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1.  Efficacy and Safety of High-Dose-Rate Brachytherapy of Single Implant with Two Fractions Combined with External Beam Radiotherapy for Hormone-Naïve Localized Prostate Cancer 
Cancers  2011;3(3):3585-3600.
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.
doi:10.3390/cancers3033585
PMCID: PMC3759211  PMID: 24212968
prostate cancer; high dose rate brachytherapy; external beam radiation therapy; radical prostatectomy
2.  Surgical resection with adjuvant brachytherapy in soft tissue sarcoma of the extremity – a case report 
Purpose
Surgery is the major therapeutic method in soft tissue sarcomas of the extremity (E-STS). Treatment of large high-grade tumours, which resection cannot be performed with a wide safe margin, should include complementary radiation and/or chemo-therapy. Hopefully, the use of adjuvant brachytherapy will improve the prognosis of E-STS.
Case description
After a long process of diagnosing a tumour in the medial compartment of the thigh, a 65-year-old woman with diagnosed synovial sarcoma underwent a surgery. Compartment resection was performed and the tumour was removed with a 10 mm safety margin of healthy tissue. Adjuvant brachytherapy was delivered with 192Ir (MicroSelectron, Nucletron Electa Group, Stockholm, Sweden®) with 10 Ci of nominal activity to a dose of 55 Gy in 16 days because of large tumour size (99 × 78 × 73 mm) and its proximity to the neurovascular bundle. No complications were reported. The patient was discharged from the hospital on the 28th day after the surgery. The wound healed without any complications and the outpatient follow-up is being continued.
Discussion
Adjuvant brachytherapy is rarely used after surgical treatment due to its limited accessibility in hospitals with surgical and orthopaedic departments. There are numerous publications proving positive influence of brachytherapy on local control and decreased number of recurrences. The recurrence-free survival time also increased significantly, however no direct impact on the number of distant metastases was found. Treatment is well tolerated and short. The complication rate varies between centres from 5 to 30%. The most common adverse effects include: peripheral neuropathy, skin necrosis and osteonecrosis of the long bones.
Conclusions
Treatment of large soft tissue sarcomas of the extremity (E-STS) should include combination of surgical intervention and external beam radiotherapy or brachytherapy. Adjuvant brachytherapy improves local control rate up to 78%, is well tolerated and rarely causes complications. We couldn't determine which type of adjuvant radiation therapy is more effective.
doi:10.5114/jcb.2012.32557
PMCID: PMC3561605  PMID: 23378852
soft tissue sarcoma; brachytherapy; compartment surgery
3.  Thermal boost combined with interstitial brachytherapy in breast conserving therapy – Assessment of early toxicity 
Background
Hyperthermia (HT) causes a direct damage to cancerous cells and/or sensitize them to radiotherapy with usually minimal injury to normal tissues. Adjuvant HT is probably one of the most effective radiation sensitizers known and works best when delivered simultaneously with radiation. In breast conserving therapy, irradiation has to minimize the risk of local relapse within the treated breast, especially in an area of a tumor bed. Brachytherapy boost reduces 5-year local recurrence rate to mean 5,5%, so there still some place for further improvement. The investigated therapeutic option is an adjuvant single session of local HT (thermal boost) preceding standard CT-based multicatheter interstitial HDR brachytherapy boost in order to increase the probability of local cure.
Aim
To report the short-term results in regard to early toxicity of high-dose-rate (HDR) brachytherapy (BT) boost with or without interstitial microwave hyperthermia (MV HT) for early breast cancer patients treated with breast conserving therapy (BCT).
Materials and methods
Between February 2006 and December 2007, 57 stage IA–IIIA breast cancer patients received a 10 Gy HDR BT boost after conservative surgery and 42.5–50 Gy whole breast irradiation (WBI) ± adjuvant chemotherapy. 32 patients (56.1%) were treated with additional pre-BT single session of interstitial MW HT to a tumor bed (multi-catheter technique). Reference temperature was 43 °C and therapeutic time (TT) was 1 h. Incidence, severity and duration of radiodermatitis, skin oedema and skin erythema in groups with (I) or without HT (II) were assessed, significant p-value ≤ 0.05.
Results
Median follow-up was 40 months. Local control was 100% and distant metastasis free survival was 91.1%. HT sessions (median): reference temperature 42.2 °C, therapeutic time (TT) 61.4 min, total thermal dose 42 min and a gap between HT and BT 30 min. Radiodermatitis grades I and II occurred in 24 and 6 patients, respectively, differences between groups I and II were not significant. Skin oedema and erythema occurred in 48 (85.7%) and 36 (64.3%) cases, respectively, and were equally distributed between the groups. The incidence and duration of skin oedema differed between the subgroups treated with different fractionation protocols of WBI, p = 0.006. Skin oedema was present up to 12 months. No difference in pattern of oedema regression between groups I and II was observed, p = 0.933.
Conclusion
Additional thermal boost preceding standard HDR BT boost has a potential of further improvement in breast cancer local control in BCT. Pre-BT hyperthermia did not increase early toxicity in patients treated with BCT and was well tolerated. All side effects of combined treatment were transient and were present for up to 12 months. The increase in incidence of skin oedema was related to hypofractionated protocols of WBI. The study has to be randomized and continued on a larger group of breast cancer patients to verify the potential of local control improvement and to assess the profile of late toxicity.
doi:10.1016/j.rpor.2011.02.004
PMCID: PMC3863141  PMID: 24376963
Hyperthermia; Brachytherapy boost; Breast cancer
4.  Radiation therapy for primary vaginal carcinoma 
Journal of Radiation Research  2013;54(5):931-937.
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.
doi:10.1093/jrr/rrt028
PMCID: PMC3766300  PMID: 23559599
primary vaginal cancer; radiation therapy; high-dose-rate brachytherapy; intracavitary brachytherapy; interstitial brachytherapy
5.  Dosimetric analysis and comparison of IMRT and HDR brachytherapy in treatment of localized prostate cancer 
Radical radiotherapy is one of the options for the management of prostate cancer. In external beam therapy, 3D conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) are the options for delivery of increased radiation dose, as vital organs are very close to the prostate and a higher dose to these structures leads to an increased toxicity. In brachytherapy, low dose rate brachytherapy with permanent implant of radioactive seeds and high dose rate brachytherapy (HDR) with remote after loaders are available. A dosimetric analysis has been made on IMRT and HDR brachytherapy plans. Ten cases from each IMRT and HDR brachytherapy have been taken for the study. The analysis includes comparison of conformity and homogeneity indices, D100, D95, D90, D80, D50, D10 and D5 of the target. For the organs at risk (OAR), namely rectum and bladder, V100, V90 and V50 are compared. In HDR brachytherapy, the doses to 1 cc and 0.1 cc of urethra have also been studied. Since a very high dose surrounds the source, the 300% dose volumes in the target and within the catheters are also studied in two plans, to estimate the actual volume of target receiving dose over 300%. This study shows that the prescribed dose covers 93 and 92% of the target volume in IMRT and HDR brachytherapy respectively. HDR brachytherapy delivers a much lesser dose to OAR, compared to the IMRT. For rectum, the V50 in IMRT is 34.0cc whilst it is 7.5cc in HDR brachytherapy. With the graphic optimization tool in HDR brachytherapy planning, the dose to urethra could be kept within 120% of the target dose. Hence it is concluded that HDR brachytherapy may be the choice of treatment for cancer of prostate in the early stage.
doi:10.4103/0971-6203.62201
PMCID: PMC2884303  PMID: 20589121
Brachytherapy; conformity; intensity modulated radiotherapy; prostate
6.  The emerging role of high-dose-rate (HDR) brachytherapy as monotherapy for prostate cancer 
Journal of Radiation Research  2013;54(5):781-788.
High-dose-rate (HDR) brachytherapy as monotherapy is a comparatively new brachytherapy procedure for prostate cancer. In addition to the intrinsic advantages of brachytherapy, including radiation dose concentration to the tumor and rapid dose fall-off at the surrounding normal tissue, HDR brachytherapy can yield a more homogeneous and conformal dose distribution through image-based decisions for source dwell positions and by optimization of individual source dwell times. Indication can be extended even to T3a/b or a part of T4 tumors because the applicators can be positioned at the extracapsular lesion, into the seminal vesicles, and/or into the bladder, without any risk of source migration or dropping out. Unlike external beam radiotherapy, with HDR brachytherapy inter-/intra-fraction organ motion is not problematic. However, HDR monotherapy requires patients to stay in bed for 1–4 days during hospitalization, even though the actual overall treatment time is short. Recent findings that the α/β value for prostate cancer is less than that for the surrounding late-responding normal tissue has made hypofractionation attractive, and HDR monotherapy can maximize this advantage of hypofractionation. Research on HDR monotherapy is accelerating, with a growing number of publications reporting excellent preliminary clinical results due to the high ‘biologically effective dose (BED)’ of >200 Gy. Moreover, the findings obtained for HDR monotherapy as an early model of extreme hypofractionation tend to be applied to other radiotherapy techniques such as stereotactic radiotherapy. All these developments point to the emerging role of HDR brachytherapy as monotherapy for prostate cancer.
doi:10.1093/jrr/rrt027
PMCID: PMC3766299  PMID: 23543798
prostate cancer; high-dose-rate (HDR); brachytherapy; monotherapy; hypofractionation
7.  Low-dose-rate or high-dose-rate brachytherapy in treatment of prostate cancer – between options 
Purpose
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.
Conclusions
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.
doi:10.5114/jcb.2013.34342
PMCID: PMC3635047  PMID: 23634153
brachytherapy; HDR; LDR; prostate cancer; seeds
8.  Accelerated partial breast irradiation using multicatheter brachytherapy for select early-stage breast cancer: local control and toxicity 
Background
To investigate the efficacy and safety of accelerated partial breast irradiation (APBI) via high-dose-rate (HDR) multicatheter interstitial brachytherapy for early-stage breast cancer.
Methods
Between 2002 and 2006, 48 prospectively selected patients with early-stage breast cancer received APBI using multicatheter brachytherapy following breast-conserving surgery. Their median age was 52 years (range 36-78). A median of 34 Gy (range 30-34) in 10 fractions given twice daily within 5 days was delivered to the tumor bed plus a 1-2 cm margin. Most (92%) patients received adjuvant systemic treatments. The median follow-up was 53 months (range 36-95). Actuarial local control rate was estimated from surgery using Kaplan-Meier method.
Results
Local recurrence occurred in two patients. Both were true recurrence/marginal miss and developed in patients with close (< 0.2 cm) surgical margin after 33 and 40 months. The 5-year actuarial local recurrence rate was 4.6%. No regional or distant relapse and death has occurred to date. Late Grade 1 or 2 late skin and subcutaneous toxicity was seen in 11 (22.9%) and 26 (54.2%) patients, respectively. The volumes receiving 100% and 150% of the prescribed dose were significantly higher in the patients with late subcutaneous toxicity (p = 0.018 and 0.034, respectively). Cosmesis was excellent to good in 89.6%.
Conclusions
APBI using HDR multicatheter brachytherapy yielded local control, toxicity, and cosmesis comparable to those of conventional whole breast irradiation for select early-stage breast cancer. Patients with close resection margins may be ineligible for APBI.
doi:10.1186/1748-717X-5-56
PMCID: PMC2905428  PMID: 20565899
9.  Angiosarcoma of the scalp: a case report 
Purpose
The aim of this paper is to report the treatment of angiosarcoma of the scalp. High-dose-rate (HDR) brachytherapy with an individual mold applicator is presented.
Case description
A case of a 75-year-old male will be presented with multicentric lesions over the scalp in the temple and crown region. Biopsy diagnosis was angiosarcoma of the scalp, nonoperable. The patient was qualified for chemotherapy combined with radiotherapy.
Discussion
Angiosarcoma of the scalp is a very aggressive tumor. The main aim of the treatment of angiosarcoma is local control of the tumor. Most cases are treated with wide excision surgery. The use of surgery with adjuvant radiotherapy or chemotherapy is recommended in some cases. Chemotherapy and radiotherapy are suggested in the recurrent or extensive lesions with regional or distant metastasis. Radiation therapy can be realized with external beam therapy or brachytherapy. High-dose-rate brachytherapy is an effective, adequate, well tolerated by patients treatment method. In every case, an individual approach is needed.
Conclusions
The HDR brachytherapy technique is useful and practicable. The advantages of brachytherapy are: targeted dose distribution, low integral dose, and short time of treatment. The mold HDR brachytherapy treatment using an individual applicator was an appropriate tool for the presented patient.
doi:10.5114/jcb.2014.43183
PMCID: PMC4105641  PMID: 25097563
angiosarcoma; HDR brachytherapy; mold applicator
10.  Tolerance of the vaginal vault to high-dose rate brachytherapy and concomitant chemo-pelvic irradiation: Long-term perspective☆ 
Aim/background
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.
Results
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.
Conclusions
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.
doi:10.1016/j.rpor.2013.09.005
PMCID: PMC4056520  PMID: 24936320
Tolerance; Vagina; Irradiation; High-dose-rate; Brachytherapy
11.  The role of high-dose-rate brachytherapy boost in breast-conserving therapy: Long-term results of the Hungarian National Institute of Oncology 
Aim
To report the long-term results of high-dose-rate (HDR) brachytherapy (BT) boost for breast cancer patients treated with conservative surgery and radiotherapy.
Materials and methods
Between 1995 and 2007, 100 early-stage breast cancer patients received an HDR BT boost after conservative surgery and whole breast irradiation. Ten patients (10%) received a single-fraction HDR boost of 8–10.35 Gy using rigid needles, while 90 (90%) were treated with a fractionated multi-catheter HDR BT boost. The latter consisted of 3 × 4 Gy (n = 19), 3 × 4.75 Gy (n = 70), and 2 × 6.4 Gy (n = 1). Breast cancer related events, cosmetic results and side effects were assessed.
Results
At a median follow-up time of 94 months (range: 8–152) only 7 (7%) ipsilateral breast failures were observed for a 5- and 8-year actuarial rate of 4.5 and 7.0%, respectively. The 8-year disease-free, cancer-specific, and overall survival was 76.1, 82.8, and 80.4%, respectively. Cosmetic outcome was rated excellent in 17%, good in 39%, fair in 33%, and poor in 11%. Data on late radiation side effects were available for 91 patients (91%). Grade 3 fibrosis and grade 3 telangiectasia occurred in 6 (6.6%) and 2 (2.2%) patients, respectively. In univariate analysis only positive margin status had a significant negative effect on local control.
Conclusions
HDR BT boost using multi-catheter implants produce excellent long-term local tumour control with acceptable cosmetic outcome and low rate of grade 3 late radiation side effects.
doi:10.1016/j.rpor.2010.01.002
PMCID: PMC3863209  PMID: 24376915
Breast-conserving therapy; Radiotherapy; High-dose-rate brachytherapy; Boost
12.  Analysis of prognostic factors in localized high-risk prostate cancer patients treated with HDR brachytherapy, hypofractionated 3D-CRT and neoadjuvant/adjuvant androgen deprivation therapy (trimodality therapy) 
Journal of Radiation Research  2013;55(3):527-532.
Trimodality therapy consisting of high dose rate (HDR) brachytherapy combined with external beam radiation therapy (EBRT), neoadjuvant hormonal therapy (NHT) and adjuvant hormonal therapy (AHT) has been used to treat localized high-risk prostate cancer. In this study, an analysis of patients receiving the trimodality therapy was performed to identify prognostic factors of biochemical relapse-free survival (bRFS). Between May 2005 and November 2008, 123 high-risk prostate cancer patients (D'Amico classification) were treated with NHT prior to HDR brachytherapy combined with hypofractionated EBRT. Among these patients, 121 had completed AHT. The patients were assigned by time to be treated with a low-dose or high-dose arm of HDR brachytherapy with subsequent hypofractionated 3D conformal radiation therapy (3D-CRT). Multivariate analysis was used to determine prognostic factors for bRFS. With a median follow-up of 60 months, the 5-year bRFS for all patients was 84.3% (high-dose arm, 92.9%; low-dose arm, 72.4%, P = 0.047). bRFS in the pre-HDR PSA ≤ 0.1 ng/ml subgroup was significantly improved compared with that in the pre-HDR PSA > 0.1 ng/ml subgroup (88.3% vs 68.2%, P = 0.034). On multivariate analysis, dose of HDR (P = 0.045, HR = 0.25, 95% CI = 0.038–0.97) and pre-HDR PSA level (P = 0.02 HR = 3.2, 95% CI = 1.18–10.16) were significant prognostic factors predicting bRFS. In high-risk prostate cancer patients treated with the trimodality therapy, the dose of HDR and pre-HDR PSA were significant prognostic factors. The pre-HDR PSA ≤ 0.1 subgroup had significantly improved bRFS. Further studies are needed to confirm the relevance of pre-HDR PSA in trimodality therapy.
doi:10.1093/jrr/rrt134
PMCID: PMC4014157  PMID: 24351458
high-risk prostate cancer; HDR; trimodality therapy; PSA response
13.  In vivo assessment of catheter positioning accuracy and prolonged irradiation time on liver tolerance dose after single-fraction 192Ir high-dose-rate brachytherapy 
Background
To assess brachytherapy catheter positioning accuracy and to evaluate the effects of prolonged irradiation time on the tolerance dose of normal liver parenchyma following single-fraction irradiation with 192 Ir.
Materials and methods
Fifty patients with 76 malignant liver tumors treated by computed tomography (CT)-guided high-dose-rate brachytherapy (HDR-BT) were included in the study. The prescribed radiation dose was delivered by 1 - 11 catheters with exposure times in the range of 844 - 4432 seconds. Magnetic resonance imaging (MRI) datasets for assessing irradiation effects on normal liver tissue, edema, and hepatocyte dysfunction, obtained 6 and 12 weeks after HDR-BT, were merged with 3D dosimetry data. The isodose of the treatment plan covering the same volume as the irradiation effect was taken as a surrogate for the liver tissue tolerance dose. Catheter positioning accuracy was assessed by calculating the shift between the 3D center coordinates of the irradiation effect volume and the tolerance dose volume for 38 irradiation effects in 30 patients induced by catheters implanted in nearly parallel arrangement. Effects of prolonged irradiation were assessed in areas where the irradiation effect volume and tolerance dose volume did not overlap (mismatch areas) by using a catheter contribution index. This index was calculated for 48 irradiation effects induced by at least two catheters in 44 patients.
Results
Positioning accuracy of the brachytherapy catheters was 5-6 mm. The orthogonal and axial shifts between the center coordinates of the irradiation effect volume and the tolerance dose volume in relation to the direction vector of catheter implantation were highly correlated and in first approximation identically in the T1-w and T2-w MRI sequences (p = 0.003 and p < 0.001, respectively), as were the shifts between 6 and 12 weeks examinations (p = 0.001 and p = 0.004, respectively). There was a significant shift of the irradiation effect towards the catheter entry site compared with the planned dose distribution (p < 0.005). Prolonged treatment time increases the normal tissue tolerance dose. Here, the catheter contribution indices indicated a lower tolerance dose of the liver parenchyma in areas with prolonged irradiation (p < 0.005).
Conclusions
Positioning accuracy of brachytherapy catheters is sufficient for clinical practice. Reduced tolerance dose in areas exposed to prolonged irradiation is contradictory to results published in the current literature. Effects of prolonged dose administration on the liver tolerance dose for treatment times of up to 60 minutes per HDR-BT session are not pronounced compared to effects of positioning accuracy of the brachytherapy catheters and are therefore of minor importance in treatment planning.
doi:10.1186/1748-717X-6-107
PMCID: PMC3179944  PMID: 21892943
14.  Age is not a limiting factor for brachytherapy for carcinoma of the node negative oral tongue in patients aged eighty or older 
Background
To examine the role of brachytherapy for aged patients 80 or more in the trend of rapidly increasing number.
Methods
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.
Results
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.
Conclusion
Age is not a limiting factor for brachytherapy for appropriately selected elderly patients, and brachytherapy achieved good local control with acceptable morbidity.
doi:10.1186/1748-717X-5-116
PMCID: PMC3016284  PMID: 21143904
15.  Electronic brachytherapy as adjuvant therapy for early stage breast cancer: a retrospective analysis 
OncoTargets and therapy  2011;4:13-20.
Purpose:
This multicenter, retrospective study evaluated treatment and clinical outcomes of patients with early stage breast cancer who received adjuvant high-dose rate (HDR) electronic brachytherapy (EBT) treatment post-lumpectomy using the Axxent® EBT system. Dosimetric data from the EBT treatment plans were compared with those based on iridium-192 HDR brachytherapy.
Material and methods:
Medical records of 63 patients with early stage breast cancer (Tis, T1a, T1b, T1c, and T2) who were treated post-lumpectomy with EBT alone or in combination with external beam radiation therapy were reviewed. The prescribed EBT dose was 34 Gy (10 fractions over 5 days, 3.4 Gy each) to 1 cm from the balloon surface. Dosimetry data from 12 patients were compared with these of treatment plans using an iridium-192 source prepared for the same 12 patients.
Results:
The majority of patients (90.5%) were older than 50 years and had one or more risk factors for breast cancer (80.6%). Tumor sizes were 0.1 cm to 3.5 cm (mean 1.3 cm). Median follow-up was 7 months (1 to 18 months) post-EBT. Balloon applicators were implanted 0 to 85 days (mean 13.4 days) post-lumpectomy/re-excision. The most common adverse events were erythema, rash dermatitis, and pain or breast tenderness. No recurrences were reported. Dosimetric analyses demonstrated comparable target coverage, increased high-dose regions, and a significantly reduced dose to the ipsilateral breast and lungs as well as the heart with EBT as compared with the iridium-192 treatment plans.
Conclusion:
This retrospective, multicenter study showed that postsurgical adjuvant radiation therapy for early stage breast cancer can be administered using the EBT system with similar toxicity outcomes to those reported with iridium-192 brachytherapy. EBT offers a convenient, portable, nonisotope alternative to HDR brachytherapy using iridium-192.
doi:10.2147/OTT.S15297
PMCID: PMC3084303  PMID: 21552411
electronic brachytherapy; breast cancer; radiation therapy
16.  The relationship between the biochemical control outcomes and the quality of planning of high-dose rate brachytherapy as a boost to external beam radiotherapy for locally and locally advanced prostate cancer using the RTOG-ASTRO Phoenix definition 
Purpose: To evaluated prognostic factors and impact of the quality of planning of high dose rate brachytherapy (HDR-BT) for patients with local or locally advanced prostate cancer treated with external beam radiotherapy (EBRT) and HDR-BT.
Methods and Materials: Between 1997 and 2005, 209 patients with biopsy proven prostate adenocarcinoma were treated with localized EBRT and HDR-BT at the Department of Radiation-Oncology, Hospital A. C. Camargo, Sao Paulo, Brazil. Patient's age, Gleason score (GS), clinical stage (CS), initial PSA (iPSA), risk group for biochemical failure (GR), doses of EBRT and HDR-BT, use of three-dimensional planning for HDR-BT (3DHDR) and the Biological Effective Dose (BED) were evaluated as prognostic factors for biochemical control (bC).
Results: Median age and median follow-up time were 68 and 5.3 years, respectively. Median EBRT and HDR-BT doses were 45 Gy and 20 Gy. The crude bC at 3.3 year was 94.2%. For the Low, intermediate and high risk patients the bC rates at 3.3 years were 91.5%, 90.2% and 88.5%, respectively. Overall survival (OS) and disease specific survival rates at 3.3 years were 97.8% and 98.4%, respectively. On univariate analysis the prognostic factors related bC were GR (p= 0.040), GS ≤ 6 (p= 0.002), total dose of HDR-BT ≥ 20 Gy (p< 0.001), 3DHDR (p< 0.001), BED-HDR ≥ 99 Gy1.5 (p<0.001) and BED-TT ≥ 185 (p<0.001). On multivariate analysis the statistical significant predictive factors related to bC were RG (p< 0.001), HDR-BT ≥ 20 Gy (p=0.008) and 3DHDR (p<0.001).
Conclusions: we observed that the bC rates correlates with the generally accepted risk factors described in the literature. Dose escalation, evaluated through the BED, and the quality of planning of HDR-BT are also important predictive factors when treating prostate cancer.
PMCID: PMC2424177  PMID: 18566673
high-dose rate brachytherapy; external beam radiotherapy; prostate cancer; RTOG-ASTRO Phoenix; biochemical failure; biochemical control
17.  Role of high dose rate interstitial brachytherapy in early and locally advanced squamous cell carcinoma of buccal mucosa 
SpringerPlus  2014;3:590.
Background
The study aimed to assess the effect of High Dose Rate (HDR) Interstitial Brachytherapy when used alone or in combination with External Beam Radiotherapy (EBRT), in early and locally advanced squamous cell carcinoma of buccal mucosa.
Materials and methods
Thirty three patients with histologically proven squamous cell carcinoma of the buccal mucosa received high dose rate interstitial brachytherapy either as primary treatment or as a boost from November 2008 to April 2013. Stage I patients received interstitial brachytherapy alone to a dose of 38.50 Gy, 3.5 Gy per fraction, twice daily at six hours apart for 11 fractions. Stage II patients received EBRT to a dose of 50 Gy in 25 fractions of two Gy each followed by brachytherapy boost to 21 Gy, 3.5 Gy per fraction, twice daily at six hours apart for six fractions. Stage III patients received the same radiotherapy schedule (i.e., same EBRT & Brachytherapy schedule) and with addition of Injection Cisplatin 70 mg/m2 in three divided doses every three weeks along with EBRT.
Results
Follow up ranged from 12 to 60 months, median follow up was 26 months. Complete response was observed in 28 patients. Five patients had residual disease and were referred for surgical salvage. One patient died of disease progression. Stage I patients had 100% local control, whereas Stage II and Stage III patients had 84.6% and 80% local control respectively.
Conclusion
HDR Interstitial Brachytherapy used either as a primary treatment modality or as a boost in buccal mucosal cancers provides results comparable to that of surgery, with the advantages of organ preservation, better cosmetic and functional outcomes.
doi:10.1186/2193-1801-3-590
PMCID: PMC4197196  PMID: 25332889
High dose rate interstitial brachytherapy; Buccal mucosal cancer; Organ preservation
18.  Prospective multi-center trial utilizing electronic brachytherapy for the treatment of endometrial cancer 
Background
A modified form of high dose rate (HDR) brachytherapy has been developed called Axxent Electronic Brachytherapy (EBT). EBT uses a kilovolt X-ray source and does not require treatment in a shielded vault or a HDR afterloader unit. A multi-center clinical study was carried out to evaluate the success of treatment delivery, safety and toxicity of EBT in patients with endometrial cancer.
Methods
A total of 15 patients with stage I or II endometrial cancer were enrolled at 5 sites. Patients were treated with vaginal EBT alone or in combination with external beam radiation.
Results
The prescribed doses of EBT were successfully delivered in all 15 patients. From the first fraction through 3 months follow-up, there were 4 CTC Grade 1 adverse events and 2 CTC Grade II adverse events reported that were EBT related. The mild events reported were dysuria, vaginal dryness, mucosal atrophy, and rectal bleeding. The moderate treatment related adverse events included dysuria, and vaginal pain. No Grade III or IV adverse events were reported. The EBT system performed well and was associated with limited acute toxicities.
Conclusions
EBT shows acute results similar to HDR brachytherapy. Additional research is needed to further assess the clinical efficacy and safety of EBT in the treatment of endometrial cancer.
doi:10.1186/1748-717X-5-67
PMCID: PMC2914666  PMID: 20646289
19.  High dose rate brachytherapy for oral cancer 
Journal of Radiation Research  2012;54(1):1-17.
Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer.
doi:10.1093/jrr/rrs103
PMCID: PMC3534285  PMID: 23179377
brachytherapy; oral cancer; high dose rate
20.  Attenuation measurements show that the presence of a TachoSil surgical patch will not compromise target irradiation in intra-operative electron radiation therapy or high-dose-rate brachytherapy 
Background
Surgery of locally advanced and/or recurrent rectal cancer can be complemented with intra-operative electron radiation therapy (IOERT) to deliver a single dose of radiation directly to the unresectable margins, while sparing nearby sensitive organs/structures. Haemorrhages may occur and can affect the dose distribution, leading to an incorrect target irradiation. The TachoSil (TS) surgical patch, when activated, creates a fibrin clot at the surgical site to achieve haemostasis. The aim of this work was to determine the effect of TS on the dose distribution, and ascertain whether it could be used in combination with IOERT. This characterization was extended to include high dose rate (HDR) intraoperative brachytherapy, which is sometimes used at other institutions instead of IOERT.
Methods
CT images of the TS patch were acquired for initial characterization. Dosimetric measurements were performed in a water tank phantom, using a conventional LINAC with a hard-docking system of cylindrical applicators. Percentage Depth Dose (PDD) curves were obtained, and measurements made at the depth of dose maximum for the three clinically used electron energies (6, 9 and 12MeV), first without any attenuator and then with the activated patch of TS completely covering the tip of the IOERT applicator. For HDR brachytherapy, a measurement setup was improvised using a solid water phantom and a Farmer ionization chamber.
Results
Our measurements show that the attenuation of a TachoSil patch is negligible, both for high energy electron beams (6 to 12MeV), and for a HDR 192Ir brachytherapy source. Our results cannot be extrapolated to lower beam energies such as 50 kVp X-rays, which are sometimes used for breast IORT.
Conclusion
The TachoSil surgical patch can be used in IORT procedures using 6MeV electron energies or higher, or HDR 192Ir brachytherapy.
doi:10.1186/s13014-014-0316-1
PMCID: PMC4293105  PMID: 25572977
Intra-operative electron radiation therapy; TachoSil; Haemostatic patch; Rectal cancer
21.  High Dose Rate Brachytherapy in the Treatment of cervical cancer: preliminary experience with cobalt 60 Radionuclide source—A Prospective Study 
Iridium-192 is widely used for high-dose rate brachytherapy. Co-60 source with similar geometric and dosimetric properties are now available. It has a longer half life but higher energy than Iridium-192. If Co-60 source can produce similar results, it will be more economical for low resource settings.
Objective:
To evaluate the acute gastrointestinal and genitourinary toxicity associated with Co-60 source in the brachytherapy of cervical cancer.
Methods:
Seventy patients with cervical cancer received 45 Gy in 22 fractions of pelvic external beam radiotherapy and 19.5 Gy in 3 fractions of HDR with Co-60 source using tandem and ring applicators with 6 courses of cisplatin 50 mg/m2 and 5 fluorouracil 1000 mg/m2 every 3 weeks Toxicity was scored using NCI-CTC version 4.0.
Results:
The median total BED (Gy10) for tumor was 86.2 (84.4–88.8) while that for rectum (BED Gy3) was 124.4 (120–133). Two patients (3%) had grade 3 gastrointestinal toxicity while all others had ≤grade 2 toxicity and this is comparable with previous results.
Conclusion:
Co-60 as HDR brachytherapy source is tolerable and is economical for low resource settings.
PMCID: PMC2934612  PMID: 20838638
HDR brachytherapy; Co-60 source; cervical cancer; acute toxicity
22.  A survey of quality control practices for high dose rate (HDR) and pulsed dose rate (PDR) brachytherapy in the United Kingdom 
Purpose
A survey of quality control (QC) currently undertaken in UK radiotherapy centres for high dose rate (HDR) and pulsed dose rate (PDR) brachytherapy has been conducted. The purpose was to benchmark current accepted practice of tests, frequencies and tolerances to assure acceptable HDR/PDR equipment performance. It is 20 years since a similar survey was conducted in the UK and the current review is timed to coincide with a revision of the IPEM Report 81 guidelines for quality control in radiotherapy.
Material and methods
All radiotherapy centres in the UK were invited by email to complete a comprehensive questionnaire on their current brachytherapy QC practice, including: equipment type, patient workload, source calibration method, level of image guidance for planning, prescribing practices, QC tests, method used, staff involved, test frequencies, and acceptable tolerance limits.
Results
Survey data was acquired between June and August 2012. Of the 64 centres invited, 47 (73%) responded, with 31 centres having brachytherapy equipment (3 PDR) and fully completing the survey, 13 reporting no HDR/PDR brachytherapy, and 3 intending to commence HDR brachytherapy in the near future. All centres had comprehensive QC schedules in place and there was general agreement on key test frequencies and tolerances. Greatest discord was whether source strength for treatment planning should be derived from measurement, as at 58% of centres, or from the certified value, at 42%. IPEM Report 81 continues to be the most frequently cited source of QC guidance, followed by ESTRO Booklet No. 8.
Conclusions
A comprehensive survey of QC practices for HDR/PDR brachytherapy in UK has been conducted. This is a useful reference to which centres may benchmark their own practice. However, individuals should take a risk-assessment based approach, employing full knowledge of local equipment, clinical procedures and available test equipment in order to determine individual QC needs.
doi:10.5114/jcb.2012.32558
PMCID: PMC3561606  PMID: 23378853
high dose rate (HDR); brachytherapy; quality control (QC); quality assurance (QA); survey
23.  Brachytherapy in the therapy of prostate cancer – an interesting choice 
Contemporary Oncology  2013;17(5):407-412.
Brachytherapy is a curative alternative to radical prostatectomy or external beam radiation [i.e. 3D conformal external beam radiation therapy (CRT), intensity-modulated radiation therapy (IMRT)] with comparable long-term survival and biochemical control and the most favorable toxicity. HDR brachytherapy (HDR-BT) in treatment of prostate cancer is most frequently used together with external beam radiation therapy (EBRT) as a boost (increasing the treatment dose precisely to the tumor). In the early stages of the disease (low, sometimes intermediate risk group), HDR-BT is more often used as monotherapy. There are no significant differences in treatment results (overall survival rate – OS, local recurrence rate – LC) between radical prostatectomy, EBRT and HDR-BT. Low-dose-rate brachytherapy (LDR-BT) is a radiation method that has been known for several years in treatment of localized prostate cancer. The LDR-BT is applied as a monotherapy and also used along with EBRT as a boost. It is used as a sole radical treatment modality, but not as a palliative treatment. The use of brachytherapy as monotherapy in treatment of prostate cancer enables many patients to keep their sexual functions in order and causes a lower rate of urinary incontinence. Due to progress in medical and technical knowledge in brachytherapy (“real-time” computer planning systems, new radioisotopes and remote afterloading systems), it has been possible to make treatment time significantly shorter in comparison with other methods. This also enables better protection of healthy organs in the pelvis. The aim of this publication is to describe both brachytherapy methods.
doi:10.5114/wo.2013.38557
PMCID: PMC3934024  PMID: 24596528
HDR brachytherapy; LDR brachytherapy; prostate cancer; seeds
24.  18 Years’ experience with high dose rate strontium-90 brachytherapy of small to medium sized posterior uveal melanoma 
The British Journal of Ophthalmology  2005;89(10):1306-1310.
Aim: To analyse local tumour control, radiation related complications, visual acuity, enucleation rate, and survival after brachytherapy of small to medium sized choroidal melanoma (CM) with a high dose rate (HDR) strontium-90 (Sr-90) applicator.
Methods: From 1983 until 2000, 98 eyes with CM were treated with Sr-90 brachytherapy. The main outcome measures were actuarial rates of the patients’ survival, ocular conservation rate, tumour regression, complication rates, and preservation of visual acuity. End point rates were estimated using Kaplan-Meier analysis.
Results: The median follow up time was 6.7 years (0.5–18.8 years). Actuarial melanoma free patient survival rate was 85% (SE 4.8%) after 18 years. Actuarial rate of ocular conservation and complete tumour regression was 90% (SE 3.8%) after 15 years. In 93% local tumour control was achieved, 88% showed a stable scar. Recurrence of the tumour on the border caused enucleation of six eyes (7%). In three cases (4%) retinal detachment was the end point. No cases of optic atrophy or of sight impairing retinopathy outside the treated area were found. Actuarial rate of preservation of visual acuity of 1/10 was 65% at 5 years and 45% at 15 years of follow up (SE 5.9% and 8.8%).
Conclusions: Sr-90 brachytherapy is as effective as iodine or ruthenium brachytherapy for small to medium sized CM but causes fewer complications. The preservation of vision is better than with all other described radioisotopes. HDR Sr-90 brachytherapy can therefore safely be recommended for small to medium sized CM.
doi:10.1136/bjo.2005.068460
PMCID: PMC1772893  PMID: 16170122
choroidal melanoma; strontium; brachytherapy
25.  The Role of Irradiation in the Management of Locally Recurrent Non-Metastatic Soft Tissue Sarcoma of Extremity/Trunkal Locations 
Sarcoma  2004;8(2-3):57-61.
Background: Patients who have had initial curative intent therapy for non-metastatic soft tissue sarcoma, and who subsequently relapse at the initial site without evidence of metastatic disease, have various options regarding local treatment. The treatment options available will be determined by the extent of relapse, previous therapy rendered, and patient characteristics. We reported on a series of 31 patients treated initially with only surgery for extremity/trunkal high-grade soft tissue sarcoma and then seen for recurrence at our institution between 1980 and 1999. Local re-treatment consisted of combined modality therapy, most often aggressive surgical debulking/resection and irradiation, in an effort to reduce the need for amputation and, where anatomically allowable, to maintain a functional limb. We report our results in re-establishing local control, subsequent survival, and complication rates.
Methods: Thirty-one patients with locally recurrent, non-metastatic high-grade soft tissue sarcoma, (excluding extraabdominal desmoid) were retrospectively reviewed to determine local control, survival, and complication rates associated with the relapsed disease. All patients had multimodality re-treatment most often utilizing aggressive surgical debulking and irradiation. The irradiation consisted of either external beam alone, brachytherapy alone, or a combination of external beam and brachytherapy. Nine patients also received multi-agent, multi-cycle chemotherapy using various regimens. In addition, the impact of surgical margin at the time of re-resection (gross versus microscopic disease), radiation treatment type, total radiation dose delivered, size of relapse, histological sub-type, sex and age, were evaluated to determine if they had any impact on the re-establishment of local control and subsequent survival.
Results: Local control was re-established in 25 of 31 (80.6%) patients. Two additional patients with isolated local relapse after irradiation were salvaged with amputation and remain NED at last follow-up. With these patients a total of 27/31 (87%) are now with local control. At last follow-up, which ranged from 23 to 192 months, 23 of 31 (74%) remained alive. Of the eight patients who have died, four had evidence of local and distant failure. Two additional patients died of distant failure while the treated sites remained in local control and two patients, both NED, died of intracurrent processes. Follow-up for those patients who had re-established local control has ranged from 23 to 192 months (median=60.5 months). Time to local failure following re-treatment ranged between 3 and 72 months following re-treatment (median=12 months). Five patients had significant treatment related complications. Included are two patients in which amputation was required due to local recurrences. Two patients developed a soft tissue necrosis and one patient had a wound healing problem that resolved with conservative management. No statistical significance in the development of local control could be found based on surgical margin status, total dose of irradiation (greater or less than 60 Gy), size of recurrence (greater than 5 cm), histological sub-type, sex, or age (greater than 50 years). There was a trend for negative impact for those patients receiving only external beam irradiation.
Conclusion: Selective locally recurrent, non-metastatic soft tissue sarcoma of the extremity/trunkal regions should still be considered eligible for aggressive limb-sparing therapy. Our experience suggests that a majority of patients re-establish local control following aggressive surgical resection/debulking and irradiation and this appears to be durable in its nature. The role of chemotherapy in this group of patients remains investigational. In a surprising finding, one patient re-relapsed in the re-treatment site at 72 months, thus justifying continued strict surveillance not only in the primary site but also for subsequent metastatic disease.
doi:10.1080/13577140412331332785
PMCID: PMC2395609  PMID: 18521396

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