High-dose-rate interstitial brachytherapy for gynecologic malignancies

doi:10.1016/j.brachy.2006.09.002

Brachytherapy

Volume 5, Issue 4, October–December 2006, Pages 218-222

https://doi.org/10.1016/j.brachy.2006.09.002 Get rights and content

Abstract

Purpose

The study aimed to assess the outcome of locally advanced cervical and vaginal cancer treated with high-dose-rate interstitial brachytherapy (HDRB).

Methods and materials

Between 1998 and 2004, 16 previously unirradiated patients with locally advanced cervical and vaginal cancer not suitable for intracavitary brachytherapy because of distorted anatomy or extensive vaginal disease were treated with HDRB in combination with external beam radiotherapy. All patients received whole pelvis external beam radiation therapy (EBRT) followed by interstitial implantation. The median whole pelvis external beam dose was 45 Gy (range, 39.6–50.4 Gy) with 11 patients receiving parametrial boost to a median dose of 9 Gy. Twelve (75%) of these patients received chemotherapy concurrent with external beam. All patients received a single HDRB procedure using a modified Syed–Neblett template. A CT scan was performed postimplant for needle placement verification and treatment planning purpose. Dose was prescribed to the tumor volume based on the radiographic and clinical examination. All patients received 18.75 Gy in five fractions delivered twice daily. The median followup was 25 months (6–69 months).

Results

Median cumulative biologic effective dose (EBRT + HDRB) to tumor volume was 78.9 Gy₁₀ with the range of 72.5–85.2 Gy_10. Median cumulative biologic effective dose for the rectum and bladder were 99.4 Gy₃ (range, 79.6–107.8 Gy₃) and 96.4 Gy₃ (range, 78.3–105.3 Gy₃), respectively. Complete response was achieved in 13 (81%) patients with 3 patients having persistent disease. Five of these 13 patients developed recurrence at a median time of 14 months (distant in 4 and local and distant in 1). The 5-year actuarial local control and cause-specific survival were 75% and 64%, respectively. In subset analysis, 5-year actuarial local control was 63% for cervical cancer patients and 100% for vaginal cancer patients. No patient had acute Grade 3 or 4 morbidity. Grade 3 or 4 delayed morbidity resulting from treatment occurred in 1 patient with 5-year actuarial rate of 7%. Three patients had late Grade 2 rectal morbidity and 1 patient had Grade 2 small bowel morbidity.

Conclusions

Our series suggests that single interstitial implantation procedure with five fractions of 3.75 Gy each to target volume is an effective and safe fractionation schedule. The integration of imaging modality helps in decreasing dose to the critical organs. Additional patients and followup are ongoing to determine the long-term efficacy of this approach.

Introduction

The role of interstitial brachytherapy for the management of gynecologic malignancies, especially those involving the lower third of the vagina or for patients who are unsuitable for intracavitary brachytherapy, has been well established [1], [2], [3], [4], [5], [6]. The aim of the technique is to tailor the dose of irradiation to the anatomy of the patient with a better target volume coverage. These implants are performed under the guidance of transperineal or transvaginal templates with use of various techniques to improve accuracy of needle placement including fluoroscopy, transabdominal or transrectal ultrasound, CT, MRI, and laparoscopy [7], [8], [9], [10], [11], [12], [13], [14].

Historically these implantations have been performed using low-dose-rate (LDR) brachytherapy sources. However, high-dose-rate (HDR) brachytherapy offers advantages over LDR with respect to reduced occupational radiation exposure and superior ability to create optimal dosimetry. There is a paucity of published experience with HDR interstitial brachytherapy in gynecologic malignancies. The numbers of implant procedures and the “fractions” per implant session have not been standardized. The American Brachytherapy Society (ABS) in its guidelines recommended the treatment protocol used at California Endocurietherapy Cancer Center [15], [16]. This protocol involves three implantation procedures with two HDR fraction of 5.5 or 6 Gy delivered per implant (15).

We started using HDR interstitial brachytherapy for gynecologic malignancies in 1998 using CT guidance for verification of needle placement and treatment planning. We designed a fractionation schedule, which would enable us to treat with single implantation procedure. We herein report our experience in 16 patients with this high-dose-rate interstitial brachytherapy (HDRB).

Section snippets

Methods and materials

Between 1998 and 2004, 16 previously unirradiated patients of median age 61 years (range, 37–76 years) with locally advanced cervical and vaginal cancer not suitable for intracavitary brachytherapy because of distorted anatomy or extensive vaginal disease were treated with HDR interstitial brachytherapy in combination with external beam radiotherapy. There were 11 patients with carcinoma cervix (International Federation of Gynecology and Obstetrics [FIGO] Stage IIA 1, IIB 3, IIIA 1, IIIB 5, and

Results

The prescribed dose was computed to target volume based on clinical and radiographic findings. Based on linear-quadratic model, biologic effective dose (BED) to prescription point, resulting from contribution of EBRT and HDR brachytherapy, was determined for all patients, considering an α/β value of 10, according to Fowler (19). Total BED to target volume ranged from 72.5 to 85.2 Gy₁₀ with a median of 78.9 Gy₁₀. As the dose and fractions of HDR brachytherapy were the same for all patients, the

Discussion

Interstitial brachytherapy in gynecologic cancer is reserved for patients with extensive pelvic and/or vaginal disease or with anatomy not allowing intracavitary brachytherapy with standard applicators. It is also used for patients with recurrence at vaginal vault recurrence or in previously radiated patients [1], [2], [3], [4], [5], [6]. These implants are more elaborate and invasive than intracavitary procedures. Consequently, greater attention to the needle placement is necessary to fully

Conclusion

Our small series suggests that a single interstitial implantation procedure with five fractions of 3.75 Gy each to target volume is an effective and safe fractionation schedule. The integration of imaging modality helps in decreasing dose to the critical organs. More studies with a larger number of patients are needed to establish optimal imaging modality and fractionation schedule for HDR interstitial brachytherapy in gynecologic malignancies.

References (29)

S. Nag et al.
Interstitial brachytherapy in the management of primary carcinoma of the cervix and vagina
Gynecol Oncol
(1998)
A.M. Syed et al.
Long-term results of low-dose-rate interstitial-intracavitary brachytherapy in the treatment of carcinoma of the cervix
Int J Radiat Oncol Biol Phys
(2002)
K. Tewari et al.
Interstitial brachytherapy in the treatment of advanced and recurrent vulvar cancer
Am J Obstet Gynecol
(1999)
C. Charra et al.
Outcome of treatment of upper third vaginal recurrences of cervical and endometrial carcinomas with interstitial brachytherapy
Int J Radiat Oncol Biol Phys
(1998)
S. Nag et al.
The use of fluoroscopy to guide needle placement in interstitial gynecology brachytherapy
Int J Radiat Oncol Biol Phys
(1998)
B. Erickson et al.
CT-guided interstitial implantation of gynecological malignancies
Int J Radiat Oncol Biol Phys
(1996)
B.W. Corn et al.
Improved treatment planning for the Syed-Neblett template using endorectal-coil magnetic resonance and intraoperative (laparotomy/laparoscopy) guidance: A new integrated technique for hysterectomized women with vaginal tumors
Gynecol Oncol
(1995)
R.G. Stock et al.
A new technique for performing Syed-Neblett template interstitial implants for gynecological malignancies using transrectal-ultrasound guidance
Int J Radiat Oncol Biol Phys
(1997)
D.J. Demanes et al.
High dose rate transperineal interstitial brachytherapy for cervical cancer: High pelvic control and low complication rates
Int J Radiat Oncol Biol Phys
(1999)
S. Nag et al.
The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix
Int J Radiat Oncol Biol Phys
(2000)

F. Ampuero et al.

The Syed-Neblett interstitial template in locally advanced gynecological malignancies

Int J Radiat Oncol Biol Phys

(1983)

S. Nag et al.

A simple method of obtaining equivalent doses for use in HDR brachytherapy

Int J Radiat Oncol Biol Phys

(2000)

R. Ferrigno et al.

High-dose-rate brachytherapy in the treatment of uterine cervix cancer. Analysis of dose effectiveness and late complications

Int J Radiat Oncol Biol Phys

(2001)

A. Eisbruch et al.

Customized gynecologic interstitial implants: CT-based planning, dose evaluation, and optimization aided by laparotomy

Int J Radiat Oncol Biol Phys

(1998)

Cited by (76)

Image-guided Interstitial Brachytherapy in the Treatment of Primary and Recurrent Vulvovaginal Gynaecological Malignancies
2024, Clinical Oncology
To evaluate the use, outcomes and toxicities of high dose rate brachytherapy (HDRB) to the vulvovaginal region in previously irradiated and radiotherapy-naïve patients for primary or recurrent gynaecological malignancies.
From January 2010 to December 2020, 94 women with a median age of 64 years (range 31–88 years) were treated with interstitial HDRB for vulvovaginal disease. Treatment details, including cumulative radiotherapy doses, were recorded together with reported toxicity, using Common Terminology Criteria for Adverse Events (CTCAE) grading. Dosimetric parameters, including D90, V100 and V150 together with treatment response at 3 months, overall survival, relapse-free survival and long-term toxicity data, were collated from referring centres.
The median follow-up was 78 months (range 2–301). Primary sites of disease included vagina (37), endometrium (29), vulva (16), ovary (7) and cervix (5). Eighty-six (91.5%) patients were treated with curative intent, eight (8.5%) were palliative treatments. Fifty patients received HDRB for recurrent disease, 39 patients for primary disease and five as part of adjuvant treatment. The anatomical site of disease treated with HDRB ranged from vagina (76), vulva (14) and peri-urethral sites (four). The 2- and 5-year local relapse-free survival rates were 76% and 72%, respectively; 15 patients experienced local failure only, whereas six patients had local and nodal/distant failure. The median time to local recurrence was 8 months (range 2–88 months). The 2- and 5-year overall survival rates for all patients were 67% and 47%, respectively; the median overall survival was 59 months. Seventy-nine (84%) patients had a complete response measured with imaging at 3 months. Grade 3 toxicity was reported in 14 patients (14.8%).
This retrospective series suggests the use of interstitial brachytherapy for vulvovaginal gynaecological malignancy to be an effective and safe treatment option. Good local control was achieved with a tolerable toxicity profile; it is a valuable treatment modality.
Embracing a future of progress in gynecologic brachytherapy
2023, Brachytherapy
In the last 20 years, gynecologic brachytherapy has made tremendous advancements, most prominently evidenced by the evolution of cervical cancer brachytherapy. In its 20 year history, Brachytherapy has become known as a journal of science, education, and advocacy for our specialty and for our patients. In this review, we celebrate the 25 most impactful manuscripts in gynecologic brachytherapy in the journal's history.
The impact of tumor size and histology on local control when utilizing high-dose-rate interstitial brachytherapy for gynecologic malignancies
2022, Gynecologic Oncology
To report long-term results of an outpatient template-based high-dose-rate interstitial brachytherapy (HDR ISBT) program for the treatment of gynecologic malignancies.
Patients treated between 2006 and 2020 at an academic hospital with outpatient template based HDR ISBT without spinal or general anesthesia were reviewed. Patients who had previously received HDR ISBT were excluded. Baseline patient, tumor, and treatment characteristics, such as tumor size, histology, and/or total EQD2 including prior external beam radiation therapy (EBRT) were recorded. Local control and overall survival were estimated using the Kaplan-Meier method, and factors associated with local control and overall survival were evaluated using Cox regression analyses.
150 patients received HDR ISBT for a gynecologic tumor and the median follow-up time was 2.98 years (0.89–4.82). Of those, 74/150 (49%) were treated definitively, 69/150 (46%) were treated for tumor recurrence/persistence, and 7/150 (5%) were treated for durable palliation. Median tumor size was 3.00 cm (1.50–4.00). 124/150 (83%) patients received EBRT prior to HDR ISBT. Median HDR ISBT dose was 18 Gy delivered in eight fractions. Local control was 71% (64%–79%), 58% (50%–68%), and 57% (48%–67%) at one, three, and five years, respectively. On multivariate analysis, non-endometrial adenocarcinoma histology (HR = 2.423, 95% CI = 1.011–5.808, p = 0.047) and tumor size ≥ 3 cm (HR = 2.903, 95% CI 1.053–3.441, p = 0.033) were associated with lower local control.
The majority of patients who received outpatient-based twice daily HDR ISBT had long-term local control. Larger tumor size and non-endometrial adenocarcinoma histology were detrimental to local control.
Changing Landscape of Radiation Therapy for Advanced Cervical Cancer With a Focus on Interstitial Brachytherapy: A Canadian Practice Patterns Survey
2022, Practical Radiation Oncology
To document the evolution of radical radiation therapy and interstitial brachytherapy (ISBT) utilization practice patterns across Canada, including use of imaging, technical details, and usage of anesthesia/analgesia, and to compare advanced (AC) versus nonadvanced (nAC) brachytherapy (BT) center practices.
All Canadian centers with BT services were identified. One gynecology radiation oncologist per center was sent a 64-item questionnaire regarding the center's practice for patients with cervical cancer. Centers were categorized based on availability of advanced BT expertise (AC) versus those referring patients to other centers for advanced BT techniques (nAC). Aggregate responses are reported and compared with practice patterns identified in our previous survey. Descriptive statistics were used to summarize data, and the Fisher exact test, Fisher-Freeman-Halton, or Mann-Whitney-Wilcox test was used for comparisons.
Thirty-seven of 38 respondents completed the survey (response rate: 97.4%). Compared with 2015, there has been an increase in utilization of magnetic resonance imaging as the sole imaging modality for BT planning: 3 of 26 (11%) versus 12 of 37 (32%; P = .03). The number of centers with the ability to perform ISBT increased in 2020 compared with 2015 (26/37 [70%] vs 13/26 [50%], P = .710); this trend is likely due to an increase in use of hybrid (Vienna, Utrecht, Venezia) applicators (36% [2015] vs 84% [2020]; P = .175). Fifteen (40%) centers had the ability to perform perineal-ISBT (P-ISBT). Sixteen and 21 centers were identified as AC and nAC, respectively. All 16 AC centers had the ability to perform ISBT, compared with only 10 nAC centers (P < .001). A higher proportion of AC centers had fellowship-trained radiation oncologists performing brachytherapy, compared with nAC centers (94% vs 14%, P < .001). In terms of anesthesia, conscious sedation was the only available choice at low-patient-volume centers (8/37, 21%) performing intracavitary BT only. Those performing ISBT had choice of general, spinal, and epidural anesthesia.
In Canada, high-quality, modern management radiation therapy practices are consistently offered to patients with cervical cancer. There is a trend toward increased utilization of ISBT. Accumulation of evidence toward the use of ISBT, increased utilization of high-quality imaging modalities such as magnetic resonance imaging, and availability of hybrid applicators are potential contributors for this upward trend.
Dosimetric predictors of local control and complications in gynecologic transperineal implant patients: The medical college of wisconsin experience
2022, Brachytherapy
Citation Excerpt :
Initially, there was concern that delivering this significant central dose over a short period of time may lead to significant toxicities. A review of our series and an increasing number of other institutional series is reassuring (7-13), and compressed treatment time may be advantageous (14,15). Earlier series had used 2–3 implants (6 fractions) divided over several weeks to decrease hospital time and allow for tumor downstaging (16-18).
Investigate the relationship between dosimetric parameters with local control (LC) and complications following transperineal high-dose rate (HDR) interstitial brachytherapy (ISBT) for gynecologic (GYN) malignancies.
Between 2001 and 2016, 59 patients were treated for primary or recurrent GYN malignancies. Most patients received external beam irradiation, followed by transperineal ISBT via the Syed-Neblett applicator set with CT-based planning. Treatment plans were retrospectively reviewed to evaluate for an association among LC or toxicity with the equivalent dose at 2 Gy per fraction (EQD2) for the clinical target volume (CTV), 0.1 cc (D0.1cc), and 2 cc (D2cc) volumes of the organs at risk (OAR), low/high dose volumes for the OAR and CTV, and ratio of dose at the core vs. the implant periphery.
The median follow-up among survivors was 24 months. 34% of patients had a component of local failure and in 12%, this was isolated. Late grade 3 (G3) toxicity occurred in 15% of patients. There were no G4–5 toxicities. Rectal D0.1cc > 75 Gy trended toward significance in predicting the development of non-fistula late G2–3 rectal complications. Bladder D0.1cc > 94 Gy significantly predicted for the development of late G2–3 vesicovaginal fistula formation. The ratio of the total dose at the vaginal surface to the needle periphery above 121% trended in predicting for any complication or fistula formation.
HDR ISBT combined with EBRT achieved LC in 66% of patients with advanced or recurrent GYN cancers. Rectal and bladder D0.1cc doses may be predictive of complications as may the ratio of the implant dose at the core vs. periphery.
Inter-fractional variation of markers and applicators in single-implant high-dose-rate interstitial brachytherapy for gynecologic malignancies
2021, Brachytherapy
Citation Excerpt :
Intracavitary brachytherapy (ICBT) is the most common form of brachytherapy, however, the use of interstitial brachytherapy (ISBT) brachytherapy is essential for bulky or recurrent gynecologic malignancies. It is typically based on computed tomography (CT) and increasingly on magnetic resonance imaging (MRI) based 3D planning (3–6). Compared to an intracavitary technique, interstitial implants may allow for better target coverage by escalating dose to the tumor while sparing adjacent normal structures.
Implanted fiducial markers are a commonly used tool in delineating the CTV in high-dose-rate interstitial brachytherapy (HDR-ISBT) for gynecologic malignancy, but their reliability in gynacological sites is not well understood. These markers and interstitial applicators can experience interfractional motion due to organ swelling or other anatomical changes. The purpose of this study was to evaluate the spatial variation of these features.
The spatial positions of 50 implanted markers and 202 needles were tracked in 15 patients treated over 70 fractions of HDR brachytherapy. Marker and/or needle coordinates were extracted from CT images with contours and dose distributions. Automated analysis determined marker self-consistency and displacements between various elements of the implant.
From start to end fraction, the relative positions of the markers experienced an average magnitude displacement of 4.5 ± 3.0 mm while the average displacement of the applicator tips was 11 ± 8 mm, relative to their respective centers of mass (CM).
Markers implanted lateral and superior to the CTV experience greater drift than other implant locations.

View all citing articles on Scopus

: This study was presented in part at the 2005 American Brachytherapy Society Annual Meeting, San Francisco, CA.

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High-dose-rate interstitial brachytherapy for gynecologic malignancies

Abstract

Purpose

Methods and materials

Results

Conclusions

Introduction

Section snippets

Methods and materials

Results

Discussion

Conclusion

Gynecol Oncol

Int J Radiat Oncol Biol Phys

Am J Obstet Gynecol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Gynecol Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys