Vaginal intraepithelial neoplasia (VAIN), a rare premalignant condition, is difficult to eradicate. We assess the effectiveness of high-dose rate intracavitary brachytherapy (HDR-ICR) in patients with VAIN or carcinoma in situ (CIS) of the vagina after hysterectomy.
Materials and Methods
We reviewed 34 patients treated for posthysterectomy VAIN or CIS of the vagina by brachytherapy as the sole treatment. All patients underwent a coloposcopic-directed punch biopsy or had abnormal cytology, at least 3 consecutive times. All patients were treated with a vaginal cylinder applicator. The total radiation dose was mainly 40 Gy in 8 fractions during the periods of 4 weeks at a prescription point of the median 0.2 cm (range, 0 to 0.5 cm) depth from the surface of the vaginal mucosa.
Acute toxicity was minimal. Seven patients had grade 1/2 acute urinary and rectal complications. There were 15 cases of late toxicity, predominantly vaginal mucosal reaction in 12 patients. Of these patients, two patients suffered from grade 3 vaginal stricture and dyspareunia continuously. After a median follow-up time of 48 months (range, 4 to 122 months), there were 2 recurrences and 2 persistent diseases, in which a second-line therapy was needed. The success rate was 88.2%. The average prescription point in failure patients was 1.1 mm from the surface of the vagina compared to an average of 2.6 mm in non-recurrent patients (p=0.097).
HDR-ICR is an effective treatment method in VAIN patients. In spite of high cure rates, we should consider issues regarding vaginal toxicity and radiation techniques to reduce the occurrence of failure and toxicity.
Vaginal neoplasms; Carcinoma in situ; Radiotherapy; Brachytherapy
We sought to determine the tolerance level and complication rates of the vaginal vault to combined high-dose-rate intra-cavitary brachytherapy with concomitant chemo-radiotherapy.
Patients and methods
A retrospective review of medical records of all the patients who received definitive chemo-radiotherapy for cervical cancer between 1998 and 2002 was undertaken. The records were reviewed for doses and for radiation-associated early and late sequelae of the vagina, rectum and bladder. Cumulative biological effective dose was calculated for two reference vaginal surface points.
Fifty patients were included. Average age at diagnosis was 54 years. Median follow-up was 59 months. There were no recorded instances of acute grade IV toxicity. Maximal high-dose-rate vaginal surface dose (upper central point) was 103 Gy, and maximal brachytherapy lateral surface dose was 70 Gy. Maximal cumulative biological effective dose for the lateral surface reference point was 465.5 Gy3, and the maximal cumulative biological effective dose for the superior reference point was 878.6 Gy3. There were no cases of vaginal necrosis or fistulas, and no cases of grade IV late vaginal, rectal or bladder toxicity. No correlation was found between the maximal vaginal surface dose and vaginal, rectal or bladder toxicity.
The maximal surface HDR brachytherapy dose of 103 Gy and the maximal cBED of 878.6 Gy3 were not associated with fistula or necrosis or other grade 3–4 vaginal complications. Concomitant chemo-radiotherapy, including pelvic radiotherapy and high-dose-rate intracavitary brachytherapy, is relatively safe for cervical cancer patients.
Tolerance; Vagina; Irradiation; High-dose-rate; Brachytherapy
Brachytherapy plays a significant role in the management of cervical cancer, but the clinical significance of brachytherapy in the management of vaginal cancer remains to be defined. Thus, a single institutional experience in the treatment of primary invasive vaginal carcinoma was reviewed to define the role of brachytherapy. We retrospectively reviewed the charts of 36 patients with primary vaginal carcinoma who received definitive radiotherapy between 1992 and 2010. The treatment modalities included high-dose-rate intracavitary brachytherapy alone (HDR-ICBT; two patients), external beam radiation therapy alone (EBRT; 14 patients), a combination of EBRT and HDR-ICBT (10 patients), or high-dose-rate interstitial brachytherapy (HDR-ISBT; 10 patients). The median follow-up was 35.2 months. The 2-year local control rate (LCR), disease-free survival (DFS), and overall survival (OS) were 68.8%, 55.3% and 73.9%, respectively. The 2-year LCR for Stage I, II, III and IV was 100%, 87.5%, 51.5% and 0%, respectively (P = 0.007). In subgroup analysis consisting only of T2–T3 disease, the use of HDR-ISBT showed marginal significance for favorable 5-year LCR (88.9% vs 46.9%, P = 0.064). One patient each developed Grade 2 proctitis, Grade 2 cystitis, and a vaginal ulcer. We conclude that brachytherapy can play a central role in radiation therapy for primary vaginal cancer. Combining EBRT and HDR-ISBT for T2–T3 disease resulted in good local control.
primary vaginal cancer; radiation therapy; high-dose-rate brachytherapy; intracavitary brachytherapy; interstitial brachytherapy
To evaluate local control, survival and toxicity in patients with early-stage endometrioid adenocarcinoma of the uterus treated with adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) alone using a novel low dose regimen
We reviewed records of 414 patients with stage IA to stage II endometrial adenocarcinoma treated with VB alone from 2005 to 2011. Of these, 157 patients with endometrioid histology received 24 Gy in 6 fractions of HDR vaginal cylinder brachytherapy and constitute the study population. Dose was prescribed at the cylinder surface and delivered twice weekly in the post-operative setting. Local control and survival rates were calculated by the Kaplan-Meier method.
All 157 patients completed the prescribed course of VB. Median follow-up time was 22.8 months (range, 1.5–76.5). Two patients developed vaginal recurrence, one in the periurethral region below the field and one in the fornix after treatment with a 2.5-cm cylinder. Three patients developed regional recurrence in the para-aortic region. Two patients developed distant metastasis (lung and carcinomatosis). The 2-year rate of vaginal control was 98.6%, locoregional control was 97.9% and disease-free survival was 96.8%. The 2-year overall survival rate was 98.7%. No Grade 2 or higher vaginal, gastrointestinal, genitourinary or skin long-term toxicity was reported for any patient.
Vaginal brachytherapy alone in early-stage endometrial cancer provides excellent results in terms of locoregional control and disease-free survival. The fractionation scheme of 24 Gy in 6 fractions prescribed to the cylinder surface was well-tolerated with minimal late toxicity.
Endometrial cancer; vaginal brachytherapy; high-dose-rate
The purpose was to determine whether a brachytherapy boost improves outcomes in patients with advanced nasopharyngeal carcinoma treated with standard chemo-radiotherapy.
Patients with nasopharyngeal carcinoma WHO grades I-III and TNM stages III or non-metastatic stage IV were eligible for this phase III study. Patients were randomized to either arm (A) induction chemotherapy, followed by external beam radiotherapy (EBRT) with concomitant cisplatin (n = 139) or arm (B), the same schedule plus a brachytherapy boost to the nasopharynx (n = 135). The EBRT doses given were 70 Gy to the primary tumour and positive lymph nodes and 46 Gy to the negative neck. The additional brachytherapy boost in arm (B) was given by either low dose-rate (LDR – 11 Gy) or high dose-rate (HDR – 3 fractions of 3.0 Gy) brachytherapy. The primary endpoint was 3-year overall survival (OS) and secondary endpoints were: local control, regional control, distant metastasis and grade 3–4 adverse events.
274 patients were randomized between September 2004 and December 2008. The two arms were comparable with regard to age, gender, stage and grade. 273 patients completed treatment. Median follow-up was 29 months (0.2-67 months). The effect of treatment arm, country, age, gender, WHO pathology, stage (T3-4, N2-3 versus other) and chemotherapy on overall survival (OS), disease-free survival (DFS) and local recurrence-free survival (LRFS) was studied. Stage significantly affected OS (p = 0.024) and DFS (p = 0.018) while age significantly affected OS (p = 0.014). None of the other factors studied were significant. The 3-year LRFS was 60.5% and 54.4% in arms A and B respectively (p = 0.647). The 3-year regional control rate in the neck was 59.7% and 54.3% respectively (p = 0.7). Distant metastasis developed in 59.7% of patients in arm A and 55.4% in arm B (p = 0.377). Patients with T1/T2 N + had a 3 year LRFS of 51.8% in Arm A (62 patients) versus 57.9% in Arm B (67 patients) (p = 0.343). The grade 3–4 toxicity rate was 21.6% (30/139) and 24.4% (33/135) respectively (p = 0.687).
The addition of a brachytherapy boost to external beam radiotherapy and chemotherapy did not improve outcome in loco-regionally advanced nasopharyngeal carcinoma.
Nasopharynx; Nasopharyngeal carcinoma; Brachytherapy boost
To investigate the role of low dose rate (LDR) brachytherapy-based multimodal therapy in high-risk prostate cancer (PCa) and analyze its optimal indications.
Materials and Methods
We reviewed the records of 50 high-risk PCa patients [clinical stage ≥T2c, prostate-specific antigen (PSA) >20 ng/mL, or biopsy Gleason score ≥8] who had undergone 125I LDR brachytherapy since April 2007. We excluded those with a follow-up period <3 years. Biochemical recurrence (BCR) followed the Phoenix definition. BCR-free survival rates were compared between the patients with Gleason score ≥9 and Gleason score ≤8.
The mean initial PSA was 22.1 ng/mL, and mean D90 was 244.3 Gy. During a median follow-up of 39.2 months, biochemical control was obtained in 72% (36/50) of the total patients; The estimated 3-year BCR-free survival was 92% for the patients with biopsy Gleason scores ≤8, and 40% for those with Gleason scores ≥9 (p<0.001). In Cox multivariate analysis, only Gleason score ≥9 was observed to be significantly associated with BCR (p=0.021). Acute and late grade ≥3 toxicities were observed in 20% (10/50) and 36% (18/50) patients, respectively.
Our results showed that 125I LDR brachytherapy-based multimodal therapy in high-risk PCa produced encouraging relatively long-term results among the Asian population, especially in patients with Gleason score ≤8. Despite small number of subjects, biopsy Gleason score ≥9 was a significant predictor of BCR among high risk PCa patients after brachytherapy.
Prostate cancer; brachytherapy; high risk group; biochemical recurrence
To assess clinical outcomes of patients treated with a high-dose rate brachytherapy boost for anal canal cancer (ACC).
From August 2005 to February 2013, 28 patients presenting an ACC treated by split-course external beam radiotherapy (EBRT) and HDR brachytherapy with or without chemotherapy in a French regional cancer center in Nice were retrospectively analyzed.
Median age was 60.6 years [34 – 83], 25 patients presented a squamous cell carcinoma and 3 an adenocarcinoma; 21 received chemotherapy. Median dose of EBRT was 45 Gy [43.2 – 52]. Median dose of HDR brachytherapy was 12 Gy [10 - 15] with a median duration of 2 days. Median overall treatment time was 63 days and median delay between EBRT and brachytherapy was 20 days. Two-year local relapse free, metastatic free, disease free and overall survivals were 83%, 81.9%, 71.8% and 87.7% respectively. Acute toxicities were frequent but not severe with mostly grade 1 toxicities: 37% of genito-urinary, 40.7% of gastro-intestinal and 3.7% of cutaneous toxicities. Late toxicities were mainly G1 (43.1%) and G2 (22%). Two-year colostomy-free survival was 75.1%, one patient had a definitive sphincter amputation.
High-dose rate brachytherapy for anal canal carcinoma as boost represents a feasible technique compared to low or pulsed-dose rate brachytherapy. This technique remains an excellent approach to precisely boost the tumor in reducing the overall treatment time.
Brachytherapy; Anal canal cancer; High-dose rate; Boost; Radiotherapy
To report the relapse and survival rates associated to treatment for patients with stage IC, grade 2 or grade 3 and IB grade 3 diseases considered high risk patients group for relapse.
Materials and methods
From January 1993 to December 2003, 106 patients with endometrial cancer stage I were managed surgically in our institution. Based on data from the medical records, 106 patients with epithelial endometrial cancer met the following inclusion criteria: stage IC grade 2 or 3 and IB grade 3 with or without lymphovascular invasion. Staging was defined according to the FIGO surgical staging system. Postoperative adjuvant radiotherapy consisted of external beam pelvic radiation, vaginal brachytherapy alone or both. The median age was 65 years (range, 32–83 years), lymph node dissection was performed in 45 patients (42.5%) and 14 patients (13.2%) received vaginal brachytherapy only, and 92 (86.8%) received combined vaginal brachytherapy and external beam radiotherapy. The median dose of external beam radiotherapy administered to the pelvis was 4500 cGy (range 4000 – 5040). The median dose to vaginal surface was 2400 cGy (range 2000 – 3000). Predominant pathological stage and histological grade were IC (73.6%) and grade 3 (51.9%). The lymphovascular invasion was present in 33 patients (31.1%) and pathological stage IC grade 2 was most common (48. 1%) combination of risk factors in this group.
With a follow up median of 58.3 months (range 12.8 – 154), five year overall survival and event free survival were 78.5% and 72.4%, respectively. Locoregional control in five year was 92.4%. Prognostic factors related with survival in univariate analyses were: lymphadenectomy (p = 0.045), lymphovascular invasion (p = 0.047) and initial failure site (p < 0.0001). In multivariate analyses the initial failure in distant sites (p < 0.0001) was the only factor associated with poor survival. Acute and chronic gastrointestinal and genitourinary toxicity grades 3 were not observed.
In conclusion, our results showed that the stage IC, grade 2, 3 and IB grade 3 endometrial cancer was associated with significantly increased risk of distant relapse and endometrial carcinoma-related death independently of salvage treatment modality.
To compare long-term prostate-specific antigen relapse-free survival outcome and incidence of toxicity for low-risk prostate cancer treated with brachytherapy or intensity-modulated radiotherapy.
729 consecutive patients were treated with BRT (n=448; prescription dose, 144 Gy) and intensity-modulated radiotherapy alone (n=281; prescription dose, 81 Gy). Prostate-specific antigen relapse-free survival using nadir +2 definitions, and late toxicity using the National Cancer Institute's Common Terminology Criteria for Adverse Events.
Seven-year prostate-specific antigen relapse-free survival for brachytherapy and intensity-modulated radiotherapy was 95% and 89% for low-risk patients (p=0.004). Cox regression analysis demonstrated that brachytherapy was associated with improved prostate-specific antigen relapse-free survival even when adjusted for other variables. Incidence of metastatic disease between treatments was low for both treatment groups. Late grade 2 gastrointestinal toxicities were observed in 5.1% and 1.4% of the brachytherapy and intensity-modulated radiotherapy groups, respectively (p=0.02). There were no significant differences between treatment groups for late grade ≥3 rectal complications (brachytherapy, 1.1%; intensity-modulated radiotherapy, 0%; p=0.19). Late grade 2 urinary toxicities were more often observed for brachytherapy than intensity-modulated radiotherapy (15.6% and 4.3%, respectively; p<0.0001). There were no significant differences between treatment groups for late grade 3 urinary toxicity (brachytherapy, 2.2%; intensity-modulated radiotherapy, 1.4%; p=0.62).
Among low risk prostate cancer patients, 7-year biochemical tumor control is superior for intraoperative-planning brachytherapy compared with high-dose intensity-modulated radiotherapy. While significant toxicities were minimal for both groups, modest but significant increases in grade 2 urinary and rectal symptoms were noted for brachytherapy compared with intensity-modulated radiotherapy.
Low dose rate; Iodine-125; Prostate cancer; PSA-relapse–free survival; Brachytherapy; Toxicity
To evaluate whether Point A asymmetry in low dose-rate (LDR) brachytherapy is associated with local control (LC), disease-free survival (DFS) and/or overall survival (OS).
Material and methods
A retrospective analysis of disease control and survival outcomes was conducted for patients who underwent LDR brachytherapy for advanced cervical cancer. Institutional protocol entailed concurrent chemotherapy and whole pelvis radiotherapy (WPRT) over 5 weeks, followed by placement of Fletcher-Suit tandem and colpostat applicators at weeks 6 and 8. Objective Point A doses, 80-85 Gy, were accomplished by placement of Cesium-137 (Cs-137) sources. Cox proportional hazards regression models were used to assess associations between disease control and survival endpoints with variables of interest.
The records of 50 patients with FIGO stage IB1-IVA cervical cancer undergoing LDR brachytherapy at our institution were identified. Thirty of these patients had asymmetry > 2.5%, and 11 patients had asymmetry > 5%. At a median survivor follow-up of 20.25 months, 15 patients had experienced disease failure (including 5 cervical/vaginal apex only failures and 2 failures encompassing the local site). Right/left dose asymmetry at Point A was associated with statistically significantly inferior LC (p = 0.035) and inferior DFS (p = 0.011) for patients with mean Point A dose of > 80 Gy. Insufficient evidence existed to conclude an association with OS.
LDR brachytherapy may be associated with clinically significant dose asymmetry. The present study demonstrates that patients with Point A asymmetry have a higher risk of failure for DFS and LC.
brachytherapy; cervical; point A; Fletcher-Suit system
To examine the role of brachytherapy for aged patients 80 or more in the trend of rapidly increasing number.
We examined the outcomes for elderly patients with node negative oral tongue cancer (T1-3N0M0) treated with brachytherapy. The 21 patients (2 T1, 14 T2, and 5 T3 cases) ranged in age from 80 to 89 years (median 81), and their cancer was pathologically confirmed. All patients underwent definitive radiation therapy, with low dose rate (LDR) Ra-226 brachytherapy (n = 4; median 70Gy), with Ir-192 (n = 12; 70Gy), with Au-198 (n = 1) or with high dose rate (HDR) Ir-192 brachytherapy (n = 4; 60 Gy). Eight patients also underwent external radiotherapy (median 30 Gy). The period of observation ranged from 13 months to 14 years (median 2.5 years). We selected 226 population matched younger counterpart from our medical chart.
Definitive radiation therapy was completed for all 21 patients (100%), and acute grade 2-3 mucositis related to the therapy was tolerable. Local control (initial complete response) was attained in 19 of 21 patients (90%). The 2-year and 5-year local control rates were 91%, (100% for T1, 83% for T2 and 80% for T3 tumors after 2 years). These figures was not inferior to that of younger counterpart (82% at 5-year, n.s.). The cause-specific survival rate was 83% and the regional control rate 84% at the 2-years follow-up. However, 12 patients died because of intercurrent diseases or senility, resulting in overall survival rates of 55% at 2 years and 34% at 5 years.
Age is not a limiting factor for brachytherapy for appropriately selected elderly patients, and brachytherapy achieved good local control with acceptable morbidity.
The purpose of this study was to evaluate the efficacy of HDR brachytherapy for primary or recurrent vaginal cancer.
Between the years 2000 to 2006, 18 patients with primary or recurrent vaginal cancer were treated with brachytherapy (HDRB). Six patients had primary vaginal cancer (stage II to IVA) while 12 were treated for isolated vaginal recurrence (primary cervix = 4, vulva = 1 and endometrium = 7). Five patients had previous pelvic radiation therapy. All except one patient received external beam radiation therapy to a median dose of 45 Gy (range 31.2–55.8 Gy). The HDRB was intracavitary using a vaginal cylinder in 5 patients and interstitial using a modified Syed-Nesblett template in 13 patients. The dose of interstitial brachytherapy was 18.75 Gy in 5 fractions delivered twice daily. The median follow-up was 18 months (range 6–66 months).
Complete response (CR) was achieved in all but one patient (94%). Of these 17 patients achieving a CR, 1 had local recurrence and 3 had systemic recurrence at a median time of 6 months (range 6–22 months). The 2-year actuarial local control and cause-specific survival for the entire group were 88% and 82.5%, respectively. In subset analysis, the crude local control was 100% for primary vaginal cancer, 100% for the group with recurrence without any prior radiation and 67% for group with recurrence and prior radiation therapy. Two patients had late grade 3 or higher morbidity (rectovaginal fistula in one patient and chronic vaginal ulcer resulting in bleeding in one patient). Both these patients had prior radiation therapy.
Our small series suggests that HDRB is efficacious for primary or recurrent vaginal cancer. Patients treated with primary disease and those with recurrent disease without prior irradiation have the greatest benefit from HDRB in this setting. The salvage rate for patients with prior radiation therapy is lower with a higher risk of significant complications. Additional patients and follow-up are ongoing to determine the long-term efficacy of this approach.
Permanent low-dose-rate (LDR-BT) and temporary high-dose-rate (HDR-BT) brachytherapy are competitive techniques for clinically localized prostate radiotherapy. Although a randomized trial will likely never to be conducted comparing these two forms of brachytherapy, a comparative analysis proves useful in understanding some of their intrinsic differences, several of which could be exploited to improve outcomes. The aim of this paper is to look for possible similarities and differences between both brachytherapy modalities. Indications and contraindications for monotherapy and for brachytherapy as a boost to external beam radiation therapy (EBRT) are presented. It is suggested that each of these techniques has attributes that advocates for one or the other. First, they represent the extreme ends of the spectrum with respect to dose rate and fractionation, and therefore have inherently different radiobiological properties. Low-dose-rate brachytherapy has the great advantage of being practically a one-time procedure, and enjoys a long-term follow-up database supporting its excellent outcomes and low morbidity. Low-dose-rate brachytherapy has been a gold standard for prostate brachytherapy in low risk patients since many years. On the other hand, HDR is a fairly invasive procedure requiring several sessions associated with a brief hospital stay. Although lacking in significant long-term data, it possesses the technical advantage of control over its postimplant dosimetry (by modulating the source dwell time and position), which is absent in LDR brachytherapy. This important difference in dosimetric control allows HDR doses to be escalated safely, a flexibility that does not exist for LDR brachytherapy.
Radiobiological models support the current clinical evidence for equivalent outcomes in localized prostate cancer with either LDR or HDR brachytherapy, using current dose regimens. At present, all available clinical data regarding these two techniques suggests that they are equally effective, stage for stage, in providing high tumor control rates.
brachytherapy; HDR; LDR; prostate cancer; seeds
To review institutional experience treating patients who underwent breast conserving surgery and adjuvant accelerated partial breast irradiation with multilumen balloon brachytherapy (MLB) with close skin spacing (≤7 mm).
Material and methods
Since July 2009, 26 patients with skin spacing ≤ 7.0 mm were treated with breast-conserving therapy and adjuvant MLB brachytherapy. Patients were treated with either the Contura or MammoSite ML catheter to a total dose of 34 Gy in 10 fractions. Patients were assessed for acute toxicity at the completion of treatment and 1-month post treatment. Cosmesis and late toxicity were assessed at three-month intervals thereafter.
The median age of the patients was 56 years and median follow-up was 9 months. Sixteen patients had skin spacing of 5.0–7.0 mm, 10 with < 5.0 mm (median 5.8). The median percentage of the target (PTV_EVAL) receiving ≥ 95% of the prescription dose was 95.6%. The median volume of PTV_EVAL receiving ≥ 200% of the prescription dose was 6.1 cc. The maximum skin dose was 118.2% (median). The most commonly observed acute toxicity was grade 1-2 dermatitis (65.4%). The rate of post-treatment seroma and infection was 38.5% and 3.8%, respectively. Excellent/good cosmetic outcomes seen at the time of last follow-up was 92.3%.
MLB brachytherapy is safe and feasible in patients with close skin spacing, with acute toxicity and early cosmesis similar to other published series. These devices may broaden the application of balloon brachytherapy in patients previously excluded from this treatment based on anatomy.
brachytherapy; APBI; Contura; MammoSite; Multi-catheter
This retrospective, multicenter study evaluated the feasibility and safety of high-dose rate electronic brachytherapy (EBT) as a postsurgical adjuvant radiation therapy for endometrial cancer.
Medical records were reviewed from 41 patients (age 40–89 years) with endometrial cancer (Federation of International Gynecology and Obstetrics stages IA–IIIC) treated at nine centers between April 2008 and October 2009. Treatment included intracavitary vaginal EBT alone (n = l6) at doses of 18.0–24.0 Gy in 3–4 fractions and EBT in combination with external beam radiation therapy (EBRT, n = 25) at a total radiation dose range of 40.0–80.4 Gy. Doses were prescribed to a depth of 5 mm from the applicator surface and to the upper third (n = 15) and the upper half (n = 26) of the vagina.
Median follow-up was 3.8 (range 0.5–12.0) months. All 41 patients received the intended dose of radiation as prescribed. Adverse events occurred in 13 of 41 patients and were mild to moderate (Grade 1–2), consisting primarily of vaginal mucositis, rectal mucosal irritation and discomfort, and temporary dysuria and diarrhea. There were no Grade 3 adverse events in the EBT-only treatment group. One patient, who was being treated with the combination of EBT and EBRT for recurrent endometrial cancer, had a Grade 3 adverse event. No recurrences have been reported to date.
Electronic brachytherapy provides a feasible treatment option for postoperative adjuvant vaginal brachytherapy as sole radiation therapy and in combination with EBRT for primary endometrial cancer. Early and late toxicities were mild to moderate.
endometrial cancer; electronic brachytherapy; radiation therapy
Purpose of this study was to identify predictors of vaginal ulcer after CT based three-dimensional image-guided high-dose-rate interstitial brachytherapy (HDR-ISBT) for gynecologic malignancies.
Records were reviewed for 44 female (14 with primary disease and 30 with recurrence) with gynecological malignancies treated with HDR-ISBT with or without external beam radiation therapy. The HDR-ISBT applicator insertion was performed with image guidance by trans-rectal ultrasound and CT.
The median clinical target volume was 35.5 ml (2.4-142.1 ml) and the median delivered dose in equivalent dose in 2 Gy fractions (EQD2) for target volume D90 was 67.7 Gy (48.8-94.2 Gy, doses of external-beam radiation therapy and brachytherapy were combined). For re-irradiation patients, median EQD2 of D2cc for rectum and bladder, D0.5cc, D1cc, D2cc, D4cc, D6cc and D8cc for vaginal wall was 91.1 Gy, 100.9 Gy, 260.3 Gy, 212.3 Gy, 170.1 Gy, 117.1 Gy, 105.2 Gy, and 94.7 Gy, respectively. For those without prior radiation therapy, median EQD2 of D2cc for rectum and bladder, D0.5cc, D1cc, D2cc, D4cc, D6cc and D8cc for vaginal wall was 56.3 Gy, 54.3 Gy, 147.4 Gy, 126.2 Gy, 108.0 Gy, 103.5 Gy, 94.7 Gy, and 80.7 Gy, respectively. Among five patients with vaginal ulcer, three had prior pelvic radiation therapy in their initial treatment and three consequently suffered from fistula formation. On univariate analysis, re-irradiation and vaginal wall D2cc in EQD2 was the clinical predictors of vaginal ulcer (p = 0.035 and p = 0.025, respectively). The ROC analysis revealed that vaginal wall D2cc is the best predictor of vaginal ulcer. The 2-year incidence rates of vaginal ulcer in the patients with vaginal wall D2cc in EQD2 equal to or less than 145 Gy and over 145 Gy were 3.7% and 23.5%, respectively, with a statistically significant difference (p = 0.026).
Re-irradiation and vaginal D2cc is a significant predictor of vaginal ulcer after HDR-ISBT for gynecologic malignancies. Three-dimensional image-guided treatment planning should be performed to ensure adequate target coverage while minimizing vaginal D2cc in order to avoid vagina ulcer.
Gynecologic brachytherapy; High-dose-rate brachytherapy; Interstitial brachytherapy; Vaginal ulcer
The aim of this study is to describe the feasibility and efficacy of the laparoscopic upper vaginectomy (LUV) in vaginal intraepithelial neoplasia(VAIN) and superficially invasive vaginal carcinoma.
We studied patients with vaginal intraepithelial neoplasia (VAIN) 2, VAIN 3, and superficially invasive vaginal carcinoma after hysterectomy who have been under laparoscopic upper vaginectomy between March 2010 and March 2012.
Four patients underwent LUV after hysterectomy for high risk VAIN and early vaginal cancer. The mean age was 50.8 (range 40–56) years; the mean operation time was 162.5 (range 145–205) minutes; and the mean estimated blood loss was 55 (range 20–100) ml. All the patients restituted bladder function after the removal of the foley catheter. Mean hospital stay was 2 days. Two patients had postoperative complications. One patient with warfarin administration had vaginal stump bleeding and another developed vesico-vaginal fistula. Three of the patients had no residual lesion, but 1 patient had VAIN 1 in the resection margin. Colposcopy was followed on all patients and cytology proved no recurrence.
LUV after hysterectomy is a feasible procedure and attentively applicable to high risk VAIN or superficially invasive vaginal carcinoma.
Vaginal carcinoma; Vaginal intraepithelial neoplasia; Vaginectomy
Brachytherapy, interstitial tumor bed irradiation, following conservative surgery has been shown to provide excellent local control and limb preservation in patients with soft tissue sarcomas (STS), whereas little is known about the tolerance of peripheral nerves to brachytherapy. In particular, nerve tolerance to high-dose-rate (HDR) brachytherapy has never been properly evaluated. In this study, we examined the efficacy and radiation neurotoxicity of HDR brachytherapy in patients with STS in contact with neurovascular structures.
Between 1995 and 2000, seven patients with STS involving the neurovascular bundle were treated in our institute with limb-preserving surgery, followed by fractionated HDR brachytherapy. Pathological examination demonstrated that 6 patients had high-grade lesions with five cases of negative margins and one case with positive margins, and one patient had a low-grade lesion with a negative margin. Afterloading catheters placed within the tumor bed directly upon the preserved neurovascular structures were postoperatively loaded with Iridium-192 with a total dose of 50 Gy in 6 patients. One patient received 30 Gy of HDR brachytherapy combined with 20 Gy of adjuvant external beam radiation.
With a median follow-up of 4 years, the 5-year actuarial overall survival, disease-free survival, and local control rates were 83.3, 68.6, and 83.3%, respectively. None of the 7 patients developed HDR brachytherapy-induced peripheral neuropathy. Of 5 survivors, 3 evaluable patients had values of motor nerve conduction velocity of the preserved peripheral nerve in the normal range.
In this study, there were no practical and electrophysiological findings of neurotoxicity of HDR brachytherapy. Despite the small number of patients, our encouraging results are valuable for limb-preserving surgery of unmanageable STS involving critical neurovascular structures.
To report the outcomes of patients receiving vaginal brachytherapy and/or external beam radiation therapy (EBRT) for primary vaginal cancer.
Material and methods
Between 1983 and 2009, 63 patients received brachytherapy and/or EBRT for primary tumors of the vagina at a single tertiary center. Patient data was collected via chart review. The Kaplan-Meier method was used to calculate actuarial pelvic local control (LC), disease-free survival (DFS), overall survival (OS), and severe late toxicity rates. Acute and late toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3 (CTCAE v3.0).
Median follow up was 44.2 months. Patients with early stage disease (stages I and II) had significantly improved 5-year OS when compared to patients with locally advanced disease (stages III and IVA) (73.3 vs. 34.4%, p = 0.032). Patients with greater than 1/3 vaginal involvement had significantly worse prognosis than patients with tumors involving 1/3 or less of the vagina, with the later having superior DFS (84.0 vs. 52.4%, p = 0.007) and LC (86.9 vs. 60.4%, p = 0.018) at 5-years. Age, histology, and brachytherapy technique did not impact treatment outcomes. The 5-year actuarial grade 3 or higher toxicity rate was 23.1% (95% CI: 10.6-35.6%). Concurrent chemotherapy had no impact on outcomes or toxicity in this analysis.
Success of treatment for vaginal cancer depends primarily on disease stage, but other contributing factors such as extent of vaginal involvement and tumor location significantly impact outcomes. Treatment of vaginal cancer with primary radiotherapy yields acceptable results with reasonable toxicity rates. Management of this rare malignancy requires a multidisciplinary approach to appropriately optimize therapy.
brachytherapy; radiation therapy; vaginal cancer
The literature supporting high-dose rate brachytherapy (HDR) in the treatment of cervical carcinoma derives primarily from retrospective series. However, controversy still persists regarding the efficacy and safety of HDR brachytherapy compared to low-dose rate (LDR) brachytherapy, in particular, due to inadequate tumor coverage for stage III patients. Whether LDR or HDR brachytherapy produces better results for these patients in terms of survival rate, local control rate and the treatment complications remain controversial.
A meta-analysis of RCT was performed comparing LDR to HDR brachytherapy for cervix cancer treated for radiotherapy alone. The MEDLINE, EMBASE, CANCERLIT and Cochrane Library databases, as well as abstracts published in the annual proceedings were systematically searched. We assessed methodological quality for each outcome by grading the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. We used "recommend" for strong recommendations, and "suggest" for weak recommendations.
Pooled results from five randomized trials (2,065 patients) of HDR brachytherapy in cervix cancer showed no significant increase of mortality (p = 0.52), local recurrence (p = 0.68), or late complications (rectal; p = 0.7, bladder; p = 0.95 or small intestine; p = 0.06) rates as compared to LDR brachytherapy. In the subgroup analysis no difference was observed for overall mortality and local recurrence in patients with clinical stages I, II and III. The quality of evidence was low for mortality and local recurrence in patients with clinical stage I, and moderate for other clinical stages.
Our meta-analysis shows that there are no differences between HDR and LDR for overall survival, local recurrence and late complications for clinical stages I, II and III. By means of the GRADE system, we recommend the use of HDR for all clinical stages of cervix cancer.
The purpose of this study was to evaluate the efficacy and safety of high-dose-rate (HDR) brachytherapy of a single implant with two fractions plus external beam radiotherapy (EBRT) for hormone-naïve prostate cancer in comparison with radical prostatectomy. Of 150 patients with localized prostate cancer (T1c–T2c), 59 underwent HDR brachytherapy plus EBRT, and 91 received radical prostatectomy. The median follow-up of patients was 62 months for HDR brachytherapy plus EBRT, and 64 months for radical prostatectomy. In patient backgrounds between the two cohorts, the frequency of T2b plus T2c was greater in HDR brachytherapy cohort than in prostatectomy cohort (27% versus 12%, p = 0.029). Patients in HDR brachytherapy cohort first underwent 3D conformal RT with four beams to the prostate to an isocentric dose of 50 Gy in 25 fractions and then, a total of 15–18 Gy in two fractions at least 5 hours apart. We prescribed 9 Gy/fraction for target (prostate gland plus 3 mm lateral outside margin and seminal vesicle) using CT image method for radiation planning. The total biochemical failure-free control rates (BF-FCR) at 3 and 5 years for the HDR brachytherapy cohort, and for the prostatectomy cohort were 92% and 85%, and 72% and 72%, respectively (significant difference, p = 0.0012). The 3-and 5-year BF-FCR in the HDR brachytherapy cohort and in the prostatectomy cohort by risk group was 100 and 100%, and 80 and 80%, respectively, for the low-risk group (p = 0.1418); 92 and 92%, 73 and 73%, respectively, for the intermediate-risk group (p = 0.0492); and 94 and 72%, 45 and 45%, respectively, for the high-risk group (p = 0.0073). After HDR brachytherapy plus EBRT, no patient experienced Grade 2 or greater genitourinay toxicity. The rate of late Grade 1 and 2 GI toxicity was 6% (n = 4). No patient experienced Grade 3 GI toxicity. HDR brachytherapy plus EBRT is useful for treating patients with hormone-naïve localized prostate cancer, and has low GU and GI toxicities.
prostate cancer; high dose rate brachytherapy; external beam radiation therapy; radical prostatectomy
To investigate the dosimetric difference due to the different point A definitions in cervical cancer low-dose-rate (LDR) intracavitary brachytherapy.
Material and methods
Twenty CT-based LDR brachytherapy plans of 11 cervical patients were retrospectively reviewed. Two plans with point As following the modified Manchester system which defines point A being 2 cm superior to the cervical os along the tandem and 2 cm lateral (Aos), and the American Brachytherapy Society (ABS) guideline definition in which the point A is 2 cm superior to the vaginal fornices instead of os (Aovoid) were generated. Using the same source strength, two plans prescribed the same dose to Aos and Aovoid. Dosimetric differences between plans including point A dose rate, treatment volume encompassed by the prescription isodose line (TV), and dose rate of 2 cc of the rectum and bladder to the prescription dose were measured.
On average Aovoid was 8.9 mm superior to Aos along the tandem direction with a standard deviation of 5.4 mm. With the same source strength and arrangement, Aos dose rate was 19% higher than Aovoid dose rate. The average TV(Aovoid) was 118.0 cc, which was 30% more than the average TV(Aos) of 93.0 cc. D2cc/D(Aprescribe) increased from 51% to 60% for rectum, and increased from 89% and 106% for bladder, if the prescription point changed from Aos to Aovoid.
Different point A definitions lead to significant dose differences. Careful consideration should be given when changing practice from one point A definition to another, to ensure dosimetric and clinical equivalency from the previous clinical experiences.
cervical cancer; LDR brachytherapy; point A
Prostate brachytherapy can be used as a monotherapy for low- and intermediate-risk patients or in combination with external beam radiation therapy (EBRT) as a form of dose escalation for selected intermediate- and high-risk patients. Prostate brachytherapy with either permanent implants (low dose rate [LDR]) or temporary implants (high dose rate [HDR]) is emerging as the most effective radiation treatment for prostate cancer. Several large Canadian brachytherapy programs were established in the mid- to late-1990s. Prostate brachytherapy is offered in British Columbia, Alberta, Manitoba, Ontario, Quebec and New Brunswick. We anticipate the need for brachytherapy services in Canada will significantly increase in the near future. In this review, we summarize brachytherapy programs across Canada, contemporary eligibility criteria for the procedure, toxicity and prostate-specific antigen recurrence free survival (PRFS), as published from Canadian institutions for both LDR and HDR brachytherapy.
Background and Purpose
To evaluate the proximity, variance, predictors of dose, and complications to the sigmoid in cervical-cancer brachytherapy using 3D planning.
Materials and Methods
Over 36 months, 50 patients were treated for cervical cancer with either low-dose-rate (LDR) or high-dose-rate (HDR) brachytherapy. The distance from the central tandem to the sigmoid, the D0.1cc and the D2cc to the sigmoid, rectum and bladder doses, and toxicity were analyzed.
The median sigmoid EQD2 D0.1cc and D2cc were 84 Gy and 68.3 Gy for HDR versus 71.1 Gy and 65.9 Gy for LDR (p=0.02 and 0.98, respectively). Twenty percent of the HDR fractions required manipulation of the superior dwell positions to decrease the sigmoid dose. The median distance from the sigmoid to the tandem was 1.7 cm (range [rg], 0.1 – 6.16 cm) for HDR and 2.7 cm (rg, 1.17 – 4.52 cm) for LDR; from the sigmoid to the 100% isodose region the median distances were – 0.1 cm (rg, -1.4 – 2.5 cm) and 0.44 cm (rg. -0.73 – 5.2 cm), respectively. The proximity of the sigmoid to the tandem is significantly related to sigmoid dose (p<0.0001). Within-patient (among-fraction) variation in sigmoid-to-tandem distance during HDR was substantial (coefficient of variation = 40%). No grade 3-4 sigmoid toxicity was seen after a median 31-month follow-up period.
3D imaging in cervical cancer brachytherapy shows the sigmoid in close proximity to the tandem. The sigmoid to tandem distance varies substantially between fractions, indicating the importance of sigmoid dose-volume evaluation with each fraction.
cervical cancer; brachytherapy; normal tissue dose
A crucial factor concerning the utility of Cancer Registries is the data quality with respect to comparability, completeness, validity and timeliness. However, the data quality of the registration of premalignant lesions has rarely been addressed. High grade vulvar intraepithelial neoplasia (VIN) and vaginal intraepithelial neoplasia (VaIN) are premalignant lesions which may develop into cancer, and are often associated with infection with the human papillomarvirus (HPV). The aim was to evaluate the quality of registration of VIN and VaIN at the Cancer Registry of Norway (CRN).
Material and methods
We re-collected all notifications with high grade VIN and VaIN diagnoses during 2002 to 2007 from pathology laboratories, and compared these to the data in the CRN database so as to quantitatively measure the completeness, validity and timeliness of the data.
Over the period 2002 to 2007 we estimated the completeness of the 1556 VIN and 297 VaIN notifications to be 95.0% and 92.9%, respectively. The original and reabstracted topography codes showed major discrepancies for 12 of 642 (1.9%) VIN and 7 of 128 (5.5%) VaIN notifications. The original and reabstracted morphology codes for VIN and VaIN were identical for 724 out of 814 notifications. Sixteen notifications had a major discrepancy. For the period 2002 to 2007 the median time elapsed between date of diagnosis and date of registration were 436 and 441 days for VTN and VaIN cases, respectively.
Based on the present analysis of the comparability, completeness, validity and timeliness of premalignant lesions of vulva and vagina, we conclude that the Cancer Registry of Norway is able to monitor such premalignant lesions satisfactorily.