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ORIGINAL ARTICLE
Year : 2014  |  Volume : 10  |  Issue : 1  |  Page : 153-158

Dosimetric comparison of vaginal vault ovoid brachytherapy versus intensity-modulated radiation therapy plans in postoperative patients of cervical carcinoma following whole pelvic radiotherapy


Department of Radiotherapy and Oncology, Regional Cancer Centre, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, India

Date of Web Publication23-Apr-2014

Correspondence Address:
Divya Khosla
Department of Radiotherapy and Oncology, Regional Cancer Centre, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.131449

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 > Abstract 

Introduction: Dosimetric study to compare high dose rate (HDR) vaginal vault ovoid brachytherapy plan versus intensity-modulated radiation therapy (IMRT) boost plan for doses delivered to target volume and organs at risk (OAR) in postoperative patients of cervical carcinoma following whole pelvic radiotherapy (WPRT).
Materials and Methods: Fifteen postoperative patients of cervical carcinoma suitable for vaginal ovoid brachytherapy following WPRT of 46 Gy/23 fractions/4.5 weeks were included. All were treated with brachytherapy (two sessions of 8.5 Gy each). The equivalent dose for IMRT was calculated by computing biologically effective dose of brachytherapy by linear quadratic model. Dose of brachytherapy (two sessions of 8.5 Gy) was equivalent to IMRT dose of 26 Gy/13 fractions. Doses to target volume and OAR were compared between HDR and IMRT plans.
Results: Target volume was well covered with both HDR and IMRT plans, but dose with brachytherapy was much higher (P < 0.05). Mean doses, doses to 0.1, 1, 2, and 5cc, 1/3 rd , 1/2, and 2/3 rd volume of bladder and rectum were significantly lower with HDR plans.
Conclusion: In postoperative patients of cervical carcinoma, HDR brachytherapy following WPRT appears to be better than IMRT for tumor coverage and reducing dose to critical organs.

 > Abstract in Chinese 

宫颈癌术后全盆腔放疗后阴道穹窿卵球形的近距离放射治疗与调强放射治疗计划的剂量学比较
引言:用剂量学研究比较宫颈癌术后全盆腔放疗(WPRT)后阴道穹窿卵球形的高剂量率(HDR)近距离放射治疗计划与调强放射治疗(IMRT)计划传递到靶区和危及器官(OAR)的剂量。
材料和方法:包含了15例宫颈癌术后病例,均适用全盆腔放疗(46Gy / 23F/ 4.5w)+阴道卵球形近距离放疗(每次8.5Gy,共2次)。通过线性二次模型计算近距离照射的生物有效剂量的调强放疗等效剂量。近距离照射的剂量(2次8.5Gy)相当于调强剂量的26Gy/ 13F。将近距离放疗和调强计划的靶区和危险器官的剂量进行比较。
结果:近距离放疗和调强放疗计划均很好地覆盖靶区,但(靶区内)近距离放疗剂量高出很多(P<0.05)。平均剂量,0.1、1、2和5cc,1/3,1/2,2/3体积的膀胱和直肠剂量在近距离放疗计划中明显降低。
结论:对宫颈癌患者术后,全盆腔放疗+HDR近距离放疗优于调强放疗,无论在肿瘤覆盖上还是危及器官剂量减少上。
关键词:宫颈癌,高剂量率,调强放射治疗,术后,阴道穹窿卵球形近距离放射治疗


Keywords: Cervical carcinoma, high dose rate, intensity-modulated radiation therapy, postoperative, vaginal vault ovoid brachytherapy


How to cite this article:
Khosla D, Patel FD, Oinam AS, Tomar P, Sharma SC. Dosimetric comparison of vaginal vault ovoid brachytherapy versus intensity-modulated radiation therapy plans in postoperative patients of cervical carcinoma following whole pelvic radiotherapy. J Can Res Ther 2014;10:153-8

How to cite this URL:
Khosla D, Patel FD, Oinam AS, Tomar P, Sharma SC. Dosimetric comparison of vaginal vault ovoid brachytherapy versus intensity-modulated radiation therapy plans in postoperative patients of cervical carcinoma following whole pelvic radiotherapy. J Can Res Ther [serial online] 2014 [cited 2019 Sep 17];10:153-8. Available from: http://www.cancerjournal.net/text.asp?2014/10/1/153/131449


 > Introduction Top


Cervical cancer is the most common malignancy affecting women in India. [1] The treatment of choice for early stage disease is radical surgery or radical radiotherapy. Radiotherapy is an integral component in the management of patients undergoing incomplete surgery and is also beneficial as an adjuvant treatment after hysterectomy for patients with high risk features. [2]

Whole pelvic radiotherapy (WPRT) followed by a boost to the tumor site is the standard of practice for the radiotherapeutic management of patients with microscopic residual disease after inadvertent surgery. WPRT is used to treat the tumor bed and the regional lymph nodes, whereas brachytherapy is used to boost the vaginal cuff as recurrences due to microscopic residual disease are mainly located in vaginal vault and upper vagina.

Intensity-modulated radiation therapy (IMRT) is increasingly receiving attention in the management of gynecologic malignancies, because dose can be sculpted to shape of planning target volume (PTV) while minimizing the dose to surrounding normal tissues. Interest in the application of IMRT for gynecologic cancer has been increasingly supported by retrospective analyses reporting favorable toxicity rates compared with conventional techniques. Most attention has focused on the use of IMRT to deliver WPRT in these patients. [3],[4] Also proposed are the potential replacements of brachytherapy with IMRT in cervical cancer patients [5],[6] and simultaneously integrated boost with IMRT for locally advanced gynecologic cancers that may not be amenable to brachytherapy for anatomic or medical reasons. [7]

At our institute after WPRT dose of 46 Gy in 23 fractions, high dose rate (HDR) vaginal vault ovoid brachytherapy is delivered at 0.5 cm from surface of ovoids in two fractions of 8.5 Gy each at one week apart. This prospective study was carried out to test if IMRT can be an alternative to HDR vaginal vault ovoid brachytherapy after WPRT. We generated HDR and IMRT plans and further compared the two plans for doses delivered to target structures and critical normal tissues in postoperative patients of cervical carcinoma following WPRT.


 > Materials and Methods Top


Fifteen histological proven postoperative cases of cervical carcinoma referred to our institute after inadvertent hysterectomy and who were suitable for vaginal vault ovoid brachytherapy after being treated with WPRT at our institute were enrolled in this study from July 2007 to August 2010. Eleven patients had positive surgical margins and four patients had deep stromal invasion. Out of 15, 8 patients also had lymph vascular space invasion. All patients signed a written informed consent prior to participation in the study. Ethical clearance for the conduction of the study was obtained from the Institutional Ethics Committee prior to the inception of the study.

All patients received a combination of WPRT (to treat the original tumor site and the regional lymph nodes) and HDR vaginal vault ovoid brachytherapy (to boost the vaginal cuff). The prescribed WPRT dose in all patients was 46 Gy in 2 Gy daily fractions. Concurrent chemotherapy was given in eight patients. For WPRT, treatment was executed by four-field box technique on linear accelerator with 6 MV or 15 MV energies. After completion of WPRT, patients were assessed for vaginal vault brachytherapy.

All planning computed tomography (CT) were helical scans with 2.5 mm slices, acquired in the Light Speed VFX-16 CT simulator (GE Medical Systems, Waukesha, WI, USA). Two series of CT scans were done for each patient - one for IMRT plan and second with HDR MicroSelectron vaginal ovoid applicator (Nucletron, Veenendaal, The Netherlands) in situ without packing (as per institutional protocol) for HDR plan. Planning for vaginal vault ovoid HDR brachytherapy was done on Oncentra MasterPlan treatment planning system (Nucletron, Veenendaal, The Netherlands) before treatment execution and IMRT planning was done on Eclipse treatment planning system version 8.6 (Varian Medical Systems, Palo Alto, CA, USA). Patient was then shifted to HDR room for treatment, where vaginal vault ovoid brachytherapy was carried out. Vault ovoid brachytherapy was delivered by remote-controlled afterloading technique using MicroSelectron HDR V3 (Nucletron, Veenendaal, The Netherlands) which contains single iridium-192 source with maximum activity of 10 curie. The dose delivered was 8.5 Gy at 0.5 cm from vaginal ovoids. The treatment was repeated after one week to give a total brachytherapy dose of 17 Gy at 0.5 cm from vaginal mucosa in two fractions.

Contouring was done both for brachytherapy and IMRT planning. Target volumes were contoured on individual axial CT slices for each patient for both HDR and IMRT plans which included subclinical microscopic disease. Thus, the clinical target volume (CTV) included vault and the upper 3 cm of vagina. The bladder and rectum were contoured as entire organ. The rectum was contoured and delineated from anal margin to sigmoid flexure. The CTV is the volume which must receive adequate dose to achieve the therapeutic aim. In brachytherapy, the applicator is in situ and moves together with the target volume; hence, no extra margin is required, and therefore, PTV was not generated. However in IMRT, to account for organ motion and set up uncertainty, CTV was uniformly expanded by 1 cm in anterior-posterior, lateral, and craniocaudal directions (as per institutional protocol) to create PTV to which dose was prescribed to ensure that the prescribed dose is actually delivered to the CTV. The dose of 26 Gy in 13 fractions was prescribed to PTV in IMRT. As there is no concept of PTV in brachytherapy plans, so the absorbed dose in CTV was compared between HDR and IMRT plans.

The equivalent dose for IMRT was calculated by computing biologically effective dose (BED) of brachytherapy dose by linear quadratic model and equating it for 2 Gy per fraction. Hence, dose of brachytherapy (2 × 8.5 Gy) was equivalent to IMRT dose of 26 Gy/13#. Thus, total EQD2 (equivalent dose in 2 Gy per fraction) of WPRT and vaginal vault ovoid brachytherapy/IMRT was equal to 72 Gy.

Organs at risk (OAR) dose constraints were specified for IMRT planning so that 20% and 50% volume of rectum received doses ≤14 Gy and <10 Gy, respectively, and in case of bladder, 20% and 50% volume received doses ≤20 Gy and <16 Gy, respectively. Seven to nine field coplanar IMRT plans were generated for each patient. Plans were evaluated both quantitatively (by analyzing DVH) and qualitatively (by visually inspecting isodose curves). Plans were inspected for conformity of 95% isodose curve to PTV in IMRT and 100% isodose curve to CTV in HDR planning.

HDR and IMRT plans were evaluated and doses to target volume and OAR were compared. Mean doses, doses to 0.1, 1, 2, and 5 cc bladder and rectum were compared between HDR and IMRT plans. With IMRT planning and dose delivery, there is a need for more accurate information about the partial volumes of critical tissues receiving variable dose levels because accurate volumetric and dosimetric measurements of critical tissues may ultimately be correlated with complications. Therefore, doses to 1/3 rd , 1/2, and 2/3 rd volume of bladder and rectum were also compared between HDR and IMRT. BED and EQD2 were also calculated and compared for HDR and IMRT bladder and rectal doses. Integral doses were calculated separately for HDR and IMRT plans.

Mean and standard deviation were calculated. Comparison of means was done for each group. HDR and IMRT bladder and rectum doses were compared using Wilcoxon signed rank test. Integral doses were compared between two groups using Mann-Whitney U test. All tests were two-tailed and P < 0.05 was taken as statistically significant.


 > Results Top


In HDR, target volume was covered with 150%-200% isodose curves. Significant areas within target volume received average maximum target dose of 374% ranging from 260% to 410%, which signifies that target volume was well covered and received a high dose with HDR. In brachytherapy, the mean D 90 (minimum dose delivered to 90% of the CTV) of 15 patients was 108%. In IMRT, the PTV was covered with 95% isodose curve and CTV was covered with 100% isodose curve. Though the target volume was well covered with both HDR and IMRT plans, dose with brachytherapy was much higher than IMRT (P < 0.05) which could be more favorable for tumor control.

Mean doses to bladder and rectum were lower with HDR as compared to IMRT plans (2.95 Gy vs. 11.69 Gy for bladder and 5.84 Gy vs. 12.56 Gy for rectum, respectively, P < 0.05). BED was calculated for HDR and IMRT bladder and rectum doses for each patient (by keeping α/β ratio of 3). BED was more for IMRT as compared to HDR for mean doses to bladder and rectum (15.45 vs. 4.46 Gy 3 for bladder and 16.53 vs. 11.59 Gy 3 for rectum, P = 0.001, respectively) [Figure 1]. Similarly, EQD2 was also calculated for HDR and compared with IMRT boost (given as 2 Gy per fraction). Mean EQD2 was more for IMRT as compared to HDR for mean doses to bladder and rectum (11.69 vs. 2.67 Gy for bladder and 12.56 vs. 6.94 Gy for rectum, P = 0.001, respectively).
Figure 1: Box plot curve showing comparison of BED of mean doses to bladder and rectum between HDR and IMRT

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Doses to 0.1, 1, 2, and 5 cc bladder and rectum were significantly lower with HDR plans as compared to IMRT plans (P < 0.05), respectively [Table 1]. The mean BED for 1, 2, and 5 cc volume of bladder was significantly more with IMRT as compared to HDR (45.08, 44.67, 43.76 Gy 3 vs . 28.16, 23.61, 17.68 Gy 3 , P < 0.05, respectively). While mean BED for 0.1 cc was also more with IMRT as compared to HDR (45.81 Gy 3 vs . 42.54 Gy 3 ) but was statistically not significant (P = 0.36). Similarly, mean EQD2 was more with IMRT as compared to HDR for doses to 0.1, 1, 2, and 5 cc volume of bladder (27.04, 26.74, 26.57, 26.17 Gy vs. 25.47, 16.86, 14.13, 10.58 Gy, respectively). It was statistically significant for 1, 2, and 5 cc (P < 0.05) but not for 0.1 cc (P = 0.42). The mean BED for 0.1 and 1 cc volume of rectum was more with HDR (75.22 and 47.90 Gy 3 ) as compared to IMRT (45.02 and 44.09 Gy 3 ), respectively. It was statistically significant for 0.1 cc (P = 0.001) but not for 1 cc (P = 0.07). The mean BED for 2 and 5cc was significantly more with IMRT (42.16 and 39.03 Gy 3 ) as compared to HDR (39.28 and 28.81 Gy 3 ) (P < 0.05), respectively. Mean EQD2 was more with HDR as compared to IMRT for dose to 0.1 and 1 cc volume of rectum (45.04, 28.67 Gy vs. 26.71, 26.32 Gy), respectively. It was statistically significant for 0.1 cc (P = 0.001) but not for 1 cc (P = 0.06). Mean EQD2 was more with IMRT as compared to HDR for dose to 2 and 5 cc volume of rectum (25.98, 24.10 Gy vs. 23.52, 17.25 Gy, P = 0.01 for 2 cc and P = 0.001 for 5 cc rectum).
Table 1: Comparison of doses to 0.1, 1, 2, and 5cc volumes of bladder and rectum between HDR and IMRT

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Another parameter which was compared was doses to 1/3 rd , 1/2, and 2/3 rd volume of critical organs. Doses to 1/3 rd , 1/2, and 2/3 rd volume of bladder and rectum were significantly lower with HDR plans as compared to IMRT plans [P < 0.05; [Table 2]]. The mean BED for volume 1/3 rd , 1/2, and 2/3 rd of bladder and rectum was significantly lower with HDR (4.15, 3.11, 2.04 Gy 3 for bladder and 13.01, 8.58, 5.88 Gy 3 for rectum) as compared to IMRT (20.24, 13.80, 9.16 Gy 3 for bladder and 23.37, 16.46, 12.60 Gy 3 for rectum) (P < 0.05). Mean EQD2 for volume 1/3 rd , 1/2, and 2/3 rd of bladder and rectum was significantly lower with HDR (2.49, 1.86, 1.22 Gy for bladder and 7.79, 5.13, 3.52 Gy for rectum) as compared to IMRT (14.53, 10.48, 7.22 Gy for bladder and 16.35, 12.37, 9.87 Gy for rectum) (P < 0.05). Thus, significantly lesser doses were delivered to OAR with HDR as there is sharp fall off of dose with brachytherapy whereas with IMRT dose to OAR is more homogenous as the beams are delivered from different directions.

Cumulative EQD2 was calculated for WPRT plus HDR and WPRT plus IMRT boost, as shown in [Table 3].
Table 2: Comparison of doses to 1/3rd, 1/2, and 2/3rd volume of bladder and rectum between HDR and IMRT

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Table 3: Cumulative EQD2 with WPRT and HDR/IMRT boost

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Whole-body dose may be a concern when treating with IMRT. So, integral doses for HDR and IMRT were calculated for all the patients. Mean (± standard deviation) of integral doses of 15 patients was 0.1798 (±0.011) J with HDR plans and 1.093 (±0.13) J with IMRT plans. Mean integral dose was significantly less with HDR as compared to IMRT (P < 0.05).


 > Discussion Top


Cervical cancer is the most common malignancy affecting women in India and the performance of inadequate hysterectomy is not uncommon owing to the lack of proper investigative evaluations and/or a lack of expertise in primary care hospitals. At our institute, being one of the major referral centers in India, many patients are referred following inadvertent surgery. These patients are treated with WPRT followed by boost with vaginal vault ovoid brachytherapy if suitable or supplementary radiotherapy if there is gross local disease not likely to be covered by brachytherapy. HDR vaginal vault brachytherapy is an established modality after WPRT for postoperative patients of carcinoma cervix following simple hysterectomy. Ampil et al. described results in 44 patients who received postoperative irradiation after hysterectomy for stage IB or IIA cervical cancer (15 patients were treated with radical hysterectomy). They suggested that the combination of EBRT with additional vaginal cuff irradiation is recommended for patients treated with simple hysterectomy. [8] The feasibility of IMRT boost as an alternative to HDR vaginal vault ovoid brachytherapy after WPRT in postoperative patients of cervical carcinoma treated with inadvertent hysterectomy is investigated in this study. We conducted this study by comparing the IMRT and HDR plans performed separately on two series of CT scan taken for each patient.

Aydogan et al. [9] evaluated the role of IMRT as an alternative to HDR brachytherapy in the treatment of the vagina in postoperative early endometrial cancer patients after surgery. In this study, comparison between brachytherapy and IMRT in endometrial cancer was done by keeping the same dose schedule for both the treatment modalities, i.e., 7 Gy ×3 fractions each one week apart. The maximum and mean bladder doses were comparable between HDR and IMRT. However, IMRT provided relatively lower rectal doses than HDR and with PTV coverage comparable with HDR. In our study, we compared between brachytherapy and IMRT boost plans in postoperative patients of carcinoma cervix treated with WPRT. For comparison of doses between brachytherapy and IMRT, BED based on concept of linear quadratic model was calculated and number and dose per fraction was calculated for IMRT. BED of Brachytherapy (8.5 Gy in two sessions) came out to be 31.45 Gy . Using the same BED value, we calculated the equivalent IMRT dose to be delivered in 2 Gy per fraction. The equivalent dose for IMRT was calculated to be 26 Gy/13#/2.3 weeks.

Target volume was well covered with both HDR and IMRT plans. but dose with brachytherapy was much higher than IMRT which could be more favorable for tumor control. Pieters et al. [10] carried out comparison of biologically equivalent dose-volume parameters for the treatment of prostate cancer with concomitant boost IMRT versus IMRT combined with pulsed dose rate (PDR) or HDR brachytherapy boost. While comparing PDR or HDR brachytherapy boost with IMRT boost in carcinoma prostate, it was seen that prostate receives at least 7-13 Gy more dose with brachytherapy. Rectum and bladder doses for IMRT-only are significantly higher (P < 0.001). Because of the high doses within an implant, the dose in 50% of the prostate volume is much higher with the brachytherapy modalities than IMRT-only, which may have clinical consequences. With brachytherapy, the doses to the OAR are lower or similar to IMRT-only. So, he concluded that dose escalation for prostate tumors is more easily achieved with brachytherapy than with IMRT alone. Therefore, brachytherapy might be the preferred modality to achieve further dose escalation.

In treatment of postoperative patients of cervical cancer, bladder and rectum are the primary critical organs of concern. In our study, mean dose to rectum and bladder was significantly lower with HDR vaginal vault ovoid brachytherapy. Small organ volumes irradiated to high dose seem to be of major interest. As there is rapid dose fall-off near the sources, the dose assessment has to refer to one (or more) defined dose point (s) in these limited volumes. For OAR, the minimum dose in the most irradiated tissue volume is recommended for reporting: 0.1, 1, and 2 cc; optional 5 and 10 cc by GEC ESTRO. [11] Keeping this in mind, we have also compared doses to 0.1, 1, 2, and 5 cc volume of bladder and rectum between HDR and IMRT. On comparing, it was seen that mean doses to 0.1, 1, 2, and 5 cc volume of bladder and rectum were significantly less with HDR vaginal vault ovoid brachytherapy as compared to IMRT (P < 0.05).

In clinical radiotherapy, the total dose that can be tolerated depends on the volume of tissue irradiated. With three-dimensional treatment planning and dose delivery, there is a need for more accurate information about the partial volumes of critical tissues receiving variable dose levels because accurate volumetric and dosimetric measurements of critical tissues may ultimately be correlated with complications. [12] Therefore, doses to 1/3 rd , 1/2, and 2/3 rd volume of bladder, rectum, and intestines were also compared between HDR and IMRT. It was seen that significantly lesser doses were delivered to OAR with HDR as there is sharp fall off dose with brachytherapy, whereas with IMRT the dose to OAR is more homogenous as beams are delivered from different directions.

Above parameters, which are compared between HDR and IMRT, represent physical doses to critical organs. It was seen that physical doses to critical organs were more with IMRT as compared to HDR brachytherapy. Direct comparison of physical doses may not be relevant as far as biological end points like late effects are concerned. So, we have also calculated and compared the BED and EQD2 for bladder and rectal doses for HDR and IMRT. Linear quadratic model was applied and BED was calculated for OAR with uniform α/β value of 3 Gy. Mean BED and EQD2 were less for HDR for mean doses to bladder and rectum (P < 0.05). Also mean BED and EQD2 for 0.1, 1, 2, and 5 cc volume of bladder were more with IMRT as compared to HDR. The mean BED and EQD2 for 0.1 and 1 cc volume of rectum were more with HDR as compared to IMRT. It was statistically significant for 0.1 but not for 1 cc. Mean BED and EQD2 were significantly more with IMRT as compared to HDR for doses to 2 and 5 cc volume of rectum. In clinical routine, the minimum dose to most exposed 2 cc organ volume is taken as parameter for treatment plan optimization and comparison. [13] In our study, both physical and biologically weighted dose to 2 cc volume of bladder and rectum were significantly lower with HDR. The mean BED and EQD2 for volume 1/3 rd , 1/2, and 2/3 rd of bladder and rectum were significantly lower for HDR as compared to IMRT (P < 0.05 in all).

In comparison of two treatment techniques, HDR plans resulted in significantly less integral dose as compared to IMRT (P < 0.05). Hall and Wuu [14] estimated that the secondary cancer risk would increase from 1% for conventional radiation therapy to 1.75% for IMRT. Based on these, we can say that HDR brachytherapy may provide significant advantages because it delivers very high dose to the target volume, reduces the bladder and rectum doses, and also significantly lower integral dose as compared to IMRT.

WPRT followed by HDR vaginal vault ovoid brachytherapy is an established modality for treatment in patients of cervical carcinoma with inadvertent surgery. The target volume was well covered with both HDR brachytherapy and IMRT plans, but dose with brachytherapy is much higher than IMRT which could be more favorable for tumor control. Doses to rectum and bladder are lower with HDR brachytherapy than with IMRT, illustrating better sparing of surrounding OAR for brachytherapy. Whole body dose may be a concern when treating with IMRT, which results in larger volumes that are irradiated to low doses.

This study was done for patients with inadvertent hysterectomy and postsurgical positive margins who were treated with WPRT followed by vaginal vault ovoid brachytherapy. In this group of patients, HDR brachytherapy appears to be better than IMRT for tumor coverage as a very high dose can be given locally and dose to critical organs can be reduced.

 
 > References Top

1.Parkin DM, Pisani P, Ferlay J. Estimates of the worldwide incidence of 25 major cancers in 1990. Int J Cancer 1999;80:827-41.  Back to cited text no. 1
    
2.Ahamad A, Jhingran A. New radiation techniques in gynecological cancer. Int J Gynecol Cancer 2004;14:569-79.  Back to cited text no. 2
    
3.Mundt AJ, Lujan AE, Rotmensch J, Waggoner SE, Yamada SD, Fleming G, et al. Intensity-modulated whole pelvic radiotherapy in women with gynecologic malignancies. Int J Radiat Oncol Biol Phys 2002;52:1330-7.  Back to cited text no. 3
    
4.Roeske JC, Lujan A, Rotmensch J, Waggoner SE, Yamada D, Mundt AJ. Intensity-modulated whole pelvic radiation therapy in patients with gynecologic malignancies. Int J Radiat Oncol Biol Phys 2000;48:1613-21.  Back to cited text no. 4
    
5.Wahab SH, Malyapa RS, Mutic S, Grigsby PW, Deasy JO, Miller TR, et al. A treatment planning study comparing HDR and AGIMRT for cervical cancer. Med Phys 2004;31:734-43.  Back to cited text no. 5
    
6.Roeske JC, Lujan AE, Rotmensch J, Mundt AJ. A feasibility study of IMRT for the treatment of cervical cancer patients unable to receive intracavitary brachytherapy. In: Enderle JD, editor. 22 nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society. Vol. 1. Los Alamitos, CA: EEE Publications; 2000. p. 463-5.  Back to cited text no. 6
    
7.Guerrero M, Li XA, Ma L, Linder J, Deyoung C, Erickson B. Simultaneous integrated intensity-modulated radiotherapy boost for locally advanced gynecological cancer: Radiobiological and dosimetric considerations. Int J Radiat Oncol Biol Phys 2005;62:933-9.  Back to cited text no. 7
    
8.Ampil V, Datta R, Datta S. Elective postoperative external radiotherapy after hysterectomy in early- stage Carcinoma of the cervix. Cancer 1987;60:280-8.  Back to cited text no. 8
    
9.Aydogan B, Mundt AJ, Smith BD, Mell LK, Wang S, Sutton H, et al. A Dosimetric analysis of intensity-modulated radiation therapy (IMRT) as an alternative to adjuvant high dose rate (HDR) brachytherapy in early endometrial cancer patients. Int J Radiat Oncol Biol Phys 2006;65:266-73.  Back to cited text no. 9
    
10.Pieters BR, van de Kamer JB, van Herten YR, van Wieringen N, D′Olieslager GM, van der Heide UA, et al. Comparison of biologically equivalent dose-volume parameters for the treatment of prostate cancer with concomitant boost IMRT versus IMRT combined with brachytherapy. Radiother Oncol 2008;88:46-52.  Back to cited text no. 10
    
11.Potter R, Haie-Meder C, Van Limbergen E, Barillot I, De Brabandere M, Dimopoulos J, et al. Recommendations from gynecological (GYN) GEC ESTRO working group (II): Concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy-3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, radiobiology. Radiother Oncol 2006;78:67-77.  Back to cited text no. 11
    
12.Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991;21:109-22.  Back to cited text no. 12
    
13.Potter R, Kirisits C, Fidarova EF, Dimopoulos JC, Berger D, Tanderup K, et al. Present status and future of high-precision image guided adaptive brachytherapy for cervix carcinoma. Acta Oncol 2008;47:1325-36.  Back to cited text no. 13
    
14.Hall EJ, Wuu CS. Radiation-induced second cancers: The impact of 3D-CRT and IMRT. Int J Radiat Oncol Biol Phys 2003;56:83-8.  Back to cited text no. 14
    


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