Fraction High Dose Rate Brachytherapy Research Articles

Dosimetric variations due to interfraction organ deformation in cervical cancer brachytherapy

We quantitatively estimated dosimetric variations due to interfraction organ deformation in multi-fractionated high-dose-rate brachytherapy (HDRBT) for cervical cancer using a novel surface-based non-rigid deformable registration. As the number of consecutive HDRBT fractions increased, simple addition of dose–volume histogram parameters significantly overestimated the dose, compared with distribution-based dose addition.

Three-dimensional dose accumulation in pseudo-split-field IMRT and brachytherapy for locally advanced cervical cancer.

Dose accumulation of split-field external beam radiotherapy (EBRT) and brachytherapy (BT) is challenging because of significant EBRT and BT dose gradients in the central pelvic region. We developed a method to determine biologically effective dose parameters for combined split-field intensity-modulated radiation therapy (IMRT) and image-guided BT in locally advanced cervical cancer. Thirty-three patients treated with split-field-IMRT to 45.0-51.2 Gy in 1.6-1.8 Gy per fraction to the elective pelvic lymph nodes and to 20 Gy to the central pelvis region were included in this study. Patients received six weekly fractions of high-dose rate BT to 6.5-7.3 Gy per fraction. A dose tracker software was developed to compute the equivalent dose in 2-Gy fractions (EQD2) to gross tumor volume (GTV), organs-at-risk and point A. Total dose-volume histogram parameters were computed on the 3D combined EQD2 dose based on rigid image registration. The dose accumulation uncertainty introduced by organ deformations between IMRT and BT was evaluated. According to International Commission on Radiation Unit and Measurement and GEC European Society for Therapeutic Radiology and Oncology recommendations, D98, D90, D50, and D2cm3 EQD2 dose-volume histogram parameters were computed. GTV D98 was 84.0 ± 26.5 Gy and D2cc was 99.6 ± 13.9 Gy, 67.4 ± 12.2 Gy, 75.0 ± 10.1 Gy, for bladder, rectum, and sigmoid, respectively. The uncertainties induced by organ deformation were estimated to be -1 ± 4 Gy, -3 ± 5 Gy, 2 ± 3 Gy, and -3 ± 5 Gy for bladder, rectum, sigmoid, and GTV, respectively. It is feasible to perform 3D EQD2 dose accumulation to assess high and intermediate dose regions for combined split-field IMRT and BT.

Single 15 Gy High-Dose-Rate Brachytherapy Boost for Treatment of Prostate Cancer: Clinical Implications of Dosimetric Parameters

We previously reported our observations on toxicities and clinical outcomes in patients treated with an inversely planned single fraction High Dose Rate Brachytherapy (HDR-BT) boost followed by hypofractionated External Beam Radiotherapy (EBRT). More recently, results with longer follow-up became available, revealing more information about long-term toxicities and clinical failures. This report aims to determine an optimal set of dosimetric constraints based on our experience. A Phase I-II clinical trial protocol evaluating single-fraction HDR-BT combined with EBRT was undertaken in our institution. Eligible patients had clinically localized intermediate-risk prostate cancer. The patients received HDR-BT as a single 15-Gy implant, followed by EBRT to 37.5 Gy in 15 fractions. The patients were monitored prospectively for toxicity (Common Terminology Criteria for Adverse Events, version 3.0) and health-related quality of life (Expanded Prostate Cancer Index Composite [EPIC] and post-treatment PSA obtained q3 monthly for the first year, q6 monthly for 4 years, and annually thereafter. Kaplan-Meier biochemical Disease Free Survival (bDFS) curves were generated. Univariate and multivariate logistic regression analysis were used to investigate associations between clinical/functional outcomes and baseline covariates. A ROC curve analysis was used to determine threshold values predictive for toxicities. Median follow-up was 73 months. Five years bDFS was 97.4% (95% confidence interval 94.5-100%). The Mean V100 was 96.5%(interquartile range [IQR], 95.1-98.3%). The mean D90 was 101.5%(IQR, 100.1-104.4%). There was no association between either V100, or D90 and bDFS in our cohort (p=0.1657 and 0.1659). However patients with lower V100 were more likely to have malignant biopsy results on univariate and multivariate analysis (median V100=94.8% for patients having malignant cell on post treatment biopsies vs. 96.9% for patients with no malignant cells on post treatment biopsies; p=0.0271). On univariate analysis D90≥100% was associated with achieving a nadir PSA <0.1 ng/mL with a trend toward significance (p=0.084;OR=2.140; 0.912, 5.194). From our previous Toxicity and QOL analysis, we identified V200 with a threshold of 11%, Urethral D10 with a threshold of 120% and rectal V80 with a threshold of 0.9cc as predictors of worse functional outcomes. We have been able to identify dosimetric constraints for use in HDR planning to optimize clinical outcome. Achieving a V100 ≥95% and a D90≥100% while keeping the V200 < 11%, Urethral D10 < 120% and Rectal V80 < 0.9 cc is likely to ensure a balance between therapeutic efficacy and toxicity.

Single Fraction High Dose Rate Brachytherapy and Two Schemes of External Radiotherapy for Prostate Adenocarcinoma

Single Fraction High Dose Rate Brachytherapy and Two Schemes of External Radiotherapy for Prostate Adenocarcinoma

Cost-Effectiveness Analysis of 3D Image-Guided Brachytherapy Compared to 2D Brachytherapy in the Treatment of Locally Advanced Cervical Cancer

3D Image-guided brachytherapy (IGBT) is a significant advancement in locally advanced cervical cancer treatment. Prospective and retrospective data have shown improved local control and decreased morbidity with this technique. However, the cost-effectiveness of this approach, which requires additional resources including repetitive cross-sectional imaging, is not known. We performed a cost-effectiveness (C/E) analysis of IGBT compared to conventional (2D) brachytherapy in the treatment of locally-advanced cervical cancer. A Markov model using a 1-month cycle with a 3-year follow-up period after completion of treatment was constructed to model locally advanced cervical cancer treated with five fractions of high-dose rate brachytherapy. The model captured clinical parameters (including improvement in survival, local control and RTOG late Grade 3 and above complication rates), quality of life utility, and cost associated with IGBT and 2D brachytherapy. Model assumptions regarding clinical outcomes and quality of life utility were obtained through a comprehensive literature review. Cost was based on Medicare reimbursement in 2013. Strategies were compared using the incremental cost effectiveness ratio (ICER), and effectiveness was measured in quality-adjusted life years (QALYs). To account for uncertainty, one-way and Monte Carlo probabilistic sensitivity analyses were performed. Strategies were evaluated from the health care system perspective with a willingness-to-pay threshold of $50,000/QALY gained. The base cost of treatment for five fractions of IGBT and 2D brachytherapy was $21000 and $17000, respectively. In the base case analysis, the IGBT strategy cost $3555 more than 2D while gaining 0.16 QALYs, resulting in an ICER of $22,453 per QALY gained. In one-way sensitivity analyses, which varied all parameters individually, results were most sensitive to variation of treatment costs (range: ICER of -$4000 to $49000/QALY gained), but the ICER remained <$50,000/QALY gained if IGBT costs were <$25,400 (baseline $21,000). Variation of survival, local control, and complication rates were less influential. A Monte Carlo probabilistic sensitivity analysis, which varied all model parameters simultaneously 5000 times, demonstrated that IGBT was favored in 63% of model iterations at a $50,000/QALY gained threshold. IGBT for locally-advanced cervical cancer is a cost effective option compared to 2D brachytherapy based upon the ICER analysis. These findings were robust to variation of parameter values, both individually and collectively, supporting the routine use of IGBT in locally-advanced cervical cancer.

Dosimetric evaluation of manually and inversely optimized treatment planning for high dose rate brachytherapy of cervical cancer

Background. To compare five inverse treatment planning methods with the conventional manually optimized planning approach for brachytherapy of cervical cancer with respect to dosimetric parameters.Material and methods. Eighteen cervical cancer patients treated with magnetic resonance imaging (MRI)-guided high dose rate (HDR) brachytherapy were included in this study. Six plans were created for each of the 4 HDR brachytherapy fractions for each patient: 1 manually optimized and 5 inversely planned. Three of these were based on inverse planning simulated annealing (IPSA) with and without extra constraints on maximum doses of the target volume, and different constraints on doses to the organs at risk (OARs). In addition there were two plans based on dose to target surface points. The resulting dose-volume histograms were analyzed and compared from the dosimetric point of view by quantifying specific dosimetric parameters, such as clinical target volume (CTV) D90, CTV D100, conformal index (COIN), and D2cm3 for rectum, bladder and the sigmoid colon.Results. Manual optimization led to a mean target coverage of 78.3% compared to 87.5%, 91.7% and 82.5% with the three IPSA approaches (p < 0.001). Similar COIN values for manual and inverse optimization were found. The manual optimization led to better results with respect to the dose to the OARs expressed as D2cm3. Overall, the best results were obtained with manual optimization and IPSA plans with volumetric constraints including maximum doses to the target volume.Conclusions. Dosimetric evaluation of manual and inverse optimization approaches is indicating the potential of IPSA for brachytherapy of cervical cancer. IPSA with constraints of maximum doses to the target volume is closer related to manual optimization than plans with constraints only to minimum dose to the target volume and maximum doses to OARs. IPSA plans with proper constraints performed better than those based on dose to target surface points and manually optimized plans.

High-dose-rate brachytherapy alone given as two or one fraction to patients for locally advanced prostate cancer: Acute toxicity

BackgroundTo evaluate early urinary (GU) and gastrointestinal (GI) adverse events (AEs) after two or one fraction of high-dose rate brachytherapy (HDR-BT) in advanced prostate cancer. Patients and methods165 patients were treated with 2×13Gy (n=115), or a single dose of 19Gy (n=24) or 20Gy (n=26) HDR-BT. Early AEs were assessed using the RTOG scoring system and the International Prostate Symptom Score (IPSS). ResultsWeek-2 prevalence of severe IPSS symptoms was higher after 20Gy than after 26 or 19Gy but by 12weeks all groups were at pre-treatment levels or less. Grade-3 GU toxicity was observed ⩽9% of patients. No Grade 4 GU and no Grade 3 or 4 GI complications were observed. However, there was a significant increase in catheter use in the first 12weeks after implant after 19 and 20Gy compared with 2×13Gy. ConclusionSingle dose HDR-BT is feasible with acceptable levels of acute complications; tolerance may have been reached with the single 19Gy schedule.

High-dose-rate brachytherapy with or without intensity modulated radiation therapy as salvage treatment for an isolated, gross local recurrence of prostate cancer post-prostatectomy

To evaluate the use of high-dose-rate (HDR) brachytherapy±intensity modulated radiation therapy (IMRT) as salvage therapy for patients with an isolated, gross local recurrence of prostate cancer after radical prostatectomy. Between October 2009 and May 2013, the authors treated six patients with salvage iridium-192 HDR brachytherapy±IMRT for biopsy-proven, recurrent prostate cancer post-prostatectomy. In each patient, a pelvic MRI scan or CT scan demonstrated a nodule (range 1.6, 4.7cm) in the prostate bed. Although prostate-specific antigen values were 0.2-9.5ng/mL at the time of salvage brachytherapy, there was no pelvic adenopathy on CT or MRI scan, and a bone scan was negative in all cases. Five patients were treated with IMRT to 4500-5040cGy in 25-28 fractions to the prostate bed followed by two 950cGy HDR brachytherapy fractions separated by 1-2weeks. A sixth patient underwent HDR brachytherapy monotherapy consisting of 3800cGy in four fractions over 3 days. Toxicities were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Median followup was 9 months (range 3, 40 months). All six patients have been free of androgen deprivation therapy and have an undetectable prostate-specific antigen. One patient developed late Grade 2 urinary incontinence. There was no late grade ≥2 gastrointestinal toxicity. HDR brachytherapy±IMRT is a safe and effective salvage therapy option for an isolated, gross local recurrence of prostate cancer after radical prostatectomy and merits further study.

A dual-plane co-RASOR technique for accurate and rapid tracking and position verification of an Ir-192 source for single fraction HDR brachytherapy

Effective high-dose-rate (HDR) treatment requires accurate and independent treatment verification to ensure that the treatment proceeds as prescribed, in particular if a high dose is given, as in single fraction therapy. Contrary to CT imaging and fluoroscopy, MR imaging provides high soft tissue contrast. Conventional MR techniques, however, do not offer the temporal resolution in combination with the 3D spatial resolution required for accurate brachytherapy source localization. We have developed an MR imaging method (center-out RAdial Sampling with Off-Resonance (co-RASOR)) that generates high positive contrast in the geometrical center of field perturbing objects, such as HDR brachytherapy sources. co-RASOR generates high positive contrast in the geometric center of an Ir-192 source by applying a frequency offset to center-out encoded data. To obtain high spatial accuracy in 3D with adequate temporal resolution, two orthogonal center-out encoded 2D images are applied instead of a full 3D acquisition. Its accuracy in 3D is demonstrated by 3D MRI and CT. The 2D images show high positive contrast in the geometric center of non-radioactive Ir-192 sources, with signal intensities up to 160% of the average signal intensity in the surrounding medium. The accuracy with which the center of the Ir-192 source is located by the dual-plane MRI acquisition corresponds closely to the accuracy obtained by 3D MRI and CT imaging. The positive contrast is shown to be obtained in homogeneous and in heterogeneous tissue. The dual-plane MRI technique allows the brachytherapy source to be tracked in 3D with millimeter accuracy with a temporal resolution of approximately 4 s.

Urethral dosimetry and toxicity with high-dose-rate interstitial brachytherapy for vaginal cancer

The tolerance and complication rates of the urethra are unknown for the interstitial high-dose-rate brachytherapy (HDR-BT) for vaginal cancer. Patients with vaginal cancer near/involving the urethra who were treated with HDR-BT between 2008 and 2011 were included. Patients received mean external beam dose of 48.0Gy followed by mean HDR-BT dose of 4.5Gy/fraction for five fractions. With CT-based planning, the urethra was contoured from the bladder neck to the meatus. Doses were converted to the biologically equivalent dose in 2Gy/fraction (EQD2). A total of 16 patients were included, and the EQD2D90 was 74.9Gy. The urethral volume was 1.31cm(3), and the EQD2 to 0.1 and 1cm(3) were 76.2 and 48.9Gy, respectively. Two of the 6 patients with urethral involvement developed urethral necrosis. The D90 for these 2 patients was 76.8Gy, and the urethral doses to 0.1 and 1cm(3) were 95.1 and 45.8, respectively. Those who developed severe urethral toxicity had a trend to urethral EQD2 (95.1Gy vs. 73.4Gy, p=0.1) and significantly higher dose per fraction of HDR-BT to 0.1cm(3) of the urethra (5.7Gy vs. 3.7Gy, p=0.02) when compared with those who did not develop severe urethral toxicity. This study is among the first to assess urethral dosimetry for patients treated with HDR-BT for vaginal cancer. Patients who received five fractions of higher than 5Gy/fraction to 0.1cm(3) of urethra (estimated EQD2 of 85Gy) are at increased risk of severe urethral toxicity.

Target volume changes through high-dose-rate brachytherapy for cervical cancer when evaluated on high resolution (3.0 Tesla) magnetic resonance imaging

PurposeTo evaluate tumor volume changes that occurred during courses of high-dose-rate brachytherapy (HDR) using high resolution (3.0 Tesla) magnetic resonance imaging (MRI), along with the regression after external beam radiation therapy (EBRT). Methods and MaterialsFourteen patients with International Federation of Gynecology and Obstetrics stage IB1-IV cervical cancer were studied retrospectively. All patients underwent EBRT with concurrent chemotherapy followed by HDR brachytherapy. Gross tumor volume (GTV) and high-risk clinical target volume (HR-CTV) were contoured on a 3.0 Tesla MRI on the day of the HDR and on diagnostic MRI (1.5 Tesla) prior to EBRT. Two physicians independently contoured the GTV and HR-CTV on a total of 46 MRI data sets for the HDR plans. The percent volume changes of GTV and HR-CTV were quantified after EBRT and again after each HDR. The conformity indices (CIs) of the 2 contours were assessed. ResultsGTV and HR-CTV considerably regressed after the first ( --31.7% ± 19.3% and --26.4% ± 6.9%, respectively) and the second (--26.8% ± 14.3% and --23.8% ± 11.0%) fraction of HDR while relatively small regressions were observed after the third (--16.3% ± 14.2% and --10.6% ± 13.4%) and the fourth (--8.0% ± 3.4% and --9.0% ± 8.0%) fractions. The lymph node-positive on positron emission tomography (PET) and stage III or IV group showed, on average, more than 200% larger GTV and HR-CTV before EBRT than those of the other patients. The GTV and HR-CTV for the group were larger on average more than 150% after EBRT and before the first HDR fraction than the other group. Interobserver CI did not vary significantly (0.75 ± 0.11) for HR-CTV, although a smaller CI (0.56 ± 0.21) was found for GTV. ConclusionsLarger tumor regressions were observed after the first and second fractions of HDR than after all subsequent fractions. The PET-identified lymph node-positive patient group and stage III or higher tumors showed larger tumor volumes before and after EBRT than other cases.

High-Dose-Rate Brachytherapy Alone for Localized Prostate Cancer in Patients at Moderate or High Risk of Biochemical Recurrence

To evaluate genitourinary (GU) and gastrointestinal (GI) morbidity and biochemical control of disease in patients with localized prostate adenocarcinoma treated with escalating doses per fraction of high-dose rate brachytherapy alone. A total of 197 patients were treated with 34 Gy in four fractions, 36 Gy in four fractions, 31.5 Gy in three fractions, or 26 Gy in two fractions. Median follow-up times were 60, 54, 36, and 6 months, respectively. Incidence of early Grade ≥ 3 GU morbidity was 3% to 7%, and Grade 4 was 0% to 4%. During the first 12 weeks, the highest mean International Prostate Symptom Score (IPSS) value was 14, and between 6 months and 5 years it was 8. Grade 3 or 4 early GI morbidity was not observed. The 3-year actuarial rate of Grade 3 GU was 3% to 16%, and was 3% to 7% for strictures requiring surgery (4-year rate). An incidence of 1% Grade 3 GI events was seen at 3 years. Late Grade 4 GU or GI events were not observed. At 3 years, 99% of patients with intermediate-risk and 91% with high-risk disease were free of biochemical relapse (log-rank p= 0.02). There was no significant difference in urinary and rectal morbidity between schedules. Biochemical control of disease in patients with intermediate and high risk of relapse was good.

Moderate dose escalation with single-fraction high-dose-rate brachytherapy boost for clinically localized intermediate- and high-risk prostate cancer: 5-year outcome of the first 100 consecutively treated patients

Purpose To analyze the clinical outcome and toxicity data of the first 100 consecutive patients treated with a single-fraction high-dose-rate brachytherapy (HDR-BT) and external beam radiotherapy (EBRT). Methods and Materials Two-hundred eighty patients have been treated with HDR-BT boost for localized intermediate- to high-risk prostate cancer. Among these, the outcome and toxicity of the first 100 patients treated with a single HDR-BT fraction were assessed. A median dose of 60 Gy EBRT was given to the prostate and vesicles. Interstitial HDR-BT of 10 Gy was performed during the course of EBRT. Results Median followup time was 61.5 months. The 5-year actuarial rates of overall survival, cause-specific survival, disease-free survival, and biochemical no evidence of disease (bNED) for the entire cohort were 93.3%, 99.0%, 89.3%, and 85.5%, respectively. The 7-year actuarial rate of bNED was 84.2% for the intermediate-risk group and 81.6% for the high-risk group ( p = 0.8464). The 7-year actuarial rates of bNED for Grade 1, 2, and 3 tumors were 97.5%, 80.0%, and 67.1%, respectively. The 5-year probability for developing late Grade 3 gastrointestinal and genitourinary (GU) toxicity was 2.1% and 14.4%, respectively. Grade 3 GU complications occurred significantly more frequently in patients with a history of preirradiation transurethral resection (29.1% vs. 8.8%; p = 0.0047). Conclusions Five-year outcome after 60 Gy EBRT plus a single fraction of 10 Gy HDR-BT boost is encouraging. Preradiation transurethral resection significantly increases the risk of late severe GU complications.

Use of cone-beam imaging to correct for catheter displacement in high dose-rate prostate brachytherapy

Purpose To determine the magnitude of catheter displacement between time of planning and time of treatment delivery for patients undergoing high dose-rate (HDR) brachytherapy, the dosimetric impact of catheter displacement, and the ability to improve dosimetry by catheter readjustment. Methods and Materials Twenty consecutive patients receiving single fraction HDR brachytherapy underwent kilovoltage cone-beam CT in the treatment room before treatment. If catheter displacement was apparent, catheters were adjusted and imaging repeated. Both sets of kilovoltage cone-beam CT image sets were coregistered off-line with the CT data set used for planning with rigid fusion of anatomy based on implanted fiducials. Catheter displacement was measured on both sets of images and dosimetry calculated. Results Mean internal displacement of catheters was 11 mm. This would have resulted in a decrease in mean volume receiving 100% of prescription dose ( V 100) from the planned 97.6% to 77.3% ( p < 0.001), a decrease of the mean dose to 90% of the prostate ( D 90 ) from 110.5% to 72.9% ( p < 0.001), and increase in dose to 10% of urethra (urethra D 10 ) from 118% to 125% ( p = 0.0094). Each 1 cm of catheter displacement resulted in a 20% decrease in V 100 and 36% decrease in D 90 . Catheter readjustment resulted in a final treated mean V 100 of 90.2% and D 90 of 97.4%, both less than planned. Mean urethra D 10 remained higher at126% ( p = 0.0324). Conclusions Significantly, internal displacement of HDR catheters commonly occurs between time of CT planning and treatment delivery, even when only a single fraction is used. The adverse effects on dosimetry can be partly corrected by readjustment of catheter position.

Stereotactic Body Radiotherapy as Monotherapy or Post–External Beam Radiotherapy Boost for Prostate Cancer: Technique, Early Toxicity, and PSA Response

High dose rate (HDR) brachytherapy has been established as an excellent monotherapy or after external-beam radiotherapy (EBRT) boost treatment for prostate cancer (PCa). Recently, dosimetric studies have demonstrated the potential for achieving similar dosimetry with stereotactic body radiotherapy (SBRT) compared with HDR brachytherapy. Here, we report our technique, PSA nadir, and acute and late toxicity with SBRT as monotherapy and post-EBRT boost for PCa using HDR brachytherapy fractionation. To date, 38 patients have been treated with SBRT at the University of California-San Francisco with a minimum follow-up of 12 months. Twenty of 38 patients were treated with SBRT monotherapy (9.5 Gy × 4 fractions), and 18 were treated with SBRT boost (9.5 Gy × 2 fractions) post-EBRT and androgen deprivation therapy. PSA nadir to date for 44 HDR brachytherapy boost patients with disease characteristics similar to the SBRT boost cohort was also analyzed as a descriptive comparison. SBRT was well tolerated. With a median follow-up of 18.3 months (range, 12.6-43.5), 42% and 11% of patients had acute Grade 2 gastrourinary and gastrointestinal toxicity, respectively, with no Grade 3 or higher acute toxicity to date. Two patients experienced late Grade 3 GU toxicity. All patients are without evidence of biochemical or clinical progression to date, and favorably low PSA nadirs have been observed with a current median PSA nadir of 0.35 ng/mL (range, <0.01-2.1) for all patients (0.47 ng/mL, range, 0.2-2.1 for the monotherapy cohort; 0.10 ng/mL, range, 0.01-0.5 for the boost cohort). With a median follow-up of 48.6 months (range, 16.4-87.8), the comparable HDR brachytherapy boost cohort has achieved a median PSA nadir of 0.09 ng/mL (range, 0.0-3.3). Early results with SBRT monotherapy and post-EBRT boost for PCa demonstrate acceptable PSA response and minimal toxicity. PSA nadir with SBRT boost appears comparable to those achieved with HDR brachytherapy boost.

International Brachytherapy Practice Patterns: A Survey of the Gynecologic Cancer Intergroup (GCIG)

To determine current practice patterns with regard to gynecologic high-dose-rate (HDR) brachytherapy among international members of the Gynecologic Cancer Intergroup (GCIG) in Japan/Korea (Asia), Australia/New Zealand (ANZ), Europe (E), and North America (NAm). A 32-item survey was developed requesting information on brachytherapy practice patterns and standard management for Stage IB-IVA cervical cancer. The chair of each GCIG member cooperative group selected radiation oncology members to receive the survey. A total of 72 responses were analyzed; 61 respondents (85%) used HDR. The three most common HDR brachytherapy fractionation regimens for Stage IB-IIA patients were 6 Gy for five fractions (18%), 6 Gy for four fractions (15%), and 7 Gy for three fractions (11%); for Stage IIB-IVA patients they were 6 Gy for five fractions (19%), 7 Gy for four fractions (8%), and 7 Gy for three fractions (8%). Overall, the mean combined external-beam and brachytherapy equivalent dose (EQD2) was 81.1 (standard deviation [SD] 10.16). The mean EQD2 recommended for Stage IB-IIA patients was 78.9 Gy (SD 10.7) and for Stage IIB-IVA was 83.3 Gy (SD 11.2) (p = 0.02). By region, the mean combined EQD2 was as follows: Asia, 71.2 Gy (SD 12.65); ANZ, 81.18 (SD 4.96); E, 83.24 (SD 10.75); and NAm, 81.66 (SD, 6.05; p = 0.02 for Asia vs. other regions).The ratio of brachytherapy to total prescribed dose was significantly higher for Japan (p = 0.0002). Although fractionation patterns may vary, the overall mean doses administered for cervical cancer are similar in Australia/New Zealand, Europe, and North America, with practitioners in Japan administering a significantly lower external-beam dose but higher brachytherapy dose to the cervix. Given common goals, standardization should be possible in future clinical trials.

Adding external beam to intra-luminal brachytherapy improves palliation in obstructive squamous cell oesophageal cancer: A prospective multi-centre randomized trial of the International Atomic Energy Agency

Background Whether the combination of high dose-rate brachytherapy (HDRBT) and External Beam Radiation Therapy (EBRT) is superior to HDRBT alone for the palliation of oesophageal cancer has only been explored in a previous IAEA pilot randomized trial. Methods Two hundred and nineteen patients were randomized to adding EBRT or not, after receiving two fractions of HDRBT within 1 week. Each HDRBT consisted of 8 Gy prescribed at 1 cm from source centre. Patients randomized to EBRT received 30 Gy in 10 fractions. The primary outcome was dysphagia-relief experience (DRE). Additional outcomes included various scores, performance status, weight and adverse events. A majority of charts, imaging and radiotherapy plans were externally audited. Results Median follow-up was 197 days, with a median OS of 188 days and an 18% survival rate at 1 year. DRE was significantly improved with combined therapy, for an absolute benefit of +18% at 200 days from randomization ( p = 0.019). In longitudinal regression analyses, scores for dysphagia ( p = 0.00005), odynophagia ( p = 0.006), regurgitation ( p = 0.00005), chest pain ( p = 0.0038) and performance status ( p = 0.0015) were all significantly improved. In contrast, weight, toxicities and overall survival were not different between study arms. Conclusion Symptom improvement occurs with the addition of EBRT to standard HDRBT. The combination is well tolerated and relatively safe.

Combined radiofrequency ablation and high–dose rate brachytherapy for early-stage non–small-cell lung cancer

Purpose This retrospective analysis reports the results of patients with early-stage inoperable non–small-cell lung cancer treated with radiofrequency ablation (RFA) followed by adjuvant high–dose rate (HDR) brachytherapy. Methods and Materials Seventeen medically inoperable patients with biopsy-proven Stage I non–small-cell lung cancer were treated with RFA followed by single fraction HDR brachytherapy. Brachytherapy catheters were inserted immediately after RFA, and one fraction of HDR brachytherapy was delivered on the same day. Doses of brachytherapy ranged from 14.4 to 20 Gy (median, 18 Gy). Patients were followed clinically and radiographically to determine tumor control and toxicity profile. Results Median followup time was 22 months. Of the 17 patients, 3 patients have recurred locally. Each of the patients with local recurrences was originally treated for T2 disease. In total, three of seven cases with T2N0 disease experienced local recurrences, whereas all 9 patients with T1 disease were controlled locally. Five of the 17 patients required a chest tube posttreatment, and 1 patient developed an empyema. There were no deaths within 1 month of treatment. Conclusions RFA followed by HDR brachytherapy yields excellent local control with an acceptable toxicity profile for patients with otherwise inoperable early-stage lung cancer.

Dosimetric Impact of Interfraction Catheter Movement in High-Dose Rate Prostate Brachytherapy

To evaluate the impact of interfraction catheter movement on dosimetry in prostate high-dose-rate (HDR) brachytherapy. Fifteen patients were treated with fractionated HDR brachytherapy. Implants were performed on day 1 under transrectal ultrasound guidance. A computed tomography (CT) scan was performed. Inverse planning simulated annealing was used for treatment planning. The first fraction was delivered on day 1. A cone beam CT (CBCT) was performed on day 2 before the second fraction was given. A fusion of the CBCT and CT was performed using intraprostatic gold markers as landmarks. Initial prostate and urethra contours were transferred to the CBCT images. Bladder and rectum contours were drawn, and catheters were digitized on the CBCT. The planned treatment was applied to the CBCT dataset, and dosimetry was analyzed and compared to the initial dose distribution. This process was repeated after a reoptimization was performed, using the same constraints used on day 1. Mean interfraction catheter displacement was 5.1 mm. When we used the initial plan on day 2, the mean prostate V100 (volume receiving 100 Gy or more) decreased from 93.8% to 76.2% (p < 0.01). Rectal V75 went from 0.75 cm(3) to 1.49 cm(3) (p < 0.01). A reoptimization resulted in a mean prostate V100 of 88.1%, closer to the initial plan (p = 0.05). Mean rectal V75 was also improved with a value of 0.59 cm(3). There was no significant change in bladder and urethra dose on day 2. A mean interfraction catheter displacement of 5.1 mm results in a significant decrease in prostate V100 and an increase in rectum dose. A reoptimization before the second treatment improves dose distribution.

Three-dimensional image-based planning for cervix brachytherapy with bilateral hip prostheses: A solution using MVCT with helical tomotherapy

Purpose We present a method of three-dimensional image-based planning for cervix high-dose-rate (HDR) brachytherapy for patients with bilateral metal hip prostheses using megavoltage computed tomography (MVCT) imaging. Methods and Materials Two patients with bilateral metal hip prostheses were treated with our standard HDR brachytherapy fractionation and critical structure tolerance limits for cervical cancer. MVCT imaging was used for treatment planning because of artifacts present in kilovoltage computed tomography (kVCT), which did not allow visualization of the organs of interest. Results The MVCT images provided adequate contrast to allow the contouring of organs at risk and the digitization of HDR applicators. HDR brachytherapy treatment planning was successfully accomplished based on MVCT images for 2 patients with bilateral metal hip prostheses. Conclusions Using MVCT imaging eliminated streak artifacts, which improved the image quality for treatment planning. MVCT offers an option for three-dimensional planning for cervix brachytherapy in patients with bilateral hip prostheses.