A precise and simple isodose-volume-based verification method for HDR and LDR brachytherapy plans

PURPOSEThe American Association of Physicists in Medicine (AAPM) code of practice for brachytherapy physics recommends performing an independent treatment time calculation. For this we implemented an easy to use isodose-based verification method for HDR (high-dose-rate) and LDR (low-dose-rate) brachytherapy plans.MATERIAL AND METHODSDose-volume-based methods have been developed for Ir-192-based high-dose-rate (HDR) and I-125 prostate low-dose-rate (LDR) brachytherapy. They allow checking the integral dwell time or activity when the volume of a suitable isodose is known. The verification method was validated for 55 clinical HDR and 243 clinical LDR plans.RESULTSFor HDR brachytherapy, the mean absolute difference between the estimated and calculated integral dwell time was 0.8% ± 1.0% (n = 30) with a single-source path and 2.7% ± 1.1% (n = 25) for multiple source paths. The corresponding value for LDR brachytherapy was 1.8% ± 2.0% (n = 243). In HDR brachytherapy, the verification method depends slightly on the plan class when considering one or more than one source paths. Good agreement between the estimated and calculated integral dwell times was obtained based on the 2 Gy isodose. Unlike HDR brachytherapy, the parameters used in the verification method for LDR brachytherapy plan verification strongly depend on the type of seed distribution. So, we recommend using an isodose at the prescribed dose for prostate HDR therapy.CONCLUSIONSIsodose-based verification methods are precise, do not presuppose dedicated tools, and are simple to implement in clinical practice.     

Brachytherapy provides comparable outcomes and improved cost-effectiveness in the treatment of low/intermediate prostate cancer

PurposeTo evaluate the cost-effectiveness and outcomes of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy compared with intensity-modulated radiation therapy (IMRT) in patients with low/intermediate risk of prostate cancer.Methods and MaterialsOne thousand three hundred twenty-eight patients with low or intermediate risk of prostate cancer were treated with LDR (n = 207), HDR with four fractions (n = 252), or IMRT (n = 869) between January 1992 and December 2008. LDR patients were treated with palladium seeds to a median dose of 120 Gy, whereas HDR patients were treated to a median dose 38.0 Gy (four fractions). IMRT patients received 42–44 fractions with a median dose of 75.6 Gy. Clinical outcomes were compared, including biochemical failure, cause-specific survival, and overall survival.ResultsOverall, no differences in 5-year biochemical control (BC) or cause-specific survival were noted among treatment modalities. The calculated reimbursement for LDR brachytherapy, HDR brachytherapy with four fractions, and IMRT was $9,938; $17,514; and $29,356, respectively. HDR and LDR brachytherapy were statistically less costly to Medicare and the institution than IMRT (p < 0.001), and LDR brachytherapy was less costly than HDR brachytherapy (p = 0.01 and p < 0.001). Incremental cost-effectiveness ratios for cost to Medicare for BC with IMRT were $4045 and $2754 per percent of BC for LDR and HDR brachytherapy, respectively. Incremental cost-effectiveness ratio using institutional cost comparing IMRT with LDR and HDR brachytherapy was $4962 and $4824 per 1% improvement in BC.ConclusionsIn this study of patients with low and intermediate risk of prostate cancer, comparable outcomes at 5 years were noted between modalities with increased costs associated with IMRT.     

Dose to the dominant intraprostatic lesion using HDR vs. LDR monotherapy: A Phase II randomized trial

PurposeTo present the dosimetric results of a Phase II randomized trial comparing dose escalation to the MRI-defined dominant intraprostatic lesion (DIL) using either low-dose-rate (LDR) or high-dose-rate (HDR) prostate brachytherapy.Material and MethodsPatients receiving prostate brachytherapy as monotherapy were randomized to LDR or HDR brachytherapy. Prostate and DILs were contoured on preoperative multiparametric MRI. These images were registered with transrectal ultrasound for treatment planning. LDR brachytherapy was preplanned using I-125 seeds. HDR brachytherapy used intraoperative transrectal ultrasound–based planning to deliver 27 Gy/2 fractions in separate implants. DIL location was classified as peripheral, central, or anterior. A student t-test compared DIL D₉₀ between modalities and DIL locations.ResultsOf 60 patients, 31 underwent LDR and 29 HDR brachytherapy. Up to three DILs were identified per patient (100 total) with 74 peripheral, six central, and 20 anterior DILs. Mean DIL volume was 1.9 cc (SD: 1.7 cc) for LDR and 1.6 cc (SD 1.3 cc) for HDR (p = 0.279). Mean DIL D₉₀ was 151% (SD 30%) for LDR and 132% (SD 13%) for HDR. For LDR, mean peripheral DIL D₉₀ was 159% (SD 27%) and central or anterior 127% (SD 13%). HDR peripheral DILs received 137% (SD 12%) and central or anterior 119% (SD 7%). DIL D₉₀ for peripheral lesions was higher than anterior and central (p < 0.001).ConclusionsDIL location affects dose escalation, particularly because of urethral proximity, such as for anterior and central DILs. HDR brachytherapy may dose escalate better when target DIL is close to critical organs.     

Compendium of fractionation choices for gynecologic HDR brachytherapy—An American Brachytherapy Society Task Group Report

PurposeThe purpose of this study was to report a list of accepted fractionation schemes for high-dose-rate (HDR) brachytherapy for gynecological cancers in a definitive, neoadjuvant, or adjuvant setting.Methods and MaterialsMembers of the American Brachytherapy Society (ABS) Task Force with expertise in gynecological brachytherapy reviewed the literature and existing ABS guidelines regarding various dose-fractionation schedules for HDR brachytherapy to create this compendium. Other resources include current guidelines published by medical societies, clinical trials, the published medical literature, and the clinical experience of the ABS Task Force members. The ABS consensus statements for HDR brachytherapy practice were reviewed for these fractionation schemes and form the major source for this report. Specific recommendations for therapy and recommendations for further investigations were made when there was agreement.ResultsA variety of dose-fractionation schedules for HDR brachytherapy alone or integrating brachytherapy with external-beam radiation exist. The choice of a given fractionation schedule may be appropriate depending on the practice situation for the patient and the resources available. While there is no single optimal dose-fractionation scheme for any disease site or clinical situation, higher doses per fraction with fewer fractions per regimen have been known to increase toxicity. The corresponding 2-Gray (Gy) per fraction radiobiologic equivalent doses have been provided (normalized therapy dose) to compare the various regimens where indicated and can be used to estimate isoeffective schedules.ConclusionsThis compendium of HDR brachytherapy fractionation schedules provides various options to the gynecologic brachytherapist and a ready reference for clinical use in the management of gynecological cancer treatments.     

LDR vs. HDR brachytherapy for localized prostate cancer: the view from radiobiological models

PURPOSE: Permanent LDR brachytherapy and temporary HDR brachytherapy are competitive techniques for clinically localized prostate radiotherapy. Although a randomized trial will likely never be conducted comparing these two forms of brachytherapy, a comparative radiobiological modeling analysis proves useful in understanding some of their intrinsic differences, several of which could be exploited to improve outcomes. METHODS AND MATERIALS: Radiobiological models based upon the linear quadratic equations are presented for fractionated external beam, fractionated (192)Ir HDR brachytherapy, and (125)I and (103)Pd LDR brachytherapy. These models incorporate the dose heterogeneities present in brachytherapy based upon patient-derived dose volume histograms (DVH) as well as tumor doubling times and repair kinetics. Radiobiological parameters are normalized to correspond to three accepted clinical risk factors based upon T-stage, PSA, and Gleason score to compare models with clinical series. Tumor control probabilities (TCP) for LDR and HDR brachytherapy (as monotherapy or combined with external beam) are compared with clinical bNED survival rates. Predictions are made for dose escalation with HDR brachytherapy regimens. RESULTS: Model predictions for dose escalation with external beam agree with clinical data and validate the models and their underlying assumptions. Both LDR and HDR brachytherapy achieve superior tumor control when compared with external beam at conventional doses (<70 Gy), but similar to results from dose escalation series. LDR brachytherapy as boost achieves superior tumor control than when used as monotherapy. Stage for stage, both LDR and current HDR regimens achieve similar tumor control rates, in agreement with current clinical data. HDR monotherapy with large-dose fraction sizes might achieve superior tumor control compared with LDR, especially if prostate cancer possesses a high sensitivity to dose fractionation (i.e., if the alpha/beta ratio is low). 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. However, HDR brachytherapy dose escalation regimens might be able to achieve higher biologically effective doses of irradiation in comparison to LDR, and hence improved outcomes. This advantage over LDR would be amplified should prostate cancer possess a high sensitivity to dose fractionation (i.e., a low alpha/beta ratio) as the current evidence suggests.     

The one hundred most cited publications in prostate brachytherapy

PurposeThe aim of this study is to identify the leaders in research on prostate brachytherapy through a bibliometric analysis of the top 100 most cited publications in the field.Methods and materialsA broad search was performed with the term “prostate brachytherapy” using the Web of Science database to generate wide-ranging results that were reviewed by reading the abstracts and, if necessary, the articles to select the top 100 most cited publications.ResultsThe median of the total citation count was 187 (range 132–1464). The median citation per year index (citations/year since publication) was 13.5 (range 6.3–379.0). In all publications, the first author was also the corresponding author. The top publishing countries of the first author included the United States (n = 78), Canada (n = 6), the UK (n = 5), and Germany (n = 4). The journal with the most publications was the International Journal of Radiation Oncology Biology Physics (n = 38). There were 27 more publications on low-dose-rate (LDR) than on high-dose-rate (HDR) (43 vs 16) among the top 100. HDR publications had only one first author that had three articles in comparison to LDR publications, which had four first authors, each with three articles on LDR. The United States was the leading country in 43.8% of HDR publications (n = 7) and 88.4% of LDR publications (n = 38).ConclusionsOur bibliometric analysis of the top 100 most cited publications clearly demonstrates the North American dominance in the publications of prostate brachytherapy, especially in LDR. However, European first authors were more frequent in HDR publications.     

American Brachytherapy Society–Groupe Européen de Curiethérapie–European Society of Therapeutic Radiation Oncology (ABS-GEC-ESTRO) consensus statement for penile brachytherapy

PurposeTo develop a consensus statement between the American Brachytherapy Society (ABS) and Groupe Européen de Curiethérapie/European Society for Therapeutic Radiation and Oncology (GEC-ESTRO) for the use of brachytherapy in the primary management of carcinoma of the penis.Methods and MaterialsThe American Brachytherapy Society and Groupe Européen de Curiethérapie/European Society for Therapeutic Radiation and Oncology convened a group of expert practitioners and physicists to develop a statement for the use of ¹⁹²Ir in low-dose-rate (LDR), pulse-dose-rate, and high-dose-rate (HDR) brachytherapy for penile cancer.ResultsDecades of brachytherapy experience with LDR ¹⁹²Ir wire and pulse-dose-rate ¹⁹²Ir sources for this rare malignancy indicate a penile preservation rate of 70% at 10 years postimplant. Chief morbidities remain stenosis of the urethral meatus and soft tissue ulceration at the primary site. Nonhealing ulceration can be successfully managed with various measures including hyperbaric oxygen treatment. HDR brachytherapy implant procedures are technically similar to LDR. The optimal HDR dose and fractionation schemes are being developed.ConclusionsThe good tumor control rates, acceptable morbidity, and functional organ preservation warrant recommendation of brachytherapy as the initial treatment for invasive T1, T2, and selected T3 penile cancers.     

Low dose rate brachytherapy for primary treatment of localized prostate cancer: A systemic review and executive summary of an evidence-based consensus statement

PURPOSEThe purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of prostate cancer.METHODS AND MATERIALSThe American Brachytherapy Society convened a task force for addressing key questions concerning ultrasound-based LDR prostate brachytherapy for the primary treatment of prostate cancer. A comprehensive literature search was conducted to identify prospective and multi-institutional retrospective studies involving LDR brachytherapy as monotherapy or boost in combination with external beam radiation therapy with or without adjuvant androgen deprivation therapy. Outcomes included disease control, toxicity, and quality of life.RESULTSLDR prostate brachytherapy monotherapy is an appropriate treatment option for low risk and favorable intermediate risk disease. LDR brachytherapy boost in combination with external beam radiation therapy is appropriate for unfavorable intermediate risk and high-risk disease. Androgen deprivation therapy is recommended in unfavorable intermediate risk and high-risk disease. Acceptable radionuclides for LDR brachytherapy include iodine-125, palladium-103, and cesium-131. Although brachytherapy monotherapy is associated with increased urinary obstructive and irritative symptoms that peak within the first 3 months after treatment, the median time toward symptom resolution is approximately 1 year for iodine-125 and 6 months for palladium-103. Such symptoms can be mitigated with short-term use of alpha blockers. Combination therapy is associated with worse urinary, bowel, and sexual symptoms than monotherapy. A prostate specific antigen <= 0.2 ng/mL at 4 years after LDR brachytherapy may be considered a biochemical definition of cure.CONCLUSIONSLDR brachytherapy is a convenient, effective, and well-tolerated treatment for prostate cancer.     

Concurrent chemoradiation for cervical cancer: Comparison of LDR and HDR brachytherapy

PurposeTo compare clinical outcomes between low-dose-rate (LDR) brachytherapy and high-dose-rate (HDR) brachytherapy for cervical cancer patients.Methods and MaterialsAll consecutive newly diagnosed cervical cancer patients undergoing pretreatment 18-fluorodeoxyglucose positron emission tomography imaging and treated with curative-intent definitive chemoradiation from 1997 to 2016 at a U.S. academic center were included. Brachytherapy boost was LDR or HDR 2D treatment planning from 1997 to 2005 and HDR with MR-based 3D planning from 2005 to 2016. Local control (LC), cancer-specific survival (CSS), and late bowel/bladder complications were evaluated.ResultsTumor stages were International Federation of Gynecology and Obstetrics IB1-IIB (n = 457; 75%) and III-IVA (n = 152; 25%). Brachytherapy was LDR for 104 patients and HDR for 505 patients. Concurrent weekly cisplatin was administered to 536 patients (88%). With median followup of 9.4 years, there was no difference in LC (p = 0.24) or CSS (p = 0.50) between LDR and HDR brachytherapy. Cox multivariable regression showed that only International Federation of Gynecology and Obstetrics stage III-IVA (HR=2.4, p = 0.004) was associated with worse LC. A propensity-matched cohort (90 LDR vs. 90 HDR) was created, and the 5-year LC rates were 88% LDR and 82% HDR, p = 0.26; 5-year CSS rates were 66% LDR and 58% HDR, p = 0.19; 5-year grade ≥3 bowel/bladder toxicities were 23% LDR and 16% HDR, p = 0.44. For all patients, the 5-year late toxicity in stage III-IVA patients was higher with LDR 47% vs. HDR 15%, p = 0.03, with no difference in LC, 86% and 75%, respectively (p = 0.09).ConclusionsThere was no difference in LC with either LDR or HDR brachytherapy. The late complication rate was reduced with HDR and 3D-planned brachytherapy compared to LDR and 2D-planned brachytherapy.     

Semiconductor real-time quality assurance dosimetry in brachytherapy

With the increase in complexity of brachytherapy treatments, there has been a demand for the development of sophisticated devices for delivery verification. The Centre for Medical Radiation Physics (CMRP), University of Wollongong, has demonstrated the applicability of semiconductor devices to provide cost-effective real-time quality assurance for a wide range of brachytherapy treatment modalities. Semiconductor devices have shown great promise to the future of pretreatment and in vivo quality assurance in a wide range of brachytherapy treatments, from high-dose-rate (HDR) prostate procedures to eye plaque treatments. The aim of this article is to give an insight into several semiconductor-based dosimetry instruments developed by the CMRP. Applications of these instruments are provided for breast and rectal wall in vivo dosimetry in HDR brachytherapy, urethral in vivo dosimetry in prostate low-dose-rate (LDR) brachytherapy, quality assurance of HDR brachytherapy afterloaders, HDR pretreatment plan verification, and real-time verification of LDR and HDR source dwell positions.     

Evaluation of time,attendance of medical staff,and resources during interstitial brachytherapy for prostate cancer

Introduction

The German Society of Radiation Oncology initiated a multicenter trial to evaluate core processes and subprocesses of radiotherapy by prospective evaluation of all important procedures in the most frequent malignancies treated by radiation therapy. The aim of this analysis was to assess the required resources for interstitial high-dose-rate (HDR) and low-dose-rate (LDR) prostate brachytherapy (BRT) based on actual time measurements regarding allocation of personnel and room occupation needed for specific procedures.

Patients and methods

Two radiotherapy centers (community hospital of Offenbach am Main and community hospital of Eschweiler) participated in this prospective study. Working time of the different occupational groups and room occupancies for the workflow of prostate BRT were recorded and methodically assessed during a 3-month period.

Results

For HDR and LDR BRT, a total of 560 and 92 measurements, respectively, were documented. The time needed for treatment preplanning was median 24 min for HDR (n?=?112 measurements) and 6 min for LDR BRT (n?=?21). Catheter implantation with intraoperative HDR real-time planning (n?=?112), postimplantation HDR treatment planning (n?=?112), and remotely controlled HDR afterloading irradiation (n?=?112) required median 25, 39, and 50 min, respectively. For LDR real-time planning (n?=?39) and LDR treatment postplanning (n?=?32), the assessed median duration was 91 and 11 min, respectively. Room occupancy and overall mean medical staff times were 194 and 910 min respectively, for HDR, and 113 and 371 min, respectively, for LDR BRT.

Conclusion

In this prospective analysis, the resource requirements for the application of HDR and LDR BRT of prostate cancer were assessed methodically and are presented for first time.     

Quality assurance of HDR prostate plans: Program implementation at a community hospital

Adenocarcinoma of the prostate is currently the most commonly diagnosed cancer in men in the United States, and the second leading cause of cancer mortality. The utilization of radiation therapy is regarded as the definitive local therapy of choice for intermediate- and high-risk disease, in which there is increased risk for extracapsular extension, seminal vesicle invasion, or regional node involvement. High-dose-rate (HDR) brachytherapy is a logical treatment modality to deliver the boost dose to an external beam radiation therapy (EBRT) treatment to increase local control rates. From a treatment perspective, the utilization of a complicated treatment delivery system, the compressed time frame in which the procedure is performed, and the small number of large dose fractions make the implementation of a comprehensive quality assurance (QA) program imperative. One aspect of this program is the QA of the HDR treatment plan. Review of regulatory and medical physics professional publications shows that substantial general guidance is available. We provide some insight to the implementation of an HDR prostate plan program at a community hospital. One aspect addressed is the utilization of the low-dose-rate (LDR) planning system and the use of existing ultrasound image sets to familiarize the radiation therapy team with respect to acceptable HDR implant geometries. Additionally, the use of the LDR treatment planning system provided a means to prospectively determine the relationship between the treated isodose volume and the product of activity and time for the department’s planning protocol prior to the first HDR implant. For the first 12 HDR prostate implants, the root-mean-square (RMS) deviation was 3.05% between the predicted product of activity and time vs. the actual plan values. Retrospective re-evaluation of the actual implant data reduced the RMS deviation to 2.36%.     

Quality assurance of HDR prostate plans: Program implementation at a community hospital

Adenocarcinoma of the prostate is currently the most commonly diagnosed cancer in men in the United States, and the second leading cause of cancer mortality. The utilization of radiation therapy is regarded as the definitive local therapy of choice for intermediate- and high-risk disease, in which there is increased risk for extracapsular extension, seminal vesicle invasion, or regional node involvement. High-dose-rate (HDR) brachytherapy is a logical treatment modality to deliver the boost dose to an external beam radiation therapy (EBRT) treatment to increase local control rates. From a treatment perspective, the utilization of a complicated treatment delivery system, the compressed time frame in which the procedure is performed, and the small number of large dose fractions make the implementation of a comprehensive quality assurance (QA) program imperative. One aspect of this program is the QA of the HDR treatment plan. Review of regulatory and medical physics professional publications shows that substantial general guidance is available. We provide some insight to the implementation of an HDR prostate plan program at a community hospital. One aspect addressed is the utilization of the low-dose-rate (LDR) planning system and the use of existing ultrasound image sets to familiarize the radiation therapy team with respect to acceptable HDR implant geometries. Additionally, the use of the LDR treatment planning system provided a means to prospectively determine the relationship between the treated isodose volume and the product of activity and time for the department’s planning protocol prior to the first HDR implant. For the first 12 HDR prostate implants, the root-mean-square (RMS) deviation was 3.05% between the predicted product of activity and time vs. the actual plan values. Retrospective re-evaluation of the actual implant data reduced the RMS deviation to 2.36%.     

A comparative analysis of overall survival between high-dose-rate and low-dose-rate brachytherapy boosts for unfavorable-risk prostate cancer

Purpose

External beam radiation therapy (EBRT) with low-dose-rate (LDR) brachytherapy boost has been associated with improved biochemical progression–free survival and overall survival (OS) compared with dose-escalated EBRT (DE-EBRT) alone for unfavorable-risk prostate cancer. However, it is not known whether high-dose-rate (HDR) boost provides a similar benefit. We compare HDR boost against LDR boost and DE-EBRT with respect to OS.

Low-Dose-Rate versus High-Dose-Rate intracavitary brachytherapy in cervical cancer - Final Results of a Phase III randomized trial

PURPOSEIntracavitary brachytherapy using High-Dose-Rate (HDR) and Low-dose-rate (LDR) in cervical cancer has been utilized. We report the long-term final results of a large randomized trial in terms of toxicities and efficacy.METHODS AND MATERIALSBetween 1996 to 2005, 816 patients were randomized to LDR (n = 441 patients) or HDR brachytherapy (n = 369 patients) stratified by FIGO Stage grouping. Patients with Stage I-II received external irradiation of 40 Gy in 20 fractions (with midline block (MLB)) followed by either 2 LDR Intracavitary applications of 30 Gy to point A (2–3 weeks apart) or 5 HDR Intracavitary applications of 7 Gy to point A once weekly. Patients with Stage III received 50 Gy in 25 fractions (with MLB after 40 Gy) followed by either one application of LDR 30 Gy to point A or three applications of HDR 7 Gy to point A once weekly.RESULTSWith a median follow-up was 64 months (interquartile range [IQR]: 21 - 111), moderate to severe rectal and bladder complications were higher in LDR arm as compared to HDR arm (9.7% vs. 3.6%; p = 0.02) and (10.5% vs. 5.5%; p = 0.06) for Stage I-II. No difference in rectal or bladder complications for Stage III patients. Disease free and overall survivals were similar in both the arms for all stages.CONCLUSIONSHDR intracavitary brachytherapy with 7 Gy per fraction weekly is superior to LDR in terms of late rectal and bladder complications. Local control rates and survivals are similar irrespective of stages.