|Year : 2018 | Volume
| Issue : 6 | Page : 1191-1195
Dosimetric comparison of bladder, rectal, and vaginal surface doses between ovoids and cylinder-based vaginal brachytherapy in carcinoma of the endometrium
Naveen Pradeep Kumar1, Aswin Kumar1, Puthuveettil G Jayaprakash1, P Raghukumar2, Francis V James1
1 Division of Radiation Oncology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India
2 Division of Radiation Physics, Regional Cancer Centre, Thiruvananthapuram, Kerala, India
|Date of Web Publication||28-Nov-2018|
Naveen Pradeep Kumar
Division of Radiation Oncology, Regional Cancer Centre, Thiruvananthapuram - 695 006, Kerala
Source of Support: None, Conflict of Interest: None
Purpose: The study aims to estimate the differences in vaginal surface, bladder, and rectal doses when adjuvant intracavitary brachytherapy is carried out with ovoids or with vaginal cylinders, in postoperative carcinoma endometrium and to assess the difference in variability in organs at risk (OAR) doses and thereby the reproducibility of application in subsequent sittings.
Materials and Methods: Fifteen patients each received vaginal brachytherapy with ovoid and cylindrical applicators. The dose received by 0.1 cc, 1.0 cc, 2.0 cc, 5.0 cc, and 10.0 cc volumes of the OAR, namely, bladder, and rectum were analyzed using independent t-test. Interfractional variation in dose to OAR was evaluated using a two-way repeated ANOVA test. The dose received by the upper 2 cm of vagina was assessed using volume receiving 100% (V100) and dose received by 100% (D100) for documenting dose distribution to the target volume.
Results: The mean dose to rectum and bladder were significantly lesser with ovoids (P < 0.0001). This difference was seen in all volumes analyzed. V100 (99.05% vs. 67.7%, P < 0.0001) and D100 (95.70% vs. 53.08%, P < 0.0001) were significantly better with cylinders compared to ovoids. There was no statistically significant interfractional variation between sittings with either applicator.
Conclusion: The two applicators studied have different dosimetric properties conferring specific advantages and disadvantages as far as dose to OARs and target is concerned. Both applicators provide good reproducibility. The choice of applicator would ultimately depend on the clinical outcomes of these dosimetric differences which need to be prospectively analyzed.
Keywords: Carcinoma endometrium, dosimetry, ovoids, vaginal brachytherapy, vaginal cylinders
|How to cite this article:|
Kumar NP, Kumar A, Jayaprakash PG, Raghukumar P, James FV. Dosimetric comparison of bladder, rectal, and vaginal surface doses between ovoids and cylinder-based vaginal brachytherapy in carcinoma of the endometrium. J Can Res Ther 2018;14:1191-5
|How to cite this URL:|
Kumar NP, Kumar A, Jayaprakash PG, Raghukumar P, James FV. Dosimetric comparison of bladder, rectal, and vaginal surface doses between ovoids and cylinder-based vaginal brachytherapy in carcinoma of the endometrium. J Can Res Ther [serial online] 2018 [cited 2020 Sep 22];14:1191-5. Available from: http://www.cancerjournal.net/text.asp?2018/14/6/1191/231356
| > Introduction|| |
Malignancy of the corpus uteri accounts for 4.8% of all malignancies in women making it the second-most common gynecological malignancy worldwide. Approximately 90% of tumors arise within the epithelium of the uterus with majority consisting of typical endometrioid adenocarcinomas., Most women present with early-stage disease and are cured by surgery alone.,,, However, there are subsets of women who are at higher risk of relapse who may need adjuvant treatment., Many of the women with high intermediate risk of relapse used to receive pelvic external beam radiotherapy to reduce pelvic recurrence., However, the ASTEC study and PORTEC-2 study reports resulted in the use of brachytherapy alone in majority of intermediate risk patients., This has been because of lack of survival advantage of external beam radiotherapy and associated higher toxicity.,, The cohort of early endometrial cancer patients with high intermediate risk features is treated at our institute with vaginal brachytherapy alone after surgical treatment. This is to reduce vault recurrence and at the same time reduce the morbidity of treatment by reducing the dose to the organs in proximity to the vagina namely the bladder and rectum.,
Brachytherapy is delivered in three sittings each 1 week apart using either cylindrical applicators or ovoid applicators. The choice of applicator varies among consultants and according to the clinical scenario. These two applicators have inherently different dosimetric properties; and hence, there is bound to be the difference in the doses received by the vagina and the organs at risk (OAR). The difference is also probable between each sitting for a particular patient. These differences have not been well studied. The present study aims to analyze the differences in dose received by the vagina, bladder, and rectum with the different applicators used and to explore the variability in doses to the organs between individual sittings thereby documenting reproducibility for each of the two applicators.
| > Materials and Methods|| |
The study was conducted as an observational dosimetric analysis. Approval for the study was obtained from the Institutional Ethics Committee. The study population consisted of 30 women between 18 and 75 years having a World Health Organization performance status 0–2 with carcinoma endometrium who needed postoperative vaginal brachytherapy. Women with serous or clear cell histology and those with a history of previous radiotherapy, hormone therapy, chemotherapy, previous malignant disease, ulcerative colitis, or Crohn's disease were excluded. Fifteen patients treated with cylinders and 15 patients using ovoids were observed. Patients were assigned to treatment with ovoids or vaginal cylinder as per the preference of the consultant. The primary objective of the study was to estimate the differences in vaginal surface, bladder, and rectal doses when adjuvant intracavitary brachytherapy is carried out with ovoids or with vaginal cylinders, in carcinoma endometrium. The study also aimed to estimate the difference in variability in OAR doses and thereby the reproducibility of application in subsequent sittings using either ovoids or vaginal cylinder.
Written informed consent was obtained from all patients before the procedure. The patient and attendant were informed about the nature of the procedure, the possible side effects, and associated morbidity. Patients underwent brachytherapy once the vault had healed satisfactorily. An in house pretreatment bowel protocol was followed to ensure an empty rectum during treatment. Patients were advised to use a laxative starting 2 days before the scheduled day of the procedure and a cathartic rectal suppository on the day of the application. Patients were assessed clinically with an on the table per vaginal examination to ensure that the vault was healthy and to select the appropriate size of the applicator. The urinary bladder was catheterized using a Foleys catheter. The bulb was inflated with 7 cc of contrast. Patients were placed in lithotomy position and the applicators were introduced taking aseptic precautions. The largest applicator that could fit was selected as per the American Brachytherapy Society guidelines. If ovoids were used, care was taken to ensure that the medial ends touched each other so as to avoid any underdosing at the vault. Adequate posterior and anterior packing was done with saline soaked gauze. Applicator placement and packing was done by same radiation oncologist for all the three sittings to obtain maximum possible reproducibility. Then patient was simulated with computerized tomography slices of 2.5 mm thickness (300 mas, 120 kV), from 3rd lumbar vertebra to 5 cm below ischium. Computed tomography (CT) scan was taken on all three sittings. CT parameters were adjusted to reduce the metal artefact from the stainless steel applicator. Images were then transferred to the ONCENTRA planning system version 4.3 (Elekta Medical Systems, Stockholm, Sweden). The organs of interest, namely, bladder, rectum, and the vagina were contoured on the CT slices. The applicators were digitally reconstructed, dwell positions, and dwell time specified and dose prescribed. The patients were treated with high dose rate brachytherapy afterloader with Iridium-192 stepping source. After treatment, patients were observed for 1 h before discharge.
Contouring and planning procedure
The upper 2 cm of vagina was contoured as the target volume. The empty bladder and the rectum were defined as the OAR and contoured in accordance with the Radiation Therapy Oncology Group normal tissue contouring guidelines. There were no published guidelines for contouring the vagina as an organ. In a study by Chino et al. the vagina was contoured as a three-dimensional organ on CT images. A 0.4 cm fixed brush was used to outline the applicator and packing as the case may be, and expanded to include any additional visualized vagina. The same protocol was adopted to contour the upper 2 cm of vagina in the present study. The images were imported into the Oncentra treatment planning system and were converted into multi-planar reconstruction views (MPR). MPR allows one to view structures and applicator in sagittal and coronal planes within the anatomy. Applicators were then reconstructed on these images using tracking method. If vaginal cylinder was used, the dwell positions were activated alternately for the desired length to be treated. If ovoids were used, the dwell positions three, four, and five were activated for each ovoid. For vaginal cylinders, catheter points were defined 5 mm from the surface of the cylinder. For ovoids, catheter points were defined 5 mm laterally from the surface. Normalization and optimization was done to ensure 100% dose to the catheter points. Dose was prescribed to the catheter points. The dose schedule was as follows: 21 Gy at 0.5 mm from the surface of applicator, in 3 weekly fractions. If a vaginal applicator was being used, the upper 5 cm of vagina was treated. The final plan was then sent to the afterloader for treatment delivery. Treatment was delivered with an empty bladder.
Data collection and analysis
Dose-volume histograms of the OARs were generated. For each OAR, the volume dose was defined using five different criteria. The minimum dose value in a 0.1 cc, 1.0 cc, 2.0 cc, 5 cc, and 10 cc volumes receiving the highest dose were defined as D0.1 cc, D1.0 cc, D2.0 cc, D5.0 cc, and D10.0 cc, respectively. The whole organ volumes were also noted. The upper 2 cm of vagina was taken as the vaginal volume for analysis. The dose received by 100% (D100) of the total 2 cm of contoured vaginal volume and the volume receiving 100% (V100) of the prescribed dose was recorded. Differences in the mean three-dimensional volume doses to the OARs and the mean dose to target volume using the two applicators were assessed using independent t-test. A difference was considered statistically significant at P < 0.05. To assess the interfraction variability, the difference in the mean dose to 0.1 cc and 2.0 cc of rectum and bladder during each of the sittings was assessed for both types of applicators by two-way ANOVA. The difference in means were analyzed for significance. All statistical calculations were done with SPSS v. 17 (IBM Analytics, Armonk, New York, United States) and Microsoft Excel 2010.
| > Results|| |
Comparison of bladder and rectal dose
The mean rectal volume was 29.13 cc (standard deviation [SD]-9.29) for patients using vaginal cylinder and 26.88 cc (SD-10.02) for patients using ovoids. The mean bladder volume was 53.73 cc (SD-19.74) for patients with ovoids and 51.91 cc (SD-11.45) for patients with vaginal cylinder. The results of bladder and rectal doses are given in [Table 1] and [Table 2]. The D0.1 cc, D1.0 cc, D2.0 cc, D5.0 cc, and D10.0 cc for both bladder and rectum were all higher for the cohort using vaginal cylinders with a significant P < 0.0001.
|Table 1: Comparison of rectal doses between ovoids and cylindrical applicator|
Click here to view
|Table 2: Comparison of bladder doses between ovoids and cylindrical applicator|
Click here to view
Comparison of dose received by 100% and volume receiving 100% between ovoids and cylinders
V100 is defined as the percentage volume of the 2 cm of vagina contoured that received 100% of the prescribed dose (7 Gy). 67.70% (SD-11.24) of the upper 2 cm of vagina received the full prescribed dose of 7 Gy with ovoid applicators whereas 99.06% (SD-1.82) volume received the prescribed dose when a vaginal cylinder was used as given in [Table 3].
|Table 3: Comparison of volume receiving 100% between ovoids and cylindrical applicator|
Click here to view
D100 was defined as the minimum dose received by the entire 2 cm of vagina. The mean D100 for patients using ovoids was 53.08% (SD-9.67) of the prescribed dose while it was 95.70% (SD-10.57) for those who received cylinders as given in [Table 4]. The differences in V100 and D100 were found to be statistically significant with P < 0.0001.
|Table 4: Comparison of dose received by 100% between ovoid and cylindrical applicators|
Click here to view
Assessment of interfraction variability
Variability in the mean dose to 0.1 cc and 2.0 cc of rectum and bladder during each of the sittings was assessed for both types of applicators by two-way ANOVA. There was no statistically significant difference in variability between sittings when ovoids and cylinders were compared.
| > Discussion|| |
The present study is an attempt to document the differences in dosimetry during vaginal brachytherapy for postoperative carcinoma endometrium with two commonly used applicators. All patients belonged to the high intermediate risk group. Vaginal brachytherapy was delivered with dose specified at 0.5 cm from the surface of the applicators.
The vaginal mucosa is the target of postoperative adjuvant treatment in early-stage endometrial cancer. However, even in the era of image-guided brachytherapy, the vagina is not routinely contoured and the dose received by the organ has been poorly understood. The two commonly used applicators for this purpose has different dosimetric properties.
The mean doses to rectum and bladder were found to be significantly higher when cylinders were used. The difference in mean doses was consistently seen in all volumes analyzed. This can probably be attributed to the displacement of the OARs away from the high dose regions by the vaginal packing used with ovoids. Packing is however not done for cylindrical applicators. The phenomenon of axial source anisotropy also provides additional reduction in doses to the OARs which are anatomically oriented perpendicular to the longitudinal axes of the ovoids. On the other hand, a vaginal cylinder provides uniform dose circumferentially leading to uniformly higher dose to rectum and bladder.
Similar results were obtained in a dosimetric study by Zingoni et al. The study assessed the variation in doses to critical structures when different applicators were used in vaginal cuff brachytherapy. The average percentage doses to the OAR were lower using the ovoids when compared to cylinders: rectum (78.4 vs. 84.8) and bladder (65.1 vs. 67.2).
The minimum dose received by the entire target volume was closer to the prescribed dose with vaginal cylinders than with ovoids. The D100 for ovoids was 53.8%. In other words, there were areas within the target volume that received doses as low as 53.8% of the prescribed dose. Similar results were obtained when the volume of vagina receiving the prescribed dose was analyzed (V100). Only 67.7% received the prescribed dose with ovoids whereas 99.06% received the prescribed dose with cylinders. These two findings can probably be explained by the irregular contour of the vaginal sleeve brought about by the applicator placement and the packing while the isodose distribution follows a regular pattern. This could result in geometric underdosing. The vaginal cylinder, on the other hand, provides a uniform shape and surface to the vaginal mucosa to which a more homogenous dose can be delivered. This reflects in the high D100 and V100 with cylinders.
In a comparative dosimetric analysis of colpostats (ovoids) and cylinders by Kim et al., axial anisotropy produced higher percentage depth doses in the anterior-posterior and lateral directions for the cylinder. Dose fall-off along the longitudinal patient axis was less pronounced for the colpostats. When vaginal packing at the anterior and posterior surface of the colpostats was increased from 0 to 5, 10, and then 15 mm, the corresponding vaginal dose decreased from 97% of the prescription dose to 60%, 39%, and 26%, respectively. The study concluded that vaginal packing should be applied with great care to avoid generating cold spots along the upper vaginal surface and vaginal cuff. The low dose areas seen in the present study when ovoids were used could be explained thus.
The inter fraction variability assessment did not show any significant advantage with either of the two applicators. In this study, both applicators were found to have little interfraction variability, and there was nothing to choose between them. Both of them produced reproducible dose distributions to the OARs during each sitting.
One dosimetric study by Garipagaoglu et al. evaluated the interfractional dosimetric differences in International Commission on Radiation Units and Measurements bladder and rectal point dose during vaginal cuff irradiation with ovoids. The study did not find any significant interfractional variation in the doses to rectal and bladder points. Their results parallel the results of the present study even though the above-mentioned study used only a single type of applicator.
Inhomogeneity of dose distribution with the use of vaginal ovoids is expected when it is used with packing, because this technique has been adapted from brachytherapy for cervical cancer. When ovoids and tandem are used for cervical cancer, the dose prescription is to Point A which is located 2 cm superior to the external os and 2 cm lateral to the uterine canal. The whole of vaginal mucosa comes within the treated volume regardless of the geometric variations brought about by vaginal packing. Hence, vagina receives adequate dose. However, when ovoids are used in the adjuvant setting of endometrial cancer after hysterectomy, the prescription dose point is at 0.5 cm from the vaginal surface, and thus, it is much closer to the radiation source than point A. In addition, due to the absence of uterine canal, no central tandem is inserted. Due to these differences, vaginal packing plays an important role in determining the vaginal dose in the postoperative treatment of endometrial cancer. Although the clinical implication of these dose reductions is unclear, the potential for local recurrence remains a concern. On the other hand, the advantage with packing is that the doses to rectum and bladder can be reduced. Unlike ovoids, vaginal cylinders have been specially designed to produce good vaginal mucosal contact. Therefore the dose received by the vaginal mucosa will be more uniform with vaginal cylinders.
The current PORTEC-4 trial will address whether less dose is adequate for vaginal brachytherapy when 5 and 7 Gy are compared. If 5 Gy is found sufficient, the doses to rectum and bladder will be significantly lower.
| > Conclusion|| |
The present study demonstrated that the use of vaginal cylinders resulted in a more homogeneous dose to the vault of vagina at the cost of a higher dose to the OAR while treatment with ovoids resulted in a less homogeneous dose to the vault with lower dose to the OAR. Both applicators have good reproducibility if applicator selection and placement is carefully done.
Each of the two applicators differs in their dosimetric properties and selection of one over the other can only be established based on the clinical impact these dosimetric differences would bring to OARs and target volume. The clinical implications are at present unclear and would require a large randomized study with subjects followed up over a long period to assess toxicity and disease control.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Zaino RJ, Kurman R, Herbold D, Gliedman J, Bundy BN, Voet R, et al.
The significance of squamous differentiation in endometrial carcinoma. Data from a Gynecologic Oncology Group Study. Cancer 1991;68:2293-302.
Gusberg SB. Virulence factors in endometrial cancer. Cancer 1993;71:1464-6.
Sorosky JI. Endometrial cancer. Obstet Gynecol 2012;120:383-7.
ASTEC/EN.5 Study Group, Blake P, Swart AM, Orton J, Kitchener H, Whelan T, et al.
Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): Pooled trial results, systematic review, and meta-analysis. Lancet 2009;373:137-46.
Creutzberg CL, van Putten WL, Koper PC, Lybeert ML, Jobsen JJ, Wárlám-Rodenhuis CC, et al.
Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: Multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet 2000;355:1404-11.
Sorbe B, Nordström B, Mäenpää J, Kuhelj J, Kuhelj D, Okkan S, et al.
Intravaginal brachytherapy in FIGO stage I low-risk endometrial cancer: A controlled randomized study. Int J Gynecol Cancer 2009;19:873-8.
Creutzberg CL, van Stiphout RG, Nout RA, Lutgens LC, Jürgenliemk-Schulz IM, Jobsen JJ, et al.
Nomograms for prediction of outcome with or without adjuvant radiation therapy for patients with endometrial cancer: A pooled analysis of PORTEC-1 and PORTEC-2 trials. Int J Radiat Oncol Biol Phys 2015;91:530-9.
Bendifallah S, Canlorbe G, Collinet P, Arsène E, Huguet F, Coutant C, et al.
Just how accurate are the major risk stratification systems for early-stage endometrial cancer? Br J Cancer 2015;112:793-801.
Keys HM, Roberts JA, Brunetto VL, Zaino RJ, Spirtos NM, Bloss JD, et al.
A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: A Gynecologic Oncology Group study. Gynecol Oncol 2004;92:744-51.
Nout RA, Smit VT, Putter H, Jürgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, et al.
Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): An open-label, non-inferiority, randomised trial. Lancet 2010;375:816-23.
Creutzberg CL, van Putten WL, Koper PC, Lybeert ML, Jobsen JJ, Wárlám-Rodenhuis CC, et al.
The morbidity of treatment for patients with stage I endometrial cancer: Results from a randomized trial. Int J Radiat Oncol Biol Phys 2001;51:1246-55.
Jhingran A, Burke TW, Eifel PJ. Definitive radiotherapy for patients with isolated vaginal recurrence of endometrial carcinoma after hysterectomy. Int J Radiat Oncol Biol Phys 2003;56:1366-72.
Creutzberg CL, Nout RA, Lybeert ML, Wárlám-Rodenhuis CC, Jobsen JJ, Mens JW, et al.
Fifteen-year radiotherapy outcomes of the randomized PORTEC-1 trial for endometrial carcinoma. Int J Radiat Oncol Biol Phys 2011;81:e631-8.
Nag S, Erickson B, Parikh S, Gupta N, Varia M, Glasgow G, et al.
The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the endometrium. Int J Radiat Oncol Biol Phys 2000;48:779-90.
Gay HA, Barthold HJ, O'Meara E, Bosch WR, El Naqa I, Al-Lozi R, et al.
Pelvic normal tissue contouring guidelines for radiation therapy: A Radiation Therapy Oncology Group consensus panel atlas. Int J Radiat Oncol Biol Phys 2012;83:e353-62.
Chino J, Meltsner S, Yang Y, Steffey B, Cai J, Craciunescu O, et al
. Vaginal dose and toxicity with image-guided brachytherapy. Int J Radiat Oncol Biol Phys 2013;2:S31.
Zingoni A, Bonetta A, D'Abbiero N, Armaroli L, di Fisica Sanitaria S, Cremona H, et al
. Influence of applicator shape on the dose to rectum and bladder in vaginal cuff brachytherapy. Radiother Oncol 1998;47:82.
Kim RY, Pareek P, Duan J, Murshed H, Brezovich I. Postoperative intravaginal brachytherapy for endometrial cancer; dosimetric analysis of vaginal colpostats and cylinder applicators. Brachytherapy 2002;1:138-44.
Garipagaoglu M, Tuncel N, Köseoglu FG, Gülkesen H, Kizildag AU, Toy A, et al.
Geometric and dosimetric variations of ICRU bladder and rectum reference points in vaginal cuff brachytherapy using ovoids. Int J Radiat Oncol Biol Phys 2004;58:1607-15.
[Table 1], [Table 2], [Table 3], [Table 4]