METHODS

published: 26 January 2022

doi: 10.3389/fonc.2021.808721

High-Dose-Rate Interstitial
Brachytherapy for Deeply Situated
Gynecologic Tumors Guided by
Combination of Transrectal and
Transabdominal Ultrasonography:
A Technical Note
Yuri Shimizu 1, Naoya Murakami 1*, Takahito Chiba 2, Tomoya Kaneda 1,
Edited by: Hiroyuki Okamoto 2, Satoshi Nakamura 2, Ayaka Takahashi 1, Tairo Kashihara 1,
Nikolaos Zamboglou, Kana Takahashi 1, Koji Inaba 1, Kae Okuma 1, Yuko Nakayama 1,
German Oncology Center, Cyprus Jun Itami 1,3 and Hiroshi Igaki 1
Reviewed by:
1 Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan, 2 Department of Medical Physics,
Nikolaos Tselis,
National Cancer Center Hospital, Tokyo, Japan, 3 Radiation Therapy Center, Shin-Matsudo Central General Hospital,
University Hospital Frankfurt, Germany
Matsudo City, Japan
Tanja Sprave,
University of Freiburg, Germany
Pascal Pommier,
Background and Purpose: High-dose-rate interstitial brachytherapy (HDR-ISBT) is
Centre Régional de Lutte Contre le
Cancer Centre Léon Bérard, France recommended to obtain a better local tumor control for uterine cancer patients in
*Correspondence: specific situations such as bulky lesions, an extension to the lateral parametrium, or
Naoya Murakami tumors with irregular shapes. Our group uses real-time transrectal ultrasonography
[email protected]
orcid.org/0000-0003-0660-9987
(TRUS) to guide freehand interstitial needle insertion. Occasionally, target tumors locate
deeper beyond the rectum and cannot be visualized by TRUS. CT can guide needles to
Specialty section: deeply located tumors, but in such cases, repeated image obtainment is required to
This article was submitted to
achieve ideal needle localization. In this report, we present nine cases of patients who
Radiation Oncology,
a section of the journal underwent HDR-ISBT for deeply situated tumors guided by a combination of transrectal
Frontiers in Oncology and transabdominal ultrasonography (TR/TA-US).
Received: 03 November 2021
Accepted: 30 December 2021
Material and Methods: Nine uterine cancer patients whose tumors were located deeper
Published: 26 January 2022 than the reach of TRUS and underwent HDR-ISBT guided by TR/TA-US were presented.
Citation: All nine cases had no distal organ metastasis and underwent external beam radiation
Shimizu Y, Murakami N, Chiba T,
therapy (EBRT) to the pelvic region for 45–50.4 Gy in 25–28 fractions followed by boost
Kaneda T, Okamoto H, Nakamura S,
Takahashi A, Kashihara T, HDR-ISBT for deeply situated tumors guided by TR/TA-US.
Takahashi K, Inaba K, Okuma K,
Nakayama Y, Itami J and Igaki H (2022)
Results: There were seven cervical cancer and two endometrial cancer patients: six with
High-Dose-Rate Interstitial extensive uterine corpus invasion, one cervical cancer with massive pelvic lymph node
Brachytherapy for Deeply Situated
metastasis, one cervical cancer with postoperative pelvic recurrence, and one with left
Gynecologic Tumors Guided by
Combination of Transrectal and ovarian direct tumor invasion. The median follow-up period was 15 months (range 3–28
Transabdominal Ultrasonography: months). The average clinical target volume at the time of first HDR-ISBT was 131 ml
A Technical Note.
Front. Oncol. 11:808721.
(range 44–335 ml). The linear distance from the vaginal entrance to the deepest part of the
doi: 10.3389/fonc.2021.808721 tumor at first time brachytherapy of nine cases was 14.0 (9.0–17.0) cm. HDR-ISBT dose

Frontiers in Oncology | www.frontiersin.org 1 January 2022 | Volume 11 | Article 808721

Shimizu et al. TR/TA-US-Guided HDR-ISBT for Gynecologic Malignancies

fractionation was 24–30 Gy in four or five fractions. Seven out of nine cases had no local
recurrence in the follow-up period. One had local in-field recurrence 25 months after HDR-
ISBT. Another case with carcinosarcoma could not obtain local control and underwent
salvage hysterectomy for a residual uterine tumor 11 months after HDR-ISBT. Four cases
had extra-field recurrence in lymph nodes or distant organs.
Conclusions: In brachytherapy for gynecologic malignancies, deeply situated tumors
located out of reach of TRUS may obtain favorable local control by HDR-ISBT guided with
TR/TA-US.
Keywords: interstitial brachytherapy (ISBT), gynecologic malignancies, transrectal ultrasonography (TRUS),
transabdominal ultrasonography (TUS), image-guided adaptive brachytherapy (IGABT)

PURPOSE Treatment
The patients were treated with a combination of pelvic external
Brachytherapy plays an important role in cervical cancer for beam RT (EBRT) and brachytherapy. In all cases, EBRT was up to
definitive radiation therapy (RT) because it can give a relatively a dose of 50–50.4 Gy at 1.8–2.0 Gy per fraction in 25–28 fractions
significant dosage while preserving the surrounding organ at risk with 5 fractions per week. The initial 30–41.4 Gy was delivered to
(OAR) (1, 2). Small tumors that fall within the isodose line the whole pelvis, and then pelvic irradiation was delivered with a
produced by traditional intracavitary brachytherapy (ICBT) can 4-cm width of the central shield (CS), reducing OAR exposure.
be successfully treated (3, 4). The initiation of CS depended upon tumor shrinkage. After the CS
Tumors tend to expand laterally with the cardinal ligament in was inserted or EBRT was accomplished, HDR-ISBT was
locally advanced cervical cancer. In specific clinical situations, performed in 1–2 sessions/week. In seven of the nine cases, the
such as large lesions, extension to the lateral parametrium, or needle and applicator were removed after irradiation, and
pelvic sidewall, the American Brachytherapy Society (ABS) applicator insertion was performed at each treatment (multiple
guidelines recommend high-dose-rate interstitial brachytherapy implants). In the remaining two cases, more emphasis was placed
(HDR-ISBT) for such cervical cancer patients (1). It was also on the difficulty of the needle insertion technique into the target,
recommended to combine ICBT and a few interstitial needles in and in order to avoid multiple needle insertions, irradiation was
this area to help with dosage coverage and tumor control (5–9). performed every day, twice daily irradiation at 6-h intervals
The combination of ICBT and ISBT is the so-called without removing the needles, and needle insertion was
intracavitary/interstitial brachytherapy (IC/IS) (10). Usually, performed only once throughout the entire period.
tandem and transperineal needle insertion was guided by Cervical cancer patients were treated with concurrent
transrectal ultrasonography (TRUS). However, sometimes chemotherapy basically with weekly cisplatin at 40 mg/m2,
tumors located deeper than the rectum need to be visualized during the EBRT period. Uterine body cancer patients were
by TRUS view. In such cases, there is a risk of accidentally treated with RT alone.
puncturing surrounding normal tissues when inserting a needle
blinded beyond the reach of TRUS. High-Dose-Rate Interstitial
CT can guide needles to deeply located tumors, but in such Brachytherapy Needle Insertion
cases, repeated image obtainment is required to achieve ideal Technique With Transrectal and
needle localization. In such cases, we used transabdominal Transabdominal Ultrasonography
ultrasonography (TAUS) to obtain real-time visualization of a All patients lay in lithotomy position after saddle block anesthesia
tumor and insert a needle to reduce this risk of normal tissue or local anesthesia and intravenous sedation. For better pelvic
injury and ensure that the needle tip is within the target. visualization of US, Foley catheterization was performed, and 100
Here, we presented nine cases of patients who underwent ml of normal saline was instilled into the urinary bladder
HDR-ISBT for deeply situated tumors guided by a combination retrogradely to reduce poor visualization due to intestinal gas.
of transrectal and transabdominal ultrasonography (TR/TA-US). Transperineal freehand interstitial needle insertion was
guided by TR/TA-US. The quality of TA-US is dependent on
the examiner’s experience. Adequately inflating the bladder with
MATERIALS AND METHODS more than 100 ml of saline is essential in order to obtain a
favorable image. It is also important to avoid the pubic bone,
Patients apply adequate echo jelly, and compress the probe to the
Uterine cancer patients who underwent HDR-ISBT for deeply abdominal wall. If these points are observed, even residents
situated tumors guided by TR/TA-US between January 2019 and with limited experience also can insert needles under TA-
November 2020 were included in this report. US guidance.

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Shimizu et al. TR/TA-US-Guided HDR-ISBT for Gynecologic Malignancies

After needle insertion, ICBT applicators, tandem, and ovoid/ examination and blood tests were performed regularly every 1–
cylinder were inserted. Figure 1 shows the schematic image of 6 months. Adverse events were assessed by Common
the procedure of inserting a needle under TR/TA-US guidance. Terminology Criteria for Adverse Events (CTCAE) version 4.0.
The geometry of the needles relative to the target tumor, bladder,
intestinal canal, and vessels was confirmed visually before Statistical Analysis
inserting needles. In this report, deeply situated tumors are All analyses were performed using computer software (Excel
defined as tumors that are located beyond the reach of the Statistics for Windows, Microsoft Excel 2012, Social Survey
rectosigmoid junction and cannot be physically visualized by Research Information, Tokyo, Japan).
TRUS (Figure 2). This study was also approved by the Institutional Review
At each brachytherapy session, a CT image of 2-mm slice Board of our hospital, the Ethics Committee of National Cancer
thickness was taken by a CT simulator (Aquilion™, Toshiba, Center Hospital (approved number 2017-091), according to the
Tokyo, Japan) situated in the operating room with the patient ethical standards laid down in the Declaration of Helsinki.
lying in lithotomy position with the applicators in place. High-
risk clinical target volume (CTVHR) at HDR-ISBT is delineated
on this CT using MRI taken immediately before the initial HDR- RESULTS
ISBT and TRUS as a reference (6, 11, 12). The definition of
CTVHR is based on the CT-based contouring guideline proposed Nine uterine cancer patients were entered into this report. The
by Viswanathan et al. (13). Treatment planning was executed patient’s demographics are summarized in Table 1. There were
using the planning software Oncentra® (Elekta, Veenendaal, seven cervical cancer and two endometrioid cancer patients.
Netherlands). Dose calculation of HDR-ISBT was based on Histopathology was three cervical squamous cell cancers, two
CT. Dose constraints of HDR-ISBT and the goal are to deliver cervical adenocarcinomas, two cervical sarcomas, and two
more than 6 Gy to CTVHR D90 (dose covering 90% of the uterine endometrioid cancers. The median age at treatment was
CTV H R ) and total CTV HR D 90 combining EBRT and 53 years (range 34–78). All nine cases had no distant metastasis.
brachytherapy to be >85 Gy equivalent dose in 2-Gy fractions The breakdown of the deep located target was four cervical cancers
(EQD2). The rectum and bladder were contoured as OARs. Dose with excessive uterine corpus invasion, two uterine endometrioid
constraints for OARs were determined as follows: bladder D2cc cancer with inoperable bulky tumors, one cervical cancer with
< 90 Gy EQD2 and rectum D2cc < 75 Gy EQD2. inoperable pelvic lymph node metastasis, one cervical cancer with
All brachytherapy was carried out by 192 Ir remote postoperative pelvic sidewall recurrence, and one cervical cancer
afterloading system (RALS, Micro Selectron HDR ™ , with left ovarian direct tumor invasion. Five cases underwent
Nucletron, Veenendaal, Netherlands). extended whole pelvic irradiation, which included para-aortic
lymph node metastasis in the target area. Seven cervical cancer
Follow-Up cases were given concurrent platinum-based chemotherapy
All patients were followed up by CT and/or MRI scans with EBRT.
performed 1–3 months after radiotherapy, and physical The median follow-up period was 15 months (range 3–28
months). The median volume of CTVHR at first HDR-ISBT was
131 ml (range 44–335 ml). The median linear distance from the
vaginal introitus to the deepest part of the tumor at first time
brachytherapy was 14.0 cm (9.0–17.0 cm). The prescribed dose
of HDR-ISBT was 24–30 Gy in four or five fractions. Median
CTVHR D90 (EQD2) was 85 Gy (73–93 Gy). Median bladder D2cc
(EQD2) was 71 Gy (58–77 Gy). Median rectum D2cc (EQD2) was
70 Gy (48–85 Gy).
An example of an MRI taken within 1 week before the first
brachytherapy and TAUS taken during the brachytherapy of three
typical cases is demonstrated in Figure 2A. The dose distribution
of brachytherapy of the same cases is demonstrated in Figure 2B.
Seven cases had no local recurrence in the follow-up period. One
case had in-field recurrence at 25 months after HDR-ISBT in the
initially inoperable massive iliac lymph node. Another case with
initially inoperable carcinosarcoma could not obtain local control
and subsequently underwent salvage simple hysterectomy for a
residual uterine tumor at 11 months after HDR-ISBT and finally
achieved local control. Four cases had extra-field recurrence in
lymph nodes or distant metastases. Acute adverse events were
grade 2 fever in two cases, and grade 2 vesical bleeding in one case,
FIGURE 1 | The schema of transabdominal and transrectal ultrasonography-
and grade 2 vaginal bleeding in one case. Late adverse events were
guided interstitial needle insertion.
grade 2 vesical bleeding in one case. No organ or vessel injury was

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Shimizu et al. TR/TA-US-Guided HDR-ISBT for Gynecologic Malignancies

FIGURE 2 | Pre-brachytherapy MRI and brachytherapy dose distribution of cases 1–9. (A, B) The transverse and sagittal MRI images at the rectosigmoid junction taken within 1 week
before the first brachytherapy. (C) The view of transabdominal ultrasonography (TA-US) obtained during the brachytherapy (in cases 4, 6, and 7; TA-US images were unfortunately not
saved in the medical record and are lacking). The thick white arrows indicate lymph node metastasis or massive uterine body tumor. The white arrowheads indicate interstitial needles
within the tumor. (D–F) The brachytherapy dose distribution. The blue, orange, red, green, and sky-blue isodose lines represent 200%, 150%, 100%, 80%, and 50% of the prescription
dose (6 Gy), respectively. Case 1: A 34-year-old female patient underwent robotic-assisted hysterectomy with right salpingo-oophorectomy and pelvic lymph node dissection in another
hospital for cervical squamous cell carcinoma pT1bN1M0 stage 3B according to the 2017 Union for International Cancer Control (UICC) 8th edition classification system. She
experienced massive left internal iliac lymph node metastasis. The internal iliac lymph node metastasis was too deep to be visualized by transrectal ultrasonography (TRUS), so TA-US
was used for needle insertion guidance. The volumetrically calculated CTVHR and the linear distance from the vaginal entrance to the deepest part of the target tumor at the first
brachytherapy were 132 ml and 13.1 cm, respectively. The respective cumulative dose of brachytherapy and external beam radiation therapy (EBRT) was CTVHRD90 85 Gy, rectum D2cc
58 Gy, and bladder D2cc 58 Gy. Case 2: A 39-year-old female patient with cervical squamous cell carcinoma cT2bN1M1 (para-aortic lymph node metastasis) stage 3C2. Though radical
hysterectomy was attempted, she was judged inoperable at the time of laparotomy due to an external iliac node fixed to the external iliac vein. After EBRT, she underwent high-dose-rate
interstitial brachytherapy (HDR-ISBT) for the cervical region and also the external iliac node and internal iliac node, which consisted of 24 Gy delivered in four fractional HDR-ISBT doses of
6.0 Gy per fraction in February 2019. The iliac lymph node metastasis was too deep to be visualized by TRUS, and TA-US was used for needle insertion guidance. The volumetrically
calculated CTVHR and the linear distance from the vaginal entrance to the deepest part of CTVHR at first time brachytherapy were 86 ml and 13.0 cm, respectively. The respective
cumulative dose of brachytherapy and EBRT was CTVHR D90 73 Gy, D90 (left external iliac node D90 87 Gy, rectum D2cc 48 Gy, and bladder D2cc 68 Gy. Case 3: A 78-year-old female
patient with inoperable uterine endometrioid cancer cT3bN2M1 (para-aortic lymph node metastasis) stage 4B. She underwent whole pelvic radiation therapy alone, including a para-aortic
node, with a dose was 50.4 Gy/28 fr in November 2019. She underwent HDR-ISBT for huge uterine body cancer, which consisted of 24 Gy delivered in four fractional HDR doses of
6.0 Gy per fraction in December 2019. The uterine body tumor was too large and was too deep to be visualized by TRUS, and TA-US was used for needle insertion guidance. The
volumetrically calculated CTV and the linear distance from the vaginal entrance to the deepest part of the tumor at first time brachytherapy were 335 ml and 16.5 cm, respectively. The
respective cumulative dose of brachytherapy and EBRT was CTV D90 85 Gy, rectum D2cc 70 Gy, and bladder D2cc 70 Gy. Case 4: A 73-year-old female patient with carcinosarcoma of
the cervix cT2N1M1a (para-aortic lymph node metastasis) stage 4B. She underwent whole pelvic radiation therapy, including a para-aortic node, with 50.4 Gy/28 fr in July 2019. She had
a massive uterine body invasion and needed TA-US because TRUS could not visualize the whole uterine body lesion. After EBRT, she underwent HDR-ISBT for the cervical region,
which consisted of 24 Gy delivered in four fractional HDR-ISBT doses of 6.0 Gy per fraction in September 2019. The volumetrically calculated CTV and the linear distance from the
vaginal entrance to the deepest part of the tumor at first time brachytherapy were 145 ml and 12.2 cm, respectively. The respective cumulative dose of brachytherapy and EBRT was
CTV D90 93 Gy, rectum D2cc 75 Gy, and bladder D2cc 77 Gy. Case 5: A 52-year-old female patient with cervical adenocarcinoma cT1b2N1M1a (para-aortic lymph node metastasis)
stage 4B. She underwent whole pelvic radiation therapy, including a para-aortic node, with 50.4 Gy/28 fr in January 2020. After EBRT, she underwent HDR-ISBT for the cervical region,
which consisted of 22 Gy delivered in five fractional HDR-ISBT in March 2020. She had a massive myoma near the external uterine ostium, which made TRUS unable to see the tumor
clearly; therefore, TA-US was required to visualize the lesion. The volumetrically calculated CTV and the linear distance from the vaginal entrance to the deepest part of the tumor at first
time brachytherapy were 200 ml and 17 cm, respectively. The respective cumulative dose of brachytherapy and EBRT was CTV D90 80 Gy, rectum D2cc 56 Gy, and bladder D2cc 76
Gy. Case 6: A 53-year-old female patient with cervical cancer cT2bN1M1a (para-aortic lymph node metastasis) stage 4B. She underwent whole pelvic radiation therapy, including a para-
aortic node, with 50.4 Gy/28 fr in January 2020. After EBRT, she underwent HDR-ISBT for the cervical region, which consisted of 24 Gy delivered in four fractional HDR-ISBT doses of
6.0 Gy per fraction in March 2020. She had a massive uterine body invasion and needed TA-US because TRUS could not visualize the whole uterine body lesion. The volumetrically
calculated CTV and the linear distance from the vaginal entrance to the deepest part of the tumor at first time brachytherapy were 130 ml and 12.5 cm, respectively. The respective
cumulative dose of brachytherapy and EBRT were CTV D90 85 Gy, rectum D2cc 58 Gy, and bladder D2cc 65 Gy. Case 7: A 47-year-old female patient with cervical carcinosarcoma
cT1b2N0M0 stage 1B. She was severely obese, which made surgery difficult; therefore, she underwent definitive radiotherapy. She underwent whole pelvic radiation therapy with 50 Gy/
25 fr in December 2020. After EBRT, she underwent HDR-ISBT for the cervical region, which consisted of 30 Gy delivered in five fractional HDR-ISBT doses of 6.0 Gy per fraction in
December 2020. She had a massive uterine body invasion and needed TA-US because TRUS could not visualize the whole uterine body lesion. The volumetrically calculated CTV and
the linear distance from the vaginal entrance to the deepest part of the tumor at first time brachytherapy were 104 ml and 17.4 cm, respectively. The respective cumulative dose of
brachytherapy and EBRT were CTV D90 103 Gy, rectum D2cc 85 Gy, and bladder D2cc 71 Gy. Case 8: A 55-year-old female patient with cervical adenocarcinoma cT3bN1M1a (para-
aortic lymph node metastasis, left ovarian direct tumor invasion) stage 4B. She underwent whole pelvic radiation therapy, including a para-aortic node with 50 Gy/25 fr in November
2020. After EBRT, she underwent HDR-ISBT for the cervical region, which consisted of 24 Gy delivered in four fractional HDR-ISBT doses of 6.0 Gy per fraction in December 2020. She
had left ovarian tumor direct invasion and required TA-US because TRUS could not visualize the whole image of the ovarian invasion. The volumetrically calculated CTV and the linear
distance from the vaginal entrance to the deepest part of the tumor at first time brachytherapy were 69 ml and 12.2 cm, respectively. The respective cumulative dose of brachytherapy
and EBRT were CTV D90 94 Gy, rectum D2cc 70 Gy, and bladder D2cc 75 Gy. Case 9: A 58-year-old female patient with inoperable uterine endometrioid cancer cT3bN2M1 (para-aortic
lymph node metastasis) stage 4B. She underwent whole pelvic radiation therapy, including a para-aortic node with 45 Gy/25 fr and 14 Gy/7 fr boost irradiation for pelvic lymph node
metastasis in December 2020. She underwent HDR-ISBT for huge uterine body cancer, which consisted of 24 Gy delivered in four fractional HDR-ISBT doses of 6.0 Gy per fraction in
January 2021. The huge uterine body lesion was too deep to be visualized by TRUS, and TA-US was used for needle insertion guidance. The volumetrically calculated CTV and the
linear distance from the vaginal entrance to the deepest part of the tumor at first time brachytherapy were 173 ml and 16.2 cm, respectively. The respective cumulative dose of
brachytherapy and EBRT were CTV D90 79 Gy, rectum D2cc 70 Gy, and bladder D2cc 72 Gy.

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Shimizu et al. TR/TA-US-Guided HDR-ISBT for Gynecologic Malignancies

Rectum D2cc noted due to interstitial needle insertion. In one case of acute
(Gy, EQD2) vaginal hemorrhage, hemoglobin decreased from 10.8 g/dl before

58
48

70

75
56
58
85
70
70
–
–
treatment to 8.0 g/dl after ISBT, and it improved to 11.0 g/dl after
blood transfusion. In another case, bladder hemorrhage was
observed in the acute and late stages without hemoglobin
Bladder D2cc
(Gy, EQD2)

decrease. Although the acute bladder hemorrhage was not

58
68

70

77
76
65
71
75
72
–
–
accompanied by a decrease in hemoglobin, approximately 200
ml of blood loss was observed when the applicators were removed,
necessitating blood transfusion. Because the bladder hemorrhage
(Gy, EQD2)
CTVHR D90

in the later stage was not accompanied by a decrease in

103
85
73
87
94
85

93
80
85

94
79
hemoglobin, no blood transfusion was administered.
Distance between

and deepest part

vaginal introitus

of tumor (cm)

DISCUSSION
13.1

16.5

12.2

12.5
17.4
12.2
16.2
15
13

17
9

It has been demonstrated that HDR-ISBT should be offered for

large tumors with irregular shapes (9, 14–16). Interstitial needles
are inserted either by template guided or freehand guided by
TRUS or CT. The use of US in application assistance and
CTVHR (ml)

treatment planning in image-guided brachytherapy (IGBT) had

132

335

145
200
130
104

173
86
44

69
2

been well acknowledged by Groupe Europé en de Curiethé rapie

of the European Society for Radiotherapy and Oncology (GEC-
ESTRO) (17). CT has the advantage of superior visualization
Primary and left ovarian direct inv.
Postop lymph node recurrence

compared with US. Kunogi et al. reported that with CT-guided

needle insertion, it is even possible to treat iliac lymph nodes
Lymph node metastasis
Lymph node metastasis

(18). However, US has an advantage of real-time image

Target

acquisition without exposing radiation to patients and

physicians. Real-time image acquisition is a tremendous
advantage in inserting interstitial needles into a region where
Primary

Primary

Primary
Primary
Primary
Primary

Primary

critical structures such as great vessels or bowel exist. TRUS has

also long been used for prostate brachytherapy. Therefore, it is
familiar with most brachytherapists. If a tumor can be visualized
Cisplatin + fluorouracil

by TRUS, it is possible to treat iliac lymph nodes by TRUS-

chemotherapy
Concurrent

guided HDR-ISBT (19). However, when a target is located

beyond the rectum, it is impossible to visualize the tumor only
with TRUS because the TRUS probe cannot be inserted deeper
Cisplatin

Cisplatin
Cisplatin
Cisplatin
Cisplatin
Cisplatin

than the rectum. In such cases, switching to TAUS has the

–
–
–

advantage of obtaining images for tumors located in the deep

pelvis (Figure 1). Thibodeau et al. reported the usefulness of
Adenocarcinoma

Adenocarcinoma
Carcinosarcoma

Carcinosarcoma
Histology

TAUS in detecting uterine perforation with tandem and in

visualizing interstitial needles in IC/IS (20). With TR/TA-US
guidance, it was shown in this report that not only intrauterine
SCC
SCC

SCC
EC

EC

needle insertion but also iliac lymph nodes or ovarian direct

–
–

SCC, squamous cell carcinoma; EC, endometrial cancer.

tumor invasion could be treated with HDR-ISBT.

cT1b2N1M1a
pT1b1N1M0

cT1b2N0M0
cT2bN1M1a

cT2bN1M1a

cT2bN1M1a

cT3bN1M1a
cT3bN2M1a
cT3bN2M0
Stage

In this report, the median CTVHR D90 for all nine cases was
85 Gy (range 73–103 Gy), which is above the recommended dose
by ABS and GEC-ESTRO guidelines (1, 2, 14). Median bladder
–
–

D2cc (EQD2) and median rectum D2cc (EQD2) were also below
–
–
TABLE 1 | Patient characteristics.

Cervical cancer
Cervical cancer

Cervical cancer
Cervical cancer
Cervical cancer
Cervical cancer
Cervical cancer

the recommended dose by ABS and GEC-ESTRO guidelines.

Diagnosis

Uterine body

Uterine body

Even though patients included in this study had extremely

cancer

cancer

massive tumors or tumors in locations where it is impossible to

treat HDR-ISBT with usual methods, seven out of nine patients
achieved local control. Moreover, even tumors were located
Age

34
39

78

73
52
53
47
55
58
–
–

challenging to treat locations; no grade ≥ 3 adverse events were

reported related to HDR-ISBT under TR/TA-US guidance.
Case 2–1
Case 2–2
Case 2–3
Case 1

Case 3

Case 4
Case 5
Case 6
Case 7
Case 8
Case 9

Therefore, it is likely that deeply situated tumors that localized

out of the reach of TRUS may obtain favorable dose coverage and

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Shimizu et al. TR/TA-US-Guided HDR-ISBT for Gynecologic Malignancies

have a possibility to achieve a better prognosis by HDR-ISBT CONCLUSION

guided by TR/TA-US.
In this report, transperineal needle insertion was primarily In uterine cancer treatment, deeply situated tumors that localized
used. Interstitial transvaginal needles can sometimes be used for out of the reach of TRUS may obtain favorable dose distribution
uterine body involvement, and the depth of transvaginal needles by HDR-ISBT guided with TR/TA-US.
can be monitored using TA-US. However, due to the space
limitation or interference from the other applicators, it is
sometimes difficult to change the needle angle freely with the DATA AVAILABILITY STATEMENT
transvaginal approach. Therefore, in our institution, the
transperineal approach is generally preferred. The raw data supporting the conclusions of this article will be
The limitations of this report are that the number of patients made available by the authors, without undue reservation.
included was only nine, the follow-up period was short, and there
was no control cohort to compare clinical outcomes of this new ETHICS STATEMENT
method. Therefore, it is difficult to draw firm conclusions from
this report. The limiting factor of TA-US is that the deep pelvic The studies involving human participants were reviewed and
lesion is not always well delineated due to bowel gas and other approved by the Ethics Committee of National Cancer Center
factors such as thick subcutaneous fat tissue, and TA-US cannot Hospital (approved number 2017-091). The patients/
be used as real-time needle insertion guidance in such cases. participants provided their written informed consent to
Generally, lymph node or ovarian metastases are boosted by participate in this study. Written informed consent was
EBRT, and it is unusual for HDR-ISBT to be chosen as a obtained from the individual(s) for the publication of any
modality to deliver a boost dose. However, we thought that potentially identifiable images or data included in this article.
even with the technique of stereotactic body RT, delivering
adequate tumoricidal doses to such lesions is difficult.
Brachytherapy has the physical advantage of being able to AUTHOR CONTRIBUTIONS
deliver a localized high dose of radiation with rapid fall-off and
TaK, AT, ToK, KT, KI, KO, YN, JI, and HI contributed to
capable of sparing surrounding adjacent normal tissues, as well
patients’ treatment and data collection. TC, HO, and SN
as the technical feasibility of inserting interstitial needles with the
contributed to data analysis and figure creation. All the
new technique presented in this article; therefore, we decided to
authors contributed to manuscript editing and approved it.
deliver the boost dose with HDR-ISBT for these patients. With
this new technique, it is possible to treat challenging diseases that
are otherwise impossible to treat with current treatment FUNDING
methods. Further accumulation of patients, experience, and
knowledge is needed to implement this novel technique to We received a grant for the cost of this study from the hospital's
spread widely. collaborative research fund C2019-121.

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