Single-dose high-dose-rate brachytherapy versus two and three fractions for locally advanced prostate cancer.

BACKGROUND: Single-dose high-dose-rate brachytherapy (SD-HDR-BT) was compared to two or three fraction HDR BT in intermediate and high-risk localized prostate cancer with median follow-up of 10 years. MATERIALS AND METHODS: 293 patients received 1 × 19Gy or 1 × 20Gy (Group A = 49), 2 × 13Gy (Group B = 138), or 3 × 10.5 Gy (Group C = 106) HDR BT. The primary endpoint was biochemical relapse-free interval (bRFI). Late genitourinary (GU) and gastrointestinal (GI) morbidity used RTOG scales and the International Prostate Symptom Score (IPSS). Freedom from biochemical relapse (bRFI), overall survival (OS) and GU, GI and IPSS morbidity were calculated using Kaplan-Meier (K-M) method and log-rank test. Univariate and multivariate hazard ratios (HR) were obtained using Cox's proportional hazard. RESULTS: At 10 years, K-M estimates of bRFI were 64 % (Group A), 72 % (Group B), and 76 % (Group C) (p = 0.2). No statistically significant difference was seen in OS. In multivariate analysis risk-category and ADT administration, but not dose, were significant predictors of relapse (p = 0.0003 and 0.03, respectively). At ten years, GU grade 3 events were 8 % (A), 2 % (B) and 13 % (C); (p = 0.01). IPSS ≥ 20 was 31 % (A), 20 % (B) and 23 % (C); (p = 0.6) and grade 3 GI was 0 % in groups A and B and 2 % in C; (p = 0.3). No GU or GI grade-4 events were observed. Pre-treatment IPSS was a highly significant predictor of failure in multivariate analysis. CONCLUSIONS: Long-term outcome data show reduced but not statistically significant difference in PSA control, and no difference in overall survival, between SD-HDR-BT and 2 or 3 fractions of HDR-BT.

Towards estimating the carbon footprint of external beam radiotherapy.

PURPOSE: The National Health Service (NHS) in the United Kingdom (UK) is aiming to be carbon net zero by 2040 to help limit the dangerous effects of climate change. Radiotherapy contributes to this with potential sources quantified here. METHOD: Activity data for 42 patients from within the breast IMRT and prostate VMAT pathways were collected. Data for 20 prostate patients was also collected from 3 other centres to enable cross centre comparison. A process-based, bottom-up approach was used to calculate the carbon footprint. Additionally, patients were split into pre-COVID and COVID groups to assess the impact of protocol changes due to the pandemic. RESULTS: The calculated carbon footprint for prostate and breast pre-COVID were 148 kgCO2e and 101 kgCO2e respectively, and 226 kgCO2e and 75 kgCO2e respectively during COVID. The energy usage by the linac during treatment for a total course of radiotherapy for prostate treatments was 2-3 kWh and about 1 kWh for breast treatments. Patient travel made up the largest proportion (70-80%) of the calculated carbon footprint, with linac idle power second with âˆ¼ 10% and PPE and SF6 leakage were both between 2 and 4%. CONCLUSION: These initial findings highlight that the biggest contributor to the external beam radiotherapy carbon footprint was patient travel, which may motivate increased used of hypofractionation. Many assumptions and boundaries have been set on the data gathered, which limit the wider application of these results. However, they provide a useful foundation for future more comprehensive life cycle assessments.

Dosimetric comparison of volumetric modulated arc therapy (VMAT) and high-dose-rate brachytherapy (HDR-BT) for superficial skin irradiation with significant curvature in one or more planes.

PURPOSE: This study compares the plan quality of high-dose-rate brachytherapy (HDR-BT) and volumetric modulated arc therapy (VMAT) for superficial irradiation of large areas of skin with significant curvature in one or more planes. METHODS: A total of 14 patients from two centres previously treated with either HDR-BT or VMAT were retrospectively replanned using the alternative technique. Sites included scalp and lower limbs. Identical computed tomography (CT) scans, clinical target volume (CTV) and organs at risk (OARs) and prescription were used for both techniques. Conformity, skin surface dose and OAR doses were compared. RESULTS: Conformity index was consistently better with VMAT than HDR-BT (p < 0.01). Maximum skin surface dose (D0.1cc) had a higher mean of 49.6 Gy with HDR-BT compared to 31.4 Gy for VMAT (p < 0.01). Significantly smaller volumes of healthy tissue were irradiated with VMAT than with HDR-BT. This can be seen in brain volumes receiving 10, 20 and 30 Gy EQD2 and in extremities receiving 5 and 10 Gy. When close to the volume, the lens received significantly lower doses with VMAT (p < 0.01). CONCLUSION: In this small sample, VMAT gives equal coverage with lower OAR and skin surface doses than HDR-BT for both scalp and extremities. VMAT is a useful technique for treating large, superficial volumes with significant curvature in one or more planes.

Dosimetry of local failure with single dose 19 Gy high-dose-rate brachytherapy for prostate cancer.

PURPOSE/OBJECTIVE: Long-term follow up of single dose high-dose rate brachytherapy (HDR BT) for localised prostate cancer has revealed higher than expected rates of biochemical and local failure. This study aimed (i) to investigate the pattern of relapse within the prostate with reference to the initial site of disease in those patients; and (ii) to examine if there were any relationships between the HDR BT dosimetric parameters to these areas of recurrence. MATERIALS/METHODS: A retrospective review of treatment records of patients who received 19 Gy single fraction of HDR BT was carried out. A matched pair analysis used one control for each biochemical recurrence case matched with pre-treatment Clinical target volume (CTV) size, Gleason score, T stage, risk category and presence of an identifiable dominant intraprostatic nodule (DIL) for each biochemical recurrence case identified. For all datasets, the pre HDR BT DILs were delineated on the diagnostic pre-treatment T2-weighted MRI and planning CT images. For patients with local recurrence post HDR BT, the recurrent nodules were contoured on the diagnostic T2-weighted MRI and choline PET which were registered to the original HDR BT planning CT. Dosimetric parameters of CTV, planning target volume (PTV), DIL and organs at risk (OARs) were evaluated. Wilcoxon signed-rank test was performed to investigate if there were any significant differences in dosimetric parameters between cases and controls. Cox regression analysis was performed to explore if there were any clinical and dosimetric parameters predicting for biochemical progression free survival (bPFS), local recurrence free survival (LR-PFS) and DIL recurrence free survival (DIL-PFS). RESULTS: Between 2013 and 2018, 180 patients received 19 Gy HDR-BT monotherapy. With a median follow up of 36 months, 19 (10.6%) patients developed biochemical recurrence. Of the 19 patients with biochemical failure, 13 had a local recurrence, including 7 who occurred at the site of DIL. Thirty-eight intermediate/high risk patients were included in the matched pair analysis. No statistically significant differences were found in all CTV, PTV, DIL and OAR dosimetric parameters between cases and controls (p > 0.05). For the Cox regression analysis, none of the covariates investigated were found to be statistically significant factors to predict for bPFS, LC-PFS and DIL-PFS. CONCLUSION: No associations between biochemical recurrences and HDR BT dosimetry were identified in our cohort of patients receiving 19 Gy single fraction HDR BT. A large proportion of recurrences occurred at the site of original disease. HDR BT for intermediate/high risk prostate cancer should be undertaken using a minimum of two fractions.

Risk factors for urethral stricture following external beam radiotherapy and HDR brachytherapy for prostate cancer.

PURPOSE: A potential late side effect of high-dose-rate (HDR) prostate brachytherapy combined with external beam radiotherapy (EBRT) is urethral stricture. The purpose of this study was to evaluate dosimetric parameters possibly contributing to stricture development, including dose to bladder base and D2cc(Gy) within 10 mm of prostatic urethra (D2cc 10 mm), which has, so far, not been reported in the literature. METHODS AND MATERIALS: Patients developing urethral stricture, and matched controls, were identified from a prospective database of those receiving 46 Gy in 23 fractions of EBRT, followed by a single 15 Gy HDR brachytherapy dose. Patients had locally advanced, high- and intermediate-risk prostate cancer. Brachytherapy treatment planning parameters (planning target volume (PTV) size (cm 3), V110(%) bladder base, D2cc 10mm, number of HDR catheters, number of source dwell positions, and total source dwell time within 10 mm of the prostatic urethra) were analyzed to determine potential risk factors for urethral stricture. RESULTS: Seventy-two patients were treated, 22 of whom developed a urethral stricture. Univariate logistic regression performed on the planning parameters identified increased PTV size and D2cc 10 mm, with decreased V110(%) bladder base as risk factors for stricture formation. CONCLUSIONS: It is suggested that PTV size, V110(%) bladder base, and D2cc 10mm are predictive of urethral stricture formation following EBRT and brachytherapy to the prostate. This study demonstrates the importance of minimizing high dwell times and hot spots close to organs at risk and also the correction of any craniocaudal movement of catheters to avoid potential hot spots in the bulbomembranous urethra where there may be increased dose sensitivity.

Randomised trial of external-beam radiotherapy alone or with high-dose-rate brachytherapy for prostate cancer: Mature 12-year results.

BACKGROUND AND PURPOSE: A randomised phase-III trial compared external beam radiotherapy (EBRT) alone with EBRT combined with high-dose-rate brachytherapy boost (HDR-BTb) in localised prostate adenocarcinoma. Previous analysis, at median follow up of 85 months, demonstrated improved relapse free survival (RFS) with EBRT + HDR-BTb. This data has now been updated with a median follow up of 131 months. MATERIALS AND METHODS: From December 1997 to August 2005, patients were assigned either to EBRT alone delivering 55 Gy in 20 fractions over 4 weeks or EBRT followed by a temporary high-dose-rate implant delivering 2 × 8·5 Gy over 24 h. The primary endpoint was RFS defined by a PSA rise ≥2.0 µg/l above nadir, clinical progression or death. Actuarial survival rates and Hazard Ratios (HRs) were calculated using the Kaplan-Meier method and Cox's Proportional Hazard Model, respectively. Secondary endpoints were overall survival (OS), urinary and bowel toxicity. RESULTS: One hundred and six patients received EBRT alone and 110 EBRT + HDR-BTb. Median time to relapse was 137 months in the HDR-BTb arm compared to 82 months for EBRT alone (p = 0·01). A 27% risk of recurrence with EBRT alone was observed (p = 0·001), resulting in a 21% improvement in RFS at 12 years with EBRT + HDR-BTb. In multivariate analysis treatment arm, risk category and no androgen deprivation therapy were significant covariates for risk of relapse. Differences in overall survival were not significant. CONCLUSION: At 12 years there remains a significant improvement in RFS after EBRT + HDR-BTb; both treatments were equitoxic for severe late urinary and bowel events and urethral strictures.

Positron emission tomography PET/CT harmonisation study of different clinical PET/CT scanners using commercially available software.

OBJECTIVES: Harmonisation is the process whereby standardised uptake values from different scanners can be made comparable. This PET/CT pilot study aimed to evaluate the effectiveness of harmonisation of a modern scanner with image reconstruction incorporating resolution recovery (RR) with another vendor older scanner operated in two-dimensional (2D) mode, and for both against a European standard (EARL). The vendor-proprietary software EQ•PET was used, which achieves harmonisation with a Gaussian smoothing. A substudy investigated effect of RR on harmonisation. METHODS: Phantom studies on each scanner were performed to optimise the smoothing parameters required to achieve successful harmonisation. 80 patients were retrospectively selected; half were imaged on each scanner. As proof of principle, a cohort of 10 patients was selected from the modern scanner subjects to study the effects of RR on harmonisation. RESULTS: Before harmonisation, the modern scanner without RR adhered to EARL specification. Using the phantom data, filters were derived for optimal harmonisation between scanners and with and without RR as applicable, to the EARL standard. The 80-patient cohort did not reveal any statistically significant differences. In the 10-patient cohort SUVmax for RR > no RR irrespective of harmonisation but differences lacked statistical significance (one-way ANOVA F(3.36) = 0.37, p = 0.78). Bland-Altman analysis showed that harmonisation reduced the SUVmax ratio between RR and no RR to 1.07 (95% CI 0.96-1.18) with no outliers. CONCLUSIONS: EQ•PET successfully enabled harmonisation between modern and older scanners and against the EARL standard. Harmonisation reduces SUVmax and dependence on the use of RR in the modern scanner. ADVANCES IN KNOWLEDGE: EQ•PET is feasible to harmonise different PET/CT scanners and reduces the effect of RR on SUVmax.

Radionuclide calibrator intercomparison study of clinical PET centres in England to a single traceable 68Ge syringe source.

OBJECTIVES: The aim of this study was to characterize national variation in radionuclide calibrator activity response to a single National Institute of Standards and Technology (NIST) traceable reference Ge source used as a surrogate for F at clinical PET centres in England using National Physical Laboratory approved techniques. METHODS: Readings from 20 instruments at 13 centres using local F and Ge factor settings were recorded with the source located in vial and syringe positions. Ten repeat measurements were conducted to investigate repeatability using % coefficient of variability (COV). Comparison ratios to investigate accuracy were made between calibrator responses and decay-corrected NISTref reference activity for syringe and vial position measurements. RESULTS: The maximum %COV was 0.79%, while 90, 95 and 80% of calibrators conformed to 5% accuracy for F syringe, Ge syringe and Ge vial position readings, respectively. We revealed a trend towards reduced bias in measurements using Veenstra devices for F and using Capintec devices for Ge factor settings. CONCLUSIONS: This study demonstrated good repeatability in local device measurements. In total, 70% of English calibrators tested and 88% of all measurements performed achieved 5% accuracy. While statistically significant bias was exhibited between different vendor equipment dependent upon radioisotope selected, our study recommends regular traceability checks for optimum instrument performance conducted within National Metrology Institutes guidelines.

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 pilot study on dosimetric and radiomics analysis of urethral strictures following HDR brachytherapy as monotherapy for localized prostate cancer.

OBJECTIVE: A cohort of high dose-rate (HDR) monotherapy patients was analyzed to (i) establish the frequency of non-malignant urethral stricture; (ii) explore the relation between stricture formation with the dose distribution along the length of the urethra, and MRI radiomics features of the prostate gland. METHODS: A retrospective review of treatment records of patients who received 19 Gy single fraction of HDR brachytherapy (BT) was carried out. A matched pair analysis used one control for each stricture case matched with pre-treatment International Prostate Symptom Score (IPSS) score, number of needles used and clinical target volume volume for each stricture case identified.For all data sets, pre-treatment T2 weighted MRI images were used to define regions of interests along the urethra and within the whole prostate gland. MRI textural radiomics features-energy, contrast and homogeneity were selected. Wilcoxon signed-rank test was performed to investigate significant differences in dosimetric parameters and MRI radiomics feature values between cases and controls. RESULTS: From Nov 2010 to July 2017, there were 178 patients treated with HDR BT delivering 19 Gy in a single dose. With a median follow-up of 28.2 months, a total of 5/178 (3%) strictures were identified.10 patients were included in the matched pair analysis. The urethral dosimetric parameters investigated were not statistically different between cases and controls (p > 0.05). With regards to MRI radiomics feature analysis, significant differences were found in contrast and homogeneity between cases and controls (p < 0.05). However, this did not apply to the energy feature (p = 0.28). CONCLUSION: In this matched pair analysis, no association between post-treatment stricture and urethral dosimetry was identified. Our study generated a preliminary clinical hypothesis suggesting that the MRI radiomics features of homogeneity and contrast of the prostate gland can potentially identify patients who develop strictures after HDR BT. Although the sample size is small, this warrants further validation in a larger patient cohort. ADVANCES IN KNOWLEDGE: Urethral stricture has been reported as a specific late effect with prostate HDR brachytherapy. Our study reported a relatively low stricture rate of 3% and no association between post-treatment stricture and urethral dosimetry was identified. MRI radiomics features can potentially identify patients who are more prone to develop strictures.

Importance of Technique, Target Selection, Contouring, Dose Prescription, and Dose-Planning in External Beam Radiation Therapy for Cervical Cancer: Evolution of Practice From EMBRACE-I to II.

PURPOSE: To describe the evolution of external beam radiation therapy (EBRT) from EMBRACE-I (general guidelines for EBRT) to the initial phase of the EMBRACE-II study (detailed protocol for EBRT). METHODS AND MATERIALS: EMBRACE-I enrolled 1416 locally advanced cervical cancer patients treated with chemoradiation including image-guided adaptive brachytherapy during 2008 to 2015. From March 2016 until March 2018, 153 patients were enrolled in the ongoing EMBRACE-II study, which involves a comprehensive detailed strategy and accreditation procedure for EBRT target contouring, treatment planning, and image guidance. EBRT planning target volumes (PTVs), treated volumes (V43 Gy), and conformity index (CI; V43 Gy/PTV) were evaluated in both studies and compared. RESULTS: For EMBRACE-I, conformal radiation therapy (60% of patients) or intensity-modulated radiation therapy (IMRT) and volumetric arc therapy (VMAT; 40%) was applied with 45 to 50 Gy over 25 to 30 fractions to the elective clinical target volume (CTV). For pelvic CTVs (82%), median PTV and V43 Gy volumes were 1549 and 2390 mL, respectively, and CI was 1.54. For pelvic plus paraortic nodal (PAN) CTVs (15%), median PTV and V43 Gy volumes were 1921 and 2895 mL, and CI was 1.51. For pelvic CTVs treated with 45 to 46 Gy, the use of conformal radiation therapy was associated with a median V43 Gy volume that was 546 mL larger than with IMRT/VMAT. For pelvic CTVs treated with IMRT, the use of a dose prescription ≥48 Gy was associated with a median V43 Gy volumes that was 428 mL larger than with a dose prescription of 45 to 46 Gy. For EMBRACE-II, all patients were treated with: IMRT/VMAT, daily IGRT, 45 Gy over 25 fractions for the elective CTV, and simultaneously integrated boost for pathologic lymph nodes. For pelvic CTVs (61%), median PTV and V43 Gy volumes were 1388 and 1418 mL, and CI was 1.02. For pelvic plus PAN CTVs (32%), median PTV and V43 Gy volumes were 1720 and 1765 mL, and CI was 1.03. From EMBRACE-I to initial II, median V43 Gy was decreased by 972 mL (41%) and 1130 mL (39%), and median CI decreased from 1.54 to 1.02 and 1.51 to 1.03 for pelvic and pelvic plus PAN irradiation, respectively. CONCLUSIONS: Application of IMRT/VMAT, IGRT, and a 45-Gy dose provides the potential of higher conformality inducing significant reduction of treated volume. Adherence to a detailed protocol including comprehensive accreditation, as in EMBRACE-II, reduces considerably V43 Gy and V50 Gy and improves conformality and interinstitutional consistency.

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.

Focal boost to residual gross tumor volume in brachytherapy for cervical cancer-A feasibility study.

PURPOSE: Image-guided plan optimization with MRI and CT for interstitial and intracavitary brachytherapy is an established technique in treating cervical cancer. The purpose of this study was to assess the feasibility of boosting the dose to the residual gross tumor volume (GTV-Tres) to 140% of the high-risk clinical target volume (HR-CTV) prescription. METHODS AND MATERIALS: Brachytherapy plans from 50 consecutive patients were analyzed in this study. All received external beam radiotherapy followed by brachytherapy (6 Gy × 4 fraction or 7 Gy × 4 fraction to HR-CTV). The original treatment plans were reoptimized escalating the GTV-Tres dose 140% of the original HR-CTV prescription dose to 8.4 Gy and 9.8 Gy/ per fraction, respectively, with the aim of achieving GTV-TresV140 ≥ 90% and D98 ≥ 100 Gy. The HR-CTV coverage and organ at risk (OAR) dose-volume histogram values were kept within the tolerance, which had been accepted for the original clinical plans. RESULTS: A total of 24 patients (48%) achieved the planning goal after reoptimization. There was no significant difference between the D2cc of the OARs of the clinical plan and the study boost plan. The factors having greatest impact on the delivered dose to the GTV-Tres are proximity of the OAR, intrauterine positioned outside the GTV-Tres, and suboptimal interstitial placement for boosting GTV-Tres. CONCLUSIONS: It is possible to boost the prescription dose to the GTV-Tres achieving 140% increase, which equates to an EQD2α/ß=10 > 100 Gy. Plans without both interstitial catheters and/or intrauterine within the GTV-Tres are most likely to be suboptimal. This planning study demonstrates that dose escalation to the GTV-Tres is feasible and further work into clinical application should be considered.

Single-dose high-dose-rate brachytherapy compared to two and three fractions for locally advanced prostate cancer.

BACKGROUND: Single-dose high-dose-rate brachytherapy (HDR-BT), in a Phase-II study, was compared to two or three fractions in intermediate and high-risk localized prostate cancer. PATIENTS AND METHODS: 293 patients received 1×19Gy or 1×20Gy (A=49), 2×13Gy (B=138), or 3×10.5Gy (C=106) and assessed with prospective measures of serum PSA, late genitourinary (GU) and gastrointestinal (GI) morbidity using RTOG scales and the International Prostate Symptom Score (IPSS). RESULTS: Median follow-up is 49, 63 and 108months (A, B and C, respectively). At 4years biochemical relapse free survival was 94% (A), 93% (B) and 91% (C) (p=0.54). Risk-category was the only significant independent predictor of relapse (p<0.0001). Kaplan-Meier 4-year-estimates of GU-3 were 2% (A and B) and 11% (C). GI-3 was 0% (A and B) and 1% (C). No GU or GI grade-4 events were observed. IPSS≥20 was 11% (A), 9% (B) and 16% (C) (p=0.9). Prevalence of GU-3 was ≤4% in the 3 groups at all times; GI-3 was low or non-existent. Prevalence of catheter use was ≤6% in all groups. CONCLUSIONS: A single dose of 19-20Gy achieves similar rates of late morbidity and biochemical control compared to 2 and 3 fractions.

The dosimetric impact of air in vaginal vault brachytherapy.

PURPOSE: Vaginal vault brachytherapy is an adjuvant treatment to reduce risk of local recurrence in endometrial cancer. Axial imaging has demonstrated the presence of air gaps between the surface of a cylindrical applicator and mucosal wall. The impact of these on dosimetry and applicability of the TG-43 formalism in the presence of air has been assessed. METHODS AND MATERIALS: The planning CT scans for a retrospective sample of 82 patients were examined for the presence of air gaps. These were quantified in terms of the radial and longitudinal aspect with reference to the applicator, frequency per patient, and location along the applicator. Monte Carlo calculations and ionization chamber measurements were made in a phantom to estimate the uncertainty of the TG-43 algorithm. RESULTS: The overall incidence of air gaps was 91.4%. The most common radial size was between 2 and 3 mm (43.0%) that resulted in an average dose reduction of 14.8%. There is a strong correlation between radial dimension and TG-43 calculated dose reduction. Monte Carlo simulations and phantom measurements indicated that the inhomogeneity resulted in a maximum of 2.4% deviation from doses calculated using TG-43. CONCLUSIONS: Air gaps are common. TG-43 formalism is not significantly compromised by the presence of air. However, the presence of the air does produce a displacement of the mucosal surface away from the applicator and this causes a significant dose reduction.

Pre-clinical Positron Emission Tomography Reconstruction Algorithm Effect on Cu-64 ATSM Lesion Hypoxia.

OBJECTIVE: Application of distinct positron emission tomography (PET) scan reconstruction algorithms can lead to statistically significant differences in measuring lesion functional properties. We looked at the influence of two-dimensional filtered back projection (2D FBP), two-dimensional ordered subset expectation maximization (2D OSEM), three-dimensional ordered subset expectation maximization (3D OSEM) without 3D maximum a posteriori and with (3D OSEM MAP) on lesion hypoxia tracer uptake using a pre-clinical PET scanner. METHODS: Reconstructed images of a rodent tumor model bearing P22 carcinosarcoma injected with hypoxia tracer Copper-64-Diacetyl-bis (N4-methylthiosemicarbazone) (i.e. Cu-64 ATSM) were analyzed at 10 minute intervals till 60 minute post injection. Lesion maximum standardized uptake values (SUVmax) and SUVmax/background SUVmean (T/B) were recorded and investigated after application of multiple algorithm and reconstruction parameters to assess their influence on Cu-64 ATSM measurements and associated trends over time. RESULTS: SUVmax exhibited convergence for OSEM reconstructions while ANOVA results showed a significant difference in SUVmax or T/B between 2D FBP, 2D OSEM, 3D OSEM and 3D OSEM MAP reconstructions across all time frames. SUVmax and T/B were greatest in magnitude for 2D OSEM followed by 3D OSEM MAP, 3D OSEM and then 2D FBP at all time frames respectively. Similarly SUVmax and T/B standard deviations (SD) were lowest for 2D OSEM in comparison with other algorithms. CONCLUSION: Significantly higher magnitude lesion SUVmax and T/B combined with lower SD were observed using 2D OSEM reconstruction in comparison with 2D FBP, 3D OSEM and 3D OSEM MAP algorithms at all time frames. Results are consistent with other published studies however more specimens are required for full validation.

Image guided brachytherapy in locally advanced cervical cancer: Improved pelvic control and survival in RetroEMBRACE, a multicenter cohort study.

PURPOSE: Image guided brachytherapy (IGBT) for locally advanced cervical cancer allows dose escalation to the high-risk clinical target volume (HRCTV) while sparing organs at risk (OAR). This is the first comprehensive report on clinical outcome in a large multi-institutional cohort. PATIENTS AND METHODS: From twelve centres 731 patients, treated with definitive EBRT±concurrent chemotherapy followed by IGBT, were analysed. Kaplan-Meier estimates at 3/5years were calculated for local control (LC, primary endpoint), pelvic control (PC), overall survival (OS), cancer specific survival (CSS). In 610 patients, G3-4 late toxicity (CTCAEv3.0) was reported. RESULTS: Median follow up was 43months, percent of patients per FIGO stage IA/IB/IIA 22.8%, IIB 50.4%, IIIA-IVB 26.8%. 84.8% had squamous cell carcinomas; 40.5% lymph node involvement. Mean EBRT dose was 46±2.5Gy; 77.4% received concurrent chemotherapy. Mean D90 HRCTV was 87±15Gy (EQD210), mean D2cc was: bladder 81±22Gy, rectum 64±9Gy, sigmoid 66±10Gy and bowel 64±9Gy (all EQD23). The 3/5-year actuarial LC, PC, CSS, OS were 91%/89%, 87%/84%, 79%/73%, 74%/65%. Actuarial LC at 3/5years for IB, IIB, IIIB was 98%/98%, 93%/91%, 79%/75%. Actuarial PC at 3/5years for IB, IIB, IIIB was 96%/96%, 89%/87%, 73%/67%. Actuarial 5-year G3-G5 morbidity was 5%, 7%, 5% for bladder, gastrointestinal tract, vagina. CONCLUSION: IGBT combined with radio-chemotherapy leads to excellent LC (91%), PC (87%), OS (74%), CSS (79%) with limited severe morbidity.

A multicentre 'end to end' dosimetry audit for cervix HDR brachytherapy treatment.

PURPOSE: To undertake the first multicentre fully 'end to end' dosimetry audit for HDR cervix brachytherapy, comparing planned and delivered dose distributions around clinical treatment applicators, with review of local procedures. MATERIALS AND METHODS: A film-dosimetry audit was performed at 46 centres, including imaging, applicator reconstruction, treatment planning and delivery. Film dose maps were calculated using triple-channel dosimetry and compared to RTDose data from treatment planning systems. Deviations between plan and measurement were quantified at prescription Point A and using gamma analysis. Local procedures were also discussed. RESULTS: The mean difference between planned and measured dose at Point A was -0.6% for plastic applicators and -3.0% for metal applicators, at standard uncertainty 3.0% (k=1). Isodose distributions agreed within 1mm over a dose range 2-16Gy. Mean gamma passing rates exceeded 97% for plastic and metal applicators at 3% (local) 2mm criteria. Two errors were found: one dose normalisation error and one applicator library misaligned with the imaged applicator. Suggestions for quality improvement were also made. CONCLUSIONS: The concept of 'end to end' dosimetry audit for HDR brachytherapy has been successfully implemented in a multicentre environment, providing evidence that a high level of accuracy in brachytherapy dosimetry can be achieved.

Dosimetric analysis of urethral strictures following HDR (192)Ir brachytherapy as monotherapy for intermediate- and high-risk prostate cancer.

BACKGROUND AND PURPOSE: To evaluate dosimetric parameters related to urethral strictures following high dose-rate brachytherapy (HDRBT) alone for prostate cancer. MATERIAL AND METHODS: Ten strictures were identified in 213 patients treated with HDRBT alone receiving 34Gy in four fractions, 36Gy in four fractions, 31.5Gy in 3 fractions or 26Gy in 2 fractions. A matched-pair analysis used 2 controls for each case matched for dose fractionation schedule, pre-treatment IPSS score, number of needles used and clinical target volume. The urethra was divided into membranous urethra and inferior, mid and superior thirds of the prostatic urethra. RESULTS: Stricture rates were 3% in the 34Gy group, 4% in the 36Gy group, 6% in the 31.5Gy group and 4% in the 26Gy group. The median time to stricture formation was 26months (range 8-40). The dosimetric parameters investigated were not statistically different between cases and controls. No correlation was seen between stricture rate and fractionation schedule. CONCLUSIONS: Urethral stricture is an infrequent complication of prostate HDRBT when used to deliver high doses as sole treatment, with an overall incidence in this cohort of 10/213 (4.7%). In a matched pair analysis no association with dose schedule or urethral dosimetry was identified, but the small number of events limits definitive conclusions.

Optimal source distribution for focal boosts using high dose rate (HDR) brachytherapy alone in prostate cancer.

PURPOSE: To investigate the optimal distribution of sources using high dose rate brachytherapy to deliver a focal boost to a dominant lesion within the whole prostate gland based on multi-parametric magnetic resonance imaging (mpMRI). METHODS: Sixteen patients with prostate cancer underwent mpMRI each of which demonstrated a dominant lesion. There were single lesions in 6 patients, two lesions in 4 and 3 lesions in 6 patients. Two dosimetric models and parameters were compared in each case. The first model used 10mm intervals between needles, and the second model used additional needles at 5 mm intervals between each needle in the boost area. RESULTS: Three of thirty-two plans did not achieve the plan objectives. These three plans were in the first model. A higher median urethral volume was seen in the 'unsuccessful' group (2.7 cc, and 1.9 cc, respectively, p-value=0.12). Conformity indices of the second model were also better than the first model (COIN index; 0.716 and 0.643, respectively). CONCLUSIONS: Focal monotherapy based on mpMRI achieves optimal dosimetry by individualizing the needle positions using 5mm spacing rather than 10mm spacing within the boost volume. A larger urethral volume may have an adverse effect on this distribution. Formal clinical evaluation of this approach is currently underway.