Resection and brain brachytherapy with permanent iodine-125 sources for brain metastasis.

OBJECTIVE Stereotactic radiosurgery (SRS) with or without whole-brain radiotherapy can be used to achieve local control (> 90%) for small brain metastases after resection. However, many brain metastases are unsuitable for SRS because of their size or previous treatment, and whole-brain radiotherapy is associated with significant neurocognitive morbidity. The purpose of this study was to investigate the efficacy and toxicity of surgery and iodine-125 (125I) brachytherapy for brain metastases. METHODS A total of 95 consecutive patients treated for 105 brain metastases at a single institution between September 1997 and July 2013 were identified for this analysis retrospectively. Each patient underwent MRI followed by craniotomy with resection of metastasis and placement of 125I sources as permanent implants. The patients were followed with serial surveillance MRIs. The relationships among local control, overall survival, and necrosis were estimated by using the Kaplan-Meier method and compared with results of log-rank tests and multivariate regression models. RESULTS The median age at surgery was 59 years (range 29.9-81.6 years), 53% of the lesions had been treated previously, and the median preoperative metastasis volume was 13.5 cm3 (range 0.21-76.2 cm3). Gross-total resection was achieved in 81% of the cases. The median number of 125I sources implanted per cavity was 28 (range 4-93), and the median activity was 0.73 mCi (range 0.34-1.3 mCi) per source. A total of 476 brain MRIs were analyzed (median MRIs per patient 3; range 0-22). Metastasis size was the strongest predictor of cavity volume and shrinkage (p < 0.0001). Multivariable regression modeling failed to predict the likelihood of local progression or necrosis according to metastasis volume, cavity volume, or the rate of cavity remodeling regardless of source activity or previous SRS. The median clinical follow-up time in living patients was 14.4 months (range 0.02-13.6 years), and crude local control was 90%. Median overall survival extended from 2.1 months in the shortest quartile to 62.3 months in the longest quartile (p < 0.0001). The overall risk of necrosis was 15% and increased significantly for lesions with a history of previous SRS (p < 0.05). CONCLUSIONS Therapeutic options for patients with large or recurrent brain metastases are limited. Data from this study suggest that resection with permanent 125I brachytherapy is an effective strategy for achieving local control of brain metastasis. Although metastasis volume significantly influences resection cavity size and remodeling, volumetric parameters do not seem to influence local control or necrosis. With careful patient selection, this treatment regimen is associated with minimal toxicity and can result in long-term survival for some patients. ▪ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: retrospective case series; evidence: Class IV.

Dosimetric analysis of radiation therapy oncology group 0321: the importance of urethral dose.

PURPOSE: Radiation Therapy Oncology Group 0321 is the first multi-institutional cooperative group high-dose-rate (HDR) prostate brachytherapy trial with complete digital brachytherapy dosimetry data. This is a descriptive report of the data and an analysis of toxicity. METHODS AND MATERIALS: Patients are treated with external beam radiation therapy at 45 Gy and 1 HDR implant with 19 Gy in 2 fractions. Implants are done with transrectal ultrasound guidance, and computed tomography (CT)-compatible nonmetallic catheters. HDR planning is done on ≤3-mm-thick CT slices. The "mean DVH" (dose-volume histogram) of the planning target volume (PTV), implanted volume (IP), and organs at risk are calculated. This includes the mean and standard deviation (SD) of the volume at 10-percentage-point intervals from 10% to 200% of the prescribed dose. The conformal index (COIN), homogeneity index (HI), catheters per implant, and patients per institution are calculated. Multivariate analysis and hazard ratios calculation of all the variables against reported grade ≥2 (G2+) genitourinary (GU) adverse events (Common Terminology Criteria for Adverse Events, version 3) are performed. RESULTS: Dosimetry data are based on 122 eligible patients from 14 institutions. The mean of PTV, IP, catheters per implant, and patients per institution are 54 cc, 63 cc, 19 and 9, respectively. The mean of %V100PTV, V80Bladder, V80Rectum, and V120Urethra were 94%, 0.40 cc, 0.15 cc, and 0.25 cc, respectively. There are too few G2+ gastrointestinal adverse event (GI AE) for correlative analysis; thus, the analysis has been performed on the more common G2+ GU AE. There are positive correlations noted between both acute and late G2+ GU AE and urethral dose at multiple levels. Positive correlations with late AE are seen with PTV and IP at high-dose levels. A negative correlation is seen between HI and acute AE. A higher patient accrual rate is associated with a lower rate of G2+ acute and late AE. CONCLUSIONS: Higher urethral dose, larger high-dose volumes, and lower dose homogeneity are associated with greater toxicities. A mean dose-volume histogram comparison at all dose levels should be used for quality control and future research comparison.

Cold spot mapping inferred from MRI at time of failure predicts biopsy-proven local failure after permanent seed brachytherapy in prostate cancer patients: implications for focal salvage brachytherapy.

BACKGROUND AND PURPOSE: (1) To establish a method to evaluate dosimetry at the time of primary prostate permanent implant (pPPI) using MRI of the shrunken prostate at the time of failure (tf). (2) To compare cold spot mapping with sextant-biopsy mapping at tf. MATERIAL AND METHODS: Twenty-four patients were referred for biopsy-proven local failure (LF) after pPPI. Multiparametric MRI and combined-sextant biopsy with a central review of the pathology at tf were systematically performed. A model of the shrinking pattern was defined as a Volumetric Change Factor (VCF) as a function of time from time of pPPI (t0). An isotropic expansion to both prostate volume (PV) and seed position (SP) coordinates determined at tf was performed using a validated algorithm using the VCF. RESULTS: pPPI CT-based evaluation (at 4weeks) vs. MR-based evaluation: Mean D90% was 145.23±19.16Gy [100.0-167.5] vs. 85.28±27.36Gy [39-139] (p=0.001), respectively. Mean V100% was 91.6±7.9% [70-100%] vs. 73.1±13.8% [55-98%] (p=0.0006), respectively. Seventy-seven per cent of the pathologically positive sextants were classified as cold. CONCLUSIONS: Patients with biopsy-proven LF had poorer implantation quality when evaluated by MRI several years after implantation. There is a strong relationship between microscopic involvement at tf and cold spots.

A dosimetric evaluation of using a single treatment plan for multiple treatment fractions within a given applicator insertion in gynecologic brachytherapy.

PURPOSE: To evaluate the dosimetric impact of using one treatment plan for multiple fractions from a single tandem and ring applicator insertion of high-dose-rate brachytherapy for cervical cancer. METHODS AND MATERIALS: Thirteen cervical cancer patients undergoing high-dose-rate brachytherapy were followed. Patients received the total dose from a single applicator insertion in two fractions, given with at least 6 hours apart within 24 hours. The treatment plan was based on a CT scan taken before the first treatment fraction. A second CT was obtained before the second treatment fraction. The co-registered image series were used to evaluate the dosimetric impact of using a single treatment plan for both fractions. Applicator and catheters were measured to quantify interfraction displacement. RESULTS: When the Day 1 plan was applied to the Day 2 images, high-risk clinical target volume (HR-CTV) coverage was reduced by as much as 17.4 percentage points. The mean decrease was 9.4 ± 5.0 percentage points (p < 0.0001). The rectum V75 increase was significant (p = 0.03), whereas the bladder V75 increase was not significant (p = 0.28). Volume changes in the HR-CTV contour from Day 1 to Day 2 were also observed (p = 0.29). Maximum applicator and catheter displacements of 10-30mm were seen, from Day 1 to Day 2. CONCLUSIONS: When the Day 1 plan was used on the Day 2, the HR-CTV coverage decreased significantly (p < 0.0001). Our study establishes the need for institutions to evaluate the necessity for replanning based on imaging obtained before each treatment fraction for their gynecologic brachytherapy techniques.

Comparison of high-dose rate prostate brachytherapy dose distributions with iridium-192, ytterbium-169, and thulium-170 sources.

PURPOSE: Recent studies have identified that among different available radionuclides, the dose characteristics and shielding properties of ytterbium-169 ((169)Yb) and thulium-170 ((170)Tm) may suit high-dose rate (HDR) brachytherapy needs. The purpose of this work was to compare clinically optimized dose distributions using proposed (169)Yb and (170)Tm HDR sources with the clinical dose distribution from a standard microSelectron V2 HDR iridium-192 ((192)Ir) brachytherapy source (Nucletron B.V., Veenendaal, The Netherlands). METHODS AND MATERIALS: CT-based treatment plans of 10 patients having prostate volumes ranging from 17 to 92cm(3) were studied retrospectively. Clinical treatment of these patients involved 16 catheters and a microSelectron V2 HDR (192)Ir source. All dose plans were generated with inverse planning simulated annealing optimization algorithm. Dose objectives used for the (192)Ir radionuclide source were used for the other two radionuclides. The dose objective parameters were adjusted to obtain the same clinical target (prostate) volume coverage as the original (192)Ir radionuclide plan. A complete set of dosimetric indices was used to compare the plans from different radionuclides. A pairwise statistical analysis was also performed. RESULTS AND CONCLUSIONS: All the dose distributions optimized with specific (192)Ir, (169)Yb, and (170)Tm sources satisfied the standard clinical criteria for HDR prostate implants, such as those for the Radiation Therapy Oncology Group clinical trial 0321, for combined HDR and external beam treatment for prostate adenocarcinoma. For equivalent clinical target volume dose coverage, the specific (169)Yb and (170)Tm sources resulted in a statistically significant dose reduction to organs at risk compared with microSelectron V2 HDR (192)Ir source. This study indicates that a (170)Tm or (169)Yb radionuclide source may be an alternative to the (192)Ir radionuclide sources in HDR brachytherapy.

Dosimetric impact of interfraction catheter movement in high-dose rate prostate brachytherapy.

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