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. Author manuscript; available in PMC: 2020 Aug 6.
Published in final edited form as: Gynecol Oncol. 2018 Aug;150(2):293–299. doi: 10.1016/j.ygyno.2018.06.011

Image-based multichannel vaginal cylinder brachytherapy for the definitive treatment of gynecologic malignancies in the vagina

Brian J Gebhardt a, John A Vargo a,1, Hayeon Kim a, Christopher J Houser a, Scott M Glaser a,2, Paniti Sukumvanich b, Alexander B Olawaiye b, Joseph L Kelley b, Robert P Edwards b, John T Comerci b, Madeleine Courtney-Brooks b, Sushil Beriwal a,*
PMCID: PMC7409556  NIHMSID: NIHMS1614394  PMID: 29929925

Abstract

Purpose.

Brachytherapy is integral to vaginal cancer treatment and is typically delivered using an intracavitary single-channel vaginal cylinder (SCVC) or an interstitial brachytherapy (ISBT) applicator. Multi-channel vaginal cylinder (MCVC) applicators allow for improved organ-at-risk (OAR) sparing compared to SCVC while maintaining target coverage. We present clinical outcomes of patients treated with image-based high dose-rate (HDR) brachytherapy using a MCVC.

Methods and materials.

Sixty patients with vaginal cancer (27% primary vaginal and 73% recurrence from other primaries) were treated with combination external beam radiotherapy (EBRT) and image-based HDR brachytherapy utilizing a MCVC if residual disease thickness was 7 mm or less after EBRT. All pts received 3D image-based BT to a total equivalent dose of 70–80 Gy.

Results.

The median high-risk clinical target volume was 24.4 cm3 (interquartile range [IQR], 14.1), with a median dose to 90% of 77.2 Gy (IQR, 2.8). After a median follow-up of 45 months (range, 11–78), the 4-year local-regional control, distant control, DFS, and OS rates were 92.6%, 76.1%, 64.0%, and 67.2%, respectively. The 4-year LRC rates were similar between the primary vaginal (92%) and recurrent (93%) groups (p = 0.290). Pts with lymph node positive disease had a lower rate of distant control at 4 years (22.7% vs. 89.0%, p < 0.001). There were no Grade 3 or higher acute complications. The 4-year rate of late Grade 3 or higher toxicity was 2.7%.

Conclusions.

Clinical outcomes of pts with primary and recurrent vaginal cancer treated definitively in a systematic manner with combination EBRT with image-guided HDR BT utilizing a MCVC applicator demonstrate high rates of local control and low rates of severe morbidity. The MCVC technique allows interstitial implantation to be avoided in select pts with ≤7 mm residual disease thickness following EBRT while maintaining excellent clinical outcomes with extended 4-year follow-up in this rare malignancy.

Keywords: Vaginal cancer, Brachytherapy, Intracavitary, Multi-channel vaginal cylinder

1. Introduction

Primary vaginal cancer is a rare malignancy, though incidence of HPV-associated carcinomas has been rising in recent years [1-3]. Recurrences within the vagina of primary cancers from other gynecologic sites are more frequently encountered entities. Due to the relative rarity of vaginal cancer, there is no randomized evidence to guide therapy, and management decisions are based upon retrospective series and extrapolation of data from other gynecologic sites. Single-institutional series demonstrate that definitive radiotherapy (RT) provides high rates of local control while avoiding the morbidity of surgical resection in properly selected patients [4, 5]. Treatment typically consists of combination external beam RT (EBRT) to the pelvis with brachytherapy boost [6]. Concurrent platinum-based chemoradiotherapy (CCRT) is added to definitive RT for Stage II-IV vaginal cancers based upon superior outcomes demonstrated with this approach in cervical cancer [7]. Recent trends demonstrate increased utilization of concurrent CCRT in the U.S. with an associated improvement in survival [8].

Vaginal brachytherapy has traditionally been delivered using either single-channel vaginal cylinder (SCVC) or template-based interstitial brachytherapy (ISBT) applicators depending upon the location and extent of residual disease following EBRT. Guidelines recommend ISBT for tumors with >0.5 cm residual thickness or for distal vaginal involvement [9]. While ISBT is often necessary to provide adequate coverage of bulky tumors while respecting organ-at-risk (OAR) constraints, this technique requires greater technical skill than intracavitary applicators and necessitates prolonged immobilization and hospitalization of patients. Despite the established efficacy of brachytherapy, its utilization for vaginal cancers has declined in recent years in the U.S. The cause of the decline is likely multifactorial and may owe in part to a lack of physician familiarity with ISBT techniques, issues related to reimbursement, the logistical difficulties of performing brachytherapy procedures with a busy clinical schedule, and other causes [10].

Intracavitary multi-channel vaginal cylinder (MCVC) applicators have recently become available on the commercial market. Dosimetric comparisons demonstrate that image-based treatment using a MCVC can improve target coverage and spare uninvolved vagina and adjacent OAR compared with SCVC applicators while avoiding ISBT in properlyselected patients [11-14]. There is limited data evaluating whether dosimetric gains translate into clinically meaningful outcomes. Our institutional practice is to utilize the MCVC for most vaginal cancers with 7 mm or less residual thickness following EBRT [15]. Here we present clinical outcomes of a series of patients undergoing high dose-rate (HDR) image-guided brachytherapy (IGBT) using an intracavitary multichannel vaginal cylinder (MCVC) for the definitive treatment of vaginal cancers.

2. Methods and materials

2.1. Patient population

This retrospective study was approved by the Institutional Review Board of the University of Pittsburgh Cancer Institute. We reviewed records of all patients that were diagnosed with primary vaginal cancers or recurrences within the vagina from other gynecologic cancers and were subsequently treated with IGBT using a MCVC applicator at Magee Womens Hospital of UPMC from October 2011 to May 2016. Patients having undergone previous pelvic EBRT or brachytherapy were excluded. Patients receiving a lower RT dose in the adjuvant setting or treated with palliative intent were excluded. Those treated with freehand interstitial needles in addition to MCVC applicator were excluded. Patients with distant metastatic disease were excluded with the exception of those with para-aortic nodal disease and no other sites of distant metastasis.

All patients underwent vaginal biopsy for disease confirmation and were clinically staged according to the FIGO system by a gynecologic oncologist and radiation oncologist. Recurrent vaginal cancers were staged according to the FIGO stage of the primary lesion. For 85% of patients, local staging included a gadolinium contrast-enhanced pelvic MRI with water-based gel to better define the extent of disease and guide subsequent brachytherapy planning [16]. A CT scan of the chest, abdomen, and pelvis was used to assess pelvic nodal involvement and distant metastatic spread in 27% of patients, while the remaining 73% underwent 18-flurodeoxyglucose positron emission tomography (PET)/CT.

2.2. Treatment technique

Treatment consisted of a combination of EBRT followed by a brachytherapy boost. EBRT planning was completed using either a CT- or PET/ CT-based simulation. Fiducial markers were not placed prior to EBRT. Simulation scans were performed with an empty rectum and with both full and empty bladder in order to generate an internal target volume for the vaginal contour to account for daily differences in bladder filling. The clinical target volume (CTV) included the entire vagina and paravaginal tissues plus the distal common iliac, external iliac, internal iliac, and obturator lymph nodes. Inguinal lymph nodes were included if the distal one-half of the vagina was involved. The CTV was expanded to create a planning target volume by 1 cm for the vagina and 7 mm for the lymph node volumes with use of daily image guidance. The prescribed EBRT dose was 44–50.4 Gy at 1.8–2.0 Gy per fraction, with nodal metastases receiving a simultaneous integrated boost to 55 Gy at 2.2 Gy per fraction [17]. Patients underwent CCRT for advanced disease stage and for certain histologies including clear cell adenocarcinoma or small cell carcinoma.

The brachytherapy boost was delivered utilizing an HDR 192Ir afterloader (Nucletron, an Elekta Company, Elekta AB, Stockholm, Sweden). We initially utilized a non-MR-compatible custom fivechannel MCVC applicator with one central and four peripheral channels. This was followed by commercially available MR-compatible applicators with one central and either six or eight peripheral channels (Nucletron, an Elekta Company, Elekta AB, Stockholm, Sweden). The MCVC applicator was placed prior to each treatment, and then CT and/or MR imaging was obtained with the applicator in place. CT-based planning was used prior to the availability of an MR-compatible MCVC or in patients with contraindications to MRI. MRI-based planning was utilized when possible as it provides better delineation of soft tissue and visualization of the extent of local disease [16].

The gross tumor volume (GTV) was defined as clinically detectible disease as assessed by imaging and clinical examination. The High-risk CTV (CTVHR) was delineated based upon pre- and post-EBRT GTV. The length of vagina to which only the mucosal surface was treated was determined by the extent of the pre-EBRT GTV. The residual post-EBRT GTV defined the area for which the entire thickness of the vagina and residual tumor would be included [6, 15]. The vaginal surface was treated in the remaining previously involved length in order to account for non-concentric tumor regression and intervening lymphatics while sparing the full thickness of vagina in this region from receiving the full prescription dose (Fig. 1).

Fig. 1.

Fig. 1.

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Target volume delineation and treatment planning for image-based brachytherapy utilizing a MCVC applicator. (A) MRI demonstrating pre-EBRT primary vaginal cancer. (B) Post-EBRT MRI with MCVC in place showing residual disease in left side of vagina. (C) Target contouring including gross tumor volume on patient's left and CTVHR volume (black arrow) including pre-EBRT length of vagina and post-EBRT disease thickness. (D) Brachytherapy plan demonstrating asymmetric dose distribution with 100% iso-dose line covering residual disease (black arrow).

Three-dimensional CT or MR image-based planning was used in all patients with each fraction via Nucletron Plato version 14.3 or Oncentra version 4.0 (Nucletron, Veneendal, The Netherlands). The prescription dose was delivered to the reference points placed along the cylinder surface as an initial standard single channel cylinder plan utilizing only the central channel. Then dwell positions on the peripheral channels were then activated and manually optimized to cover the CTVHR while respecting normal OAR constraints. Dwell weights on peripheral channels were approximately 5–10% of the dwell weight used for the central channel.

HDR brachytherapy dose was determined based upon response to EBRT and extent of residual disease and prescribed to the CTVHR. Brachytherapy courses were delivered over 4–5 fractions at 4.3–5.5 Gy per fraction. Total EBRT and brachytherapy fraction doses were summated and converted to equivalent dose in 2 Gy fractions (EQD2 Gy) using the linear quadratic model and alpha/beta values of 10 Gy and 3 Gy for target and OARs, respectively [18]. The goal was to deliver a cumulative EQD2 Gy of between 70 and 80 Gy, delivering higher doses to patients with significant residual disease after EBRT [9]. The dose to 2 cm3 (D2 cc) constraints for OARs were 70 Gy or lower to the rectum, 70 Gy or lower to the sigmoid colon, and 85 Gy or lower to the bladder. The urethral maximum point dose was limited to <100% of the prescription dose [19]. We did not include a vaginal constraint but selected patients for MCVC only if residual disease thickness was 7 mm or less after EBRT in order to prevent excessive increases in the vaginal dose [20].

2.3. Statistical analysis

The Kaplan-Meier method was utilized to estimate rates of tumor control and survival, which were calculated from the date of diagnosis of primary or recurrent vaginal cancer to date of failure, death, or last follow-up. The primary outcome was local-regional control, which was defined as absence of recurrent disease within the vagina or pelvic lymph nodes. Toxicity was scored according to NCI CTCAE Version 4.0. Associations of patient and treatment factors and clinical outcomes were assessed with log-rank test for significance for dichotomous variables. Cox regression analysis was utilized for continuous variables. A p-value of lower than 0.05 was set as the threshold for statistical significance. Statistical analyses were conducted using SPSS Version 24 (IBM, Armonk, NY).

3. Results

Patient and treatment characteristics are listed in Table 1. Sixty patients were treated from October 2011 to May 2016, including 16 (27%) with primary vaginal cancers and 44 (73%) with vaginal recurrences of other gynecologic primary tumors. Table 2 provides additional detail of histology of primary vaginal cancers and recurrences of other gynecologic cancers listed by primary cancer site. EBRT was planned using intensity-modulated RT (IMRT) in 95% of patients, which is associated with decreased toxicity and improved quality of life during pelvic RT [21]. Nineteen patients (32%) received CCRT with EBRT, and 7 (12%) patients received adjuvant systemic therapy following RT. Forty-one (68%) patients received MRI-based brachytherapy plans and 19 (32%) CT-based plans. HDR fractionation schemas were as follows: 5.5 Gy × 5 fractions (n = 1, 2%), 5 Gy × 5 fractions (n = 42, 70%), 4.75 Gy × 5 fractions (n = 2, 3%), 4.5 Gy × 5 fractions (n = 8, 13%), 4.3 Gy × 5 fractions (n = 1,2%), 4 Gy × 5 fractions (n = 3,5%), 6Gy × 4 fractions (n = 1, 2%), and 4 Gy × 4 fractions (n = 2, 3%). The median CTVHR was 24.4 cm3 (interquartile range [IQR], 14.1), with a median dose to 90% (D90 CTVHR) of 77.2 Gy EQD2 (IQR, 2.8). The median dose to 2 cm3 (D2 cc) for the bladder, rectum, and sigmoid were 59.0 Gy (IQR, 5.9), 58.4 Gy (IQR, 4.0), and 51.6 Gy (IQR, 7.0), respectively. Dose-volume characteristics are listed in Table 3.

Table 1.

Patient and treatment characteristics.

Characteristic All patients
(n = 60)		 Primary vaginal
(n = 16)		 Recurrence
(n = 44)
Median age (years) 66 (35–87) 60 (39–87) 66 (35–85)
FIGO stagea
 I 39 (65.0%) 10 (62.5%) 29 (65.9%)
 II 14 (23.3%) 4 (25%) 10 (22.7%)
 III 4 (6.7%) 2 (12.5%) 2 (4.5%)
 IV 2 (3.3%) 0 2 (4.5%)
 Not documented 1 (1.7%) 0 1 (2.3%)
Nodal involvement
 None 49 (81.7%) 14 (87.5%) 35 (79.5%)
 Iliac 7 (11.7%) 2 (12.5%) 5 (11.4%)
 Iliac and inguinal 1 (1.7%) 0 1 (2.3%)
 Para-aortic 2 (3.3%) 0 2 (4.5%)
 Iliac and para-aortic 1 (1.7%) 0 1 (2.3%)
Vaginal tumor size (cm) 2.0 (0.5–5.8) 2.5 (1.0–5.8) 2.0 (0.5–5.70)
Location in vagina
 Proximal 1/3 40 (66.7%) 6 (37.5%) 34 (77.3%)
 Middle 1/3 7 (11.7%) 2 (12.5%) 5 (11.4%)
 Distal 1/3 13 (21.7%) 8 (50%) 5 (11.4%)
Concurrent chemotherapy
 Cisplatin 18 (30%) 11 (68.8%) 7 (15.9%)
 Paclitaxel 1 (2%) 0 1 (2.3%)
 None 41 (68%) 5 (31.2%) 36 (81.8%)
Adjuvant chemotherapy
 Yes 7 (12%) 2 (12.5%) 5 (11.4%)
 None 53 (88%) 14 (87.5%) 39 (88.6%)
Treatment planning
 MRI-based 41 (68%) 15 (93.8%) 26 (59.1%)
 CT-based 19 (32%) 1 (6.2%) 18 (40.9%)
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a

For recurrence vaginal cancer, FIGO staging represents the stage of the primary lesion.

Table 2.

Histologies of primary vaginal cancers and vaginal recurrences of other primary malignancies.

Histology Number (percentage)
Primary vaginal cancer
 Squamous cell carcinoma 9 (56.3%)
 Adenocarcinoma 2 (12.5%)
 Clear cell adenocarcinoma 1 (6.3%)
 Melanoma 1 (6.3%)
 Small cell carcinoma 2 (12.5%)
 Urothelial carcinoma 1 (6.3%)
Recurrent uterine
 Endometrioid adenocarcinoma 33 (84.6%)
 Papillary serous carcinoma 2 (5.1%)
 Clear cell adenocarcinoma 3 (7.7%)
 Mixed serous and clear cell 1 (2.6%)
Recurrent cervical
 Squamous cell carcinoma 1 (33.3%)
 Adenocarcinoma 1 (33.3%)
 Small cell 1 (33.3%)
Recurrent ovarian
 Papillary serous carcinoma 1 (50.0%)
 Endometrioid adenocarcinoma 1 (50.0%)
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Table 3.

Dose-volume characteristics.

Dose-volume characteristics Median
(interquartile range)
HR-CTV volumea 24.4 cm3 (14.1)
Dose to 90% of the volume (D90) 77.2 Gy (2.8)
Volume receiving 100% of the prescribed dose (V100%)a 92.8% (4.2)
Volume receiving 100% of the prescribed dose (V100cc)a 23.9 cm3 (11.5)
Volume receiving 150% of the prescribed dose (V150%)a 56.1% (5.4)
Volume receiving 150% of the prescribed dose (V150cc)a 14.7 cm3 (7.9)
Volume receiving 200% of the prescribed dose (V200%)a 37.0% (6.1)
Volume receiving 200% of the prescribed dose (V200cc)a 9.8 cm3 (5.0)
Bladder D2cc 59.0 Gy (5.9)
Rectum D2cc 58.4 Gy (4.0)
Sigmoid D2cc 51.6 Gy (7.0)
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a

The HR-CTV volume included the vaginal cylinder thus over-represents the true HR-CTV volume and respective V100, V150, and V200. HR-CTV = high risk clinical target volume. Cc = cubic centimeters. Gy = Gray D2cc = Dose to 2 cm3. All presented doses represent the equivalent dose at 2Gy per fraction (EQD2Gy).

3.1. Outcomes

Complete clinical response was defined as complete resolution of disease on clinical exam and imaging, and was documented in 98% of patients. After a median follow-up of 45 months (range, 11–78) among living patients, the 4-year local-regional (Fig. 2) and distant control rates were 92.6% and 76.1%, respectively. The 4-year disease-free survival (DFS) (Fig. 3) and overall survival (OS) rates were 64.0%, and 67.2%, respectively. There was no significant difference in local failure by CTVHR volume (continuous) (p = 0.526), D90 CTVHREQD2Gy (continuous) (p = 0.218), primary vs. recurrent vaginal cancer (p = 0.906), CT- vs. MRI-based brachytherapy planning (p = 0.773), or use of CCRT (p = 0.367). There was no significant difference in distant control by primary vs. recurrent vaginal cancer (p = 0.290), PET-CT vs. CT staging (p = 0.343), or use of concurrent (p = 0.932) or adjuvant systemic chemotherapy (p = 0.762). Patients with lymph node positive disease had a significantly lower rate of distant control at 4 years (22.7% vs. 89.0%, p < 0.001).

Fig. 2.

Fig. 2.

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Kaplan-Meier estimate of LRC.

Fig. 3.

Fig. 3.

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Kaplan-Meier estimate of DFS.

3.2. Subgroup analyses

For 16 patients with primary vaginal cancers, the median follow-up among living patients was 38.5 months (range, 25–59). The 4-year LRC, distant control, DFS, and OS were 93.3%, 83.0%, 77.0%, and 71.1%, respectively. There was no significant difference in local failure by CTVHR volume (p = 0.857), D90 CTVHR EQD2 Gy (p = 0.335), CT- vs. MRI-based brachytherapy planning (p = 0.789), or use of concurrent chemotherapy (p = 0.480). Nodal involvement was associated with decreased distant control at 4 years (0% vs. 92.9%, p = 0.040). There was no difference in distant control by use of adjuvant systemic chemotherapy (p = 0.508), but use of concurrent chemotherapy was associated with improved distant control (100% vs. 53.3%, p = 0.046).

For the 44 patients with recurrences from non-vaginal primary cancers, the median follow-up among living patients was 47 months (range, 11–78). The 4-year LRC, distant control, DFS, and OS rates were 92.2%, 73.3%, 59.4%, and 66.5%, respectively. There was no difference in local failure by CTVHR volume (p = 0.528), D90 CTVHR EQD2 Gy (p = 0.338), CT- vs. MRI-based brachytherapy planning (p = 0.782), or use of concurrent chemotherapy (p = 0.404). There was no difference in distant control by PET-CTvs. CT staging (p = 0.181), or use of adjuvant systemic chemotherapy (p = 0.506). Patients with lymph node positive disease had a significantly lower rate of distant control at 4 years (26.7% vs. 87.2%, p < 0.001).

3.3. Toxicity

There were no Grade 3 or higher acute complications. The 4-year actuarial rate of late Grade 3 or higher toxicity was 2.9%. There were no late Grade 3 or higher vaginal, bladder, or urethral toxicities. One patient developed a severe small bowel toxicity manifested as adhesions of the terminal ileum 13 months after completing treatment. She underwent CCRT for a recurrence of endometrial adenocarcinoma involving the vagina and a left obturator node.

4. Discussion

We present outcomes of 60 patients with vaginal cancer (27% primary vaginal and 73% recurrence within the vagina from other gynecologic primaries) systematically treated with combination EBRT and HDR IGBT using a MCVC. With median follow-up of 45 months, the 4-year LRC, distant control, DFS, and OS rates were 92.6%, 76.1%, 64.0%, and 67.2%, respectively. There were no significant differences in LRC by any of the examined patient and treatment factors. Though treatmentrelated factors including the use of chemotherapy did not appear to impact outcomes, this could be due to factors such as disease biology and selection bias or inadequate statistical power. The 4-year LRC rates were similar between the primary vaginal (92%) and recurrent (93%) groups. All 4 documented local recurrences were within the initial 2 years of follow-up, which suggests durable LRC with this technique with extended follow-up.

A growing body of literature demonstrates the superiority of IGBT techniques in more prevalent gynecologic sites, though the principles are applicable to vaginal cancers. The prospective STIC study found improved LRC of cervical cancer with IGBT compared with 2D planning, and the grade 3–4 toxicity rate was 23% with 2D dosimetry compared with 3% with 3D planning [22]. Single-institutional series have reported similar rates of LRC of locally-advanced cervical cancer and limited toxicity [23-27]. The EMBRACE study was initiated to investigate outcomes with IGBT in a prospective multi-institutional setting. RetroEMBRACE recently reported retrospective outcomes of 731 patients and estimated a 10% LRC improvement compared with historical series as well as a combined grade 3 or greater toxicity rate of only 11% [28]. Early data from the EMBRACE trial suggest favorable rates of bladder and small bowel toxicity and reduced rates of late functional outcomes such as proctitis and severe toxicity including fistula formation when restricting the rectum D2cc [29-31]. There are currently limited data investigating the application of these techniques to vaginal cancers.

Recommended treatment of vaginal cancers involves pelvic EBRT with brachytherapy boost to a total dose of 70–85 Gy EQD2 due to a demonstrated LRC benefit with combination therapy [9, 32, 33]. In recent years, there has been a concerning trend toward decreased utilization of brachytherapy with a corresponding increase in IMRT-based boost [10, 34]. Brachytherapy techniques include intracavitary treatment with SCVC for smaller lesions, though ISBT is traditionally required for tumors with >5 mm residual thickness following EBRT [9]. Decreased BT utilization may be due to multiple causes including a lack of physician familiarity with this technique and greater comfort with IMRT [10]. MCVC applicators have recently become available on the commercial market. Dosimetric studies demonstrate improved ability to sculpt target coverage while reducing dose to surrounding OAR compared with SCVC applicators, though clinical outcomes data is lacking [11-14]. While ISBT is required for bulky residual disease, the MCVC is an alternative for select patients with disease too thick to cover with SCVC while avoiding an interstitial implantation and associated patient discomfort, need for sedation, and extended immobilization [6, 15, 35].

Our institutional protocol is to use MCVC for treatment of patients with vaginal lesions measuring 7 mm or less in thickness following EBRT. Our data show comparable LRC rates with IGBT series utilizing predominantly ISBT [36-39]. In a Harvard series of 44 patients with vaginal recurrences treated primarily with ISBT, 6 patients experienced local failure after ISBT, though 5 occurred in patients who had received prior RT, suggesting aggressive disease [36]. A more recent series of 72 patients with predominantly primary vaginal cancer treated with ISBT found that 2-year local control was 93% with IGBT compared with 71% with 2D planning [37]. A series of 13 patients with primary vaginal cancers treated with IGBT from the Vienna group demonstrated 92% local control despite the fact that 69% of the cohort had Stage III/IV disease [38]. The crude toxicity rate was 23%, largely due to organ fistulas at the site of initial invasion, consistent with advanced stage of presentation. This series is not directly comparable with the present study due to the more advanced stage of presentation, which may have predisposed patients to higher toxicity from treatment. The high rate of LRC demonstrated in the present series combined with low severe morbidity suggests that the image-guided approach allowed us to limit the dose to OARs while maintaining adequate target coverage. Furthermore, limiting CTVHR to the involved vaginal length did not appear to compromise tumor control, though it would be necessary to systematically track low grade vaginal toxicity to assess whether or not this reduces the rates of vaginal stenosis. EMBRACE data demonstrate an association between vaginal toxicity and dose to the ICRU recto-vaginal point, which highlights the potential advantage of limiting dose to uninvolved vagina [40].

We previously published a series of 41 patients with vaginal cancer undergoing IGBT using a MCVC demonstrating clinical feasibility and excellent response rates [15]. At a median follow-up of 16 months, the 2-year rates of LRC, distant control, DFS, and OS were 93%, 81%, 78%, and 88%, respectively. There were no severe acute toxicities, and only 1 late Grade 3+ toxicity. Here we present clinical outcomes and late toxicities among a group of 60 patients with this uncommon malignancy and demonstrate durable LRC with extended follow-up of 45 months. The predominant pattern of failure in our cohort was distant metastasis, which was strongly associated with lymph node involvement. No other factors predicted for distant control, though there was likely inadequate statistical power to detect potentially associated factors. The CTVHR in our series included the mucosal surface of the length of vagina involved pre-EBRT, while the entire thickness of the vagina and residual tumor was included based on the post-EBRT GTV. While GEC-ESTRO has published CTVHR definitions for cervical cancer, there is currently no consensus in brachytherapy volume definitions for the treatment of vaginal cancers [34, 41]. Establishing standardized definitions for target volumes is necessary to systematically incorporate IGBT techniques and track outcomes.

Some weaknesses of this study include its retrospective design and inherent selection bias. Included patients had 7 mm or less residual disease thickness, and thus our cohort had less bulk of disease than comparable series utilizing ISBT. A potential limitation of this technique arises from the inability to confirm the orientation of MCVC, though LRC remained high. While our data show low severe morbidity, rates of grade 1–2 vaginal stenosis and other late effects were not reported. As this data was not prospectively tracked, it was felt that low-grade toxicity would likely be underreported within a retrospective analysis. Despite these limitations, this study represents a large series of patients with vaginal malignancies treated with definitive RT including IGBT utilizing a MCVC applicator, for which long term outcomes have not otherwise been reported.

5. Conclusions

This retrospective analysis of patients with primary or recurrent vaginal cancer treated in a systematic manner with combination EBRT with IGBT using a MCVC applicator demonstrates high LRC and low morbidity due to the ability to maximize dose to the CTVHR while limiting dose to surrounding OAR. The MCVC technique allows interstitial implantation to be avoided in select patients with 7 mm or less residual disease thickness following EBRT while maintaining excellent clinical outcomes with extended follow-up, though prospective data are ultimately needed to validate these findings.

HIGHLIGHTS.

  • Treatment of vaginal cancers with multi-channel cylinder produced high local control.

  • There were no severe acute complications and only 3% severe late morbidity.

  • Interstitial implantation can be avoided in select patients with good outcomes.

Footnotes

Conflicts of interest

There are no conflicts of interest to disclose.

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