Radiotherapy is the main therapeutic modality in the management of primary or recurrent vaginal cancer. Brachytherapy remains integral part of definitive radiation therapy for these patients [2
]. The preponderance of the published literature on brachytherapy in this setting demonstrates a wide variation on techniques and dose utilized for LDRB. Although HDRB is widely available and used for a variety of gynecologic malignancies, the published data on this technique for vaginal cancer treatment are limited. The HDR planning software offers the ability to optimize the dwell time and position of the radioisotope source (Ir-192) in order to create conformal radiation treatment to a specified target. This improvement in dose uniformity and ratios between tumor and normal tissue is important advantage of HDR brachytherapy. These advantages of HDRB over LDRB have to be weighed against the need to use a larger number of HDR fractions and the inconvenience of multiple implantations.
In a review of the literature regarding salvage treatment options for vaginal recurrence, only two studies have examined the efficacy of HDRB for treatment of vaginal recurrences [11
]. The study by Petignat, et al.
on 22 patients with recurrent endometrial cancer reported local tumor control rate and the 5-year disease-specific survival rate of 100% and 96%, respectively [11
]. Similarly, in the series by Pai, et al.
on 20 patients, 10-year local control rate and disease-free survival rates were 74% and 46%, respectively [15
]. Our study with shorter follow-up shows comparable local control and cause-specific survival. The major difference between the published series and our data is the technique of HDRB. The majority of the patients in either study were treated with intracavitary brachytherapy with only 2 patients having interstitial implantation. In contrast, in our study 13/18 patients had interstitial brachytherapy. The technique of intracavitary is recommended for non-bulky recurrences (thickness < 5 mm after the completion of EBRT) while interstitial brachytherapy is preferred approach for bulky recurrences [16
Interstitial brachytherapy has been traditionally performed using LDRB techniques in this setting. Our technique involved one Syed-Neblett
template implantation procedure delivering 5 fractions twice a day for a total HDRB dose of 18.75 Gy over 48 – 56 hours. Because of lack of published data, the American Brachytherapy Society (ABS) did not make any recommendation on HDRB interstitial brachytherapy dose and fractionation schedule for vaginal recurrences and preferred LDRB as the technique for interstitial brachytherapy [16
]. Our treatment regimen was well tolerated with excellent local control and low toxicities in patients with no prior radiation.
Similarly, there are only few published studies on HDRB for primary vaginal cancer. Kusher, et al.
first reported on 19 patients treated with the combination of intracavitary and interstitial brachytherapy [10
]. The median HDRB dose was 23 Gy (LDR equivalent of 29.8 Gy) after median EBRT dose of 40 Gy. The 2-year progression-free survival was 39.3% while the 2-year overall survival was 66.1%. Three patients developed serious and/or late complications including urethral stenosis, painful vaginal necrosis and small bowel obstruction of which two had interstitial brachytherapy. The largest series of HDRB for vaginal cancer is from Vienna reporting on a total of 86 patients of primary vaginal carcinoma treated with HDRB [12
]. Early stages of disease (stages 0–II) were treated with intravaginal HDR brachytherapy alone (n
= 26/86), whereas patients with locally advanced disease (stages II-IV) received HDR brachytherapy combined with external beam therapy (n
= 55/86). The prescribed dose per fraction varied from 5 Gy to 8 Gy, with a mean dose of 7 Gy. In this large series only 8 patients had interstitial brachytherapy. The 5-year recurrence-free survival were 100%, 77%, 50%, 23%, and 0% for stage 0, I, II, III and IV respectively. Chronic grade 1–4 side effects were observed in ≤ 2% (bladder, rectum) and 1%–6% (vagina). Our series only had 6 patients of primary vaginal cancer and all had interstitial brachytherapy with 2-year local control of 100%. The toxicity profile was favorable with no grade 3 or higher toxicities.
In LDRB literature for vaginal cancer, an inverse relationship between the total dose and rates of local recurrences have been reported by several authors [17
]. Chyle, et al.
noted an increasing risk of local recurrences in patients who received <55 Gy when compared with those receiving >55 Gy (53% vs. 17%) [12
]. Similarly Fine, et al.
reported local failures in 25%, 33% and 62% of patients for the administered dose of >75 Gy, 60–75 Gy and <60 Gy respectively [18
]. Our median EQ2 of 66.48 Gy is comparable with these doses recommended in LDRB literature. Besides, our calculation of biological equivalence is based on the assumption of complete repair of sub-lethal radiation damage between the two fractions [14
]. With a twice-daily (BID) fractionation schedule and time interval of 6 hours between fractionation, the sublethal damage may not be complete thereby causing more injury to both tumor and normal tissues than predicted by BED models.
Notwithstanding, our small series with preliminary results shows that HDRB is efficacious for primary or recurrent vaginal cancer. The fractionation schedule used was well tolerated with a low incidence of acute or later toxicities. Additional patients and follow-up are ongoing to determine the long-term efficacy of this approach. The limitation of our retrospective study is small size with limited follow up and heterogeneous patient population evaluated (inclusion of both primary and recurrent disease). The incidence of primary or recurrent vaginal cancer is low so that it is difficult for a single institution to have a large series. That was the rationale to combine heterogeneous disease together to see the efficacy and toxicities of this approach. As HDR equipment is widely available, there are more institution doing HDR interstitial brachytherapy. We may need to consider multi-institutional pooled analysis similar to the LDR experience [19
] to see the impact of this technique for local control and toxicities and to define optimal fractionation schedules.