Low Dose Rate Treatment Research Articles

Low-dose-rate, high-dose-rate, and pulsed-dose-rate intra-cavitary brachytherapy for cervical cancer: The very first comparison study.

For cervical cancer patients, intra-cavitary brachytherapy (ICBT) is utilized with various dose-rate systems, such as low-dose-rate (LDR), high-dose-rate (HDR), and pulsed-dose-rate (PDR). This retrospective analysis aimed to compare the therapeutic outcomes of cervical cancer patients treated with either LDR-, HDR-, or PDR-ICBT. A total of 613 patients were treated with pelvic external beam radiation therapy (EBRT), followed by either LDR- (271 patients), HDR- (259 patients), or PDR- (83 patients) ICBT. Point-based planning was performed according to orthogonal radiographs in LDR patients, and computed tomography (CT) imaging in HDR and PDR patients. ICBT prescribed dose was as follows: for LDR treatment, 30 Gy in a single-session; for HDR: 7 Gy × 3 fractions (once a week fraction); and for PDR: 27 Gy in an hourly pulse of 70 cGy, with all the doses prescribed at point A. Radioactive source used was cesium-137 for LDR, and iridium-192 for HDR and PDR treatments. Loco-regional control (LRC) rate was 74%, 75%, and 77% in LDR, HDR, and PDR groups, respectively (p = 0.80). The 5-year overall survival (OS) in the three groups, i.e., LDR, HDR, and PDR was 63%, 64%, and 68%, respectively (p = 0.77). Severe late toxicity (RTOG grade ≥ 3) rate in the three groups was comparable (LDR, 12%; HDR, 8%; and PDR, 8.9%, p = 0.36). Our study revealed comparable LRC, 5-year OS, and late toxicity rates using three dose-rate systems. Lower OS rates were observed in LDR group for stage III patients compared with patients in HDR and PDR groups. Therefore, we suggest that LDR should be used with caution while treating stage III patients.

Impact of Prostate Cancer Treatment with Low Dose Rate Brachytherapy on Testosterone: A Retrospective Analysis

Decrease in serum testosterone counts have been reported in the literature following external beam radiotherapy (EBRT), with a suggested association to low dose irradiation of the testes occurring with historical and modern external techniques. Low dose rate (LDR) brachytherapy has been described as exposing the testes to between 2 and 19 cGy compared with 196-220 cGy with EBRT. This decrease in excess dose is hypothesized to spare post-treatment testosterone decrease and subsequent change in patient-perceived quality of life. Here, we retrospectively evaluate LDR-treated prostate cancer patient testosterone change in a single-institution patient cohort. Patients with prostate cancer who had previously received LDR brachytherapy were identified, and patients with prior baseline total testosterone lab values as well as a lab value within one year post-treatment were identified. Patients receiving concurrent androgen deprivation therapy or EBRT were excluded. The closest baseline values prior to and after LDR treatment were used for before/after comparison. Samples were compared using the paired t-test. A total of 1,463 patients receiving LDR were identified with data available for analysis between 1998 and 2023; of these, 139 patients met the above criteria for analysis. Mean age was 66 (median 67; range: 47 - 79). 5 patients received 110 Gy, 2 received 120 Gy, and the remainder 145 Gy, all conducted with I-125. Total mCi delivered ranged from 20.3 mCi to 56.7 mCi (median 37.6 mCi). Approximately 57% were GS6, 42% G7, and < 1% G8. Approximately 80% of patients had T1c disease, with 19% T2 and < 1% T3a. All patients were cN0M0. Mean pre- and post-treatment testosterone were 385.5 ng/dL and 382.9 (SD: 170.9, 150.9; mean difference 2.65 [95% CI: -15.6, 20.9]), respectively, with no statistical change noted (p = 0.774). Testosterone levels have been reported to drop following definitive EBRT owing to excess dose delivery to the testes. On review of our institutional experience in definitive LDR brachytherapy for patients treated without ADT administration, no change in testosterone levels were noted.

Determining Combined Modality Dosimetric Constraints by Integration of IMRT and LDR Prostate Brachytherapy Dosimetry and Correlation with Toxicity

Intermediate- and high-risk prostate cancer patients undergoing combination external beam radiation therapy (EBRT) and low dose rate (LDR) brachytherapy have demonstrated increased genitourinary (GU) toxicity. We have previously demonstrated a method to combine EBRT and LDR dosimetry. In this work, we use this technique for a sample of patients with intermediate- and high-risk prostate cancer, correlate with clinical toxicity, and suggest preliminary summed organ-at-risk constraints for future investigation. Intensity modulated EBRT and 103Pd-based LDR treatment plans were combined for 138 patients using biological effective dose (BED) and deformable image registration. GU and gastrointestinal (GI) toxicity were compared with combined dosimetry for the urethra, bladder, and rectum. Differences between doses in each toxicity grade were assessed by analysis of variance (α=0.05). Combined dosimetric constraints are proposed using the mean organ-at-risk dose, subtracting 1 standard deviation for a conservative recommendation. The majority of our 138-patient cohort experienced grade 0 to 2 GU or GI toxicity. Six grade 3 toxicities were noted. Mean prostate BED D90 (± 1 standard deviation) was 165.5±11.1 Gy. Mean urethra BED D10 was 230.3±33.9 Gy. Mean bladder BED was 35.2±11.0 Gy. Mean rectum BED D2cc was 85.6±24.3 Gy. Significant dosimetric differences between toxicity grades were found for mean bladder BED, bladder D15, and rectum D50, but differences between individual means were not statistically significant. Given the low incidence of grade 3 GU and GI toxicity, we propose urethra D10 <200 Gy, rectum D2cc <60 Gy, and bladder D15 <45 Gy as preliminary dose constraints for combined modality therapy. We successfully applied our dose integration technique to a sample of patients with intermediate- and high-risk prostate cancer. Incidence of grade 3 toxicity was low, suggesting that combined doses observed in this study were safe. We suggest preliminary dose constraints as a conservative starting point to investigate and escalate prospectively in a future study.

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.

Evaluation of a Machine-Learning Algorithm for Treatment Planning in Prostate Low-Dose-Rate Brachytherapy

This retrospective study presents the results of a machine-learning (ML) algorithm used to automatically generate high-quality, prostate low-dose-rate (LDR) brachytherapy treatment plans. The algorithm can replicate several characteristics of expert created pre-operative LDR treatment plans. The planning efficiency, dosimetry, and quality (as assessed by experts) of pre-operative plans generated with an ML model was evaluated.

Estimation of whole-body radiation exposure from brachytherapy for oral cancer using a Monte Carlo simulation.

Early stage oral cancer can be cured with oral brachytherapy, but whole-body radiation exposure status has not been previously studied. Recently, the International Commission on Radiological Protection Committee (ICRP) recommended the use of ICRP phantoms to estimate radiation exposure from external and internal radiation sources. In this study, we used a Monte Carlo simulation with ICRP phantoms to estimate whole-body exposure from oral brachytherapy. We used a Particle and Heavy Ion Transport code System (PHITS) to model oral brachytherapy with 192Ir hairpins and 198Au grains and to perform a Monte Carlo simulation on the ICRP adult reference computational phantoms. To confirm the simulations, we also computed local dose distributions from these small sources, and compared them with the results from Oncentra manual Low Dose Rate Treatment Planning (mLDR) software which is used in day-to-day clinical practice. We successfully obtained data on absorbed dose for each organ in males and females. Sex-averaged equivalent doses were 0.547 and 0.710 Sv with 192Ir hairpins and 198Au grains, respectively. Simulation with PHITS was reliable when compared with an alternative computational technique using mLDR software. We concluded that the absorbed dose for each organ and whole-body exposure from oral brachytherapy can be estimated with Monte Carlo simulation using PHITS on ICRP reference phantoms. Effective doses for patients with oral cancer were obtained.

Evaluation of a Machine-Learning Algorithm for Treatment Planning in Prostate Low-Dose-Rate Brachytherapy

This work presents the application of a machine learning (ML) algorithm to automatically generate high-quality, prostate low-dose-rate (LDR) brachytherapy treatment plans. The ML algorithm can mimic characteristics of preoperative treatment plans deemed clinically acceptable by brachytherapists. The planning efficiency, dosimetry, and quality (as assessed by experts) of preoperative plans generated with an ML planning approach was retrospectively evaluated in this study. Preimplantation and postimplantation treatment plans were extracted from 100 high-quality LDR treatments and stored within a training database. The ML training algorithm matches similar features from a new LDR case to those within the training database to rapidly obtain an initial seed distribution; plans were then further fine-tuned using stochastic optimization. Preimplantation treatment plansgenerated by the ML algorithm were compared with brachytherapist (BT) treatment plans in terms of planning time (Wilcoxon rank sum, α=0.05) and dosimetry (1-way analysis of variance, α=0.05). Qualitative preimplantation plan quality was evaluated by expert LDR radiation oncologists using a Likert scale questionnaire. The average planning time for the ML approach was 0.84±0.57minutes, compared with 17.88±8.76minutes for the expert planner (P=.020). Preimplantation plans were dosimetrically equivalent to the BT plans; the average prostate V150% was 4% lower for ML plans (P=.002), although the difference was not clinically significant. Respondents ranked the ML-generated plans as equivalent to expert BT treatment plans in terms of target coverage, normal tissue avoidance, implant confidence, and the need for plan modifications. Respondents had difficulty differentiating between plans generated by a human or those generated by the ML algorithm. Prostate LDR preimplantation treatment plans that have equivalent quality to plans created by brachytherapists can be rapidly generated using ML. The adoption of ML in the brachytherapy workflow is expected to improve LDR treatment plan uniformity while reducing planning time and resources.

Trends in the Quality of Treatment for Patients With Intact Cervical Cancer in the United States, 1999 Through 2011

High-quality treatment for intact cervical cancer requires external radiation therapy, brachytherapy, and chemotherapy, carefully sequenced and completed without delays. We sought to determine how frequently current treatment meets quality benchmarks and whether new technologies have influenced patterns of care. By searching diagnosis and procedure claims in MarketScan, an employment-based health care claims database, we identified 1508 patients with nonmetastatic, intact cervical cancer treated from 1999 to 2011, who were <65 years of age and received >10 fractions of radiation. Treatments received were identified using procedure codes and compared with 3 quality benchmarks: receipt of brachytherapy, receipt of chemotherapy, and radiation treatment duration not exceeding 63 days. The Cochran-Armitage test was used to evaluate temporal trends. Seventy-eight percent of patients (n=1182) received brachytherapy, with brachytherapy receipt stable over time (Cochran-Armitage Ptrend=.15). Among patients who received brachytherapy, 66% had high-dose rate and 34% had low-dose rate treatment, although use of high-dose rate brachytherapy steadily increased to 75% by 2011 (Ptrend<.001). Eighteen percent of patients (n=278) received intensity modulated radiation therapy (IMRT), and IMRT receipt increased to 37% by 2011 (Ptrend<.001). Only 2.5% of patients (n=38) received IMRT in the setting of brachytherapy omission. Overall, 79% of patients (n=1185) received chemotherapy, and chemotherapy receipt increased to 84% by 2011 (Ptrend<.001). Median radiation treatment duration was 56 days (interquartile range, 47-65 days); however, duration exceeded 63 days in 36% of patients (n=543). Although 98% of patients received at least 1 benchmark treatment, only 44% received treatment that met all 3 benchmarks. With more stringent indicators (brachytherapy, ≥4 chemotherapy cycles, and duration not exceeding 56 days), only 25% of patients received treatment that met all benchmarks. In this cohort, most cervical cancer patients received treatment that did not comply with all 3 benchmarks for quality treatment. In contrast to increasing receipt of newer radiation technologies, there was little improvement in receipt of essential treatment benchmarks.

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

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

SU-E-T-412: Can Cyberknife SBRT Be an Alternative to Brachytherapy for Cervical Cancer Treatment?

To investigate the effectiveness of stereotactic body radiation therapy (SBRT) with Cyberknife for treatment of squamous cell carcinoma (SCCa) of cervix that are commonly treated with brachytherapy. SCCa of cervix is routinely treated with external beam radiation therapy (EBRT) followed by brachytherapy. Common practice is to use high-dose- rate (HDR) brachytherapy, mainly with Ir-192; however, low-dose-rate (LDR) brachytherapy with Cs-137 is also used. Three of our patients with cervical SCCa who were chosen to have LDR brachytherapy (Cs-137 with tandem and ovoids) could not tolerate the prolonged treatment or applicator placement. All these patients previously received 45Gy (1.8Gy/fratction) from EBRT and well tolerated. Planned LDR treatment dose and time were for patient-1: 42.63Gy in 73.5hr, patient-2: 42.34Gy in 73hr, patient-3: 41.76Gy in 72hr. Delivered LDR dose and time were: 3.75Gy in 6.5hr, OGy in Ohr, and 17.3Gy in 19.8hr, for patient-1, -2 and -3, respectively. Two of the three patients tolerated LDR treatment partially; the second patient could not tolerate the applicator, which required immediate removal after placement. Treatments were completed with Cyberknife SBRT (CK-SBRT)doses of 25Gy, 15Gy and 25Gy for patient-1, -2 and -3, respectively; all had 5Gy/fraction and 3fractions/week. Prescriptions were at 80% isododelines; CTV coverages were 96.6%, 99.9% and 100% for patient-1, -2 and -3, respectively. Till their last follow-up in February 2012, all three patients were doing fine clinically without any evidence of disease; none of these patients had any complications that could be related to CK-SBRT. Appears that CK-SBRT can be a viable treatment alternative to brachytherapy. CK-SBRT may also be more appealing to patients and physicians for a variety of reasons such as out-patient procedure, shorter treatment time, no need for operating room, and no need for applicator insertion and tolerance. However, extensive clinical study is warranted in this regard.

Long-term Cosmesis After Lumpectomy and Brachytherapy in the Management of Carcinoma of the Previously Irradiated Breast

To evaluate the cosmetic outcome of brachytherapy after lumpectomy in the management of carcinoma of the previously irradiated breast. Between January 1998 and April 2008, 26 patients with TIS or T1 breast carcinoma were offered interstitial or intracavitary brachytherapy after lumpectomy in a previously irradiated breast as an alternative to salvage mastectomy. Twenty-five of 26 patients had prior lumpectomy followed by standard postoperative external beam radiotherapy for early stage carcinoma of the breast [dose range 5000-6040 cGy]. One patient developed breast cancer after full mantle irradiation [4500 cGy to the mediastinum and axillae] for Hodgkin Lymphoma 27 years earlier. All tumors were excised with final margins of resection free of disease per National Surgical Adjuvant Breast and Bowel Project definition. After lumpectomy, tumor bed implantation was carried out utilizing a low dose rate interstitial technique in 22 patients, whereas 3 patients were treated with high dose rate brachytherapy using the MammoSite brachytherapy catheter and 1 patient was treated with high dose rate brachytherapy using the Contura catheter. The low dose rate treatment consisted of 4500 to 5000 cGy at 35 to 50 cGy per hour to the tumor bed plus a 1.0 cm margin, whereas the high dose rate treatment consisted of 3400 cGy in twice daily fractions of 340 cGy currently used in National Surgical Adjuvant Breast and Bowel Project B-39. Cosmesis was graded according to the B-39 cosmesis scale for de novo treatments: grade I as excellent, grade II as good, Grade III as fair, and Grade IV as poor. Eighteen patients were scored as grade I, 6 as grade II, and 2 as grade III. No patient received a Grade IV score. All 4 balloon brachytherapy patients were scored as Grade I. Twenty-five of 26 patients remained free of local failure with a median follow-up of 38 months (range 6-75 months). The only patient to develop a second local recurrence was graded as grade I before salvage mastectomy. Two patients developed wound dehiscence after immediate postlumpectomy implantation. Two have succumbed to metastatic breast carcinoma at 17 and 24 months after salvage implant therapy. An additional patient has succumbed to chronic obstructive pulmonary disease. All patients, regardless of cosmesis grade were satisfied with their decision for repeat conservation therapy. Factors affecting cosmesis were distance from the implant to the skin, the type of device used, and the amount of residual breast tissue after repeat lumpectomy. The cosmetic effect of brachytherapy after lumpectomy in the management of recurrent carcinoma of the previously irradiated breast is acceptable in highly selected patients. Intracavitary technique may provide superior cosmetic results for patients retreated with brachytherapy for salvage.

Radiation Dosimetry in Brachytherapy, Introducing A Spherical Diode Dosimeter

Brachytherapy is a cancer treatment modality in which a radiation source is inserted into the tumor. It is done in one of two ways: Low Dose Rate (LDR) treatment where seeds are permanently implanted, or High Dose Rate (HDR), a short time exposure. The isotopes mostly used for LDR treatment are I-125 and Pd-103 of activity about 18.5 MBq per seed. HDR treatment is generally done with Ir-192 sources of activity 370 GBq. We introduce a new source for both HDR and LDR treatment, namely Tm-170. Safety considerations for the medical staff, the patient and people around him include: well shielded sources, shortest handling time and keeping uninvolved people at a safe distance. HDR sources are kept in a lead container and applied by a remote controlled delivery system. Radiation dosimetry and source calibration is done before the sources are applied to the patient. The methods used for dose measurement are: TLD, diode or ion chamber. We introduced a new diode for dosimetry, micro-spherical diode. This tiny diode causes very little perturbation and provides spherically symmetrical dose measurements. Monte Carlo calculations are used to verify the measurements. Source parameters are calculated for source quality comparison.

The Use of Oral Transmucosal Fentanyl Citrate During High-Dose-Rate Gynecologic Brachytherapy

Gynecologic brachytherapy is a form of cancer treatment in which radioactive sources are placed into the pelvic organs via specialized applicators. Traditional low-dose-rate (LDR) brachytherapy has been performed over several days in a hospital setting. Since the 1990s, high-dose-rate (HDR) brachytherapy has been used increasingly because of its decreased treatment time, outpatient administration, and equal or superior efficacy compared with LDR treatment. However, the management of procedural pain in the radiation oncology setting has not been studied extensively. The purpose of this article is to discuss the use of oral transmucosal fentanyl citrate (OTFC) for the management of pain during gynecologic HDR brachytherapy. OTFC provides noninvasive, rapid analgesia with a low incidence of side effects and may be appropriate for other forms of procedure-related cancer pain.

WE‐C‐224C‐07: Cervical Cancer Treatment: 3D Dose Determination Based On Low Energy and High Energy CT Image

Purpose: To employ megavoltage CT (MVCT) to (a) generate an artifact‐free image and compared with the kilovoltage CT (kVCT) image set in presence of Fletcher‐Suit applicators, and (b) calculate precise three‐dimensional anatomical dose distribution for low dose rate (LDR) treatment which can be combined with external treatment (based on kVCT) planning. Method and Materials: Consented patients undergoing radiotherapy treatment for cervical cancer were simulated using orthogonal films and kVCT for external treatment planning and low dose rate brachytherapy. Fletcher‐Suit applicators with shielding were used for pretreatment image scans. Additionally, MVCT images were acquired using the Tomotherapy machine. These image sets (kVCT and MVCT) were fused in a Brachyvision planning system using a pixel registration method. MVCT images were then used for volumetric dose calculations using TG43 model. The MVCT image set and orthogonal film were then used to explore Monte Carlo‐based 3D dose calculations. Results: Artifact‐free images were obtained from MVCT scans using the Fletcher‐Suit applicators. kVCT images were not useful for LDR treatment planning due to the presence of substantial artifacts. The MVCT image set was used in delineating the rectal and bladder tissue margins. However, soft tissue visualization was sub‐optimal for clinical purposes. The MVCT image‐based dose calculation generated three‐dimensional dose distribution for rectum (max. dose of 56 cGy) and bladder (max. dose of 25 cGy) for single fraction prescribed dose of 600 cGy. Maximum rectum and bladder dose calculated using the MVCT image and orthogonal film based plan were very similar. Conclusions: We have showed that the artifact‐free MVCT image offers accurate three‐dimensional LDR treatment planning. In addition, the impact of dose heterogeneity will be calculated using image based Monte Carlo simulation technique. Ideally, truly individualized external beam and intracavitary radiotherapy may lead to higher cure rates and lower complication probabilities.

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%.

High-dose-rate versus low-dose-rate intracavitary therapy for carcinoma of the uterine cervix: a randomized trial

BACKGROUND This was a prospective randomized clinical trial undertaken at our institution to compare low-dose-rate (LDR) intracavitary radiation therapy versus high-dose-rate (HDR) intracavitary radiation therapy for the treatment of cervical carcinoma. METHODS From January 1984 to December 1997, a total of 132 patients with Stage II or IIIB of invasive carcinoma of the uterine cervix were entered into this randomized study. Treatment arm by HDR or LDR was allocated according to the month of each patient's birth. External irradiation consisted of whole pelvis irradiation and pelvic irradiation. Doses of external irradiation for both groups were identical. The authors used 0.588 as the conversion factor of total intracavitary dose from LDR to HDR. RESULTS The 5-year disease specific survival rates of Stage II and III patients treated with HDR were 69% and 51% whereas those with LDR were 87% and 60%, respectively. The 5-year pelvic recurrence free survival rates of Stage II and III patients treated with HDR were 89% and 73% whereas those with LDR were 100% and 70%, respectively. There was no significant difference in disease specific survival or pelvic recurrence free survival rates between HDR and LDR. The actuarial complication rate (Radiation Therapy Oncology Group Grade 3, 4, or 5) at 5 years was 10% in the HDR group and 13% in the LDR group, and the difference between the HDR and LDR groups was not statistically significant. CONCLUSIONS The pelvic control or actuarial complication rates were comparable between HDR and LDR treatment. The difference between the disease specific survival rates for HDR and LDR was not statistically significant for Stage II or III, although in Stage II, patients treated with LDR appeared to have a better survival rate than those treated with HDR. Cancer 2002;94:117–24. © 2002 American Cancer Society.

The optimal fraction size in high-dose-rate brachytherapy: dependency on tissue repair kinetics and low-dose rate

Background and Purpose : Indications of the existence of long repair half-times on the order of 2–4 h for late-responding human normal tissues have been obtained from continuous hyperfractionated accelerated radiotherapy (CHART). Recently, these data were used to explain, on the basis of the biologically effective dose (BED), the potential superiority of fractionated high-dose rate (HDR) with large fraction sizes of 5–7 Gy over continuous low-dose rate (LDR) irradiation at 0.5 Gy/h in cervical carcinoma. We investigated the optimal fraction size in HDR brachytherapy and its dependency on treatment choices (overall treatment time, number of HDR fractions, and time interval between fractions) and treatment conditions (reference low-dose rate, tissue repair characteristics). Methods and Materials : Radiobiologic model calculations were performed using the linear-quadratic model for incomplete mono-exponential repair. An irradiation dose of 20 Gy was assumed to be applied either with HDR in 2–12 fractions or continuously with LDR for a range of dose rates. HDR and LDR treatment regimens were compared on the basis of the BED and BED ratio of normal tissue and tumor, assuming repair half-times between 1 h and 4 h. Results : With the assumption that the repair half-time of normal tissue was three times longer than that of the tumor, hypofractionation in HDR relative to LDR could result in relative normal tissue sparing if the optimum fraction size is selected. By dose reduction while keeping the tumor BED constant, absolute normal tissue sparing might therefore be achieved. This optimum HDR fraction size was found to be largely dependent on the LDR dose rate. On the basis of the BED NT/TUM ratio of HDR over LDR, 3 × 6.7 Gy would be the optimal HDR fractionation scheme for replacement of an LDR scheme of 20 Gy in 10–30 h (dose rate 2–0.67 Gy/h), while at a lower dose rate of 0.5 Gy/h, four fractions of 5 Gy would be preferential, still assuming large differences between tumor and normal tissue repair half-times and equal overall treatment time. For the same fraction size, an even larger normal tissue sparing can be obtained by prolongation of the HDR overall treatment time. Conclusion : Radiobiologic model calculations presented here aim to demonstrate that hypofractionation in HDR might have its opportunities for widening the therapeutic window, but definitely has its limits. For each specific combination of the parameters, a theoretical optimal HDR fraction size with regard to relative or absolute normal tissue sparing can be estimated, but because of uncertainty in the biologic parameters, these hypofractionation schemes cannot be generalized for all HDR brachytherapy indications.

Fractionated high-dose-rate brachytherapy in the management of uterine cervical cancer.

It is well known that intracavitary radiotherapy (ICR), either alone or in combination with external-beam radiotherapy (EBRT) is an essential component of the radiation treatment of uterine cervical cancer. Although low-dose-rate (LDR) brachytherapy has been successfully applied to the management of such patients, several radiation oncologists have experience of using high-dose-rate (HDR) brachytherapy with promising clinical results over the past 4 decades. However, there has been a considerable reluctance by radiation oncologists and gynecologists in North America to employ the HDR remote afterloading technique instead of the more firmly established LDR treatment modality. In contrast, the HDR-ICR system is rapidly gaining acceptance in Korea since the introduction of the Ralstron, remotely controlled afterloading system using HDR Co-60 sources, at the Yonsei Cancer Center in 1979. According to brachytherapy statistics reported by the Korean Society of Therapeutic Radiology and Oncology, in 1997, brachytherapy was performed upon 1,758 Korean patients with uterine cervical cancer, of whom approximately 83% received HDR brachytherapy. In this review, we present our experiences of HDR-ICR for the treatment of uterine cervical cancer. In addition, we discuss the controversial points, which are raised by those considering the use of HDR-ICR for uterine cervical cancer; these issues include physical and radiobiological considerations, and the prospect of future technical improvements.

A single institutional experience with both high dose rate and low dose rate brachytherapy for cervical cancer

Purpose: Intracavitary brachytherapy was converted from a low dose rate (LDR) Fletcher system to high dose rate brachytherapy (HDRB) using the ring and tandem applicator in January, 1996. This study reviews the initial tumor control rates and complications using a standardized dose and fractionation HDRB schema compared to the LDR treatment. Materials and Methods: One hundred ten consecutive patients with cervical cancer received combined external beam irradiation (EBRT) and HDRB with a ring and tandem applicator at a single institution from January, 1996 through December, 2000. One hundred seventy-two LDR patients were treated from December, 1977 to July, 1998. The FIGO stage distribution was as follows in HDRB and LDRB pts respectively: IB = 32 (29%),45(26%); IIA = 12(11%), 25(14%); IIB = 51(46%),68 (39%); IIIA=1 LDRB pt; IIIB = 14(13%),32(19%); IVA=1pt in each cohort. The majority of tumors were squamous cell histology (97/110 HDRB, 153/172 LDRB) with a mean size of 6 cm in HDRB pts and 5 cm in LDRB pts. Mean pelvic EBRT doses were 45 Gy in both groups. Ten LDRB pts (6%) and 48 HDRB pts (44%) received concurrent chemoradiation. HDRB treatments were delivered on an outpatient basis, once or twice weekly, using oral premedication or subcutaneous morphine. The tandem was inserted into a previously placed cervical sleeve. The HDRB dose fractionation was 2500 cGy in five fractions prescribed to point A. Dosimetry was optimized to limit the dose to bladder and rectal maximum points (ICRU defined) to less than 80% of the prescribed dose. LDRB treatments were given in one to two insertions with mean point A dose of 87Gy (range 45, 100). Results: All patients were able to complete outpatient HDRB as prescribed with no procedural complications. Mean treatment duration was 59 days (range 33, 432) for HDRB patients and 67 in the LDR cohort (range 28, 248). At median followup of 21 (HDRB) and 82 months (LDRB), 3 (3%) and 18 (11%) grade 3/4 toxicities have occurred in the HDRB and LDRB pts respectively. Ten (9%) HDRB patients developed locoregional recurrence at median 13 months and 24 (22%) developed distant metastases at median 13 months. Seventy-six (69 %) remain without evidence of disease at median 21 months. The control rates in the LDRB pts are as follows: 23 (13%) locoregional recurrences at median 21 months and 42 (24%) distant recurrences at median 21 months. One hundred one (59%) remain NED at median 87 months. Conclusion: Early followup indicates that this technique and fractionation schedule of HDRB is safe and results in comparable control rates when compared to LDRB at our institution.

IUdR polymers for combined continuous low-dose rate and high-dose rate sensitization of experimental human malignant gliomas.

Local polymeric delivery enhances IUdR radiosensitization of human malignant gliomas (MG). The combined low-dose rate (LDR) (0.03 Gy/h) and fractionated high-dose rate (HDR) treatments result in cures of experimental MGs. To enhance efficacy, we combined polymeric IUdR delivery, LDR, and HDR for treatments of both subcutaneous and intracranial MGs. In vitro: Cells (U251 MG) were trypsinized and replated in triplicate 1 day prior to LDR irradiation in media either without (control) or with 10 microM IUdR. After 72 hr, LDR irradiation cells were acutely irradiated (1.1 Gy/min) with increasing (0, 1.25, 2.5, 5.0, or 10 Gy) single doses. Implantable IUdR polymers [(poly(bis(p-carboxyphenoxy)-propane) (PCPP): sebaic acid (PCPP:SA), 20:80] (50% loading; 10 mg) were synthesized. In vivo: For flank vs. intracranial tumors, mice had 6 x 10(6) subcutaneous vs. 2 x 10(5) intracranial cells. For intracranial or subcutaneous MGs, mice had intratumoral blank (empty) vs. IUdR polymer treatments. One day after implantation, mice had immediate external LDR (3 cGy/h x 3 days total body irradiation) or HDR (2 Gy BID x 4 days to tumor site) or concurrent treatments. For the in vitro IUdR treatments, LDR resulted in a striking increase in cell-killing when combined with HDR. For the in vivo LDR treatments of flank tumors, the growth delay was greater for the IUdR vs. blank polymer treatments. For the combined LDR and HDR, the IUdR treatments resulted in a dramatic decrease in tumor volumes. On day 60 the log V/V0 were -1.7 +/- 0.22 for combined LDR + HDR + IUdR polymer (P < 0.05 vs. combined LDR + HDR + blank polymer). Survival for the intracranial controls was 22.9 +/- 1.2 days. For the blank polymer + LDR vs. blank polymer + LDR + HDR treatments, survival was 25.3 +/- 1.7 (P = NS) vs. 48.1 +/- 3.5 days (P < 0.05). For IUdR polymer + LDR treatment survival was 27.3 +/- 2.3 days (P = NS). The most striking improvement in survival followed the IUdR polymer + LDR + HDR treatment: 66.0 + 6.4 days (P < 0.05 vs. blank polymer + LDR + HDR). The polymeric IUdR delivery plus combined continuous LDR and HDR treatments results in growth delay and improved survival in animals bearing the MG xenografts. This treatment may hold promise for the treatment of human MGs.