The clinical impact of removing rectal gas on high‐dose‐rate brachytherapy dose distributions for gynecologic cancers

Abstract Purpose To evaluate the impact of gas removal on bladder and rectal doses during intracavitary and interstitial high‐dose‐rate brachytherapy (HDRB) for gynecologic cancers. Material and Methods Fifteen patients treated with definitive external beam radiation followed by HDRB for gynecologic cancers for a total of 21 fractions, presented with a significant amount of rectal gas at initial CT imaging (CTGAS) after implantation. The gas was removed via rectal tubing followed by subsequent scan acquisition (CTCLINICAL), which was used for planning and treatment delivery. To assess the effect of gas removal on dosimetry, both bladder and rectum volumes were recontoured on CTGAS. In order to evaluate the clinical impact on the total Equivalent‐Dose‐in‐2Gy‐fraction (EQD2), each fraction was also replanned to maintain clinically delivered target coverage (HRCTV D90). EQD2 D2cm3 for bladder and rectum were compared between plans. The Wilcoxon signed rank test was performed to evaluate statistically significant differences for all comparisons (P < 0.05). Results Mean rectum and bladder Dmax, D0.1cm3, D1cm3, D2cm3, and D5cm3 were significantly different between CTGAS and CTCLINICAL. The mean percent increases on CTGAS for bladder were 12.3, 8.4, 9.9, 10.2, and 9.5% respectively and for rectum were 27.0, 19.6, 18.1, 18.5, and 19.4%, respectively. After replanning with CTGAS to maintain HRCTV D90 EQD2, bladder and rectum EQD2 D2 cm3 resulted in significantly higher doses. The mean EQD2 D2 cm3 difference was 2.4 and 4.1 Gy for bladder and rectum, revealing a higher impact of gas removal on rectal DVH. Conclusion Rectal gas removal resulted in statistically significant differences for both bladder and rectum. The resulting larger EQD2 D2 cm3 for bladder and rectum demonstrates that if patients were treated without removing gas, target coverage would need to be sacrificed to satisfy the rectum constraints and prevent toxicities. Therefore, this study demonstrates the importance of gas removal for gynecologic HDRB patients.


| PURPOSE
High-Dose-Rate brachytherapy (HDRB) plays a major role in the management of patients with gynecologic cancers. The advantages of brachytherapy for dose escalation include the rapid dose fall-off allowing the delivery of high doses to the target volume while sparing the organs at risk (OAR), mainly the rectum, bladder, sigmoid and bowel. Image-guided adaptive brachytherapy (IGABT) is now accepted as the gold standard for locally advanced cervical cancer. 1 RetroEMBRACE II has established new dose constraints for OARs.
The High-Risk Clinical Target Volume (HRCTV) D90 EQD 2 has been increased to >90 Gy using α/β = 10, while the planning aims for bladder D2cm 3 EQD 2 and rectum D2cm 3 EQD 2 using α/β = 3 have been lowered to <80 and <65 Gy, respectively. 2 Indeed, it has been shown that there is a linear correlation between the D2cm 3 received by the OARs with complication rates. 3 In order to meet these more challenging constraints, appropriate placement of applicators and dwell time optimization are crucial. In addition, dosimetry can be affected by the filling status of the rectum and bladder. The effect of bladder distension on dose received by OARs has been previously reported and while various filling protocols have been suggested, [4][5][6][7][8][9] no clear consensus has been reached. Since rectal dose is the hardest constraint to meet, beginning in the summer of 2019, our group has implemented the routine use of a rectal tube for removal of gas.
The goal of this study is to evaluate the effects of gas removal on rectal doses during intracavitary and interstitial HDRB for gynecologic cancers.

| MATERIALS AND METHODS
In this retrospective IRB-approved study, patients with gynecologic cancers treated with definitive EBRT followed by intracavitary or interstitial brachytherapy boost were reviewed. Patients with a significant amount of gas at the time of CT simulation requiring gas removal after insertion of HDRB applicators were eligible. No formal policy regarding rectal filling at the time of brachytherapy existed in our department at the time of study. However, gas removal using a rectal tube was often used at the discretion of the treating radiation oncologist. Interstitial applicator insertion was performed in the operating room under general and epidural anesthesia, whereas intracavitary applicator insertion was performed on an outpatient basis with PO pain medication. All patients had a Foley catheter inserted during the procedure. Tandem and ovoid applicators were used for intracavitary HDRB while a template, cylinder and interstitial needles were used for interstitial brachytherapy. In order to evaluate the impact of gas on rectal and HRCTV dose constraints, the clinically used CT without gas (CT CLINICAL ) was then registered to the initial CT with gas (CT GAS ) for each appropriate fraction. The HRCTV was transferred onto the CT GAS scan via image registration. Given the differences in rectal and bladder filling between the two CTs, rectum and bladder organ volumes were recontoured by the same physician on the CT GAS scan. Dosimetric parameters were then extracted from the clinical plan on the newly contoured rectum and bladder volumes from CT GAS for comparison.
Box plot comparisons of extracted dosimetric parameters for Bladder between the initial CT scan with gas (CT GAS ) and the CT scan after gas removal (CT CLINICAL ), which was used for clinical treatment planning and delivery.
F I G . 2. Box plot comparisons of extracted dosimetric parameters for Rectum between the initial CT scan with gas (CT GAS ) and the CT scan after gas removal (CT CLINICAL ), which was used for clinical treatment planning and delivery.  Fig. 3. The top plot reiterates the equivalence of HRCTV D90 target coverage for the replan with the clinical plan. Figure 3 also makes evident that for almost every single patient for D2cm 3 Rectum, the CT GAS replan(s) resulted in larger values than for the CT CLINICAL plans to achieve the same HRCTV D90. The D2cm 3 Bladder data points are more mixed, with about half demonstrating higher values on the CT GAS replan(s) and the rest mostly the same or slightly less than the clinically delivered plans.
Both an intracavitary and interstitial HDRB patient case are each presented in Fig. 4. The CT images shown are the CT GAS scan. The rectum contour from the clinically delivered scan (CT CLINICAL ) was F I G . 4. Rectum contours in different colors from CT CLINICAL and CT GAS shown for comparison on the CT GAS images for both an intracavitary (top row) and interstitial (bottom row) HDRB sample patients.
| 39 propagated onto this scan and simultaneously overlaid with the CT GAS rectum contour for comparison, in different colors. This figure demonstrates the significant increase in rectal gas between the two scans, as well as visualizes the increased proximity of the rectum to the HRCTV due to this gas. This inevitably challenges the ability to satisfy both the target and OAR constraints simultaneously.

| DISCUSSION
The American Brachytherapy Society suggests rectal tube insertion with or without diluted barium contrast for gas removal and better visualization of the anterior rectal wall prior to the applicator placement or at the end of the procedure. 10 In the Embrace II protocol, bowel preparation is performed to ensure an empty rectum and sigmoid, especially when interstitial needles are used. 2 Although guidelines recommend fleet enemas prior to brachytherapy, this has not been widely adopted across all institutions mainly because of the risk of dehydration and electrolyte disturbances due to radiation-induced diarrhea. The usefulness of fleet rectal enemas on HDR intracavitary brachytherapy was assessed in a prospective trial including 20 patients. The authors did not report differences in rectal volume and DVH constraints between fractions with and without rectal enemas. 11 The same authors evaluated the effect of rectal enemas on rectal dosimetry after HDR vaginal cuff brachytherapy and found similar findings: rectal enemas did not impact rectum DVH and 35.6% of patients had larger rectums after enemas. 12 To our knowledge, this is the first study to report the usefulness of rectal gas removal prior to intracavitary and interstitial HDRB for gynecologic cancers. In our study, rectal gas removal resulted in lower Bladder and Rectum mean D max , D0.1cm 3 , D1cm 3 , D2cm 3 , and D5cm 3 . In order to assess the effect of rectal gas removal on dosimetry, replanning on CT GAS was performed with the goal of achieving the same HRCTV D90 EQD 2 , as delivered with the CT CLINICAL . Bladder and rectum EQD2 D2cm 3 were significantly higher upon replanning using the CT GAS, highlighting the positive impact of rectal tube insertion for gas removal. Although the benefit was significant for both rectal and bladder DVH, gas removal was mostly advantageous for rectal dosimetry as depicted in Fig. 3.
Rectal distension has been shown to correlate with rectal DVH. 13 Despite the strong impact of gas removal on rectal and bladder DVH, our study has limitations: the retrospective nature of the study with inherent selection bias as well as the small number of patients.
Furthermore, we did not evaluate the mean rectal volume since it varies from fraction to fraction depending on the contours. Unlike EBRT, for brachytherapy, only the hottest D2cm 3 is reported, which is highest near the HRCTV. Therefore, the entire rectum as defined by Radiation Therapy Oncology Group from the anus to the sigmoid reflection is not routinely contoured. In order to assess the impact of gas on rectal DVH, replanning on CT GAS demonstrated the usefulness of gas removal since higher doses to bladder and rectum needed to be delivered to achieve the same HRCTV D90 EQD 2 .
Given the significant differences demonstrated by our results, we have clinically employed a threshold of 4 cm for the rectal diameter as an indication for rectal tube placement for interstitial and intracavitary HDRB patients. We plan on conducting future studies with a larger variety of patients and HDR brachytherapy procedures in order to more broadly investigate the impact of rectal gas.

| CONCLUSION S
High HRCTV D90 while sparing the rectum, bladder and sigmoid, using the GEC-ESTRO and Embrace II guidelines requires imageguided HDRB. The rectum is usually the limiting organ-at-risk with the tightest DVH constraints. Gas removal using a rectal tube is easy, inexpensive, minimally invasive and is performed on a case-tocase basis. It reduces the rectal and bladder doses thereby allowing optimal dosimetry without sacrificing coverage of the HRCTV for intracavitary and interstitial HDR brachytherapy for gynecologic cancers.

ACKNOWLEDG MENT
IV and LH designed the study, performed experiments, data collection, and analysis. IV drafted the manuscript with assistance from LH. RE, MS, BL, and NJY all contributed substantially to the concept, design of the study and preparation of the manuscript.