INVESTIGATION
Endometrium
INTRODUCTION
juvant therapy of selected patients and in the management of inoperable or recurrent endometrial cancers.
Brachytherapy, traditionally delivered by low-dose-rate
(LDR) techniques, is increasingly delivered by highdose-rate (HDR) techniques worldwide. However, there
are no standardized treatment recommendations. This
report was prepared to provide recommendations for
treating endometrial cancer with intracavitary HDR
brachytherapy. Details of interstitial HDR brachytherapy
will be discussed in a separate report.
Cancer of the endometrium is the most common gynecologic cancer in the United States, accounting for an
estimated 37,400 new patients in 1999 (1). The standard
management for endometrial cancer is a total abdominal
hysterectomy with bilateral salpingo-oophorectomy
(TAH/BSO) with or without pelvic lymph node sampling.
External beam radiation therapy (EBRT) and/or brachytherapy are integral components in the postoperative ad-
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Table 1. Results of postoperative adjuvant cuff radiation therapy with EBRT and HDR
Author
Reference
Lybeert (6)
291 Postop
Nori (2)
300
Algan (7)
Turner (8)
81
18 Papillary
serous
Treatment
Control/survival
Recurrence
(%)
Complications
5-year NED
I: 88%
II: 69%
III/IV: 50%
90%
7.2
None
3.7
5-year OS 83%
Grade 12: 9%
No grade 3/4
Not stated
No Grade 3/4
5-year OS 94%
None
Abbreviations: n number of patients; EBRT external beam radiotherapy; HDR high-dose rate; NED no evidence of disease;
OS overall.
METHODS
A panel of the American Brachytherapy Society (ABS)
members with clinical experience in HDR endometrial
brachytherapy performed a literature review, supplemented
their clinical experience with biomathematical modeling,
and formulated recommendations for HDR brachytherapy
for endometrial carcinoma. These recommendations were
established by consensus and supported by available evidence in the literature whenever possible. Areas of controversy and lack of consensus were noted. External experts
who were not members of the panel reviewed this report.
The Board of Directors of the ABS approved this final
document.
RESULTS
The results of the deliberations of the panel members on
patient selection, applicators, quality assurance, dosimetry,
and HDR brachytherapy techniques are presented in the
following sections.
Patient selection
Treatment of vaginal cuff as postoperative adjuvant therapy. Given the increased use of comprehensive surgical
staging, the role of adjuvant EBRT, brachytherapy, chemotherapy, or no further therapy remains controversial. A
careful consideration of risk versus benefit is especially
important when considering adjuvant irradiation. The results of postoperative adjuvant therapy of the vaginal cuff
with HDR alone or in combination with EBRT (upon which
many of the recommendations of the panel are based) are
summarized in Tables 1 and 2, respectively (218). Overall
pelvic recurrence frequency of less than 10% is reported in
these series. However, it should be pointed out that with
contemporary surgical techniques, the incidence of vaginal
cuff recurrences might be very small in low-risk endometrial carcinoma, even without any adjuvant therapy.
Patient selection is determined by histopathologic factors
such as grade, myometrial invasion, lymphatic vascular
space invasion, tumor size, lymph node status, and tumor
extension, and the presence or absence of surgical staging,
as well as consideration of comorbidity that may predispose
patients to radiation-induced morbidity. Detailed discussions regarding patient selection are beyond the scope of
this report. The ABS endorses the recently formulated
guidelines by National Comprehensive Cancer Network
(NCCN) for patient selection for adjuvant radiation therapy
post-hystrectomy for endometrial cancer (Fig. 1) (19). It is
Table 2. Results of post-operative adjuvant cuff radiation therapy with HDR alone
Author/
Reference
Peschel (9)
Rattka (10)
Sorbe (4)
Thomas (11)
Noyes (12)
Fanning (13)
Kloetzer (14)
Hong (15)
MacLeod (16)
Weiss (17)
Petereit (5)
Chadha (18)
n
115
404
Not stated
63
60
108
44
141
122
191
38
Treatment
57 Gy 3 at 0.5-cm cylinder
10 Gy 4 3-day interval
Buchler HDR, doses not stated
16.2 Gy 2 ovoids surface dose
7 Gy 3 at 0.5 cm
10 Gy 4 cuff @ 1 cm/vagina @ 0.5 cm
HDR only*
8.5 Gy 4 surface
Cylinder; 7 Gy 3 @ surface
Ovoids, 16.2 Gy 2 @ surface
7 Gy 3 cuff 0.5 cm
Control/survival
3-year NED 99%
OS 88%
5-year OS 92%
5-year OS 94%
3-year
3-year
5-year
5-year
5-year
4-year
5-year
NED 100%
OS 96%
OS 92%
OS 88%
NED 94%
OS 95%
OS 93%
Recurrence
Not stated
0.7% vaginal
8%
0%
None
03%
None
1.4%
9.8%
0%
None at 30 mo
Complications
0.3%
7%
No grade 3/4
No grade 3/4
26%
None
No grade 3/4
None
1 grade 4
No grade 3/4
* Various fractionation schemes were used. N number of patients; HDR high-dose rate; NED no evidence or disease; OS
overall survival; mo. months.
S. NAG et al.
Fig. 1. Summary of NCCN guidelines for patient selection for post-hysterectomy adjuvant radiation therapy for endometrial cancer. Reproduced with permission of the NCCN. The NCCN
guidelines are a statement of consensus of its authors regarding currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN guideline is expected to
use independent medical judgment in the context of individual clinical circumstance to determine any patients care or treatment. The NCCN makes no warranties of any kind whatsoever
regarding their content, use, or application and disclaims any responsibility for their application or use in any way.
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Treatment
Lybeert (6)
36
Pai (20)
13
Control/Survival
Recurrence
Complications
Not stated
None
CR 90%
10-year local control
74%
10-year OS 71%
6/20
15%
anatomical variants and disease presentations. Different applicators are required to accommodate these varied presentations. The applicators needed at any one institution depend on the patient case mix, the clinical expertise, and
preference of the radiation oncologist. Each HDR manufacturer offers its own set of applicators. The choice of available applicators, their design, clinical utility, and versatility
should be taken into account when considering a HDR unit
purchase. When budgeting for a HDR unit, one must also
consider the additional cost of the applicators and the need
for their periodic replacement.
HDR applicators for post-operative adjuvant therapy.
Cylinders and ovoids are commonly used for post-hysterectomy adjuvant brachytherapy of the vaginal cuff. These
are commercially available and closely model the LDR
cylinders and ovoids. The choice of applicator for treatment
of the vagina is both patient- and institution-dependent.
Some applicators, including vaginal ovoids and the Houdek
vaginal applicator, will treat only the vaginal cuff; whereas,
vaginal cylinders can treat the entire vaginal canal, including the introitus, if desired. Another factor that may determine applicator selection is the shape of the vagina. In most
patients, the postoperative vagina is cylindrical and can be
treated adequately by a vaginal cylinder. Additionally, vaginal cylinders are preferable for a narrow vagina. However,
cylinders give higher doses to the bladder and rectum for a
given vaginal dose. In some patients, the vagina may have a
dog-ear configuration that is better treated by vaginal ovoids.
Nguyen (23)
91 RT
only
19
Kucera (22)
228
Huguenin (21)
18
17
36
Nguyen (24)
Treatment
Survival
Recurrence
(%)
Complications
CO-60 HDR 5 Gy
5-year OS 47%
29
7%
None?
11%
5-year OS 60%
17.5
5%
5-year OS 64%
3-year OS 65%
12
21% (2 deaths)
Abbreviations: n number of patients; EBRT external beam radiotherapy; HDR high-dose-rate; NED no evidence of disease;
OS overall survival.
S. NAG et al.
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S. NAG et al.
785
Table 5. Suggested doses of HDR alone to be used for adjuvant treatment of postop endometrial cancer
No. of HDR
fractions
HDR dose/fx
Dose-specific point
3
4
5
2*
3
4
5
7.0
5.5
4.7
16.2*
10.5
8.8
7.5
0.5-cm depth
0.5-cm depth
0.5-cm depth
Vaginal surface
Vaginal surface
Vaginal surface
Vaginal surface
29.8
28.4
28.8
70.7
53.8
55.1
54.7
23.2
21.1
20.7
65.0
45.6
45.1
43.3
* 2 fractions of 16.2 Gy at vaginal surface using ovoids have been used by University of Madison and is given for comparison only. There
was no consensus regarding its use amongst the panel members.
Table 6. Suggested doses of EBRT and HDR to be sued for adjuvant treatment of postop endometrial cancer
EBRT (Gy) @ 1.8
Gy/fx
No. of HDR
fractions
HDR dose/fx
Dose-specific point
45
45
45
45
2
3
2
3
5.5
4.0
8.0
6.0
0.5-cm depth
0.5-cm depth
Vaginal surface
Vaginal surafce
58.5
58.3
68.3
68.3
53.7
52.9
62.5
61.3
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Fig. 2. Demonstrates an isodose distribution of a treatment plan for treating the post-hysterectomy vaginal cuff with a
vaginal cylinder if the dose optimization points are placed only along the lateral vaginal wall. The dose at the apex at
0.5-cm depth (750 cGy) is higher than the prescribed dose of 500 cGy at 0.5-cm depth within the lateral vaginal wall.
Fig. 3. Demonstrates an isodose distribution of an optimized treatment plan for treating the post-hysterectomy vaginal
cuff with a vaginal cylinder. Dose optimization points have been placed at the apex and along the curved portion of the
cylinder dome in addition to the lateral vaginal mucosa to produce a more homogenous dose.
S. NAG et al.
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Relative
dwell weight
No. of HDR
fractions
1
2
3
4
5
6
7
8
9
10
11
0.45
0.71
0.76
0.71
0.62
0.56
0.56
0.63
0.75
0.89
1.00
4
5
6
7
HDR dose/fx*
8.5
7.3
6.4
5.7
Gy
Gy
Gy
Gy
at
at
at
at
2
2
2
2
cm
cm
cm
cm
Equiv. dose
for tumor
effects
Equiv. dose
(late effects
with DRF)
52.4
52.6
52.5
52.2
42.6
41.4
40.3
39.0
Note that dwell points are 0.5-cm apart and dwell position #1 is
superior (at apex) and dwell position #11 is inferior.
applicators, the cervical canal usually does not need dilatation. The postmenopausal uterus has a relatively thin wall,
and it is important to be gentle during the insertion of any
applicators to avoid uterine perforation. Similarly, a downward traction on the uterus (by holding the cervix with a
tenaculum) helps prevent the uterus from being pushed
superiorly (and close to the bowel) as the applicators are
being inserted.
When two or more intrauterine applicators are inserted,
fluoroscopy or ultrasound is helpful in directing the applicators into the uterine cornuae.
These patients are often obese, and good treatment planning localization radiographs (especially laterals) are difficult to obtain. AP stereoshift radiographs may be useful.
They often need to be treated quickly due to their poor
medical condition. A fixed geometry applicator system is
helpful, because it allows for a reproducible set-up and
obviates the need for complex and time-consuming treatment planning with each fraction.
Table 9 gives the suggested dose-fraction schemes for
cases treated with only intracavitary brachytherapy, and
Table 10 for brachytherapy in combination with EBRT.
While several authors (2, 23) have successfully employed
doses of 20 Gy in 2 fractions (1 week apart), the ABS does
not recommend such large fraction sizes, given the potential
for late rectosigmoid toxicity.
Dose specification and optimization. The irregular shape
of the uterine cross-section in the coronal and sagittal planes
presents a challenge to satisfactory isodose distribution
from intracavitary brachytherapy.
1. The target volume is the entire uterus, cervix, and upper
35 cm of the vagina.
2. The required length of the vagina to be treated cannot be
Table 8. Suggested doses of EBRT and HDR to be used for treating vaginal cuff recurrences from endometrial cancer
EBRT (Gy) @ 1.8
Gy/fx
No. of HDR
fractions
HDR dose/fx
Dose-specification
point
45
45
45
45
3
4
5
4
7.0
6.0
6.0
7.0
0.5-cm depth
0.5-cm depth
Vaginal surface
Vaginal surface
74.0
76.3
84.3
83.9
66.4
67.4
73.4
74.2
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Table 10. Suggested doses of external beam HDR for treatment of inoperable primary endometrial cancer
EBRT (Gy)
@ 1.8 Gy/fx
No. of
HDR
fractions
HDR dose/fx
Equiv. dose
for tumor effects
Equiv. dose
(late effects with DRF)
45
45
45
2
3
4
8.5 Gy at 2 cm
6.3 Gy at 2 cm
5.2 Gy at 2 cm
70.5
69.9
70.6
64.5
62.8
62.5
Relative
dwell weight
1
3
5
7
9
11
13
15
17
19
21
1.00
0.73
0.55
0.43
0.36
0.31
0.29
0.28
0.29
0.34
0.44
CONCLUSION
Recommendations are made for HDR brachytherapy for
endometrial cancer. Practitioners and cooperative groups
are encouraged to use these recommendations as a guide to
formulate their treatment and dose reporting policies realizing that the final responsibility for the medical decisions
ultimately rests with the treating radiation oncologist. These
recommendations will be modified, as image-based treatment becomes more widely available.
S. NAG et al.
789
Fig. 4. Examples of isodose distribution of an optimized treatment plan for treating inoperable primary endometrial
cancer with a Y-shaped applicator.
DISCLAIMER
These guidelines represent consensus of the authors
regarding currently accepted treatment. The suggested
doses have been derived from a combination of literature
review, the individual clinical experiences of the authors
and modified by biomathematical modeling. While these
doses seem reasonable to the authors, some of the dose
fractionation schemes given may not have been exten-
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