Bashar Al-Qaisieh

Outcomes Following Iodine-125 Monotherapy for Localized Prostate Cancer: The Results of Leeds 10-Year Single-Center Brachytherapy Experience

PURPOSE This study reports the 10-year experience of permanent brachytherapy monotherapy at a single UK center. METHODS AND MATERIALS Between March 1995 and September 2004, 1,298 patients underwent trans-rectal ultrasound (TRUS) planned transperineal brachytherapy delivering 145 Gy using I-125. No patient received supplemental external beam; 44.2% received neoadjuvant hormones. In 688, CT postimplant dosimetry was available. Outcome data were analyzed in terms of overall survival (OS), disease specific survival (DSS), and PSA relapse-free survival (PSA-RFS). RESULTS The mean age was 62.9 (range, 34-83) years. Median follow-up was 4.9 years (range, 2.03-11.7 years). OS and DSS were 85% and 95%, respectively, at 10 years. Twenty-one patients died from prostate cancer (1.6%) and 34 (2.5%) from unrelated causes. Seventy-four (5.7%) developed evidence of clinical failure. Overall PSA-RFS was 79.9% and 72.1% at 10 years (American Society for Therapeutic Radiology and Oncology [ASTRO] and Nadir+2 definitions, respectively). Higher presenting PSA or Gleason score and use of neoadjuvant hormones were associated with an increased risk of biochemical failure (p <0.01). Biochemical control was achieved in 86.4%, 76.7%, and 60.6% (ASTRO) and 72.3%, 73.5%, and 57.6% (Nadir+2) of patients in low-, intermediate-, and high-risk groups, respectively. Biochemical control was achieved in 88% of patients with D(90) > or =140 Gy and in 78% of patients with D(90) <140 Gy (p <0.01). CONCLUSIONS I-125 brachytherapy alone achieved excellent rates of medium-term biochemical control in both low- and selected intermediate-risk localized prostate cancer patients. Postimplant dosimetry improved with experience and longer follow-up, confirming the relationship of D(90) with biochemical control.

Report of a consensus meeting on focal low dose rate brachytherapy for prostate cancer

Whats known on the subject? and What does the study add?

Outcomes from Gleason 7, intermediate risk, localized prostate cancer treated with Iodine-125 monotherapy over 10 years

BACKGROUND AND PURPOSE The effect of predominating Gleason grade (3+4 versus 4+3) in Gleason sum score (GS) 7 prostate cancer (PCa) on brachytherapy outcomes is unclear. The 10 year experience of permanent brachytherapy monotherapy at a single UK centre for GS 7, intermediate risk (Memorial Sloan-Kettering model), PSA < or = 10 ng/ml, localised PCa is reported. MATERIALS AND METHODS Between 1995 and 2004, the outcomes of 187 patients with GS 7 PCa (PSA < or = 10 ng/ml) were analysed from a cohort of 1298 men treated with permanent Iodine-125 prostate brachytherapy, including PSA relapse-free survival (PSA-RFS). RESULTS Median follow-up was 5.0 years (range 2.0-10.1 years). One patient has died of PCa. At 10 years, PSA-RFS was 82.4%/78% (ASTRO consensus and nadir +2 definitions). For GS 3+4, 5 year PSA-RFS was 86.7%/87.9% and for GS 4+3: 85.2%/96.6% respectively, with no significant difference between groups. Five year PSA-RFS (ASTRO) of 92.6% was seen for D(90) > or = 140 Gy (50% total), compared with 77.0% below 140 Gy (p=0.08). CONCLUSIONS Iodine-125 brachytherapy monotherapy achieved good rates of medium term biochemical control in GS 7, intermediate risk localised PCa patients. There was a trend to improved outcomes in men with a D90 in excess of 140 Gy.

Prostate-specific antigen relapse-free survival in patients with localized prostate cancer treated by brachytherapy

Brachytherapy has become a very popular way of treating prostate cancer worldwide, and increasing attempts are being made by radiation oncologists to find the exact type of patient for whom this treatment is the most suitable. One of the largest series has come from Leeds, and the authors present the PSA relapse‐free survival in 667 patients with localised prostate cancer treated by brachytherapy in their department.

Pre- and post-implant dosimetry: an inter-comparison between UK prostate brachytherapy centres.

The consistency and reliability of five prostate brachytherapy centres performing pre- and post-implant dosimetry were evaluated. Ultrasound based pre-planning protocols and techniques were similar although they may be slightly affected by the chosen seed activity. Computerised tomography-based post-implant dosimetry varied because of differing estimations of the prostate volume.

Dosimetry Modeling for Focal Low-Dose-Rate Prostate Brachytherapy

PURPOSE Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). METHODS AND MATERIALS Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focal (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. RESULTS WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm(3) was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. CONCLUSIONS Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable reduction to organs at risk. Treating smaller targets makes seed positioning more critical.

CORRELATION BETWEEN PRE- AND POSTIMPLANT DOSIMETRY FOR IODINE-125 SEED IMPLANTS FOR LOCALIZED PROSTATE CANCER

PURPOSE In order to evaluate implant quality for permanent prostate brachytherapy in patients with localized prostate cancer, American Brachytherapy Society and ESTRO guidelines recommend that postimplant dosimetry should be performed. To understand more about the relationship between pre- and postimplant dosimetry, a comparison was made of patients who received iodine-125 ((125)I) brachytherapy between March 1995 and the end of 2004, using a preplan technique. METHODS AND MATERIALS CT postimplant dosimetry was available for 707 patients. Detailed dose volume analysis was performed using both preimplant ultrasound and postimplant CT data sets for a subgroup of 445 patients. The following parameters were compared: prostate volume covered by 100% of the prescription dose (Vp100), Vp150, and Vp200 and dose to 90% (D90) of the prostate. In addition, volume implanted (Vi) parameters were used to compare pre- and postimplant dosimetry. Vi parameters describe dose levels inside the patient, based on number of seeds, seed activity, and their spatial distribution relative to each other, without reference to the actual prostate volume or position. RESULTS The mean +/- standard deviation values of preimplant (34.7 +/- 8.9 cm(3)) and postimplant (36.7 +/- 9.4 cm(3)) prostate volumes were similar. The mean (+/-standard deviation) planned D90 was 183.4 (+/-12.1) Gy while the D90 that was achieved was 145.5 (+/-20.4) Gy. Over the study period, there was a steady increase of the average D90. Postimplant CT D90 and Vp100 values correlated significantly (R = 0.84; p < 0.001). The Vi and Vp parameters all showed a strong correlation. CONCLUSIONS In this study, we showed that there is a strong correlation between transrectal ultrasound-based preimplant and CT-based postimplant dosimetry. The excellent correlation between prostate D90 and V100 values demonstrates they are both equally valid quality indices. Vi parameters are an additional measure that can be used to assess the quality of the implant.

Second Primary Cancers Occurring after I-125 Brachytherapy as Monotherapy for Early Prostate Cancer

AIMS Prostate brachytherapy may be associated with a lower risk of radiation-induced second primary cancer (SPC) as a significantly smaller volume of normal tissue is irradiated when compared with external beam techniques. Limited data are available as it has been a routine treatment option for less than 20 years. This study identified cases of SPC in patients who underwent I-125 prostate brachytherapy as monotherapy in a single institution. MATERIALS AND METHODS SPC incidence was retrieved by conducting a UK cancer registry search (Northern and Yorkshire Cancer Registry and Information Service) for 1805 consecutive patients with localised prostate cancer who received monotherapy with I-125 brachytherapy from 1995 to 2006 at a single public hospital. Of 1730 UK residents, the completeness of the registry match was 91% (1574 patients). The mean age at treatment (interquartile range) of the cohort was 63 (58-68) years with 1100 patients (70%) over the age of 60 years at treatment. The median (range) follow-up was 8 (6-10) years with 487 patients (31%) having 10 years or more. RESULTS In total, 170 patients (10.8%) were diagnosed with second primaries (1 year or more after implant); 20 of these were bladder and 10 rectal cancers. The 10 year cumulative incidences were 14.6, 1 and 0.84% for any second malignancy, bladder and rectal cancer, respectively. Only the standardised incidence rate (SIR) for bladder cancer was higher at 1.54 (95% confidence interval 0.96-2.46) compared with the general population. The SIR for bladder cancer was higher in the first few years after treatment, suggesting that the increased incidence of bladder cancer is due to increased urological surveillance. CONCLUSIONS Overall, the incidence of SPC after I-125 is comparable with other published data with no significant excess more than 5 years from treatment. Mortality secondary to SPC of the bladder or rectum is unusual.

Real-time in vivo dosimetry in high dose rate prostate brachytherapy

BACKGROUND AND PURPOSE Single fraction treatments of 15Gy or 19Gy are common in HDR prostate brachytherapy. In vivo dosimetry (IVD) is therefore important to ensure patient safety. This study assesses clinical IVD and investigates error detection thresholds for real-time treatment monitoring. MATERIALS AND METHODS IVD was performed for 40 treatments planned using intra-operative trans-rectal ultrasound (TRUS) with a MOSFET inserted into an additional needle. Post-treatment TRUS images were acquired for 20 patients to assess needle movement. Monte Carlo simulations of treatment plans were performed for 10 patients to assess impact of heterogeneities. Per-needle and total plan uncertainties were estimated and retrospectively applied to the measured data as error detection thresholds. RESULTS The mean measured dose was -6.4% compared to prediction (range +5.1% to -15.2%). Needle movement and heterogeneities accounted for -1.8% and -1.6% of this difference respectively (mean values for the patients analysed). Total plan uncertainty (k=2) ranged from 11% to 17% and per needle uncertainty (k=2) ranged from 18% to 110% (mean 31%). One out of 40 plans and 5% of needles were outside k=2 error detection threshold. CONCLUSIONS IVD showed good agreement with predicted dose within measurement uncertainties, providing reassurance in the accuracy of dose delivery. Thresholds for real-time error detection should be calculated on an individual plan/needle basis.

Monte Carlo investigation of I-125 interseed attenuation for standard and thinner seeds in prostate brachytherapy with phantom validation using a MOSFET.

PURPOSE In permanent seed implant prostate brachytherapy the actual dose delivered to the patient may be less than that calculated by TG-43U1 due to interseed attenuation (ISA) and differences between prostate tissue composition and water. In this study the magnitude of the ISA effect is assessed in a phantom and in clinical prostate postimplant cases. Results are compared for seed models 6711 and 9011 with 0.8 and 0.5 mm diameters, respectively. METHODS A polymethyl methacrylate (PMMA) phantom was designed to perform ISA measurements in a simple eight-seed arrangement and at the center of an implant of 36 seeds. Monte Carlo (MC) simulation and experimental measurements using a MOSFET dosimeter were used to measure dose rate and the ISA effect. MC simulations of 15 CT-based postimplant prostate treatment plans were performed to compare the clinical impact of ISA on dose to prostate, urethra, rectum, and the volume enclosed by the 100% isodose, for 6711 and 9011 seed models. RESULTS In the phantom, ISA reduced the dose rate at the MOSFET position by 8.6%-18.3% (6711) and 7.8%-16.7% (9011) depending on the measurement configuration. MOSFET measured dose rates agreed with MC simulation predictions within the MOSFET measurement uncertainty, which ranged from 5.5% to 7.2% depending on the measurement configuration (k = 1, for the mean of four measurements). For 15 clinical implants, the mean ISA effect for 6711 was to reduce prostate D90 by 4.2 Gy (3%), prostate V100 by 0.5 cc (1.4%), urethra D10 by 11.3 Gy (4.4%), rectal D2cc by 5.5 Gy (4.6%), and the 100% isodose volume by 2.3 cc. For the 9011 seed the mean ISA effect reduced prostate D90 by 2.2 Gy (1.6%), prostate V100 by 0.3 cc (0.7%), urethra D10 by 8.0 Gy (3.2%), rectal D2cc by 3.1 Gy (2.7%), and the 100% isodose volume by 1.2 cc. Differences between the MC simulation and TG-43U1 consensus data for the 6711 seed model had a similar impact, reducing mean prostate D90 by 6 Gy (4.2%) and V100 by 0.6 cc (1.8%). CONCLUSIONS ISA causes the delivered dose in prostate seed implant brachytherapy to be lower than the dose calculated by TG-43U1. MC simulation of phantom seed arrangements show that dose at a point can be reduced by up to 18% and this has been validated using a MOSFET dosimeter. Clinical simulations show that ISA reduces DVH parameter values, but the reduction is less for thinner seeds.