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1.  Hyperfractionated high-dose rate brachytherapy in the treatment of oral tongue cancer 
Low-dose rate brachytherapy is a well established treatment modality of oral cancer. Data about high-dose rate (HDR) brachytherapy are still sparse with various fractionation schedules and heterogeneous results.
The aim of our retrospective study was to evaluate the results of HDR brachytherapy with doses of 3 Gy twice daily.
Patients and methods
Twenty patients with squamous cell tongue cancer were treated in the years 2001–2009 by exclusive HDR BT 18 × 3 Gy twice daily. The plastic tube technique was used. Median follow up was 47 months (7.8–118) since brachytherapy.
The local and locoregional control was 85% and 68%, respectively. Bone necrosis developed in one case treated without mandibular shielding and soft tissue necrosis in 2 cases.
It can be concluded that HDR brachytherapy with 18 × 3 Gy twice daily is safe with promising local control. The risk of nodal recurrences is substantial.
PMCID: PMC3863239  PMID: 24376988
Oral cancer; High-dose rate brachytherapy
2.  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.
PMCID: PMC3766299  PMID: 23543798
prostate cancer; high-dose-rate (HDR); brachytherapy; monotherapy; hypofractionation
3.  Surgical resection with adjuvant brachytherapy in soft tissue sarcoma of the extremity – a case report 
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.
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.
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.
PMCID: PMC3561605  PMID: 23378852
soft tissue sarcoma; brachytherapy; compartment surgery
4.  Successful use of high dose rate brachytherapy for non-malignant bronchial obstruction 
Thorax  2001;56(5):415-416.
High dose rate (HDR) endobronchial brachytherapy is a palliative treatment for symptomatic airway obstruction by malignant tumours. We report a novel use of HDR brachytherapy for treating non-malignant bronchial obstruction. The patient had a metal stent placed in a reconstructed airway after a bronchial tear to ensure patency. Granulation tissue formation in and around the stent caused symptomatic occlusion of the airway, necessitating multiple laser applications. A single treatment of HDR brachytherapy (1000 cGy) was delivered following laser therapy. The patient remains well 15 months after treatment with no evidence of recurrent granulation tissue formation on bronchoscopy. HDR brachytherapy is an effective treatment for non-malignant airway obstruction.

PMCID: PMC1746035  PMID: 11312413
5.  Brachytherapy for cervix cancer: low-dose rate or high-dose rate brachytherapy – a meta-analysis of clinical trials 
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.
PMCID: PMC2673206  PMID: 19344527
6.  Accelerated partial breast irradiation using multicatheter brachytherapy for select early-stage breast cancer: local control and toxicity 
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.
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.
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%.
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.
PMCID: PMC2905428  PMID: 20565899
7.  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.
PMCID: PMC3534285  PMID: 23179377
brachytherapy; oral cancer; high dose rate
8.  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.
PMCID: PMC3766300  PMID: 23559599
primary vaginal cancer; radiation therapy; high-dose-rate brachytherapy; intracavitary brachytherapy; interstitial brachytherapy
9.  High-dose-rate interstitial brachytherapy for liver metastases: first study from India 
To study the safety and efficacy of high-dose-rate interstitial brachytherapy (HDRIBT) in patients with liver metastases (LM).
Material and methods
Between 2009 and 2011, 10 patients with 12 metastatic lesions in the liver were enrolled in this prospective trial. All patients had either refused surgery or found ineligible for surgery due to various factors. Under CT guidance, 16 gauze blind end stainless steel or rigid plastic brachytherapy needle was inserted in the center of lesion through the percutaneous route. Generally, a single interstitial brachytherapy (IBT) needle for lesions up to 3 cm and multiple needles for lesions more than 3 cm in diameter were inserted. Treatment was delivered with a single high-dose-rate (HDR) dose of 20 Gy prescribed to the target. The needles were removed immediately after the treatment. The endpoints of study were acute complications and local control of the disease.
The median size of the lesion was 3.8 cm (2.7-7.0 cm). The average time for the entire IBT procedure was 65 minutes (50-105 minutes). Median follow up was 9 months (3-17 months). None of the patients had fatal complications. Minor complications like pain, nausea/vomiting, and asymptomatic pleural effusion were observed in 3, 2 and 1 patients, respectively. Local control rate at 12 months was 75%. The 1-year local progression free survival (LPFS) was 33%.
Although limited by small sample size, the results of our first study from India suggest that HDRIBT is a safe and effective non surgical option for LM.
PMCID: PMC3708149  PMID: 23878550
liver metastases; interstitial brachytherapy; high-dose-rate
10.  Analysis of Fat Necrosis Following Adjuvant High-Dose-Rate Interstitial Brachytherapy for Early-Stage Breast Cancer 
Brachytherapy  2012;12(2):99-106.
To report the incidence and potential predictors of fat necrosis in women with early-stage breast cancer treated with adjuvant high-dose-rate (HDR) multicatheter interstitial brachytherapy.
Methods and Materials
Between 2003 and 2010, 238 treated breasts in 236 women were treated with accelerated partial breast irradiation (APBI) using HDR interstitial brachytherapy. Selection criteria included patients with Tis-T2 tumors measuring ≤ 3 cm, without nodal involvement, who underwent breast-conserving surgery (BCS). 99% of treatments were to a total dose of 34 Gy. The presence and severity of fat necrosis was prospectively recorded during follow up. Cosmesis was qualitatively scored in all patients. Cosmesis was quantitatively measured via the percentage breast retraction assessment (pBRA) in 151 cases.
Median follow-up was 56 months. The crude rate of fat necrosis was 17.6%. The rate of symptomatic fat necrosis was 10.1%. In univariate analysis acute breast infection and anthracycline-based chemotherapy, number of catheters, V100, V150, V200 and integrated reference air-kerma (IRAK) were significantly associated with fat necrosis. There was significant collinearity between the brachytherapy related factors, of these V150 was most predictive. In multivariate analysis only V150 was significantly associated with fat necrosis. At 3 years, patients with fat necrosis were more likely to have a fair/poor cosmetic outcome and a larger pBRA.
Mammary fat necrosis is a common adverse event after BCS and HDR interstitial brachytherapy. Fat necrosis is associated with worse qualitative and quantitative cosmetic outcomes. Minimizing exposure volumes such as V150 may decrease the incidence of fat necrosis and improve cosmesis.
PMCID: PMC3929056  PMID: 22726878
Breast cancer; brachytherapy; fat necrosis; cosmesis; partial breast
11.  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.
PMCID: PMC3759211  PMID: 24212968
prostate cancer; high dose rate brachytherapy; external beam radiation therapy; radical prostatectomy
12.  The American Brachytherapy Society Treatment Recommendations for Locally Advanced Carcinoma of the Cervix Part II: High Dose-Rate Brachytherapy 
Brachytherapy  2012;11(1):47-52.
This report presents the 2011 update to the American Brachytherapy Society (ABS) high-dose-rate (HDR) brachytherapy guidelines for locally advanced cervical cancer.
Members of the American Brachytherapy Society (ABS) with expertise in cervical cancer brachytherapy formulated updated guidelines for HDR brachytherapy using tandem and ring, ovoids, cylinder or interstitial applicators for locally advanced cervical cancer were revised based on medical evidence in the literature and input of clinical experts in gynecologic brachytherapy.
The Cervical Cancer Committee for Guideline Development affirms the essential curative role of tandem-based brachytherapy in the management of locally advanced cervical cancer. Proper applicator selection, insertion, and imaging are fundamental aspects of the procedure. Three-dimensional imaging with magnetic resonance or computed tomography or radiographic imaging may be used for treatment planning. Dosimetry must be performed after each insertion prior to treatment delivery. Applicator placement, dose specification and dose fractionation must be documented, quality assurance measures must be performed, and follow-up information must be obtained. A variety of dose/fractionation schedules and methods for integrating brachytherapy with external-beam radiation exist. The recommended tumor dose in 2 Gray (Gy) per fraction radiobiologic equivalence (EQD2) is 80–90 Gy, depending on tumor size at the time of brachytherapy. Dose limits for normal tissues are discussed.
These guidelines update those of 2000 and provide a comprehensive description of HDR cervical cancer brachytherapy in 2011.
PMCID: PMC3489267  PMID: 22265437
13.  The histopathologic evaluation of soft tissue changes in rabbit extremity after different dose-fractionation schemes of interstitial high dose rate (HDR) brachytherapy 
The use of HDR in the treatment of soft tissue sarcoma had been on the rise. However, there was limited study to evaluate the effect of different fractionation schemes on soft tissue and the optimal HDR scheme.
We aimed to assess the histopathologic changes on soft tissue after different HDR brachytherapy doses.
The subjects were divided into three groups. Each group included 10 limbs. Group A had only an applicator without radiation, group B received a total of 24 Gy at 6 Gy per fraction, twice a day, and group C received a total of 13.5 Gy in a single fraction. The histopathologic findings were grouped into soft tissue pathology-1 (edema, inflammation, endothelial proliferation, necrosis) and soft tissue pathology-2 (atrophy, calcification, vascular hyalinization, fibrosis) (STP-1–2).
The highest mean grade values of STP-1 and STP-2 were observed in group C (0.95 and 1.45) in comparison to group A (0.45 and 0.85) and group B (0.65 and 0.9). The difference in STP-1 was found significant only between groups A and C and the difference in STP-2 was found both between groups A and C and groups B and C.
In our experimental study it was shown that the fractionated interstitial HDR had both lower rate and severity of toxicity in comparison to a single high dose fraction. Before using a single fractionated regimen in the clinic, the increased morbidity related to the irreversible early toxicities or progressive late toxicities should be kept in mind.
PMCID: PMC3863242  PMID: 24376944
Interstitial HDR brachytherapy; Dose and fractionation; Soft tissue
14.  The role of high-dose-rate brachytherapy boost in breast-conserving therapy: Long-term results of the Hungarian National Institute of Oncology 
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.
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.
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.
PMCID: PMC3863209  PMID: 24376915
Breast-conserving therapy; Radiotherapy; High-dose-rate brachytherapy; Boost
15.  In vivo assessment of catheter positioning accuracy and prolonged irradiation time on liver tolerance dose after single-fraction 192Ir high-dose-rate brachytherapy 
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.
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).
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.
PMCID: PMC3179944  PMID: 21892943
16.  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.
PMCID: PMC4014157  PMID: 24351458
high-risk prostate cancer; HDR; trimodality therapy; PSA response
17.  Dosimetric comparison of high dose rate brachytherapy and intensity-modulated radiation therapy for cervical carcinoma 
Intracavitary brachytherapy is an integral part of radiotherapy for locally advanced gynecologic malignancies. A dosimetric intercomparison of high dose rate intracavitary brachytherapy (HDR_BT) and intensity-modulated radiotherapy in cervical carcinoma has been made in the present study. CT scan images of 10 patients treated with HDR_BT were used for this study. A sliding-window IMRT (IMRT_SW) and step-and-shoot IMRT plans were generated using 6-MV X-rays. The cumulative dose volume histograms of target, bladder, rectum and normal tissue were analyzed for both techniques and dose distributions were compared. It was seen that the pear-shaped dose distribution characteristic of intracavitary brachytherapy with sharp dose fall-off outside the target could be achieved with IMRT. The integral dose to planning target volume was significantly higher with HDR_BT in comparison with IMRT. Significant differences between the two techniques were seen for doses to 1 cc and 2 cc of rectum, while the differences in 1 cc and 2 cc doses to bladder were not significant. The integral doses to the nontarget critical and normal structures were smaller with HDR_BT and with IMRT. It is concluded that IMRT can be the choice of treatment in case of non-availability of HDR brachytherapy facilities or when noninvasive treatments are preferred
PMCID: PMC3119952  PMID: 21731228
Cervical carcinoma; high dose rate; intensity-modulated radiotherapy; intracavitary brachytherapy
18.  High dose rate brachytherapy for the local control of endobronchial carcinoma following external irradiation. 
Thorax  1996;51(4):354-358.
BACKGROUND: External irradiation is an established palliative treatment for patients with inoperable lung cancer. However, persistent or recurrent symptoms due to local disase are common following external irradiation. The impact of high dose rate (HDR) brachytherapy in the palliative management of patients with local sequelae of residual or recurrent endobronchial lung carcinoma following external irradiation was investigated. METHODS: A prospective cohort of 29 patients (19 men, mean age 65 years) underwent HDR brachytherapy for inoperable lung cancer. All patients had completed external irradiation at least one month before entry into the study (mean (SD) dose 4400 (1481) cGy, completed 12.9 (21.3) months previously). Patients underwent outpatient bronchoscopic placement of 1-3 HDR brachytherapy catheters for delivery of 750-1000 cGy of intraluminal irradiation every two weeks on 1-3 occasions. Prospective evaluation before and four weeks after completion of HDR brachytherapy included assessment of indices of level of function, symptoms, extent of atelectasis (chest radiography), and bronchoscopic determination of degree of endobronchial obstruction. RESULTS: One hundred and eighteen catheters were placed in 81 treatments. Eleven of the 26 patients who underwent repeat bronchoscopy showed a reduction in the degree of endobronchial obstruction; five of 18 patients had radiographic improvement in the extent of atelectasis. Positive response rates ranged from 25% for signs and symptoms related to pneumonitis to 69% for haemoptysis. Performance status improved in 24% of patients. Two patients died before completion of the study protocol. Short term complications included one episode of non-fatal, massive haemoptysis, five of minor haemoptysis, and one pneumothorax. CONCLUSIONS: HDR brachytherapy may improve the degree of endobronchial obstruction, atelectasis, symptoms, and level of function with minimal short term complications in patients with recurrent or residual symptomatic disease following external irradiation.
PMCID: PMC1090667  PMID: 8733484
19.  Salvage for cervical recurrences of head and neck cancer with dissection and interstitial high dose rate brachytherapy 
Salvage therapy in head and neck cancer (HNC) is a controversy issue and the literature is scarce regarding the use of interstitial high-dose rate brachytherapy (I-HDR) in HNC. We evaluated the long-term results of a treatment policy combining salvage surgery and I-HDR for cervical recurrences of HNC. Charts of 21 patients treated from 1994 to 2004 were reviewed. The crude local control rate for all patients was 52.4%. The 5- and 8-years overall (OS) and local relapse-free survival (LRFS) rates were 50%, 42.9%, 42.5% and 28.6%, respectively. The only predictive factor associated to LFRS and OS was negative margin status (p = 0.0007 and p = 0.0002). We conclude that complete surgery is mandatory for long term control and the doses given by brachytherapy are not high enough to compensate for microscopic residual disease after surgery.
PMCID: PMC1559626  PMID: 16895605
20.  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.
PMCID: PMC2884303  PMID: 20589121
Brachytherapy; conformity; intensity modulated radiotherapy; prostate
21.  Partial breast irradiation techniques in early breast cancer 
Whole breast irradiation represents an integral part of combined breast-conserving treatment of early breast cancer. A new concept includes replacing traditionally fractionated whole breast postoperative radiotherapy by accelerated partial breast irradiation. The latter involves a variety of techniques and may be applied intraoperatively or shortly after the surgery. The intraoperative techniques include photon or electron external beam irradiation and interstitial high dose rate (HDR) brachytherapy, whereas the postoperative techniques comprise interstitial brachytherapy, be it HDR, pulse dose rate (PDR) or low dose rate (LDR), intracavitary brachytherapy and external beam radiotherapy using electrons, photons or protons. This article presents accelerated partial breast irradiation techniques, ongoing phase III trials evaluating their value and recommendations for clinical practice.
PMCID: PMC3863308  PMID: 24376983
Breast cancer; Adjuvant radiotherapy; Whole breast irradiation; Accelerated partial breast irradiation
22.  The experience of pain and anxiety in rectal cancer patients during high-dose-rate brachytherapy 
Current Oncology  2014;21(1):e89-e95.
Pain and anxiety have been reported as primary concerns for patients with head-and-neck, gynecologic, and prostate cancers undergoing high dose rate (hdr) brachytherapy. However, almost no research has been published on the degree to which these symptoms are experienced by rectal cancer patients undergoing hdr brachytherapy. We conducted a pilot study examining the experiences of rectal cancer patients during hdr brachytherapy, specifically the intensity and trajectory of their anxiety and pain.
Rectal cancer patients (n = 25) who received hdr brachytherapy treatment at a hospital in Montreal, Quebec, completed verbal analog scales for pain and anxiety at 4 time points over 4 treatment days.
On all 4 days, a subset of patients reported moderate-to-severe anxiety before applicator insertion. Pain increased significantly from the time patients were lying on the table to immediately after insertion of the applicator (p < 0.001). Insertion of the applicator appears to be the most painful part of the procedure, and although anxiety declined to below baseline after applicator removal, pain remained somewhat elevated. Some patients required conscious sedation; however, reports of moderate-to-severe pain were more frequent from patients who received pain medications than from patients who did not receive such medication (p < 0.05).
Most patients with rectal cancer tolerated hdr rectal brachytherapy well, although the procedure is stressful and painful for some. Insertion of the applicator was found to be the point of maximal pain, and medication was not always completely successful at alleviating the pain, suggesting that additional psychosocial interventions might be needed, with particular emphasis on the time of applicator insertion.
PMCID: PMC3921053  PMID: 24523626
Brachytherapy; rectal cancer; procedural pain; anxiety; psycho-oncology; patient experience; cancer treatment
23.  Interobserver variation in rectal and bladder doses in orthogonal film-based treatment planning of cancer of the uterine cervix 
Orthogonal film-based treatment planning is the most commonly adopted standard practice of treatment planning for cancer of the uterine cervix using high dose rate brachytherapy (HDR). This study aims at examining the variation in rectal and bladder doses when the same set of orthogonal films was given to different observers. Five physicists were given 35 pairs of orthogonal films obtained from patients who had undergone HDR brachytherapy. They were given the same instructions and asked to plan the case assuming the tumor was centrally placed, using the treatment-planning system, PLATO BPS V13.2. A statistically significant difference was observed in the average rectal (F = 3.407, P = 0.01) and bladder (F = 3.284, P = 0.013) doses and the volumes enclosed by the 100% isodose curve (P < 0.01) obtained by each observer. These variations may be attributed to the differences in the reconstruction of applicators, the selection of source positions in ovoids and the intrauterine (IU) tube, and the differences in the selection of points especially for the rectum, from lateral radiographs. These variations in planning seen within a department can be avoided if a particular source pattern is followed in the intrauterine tube, unless a specific situation demands a change. Variations in the selection of rectal points can be ruled out if the posterior vaginal surface is clearly seen.
PMCID: PMC2772047  PMID: 19893709
High dose rate brachytherapy; interobserver variation; uterine cervix
24.  Age is not a limiting factor for brachytherapy for carcinoma of the node negative oral tongue in patients aged eighty or older 
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.
PMCID: PMC3016284  PMID: 21143904
25.  Canadian prostate brachytherapy in 2012 
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.
PMCID: PMC3650818  PMID: 23671495

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