Assessment of uterus position as a surrogate for high-risk clinical target volume with respect to the applicator position for multiple fractions of brachytherapy in cervical cancer.

AIM: Hybrid magnetic resonance imaging/computerized tomography (MRI/CT) planning for high-dose-rate (HDR) brachytherapy in cervical cancer with MR/CT fusion for the first fraction followed by CT for fraction 2 and 3 is used at our center. The aim of this study is to evaluate the position of applicator intrauterine tube (IU) in relation to uterine serosa with each fraction of intracavitary high-dose-rate brachytherapy. METHODS: Position of the applicator relative to uterus was measured from tip of the applicator (IU) to the top of uterus in the plane of IU and perpendicular to IU in anterior, posterior, left and right directions at the tip of IU, mid-point of the IU and 1 cm from the surface of vaginal ring. The mean absolute difference (±95 % confidence interval) between these positions at fraction 2 and 3 was calculated with fraction one as reference. RESULTS: The mean absolute difference (±95 %) of the applicator relative to uterus was 2.7 ± 0.5 mm at the tip, 1.5 ± 4 mm at mid-point and 1.1 ± 0.3 mm at 1 cm from the surface of the ring. CONCLUSION: This study shows that there is consistency in inter-fraction applicator position relative to uterus apart from at the tip and, therefore, in situations where high-risk clinical target volume (HRCTV) extends towards uterine fundus, MRI should be used for each fraction of brachytherapy planning to accurately define HRCTV.

Conformal 3D computed tomography planned endoluminal brachytherapy for the local control of esophageal cancer.

PURPOSE: To outline the toxicity, tolerability, and efficacy of a 3D conformal computed tomography planned endoluminal brachytherapy (ELBT) treatment for esophageal adenocarcinoma (OAC) or squamous cell carcinoma (OSCC). METHODS AND MATERIALS: A retrospective single-center analysis of toxicity, tolerability, and outcomes for 65 consecutive patients with OAC/OSCC who received 6-8Gy in one fraction or 12-16Gy in two fractions of high-dose-rate ELBT as salvage postchemoradiotherapy (n = 7 and n = 14 respectively), or as a boost to external beam radiotherapy (n = 14 and n = 30, respectively). RESULTS: Median overall survival from the first brachytherapy application was 7.4 (IQR 5.0-14.7) months for the boost cohort and 9.2 (IQR 5.8-20.1) months for the salvage cohort. In a univariate analysis, use of a higher, fractionated dose of radiotherapy was associated with longer overall survival. At least one-third (33%; n = 7) of the salvage cohort and 28% (n = 12) of the boost cohort exhibited a local recurrence prior to death. Overall, 66.7% of the salvage and 56.8% of the boost cohort experienced odynophagia. Swallow function stabilized or improved early after treatment, with only 11.6% of the boost and 14.3% of the salvage cohort demonstrating a long-term decline in dysphagia score. CONCLUSIONS: 3D conformal planned ELBT is safe and tolerable. Most patients exhibit an early and sustained stabilization or improvement in their swallow function and greater survival is seen with higher brachytherapy doses. Further research is required to determine the place of brachytherapy in the management of esophageal cancer, particularly when planned using contemporary conformal approaches.

Stereotactic radiosurgery for the treatment of brain metastases: impact of cerebral disease burden on survival.

Stereotactic radiosurgery (SRS) for brain metastases has been carried out at the Leeds Gamma Knife Centre since March 2009. The aim of this study was to examine the outcomes and toxicity in our initial cohort of patients. The medical records of patients with brain metastases referred to the Leeds Gamma Knife Centre between March 2009 and July 2010 were retrospectively reviewed. Data on survival, primary tumour, Karnofsky performance status, time from diagnosis to identification of brain metastases, previous treatment for brain metastases and results of staging prior to SRS were recorded. Patients were followed up with regular magnetic resonance imaging of the brain for a minimum of 6 months and data on toxicity and oral steroid dose were recorded. Statistical analysis was carried out using SPSS v14.0. Survival curves were compared using the Log Rank test. Fifty eight patients (19 male) had a median survival of 50.4 weeks (95% CI, 32.6-68.2 weeks). Lung (36%) and breast (27%) were the most common primary tumours. Patients with a total volume of metastases treated < 5000 mm(3) (p = 0.007) or between 5000 mm(3) and 10,000 mm(3) (p = 0.01) had significantly improved survival compared with patients with a total treated volume > 10,000 mm(3). In addition, largest treated lesion < 5000 mm(3) was a positive prognostic factor. Patients with a single metastasis did not survive significantly longer than those with multiple metastases. Steroid dose dropped significantly after SRS (p < 0.01) and was the same or less in 91% of patients. There were only three cases of grade 3 toxicity. Our study reports survival comparable with other series on radiosurgery and demonstrates a significant decrease in steroid dose following treatment. It also shows that the size of the largest treated metastasis and total volume of metastatic disease seemed a better predictor of outcome than number of metastases treated.

Exclusive 3D-brachytherapy as a good option for stage-I inoperable endometrial cancer: a retrospective analysis in the gynaecological cancer GEC-ESTRO Working Group.

PURPOSE: Analyse outcomes of stage-I inoperable endometrial cancer (EC) patients from seven European centres treated with 3D-image-guided brachytherapy (IGBT) alone. MATERIALS AND METHODS: From 2004 to 2018, 62 patients (41 stage-IA and 21 IB) were retrospectively studied, analysing anaesthetic procedure, applicator type, BT-planning imaging, clinical target volume (CTV), BT schedule, overall daily-dose equivalent to 2 Gy (EQD2(α/ß=4.5 or 3)) to the CTV(α/ß=4.5) and D2 cm3(α/ß=3) for organs at risk. Complications were evaluated using CTCAEv4 scores. The 2 and 5 year survival was calculated [cancer-specific survival (CSS), disease-free survival (DFS), local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS)]. Descriptive analysis and the Kaplan-Meier method were used for survival analysis. RESULTS: Mean follow-up: 32.8 months (SD 33.7). Spinal anaesthesia (38/62) followed by none (16/62) were the most common. Y-shaped Rotte applicators were used in 74% of patients. High-dose rate brachytherapy was administered in 89%. Median D90 to the CTV was 58.9 Gy (8.66-144 Gy). Eight patients presented relapse: four uterine, four nodal and four distant. The 2 and 5 year CSS was 93.3 and 80.5%, DFS 84.8 and 80.5%, LRFS was 93.1 and 88.7%, LRRFS was 91 and 91% and DMFS was 90.2 and 90.2%, respectively, CSS was better in stage-IA vs. IB (p = 0.043). Late vaginal and bladder G3-complication rates were 2.1%, respectively. CONCLUSION: Inoperable EC patients can be safely treated by BT with 2 and 5 year CSS of 93 and 80.5%, respectively, with even better results for IA cases. Prospective studies on 3D-IGBT are necessary to better analyse EC patient outcomes based on dose and treated volumes.

Reirradiation Options for Previously Irradiated Prostate cancer (RO-PIP): Feasibility study investigating toxicity outcomes following reirradiation with stereotactic body radiotherapy (SBRT) versus high-dose-rate brachytherapy (HDR-BT).

INTRODUCTION: Radiotherapy is the most common curative treatment for non-metastatic prostate cancer; however, up to 13% of patients will develop local recurrence within 10 years. Patients can undergo further and potentially curative treatment including salvage surgery, brachytherapy (BT), external beam radiotherapy, high-intensity focused ultrasound and cryotherapy. Systematic review shows that high-dose-rate (HDR) BT and stereotactic body radiotherapy (SBRT) have the best outcomes in terms of biochemical control and lowest side effects. The reirradiation options for previously irradiated prostate cancer (RO-PIP) trial aims to determine the feasibility of recruitment to a trial randomising patients to salvage HDR-BT or SBRT and provide prospective data on patient recorded toxicity outcomes that will inform a future phase III trial. METHODS AND ANALYSIS: The primary endpoint of the RO-PIP feasibility study is to evaluate the patient recruitment potential over 2 years to a trial randomising to either SBRT or HDR-BT for patients who develop local recurrence of prostate cancer following previous radiation therapy. The aim is to recruit 60 patients across 3 sites over 2 years and randomise 1:1 to SBRT or HDR-BT. Secondary objectives include recording clinician and patient-reported outcome measures to evaluate treatment-related toxicity. In addition, the study aims to identify potential imaging, genomic and proteomic biomarkers that are predictive of toxicity and outcome based on hypoxia status, a prognostic marker of prostate cancer. ETHICS AND DISSEMINATION: This study has been approved by the Yorkshire and The Humber-Bradford Leeds Research Ethics Committee (Reference: 21/YH/0305, IRAS: 297060, January 2022). The results will be presented in national and international conferences, published in peer-reviewed journals and will be communicated to relevant stakeholders. A plain English report will be shared with the study participants, patients' organisations and media. TRIAL REGISTRATION NUMBER: ISRCTN 12238218 (Amy Ackroyd NIHR CPMS Team).

Evaluation of a collapsed-cone convolution algorithm for esophagus and surface mold 192Ir brachytherapy treatment planning.

PURPOSE: TG43 does not account for a lack of scatter and tissue and applicator heterogeneities. The advanced collapsed-cone engine (ACE) algorithm available for use in the Oncentra Brachy treatment planning system (Elekta AB, Stockholm, Sweden) can model these conditions more accurately and is evaluated for esophageal and surface mold brachytherapy treatments. METHODS AND MATERIALS: ACE was commissioned for use then compared against TG43 for five esophageal and five surface mold treatment plans. Dosimetric differences between each algorithm were assessed using superimposed comparisons and dose-volume histogram statistics. RESULTS: Esophagus (6 Gy per fraction): Compared with TG43, ACE demonstrated up to a 0.63% and 0.05 Gy reduction in planning target volume (PTV) V100% and PTV D98, respectively. Lung D2cc and bone D2cc deviated by up to 0.09 Gy and 0.03 Gy, respectively. Lung D0.1 cc and bone D0.1 cc both deviated by up to 0.12 Gy. Surface mold (4.5 Gy per fraction): Compared with TG43, ACE demonstrated up to a 12.5% and 0.18 Gy reduction in PTV V80% and PTV D98, respectively. Bone D2cc and D0.1 cc both reduced by up to 0.2 Gy when modeled with ACE. Increasing mold size laterally increased the dosimetric differences between TG43 and ACE. CONCLUSIONS: TG43 generally overestimated dose delivered to the target volume and organs at risk for the sites investigated. Dosimetric differences observed for esophageal treatments were minimal; however, surface mold treatments would benefit from the increased dosimetric accuracy offered by ACE. Implementation should be considered for surface mold 192Ir treatment planning, but increased calculation time, additional contouring, and mass density assignment requirements should be scrutinized with regard to their potentially negative impact on current clinical practice.

Error detection thresholds for routine real time in vivo dosimetry in HDR prostate brachytherapy.

PURPOSE: Routine real time in vivo dosimetry (IVD) is performed in HDR prostate brachytherapy to independently verify dose delivery. This study investigates impact of position uncertainty on error detection thresholds for IVD. METHODS: IVD is implemented using a microMOSFET placed centrally in the prostate using an additional needle. 144 IVD measurements were made for 15 Gy or 19 Gy single fraction treatments. Needle insertion and treatment planning used real-time trans-rectal ultrasound. Source-MOSFET position thresholds of ±1, ±2 and ±3 mm were used to calculate per-needle and total plan error detection thresholds for the measured dose using an uncertainty analysis based on the treatment plan data. RESULTS: The median dose difference from 144 total plan measurements was -5.2% (range +7.4% to -17.3%). 3 plans measured outside the total plan error detection threshold for position threshold ±1 mm, no plans measured outside the total plan error detection threshold for larger position thresholds. For 2233 individual needle measurements, for position thresholds of ±1 mm, ±2mm and ±3 mm the number of needles outside the per-needle error detection threshold was 103, 25 and 10 respectively and the number of treatments that would have required interruption based on these thresholds for real-time IVD was 66, 16 and 8 respectively. CONCLUSION: IVD in HDR prostate brachytherapy using a microMOSFET provides a high level of confidence that we are correctly delivering the planned dose to our patients. A ±2-3 mm position threshold gives an appropriate balance between error detection and avoiding unnecessary treatment interruptions.

UK audit of target volume and organ at risk delineation and dose optimisation for cervix radiotherapy treatments.

OBJECTIVE: Assessment of the extent of variation in delineations and dose optimisation performed at multiple UK centres as a result of interobserver variation and protocol differences. METHODS: CT/MR images of 2 cervical cancer patients previously treated with external beam radiotherapy (EBRT) and Brachytherapy were distributed to 11 UK centres. Centres delineated structures and produced treatment plans following their local protocol. Organ at risk delineations were assessed dosimetrically through application of the original treatment plan and target volume delineations were assessed in terms of variation in absolute volume and length, width and height. Treatment plan variation was assessed across all centres and across centres that followed EMBRACE II. Treatment plans were assessed using total EQD2 delivered and were compared to EMBRACE II dose aims. Variation in combined intracavitary/interstitial brachytherapy treatments was also assessed. RESULTS: Brachytherapy target volume delineations contained variation due to differences in protocol used, window/level technique and differences in interpretations of grey zones. Planning target volume delineations were varied due to protocol differences and extended parametrial tissue inclusion. All centres met EMBRACE II plan aims for PTV V95 and high-riskclinical target volume D90 EQD2, despite variation in prescription dose, fractionation and treatment technique. CONCLUSION: Brachytherapy target volume delineations are varied due to differences in contouring guidelines and protocols used. Planning target volume delineations are varied due to the uncertainties surrounding the extent of parametrial involvement. Dosimetric optimisation is sufficient across all centres to satisfy EMBRACE II planning aims despite significant variation in protocols used. ADVANCES IN KNOWLEDGE: Previous multi-institutional audits of cervical cancer radiotherapy practices have been performed in Europe and the USA. This study is the first of its kind to be performed in the UK.

Ten-year longitudinal health-related quality of life following iodine-125 brachytherapy monotherapy for localized prostate cancer.

PURPOSE: This prospective longitudinal study quantifies health-related quality of life (HRQoL) up to 10 years following permanent iodine-125 (125I) prostate brachytherapy alone for localized prostate cancer. MATERIAL AND METHODS: In total, 120 patients completed a validated expanded prostate cancer index composite (EPIC) questionnaire pre-treatment and at 8 time points after treatment (6 weeks, 6, 10, 18 months, and 2, 3, 5, 10 years). At each time point, clinically relevant small, moderate, and severe declines in HRQoL were defined as 0.2-0.5 SD, 0.5-0.8 SD, and > 0.8 SD of baseline function for each of urinary, bowel, and sexual domains, respectively. RESULTS: Response rates in the first two years were > 90%, but thereafter dropped to 75% and 48% at 5 and 10 years, respectively. 50 patients (41.6%) responded at all stages. Maximal deterioration in mean urinary and sexual summary scores was noted 6 weeks after implant, with severe urinary symptoms and moderate bowel/sexual symptoms. At 6 months, urinary and bowel quality of life (QoL) had improved to mild impairment, which then fully resolved at 10 months. Sexual QoL remained mildly impaired throughout the 10 years of follow-up. At 10 years, new mild impairment of urinary and bowel QoL was found. CONCLUSIONS: Clinically mild changes in urinary, bowel, and sexual QoL are found 10 years after 125I monotherapy. The impairment in sexual function persists from treatment, but urinary and bowel symptoms are new at 10 years.

Efficacy and toxicity outcomes for patients treated with focal salvage high dose rate brachytherapy for locally recurrent prostate cancer.

INTRODUCTION: Isolated local recurrence of prostate cancer following primary radiotherapy or brachytherapy may be treated with focal salvage high dose rate brachytherapy, although there remains an absence of high quality evidence to support this approach. METHODS: Men with prostate cancer treated consecutively between 2015 and 2018 using 19 Gy in a single fraction high dose rate brachytherapy (HDR) for locally recurrent prostate cancer were identified from an institutional database. Univariable analysis was performed to evaluate the relationship between patient, disease and treatment factors with biochemical progression free survival (bPFS). RESULTS: 43 patients were eligible for evaluation. Median follow up duration was 26 months (range 1-60). Median bPFS was 35 months (95% confidence interval 25.6-44.4). Kaplan-Meier estimates for bPFS at 1, 2 and 3 years post salvage were 95.2%, 70.6% and 41.8% respectively. On univariable Cox regression analysis, only nadir PSA was significantly associated with bPFS although the majority of patients were also treated with androgen deprivation therapy. Only one late grade 3 genitourinary toxicity was observed. CONCLUSION: Focal salvage HDR brachytherapy may provide good biochemical control with a low risk of severe toxicity. Further evaluation within clinical trials are needed to establish its role in the management of locally recurrent prostate cancer.

A comparison of outcomes for patients with intermediate and high risk prostate cancer treated with low dose rate and high dose rate brachytherapy in combination with external beam radiotherapy.

INTRODUCTION: There is evidence to support use of external beam radiotherapy (EBRT) in combination with both low dose rate brachytherapy (LDR-EBRT) and high dose rate brachytherapy (HDR-EBRT) to treat intermediate and high risk prostate cancer. METHODS: Men with intermediate and high risk prostate cancer treated using LDR-EBRT (treated between 1996 and 2007) and HDR-EBRT (treated between 2007 and 2012) were identified from an institutional database. Multivariable analysis was performed to evaluate the relationship between patient, disease and treatment factors with biochemical progression free survival (bPFS). RESULTS: 116 men were treated with LDR-EBRT and 171 were treated with HDR-EBRT. At 5 years, bPFS was estimated to be 90.5% for the LDR-EBRT cohort and 77.6% for the HDR-EBRT cohort. On multivariable analysis, patients treated with HDR-EBRT were more than twice as likely to experience biochemical progression compared with LDR-EBRT (HR 2.33, 95% CI 1.12-4.07). Patients with Gleason ≥8 disease were more than five times more likely to experience biochemical progression compared with Gleason 6 disease (HR 5.47, 95% CI 1.26-23.64). Cumulative incidence of ≥grade 3 genitourinary and gastrointestinal toxicities for the LDR-EBRT and HDR-EBRT cohorts were 8% versus 4% and 5% versus 1% respectively, although these differences did not reach statistical significance. CONCLUSION: LDR-EBRT may provide more effective PSA control at 5 years compared with HDR-EBRT. Direct comparison of these treatments through randomised trials are recommended to investigate this hypothesis further.

Ring Versus Ovoids and Intracavitary Versus Intracavitary-Interstitial Applicators in Cervical Cancer Brachytherapy: Results From the EMBRACE I Study.

PURPOSE: The aim of this study was to investigate the influence of brachytherapy technique and applicator type on target dose, isodose surface volumes, and organ-at-risk (OAR) dose. METHODS AND MATERIALS: Nine hundred two patients treated with tandem/ovoids (T&O) (n = 299) and tandem/ring (T&R) (n = 603) applicators from 16 EMBRACE centers were analyzed. Patients received external beam radiation therapy and magnetic resonance imaging guided brachytherapy with dose prescription according to departmental practice. Centers were divided into 4 groups, according to applicator/technique: Ovoids and ring centers treating mainly with the intracavitary (IC) technique and ovoids and ring centers treating routinely with the intracavitary/interstitial (IC/IS) technique. V85Gy EQD210, CTVHR D90% (EQD210), and bladder, rectum, sigmoid, and vaginal 5-mm lateral-point doses (EQD23) were evaluated among center groups. Differences between T&O and T&R were tested with multivariable analysis. RESULTS: For similar point A doses, mean CTVHR D90% was 3.3 Gy higher and V85Gy was 23% lower for ring-IC compared with ovoids-IC centers (at median target volumes). Mean bladder/rectum doses (D2cm3 and ICRU-point) were 3.2 to 7.7 Gy smaller and vaginal 5-mm lateral-point was 19.6 Gy higher for ring-IC centers. Routine use of IC/IS technique resulted in increased target dose, whereas V85Gy was stable (T&R) or decreased (T&O); reduced bladder and rectum D2cm3 and bladder ICRU-point by 3.5 to 5.0 Gy for ovoids centers; and similar OAR doses for ring centers. CTVHR D90% was 2.8 Gy higher, bladder D2cm3 4.3 Gy lower, rectovaginal ICRU-point 4.8 Gy lower, and vagina 5-mm lateral-point 22.4 Gy higher for ring-IC/IS versus ovoids-IC/IS centers. The P values were <.002 for all comparisons. Equivalently, significant differences were derived from the multivariable analysis. CONCLUSIONS: T&R-IC applicators have better target dose and dose conformity than T&O-IC in this representative patient cohort. IC applicators fail to cover large target volumes, whereas routine application of IC/IS improves target and OAR dose considerably. Patients treated with T&R show a more favorable therapeutic ratio when evaluating target, bladder/rectum doses, and V85Gy. A comprehensive view on technique/applicators should furthermore include practical considerations and clinical outcome.

A standardised method for use of the Leksell GammaPlan Inverse Planning module for metastases.

AIM: The aim of this investigation was to develop a standardised method for using the inverse planning module in Leksell GammaPlan. METHODS: Leksell GammaPlan version 10 and higher contains an inverse planning module, consisting of functions to automatically fill a target volume with shots and subsequently optimise their resulting dosimetry. A standardised method for using the inverse planning module was developed for metastases, using the following optimisation parameter weightings: {coverage 0.9, selectivity 0.1, gradient index (GI) 0.2, }. 25 plans produced using these parameters were compared to manually produced clinical plans. Additionally, the 25 plans were manually adjusted to match the coverage of the clinical plans, and comparison of the PCI, GI and BOT was made. RESULTS: The average parameters for plans produced using the optimisation module were; coverage 98.7%; Paddick conformity index (PCI) 0.85; GI 2.75, compared to coverage 99.5%; PCI 0.83; GI 2.70 for manual clinical plans with BOT 21% shorter than clinical plans on average. The average parameters for the plans produced by the optimisation module after manual adjustment to match the coverage of the clinical plans were: coverage 99.5, PCI 0.83, GI 2.73 with BOT 16% shorter than clinical plans on average. CONCLUSIONS: The standardised method for using the optimisation module has potential for shortening treatment times and planning times.

A high-precision, geometric and registration accuracy full-system test method for adaptive SRS, demonstrated on Gamma Knife® Icon™.

A novel full-system test (FST) phantom and method have been developed to demonstrate and quality assure the geometric accuracy of image co-registration and overall shot delivery in the context of SRS using Gamma Knife® Icon™. The method uses Vernier scale bars to achieve sub-voxel precision co-registration measurements and pin-located radiochromic films to determine overall shot delivery precision. Validation tests demonstrated that artificially applied registration errors of < 0.15 mm could be accurately detected and quantified. Cross-validation of full-system test results with the manufacturer standard focal precision test demonstrated that both approaches measure similar focal precision errors, to within < 0.1 mm, and that registration and focal precision components of the full-system geometric error can be successfully decoupled using our Vernier FST approach. CBCT co-registration errors were shown to be of comparable magnitude to the focal precision errors, demonstrating that CBCT registration based in-mask treatments can achieve sub-voxel geometric accuracy, rivalling traditional frame-based immobilisation. This full-system geometric test method and phantom design concept is in principle applicable to any SRS technique involving image co-registration.

Intra-fraction motion gating during frameless Gamma Knife® Icon™ therapy: The relationship between cone beam CT assessed intracranial anatomy displacement and infrared-tracked nose marker displacement.

METHODS: Gamma Knife Icon™'s high-definition motion management (HDMM) system gates treatment delivery should intra-fraction displacement of a nose marker exceed some user-defined threshold. A method, previously-validated with a phantom, is used to relate intra-fractional displacements of the nose marker to displacements of patient targets. Additionally, novel analysis is performed to ascertain the relationship between nose marker displacement and displacement of a 3D grid of coordinates throughout stereotactic space. This spatial information is used to retrospectively review HDMM threshold levels based upon real target locations. RESULTS: For 41 targets from 22 patients, the mean(standard deviation) and maximum target-to-nose displacement ratio was 0.54(0.32) and 1.65, respectively. On average, displacements typically exceed those of the nose only for coordinates at the most extreme peripheral corner of the investigated 3D grid of points. Allowing target displacement of up to a maximum of 0.8mm, retrospective review indicated that at the locations of the 41 targets a median(range) HDMM threshold of 1.4(1.0-1.9) mm could have been adopted, compared to our standard threshold of 1.0mm. CONCLUSIONS: Intracranial targets typically displace by a magnitude around half that of the nose. Novel analysis to determine the spatial variation of target-to-nose displacement ratio suggests, for our 41 targets, HDMM threshold could have been increased from our standard. Cases for which HDMM threshold could be safely increased would minimise treatment gating events and expedite treatment delivery to offer patient comfort benefits.

A comparison of the convolution and TMR10 treatment planning algorithms for Gamma Knife® radiosurgery.

AIMS: To compare the accuracies of the convolution and TMR10 Gamma Knife treatment planning algorithms, and assess the impact upon clinical practice of implementing convolution-based treatment planning. METHODS: Doses calculated by both algorithms were compared against ionisation chamber measurements in homogeneous and heterogeneous phantoms. Relative dose distributions calculated by both algorithms were compared against film-derived 2D isodose plots in a heterogeneous phantom, with distance-to-agreement (DTA) measured at the 80%, 50% and 20% isodose levels. A retrospective planning study compared 19 clinically acceptable metastasis convolution plans against TMR10 plans with matched shot times, allowing novel comparison of true dosimetric parameters rather than total beam-on-time. Gamma analysis and dose-difference analysis were performed on each pair of dose distributions. RESULTS: Both algorithms matched point dose measurement within ±1.1% in homogeneous conditions. Convolution provided superior point-dose accuracy in the heterogeneous phantom (-1.1% v 4.0%), with no discernible differences in relative dose distribution accuracy. In our study convolution-calculated plans yielded D99% 6.4% (95% CI:5.5%-7.3%,p<0.001) less than shot matched TMR10 plans. For gamma passing criteria 1%/1mm, 16% of targets had passing rates >95%. The range of dose differences in the targets was 0.2-4.6Gy. CONCLUSIONS: Convolution provides superior accuracy versus TMR10 in heterogeneous conditions. Implementing convolution would result in increased target doses therefore its implementation may require a revaluation of prescription doses.

Importance of dynamic contrast enhanced magnetic resonance imaging for targeting biopsy and salvage treatments after prostate cancer recurrence.

PURPOSE: Evaluate T2 weighted MRI (T2W), diffusion weighted imaging (DWI), and dynamic contrast enhanced MRI (DCE-MRI) for determining areas of prostate cancer recurrence to target biopsy or salvage treatment in patients previously treated with I-125 seed brachytherapy. MATERIAL AND METHODS: MRI data from 15 patients, whose primary treatment was I-125 seed brachytherapy and who were subsequently treated with partial gland salvage high-dose-rate brachytherapy were retrospectively analyzed. Two radiologists independently reviewed imaging on two occasions blinded to clinical and biopsy information. At first review, the T2W and DWI sequences were assessed for likely presence of tumor and at second review, the additional DCE-MRI sequence was assessed. Results were recorded and compared on a prostate diagram divided into 12 sectors (quadrants at each of base, mid-gland, and apex) plus seminal vesicles (SV). RESULTS: Number of patients for whom recurrence was visible was 7/15 for T2W, 6.5/15 for DWI, and 15/15 for DCE-MRI (average of results for the two radiologists). Approximately, half of the sectors identified as showing recurrence were at the anterior base of the prostate. CONCLUSIONS: In prostate cancer patients previously treated with I-125 permanent seed implants, DCE-MRI is superior to T2W and DWI in defining areas of recurrence, and should be used to target biopsy and for treatment planning of focal salvage therapies.

Isodose surface volumes in cervix cancer brachytherapy: Change of practice from standard (Point A) to individualized image guided adaptive (EMBRACE I) brachytherapy.

PURPOSE: To investigate the isodose surface volumes (ISVs) for 85, 75 and 60 Gy EQD2 for locally advanced cervix cancer patients. MATERIALS AND METHODS: 1201 patients accrued in the EMBRACE I study were analysed. External beam radiotherapy (EBRT) with concomitant chemotherapy was followed by MR based image-guided adaptive brachytherapy (MR-IGABT). ISVs were calculated using a predictive model based on Total Reference Air Kerma and compared to Point A-standard loading systems. Influence of fractionation schemes and dose rates was evaluated through comparison of ISVs for α/ß 10 Gy and 3 Gy. RESULTS: Median V85 Gy, V75 Gy and V60 Gy EQD210 were 72 cm3, 100 cm3 and 233 cm3, respectively. Median V85 Gy EQD210 was 23% smaller than in standard 85 Gy prescription to Point A. For small (<25 cm3), intermediate (25-35 cm3) and large (>35 cm3) CTVHR volumes, the V85 Gy was 57 cm3, 70 cm3 and 89 cm3, respectively. In 38% of EMBRACE patients the V85 Gy was similar to standard plans with 75-85 Gy to Point A. 41% of patients had V85 Gy smaller than standard plans receiving 75 Gy at Point A, while 21% of patients had V85 Gy larger than standard plans receiving 85 Gy at Point A. CONCLUSIONS: MR-IGABT and individualized dose prescription during EMBRACE I resulted in improved target dose coverage and decreased ISVs compared to standard plans used with classical Point A based brachytherapy. The ISVs depended strongly on CTVHR volume which demonstrates that dose adaptation was performed per individual tumour size and response during EBRT.

Comprehensive I-125 multi-seed comparison for prostate brachytherapy: dosimetry and visibility analysis.

PURPOSE: To compare the visibility of different manufacturers I-125, seeds, and to investigate the effect of differences in dosimetry on treatment planning. MATERIALS AND METHODS: Oncura Oncoseed, Oncura Echoseed, IBT Intersource, Bebig Isoseed and Nucletron Selectseed were investigated. The point dose at increasing distances from each seed type was calculated for three different angles; theta=0 degrees, 45 degrees and 90 degrees (where theta=0 degrees lies parallel to seed length). 10 patient plans were used to assess the effect of a change in dosimetry on treatment planning and quality of prostate and rectum implant indices such as Vp100, Vp200, Dp90, Vr100 and Vr69. All implant indices and dosimetry data were compared to Oncoseed. Visibility under X-ray, fluoroscopy, CT and MRI was investigated using prostate phantoms created in-house. Statistical significance was calculated using paired two-tailed t-tests. RESULTS: Dosimetric analysis was carried out for seeds of the same source strength. Differences in dose increase closer to the centre of each source, with the largest changes occurring for the angle theta=0 degrees. Selectseed and Isoseed seed types provide a consistently lower dose in all three directions. Changes to Vp100 are small and statistically insignificant for all seeds except Selectseed which shows a statistically significant decrease of 0.04% (p=0.02). Changes to Vp150 and Vp200 are statistically significant (p<0.01), with Intersource showing the greatest increase in both values. Selectseed shows a decrease in both Vp150 and Vp200. Echoseed shows an increase in both Vp150 and Vp200. Changes to D90 are statistically significant (p<0.01), with Intersource showing the greatest increase, followed by Isoseed then Echoseed. Selectseed shows a decrease in D90. For Vr100 there is no statistically significant change for any seed type. However, all seeds except Selectseed show a statistically significant increase in the value of Vr69, with Intersource showing the greatest increase. On fluoroscopy and X-ray images, Intersource seeds appear least visible, Echoseed and Oncoseed are similar, and Isoseed and Selectseed are most visible. Ultrasound greyscale beam profiles show that all seed images have a FWHM larger than the Oncoseed image. The CT greyscale beam profiles are similar for all seed images. The MRI signal voids are similar for all seed images except Intersource which shows a larger signal void. CONCLUSIONS: The greatest changes to point dose occur at very close distances to the seeds. Changing seed type may require a treatment replan to maintain satisfactory DVH criteria. Visibility on US and CT is similar, though it may vary on MRI, X-ray and fluoroscopy.

High dose rate brachytherapy in combination with external beam radiotherapy in the radical treatment of prostate cancer: initial results of a randomised phase three trial.

BACKGROUND AND PURPOSE: A randomised phase III trial has compared external beam radiotherapy alone with a dose escalated schedule using high dose rate brachytherapy. Patients with histologically confirmed prostate cancer, no evidence of metastases, a PSA <50, no previous TURP and fit for general anaesthetic were included. METHODS: Patients were randomised to receive either standard radiotherapy 55 Gy in 20 fractions treating Monday to Friday over 4 weeks or a combined schedule comprising external beam treatment delivering 35.75 Gy in 13 fractions treating daily Monday to Friday over 2.5 weeks followed by a temporary high dose rate afterloading implant delivering 17 Gy in two fractions over 24h. RESULTS: A total of 220 patients were randomised, balanced for important prognostic parameters including tumour stage, presenting PSA, Gleason score and use of adjuvant anti-androgens. With a median follow up of 30 months (range 3-91) a significant improvement in actuarial biochemical relapse-free survival is seen in favour of the combined brachytherapy schedule (p=0.03). A lower incidence of acute rectal discharge was seen in the brachytherapy group (p=0.025) and other acute and late toxicities were equivalent. Patients randomised to brachytherapy had a significantly better FACT-P score at 12 weeks (p=0.02). CONCLUSIONS: The use of high dose rate brachytherapy in combination with external beam radiotherapy resulted in an improved biochemical relapse-free survival compared to external beam radiotherapy alone with less acute rectal toxicity and improved quality of life in this randomised trial.