A multicentre audit of HDR/PDR brachytherapy absolute dosimetry in association with the INTERLACE trial (NCT015662405).

A UK multicentre audit to evaluate HDR and PDR brachytherapy has been performed using alanine absolute dosimetry. This is the first national UK audit performing an absolute dose measurement at a clinically relevant distance (20 mm) from the source. It was performed in both INTERLACE (a phase III multicentre trial in cervical cancer) and non-INTERLACE brachytherapy centres treating gynaecological tumours. Forty-seven UK centres (including the National Physical Laboratory) were visited. A simulated line source was generated within each centre's treatment planning system and dwell times calculated to deliver 10 Gy at 20 mm from the midpoint of the central dwell (representative of Point A of the Manchester system). The line source was delivered in a water-equivalent plastic phantom (Barts Solid Water) encased in blocks of PMMA (polymethyl methacrylate) and charge measured with an ion chamber at 3 positions (120° apart, 20 mm from the source). Absorbed dose was then measured with alanine at the same positions and averaged to reduce source positional uncertainties. Charge was also measured at 50 mm from the source (representative of Point B of the Manchester system). Source types included 46 HDR and PDR 192Ir sources, (7 Flexisource, 24 mHDR-v2, 12 GammaMed HDR Plus, 2 GammaMed PDR Plus, 1 VS2000) and 1 HDR 60Co source, (Co0.A86). Alanine measurements when compared to the centres' calculated dose showed a mean difference (±SD) of +1.1% (±1.4%) at 20 mm. Differences were also observed between source types and dose calculation algorithm. Ion chamber measurements demonstrated significant discrepancies between the three holes mainly due to positional variation of the source within the catheter (0.4%-4.9% maximum difference between two holes). This comprehensive audit of absolute dose to water from a simulated line source showed all centres could deliver the prescribed dose to within 5% maximum difference between measurement and calculation.

The Effect of Dose and Quality Assurance in Early Prostate Cancer Treated with Low Dose Rate Brachytherapy as Monotherapy.

AIMS: To examine the relationship between post-implant computed tomography dosimetry and long-term prostate-specific antigen relapse-free survival in patients treated with iodine 125 (I-125) low dose rate prostate brachytherapy as monotherapy and, second, to audit recent practice against Royal College of Radiologists' (RCR) guidelines after the re-introduction of post-implant dosimetry for all patients in our centre. MATERIALS AND METHODS: Between March 1995 and September 2007, 2157 consecutive patients with localised prostate cancer underwent I-125 permanent prostate brachytherapy as monotherapy in a single UK centre. All patients were transrectal ultrasound planned delivering a 145 Gy (TG 43) minimum peripheral dose. None received supplemental external beam radiotherapy. Post-implant computed tomography-based dosimetry was undertaken between 4 and 6 weeks after treatment and was available for 711 (33%). Outcomes were analysed in terms of the relationship of D90 to prostate-specific antigen relapse-free survival (nadir 2+ definition) and all patients had a minimum follow-up of 5 years. For contemporary patients from 2011, quality metrics from post-implant computed tomography as defined by RCR guidelines are presented. RESULTS: A mean D90 of 138.7 Gy (standard deviation 24.7) was achieved for the historic cohort. Biochemical control at 10 years was 76% in patients with D90 > 140 Gy and 68% in those with D90 < 140 Gy (P < 0.01). In current practice, over the last 3 years the mean (standard deviation) D90 has increased from 154 (15.3) Gy in 2011 to 164 (13.5) Gy in 2013. Similarly, an increase in the mean (standard deviation) V100 from 92 (4.4) to 95 (3.2) % is noted over time. No difference between clinicians was noted. CONCLUSION: D90 values of less than 140 Gy continue to be predictive of increased risk of recurrence of prostate cancer across risk groups with longer follow-up. Quality assurance can be used to ensure improved and consistent implant quality in a team with multiple clinicians.

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.

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.

A method for scoring treatment time efficiency of Gamma Knife radiosurgical treatment plans for brain metastases.

PURPOSE: In Gamma Knife radiosurgery, an efficient plan is one that achieves dosimetric quality while minimizing treatment time. Although minimization of treatment time to improve throughput and benefit patient comfort is a common and important goal of radiosurgery planning, to date no studies have attempted to specifically quantify efficiency. The aim of this study was to define simple index to score efficiency, and by quantifying time savings achieved by replanning those cases identified as least efficient, so demonstrate the efficacy of the index. METHODS: To quantify efficiency, it is necessary to determine treatment times expected for specified lesions. However, because of numerous case-specifics, efficiency cannot be quantified in terms of treatment times alone. This study defines a new quantity, the attenuation-corrected normalized treatment time-dose rate product, nTRP(corr), to account for differing dose rates, prescriptions, and attenuation. A plan efficiency index (PEI) is then defined for lesions of similar volume and shape in terms of expected and planned nTRP(corr). nTRP(corr) was retrospectively calculated for metastatic lesions of comparable shape. A curve fitted to data describing how nTRP(corr) typically varied with volume for these lesions was then used to determine expected nTRP(corr). For each lesion, PEI was calculated as the ratio of expected-to-planned nTRP(corr). Plans with the lowest PEI were replanned, with the aim of maintaining dosimetric quality while minimizing treatment time. Dosimetric quality was defined in terms of coverage, conformity, and gradient index. Statistical significance of differences between original and replans was quantified via paired t-tests. RESULTS: The mean(standard deviation) PEI of all reviewed lesions was 1.08(0.28). The 14 least efficient plans across the range of investigated volumes (45-19 800 mm(3)) had a mean PEI of 0.64, versus 1.18 when replanned (p < 0.0001). This corresponded to a mean(range) time saving of 42%(19%-62%), [29(8-52) min at date of treatment] with no statistically significant (p > 0.05) change in dosimetric quality. CONCLUSIONS: The PEI is a viable metric for identifying those plans that benefit from a more efficient planning strategy.

A comparison of four skull models for independent dose calculations for Gamma Knife PERFEXION.

PURPOSE: It is recommended to have a method for independently verifying planned doses in stereotactic radiosurgery. The problem is one of how to model the geometry of a skull sampled by a limited number of points and how to subsequently calculate numerous attenuation pathlengths through the modeled skull. While methods of verification have been previously published for model B and C Gamma Knife units, the aims of the current work were to apply the principles of these previously published techniques for the verification of plans for Gamma Knife PERFEXIONTM, to present a new method of verification, and to compare all methods in terms of their agreement with GammaPlan. METHODS: Four algorithms were implemented: the previously published spherical approximation method (SAM) and bubble helmet skull (BHS), plus a modified BHS named interpolated BHS (IBHS) and a newly developed variable radius SAM (VRSAM). Reference point doses calculated by the four algorithms were compared to those reported by GammaPlan for 54 simple test plans and for 35 targets in 20 recent patient plans. RESULTS: For test plans, the mean (standard deviation) discrepancies against GammaPlan-reported doses were 0.3 (1.3)%, 0.3 (1.3)%, -1.6 (3.4)%, and -0.4 (1.0)% for SAM, VRSAM, BHS, and IBHS, respectively. For patient plans both the VRSAM and IBHS showed insignificant (p=0.22 and p = 0.50) discrepancies against GammaPlan of 0.38 (1.86)% and -0.11 (1.86)%, respectively. More significant discrepancies against GammaPlan (p < 0.0001) of 2.64 (2.98)% and -4.43 (3.39)% were observed for the SAM and BHS. CONCLUSIONS: The SAM can lead to large discrepancies against GammaPlan when a sphere is a poor approximation of the true skull surface, and in peripheral locations can lead to nonreal solutions to the attenuation pathlength calculations. While the BHS does not suffer the same geometric assumptions of the SAM, it can underestimate dose for peripherally located shots. The IBHS exhibits better agreement with GammaPlan than does the BHS, but requires two-dimensional interpolation that was found to be impractical to implement in the Excel-based software used in the current work. Combining aspects of both the previously published SAM and BHS algorithms, the newly presented VRSAM exhibits comparable results to the IBHS but without the need for interpolation and is therefore considered the preferred technique of the four implemented.

High dose rate iridium-192 brachytherapy as a component of radical radiotherapy for the treatment of localised prostate cancer.

AIMS: To assess the treatment outcomes and toxicity of conformal high dose rate (HDR) brachytherapy boost as a means of radiation dose escalation in patients with localised prostate cancer. MATERIALS AND METHODS: Between December 1998 and July 2004, 65 consecutive patients with localised prostate cancer (magnetic resonance imaging-staged T1-3 N0 M0) were treated with external beam radiation therapy (EBRT) followed by two fractions of HDR iridium-192 brachytherapy. The patients selected this treatment modality in preference to entering an ongoing randomised phase 3 trial. Any pre-treatment serum prostate-specific antigen (PSA) and Gleason score were included. The primary end point was biochemical disease-free progression. Late treatment-related morbidity was graded according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer criteria. RESULTS: The median patient age was 67.3 years (range 47.9-80). Sixty patients (92.3%) had intermediate- to high-risk disease defined by clinical stage, presenting PSA and Gleason score/World Health Organisation (WHO) grade. With a median follow-up of 3.5 years (range 0.6-5.8), two patients had died of metastatic disease and another four patients had PSA relapse, giving a 3-year actuarial biochemical disease-free progression of 90.8%. Three patients (4.6%) had acute grade 3 genitourinary toxicity, in the form of urinary retention. Late grade 3 and 4 genitourinary toxicities occurred in four patients (6.2%) and one patient (1.5%), respectively. No late gastrointestinal toxicities were observed. CONCLUSIONS: These results suggest that the combined modality of conformal HDR brachytherapy and EBRT is a feasible treatment modality with acceptable acute and late toxicities, comparable with those of EBRT alone. It offers an attractive conformal treatment modality with the potential of further dose escalation in the treatment of localised prostate cancer.

The influence of applicator angle on dosimetry in vaginal vault brachytherapy.

In vaginal vault brachytherapy, the critical normal tissues are bladder and rectum; doses to these tissues may be affected by the position of a single line applicator placed in the vagina. Dosimetry with the applicator lying at its "natural" angle in the vagina with the patient in the lithotomy position has been compared with the applicator held horizontal as defined by a spirit level in 30 consecutive patients. A mean change in angle of 19.7 degrees was found. This resulted in a mean decrease in ICRU (International Commission of Radiation Units and Measurements) rectal point dose when the applicator is horizontal of 12.9%, equivalent to a mean absolute dose reduction of 1.3 Gy for a prescription dose of 5.5 Gy at 5 mm depth. An increase in mean dose to the ICRU bladder point when the applicator is horizontal of 13.3%, equivalent to an absolute mean dose increase of 0.5 Gy per fraction for the same prescription dose, was also found. On the basis of these findings, it is recommended that vaginal vault brachytherapy is performed with a single line source held in the "corrected" horizontal position to reduce bowel dose as this is the most sensitive critical normal tissue.

A purpose-built iodine-125 irradiation plaque for low dose rate low energy irradiation of cell lines in vitro.

The phenomenon of hyper-radiosensitivity (HRS) to very low acute single doses of radiation has been demonstrated in several cell lines in vitro and in vivo, and has been studied in theory and in practice. The theory suggests a similar hypersensitivity when cells are continuously exposed to radiation at very low dose rates. These low dose rates are used when radioactive seed (iodine-125 or palladium-103) implants of the prostate are used as an alternative to surgery or external beam radiotherapy. To investigate the radiobiology of hypersensitivity of this type on various cell lines in vitro, an iodine-125 seed irradiator has been designed and built for safe use in the Gray Laboratory. In practice, the calculated dose rate has been used for consistency. Discrepancies between calculated and measured dose rates are discussed.