How many brain metastases can be treated with stereotactic radiosurgery before the radiation dose delivered to normal brain tissue rivals that associated with standard whole brain radiotherapy?

INTRODUCTION: Clinical trial data comparing outcomes after administration of stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT) to patients with brain metastases (BM) suggest that SRS better preserves cognitive function and quality of life without negatively impacting overall survival. Here, we estimate the maximum number of BM that can be treated using single and multi-session SRS while limiting the dose of radiation delivered to normal brain tissue to that associated with WBRT. METHODS: Multiple-tumor SRS was simulated using a Monte Carlo - type approach and a pre-calculated dose kernel method. Tumors with diameters ≤36 mm were randomly placed throughout the contoured brain parenchyma until the brain mean dose reached 3 Gy, equivalent to the radiation dose delivered during a single fraction of a standard course of WBRT (a total dose of 30 Gy in 10 daily fractions of 3 Gy). Distribution of tumor sizes, dose coverage, selectivity, normalization, and maximum dose data used in the simulations were based on institutional clinical metastases data. RESULTS: The mean number of tumors treated, mean volume of healthy brain tissue receiving > 12 Gy (V12) per tumor, and total tumor volume treated using mixed tumor size distributions were 12.7 ± 4.2, 2.2 cc, and 12.9 cc, respectively. Thus, we estimate that treating 12-13 tumors per day over 10 days would deliver the dose of radiation to healthy brain tissue typically associated with a standard course of WBRT. CONCLUSION: Although in clinical practice, treatment with SRS is often limited to patients with ≤15 BM, our findings suggest that many more lesions could be targeted while still minimizing the negative impacts on quality of life and neurocognition often associated with WBRT. Results from this in silico analysis require clinical validation.

12-year outcomes following permanent prostate brachytherapy in patients with clinically localized prostate cancer.

PURPOSE: We reviewed the outcomes in men treated with permanent prostate brachytherapy (PPB). MATERIAL AND METHODS: A total of 1,449 consecutive patients with a mean age of 68 years treated with PPB between 1992 and 2000 and mean pretreatment prostate specific antigen (PSA) 10.1 ng/ml were included in this study. Of the patients 55% presented with Gleason 6 tumors and 28% had Gleason 7 disease. A total of 400 patients (27%) were treated with neoadjuvant hormones and 301 (20%) were treated in combination with external radiation plus PPB. Several biochemical freedom from recurrence (BFR) definitions were determined. Statistical analysis consisted of log rank testing, Kaplan-Meier estimates and Cox regression analysis. RESULTS: Median followup was 82 months with 39 patients at risk at for 144 months. Overall and disease specific survival at 12 years was 81% and 93%, respectively. The 12-year BFR was 81%, 78%, 74% and 77% according to the American Society for Therapeutic Radiology and Oncology (ASTRO), ASTRO-Kattan, ASTRO-Last Call and Houston definitions, respectively. The 12-year ASTRO-Kattan BFR using risk stratification was 89%, 78% and 63% in patients at low, intermediate and high risk, respectively (p = 0.0001). Multivariate analysis identified the dose that 90% of the target volume received (p <0.0001), pretreatment PSA (p = 0.001), Gleason score (p = 0.002), the percent positive core biopsies (p = 0.037), clinical stage (p = 0.689), the addition of hormones (p = 0.655) and the addition of external radiation (p = 0.724) for predicting BFR-ASTRO. Five-year disease specific survival was 44% in patients with a PSA doubling time of less than 12 months vs 88% in those with a PSA doubling time of 12 months or greater (p = 0.0001). CONCLUSIONS: PPB offers acceptable 12-year BFR in patients who present with clinically localized prostate cancer. Implant dosimetry continues as an important predictor for BFR, while the addition of adjuvant therapies such as hormones and external radiation are insignificant. In patients who experience biochemical failure it appears that PSA doubling time is an important predictor of survival.

Is there a role for postimplant dosimetry after real-time dynamic permanent prostate brachytherapy?

PURPOSE: To evaluate the correlation of real-time dynamic prostate brachytherapy (RTDPB) dosimetry and traditional postimplant dosimetry for permanent prostate brachytherapy. METHODS AND MATERIALS: A total of 164 patients underwent RTDPB for clinically confined prostate cancer. Of these 164 patients, 45 were implanted with 103Pd and 119 with 125I. Additionally, 44 patients underwent combined external beam radiotherapy and brachytherapy and 120 patients underwent brachytherapy alone. The postimplant dosimetry with computed tomography was performed at 4 weeks and compared with the RTDPB dose plan using the intraclass correlation coefficient. The millicurie/gram of the prostate volume and the percentage of the minimal dose to 90% of the prostate relative to the prescribed implant dose (D90%) of the RTDPB patients was compared with 400 patients treated with a free-seed technique. RESULTS: The mean D90% achieved in the operating room and on the 3-week dose plan was 109% (range, 93-139%) and 105% (range, 88-140), respectively. The mean percentage of prostate volume receiving 100% of the prescribed minimal peripheral dose (V100) achieved in the operating room and on the 3-week dose plan was 93% (range, 78-98%) and 91% (range, 64-98%), respectively. The intraclass correlation coefficient for each calculated relationship was 0.586 for D90 (p<0.001), 1.19 for V100 (p=0.135), 0.692 for the urethral D90 (p<0.001), 0.602 for the maximal rectal dose (p<0.001), 0.546 for D90 with 125I (p<0.001), and 0.565 for D90 with 103Pd (p<0.001). A 12% decrease was noted in the millicurie/gram of the isotope, with a 2.5% increase in the D90 comparing RTDPB and the free-seed technique. CONCLUSION: The results of this study demonstrated a correlation between the dose assessment obtained intraoperatively and postoperatively at 3 weeks. With reliable dose data available in the operating room, our results question the need for routine postimplant dose studies. Furthermore, patients treated with RTDPB received less radioactivity per gram of the prostate with a corresponding small increase in the D90. Future analyses will assess variations in the inverse dose planning rules and the clinical correlation of patients undergoing RTDPB vs. older techniques for toxicity and biochemical outcomes.

12-year outcomes following permanent prostate brachytherapy in patients with clinically localized prostate cancer.

PURPOSE: We reviewed the outcomes in men treated with permanent prostate brachytherapy (PPB). MATERIAL AND METHODS: A total of 1,449 consecutive patients with a mean age of 68 years treated with PPB between 1992 and 2000 and mean pretreatment prostate specific antigen (PSA) 10.1 ng/ml were included in this study. Of the patients 55% presented with Gleason 6 tumors and 28% had Gleason 7 disease. A total of 400 patients (27%) were treated with neoadjuvant hormones and 301 (20%) were treated in combination with external radiation plus PPB. Several biochemical freedom from recurrence (BFR) definitions were determined. Statistical analysis consisted of log rank testing, Kaplan-Meier estimates and Cox regression analysis. RESULTS: Median followup was 82 months with 39 patients at risk at for 144 months. Overall and disease specific survival at 12 years was 81% and 93%, respectively. The 12-year BFR was 81%, 78%, 74% and 77% according to the American Society for Therapeutic Radiology and Oncology (ASTRO), ASTRO-Kattan, ASTRO-Last Call and Houston definitions, respectively. The 12-year ASTRO-Kattan BFR using risk stratification was 89%, 78% and 63% in patients at low, intermediate and high risk, respectively (p = 0.0001). Multivariate analysis identified the dose that 90% of the target volume received (p <0.0001), pretreatment PSA (p = 0.001), Gleason score (p = 0.002), the percent positive core biopsies (p = 0.037), clinical stage (p = 0.689), the addition of hormones (p = 0.655) and the addition of external radiation (p = 0.724) for predicting BFR-ASTRO. Five-year disease specific survival was 44% in patients with a PSA doubling time of less than 12 months vs 88% in those with a PSA doubling time of 12 months or greater (p = 0.0001). CONCLUSIONS: PPB offers acceptable 12-year BFR in patients who present with clinically localized prostate cancer. Implant dosimetry continues as an important predictor for BFR, while the addition of adjuvant therapies such as hormones and external radiation are insignificant. In patients who experience biochemical failure it appears that PSA doubling time is an important predictor of survival.

HDR brachytherapy with surface applicators: technical considerations and dosimetry.

HDR surface molds offer an alternative radiotherapy modality to electrons for the treatment of skin lesions. Treatment planning and dosimetry are discussed for two types of surface molds used in our clinic. Standard rectangular applicators are used on a variety of sites where surface curvature is minimal. In these cases an idealized planar geometry is used for treatment planning dose calculations. The calculations yield treatment dose uniformity at the prescription depth in tissue as well as skin dose, as a percentage of the treatment dose, and its dose uniformity. The availability of optimization techniques results in superior dose uniformity at depth but the dose at the skin has to be carefully evaluated. We have studied the dependence of these dosimetric parameters on the size of the surface mold and the type of optimization procedure used in the dosimetry calculations. The second type of surface applicator involves the use of a customized silicone rubber mold attached to a thermoplastic mask of the patient. We have used them to treat lesions of the face where surface curvatures are appreciable and reproducibility of setup is more critical. In these cases a CT data set is used for reconstruction of the catheters, activation of relevant dwell positions and dosimetry, including optimization. Towards establishing effective methods for quality assurance of the optimized HDR surface mold planning calculations, we have compared their dosimetry to both a classical brachytherapy system and to one based on an analytical model of the applicator. The classical system yields an independent verification of the integrated activity used in the planning calculations, whereas the analytical model is used to evaluate depth dose dependence on mold size and optimization.

Influence of prostate volume on dosimetry results in real-time 125I seed implantation.

PURPOSE: Achieving a minimal dose of 140 Gy to 90% of the prostate (D90) on postimplant dosimetry has been shown to yield improved biochemical control by 125I brachytherapy, and a D90 >180 Gy can be associated with increased long-term toxicity of seed implantation. Significant enlargement of the prostate on postimplant CT compared with the ultrasound (US) volume at implantation (CT/US ratio) has been associated with lower dose results, but other factors predicting for high or low doses are not well established. We determined whether the prostate size at implantation influenced the CT/US ratio results affecting postimplant dosimetry or predicted for D90 values <140 or >180 Gy in patients implanted with 125I in a community hospital setting. METHODS AND MATERIALS: The dosimetry results from 501 patients from 33 community hospitals were analyzed after full dose 125I implantation. Implant radioactivity was obtained from reference tables relating millicuries to prostate volume (PV). Seeds were placed under real-time US guidance with peripheral weighting in a uniform method for all prostate sizes. CT-based dosimetry was performed 1 month after implantation. Dose-volume histogram parameters were analyzed for volume effects, including D90, the dose to 10% and 30% of the rectal wall, and the dose to 30% of the urethra and bladder. The PV was defined as small (<25 cm3), medium (25 to <40 cm3), or large (> or =40 cm3). RESULTS: The PV ranged from 9 to 79 cm3 (median 32.7). A D90 > or =140 Gy was achieved in 452 patients (90%). The median D90 was 164 Gy (range 90-230) and increased from 149.5 Gy in small prostates to 164 Gy in medium (p <0.001) and 176 Gy in large (p <0.001) prostates. A D90 <140 Gy occurred in 20% of small vs. 9% of medium and 3% of large prostates (p = 0.003). A D90 >180 Gy occurred in 7% of small and 10% of medium vs. 25% of large glands (p <0.001). The rectal dose increased significantly with an enlarging PV. The bladder and urethral doses increased from the small to medium PVs, although did not increase further in the large glands. The median CT/US ratios showed a significant volume relationship, decreasing with enlarging PVs, but were not associated with a D90 <140 or >140 Gy. The D90 results for <140 Gy and >140 Gy occurred at equal activities per volume. CONCLUSION: Ninety percent of patients implanted by community-level practitioners using reference tables and real-time US-guided implantation achieved a D90 outcome of > or =140 Gy. Significant differences in dose outcomes <140 Gy and >180 Gy occurred related to PV. Those with prostates <25 cm3 had a 20% frequency of D90 <140 Gy, unrelated to excessive postimplant volume enlargement or insufficient activity per reference table, suggesting that the activity-to-volume recommendations may not allow for much variance in final seed position. Such seed displacement may contribute to lower doses, most commonly in small glands. One may consider increasing the activity implanted in small prostates, because a D90 >180 Gy occurred in only 7% of these cases. Patients with glands >40 cm3 were 25% likely to have a D90 result >180 Gy and were at only 3% risk of a D90 <140 Gy. These patients may benefit from intraoperative dosimetry or a reduction in implant activity.

Intrafractional stability of the prostate using a stereotactic radiotherapy technique.

PURPOSE: To evaluate the stability of the prostate during stereotactic radiation therapy. MATERIALS AND METHODS: Forty-seven patients underwent placement of three fiducial markers into the prostate as part of a pilot study of hypofractionated stereotactic radiotherapy. Portal images before and subsequent to 227 radiotherapy fractions were analyzed for prostate movement. Six patients also underwent localizing radiographs at 6-min intervals for 24 min. Relative motion of the bony landmarks and prostate markers was calculated. RESULTS: Analysis of portal images revealed the undirected average prostate movement of 2.0 mm (superior/inferior), 1.9 mm (anterior/posterior), and 1.4 mm (right/left) with maximum standard deviation (SD) of 2.0. Analysis of radiographs at 6-min intervals showed the greatest undirected average prostate motion between 0-6 min; 1.5 mm (superior/inferior), 1.4 mm (anterior/posterior), and 0.4 mm (right/left). Beyond 6 min, movements decreased to 0.4, 0.9, and 0.8 mm, respectively. Bony landmark motion was 0.9 mm (superior/inferior), 0.9 mm (anterior/posterior), and 0.4 mm (right/left) between 0-6 min. Beyond 6 min, motion decreased to less than 0.5 mm in any direction. CONCLUSIONS: Stereotactic prostate radiotherapy, utilizing fiducial marker localization, resulted in average intrafractional prostate movement of 2.0 mm or less. Most patient and organ movement occurs early and a settling-in period is advisable before treatment.