Feasibility and clinical implementation of MRI-guided surface brachytherapy.

Purpose: Best practices for high-dose-rate surface applicator brachytherapy treatment (SABT) have long relied on computed tomography (CT)-based imaging to visualize diseased sites for treatment planning. Compared with magnetic resonance (MR)-based imaging, CT provides insufficient soft tissue contrast. This work described the feasibility of clinical implementation of MR-based imaging in SABT planning to provide individualized treatment optimization. Material and methods: A 3D-printed phantom was used to fit Freiberg flap-style (Elekta, The Netherlands) applicator. Images were taken using an optimized pointwise encoding time reduction with radial acquisition (PETRA) MR sequence for catheter visualization, and a helical CT scan to generate parallel treatment plans. This clinical study included three patients undergoing SABT for Dupuytren's contracture/palmar fascial fibromatosis imaged with the same modalities.SABT planning was performed in Oncentra Brachy (Elekta Brachytherapy, The Netherlands) treatment planning software. A geometric analysis was conducted by comparing CT-based digitization with MR-based digitization. CT and MR dwell positions underwent a rigid registration, and average Euclidean distances between dwell positions were calculated. A dosimetric comparison was performed, including point-based dose difference calculations and volumetric segmentations with Dice similarity coefficient (DSC) calculations. Results: Euclidean distances between dwell positions from CT-based and MR-based plans were on average 0.68 ±0.05 mm and 1.35 ±0.17 mm for the phantom and patients, respectively. The point dose difference calculations were on average 0.92% for the phantom and 1.98% for the patients. The D95 and D90 DSC calculations were both 97.9% for the phantom, and on average 93.6% and 94.2%, respectively, for the patients. Conclusions: The sub-millimeter accuracy of dwell positions and high DSC's (> 0.95) of the phantom demonstrated that digitization was clinically acceptable, and accurate treatment plans were produced using MR-only imaging. This novel approach, MRI-guided SABT, will lead to individualized prescriptions for potentially improved patient outcomes.

Catheter reconstruction and dosimetric verification of MRI-only treatment planning (MRTP) for interstitial HDR brachytherapy using PETRA sequence.

Objective. The feasibility of MRI-only treatment planning (MRTP) for interstitial high-dose rate (HDR) brachytherapy (BT) was investigated for patients diagnosed with gynecologic cancer.Approach. A clinical MRTP workflow utilizing a 'pointwise encoding time reduction with radial acquisition (PETRA)' sequence was proposed. This is a clinically available MRI sequence optimized to improve interstitial catheter-tissue contrast. Interstitial needles outside the obturator region were reconstructed using MR images only. For catheters penetrating through the obturator, a library-based reconstruction was proposed. In this work, dwell coordinates from the clinical CT-based reconstruction were used as the surrogate for the library-based approach. For MR-only plan, dwell times were activated and assigned as in the clinical plans. The catheter reconstruction was assessed by comparing dwell position coordinates. The dosimetric comparisons between a clinical plan and MR-only plan were assessed for physical and EQD2 dose and volume parameters forD90,D50andD98for clinical target volume (CTV) andD2cc,D0.1ccandD5ccfor OARs.Main results. Catheter reconstruction was possible using the optimized PETRA sequence on MR images. An overall reconstruction difference of 1.7 ± 0.5 mm, attributed to registration-based errors, was found compared to the CT-based reconstruction. The MRTP workflow has the potential to generate a treatment plan with an equivalent dosimetric quality compared to the conventional CT/MRI-based approach. For CTVD90, physical and EQD2 dose and volume parameter differences were 1.5 ± 1.9% and 0.7 ± 1.0 Gy, respectively. ForD2ccOARs, DVH (EQD2) differences were -0.4 ± 1.1% (-0.2 ± 0.5 Gy), 0.5 ± 2.8% (0.2 ± 1.3 Gy) and -0.5 ± 1.4% (-0.2 ± 0.5 Gy) for rectum, bladder, and sigmoid, respectively.Significance. With the proposed MRTP approach, CT imaging may no longer be needed in HDR BT for interstitial gynecologic treatment. A proof-of-concept study was conducted to demonstrated that MRTP using PETRA is feasible, with comparable dosimetric results to the conventional CT/MRI-based approach.

Interfraction dose deviation and catheter position in cervical interstitial and intracavitary image guided HDR brachytherapy.

Interstitial and intracavitary gynecological HDR brachytherapy involve precise, localized delivery to targets with high dose gradients, sparing adjacent organs at risk (OAR). Due to the proximity of the rectum, bowel and bladder to the target, deviations in the applicator or catheter with respect to patient anatomy can significantly increase dose to OAR. The magnitude and direction of applicator and catheter migration at each fraction was assessed for template interstitial and tandem and ring (T&R) cohorts. The cohort included twelve gynecological patients with intact cervical lesions treated with external beam and brachytherapy. Pre-treatment CT images were registered to the simulation CT with respect to the target. Treatment catheter positions transformed into the planning CT coordinate system to evaluate localized catheter displacement and dose distributions calculated at each fraction. Dose was evaluated on the planning CT with planning contours and dwell locations at treatment position. Absolute deviation, depth and deflection angle for all patients were 4.6 ± 4.2 mm, -1.4 ± 4.0 mm, and 3.1 ± 2.3° respectively (n = 516 catheter positions for all treatment fractions and patients, mean ± SD). Absolute catheter deviation and deflection magnitude for interstitial treatments increased overall with each subsequent fraction with an overall increase of catheter retraction at each fraction (p < 0.005, n = 492 catheters, Kruskal-Wallis). A target EQD2 D90 reduction of 10 ± 10% and 7.7 ± 8.7% of the planned dose for interstitial and T&R cohorts respectively. There was an overall increase in bladder and rectal doses at each fraction. Catheter tracking in interstitial and intracavitary gynecological treatments with CT imaging revealed significant changes in catheter positioning with respect to the target volume. Overall deviations increased in magnitude with each subsequent fraction in the interstitial treatments. This caused patient dosimetry deviations, including target dose reduction and adjacent OAR doses changes.

Selection criteria for high-dose-rate surface brachytherapy and electron beam therapy in cutaneous oncology.

PURPOSE: High-dose-rate (HDR) brachytherapy is an alternative treatment to electron external beam radiation therapy (EBRT) of superficial skin lesions. The purpose of this study was to establish the selection criteria for HDR brachytherapy technique (HDR-BT) and EBRT in cutaneous oncology for various clinical scenarios. MATERIAL AND METHODS: The study consists of two parts: a) EBRT and HDR-BT treatment plans comparison analyzing clinical target volumes (CTVs) with different geometries, field sizes, and topologies, and b) development of a prediction model capable of characterization of dose distributions in HDR surface brachytherapy for various geometries of treatment sites. RESULTS: A loss of CTV coverage for the electron plans (D90, D95) was recorded up to 45%, when curvature of the applicator increased over 30°. Values for D2 cm3 for both plans were comparable, and they were in range of ±8% of prescription dose. An increase in higher doses (D0.5 cm3 and D0.1 cm3) was observed in HDR-BT plans, and it was greater for larger lesions. The average increase was 3.8% for D0.5 cm3 and 12.3% for D0.1 cm3. When CTV was approximately flat, electron plans were comparable with HDR-BT plans, having lower average D2 cm3, D0.5 cm3, and D0.1 cm3 of 7.7%. Degradation of quality of electron plans was found to be more dependent on target curvature than on CTV size. CONCLUSIONS: Both EBRT and HDR-BT could be used in treatments of superficial lesions. HDR-BT revealed superior CTV coverage when the surface was very large, complex, curvy, or rounded, and when the topology was complicated. The prediction model can be used for an approximate calculation and quick assessment of radiation dose to organs-at-risk (OARs), at a depth or at a lateral distance from CTV.

Combined interstitial and surface high-dose-rate brachytherapy treatment of squamous cell carcinoma of the hand.

PURPOSE: We present a case report of treatment using interstitial and surface high-dose-rate (HDR) brachytherapy for cutaneous squamous cell carcinoma (SCC) involving the interspace of the third and fourth digits. The patient refused two-ray amputation and the lesion was not amenable for external beam radiation therapy (EBRT). This is the first report detailing combined interstitial and surface HDR brachytherapy for a hand SCC. MATERIAL AND METHODS: The patient received 4050 cGy in 9 fractions, twice daily using 6 interstitial catheters and 8 Freiburg flap catheters. The clinical target was defined by MRI and ultrasound as a dorsal mass to the interspace between the heads of the third and fourth metacarpals measuring approximately 7 mm transverse × 5 mm volar-dorsal × 16 mm proximal-distal. RESULTS: The treatment resulted in radiographic and clinical tumor control. The patient retained functional use of her hand. However, there were both acute and late treatment-related side effects. Acutely, inpatient admission for pain control with a nerve block was needed. Long-term toxicity was notable for grade 2 skin necrosis treated with hyperbaric oxygen. CONCLUSIONS: The first interstitial and surface HDR brachytherapy for cutaneous squamous cell carcinoma of a finger interspace for hand function preservation is presented. The initial experience revealed that brachytherapy was tolerated but with notable acute and late side effects. Treatment did result in tumor shrinkage with organ preservation and function of two rays. A larger cohort of patients will be required for additional conclusions related to long-term clinical benefits in patients who refuse ray amputation.

Development and clinical implementation of semi-automated treatment planning including 3D printable applicator holders in complex skin brachytherapy.

PURPOSE: High-dose-rate brachytherapy (HDR-BT) is a treatment option for malignant skin diseases compared to external beam radiation therapy, HDR-BT provides improved target coverage, better organ sparing, and has comparable treatment times. This is especially true for large clinical targets with complex topologies. To standardize and improve the quality and efficacy of the treatments, a novel streamlined treatment approach in complex skin HDR-BT was developed and implemented. This approach consists of auto generated treatment plans and a 3D printable applicator holder (3D-AH). MATERIALS AND METHODS: The in-house developed planning system automatically segments computed tomography simulation images (a), optimizes a treatment plan (b), and generates a model of the 3D-AH (c). The 3D-AH is used as an immobilization device for the flexible Freiburg flap applicator used to deliver treatment. The developed, automated planning is compared against the standard clinical plan generation process for a flat 10 × 10 cm2 field, curved fields with radii of 4, 6, and 8 cm, and a representative clinical case. The quality of the 3D print is verified via an additional CT of the flap applicator latched into the holder, followed by an automated rigid registration with the original planning CT. Finally, the methodology is implemented and tested clinically under an IRB approval. RESULTS: All automatically generated plans were reviewed and accepted for clinical use. For the clinical workflow, the coverage achieved at a prescription depth for the flat 4, 6, and 8 cm applicator was (100.0 ± 4.9)%, (100.0 ± 4.9)%, (96.0 ± 0.3)%, and (98.4 ± 0.3)%, respectively. For auto planning, the coverage was (99.9 ± 0.3)%, (100.0 ± 0.2)%, (100.0 ± 0.3)%, and (100.1 ± 0.2)%. For the clinical test case, the D90 for the clinical workflow and auto planning was found to be 93.5% and 100.29% of the prescribed dose, respectively. Processing of the patient's CT to generate trajectories and positions as well as the 3D model of the applicator took <5 min. CONCLUSION: This workflow automates time intensive catheter digitizing and treatment planning. Compared to printing full applicators, the use of 3D-AH reduces the complexity of the 3D prints, the amount of the material to be used, the time of 3D printing, and amount of quality assurance required. The proposed methodology improves the overall treatment plan quality in complex HDR-BT and impact patient treatment outcomes potentially.

Custom-made micro applicators for high-dose-rate brachytherapy treatment of chronic psoriasis.

PURPOSE: In this study, we present the treatment of the psoriatic nail beds of patients refractory to standard therapies using high-dose-rate (HDR) brachytherapy. The custom-made micro applicators (CMMA) were designed and constructed for radiation dose delivery to small curvy targets with complicated topology. The role of the HDR brachytherapy treatment was to stimulate the T cells for an increased immune response. MATERIAL AND METHODS: The patient diagnosed with psoriatic nail beds refractory to standard therapies received monthly subunguinal injections that caused significant pain and discomfort in both hands. The clinical target was defined as the length from the fingertip to the distal interphalangeal joint. For the accurate and reproducible setup in the multi-fractional treatment delivery, the CMMAs were designed. Five needles were embedded into the dense plastic mesh and covered with 5 mm bolus material for each micro applicator. Five CMMAs were designed, resulting in the usage of 25 catheters in total. RESULTS: The prescription dose was planned to the depth of the anterior surface of the distal phalanx, allowing for the sparing of the surrounding tissue. The total number of the active dwell positions was 145 with step size of 5 mm. The total treatment time was 115 seconds with a 7.36 Ci activity of the 192Ir source. The treatment resulted in good pain control. The patient did not require further injections to the nail bed. After this initial treatment, additional two patients with similar symptoms received HDR brachytherapy. The treatment outcome was favorable in all cases. CONCLUSIONS: The first HDR brachytherapy treatment of psoriasis of the nail bed is presented. The initial experience revealed that brachytherapy treatment was well-tolerated and resulted in adequate control of the disease. A larger cohort of patients will be required for additional conclusions related to the long-term clinical benefits.

The value of systematic contouring of the bowel for treatment plan optimization in image-guided cervical cancer high-dose-rate brachytherapy.

PURPOSE: To investigate the dose-volume histogram metrics and optimization results of the contoured bowel in cervical cancer brachytherapy. METHODS AND MATERIALS: Treatment plans of cervical cancer patients treated with image-guided high dose rate were retrospectively analyzed with institutional review board approval. In addition to the clinical target volume, rectum, bladder, and sigmoid, the bowel was contoured at the time of planning (Group 1) or at the time of this analysis (Group 2). RESULTS: Thirty-two patients treated with 145 insertions were included. Before optimization, mean ± 1 standard deviation overall bowel minimum dose to the most irradiated 2 cm3 volume of an organ (D2cc) was 67.8 Gyα/ß3 ± 13.7 Gyα/ß3 (Group 1: 72.6 ± 13.2 Gyα/ß3; Group 2: 57.3 ± 8.0 Gyα/ß3). Before optimization, one patient in Group 1 presented a bowel D2cc metric exceeding 100 Gyα/ß3. After optimization, bowel D2cc mean ± 1 standard deviation was 59.4 ± 6.7 Gyα/ß3 (Group 1: 61.4 ± 6.0 Gyα/ß3, p < 0.001; Group 2: 55.2 ± 6.5 Gyα/ß3, p = 0.026). CONCLUSIONS: Given the potentially high doses and the benefit of optimization in reducing dose to the organs at risk, we recommend consideration of systematic contouring of the bowel when bowel is present in the pelvis.

Outcomes with volume-based dose specification in CT-planned high-dose-rate brachytherapy for stage I-II cervical carcinoma: A 10-year institutional experience.

OBJECTIVE: To determine prognostic factors for progression-free survival (PFS) and overall survival (OS) for stage I-II cervical-cancer patients treated using computed-tomography (CT)-planned high-dose-rate (HDR) intracavitary brachytherapy (BT). METHODS: A total of 150 patients were treated for Stage I-II cervical cancer using CT-planned BT between 4/2004 and 10/2014. Of these, 128 were eligible for inclusion. Kaplan-Meier local control (LC), pelvic control (PC), overall survival (OS), and PFS estimates were calculated. RESULTS: After a median follow-up of 30months, the 2-year LC rate was 96%, PFS was 88%, and OS was 88%. Overall, 18 patients (14%) experienced any recurrence (AR), 8 had distant recurrence only and 10 had a combination of local, pelvic, regional, and distant recurrence. No patients had LR only. A prognostic factor for AR was tumor size >4cm (p=0.01). Patients with tumors >4cm were 3.3 times more likely to have AR than those with tumors ≤4cm (hazard ratio [HR]=3.3; 95% confidence interval [CI] 1.28-9.47). Point A was 85% of prescription for tumors < 4 cm and decreased approximately 3% over 5 fractions compared to 90% of prescription for tumors > 4 cm that decreased approximately 4% over 5 fractions. Two patients (2%) experienced grade≥2 late toxicity. There were no acute or late grade≥3 toxicities. CONCLUSION: CT-planned BT resulted in excellent local control and survival. Large tumor size was associated with an increased risk of recurrence outside the radiation field and worse PFS and OS. A volume-optimized plan treated a smaller area than a point A standard plan for patients with Stage I-II cervical cancer that have received chemoradiation. Given the outstanding LC achieved with modern therapy including chemoradiation, HDR, and image-based BT, further efforts to combat spread outside the radiation field with novel therapies are warranted.

Clinical implementation of a novel applicator in high-dose-rate brachytherapy treatment of esophageal cancer.

PURPOSE: In this study, we present the clinical implementation of a novel transoral balloon centering esophageal applicator (BCEA) and the initial clinical experience in high-dose-rate (HDR) brachytherapy treatment of esophageal cancer, using this applicator. MATERIAL AND METHODS: Acceptance testing and commissioning of the BCEA were performed prior to clinical use. Full performance testing was conducted including measurements of the dimensions and the catheter diameter, evaluation of the inflatable balloon consistency, visibility of the radio-opaque markers, congruence of the markers, absolute and relative accuracy of the HDR source in the applicator using the radiochromic film and source position simulator, visibility and digitization of the applicator on the computed tomography (CT) images under the clinical conditions, and reproducibility of the offset. Clinical placement of the applicator, treatment planning, treatment delivery, and patient's response to the treatment were elaborated as well. RESULTS: The experiments showed sub-millimeter accuracy in the source positioning with distal position at 1270 mm. The digitization (catheter reconstruction) was uncomplicated due to the good visibility of markers. The treatment planning resulted in a favorable dose distribution. This finding was pronounced for the treatment of the curvy anatomy of the lesion due to the improved repeatability and consistency of the delivered fractional dose to the patient, since the radioactive source was placed centrally within the lumen with respect to the clinical target due to the five inflatable balloons. CONCLUSIONS: The consistency of the BCEA positioning resulted in the possibility to deliver optimized non-uniform dose along the catheter, which resulted in an increase of the dose to the cancerous tissue and lower doses to healthy tissue. A larger number of patients and long-term follow-up will be required to investigate if the delivered optimized treatment can lead to improved clinical outcomes.

Palliative Therapy for Recalcitrant Cutaneous T-Cell Lymphoma of the Hands and Feet With Low-Dose, High Dose-Rate Brachytherapy.

IMPORTANCE: Cutaneous T-cell lymphoma (CTCL) of the hands and feet can be challenging to treat and cause significant disability for patients. Although CTCL is a highly radiosensitive tumor, the complex topography of acral surfaces presents challenges to achieving homogeneous superficial dosing of traditional electron beam therapy. In addition, traditional dosing may result in substantial acute cutaneous toxic effects. Recent reports demonstrate that low-dose palliative radiotherapy may be as effective as traditional regimens in CTCL. High dose-rate (HDR) brachytherapy allows for control of the depth of radiation penetration over complex curved surfaces. This study investigated the role of low-dose HDR brachytherapy for acral CTCL lesions. OBSERVATIONS: Six patients with a total of 8 acral CTCL lesions received low-dose HDR brachytherapy during a 3-year period. Rapid improvement and clinical clearance were observed in all treated lesions with minimal to no acute cutaneous toxic effects. During a mean follow-up period of 15.8 months, 1 lesion recurred locally; the remaining 7 lesions had sustained clinical remission. No long-term sequelae were observed. CONCLUSIONS AND RELEVANCE: This case series demonstrates that low-dose HDR brachytherapy provides excellent palliation for local control of acral CTCL lesions, offering homogeneous, controlled dosing for complex topographic sites with minimal to no cutaneous toxic effects.

Redesign of process map to increase efficiency: Reducing procedure time in cervical cancer brachytherapy.

PURPOSE: To increase intraprocedural efficiency in the use of clinical resources and to decrease planning time for cervical cancer brachytherapy treatments through redesign of the procedure's process map. METHODS AND MATERIALS: A multidisciplinary team identified all tasks and associated resources involved in cervical cancer brachytherapy in our institution and arranged them in a process map. A redesign of the treatment planning component of the process map was conducted with the goal of minimizing planning time. Planning time was measured on 20 consecutive insertions, of which 10 were performed with standard procedures and 10 with the redesigned process map, and results were compared. Statistical significance (p < 0.05) was measured with a two-tailed t test. RESULTS: Twelve tasks involved in cervical cancer brachytherapy treatments were identified. The process map showed that in standard procedures, the treatment planning tasks were performed sequentially. The process map was redesigned to specify that contouring and some planning tasks are performed concomitantly. Some quality assurance tasks were reorganized to minimize adverse effects of a possible error on procedure time. Test dry runs followed by live implementation confirmed the applicability of the new process map to clinical conditions. A 29% reduction in planning time (p < 0.01) was observed with the introduction of the redesigned process map. CONCLUSIONS: A process map for cervical cancer brachytherapy was generated. The treatment planning component of the process map was redesigned, resulting in a 29% decrease in planning time and a streamlining of the quality assurance process.

Independent brachytherapy plan verification software: improving efficacy and efficiency.

BACKGROUND AND PURPOSE: To compare the pre-treatment brachytherapy plan verification by a physicist assisted by custom plan verification software (SAV) with those performed manually (MV). MATERIALS AND METHODS: All HDR brachytherapy plans used for treatment in 2013, verified using either SAV or MV, were retrospectively reviewed. Error rate (number of errors/number of plans) was measured and verification time calculated. All HDR brachytherapy safety events recorded between 2010 and 2013 were identified. The rate of patient-related safety events (number of events/number of fractions treated) and the impact of SAV on the underlying errors were assessed. RESULTS: Three/106 errors (2.8%) were found in the SAV group and 24/273 (8.8%) in the MV group (p=0.046). The mean ±1 standard deviation plan verification time was 8.4±4.0min for SAV and 11.6±5.3 for MV (p=0.006). Seven safety events out of 4729 fractions delivered (0.15%) were identified. Four events (57%) were associated with plan verification and could have been detected by SAV. CONCLUSIONS: We found a safety event rate in HDR brachytherapy of 0.15%. SAV significantly reduced the number of undetected errors in HDR treatment plans compared to MV, and reduced the time required for plan verification.

Variability in MRI vs. ultrasound measures of prostate volume and its impact on treatment recommendations for favorable-risk prostate cancer patients: a case series.

BACKGROUND: Prostate volume can affect whether patients qualify for brachytherapy (desired size ≥20 mL and ≤60 mL) and/or active surveillance (desired PSA density ≤0.15 for very low risk disease). This study examines variability in prostate volume measurements depending on imaging modality used (ultrasound versus MRI) and volume calculation technique (contouring versus ellipsoid) and quantifies the impact of this variability on treatment recommendations for men with favorable-risk prostate cancer. METHODS: We examined 70 patients who presented consecutively for consideration of brachytherapy for favorable-risk prostate cancer who had volume estimates by three methods: contoured axial ultrasound slices, ultrasound ellipsoid (height × width × length × 0.523) calculation, and endorectal coil MRI (erMRI) ellipsoid calculation. RESULTS: Average gland size by the contoured ultrasound, ellipsoid ultrasound, and erMRI methods were 33.99, 37.16, and 39.62 mLs, respectively. All pairwise comparisons between methods were statistically significant (all p < 0.015). Of the 66 patients who volumetrically qualified for brachytherapy on ellipsoid ultrasound measures, 22 (33.33%) did not qualify on ellipsoid erMRI or contoured ultrasound measures. 38 patients (54.28%) had PSA density ≤0.15 ng/dl as calculated using ellipsoid ultrasound volumes, compared to 34 (48.57%) and 38 patients (54.28%) using contoured ultrasound and ellipsoid erMRI volumes, respectively. CONCLUSIONS: The ultrasound ellipsoid and erMRI ellipsoid methods appeared to overestimate ultrasound contoured volume by an average of 9.34% and 16.57% respectively. 33.33% of those who qualified for brachytherapy based on ellipsoid ultrasound volume would be disqualified based on ultrasound contoured and/or erMRI ellipsoid volume. As treatment recommendations increasingly rely on estimates of prostate size, clinicians must consider method of volume estimation.

Use of a rectal spacer with low-dose-rate brachytherapy for treatment of prostate cancer in previously irradiated patients: Initial experience and short-term results.

BACKGROUND: Salvage brachytherapy in patients with prior pelvic radiation carries a risk of rectal injury. Herein, we report our initial experience using a hydrogel spacer between the prostate and the rectum during salvage brachytherapy. METHODS AND MATERIALS: A total of 11 patients with prostate cancer and prior radiotherapy (5 prostate brachytherapy, 2 prostate external beam radiation therapy [EBRT], and 4 rectal cancer EBRT) received (125)I brachytherapy after attempted placement of 10cc of a diluted hydrogel spacer between the prostate and rectum. RESULTS: Spacing was achieved in 8 of the 11 (73%) patients but was not possible in 3 (1 prior brachytherapy and 2 prior EBRT) owing to fibrosis and adhesions. For the 8 patients in whom spacing was accomplished, the median space between the prostate and rectum was 10.9mm (prior EBRT) vs. 7.7mm (prior brachytherapy), p=0.048. Median followup was 15.7 months. One patient developed a prostato-rectal fistula requiring a diverting colostomy. The 16-month estimate of late Grade 3 or 4 gastrointestinal or genitourinary toxicity was 26%. One patient developed lymph node-positive recurrence. The 16-month prostate-specific antigen failure-free survival rate was 89%. Compared with baseline, Expanded Prostate Cancer Index Composite for Clinical Practice urinary quality of life (QoL) was significantly worse at 3 and 6 months but not significantly worse by 1 year. There were no significant changes throughout the study period in bowel or sexual QoL. CONCLUSION: Hydrogel spacer placements may be feasible in most patients with prior pelvic radiation. Further followup is needed to determine whether spacer placement will produce long-term improvements in toxicity or QoL.

Placement of empty catheters for an HDR-emulating LDR prostate brachytherapy technique: comparison to standard intraoperative planning.

PURPOSE: We sought to determine whether placing empty catheters within the prostate and then inverse planning iodine-125 seed locations within those catheters (High Dose Rate-Emulating Low Dose Rate Prostate Brachytherapy [HELP] technique) would improve concordance between planned and achieved dosimetry compared with a standard intraoperative technique. METHODS AND MATERIALS: We examined 30 consecutive low dose rate prostate cases performed by standard intraoperative technique of planning followed by needle placement/seed deposition and compared them to 30 consecutive low dose rate prostate cases performed by the HELP technique. The primary endpoint was concordance between planned percentage of the clinical target volume that receives at least 100% of the prescribed dose/dose that covers 90% of the volume of the clinical target volume (V100/D90) and the actual V100/D90 achieved at Postoperative Day 1. RESULTS: The HELP technique had superior concordance between the planned target dosimetry and what was actually achieved at Day 1 and Day 30. Specifically, target D90 at Day 1 was on average 33.7 Gy less than planned for the standard intraoperative technique but was only 10.5 Gy less than planned for the HELP technique (p < 0.001). Day 30 values were 16.6 Gy less vs. 2.2 Gy more than planned, respectively (p = 0.028). Day 1 target V100 was 6.3% less than planned with standard vs. 2.8% less for HELP (p < 0.001). There was no significant difference between the urethral and rectal concordance (all p > 0.05). CONCLUSIONS: Placing empty needles first and optimizing the plan to the known positions of the needles resulted in improved concordance between the planned and the achieved dosimetry to the target, possibly because of elimination of errors in needle placement.

Equivalent uniform dose for accelerated partial breast irradiation using the MammoSite applicator.

INTRODUCTION: This study aims to quantify the radiobiology of the MammoSite applicator and examine whether there is a relationship between equivalent uniform dose (EUD) and radiotherapy-associated toxicity. METHODS AND MATERIALS: A previously-published version of the linear quadratic (LQ) model, designed to address the impact of dose-gradients in brachytherapy applications, was used to determine the biological effective dose (BED), equivalent dose in 2 Gray per fraction (EQD2) and EUD for the most common fractionation scheme for the MammoSite catheter (34 Gy in 10 fractions prescribed to 1cm from the balloon surface), using a range of balloon sizes in a series of patients treated with single or multiple dwell positions. Toxicity from the MammoSite catheter was assessed and statistical associations with the calculated EUDs were investigated. RESULTS: The acute- and late-toxicity EUDs respectively range from 34.8-39.4 Gy and 33.4-37.6 Gy, with EUD decreasing as balloon diameter increases and/or the number of dwell positions increases. There was a positive association between EUD and hyperpigmentation and telangiectasia. CONCLUSIONS: For APBI using the Mammosite applicator, EUD is higher than the marginal prescription dose and, for the dose-fractionation patterns considered here, was associated with acute and late skin toxicity. EUD is a potentially useful parameter to characterize non-uniform dose distributions related to brachytherapy treatments. Further evaluation in future studies is warranted.

Palliative treatment for in-transit cutaneous metastases of Merkel cell carcinoma using surface-mold computer-optimized high-dose-rate brachytherapy.

PURPOSE: The objective of this study was to evaluate the palliative treatment benefit of surface-mold computer-optimized high-dose-rate brachytherapy (SMBT) for in-transit cutaneous metastases of Merkel cell carcinoma (MCC). METHODS: Ten patients with in-transit cutaneous MCC metastases were treated with SMBT at the Dana-Farber/Brigham & Women's Cancer Center between 2006 and 2012. RESULTS: The median age at diagnosis was 76 years (range, 63-87 years). Seven patients had in-transit metastases on the lower extremities (70%), 2 patients on the head and neck (20%), and 1 patient on an upper extremity (10%). A total of 152 metastatic MCC lesions were treated with SMBT. All SMBT-treated lesions resolved clinically within a few weeks of therapy. The median follow-up was 34 months (range, 22-85 months). Two of 152 treated lesions recurred during the study period for a local control rate of 99%. Eight patients (80%) developed additional in-transit metastases outside the original SMBT fields. Five of these 8 patients underwent additional SMBT. At study conclusion, 3 patients (30%) are alive without disease, 3 patients (30%) are alive with disease, and 4 patients (40%) died of MCC. DISCUSSION: Surface-mold computer-optimized high-dose-rate brachytherapy offers effective and durable palliation for cutaneous metastases of MCC, although it does not appear to alter disease course.

A prospective trial of real-time magnetic resonance-guided catheter placement in interstitial gynecologic brachytherapy.

PURPOSE: To present outcome and toxicity results of the first real-time intraoperative MRI-guided interstitial approach to gynecologic cancer. METHODS AND MATERIALS: From February 2004 to December 2006, 25 patients with gynecologic malignancies were enrolled and treated in a prospective clinical trial of real-time MRI-guided interstitial brachytherapy. This was followed by a confirmatory CT imaging scan. Statistical analyses included Kaplan-Meier estimates for overall and relapse-free survival. RESULTS: MRI visualization of needles during placement permitted accurate placement with no inadvertent insertions. This prevented unnecessary normal-tissue perforation as confirmed by CT simulation. With a mean followup of 3.8 years (range, 2-6.8), 1-, 2-, and 3-year overall survival rates were 80%, 60% and 43%, respectively; corresponding relapse-free survival rates were 79%, 65%, and 59%, respectively. Actuarial acute toxicity rates for any grade were 0% at 0-14 days and 80% (all grade 1) at 14-90 days. Long-term (>180 days) actuarial toxicity rates were 8% gastrointestinal, 4% bladder and 4% vaginal. CONCLUSIONS: Real-time MRI guidance during insertion of interstitial needles followed by 3D-planning maximized opportunities for tumor targeting and sparing of normal tissues. Although image guidance requires additional anesthesia time, clinical outcomes indicate potential for a successful reduction in toxicity using 3D image-guided in addition to 3D image-planned brachytherapy.