Quantitative Analysis of Vaginal Wall Thickness in Vaginal Cuff Brachytherapy - Multichannel Balloon vs. Single-Channel Brachytherapy

Objective: To evaluate thickness of the proximal vaginal wall during vaginal cuff brachytherapy (VCB) and to compare results between cases treated using single-channel cylinder (SCC) versus multichannel balloon (MCB). Methods: A total of 82 consecutive cases, including 41 by SCC and 41 by MCB treatment, were reviewed. Vaginal wall thickness was measured using CT images captured during VCB. Multiple points along the proximal vaginal canal were measured, including the central apex position on the top of vagina and the anterior, posterior, left, and right lateral positions at planes 0.5, 1, 2, and 3-cm from the top of vagina. Independent sample’s t-tests and Wilcoxon Mann Whitney tests were used for statistical analysis. Results: The thickness of proximal vaginal wall varied significantly at different locations (apex, lateral, anterior, and posterior). The mean thickness at the apex was 0.51 and 0.50 cm for SCC and MCB cases respectively (p=0.391). The vaginal wall was much thicker at both left and right lateral positions compared to anterior and posterior positions at all measurement planes for both SCC and MCB VCB. The mean vaginal wall thickness at lateral positions exceeded 0.5 cm for all measurement planes for SCC. In contrast, the mean thickness at lateral positions was smaller than 0.5 cm in all planes except measurements done at 0.5 and 1-cm distance from the apex for MCB. Conclusion: Compared to SCC, MCB can stretch and thin the vaginal wall, especially at the lateral directions and provide dosimetric advantages.


Introduction
Cancers of the uterine corpus and cancers of the cervix represent the first and the third most common gynecologic malignancies in the United States, respectively. In 2019, 61,880 new diagnoses and 12,160 deaths are estimated to be due to uterine cancer [1]. Similarly, 13,170 new diagnoses and 4,250 deaths are estimated to be due to cervical cancer [1]. Surgery is the primary management for uterine corpus cancer and early-staged cervical cancer. Postoperatively, adjuvant vaginal cuff brachytherapy (VCB) alone or in combination with external beam radiotherapy (EBRT) has become an integral treatment to reduce risk of loco-regional disease recurrence. myometrial invasion, and lymphovascular invasion [2]. Supported by the results of the PORTEC-2 trial, postoperative VCB alone is considered a reasonable recommendation for patients with stage I endometrial cancer with high-intermediate risk [2,3].
There is no clear agreement regarding the indications of VCB for postoperative cervical cancer. Consensus guidelines from the American Brachytherapy Society (ABS) recommend using VCB for patients who have less than radical hysterectomy or who have close or positive resection margins, large or deeply invasive tumors, parametrial or vaginal involvement, or extensive lymphovascular invasion [4,5].
In general, VCB is used to cover the proximal 3 -5 cm of the vagina, and the dose is prescribed to either the vaginal surface or 0.5-cm depth [4]. However, little is known about the volume of tissue superior to the vaginal cuff and the thickness of proximal vaginal canal. Therefore, the true dosimetry to the target volume in vaginal cuff is not clear [6].
We have adopted and used multi-channel balloons (MCBs; Capri applicator, Varian Medical Systems, Inc., Palo Alto, CA) for VCB since June 2014. Compared to single-channel cylinders (SCCs), we found that MCB can cover a larger volume and deliver a more conformal and homogeneous target coverage [7]. Hypothesizing there is high variability of proximal vaginal wall thickness, we sought to evaluate and compare the thickness of the proximal vaginal wall during VCB by SCC versus MCB.

Materials and Methods
With institutional review board approval, the medical records of 82 consecutive patients treated with postoperative high-dose-rate VCB between January 2011 and December 2018 were reviewed.
There were 65 endometrial cancer and 17 cervical cancer patients. Details of VCB using either SCC or MCB were described in our previous paper [7]. Briefly, all patients underwent either VCB alone or a combination of EBRT and VCB after surgery. Patients were instructed to empty their rectum and bladder before VCB. Each patient underwent a pelvic examination to ensure adequate healing of the vaginal cuff and assess the size and length of vaginal canal.  were considered to be significant.     The goal of post-operative adjuvant VCB is to reduce local cancer recurrence. In general, the proximal vaginal canal, especially the vaginal apex, is the target of VCB. Effective VCB treatment regimens vary significantly between major institutions regarding target length coverage, depth of dose specification, dose per fraction, and total dose [8]. A pathologic study by Choo et al. demonstrated that approximately 95% of vaginal lymphatic channels were located within 3-mm depth from the vaginal surface. Therefore, VCB dose prescribed to a depth of less than 5 mm might be adequate. ABS recommends treating the proximal 3-5 cm of vagina and that the dose be specified at either the vaginal surface or 0.5-cm depth [4]. Based on the PORTEC 2, the most commonly used regimen for VCB alone is 7 Gy x 3 prescribed to 0.5-cm depth from the vaginal mucosal surface [3]. A lower dose prescribed to the vaginal surface, such as 6 Gy x 5 or 4 Gy x 6, may be effective as well. Consistent with this, a randomized study by Sorbe et al. [9] comparing 2.5

Results
Gy/fraction vs. 5.0 Gy/fraction x 6 prescribed to 0.5 cm depth had similar oncologic outcomes, with only one vaginal recurrence in each arm of the study. In addition, at the 5-year follow up, cases treated with higher dose per fraction had higher degrees of vaginal shortening, mucosal atrophy, and bleeding.
The ABS recommends using the largest diameter cylinder that can comfortably and snugly fit the vagina for treatment [4].
However, due to the wider proximal end and the high-pressure constraint over vaginal introitus [10][11][12][13], it is often difficult to insert an adequately sized cylinder so that it fits snugly to the vagina apex.
As illustrated by the current study, in cases treated by a rigid SCC, although the mean thickness of anterior and posterior wall were all equal to or less than 0.5 cm, the mean thickness of vaginal wall at lateral aspects was not stretched well enough, and most were more than 0.5 cm. This indicates a single-channel applicator with symmetric cylindrical configuration is not an ideal applicator for this type of treatment. With inflatable balloon and multi-channel capability, MCB can provide more conformal and homogeneous target coverage [7]. From the current study, compared to the results by SCC, the mean vaginal wall thickness by MCB were significantly smaller in all measurement planes except lateral aspects at 0.5-cm distance from the apex and 1-cm distance from the apex on the left side. With MCB applicators, the thickness at 0.5-cm distance on left and right directions and 1-cm distance from the apex on the left side were still more than 0.5 cm. This is likely related to the design of MCB applicator, which tends inflate easier in the middle  [15] reported that significant dose reduction to rectum and bladder could be achieved without compromising target coverage by customizing the VCB dosimetry based on individual patient anatomy by using 3-dimensional RT planning. A dosimetric study on MCB by Park et al. found dose reduction to bladder, rectum, sigmoid, and urethra when using all 13 channels compared to results using a single central channel alone. With 5 mm depth prescription, the absolute reduction of D2cc of rectum and bladder was 14.6% and 9.0% of the prescription dose, respectively. In addition, the mean dose reduction to rectum and bladder was 6.4% and 4.3%, respectively [16].
Limitations of the present study include a retrospective study design, limited case number, imbalanced patient population, lack of clinical outcome data, and lower soft tissue image resolution by CT scan compared to MRI study [6]. The MCB group had significantly older patients (mean age 60.4 versus 55.0) and higher proportion of endometrial cancer patients (90% versus 63%). One can argue women of older age and endometrial diagnosis might have significantly thinner/more atrophic vaginal mucosa than younger/ cervical cancer patients. Furthermore, the MCB group had fewer combined modalities as opposed to VCB alone patients (61.0% verse 80.5%), and it is possible that the vaginal thickness is greater in patients that received combined treatment over those treated with VCB alone due to inflammation/fibrosis. It is well known fact that the measurement of vaginal wall thickness is subjective and highly depends on individual doing the management. Therefore, further investigation will be needed to confirm the results of the current study.
In the future we plan to compare the results between a more balanced group of patients and to use MRI by dose-volume histogram (DVH)-based metrics to evaluate the actual benefit between the two types of applicators.

Conclusion
There is high variability in the thickness of proximal vaginal wall. Compared to SCC, MCB can better stretch and thin the vaginal wall, especially laterally, and can provide dosimetric advantages.
In addition, MCB offers multiple dwell channels and positions to optimize the dose distribution. To further improve the dosimetric coverage, future studies should focus on improving the inflatable multi-channel balloon to adapt to the contour of the proximal vagina and to improve opening of the lateral aspects of the vagina.