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A prospective analysis of catheter complications for gynecological cancers treated with interstitial brachytherapy in the 3D era
Brachytherapy
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(2018)
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A prospective analysis of catheter complications for gynecological cancers treated with interstitial brachytherapy in the 3D era Lucas C. Mendez1, Pencilla Lang1, Chirag Patel2, David D’Souza3, Adam Gladwish4, Laura D’Alimonte1, Amandeep Taggar1, Elizabeth Barnes1, Lisa Barbera1, Eric Leung1,* 1
Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada 2 Department of Radiology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada 3 Department of Radiation Oncology, London Regional Cancer Program, Western University, London, Ontario, Canada 4 Royal Victoria Hospital, Barrie, Ontario, Canada
ABSTRACT
PURPOSE: Perineal interstitial brachytherapy (P-ISBT) is an important component in the treatment of locally advanced gynecological cancers. However, there are concerns about potential acute complications from catheter needles. The goal is to evaluate the safety of P-ISBT by studying acute complications and radiological organ needle intrusions. MATERIALS AND METHODS: Forty-eight patients with gynecological cancers treated with PISBT at a single institution from September 2014 to April 2016 were included in a prospective registry trial. Postoperative adverse events were recorded during inpatient stay and at 6-week followup. Postprocedure CT and MRI images were reviewed by two physicians to record the number of needles intruded into organs. Discrepancies were resolved by a radiologist. RESULTS: Median followup time was at least 3 months. Forty-two patients were initially treated with external beam radiation therapy, median dose of 45 Gy. A total of 73 insertions were performed. The median number of needles for first and second insertions was 17 and 19, respectively. Twenty-eight patients had radiological evidence of needle intrusion(s) into at least one pelvic organ. The most commonly intruded organs were large bowel (18 cases) and bladder (18), followed by rectum (12). A total of nine acute toxicities from needle intrusions were found: four hematuria (1 G1, 3 G2); four perineal infections (3 G2, 1 G3); and one vaginal bleeding (G3). No gastrointestinal complications were found. CONCLUSIONS: Perineal ISBT is an effective treatment for gynecological cancers. Despite occasional radiological catheter intrusions, there are low rates of organ complications. Concern of needle complications from P-ISBT should not be a barrier to adopting this technique for effective treatment. Ó 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Keywords:
Gynecological malignancies; Perineal interstitial brachytherapy; Acute complications
Introduction Locally advanced gynecological cancers are challenging diseases that can cause significant morbidity for patients through their sensitive location in the pelvis. The tumor is often closely associated to adjacent organs, which limits
Received 12 June 2018; received in revised form 16 August 2018; accepted 6 September 2018. Conflict of interest: All authors have no conflict of interest regarding this publication. * Corresponding author. Sunnybrook Health Science Centre, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada. Tel.: 416-4803416; fax: 416-480-6002. E-mail address: [email protected] (E. Leung).
the available curative treatment options. Brachytherapy plays an important role in delivering conformal radiation in this scenario and common techniques use intracavitary applicators. However, intracavitary brachytherapy is limited by the conventional dose distribution and interstitial needles are often required to help increase dose conformality by positioning catheters directly into tumor tissue and thereby effectively treating large bulky tumors (1). Perineal interstitial brachytherapy (P-ISBT) has been a specialized technique available for decades for the treatment of locally advanced gynecological cancers (2e5). Treatment with 3D-guided P-ISBT results in high rates of local control (6) with acceptable toxicity. However, despite this, there is reluctance to adopt this technique due to its
1538-4721/$ - see front matter Ó 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.brachy.2018.09.002
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apparent challenging nature and concerns of complications from the interstitial catheter needles. There is a natural apprehension for inserting needles into the pelvis without clear image-guidance due to concerns that catheter needles may potentially intrude into organ spaces and cause severe organ injury and complications. Unlike prostate brachytherapy where transrectal ultrasound guidance can provide a clear picture of both the prostate and implant, there are limitations in visualizing the relevant anatomy in P-ISBT. Often, radiation oncologists practicing this technique rely on preoperative imaging to develop baseline treatment plans and insert needles clinically, without real-time guidance. Historically, the use of surgical/laparoscopic guidance in real time was considered an essential part of interstitial brachytherapy (7,8). This study examines a prospective cohort of gynecological oncology patients treated with clinically guided interstitial brachytherapy technique. Through CT evaluation, the number of needles intruding into adjacent organs was quantified and acute complications were evaluated.
Methods and materials Patients Between September 2014 and April 2016, 48 patients with locally advanced gynecological tumors treated with P-ISBT were enrolled into a research and ethics board approved, prospective registry trial at a single academic institution. Patients received pelvic radiotherapy before boost P-ISBT treatment or had P-ISBT as the sole modality of treatment. The combined treatment was generally given in one to two insertions with a total of three to four fractions of brachytherapy, while patients receiving P-ISBT alone had three to six fractions of treatment in one or two insertions. Implant procedure The P-ISBT implant procedure has been previously described (9). In brief, patients undergo a prebrachytherapy MRI scan with vaginal cylinder in place. Needle location and depth of insertion are then estimated by using the pre-BT cylinder position as a reference. On the procedure day with patients under general anesthesia, gynecological examination is performed to help guide and plan needle positioning. An iodopovidone solution is used to sterilize the perineum and genitalia followed by urinary catheter insertion. A disposal perineal template applicator (Best Medical Systems, Inc., Springfield, VA) is placed over the intravaginal cylinder and against the perineum. Plastic catheters (6F; 24 cm length) containing metal stylets are then inserted through the template holes and obturator grooves, piercing the perineum and cervix/vaginal wall, respectively. Antibiotic prophylaxis is not mandatory and intraoperative transrectal ultrasound may be used for real-time guidance
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as part of their procedure. For cervical cancer patients, an intrauterine tandem is inserted inside the uterus through transabdominal ultrasound guidance followed by placement of the vaginal cylinder and needle insertion. Finally, the template is sutured against the perineum. The procedure typically takes approximately 75 min, and after general anesthesia recovery, patients are imaged with CT MRI scans for treatment planning. First treatment fraction is delivered on the day of the procedure, followed by one or two fractions in the second day. On average, patients are in hospital with the applicator in situ for 32 h. After applicator insertion, patients are admitted into the inpatient ward with a urinary catheter in place. Perineal bleeding and hematuria are recorded by the nursing staff. Either oral or intravenous (via pain pump) opioids are given for pain control. Low molecular weight heparin is used for deep vein thrombosis prophylaxis. Patients also receive a low-residue diet and standing loperamide for peristalsis reduction. A minimum time of 6 h is respected between each HDR brachytherapy fractions. After last BT fraction, the applicator is removed and patients are discharged as long as there is no active bleeding present and patient is able to void. Patients receiving a subsequent applicator implant are readmitted the following week and similar clinical care is provided. Planning and treatment After the procedure, target and organs at risk are contoured at a MIM Vista (MIM Software Inc., Cleveland, OH) planning station using CT MRI scans. Planning occurs at Oncentra Brachy (Nucletron, Veenendaal, the Netherlands) after importing images and contours from MIM Vista. In Oncentra Brachy, catheters are manually reconstructed in the CT scan and a plan is created by inverse optimization with Inverse Planning Simulated Annealing algorithm. Needles found to be inside an organ at risk have their intruded section manually unloaded during planning. No attempt is made to readjust needle positioning and depth after CT imaging. Plans are evaluated and approved based on ABS and GEC-ESTRO guidelines (10,11). Data record and complications Acute complications were measured prospectively under a prospective registry trial. In this study, complications were analyzed from the day of the procedure until hospital discharge, at first followup appointment, 6 weeks after ISBT, and in any interim visits up to and including 3 months. Complications were scored by CTCAE (V4.03) score system. Radiological analysis The CT and MRI scans used during treatment planning were used for quantification of visceral intrusion. As part
L.C. Mendez et al. / Brachytherapy
of the institutional protocol, at least one scan was requested for every two BT fractions. Patients with cervical cancer commonly had one CT scan for each brachytherapy fraction. All scans used for planning were retrospectively evaluated by two physicians (LCM and PL). Intrusions to organs at risk (bladder, rectum, and bowel) were independently quantified by both authors through evaluation of the axial, sagittal, and coronal planes. Visceral intrusion was only considered when the needle tip or shaft was seen simultaneously inside an organ in all image planes (axial, sagittal, and coronal). When disagreement was found between observers, an experienced body radiologist reviewed the scans. Statistical analysis Descriptive analysis was used to describe organ intrusion and complications. Variables were analyzed with appropriate measures of central tendency and dispersion. Fisher exact test assessed intrusions and complication events. Wilcoxon rank sum test evaluated the correlation between number of inserted needles and complication events. A p-value !0.05 was considered statistically significant.
Results From the 48 patients, 46 were discharged on the day of template removal. One patient was kept an extra day due to asymptomatic hyperkalemia and the other due to vomiting. All patients were followed by at least 3 months after brachytherapy. Indications for ISBT were as follows: locally advanced cervical cancers (n 5 16), cervical cancers with postsurgery local recurrences (n 5 2), vaginal primary cancers (n 5 12), pelvic recurrent uterine cancers (n 5 13), and others (n 5 5). Six patients received ISBT only because of previous course of pelvic EBRT or in the palliative setting. Forty-two patients received EBRT to the pelvis with a median dose of 45 Gy (range 42.5e 50.4 Gy). A total of 73 applicator insertions were performed: 23 patients received one implant, whereas 25 had two. Most patients receiving a single implant had a recurrent uterine cancer with good response to EBRT or were elderly and fragile patients with a vaginal cancer primary. These patients were treated with three brachytherapy fractions. Except for one, all patients with cervical primaries were treated with four fractions in two insertions a week apart. The median clinical target volume (CTV) was 52 cm3 (range 4e205 cm3). A median of 17 (10e25) and 19 (8e 26) needles were used in the first and second insertions, respectively. The median dose prescribed was 700 cGy (range 500e700 cGy) and the mean CTV D90 was 739 cGy (range 513e845 cGy). Mean bladder, rectum and bowel/sigmoid doses (D2cc) were 489 cGy, 422 cGy, and 269 cGy, respectively. Clinical and treatment details can be seen in Table 1.
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Table 1 Clinical and treatment characteristics Characteristics
Numbers
Clinical Patients Age, median (range) Tumor type Cervix Cervix (recurrent) Vagina Uterus (recurrent) Other Treatment Total number of BT insertions Patients with second insertion Mean HRCTV volume (cm3) Mean HRCTV D90 Median number of needles inserted (range) 1st insertion 2nd insertion Mean bladder D2cc (range) Mean rectum D2cc (range) Mean bowel D2cc (range)
48 65 (23e87) 16 2 12 13 5 73 25 52 739 cGy (513e845) 17 (10e25) 19 (8e26) 489 cGy (54e662) 422 cGy (44e451) 269 cGy (92e269)
Twenty-eight patients had radiological evidence of needle intrusion(s) to at least one pelvic organ. After planning imaging, no needle was repositioned due to organ intrusion. The dwell positions within the intruded organ at risk were not loaded. From the 73 insertions, the most commonly intruded organs were bowel and bladder, both with 18 intrusions, followed by rectum with 12 intrusions (Table 2). Figure 1 shows examples of needle intrusions to organs at risk. A total of 14 acute complications were potentially related to the P-ISBT procedure (Table 3). Nine were possibly attributed to interstitial needles: four patients developed hematuria, with three of them requiring manual bladder irrigation before Foley removal (Grade 2). The other patient was completely asymptomatic (Grade 1); three patients developed perineal infections days after the procedure (Grade 2) and required oral antibiotics; 1 patient developed a pelvic abscess 2 months after brachytherapy, requiring percutaneous drainage and intravenous antibiotics (Grade 3); one patient had vaginal bleeding during applicator removal and required transfusion (Grade 3). The patient that developed the pelvic abscess had an IB2 cervical cancer treated with salvage radiotherapy (EBRT þ ISBT) after an initial trachelectomy. This patient received intraoperative antibiotic prophylaxis but
Table 2 Radiological organ intrusion Organ
Procedure with no intrusion
Procedure with intrusion
Number of intruded needles, median (range)
Bowel Bladder Rectum
55 55 61
18 18 12
2 (1e7) 2 (1e10) 1 (1e11)
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Fig. 1. Pelvic organs intruded by interstitial catheters. Planning computed tomography axial planes showing bowel (a), bladder (b), and rectum (c) intruded by interstitial catheters after interstitial brachytherapy implant.
developed an abscess in the left pelvis 2 months after the last ISBT, requiring percutaneous abscess drainage and intravenous antibiotic. The two bacteria species cultured in this collection were Peptostreptococcus anaerobius and Finegoldia magna. No bowel or bladder needle intrusion was seen. The closest needle was 3 cm away from the location of the eventual collection. This patient also had radiological left hydroureter on CT simulation with evidence of a radiological needle intrusion at the ureter. There was no clinical sequelae related to this radiological finding and kidney function was stable throughout treatment. The hydroureter resolved on followup ultrasound postapplicator removal. No patient developed acute gastrointestinal complications and five had general clinical events: hyperkalemia during hospital stay, sensitivity reaction to hydromorphone, ventricular tachycardia, pulmonary thromboembolism and moderate emesis. No difference in infection rates was seen between patients receiving one or two ISBT insertions ( p 5 1.0) and the number of catheters inserted did not correlate with the infection rate ( p 5 0.83). Four patients developed Grade 1 or 2 hematuria. One patient had G1 hematuria with no needle seen intruding the bladder in the planning CT. Table 4 depicts the number of patients with Grade 2 hematuria in comparison with the presence of bladder intrusions and number of intruding needles.
interstitial approaches due to lack of expertise and concern of complications. In a Canadian survey, only half of the responding centers indicated that they were performing ISBT, whereas 96% of them are using 3D imageeguided planning (14). Many radiation oncologists feel that it is necessary to integrate surgical guidance (laparotomy or laparoscopy) with P-ISBT to view the insertion of catheters in real-time (8). However, this resource is not readily available, can lead to surgical complications and requires additional operative time (8,15). With the advent of 3D imageebased planning, it is possible to avoid loading needles within or close to organs and P-ISBT complications can thereby be limited. It may be that the higher rates of toxicity previously seen with 2D planning for interstitial (3) are partly associated with the limitations of outdated brachytherapy dosimetry and not from any physical needle injury. We hypothesize that this is the case and that catheter injuries are rare from interstitial brachytherapy. With mounting evidence for the integration of ISBT into treatment of gynecologic tumors, barriers and myths regarding these complications should not impede the development of such a program. This prospective study quantifies radiological organ intrusion and rates of acute complication associated with P-ISBT. Overall, 73 procedures were analyzed in this study with a total of 48 pelvic organs intruded by interstitial
Discussion
Table 3 Acute complications after perineal interstitial brachytherapy
Interstitial brachytherapy has been shown to be effective at controlling locally advanced gynecological tumors in the pelvis (1,6,12,13). Data from RetroEMBRACE suggests that the use of interstitial needles in large cervical cancers improves local control by 10% (1). Although this technique has been available for decades, there has been reluctance to
Type
Total
G1
G2
G3
G4
Gastrointestinal Urinary Vaginal bleeding Infection Clinical events
0 4 1 4 5
0 1 0 0 2
0 3 0 3 1
0 0 1 1 2
0 0 0 0 0
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Table 4 Grade 2 hematuria events vs bladder intrusion and number of needles Bladder intrusion Grade 2 hematuria
Yes
No
p-value
Yes No
3 58
15 0
0.0116
Mean (SD) number of needles in the bladder 5.3 (5.8) 0.4 (1.0)
p-value 0.0006
SD 5 standard deviation.
catheters. Only nine acute complications potentially attributed to catheter intrusions were seen, with only two Grade 3 complications. One patient had vaginal bleeding after applicator removal requiring transfusion and another developed a pelvic abscess, 2 months after interstitial insertion, requiring intravenous antibiotic treatment. Organ intrusion is a common event in patients with locally advanced or recurrent gynecological cancers treated with P-ISBT. Shah et al (16) have reported that 53% and 72% of the patients had their bladder or bowel, respectively, intruded. Nevertheless, no additional toxicities were seen in their cohort of patients if compared with previous series using real-time intraoperative guidance (laparoscopy, ultrasound, and fluoroscopy) (8). Likewise, only four of these events can be attributed by visceral intrusion of 9 patients presented with postprocedure complications associated with catheters in our series. As the risk of organ damage related with needle intrusion to pelvic organ is low, real-time image-guidance or laparoscopic guidance is not a prerequisite to developing an ISBT program. The use of intraoperative transrectal ultrasound, however, may reduce the number of pelvic organ intrusions (17) while assessing needle distribution within the high-risk CTV. Hematuria was the only complication that could be directly correlated with organ intrusion, as 3 of 18 patients with bladder intrusion were found to have Grade 2 hematuria. These patients had higher number of needles intruding the bladder in comparison with patients with bladder intrusion and no urinary bleeding. Nevertheless, most patients with bladder intrusion did not have any significant urinary complication, and those that did, had low grade hematuria not requiring transfusion. A case-report described by Rossman et al. illustrates the low morbidity rate associated with bladder intrusion, as no hematuria or other urinary complication were seen in a patient with a proven bladder intrusion by a tandem applicator (18). Needle intrusions to rectum or bowel were seen in 30 postprocedural scans. However, no postoperative gastrointestinal complications such as bowel obstruction or peritonitis were found. Previously, Lee et al. have described Grade 3e4 gastrointestinal toxicity events in patients treated with P-ISBT. However, with a median time to toxicity of 11 months, it is challenging to differentiate the cause for such events between radiation toxicity, needle trauma, or tumor progression (19). Similar to results of this study, previous cohorts (16) could not correlate GI complications with visceral needle intrusions.
For the first 27 patients in this prospective registry cohort, prophylactic intraoperative antibiotics were not used. During this period, 3 patients developed perineal skin infections requiring use of therapeutic oral antibiotic. For the subsequent 21 patients in this cohort, cefazolin 2 g was given intraoperatively and no further perineal infections were seen. Therefore, IV antibiotics seemed to decrease the risk of developing acute perineal skin infection. A variable amount of vaginal and perineal bleeding is seen immediately after applicator removal. In the vast majority of the cases, the bleeding is controlled by direct compression and/or vaginal packing. Previous authors have evaluated the role of vaginal packing after pelvic floor surgery or hysterectomy and suggested the benefit of this measure in reducing the postoperative rate of pelvic hematomas (20,21). Although there is a lack of data and expert opinion in regard to bleeding management after ISBT applicator removal (22), our group agrees that the use of vaginal packing is usually effective and of little morbidity, especially if bleeding does not decrease after direct compression. Finally, 5 patients had general clinical events during brachytherapy inpatient admission. These may have not been directly related to the brachytherapy procedure but could be in part due to factors associated with the overall disease, treatment and inpatient stay. Some patients developed sensitivity to the pain medications when used via intravenous pain pumps. Efforts to adopt an oral regimen of pain control may be helpful at avoiding complications from intravenous opioids especially for opioid na€ıve patients (9). The prospective nature of the documentation of toxicity and the independent evaluation of organ intrusion are strengths of this study. Furthermore, a board-certified body radiologist verified image assessments. These points increase the robustness of the findings and more accurately correlate visceral intrusion with acute complication. This study also has limitations. The absence of MRI images in all BT plans may have decreased the accuracy in defining OAR intrusion. Another drawback of the study is that we did not capture data on late toxicity. Finally, this is a single institution study and it is possible that serious and rare events could be appreciated with a larger cohort of patients.
Conclusion Perineal ISBT is associated with low rates of organ complications from this procedure despite occasional
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radiological catheter intrusions. No acute bowel injury from needles was found in any patients. Although acute hematuria was seen in 4 patients, no serious complications were seen and the event is self-limited. Concerns of needle complications and lack of real-time imaging or laparoscopic guidance may not be barriers to adopting this technique, which is an effective treatment for locally advanced gynecological tumors. References [1] Fokdal L, Sturdza A, Mazeron R, et al. Image guided adaptive brachytherapy with combined intracavitary and interstitial technique improves the therapeutic ratio in locally advanced cervical cancer: analysis from the retroEMBRACE study. Radiother Oncol 2016; 120:434e440. [2] H€ ockel M, M€ uller T. A new perineal template assembly for highdose-rate interstitial brachytherapy of gynecologic malignancies. Radiother Oncol 1994;31:262e264. [3] Aristizabal SA, Woolfitt B, Valencia A, et al. Interstitial parametrial implants in carcinoma of the cervix stage II-B. Int J Radiat Oncol Biol Phys 1987;13:445e450. [4] Nori D, Hilaris BS, Kim HS, et al. Interstitial irradiation in recurrent gynecological cancer. Int J Radiat Oncol Biol Phys 1981;7:1513e 1517. [5] Martinez A, Herstein P, Portnuff J. Interstitial therapy of perineal and gynecological malignancies. Int J Radiat Oncol Biol Phys 1983;9: 409e416. [6] Mendez LC, Weiss Y, D’Souza D, et al. Three-dimensional-guided perineal-based interstitial brachytherapy in cervical cancer: a systematic review of technique, local control and toxicities. Radiother Oncol 2017;123:312e318. [7] Fokdal L, Tanderup K, Nielsen SK, et al. Image and laparoscopic guided interstitial brachytherapy for locally advanced primary or recurrent gynaecological cancer using the adaptive GEC ESTRO target concept. Radiother Oncol 2011;100:473e479. [8] Monk B, Walker J, Tewari K, et al. Open Interstitial Brachytherapy for the treatment of local-regional recurrences of uterine corpus and cervix cancer after primary surgery. Gynecol Oncol 1994;52: 222e228. [9] Mendez LC, Choi S, D’Alimonte L, et al. Opioid consumption and pain in gynecological cancer patients treated with interstitial brachytherapy. Brachytherapy 2017;16:870e876.
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[10] Viswanathan AN, Beriwal S, De Los Santos JF, et al. American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part II: high-dose-rate brachytherapy. Brachytherapy 2012;11:47e52. [11] Haie-Meder C, P€otter R, Van Limbergen E, et al. Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (I): concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV. Radiother Oncol 2005;74:235e245. [12] Manuel MM, Cho LP, Catalano PJ, et al. Outcomes with image-based interstitial brachytherapy for vaginal cancer. Radiother Oncol 2016; 120:486e492. [13] Wang C, Raince J, Swamy U, et al. Clinical outcomes using imageguided interstitial brachytherapy for definitive cervical cancer patients with high-risk clinical target volumes greater than 30 cc. Brachytherapy 2018;17:392e398. [14] Taggar AS, Phan T, Traptow L, et al. Cervical cancer brachytherapy in Canada: a focus on interstitial brachytherapy utilization. Brachytherapy 2017;16:161e166. [15] Corn BW, Lanciano RM, Rosenblum N, 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;56:255e261. [16] Shah AP, Strauss JB, Gielda BT, et al. Toxicity associated with bowel or bladder puncture during gynecologic interstitial brachytherapy. Int J Radiat Oncol Biol Phys 2010;77:171e179. [17] Sharma DN, Rath GK, Thulkar S, et al. Use of transrectal ultrasound for high dose rate interstitial brachytherapy for patients of carcinoma of uterine cervix. J Gynecol Oncol 2010;21:12e17. [18] Rossmann MD, Koprowski C, Lewis G, et al. Bladder puncture from fletcher-suit tandem applicator diagnosis by pelvic ultrasound. J Ultrasound Med 1989;8:403e405. [19] Lee LJ, Viswanathan AN. Predictors of toxicity after image-guided high-dose-rate interstitial brachytherapy for gynecologic cancer. Int J Radiat Oncol Biol Phys 2012;84:1192e1197. [20] Thiagamoorthy G, Khalil A, Cardozo L, et al. The value of vaginal packing in pelvic floor surgery: a randomised double-blind study. Int Urogynecol J Pelvic Floor Dysfunct 2014;25:585e591. [21] Westermann LB, Crisp CC, Oakley SH, et al. To pack or not to pack? A randomized trial of vaginal packing after vaginal reconstructive surgery. Female Pelvic Med Reconstr Surg 2016;22:111e117. [22] Beriwal S, Demanes DJ, Erickson B, et al. American Brachytherapy Society consensus guidelines for interstitial brachytherapy for vaginal cancer. Brachytherapy 2012;11:68e75.
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A prospective analysis of catheter complications for gynecological cancers treated with interstitial brachytherapy in the 3D era Lucas C. Mendez1, Pencilla Lang1, Chirag Patel2, David D’Souza3, Adam Gladwish4, Laura D’Alimonte1, Amandeep Taggar1, Elizabeth Barnes1, Lisa Barbera1, Eric Leung1,* 1
Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada 2 Department of Radiology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada 3 Department of Radiation Oncology, London Regional Cancer Program, Western University, London, Ontario, Canada 4 Royal Victoria Hospital, Barrie, Ontario, Canada
ABSTRACT
PURPOSE: Perineal interstitial brachytherapy (P-ISBT) is an important component in the treatment of locally advanced gynecological cancers. However, there are concerns about potential acute complications from catheter needles. The goal is to evaluate the safety of P-ISBT by studying acute complications and radiological organ needle intrusions. MATERIALS AND METHODS: Forty-eight patients with gynecological cancers treated with PISBT at a single institution from September 2014 to April 2016 were included in a prospective registry trial. Postoperative adverse events were recorded during inpatient stay and at 6-week followup. Postprocedure CT and MRI images were reviewed by two physicians to record the number of needles intruded into organs. Discrepancies were resolved by a radiologist. RESULTS: Median followup time was at least 3 months. Forty-two patients were initially treated with external beam radiation therapy, median dose of 45 Gy. A total of 73 insertions were performed. The median number of needles for first and second insertions was 17 and 19, respectively. Twenty-eight patients had radiological evidence of needle intrusion(s) into at least one pelvic organ. The most commonly intruded organs were large bowel (18 cases) and bladder (18), followed by rectum (12). A total of nine acute toxicities from needle intrusions were found: four hematuria (1 G1, 3 G2); four perineal infections (3 G2, 1 G3); and one vaginal bleeding (G3). No gastrointestinal complications were found. CONCLUSIONS: Perineal ISBT is an effective treatment for gynecological cancers. Despite occasional radiological catheter intrusions, there are low rates of organ complications. Concern of needle complications from P-ISBT should not be a barrier to adopting this technique for effective treatment. Ó 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Keywords:
Gynecological malignancies; Perineal interstitial brachytherapy; Acute complications
Introduction Locally advanced gynecological cancers are challenging diseases that can cause significant morbidity for patients through their sensitive location in the pelvis. The tumor is often closely associated to adjacent organs, which limits
Received 12 June 2018; received in revised form 16 August 2018; accepted 6 September 2018. Conflict of interest: All authors have no conflict of interest regarding this publication. * Corresponding author. Sunnybrook Health Science Centre, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada. Tel.: 416-4803416; fax: 416-480-6002. E-mail address: [email protected] (E. Leung).
the available curative treatment options. Brachytherapy plays an important role in delivering conformal radiation in this scenario and common techniques use intracavitary applicators. However, intracavitary brachytherapy is limited by the conventional dose distribution and interstitial needles are often required to help increase dose conformality by positioning catheters directly into tumor tissue and thereby effectively treating large bulky tumors (1). Perineal interstitial brachytherapy (P-ISBT) has been a specialized technique available for decades for the treatment of locally advanced gynecological cancers (2e5). Treatment with 3D-guided P-ISBT results in high rates of local control (6) with acceptable toxicity. However, despite this, there is reluctance to adopt this technique due to its
1538-4721/$ - see front matter Ó 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.brachy.2018.09.002
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apparent challenging nature and concerns of complications from the interstitial catheter needles. There is a natural apprehension for inserting needles into the pelvis without clear image-guidance due to concerns that catheter needles may potentially intrude into organ spaces and cause severe organ injury and complications. Unlike prostate brachytherapy where transrectal ultrasound guidance can provide a clear picture of both the prostate and implant, there are limitations in visualizing the relevant anatomy in P-ISBT. Often, radiation oncologists practicing this technique rely on preoperative imaging to develop baseline treatment plans and insert needles clinically, without real-time guidance. Historically, the use of surgical/laparoscopic guidance in real time was considered an essential part of interstitial brachytherapy (7,8). This study examines a prospective cohort of gynecological oncology patients treated with clinically guided interstitial brachytherapy technique. Through CT evaluation, the number of needles intruding into adjacent organs was quantified and acute complications were evaluated.
Methods and materials Patients Between September 2014 and April 2016, 48 patients with locally advanced gynecological tumors treated with P-ISBT were enrolled into a research and ethics board approved, prospective registry trial at a single academic institution. Patients received pelvic radiotherapy before boost P-ISBT treatment or had P-ISBT as the sole modality of treatment. The combined treatment was generally given in one to two insertions with a total of three to four fractions of brachytherapy, while patients receiving P-ISBT alone had three to six fractions of treatment in one or two insertions. Implant procedure The P-ISBT implant procedure has been previously described (9). In brief, patients undergo a prebrachytherapy MRI scan with vaginal cylinder in place. Needle location and depth of insertion are then estimated by using the pre-BT cylinder position as a reference. On the procedure day with patients under general anesthesia, gynecological examination is performed to help guide and plan needle positioning. An iodopovidone solution is used to sterilize the perineum and genitalia followed by urinary catheter insertion. A disposal perineal template applicator (Best Medical Systems, Inc., Springfield, VA) is placed over the intravaginal cylinder and against the perineum. Plastic catheters (6F; 24 cm length) containing metal stylets are then inserted through the template holes and obturator grooves, piercing the perineum and cervix/vaginal wall, respectively. Antibiotic prophylaxis is not mandatory and intraoperative transrectal ultrasound may be used for real-time guidance
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as part of their procedure. For cervical cancer patients, an intrauterine tandem is inserted inside the uterus through transabdominal ultrasound guidance followed by placement of the vaginal cylinder and needle insertion. Finally, the template is sutured against the perineum. The procedure typically takes approximately 75 min, and after general anesthesia recovery, patients are imaged with CT MRI scans for treatment planning. First treatment fraction is delivered on the day of the procedure, followed by one or two fractions in the second day. On average, patients are in hospital with the applicator in situ for 32 h. After applicator insertion, patients are admitted into the inpatient ward with a urinary catheter in place. Perineal bleeding and hematuria are recorded by the nursing staff. Either oral or intravenous (via pain pump) opioids are given for pain control. Low molecular weight heparin is used for deep vein thrombosis prophylaxis. Patients also receive a low-residue diet and standing loperamide for peristalsis reduction. A minimum time of 6 h is respected between each HDR brachytherapy fractions. After last BT fraction, the applicator is removed and patients are discharged as long as there is no active bleeding present and patient is able to void. Patients receiving a subsequent applicator implant are readmitted the following week and similar clinical care is provided. Planning and treatment After the procedure, target and organs at risk are contoured at a MIM Vista (MIM Software Inc., Cleveland, OH) planning station using CT MRI scans. Planning occurs at Oncentra Brachy (Nucletron, Veenendaal, the Netherlands) after importing images and contours from MIM Vista. In Oncentra Brachy, catheters are manually reconstructed in the CT scan and a plan is created by inverse optimization with Inverse Planning Simulated Annealing algorithm. Needles found to be inside an organ at risk have their intruded section manually unloaded during planning. No attempt is made to readjust needle positioning and depth after CT imaging. Plans are evaluated and approved based on ABS and GEC-ESTRO guidelines (10,11). Data record and complications Acute complications were measured prospectively under a prospective registry trial. In this study, complications were analyzed from the day of the procedure until hospital discharge, at first followup appointment, 6 weeks after ISBT, and in any interim visits up to and including 3 months. Complications were scored by CTCAE (V4.03) score system. Radiological analysis The CT and MRI scans used during treatment planning were used for quantification of visceral intrusion. As part
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of the institutional protocol, at least one scan was requested for every two BT fractions. Patients with cervical cancer commonly had one CT scan for each brachytherapy fraction. All scans used for planning were retrospectively evaluated by two physicians (LCM and PL). Intrusions to organs at risk (bladder, rectum, and bowel) were independently quantified by both authors through evaluation of the axial, sagittal, and coronal planes. Visceral intrusion was only considered when the needle tip or shaft was seen simultaneously inside an organ in all image planes (axial, sagittal, and coronal). When disagreement was found between observers, an experienced body radiologist reviewed the scans. Statistical analysis Descriptive analysis was used to describe organ intrusion and complications. Variables were analyzed with appropriate measures of central tendency and dispersion. Fisher exact test assessed intrusions and complication events. Wilcoxon rank sum test evaluated the correlation between number of inserted needles and complication events. A p-value !0.05 was considered statistically significant.
Results From the 48 patients, 46 were discharged on the day of template removal. One patient was kept an extra day due to asymptomatic hyperkalemia and the other due to vomiting. All patients were followed by at least 3 months after brachytherapy. Indications for ISBT were as follows: locally advanced cervical cancers (n 5 16), cervical cancers with postsurgery local recurrences (n 5 2), vaginal primary cancers (n 5 12), pelvic recurrent uterine cancers (n 5 13), and others (n 5 5). Six patients received ISBT only because of previous course of pelvic EBRT or in the palliative setting. Forty-two patients received EBRT to the pelvis with a median dose of 45 Gy (range 42.5e 50.4 Gy). A total of 73 applicator insertions were performed: 23 patients received one implant, whereas 25 had two. Most patients receiving a single implant had a recurrent uterine cancer with good response to EBRT or were elderly and fragile patients with a vaginal cancer primary. These patients were treated with three brachytherapy fractions. Except for one, all patients with cervical primaries were treated with four fractions in two insertions a week apart. The median clinical target volume (CTV) was 52 cm3 (range 4e205 cm3). A median of 17 (10e25) and 19 (8e 26) needles were used in the first and second insertions, respectively. The median dose prescribed was 700 cGy (range 500e700 cGy) and the mean CTV D90 was 739 cGy (range 513e845 cGy). Mean bladder, rectum and bowel/sigmoid doses (D2cc) were 489 cGy, 422 cGy, and 269 cGy, respectively. Clinical and treatment details can be seen in Table 1.
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Table 1 Clinical and treatment characteristics Characteristics
Numbers
Clinical Patients Age, median (range) Tumor type Cervix Cervix (recurrent) Vagina Uterus (recurrent) Other Treatment Total number of BT insertions Patients with second insertion Mean HRCTV volume (cm3) Mean HRCTV D90 Median number of needles inserted (range) 1st insertion 2nd insertion Mean bladder D2cc (range) Mean rectum D2cc (range) Mean bowel D2cc (range)
48 65 (23e87) 16 2 12 13 5 73 25 52 739 cGy (513e845) 17 (10e25) 19 (8e26) 489 cGy (54e662) 422 cGy (44e451) 269 cGy (92e269)
Twenty-eight patients had radiological evidence of needle intrusion(s) to at least one pelvic organ. After planning imaging, no needle was repositioned due to organ intrusion. The dwell positions within the intruded organ at risk were not loaded. From the 73 insertions, the most commonly intruded organs were bowel and bladder, both with 18 intrusions, followed by rectum with 12 intrusions (Table 2). Figure 1 shows examples of needle intrusions to organs at risk. A total of 14 acute complications were potentially related to the P-ISBT procedure (Table 3). Nine were possibly attributed to interstitial needles: four patients developed hematuria, with three of them requiring manual bladder irrigation before Foley removal (Grade 2). The other patient was completely asymptomatic (Grade 1); three patients developed perineal infections days after the procedure (Grade 2) and required oral antibiotics; 1 patient developed a pelvic abscess 2 months after brachytherapy, requiring percutaneous drainage and intravenous antibiotics (Grade 3); one patient had vaginal bleeding during applicator removal and required transfusion (Grade 3). The patient that developed the pelvic abscess had an IB2 cervical cancer treated with salvage radiotherapy (EBRT þ ISBT) after an initial trachelectomy. This patient received intraoperative antibiotic prophylaxis but
Table 2 Radiological organ intrusion Organ
Procedure with no intrusion
Procedure with intrusion
Number of intruded needles, median (range)
Bowel Bladder Rectum
55 55 61
18 18 12
2 (1e7) 2 (1e10) 1 (1e11)
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Fig. 1. Pelvic organs intruded by interstitial catheters. Planning computed tomography axial planes showing bowel (a), bladder (b), and rectum (c) intruded by interstitial catheters after interstitial brachytherapy implant.
developed an abscess in the left pelvis 2 months after the last ISBT, requiring percutaneous abscess drainage and intravenous antibiotic. The two bacteria species cultured in this collection were Peptostreptococcus anaerobius and Finegoldia magna. No bowel or bladder needle intrusion was seen. The closest needle was 3 cm away from the location of the eventual collection. This patient also had radiological left hydroureter on CT simulation with evidence of a radiological needle intrusion at the ureter. There was no clinical sequelae related to this radiological finding and kidney function was stable throughout treatment. The hydroureter resolved on followup ultrasound postapplicator removal. No patient developed acute gastrointestinal complications and five had general clinical events: hyperkalemia during hospital stay, sensitivity reaction to hydromorphone, ventricular tachycardia, pulmonary thromboembolism and moderate emesis. No difference in infection rates was seen between patients receiving one or two ISBT insertions ( p 5 1.0) and the number of catheters inserted did not correlate with the infection rate ( p 5 0.83). Four patients developed Grade 1 or 2 hematuria. One patient had G1 hematuria with no needle seen intruding the bladder in the planning CT. Table 4 depicts the number of patients with Grade 2 hematuria in comparison with the presence of bladder intrusions and number of intruding needles.
interstitial approaches due to lack of expertise and concern of complications. In a Canadian survey, only half of the responding centers indicated that they were performing ISBT, whereas 96% of them are using 3D imageeguided planning (14). Many radiation oncologists feel that it is necessary to integrate surgical guidance (laparotomy or laparoscopy) with P-ISBT to view the insertion of catheters in real-time (8). However, this resource is not readily available, can lead to surgical complications and requires additional operative time (8,15). With the advent of 3D imageebased planning, it is possible to avoid loading needles within or close to organs and P-ISBT complications can thereby be limited. It may be that the higher rates of toxicity previously seen with 2D planning for interstitial (3) are partly associated with the limitations of outdated brachytherapy dosimetry and not from any physical needle injury. We hypothesize that this is the case and that catheter injuries are rare from interstitial brachytherapy. With mounting evidence for the integration of ISBT into treatment of gynecologic tumors, barriers and myths regarding these complications should not impede the development of such a program. This prospective study quantifies radiological organ intrusion and rates of acute complication associated with P-ISBT. Overall, 73 procedures were analyzed in this study with a total of 48 pelvic organs intruded by interstitial
Discussion
Table 3 Acute complications after perineal interstitial brachytherapy
Interstitial brachytherapy has been shown to be effective at controlling locally advanced gynecological tumors in the pelvis (1,6,12,13). Data from RetroEMBRACE suggests that the use of interstitial needles in large cervical cancers improves local control by 10% (1). Although this technique has been available for decades, there has been reluctance to
Type
Total
G1
G2
G3
G4
Gastrointestinal Urinary Vaginal bleeding Infection Clinical events
0 4 1 4 5
0 1 0 0 2
0 3 0 3 1
0 0 1 1 2
0 0 0 0 0
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Table 4 Grade 2 hematuria events vs bladder intrusion and number of needles Bladder intrusion Grade 2 hematuria
Yes
No
p-value
Yes No
3 58
15 0
0.0116
Mean (SD) number of needles in the bladder 5.3 (5.8) 0.4 (1.0)
p-value 0.0006
SD 5 standard deviation.
catheters. Only nine acute complications potentially attributed to catheter intrusions were seen, with only two Grade 3 complications. One patient had vaginal bleeding after applicator removal requiring transfusion and another developed a pelvic abscess, 2 months after interstitial insertion, requiring intravenous antibiotic treatment. Organ intrusion is a common event in patients with locally advanced or recurrent gynecological cancers treated with P-ISBT. Shah et al (16) have reported that 53% and 72% of the patients had their bladder or bowel, respectively, intruded. Nevertheless, no additional toxicities were seen in their cohort of patients if compared with previous series using real-time intraoperative guidance (laparoscopy, ultrasound, and fluoroscopy) (8). Likewise, only four of these events can be attributed by visceral intrusion of 9 patients presented with postprocedure complications associated with catheters in our series. As the risk of organ damage related with needle intrusion to pelvic organ is low, real-time image-guidance or laparoscopic guidance is not a prerequisite to developing an ISBT program. The use of intraoperative transrectal ultrasound, however, may reduce the number of pelvic organ intrusions (17) while assessing needle distribution within the high-risk CTV. Hematuria was the only complication that could be directly correlated with organ intrusion, as 3 of 18 patients with bladder intrusion were found to have Grade 2 hematuria. These patients had higher number of needles intruding the bladder in comparison with patients with bladder intrusion and no urinary bleeding. Nevertheless, most patients with bladder intrusion did not have any significant urinary complication, and those that did, had low grade hematuria not requiring transfusion. A case-report described by Rossman et al. illustrates the low morbidity rate associated with bladder intrusion, as no hematuria or other urinary complication were seen in a patient with a proven bladder intrusion by a tandem applicator (18). Needle intrusions to rectum or bowel were seen in 30 postprocedural scans. However, no postoperative gastrointestinal complications such as bowel obstruction or peritonitis were found. Previously, Lee et al. have described Grade 3e4 gastrointestinal toxicity events in patients treated with P-ISBT. However, with a median time to toxicity of 11 months, it is challenging to differentiate the cause for such events between radiation toxicity, needle trauma, or tumor progression (19). Similar to results of this study, previous cohorts (16) could not correlate GI complications with visceral needle intrusions.
For the first 27 patients in this prospective registry cohort, prophylactic intraoperative antibiotics were not used. During this period, 3 patients developed perineal skin infections requiring use of therapeutic oral antibiotic. For the subsequent 21 patients in this cohort, cefazolin 2 g was given intraoperatively and no further perineal infections were seen. Therefore, IV antibiotics seemed to decrease the risk of developing acute perineal skin infection. A variable amount of vaginal and perineal bleeding is seen immediately after applicator removal. In the vast majority of the cases, the bleeding is controlled by direct compression and/or vaginal packing. Previous authors have evaluated the role of vaginal packing after pelvic floor surgery or hysterectomy and suggested the benefit of this measure in reducing the postoperative rate of pelvic hematomas (20,21). Although there is a lack of data and expert opinion in regard to bleeding management after ISBT applicator removal (22), our group agrees that the use of vaginal packing is usually effective and of little morbidity, especially if bleeding does not decrease after direct compression. Finally, 5 patients had general clinical events during brachytherapy inpatient admission. These may have not been directly related to the brachytherapy procedure but could be in part due to factors associated with the overall disease, treatment and inpatient stay. Some patients developed sensitivity to the pain medications when used via intravenous pain pumps. Efforts to adopt an oral regimen of pain control may be helpful at avoiding complications from intravenous opioids especially for opioid na€ıve patients (9). The prospective nature of the documentation of toxicity and the independent evaluation of organ intrusion are strengths of this study. Furthermore, a board-certified body radiologist verified image assessments. These points increase the robustness of the findings and more accurately correlate visceral intrusion with acute complication. This study also has limitations. The absence of MRI images in all BT plans may have decreased the accuracy in defining OAR intrusion. Another drawback of the study is that we did not capture data on late toxicity. Finally, this is a single institution study and it is possible that serious and rare events could be appreciated with a larger cohort of patients.
Conclusion Perineal ISBT is associated with low rates of organ complications from this procedure despite occasional
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radiological catheter intrusions. No acute bowel injury from needles was found in any patients. Although acute hematuria was seen in 4 patients, no serious complications were seen and the event is self-limited. Concerns of needle complications and lack of real-time imaging or laparoscopic guidance may not be barriers to adopting this technique, which is an effective treatment for locally advanced gynecological tumors. References [1] Fokdal L, Sturdza A, Mazeron R, et al. Image guided adaptive brachytherapy with combined intracavitary and interstitial technique improves the therapeutic ratio in locally advanced cervical cancer: analysis from the retroEMBRACE study. Radiother Oncol 2016; 120:434e440. [2] H€ ockel M, M€ uller T. A new perineal template assembly for highdose-rate interstitial brachytherapy of gynecologic malignancies. Radiother Oncol 1994;31:262e264. [3] Aristizabal SA, Woolfitt B, Valencia A, et al. Interstitial parametrial implants in carcinoma of the cervix stage II-B. Int J Radiat Oncol Biol Phys 1987;13:445e450. [4] Nori D, Hilaris BS, Kim HS, et al. Interstitial irradiation in recurrent gynecological cancer. Int J Radiat Oncol Biol Phys 1981;7:1513e 1517. [5] Martinez A, Herstein P, Portnuff J. Interstitial therapy of perineal and gynecological malignancies. Int J Radiat Oncol Biol Phys 1983;9: 409e416. [6] Mendez LC, Weiss Y, D’Souza D, et al. Three-dimensional-guided perineal-based interstitial brachytherapy in cervical cancer: a systematic review of technique, local control and toxicities. Radiother Oncol 2017;123:312e318. [7] Fokdal L, Tanderup K, Nielsen SK, et al. Image and laparoscopic guided interstitial brachytherapy for locally advanced primary or recurrent gynaecological cancer using the adaptive GEC ESTRO target concept. Radiother Oncol 2011;100:473e479. [8] Monk B, Walker J, Tewari K, et al. Open Interstitial Brachytherapy for the treatment of local-regional recurrences of uterine corpus and cervix cancer after primary surgery. Gynecol Oncol 1994;52: 222e228. [9] Mendez LC, Choi S, D’Alimonte L, et al. Opioid consumption and pain in gynecological cancer patients treated with interstitial brachytherapy. Brachytherapy 2017;16:870e876.
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[10] Viswanathan AN, Beriwal S, De Los Santos JF, et al. American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part II: high-dose-rate brachytherapy. Brachytherapy 2012;11:47e52. [11] Haie-Meder C, P€otter R, Van Limbergen E, et al. Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (I): concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV. Radiother Oncol 2005;74:235e245. [12] Manuel MM, Cho LP, Catalano PJ, et al. Outcomes with image-based interstitial brachytherapy for vaginal cancer. Radiother Oncol 2016; 120:486e492. [13] Wang C, Raince J, Swamy U, et al. Clinical outcomes using imageguided interstitial brachytherapy for definitive cervical cancer patients with high-risk clinical target volumes greater than 30 cc. Brachytherapy 2018;17:392e398. [14] Taggar AS, Phan T, Traptow L, et al. Cervical cancer brachytherapy in Canada: a focus on interstitial brachytherapy utilization. Brachytherapy 2017;16:161e166. [15] Corn BW, Lanciano RM, Rosenblum N, 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;56:255e261. [16] Shah AP, Strauss JB, Gielda BT, et al. Toxicity associated with bowel or bladder puncture during gynecologic interstitial brachytherapy. Int J Radiat Oncol Biol Phys 2010;77:171e179. [17] Sharma DN, Rath GK, Thulkar S, et al. Use of transrectal ultrasound for high dose rate interstitial brachytherapy for patients of carcinoma of uterine cervix. J Gynecol Oncol 2010;21:12e17. [18] Rossmann MD, Koprowski C, Lewis G, et al. Bladder puncture from fletcher-suit tandem applicator diagnosis by pelvic ultrasound. J Ultrasound Med 1989;8:403e405. [19] Lee LJ, Viswanathan AN. Predictors of toxicity after image-guided high-dose-rate interstitial brachytherapy for gynecologic cancer. Int J Radiat Oncol Biol Phys 2012;84:1192e1197. [20] Thiagamoorthy G, Khalil A, Cardozo L, et al. The value of vaginal packing in pelvic floor surgery: a randomised double-blind study. Int Urogynecol J Pelvic Floor Dysfunct 2014;25:585e591. [21] Westermann LB, Crisp CC, Oakley SH, et al. To pack or not to pack? A randomized trial of vaginal packing after vaginal reconstructive surgery. Female Pelvic Med Reconstr Surg 2016;22:111e117. [22] Beriwal S, Demanes DJ, Erickson B, et al. American Brachytherapy Society consensus guidelines for interstitial brachytherapy for vaginal cancer. Brachytherapy 2012;11:68e75.