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British Journal of Radiology (2003) 76, 719-725
© 2003 British Institute of Radiology
doi: 10.1259/bjr/15634046
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Full Paper

High dose rate 192Ir afterloading brachytherapy for cancer of the vagina

D M Kushner, MD 1 P A Fleming, MD 2 A W Kennedy, MD 3 D A Wilkinson, PhD 2 E Lee, MSc 4 and P A Saffle, RTT 2

1 Division of Gynecologic Oncology, Department of Obstertrics and Gynecology, University of Wisconsin Hospital and Clinics, H4/636 CSC, 600 Highland Avenue, Madison, WI 53792-3236, 2 Department of Radiation Oncology and 3 Division of Gynecologic Oncology, Cleveland Clinic Foundation–Taussig Cancer, Cleveland OH and 4 Division of Medical Physics, 21st Century Oncology, Ft Meyers, FL, USA


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
We report results of brachytherapy for carcinoma of the vagina, utilizing a NucletronTM high dose rate system for Delclos Vaginal Applicators (cylinder) and Syed Template Applicators (interstitial). The linear quadratic (LQ) model was used to determine the optimum time-dose-fractionation schedules. Interstitial doses were determined at the isodose line that included gross tumour. Cylinder doses were determined either at the vaginal surface (5 cases), at 0.5 cm depth (5 cases), or at 1.0 cm depth (1 case). For the first treatment (n=19), interstitial templates were utilized in 8 patients and vaginal cylinders in 11. 11 patients received second treatments: 6 templates and 5 cylinders. The median dose of external beam radiation (n=15) was 40.0 Gy followed, after a median 23 day interval, by high dose rate brachytherapy (HDRB) of 4 fractions in 30–42 h; then a median interval gap of 25 days, followed by repeat HDRB. The median total fractionated HDRB dose per patient was 23.0 Gy (range: 6.9 Gy to 40.4 Gy; calculated low dose rate equivalent of 29.8 Gy). Tumour histologies included 14 squamous cell carcinomas, 2 adenocarcinomas, 2 melanomas, and 1 small cell tumour. Three patients experienced early brachytherapy-related complications (diarrhoea, dysuria and labial dermatitis). Three patients (15.8%) developed serious/late complications including ureteral stenosis, painful vaginal necrosis and small bowel obstruction. The first of these patients received 2 templates, the second a cylinder followed by a template and a cylinder, and the third a single cylinder. The 2 year progression-free survival was 39.3% (median 15.7 months), while the 2 year overall survival was 66.1% (median 29.9 months). 192Ir afterloading HDRB is a feasible approach to women with vaginal cancer with acceptable toxicity and tumour response. Potential advantages include patient preference, outpatient cost-effectiveness in the case of cylinder technique, and no radiation exposure to hospital personnel. Long-term follow-up is needed to further assess late complications, and larger studies are needed to confirm our results.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Cancer of the vagina is an uncommon disease. The estimated number of new cases in the USA in 2002 was 2000, or 2.5% of all female genital tract cancers. The estimated number of deaths due to cancer of the vagina in 2002 was 800, or 3.1% of deaths due to gynaecological cancer [1]. Traditionally in the USA, except in the case of selected small T1 lesions, cancer of the vagina has been treated definitively by non-remote afterloading 137Cs intracavitary low dose rate brachytherapy (LDRB) alone, or combined external beam radiation therapy (EBRT) and non-remote afterloading intracavitary LDRB. The latter techniques necessarily result in radiation exposure to physician and nursing personnel. Post-World War II in France and England, radiation therapists/physicists pioneered the development of remote afterloading systems for intracavitary therapy, i.e. the Curietron 137-Cs System and the Cathetron 60-Co system, respectively, thus providing optimum radiation safety for hospital personnel [2–5]. In the late 1970s, Syed and Puthawala developed the vaginoperineal interstitial template technique for adjunct post-EBRT brachytherapy, utilizing non-remote afterloading, 192Ir LDRB seed-source trains, thus permitting the opportunity for improved dose distribution [6].

In 1995, the Cleveland Clinic Foundation Taussig Cancer Centre initiated a Nucletron Microselectron 192Ir remote afterloading system into the Brachytherapy Service (Microselectron/Plato Planning System, Nucletron Corporation, Columbia, MD). This system utilizes the Plato Dosimetry Planning Software, which allows source dwell-time optimization to minimize heterogeneity of dose distribution, a notable advance in the field of interstitial brachytherapy. The present brachytherapy schema incorporates optimum personnel radiation safety, radioactive source containment, improved dose distribution, and inpatient/outpatient capabilities. We report here on the first 19 consecutive patients with primary carcinoma of the vagina, treated between July 1995 and March 2000, utilizing standard orthogonal radiographic localization techniques and the Plato Planning System.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Every effort was made to achieve a rational transition from established LDRB to high dose rate brachytherapy (HDRB). An example of the LDRB technique utilized for the treatment of carcinoma of the vagina at the Cleveland Clinic Foundation Taussig Cancer Centre includes pre-implant EBRT (39.60 Gy, 22 fractions, 33 elapsed days, APPA pelvic portals, 6–18 MV photons) followed in 10–14 days by 192Ir/137Cs brachytherapy procedure number 1, delivering 30.00 Gy minimum tumour dose (MTD), at 40–50 cGy h-1. The same time-sequence-fractionation was applied to the newly introduced HDRB modality with dose determination based on a linear quadratic (LQ) dose/time/fractionation equation concept (Roger Dale, PhD, Department of Radiation Physics and Radiobiology, Charing Cross Hospital, London – personal communications).

If a patient was to receive HDRB brachytherapy for tumours greater than Stage I, the patient was admitted to the surgical suite where general anaesthesia, low spinal anaesthesia, or continuous epidural anaesthesia was administered. The patient was then placed in the lithotomy position and a careful examination of the pelvis performed. Following perineal/vaginal preparation with Hibiclens (chlorhexidine gluconate, Zeneca Pharmaceuticals, Wilmington, DE) and 70% alcohol rinse, the patient was appropriately draped and catheterized. Utilizing anterior/posterior vaginal retractors for exposure, the vaginal canal axial length was measured. Subsequently, application of the Syed GYN3 Template (Figure 1Go) was carried-out (A.O.S. number 712 15ga, Alpha-Omega Services, Inc., Bellflower, CA). In general, no endocervical canal dilatation was required when utilizing an HDRB tandem (outer diameter=3 mm).



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  		Figure 1. Syed GYN3 template placed for the treatment of primary vaginal cancer with 192Ir afterloading high dose rate brachytherapy.

 
Early in this study, a localization CAT scan of the implant site with radio-opaque iodine-impregnated flexible stents placed within the template flexiguides was routinely obtained on post-operative day 1. Next, orthogonal radiographs of the implant site with dummy-seeds in situ were obtained for purposes of computerized dosimetry by idealized dose distribution isodose patterns or by actual digitization technique. Based on the information provided by the latter studies, the physician and physicist then identified the proposed dwell-positions of the single HDRB 192Ir source-seed and then utilized the Nucletron Plato Brachytherapy Dosimetry System to develop the source dwell-times for optimum radiation dose distribution. Confirmation dosimetry was performed in each case utilizing the ROCS computerized dosimetry system (version 3.1.0, Radiation Oncology Computer Systems, Carlsbad, CA). Isodose curve overlay techniques on orthogonal radiographic films were utilized for dose distribution analysis. The patient generally received treatment fraction number 1 on the afternoon of post-operative day 1. Treatment fraction number 2 was delivered on the morning of post-operative day 2; treatment fraction number 3 6 h later; and treatment fraction number 4 was delivered on the morning of post-operative day 3. Thus, the entire dose was delivered in approximately 42 h elapsed treatment time. All brachytherapy applicators were removed in the Radiation Oncology suite. Patients were subsequently discharged from hospital on the following day. All patients utilized pneumatic air stockings while confined to bed, and prophylactic antibiotics were administered to the patients undergoing interstitial template implants. A second application was planned approximately 10–14 days following the first application if no pre-brachytherapy EBRT was delivered or if the prescribed dose was not achieved at the first brachytherapy session, i.e. two patients actually self-removed their template applications. We subsequently took steps to decrease this occurrence by both suturing the applicator in place as well as increasing the amount of tape used to secure the template to the patient.

Whenever feasible, intracavitary applications were performed as an outpatient procedure utilizing a Delclos vaginal cylinder or a multiquadrant tungsten shielded vaginal cylinder. There were 11 vaginal cylinder applications and 8 template applications in treatment session-one; 5 cylinder and 6 template applications in treatment session-two.

The clinical algorithm for dose determination was based upon the work of Thames and Hendry [7], Fowler [8], and Dale [9], i.e. the linear quadratic dose–effect equation. In this model the physical dose, D, is related to a biological effective dose (BED) for LDRB as follows: Go


where: R=dose rate, in Gy h-1, µ=0.693/repair half-time in hours, and {alpha} and {beta} are constants that are tissue dependent, the numerical values of which vary according to whether the effect (cell death) is acute or late.

For high dose rate regimens of n fractions, each of dose d: Go


Equating Equations 1 and 2GoGo permits calculation of the HDRB equivalent dose. For example, an LDRB treatment of 30 Gy at 0.5 Gy h-1 with a repair half-time of 1.5 h and {alpha}/{beta}=10 Gy (acute effects) yields a BED=36.45 Gy. Substitution of this value into Equation 2Go and using n=4 fractions, yields d=5.78 Gy. This dose per fraction (5.78 Gy) and total dose (23.12 Gy) was initially thought to be excessive with regard to possible adverse long-term normal tissue effects, given that the fractionated HDRB prescription would result in a final total dose of 62.72 Gy (EBRT=39.6 Gy; HDRB=23.12 Gy in a Syed template volume implant). The lowest total dose is obtained by setting n=1 in Equation (2)Go and yields a dose of 14.74 Gy for a single fraction equivalent dose. To introduce an element of conservatism into the treatment, this was divided into 4 fractions for the first few patients, resulting in 3.69 Gy/fraction. This arbitrary alteration in the LQ formulation resulted in calculated total LDR-equivalent doses ranging from 65.3 Gy to 75 Gy, excluding that in patient 4 (two template volume implants yielding 40 Gy). Based on the unaltered LQ formulation, the total LDR-equivalent doses varied from 58.1 Gy to 61.5 Gy (24 Gy, in the case of patient 4). Thereafter, with the lack of observed radiation-induced complications, the full-fractionated basis was utilized for dose determination, i.e. BED=nd[1 +d/({alpha} /{beta})]. The above fractions were delivered at not less than 6 h intervals over a 30 h or 42 h period.

The intracavitary cylinder HDRB doses were determined at the vaginal surface in 5 cases, at 0.5 cm perpendicular to the vaginal surface in 5 cases, and at 1.0 cm perpendicular to the vaginal surface in 1 case. Interstitial HDRB doses were determined at the isodose line that included gross tumour.

In accordance with the findings of Utley et al [10], every attempt was made to limit the combined actual rectal dose (EBRT dose + HDRB dose) to 61 Gy or less. In addition to standard hospital record keeping and treatment documentation, a separate real-time database was maintained for recording patient demographic information, treatment parameters, and patient treatment results (FileMaker Pro, v. 5.0, Claris Corporation, Santa Clara, CA).


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Patient and tumour characteristics
From May 1995 to March 2000, 19 patients were treated for vaginal cancer using brachytherapy. The high dose rate 192Ir afterloading system was utilized in all of these cases. Median follow-up is 15 months (range: 5 months to 56 months; average: 18 months). The characteristics of these women and their therapy are summarized in Table 1Go. The median age was 60 years (range 38–87 years). 10 of the patients received HDRB as part of the primary treatment of early-stage disease (defined as Stage I or II). One of these patients (number 1) had received 20 Gy of LDRB when her cylinder became dislodged. She opted to continue treatment with HDRB. Eight women underwent primary treatment of late-stage cancer (Stage III or IV), and there was one recurrent tumour. The latter patient (number 14) failed external beam radiation therapy of a Stage II lesion and underwent an anterior exenteration 1 year later. 3 years after the operation she recurred in the perirectal area and was treated with HDRB.


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  		Table 1. Clinicopathologic characteristics and outcome

 
The tumour histology included 14 squamous cell carcinomas (SCC), 2 adenocarcinomas (AC), 2 melanomas, and 1 small cell/neuroendocrine tumour. Of the 15 SCC and AC where the grade was recorded, 7 were grade 3, 6 grade 2, and 2 grade 1. Complete surgical excision of gross tumour was performed prior to radiation in 4 of the early-stage tumours. One patient (number 12) also underwent removal of a large mucosal lesion, but her disease extended to the pelvic sidewall. The majority of her tumour was thus not removed prior to starting radiation therapy.

As per inclusion criteria, none of the patients had a diagnosis of primary or recurrent cancer in the 15 years prior to the time of HDRB. It is interesting to note, however, that four patients had a remote history of pelvic radiation for gynaecological malignancy. Patient 4 had undergone a hysterectomy and received an unknown radiation regimen 20 years earlier for cervix cancer. Patients 13 and 19 also had a history of cervix cancer (22 and 42 years prior, respectively), and were known to have been treated with both external beam and intracavitary radiation. Patient 11 had received external beam and brachytherapy for endometrial cancer 33 years prior to her diagnosis of vaginal carcinoma.

Radiation characteristics
15 patients received EBRT as part of the treatment of their vaginal cancer, most being administered at the referring institutions (Table 1Go; median dose 40.0 Gy, range 39.6–57.5 Gy). The time from the last day of EBRT to the first brachytherapy treatment ranged from 11 days to 35 days with a median of 23 days. A vaginal cylinder was used in 11 patients and interstitial templates were employed in 8 patients for the first course of therapy (median dose 14.7 Gy, range 6.9–23.1 Gy). A median of 29 guides was placed in each template (range 15–40). Each tumour was measured in three dimensions and these results were multiplied to determine a crude volume. At the time of the first brachytherapy, the median clinical volume of the tumours that had not been completely removed surgically was 4.8 cm3 (range 0–128 cm3). Radiological findings often expanded the necessary treatment volume. The volume treated for each interstitial template is noted in Table 1Go.

A second course of HDRB was utilized in 10 of the patients for multiple reasons including larger tumours, slow regression of tumour volume after first treatment and inadequate EBRT given by the referring physician. Multiple courses permited tumour target volume regression between treatment sessions and the attendant more advantageous optimization of dose distribution at the second session. A vaginal cylinder was used in five cases, while the rest received interstitial templates. The median interval between courses 1 and 2 was 25 days (range 15–77 days). Eight of these tumours had not been surgically treated. Of these, three of the tumours had decreased volume, four were unchanged and one increased in size. The median volume for the 10 tumours receiving a second course of brachytherapy was 2.4 cm3 (range 0–128 cm3), and a median dose of 13.6 Gy (range 8.5–17.0 Gy) was administered. A median of 32 guides was placed in the five patients with templates (range 23–32). Of note, patient 12 was the only patient to undergo a third HDRB course. 17 days after her second course (an interstitial application that became inexplicably, totally dislodged prior to completion), a vaginal cylinder was used to deliver an additional 4.3 Gy. The median total fractionated HDRB dose per patient was 23.0 Gy (range: 6.9–40.4 Gy; calculated LDRB equivalent of 29.8 Gy).

Response to therapy
3 months after completion of therapy, there was no evidence of tumour noted in 18 of the 19 patients. This equates to a complete response in 10 patients, as 8 patients had minimal tumour volume at the time of brachytherapy. The one patient who progressed did so by 5 weeks from the end of therapy. Overall, 10 of the 19 patients recurred, giving a crude progression-free rate of 47.4%; 6 of these patients have died of disease (crude death rate=31.6.%).

Figure 2Go displays Kaplan-Meier curves for both progression-free survival (PFS) and overall survival (OS) for the entire population studied. PFS and progression-free interval are interchangeable in this analysis because all of the patients who died experienced progression first. The median PFS was 15.7 months with a 2 year PFS of 39.3%. The median PFS was 12.1 months for late-stage patients and was not yet observed for the early-stage patients. This difference (15.7 months vs 12.1 months) did not reach statistical significance, (p=0.25; results not shown). The median OS was 29.9 months for the entire population with a 2 year OS of 66.1%; dropping to 39.3% at 3 years. The median OS was 21.5 months for late-stage patients and was not yet observed for early-stage patients. Again, this difference did not reach statistical significance (p=0.20; results not shown).



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  		Figure 2. Kaplan-Meier curves estimating progression-free and overall survival for the entire population of patients receiving high dose rate brachytherapy for vaginal cancer.

 
Of the nine patients who recurred after primary therapy, three first recurred at distant sites. Two of these patients had melanoma and recurred in the lung. The other (patient 3) had Stage IV SCC and clinically recurred in a supraclavicular node. CT scan at that time showed enlarged para-aortic nodes as well. None of these three patients ever developed a local recurrence of tumour. Patient 6 is also of interest. At the time of her local recurrence, 18 months after treatment, she was noted to have marked inguinal adenopathy. She was retreated using two courses of interstitial HDRB (24.2 Gy, 15.7 Gy). She had some shrinkage of tumour in both areas at 3 months, but progressed by 7 months and died of disease 10 months after her recurrence.

Toxicity
All patients tolerated the procedure well with no intraoperative or perioperative complications. Early radiation-related complications included one patient (number 8) with grade 2 diarrhoea, one patient (number 18) with grade 2 dysuria, and one patient (number 10) with grade 3 labial dermatitis. These symptoms each spontaneously resolved in the month after treatment. One case (patient 4) of near complete vaginal stenosis was noted at 4 months. This was not troublesome to the patient, but made follow-up examinations somewhat more difficult. A mild vaginal discharge was common as seen in at least five of the patients.

There were three serious or late-occurring complications reported (16.7%). Patient 4, with a history of Crohn's disease 22 years prior to presentation, had been previously treated for carcinoma of the cervix by radiation therapy 19 years prior to presentation and had undergone large bowel resection and ileostomy for "radiation colitis" 5 years prior to presentation, experienced an obstructive left hydronephrosis at 8 weeks post-brachytherapy (grade 4). The total radiation dose delivered by two interstitial brachytherapy sessions was 22.88 Gy. She required stenting, but had no further sequelae. Patient 12, a case in which the template was inexplicably, totally dislodged between fraction 3 and 4, developed gradual necrosis of the right distal vaginal tumour bed that was quite painful (grade 4). This area was serially debrided over a 1 year period and eventually healed. The patient is currently without complaints. Lastly, patient 15 developed radiation enteritis and partial small bowel obstruction (grade 3). This was relieved with distal ileal bypass 9 months after completing her combined course of EBRT (50 Gy with midline block at 40 Gy) and intracavitary brachytherapy (22.2 Gy vaginal surface dose).


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
This report is the largest to describe 192Ir HDRB for vaginal cancer using both intracavitary and interstitial techniques. The results suggest that this is a reasonable approach for continued investigation, with good tumour response and acceptable toxicity. Of those patients who had measurable disease at the initiation of brachytherapy, 91% (10/11) experienced a complete response. The crude recurrence rate for patients with early-stage tumours that were not melanomas was only 11% (1/9). Patients with late-stage disease and melanomas faired predictably worse, decreasing the overall 2 year PFS and OS to 39.9% and 66.1%, respectively.

Conventional brachytherapy has long played a critical role in the treatment of vaginal cancer. In a review of 49 cases treated between 1970 and 1988 at Memorial Sloan-Kettering Cancer Centre, Stock et al [11] found that 38 patients had some sort of brachytherapy incorporated into their treatment regimen (78%). Chyle et al [12] reviewed the 301 patients who received radiation therapy for vaginal cancer between 1953 and 1991 at M.D. Anderson Cancer Centre and found that brachytherapy predominated for early disease, with EBRT playing a more prominent role for more advanced disease. Brachytherapy was used in 100% of cases of Stage I tumours, compared with 70% of Stage II and 25% of Stage III tumours. In a more recent review, Perez [13] also discussed the use of EBRT and conventional brachytherapy for the treatment of vaginal cancer. He found the 10 year PFS to be 80% for Stage I, 55% for Stage IIA, 35% for Stage IIB, 38% for Stage III and 0% for Stage IV patients. The incidence of distant metastasis was 13%, 30–52%, 50%, and 47% for Stages I–IV, respectively. These three large studies form a context in which to compare our above results. Of note, only three HDRB patients developed distant metastasis (one Stage IV SCC and two melanomas). It is difficult to draw conclusions about the HDRB method because of the small numbers, shorter follow-up, and heterogeneous nature of the current study population. HDRB brachytherapy appears to be no less effective in the original control of disease than conventional LDRB.

Interstitial templates were used in 8 of the 19 patients for the first treatment, and in 6 of 11 second treatments. The use of the Syed-Neblett perineal template for patients with vaginal cancer was described by Fleming et al in 1980 [6]. Utilizing LDRB 192Ir afterloading technique, they reported on 13 patients and described the procedure to provide: "1) ease and reproducibility of application by the physician; 2) homogeneous radiation dose distribution characteristics; and 3) differential radiation dose delivery capabilities." These benefits, as well as the overall safety of LDRB interstitial implants, have been supported by multiple subsequent studies [11, 14, 15]. We have found that interstitial HDRB offers these same advantages, with the additional benefit of virtually no radiation exposure to hospital personnel.

Vaginal cylinder HDRB has been investigated for the treatment of vaginal intraepithelial neoplasia (VAIN) with promising results [16, 17]. Other reports have described its use in the treatment of vaginal recurrences of cervical carcinoma [18, 19]. We are aware of only three large series of HDRB for primary vaginal cancer—all utilizing the cylinder technique alone. Stock et al described 15 patients with vaginal cylinder HDRB and 19 patients receiving LDRB (12 interstitial, 6 tandem and ovoids, and 1 cylinder) [11]. They found an increase in survival and local control for patients receiving brachytherapy versus those receiving EBRT alone. They also noted that Stage II and III patients benefited more from interstitial implants than intracavitary brachytherapy (PFS 75% vs 44%). No patients received interstitial HDRB. Nanavati et al treated 13 patients with Stage I and II tumours with HDRB intracavitary cylinders [20]. All patients experienced a complete response, and local control rate was 92% with a mean follow-up of 2.6 years. They had no grade 3 or 4 gastrointestinal or bladder toxicities. Kucera et al recently reported on a large group of women treated with HDRB cylinders compared with a historical control group of women treated with LDRB cylinders. There was no significant difference in complications, local or distant recurrence rates between the two modalities [21].

The acceptable morbidity of LDRB for gynaecological malignancies has been well established [12, 13, 22]. In a review of 327 patients treated for cervical, endometrial and vaginal cancers from 1986 to 1988, Dusenbery et al revealed a life-threatening perioperative complication rate of 6.4%, most of which were cardiac-related in elderly patients [22]. Chyle et al reported a 13% serious complication rate in treating vaginal carcinoma [12]. FIGO stage, tumour size and staging pelvic lymphadenectomy were correlated with subsequent toxicity. Small bowel injury occurred only in those patients receiving EBRT along with brachytherapy. In the current study of HDRB, serious complications were seen in three patients (16.7%). Toxicities were mostly noted in patients with higher stage tumours and those who had received EBRT.

As a regional referral institution for gynaecological brachytherapy, many of the patients had already received EBRT before consultation at the Cleveland Clinic Cancer Centre. This was a disadvantage for multiple reasons. First, we were unable to control the amount of EBRT or the manner in which it was administered. For example, certain patients had been given large EBRT doses allowing less latitude for brachytherapy applications. Second, patients varied as to the timing of referral. Most patients were seen in consultation during EBRT or even before therapy, but occasional late referrals led to delays in starting brachytherapy. We recommended starting brachytherapy within 14 days of EBRT, but the median interval was 23 days with a range from 11 days to 35 days. Delay may have a negative effect on outcome. Lee et al found that, when treating vaginal cancer, the single most important predictor of pelvic control is treatment time [23]. The pelvic control rate decreased from 97% to 54% when the total treatment time extended beyond 9 weeks.

The current study aims to address the issues of toxicity and efficacy of interstitial and intracavitary HDRB for vaginal cancer. The single-institution design combined with the rarity of the disease make the recruitment of large numbers of patients improbable. These results should act, however, as a basis for continued investigation into this worthwhile technology and its role in helping patients with vaginal cancer. The benefits of HDRB over conventional therapy are numerous. These include decreased patient immobilization and no radiation exposure to healthcare workers. HDRB also has several dosimetric advantages: 1) advanced computerized dose distribution capabilities, i.e. optimization mode combined with CT-based treatment planning (CT anatomical images are downloaded to the Plato System, thus permitting individual source-train localization and tracking within a true anatomical display); 2) continuous monitoring throughout therapy resulting in greater likelihood that the patient receives the prescribed dose [24]. We have found HDRB to be a feasible and reliable method of treating patients with gynaecological malignancies. A multi-institutional study will be needed if the questions of toxicity and efficacy are to be fully addressed in the setting of vaginal cancer.


   Acknowledgments
 
The authors would like to gratefully acknowledge the assistance of Roger Dale, PhD, Department of Radiation Physics and Radiobiology, Charing Cross Hospital, London, UK for assistance with clinical application of the linear quadratic equation.

Received for publication May 25, 2002. Revision received May 12, 2003. Accepted for publication May 30, 2003.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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