Background and purposeA substantial reduction of uncertainties in clinical brachytherapy should result in improved outcome in terms of increased local control and reduced side effects. Types of uncertainties have to be identified, grouped, and quantified.MethodsA detailed literature review was performed to identify uncertainty components and their relative importance to the combined overall uncertainty.ResultsVery few components (e.g., source strength and afterloader timer) are independent of clinical disease site and location of administered dose. While the influence of medium on dose calculation can be substantial for low energy sources or non-deeply seated implants, the influence of medium is of minor importance for high-energy sources in the pelvic region. The level of uncertainties due to target, organ, applicator, and/or source movement in relation to the geometry assumed for treatment planning is highly dependent on fractionation and the level of image guided adaptive treatment. Most studies to date report the results in a manner that allows no direct reproduction and further comparison with other studies. Often, no distinction is made between variations, uncertainties, and errors or mistakes. The literature review facilitated the drafting of recommendations for uniform uncertainty reporting in clinical BT, which are also provided. The recommended comprehensive uncertainty investigations are key to obtain a general impression of uncertainties, and may help to identify elements of the brachytherapy treatment process that need improvement in terms of diminishing their dosimetric uncertainties. It is recommended to present data on the analyzed parameters (distance shifts, volume changes, source or applicator position, etc.), and also their influence on absorbed dose for clinically-relevant dose parameters (e.g., target parameters such as D90 or OAR doses). Publications on brachytherapy should include a statement of total dose uncertainty for the entire treatment course, taking into account the fractionation schedule and level of image guidance for adaptation.ConclusionsThis report on brachytherapy clinical uncertainties represents a working project developed by the Brachytherapy Physics Quality Assurances System (BRAPHYQS) subcommittee to the Physics Committee within GEC-ESTRO. Further, this report has been reviewed and approved by the American Association of Physicists in Medicine.

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Purpose: To evaluate the performance of radiomic features (RF) derived from PSMA PET for intraprostatic tumor discrimination and non-invasive characterization of Gleason score (GS) and pelvic lymph node status. Patients and methods: Patients with prostate cancer (PCa) who underwent [ 68 Ga]-PSMA-11 PET/CT followed by radical prostatectomy and pelvic lymph node dissection were prospectively enrolled (n=20). Coregistered histopathological gross tumor volume (GTV-Histo) in the prostate served as reference. 133 RF were derived from GTV-Histo and from manually created segmentations of the intraprostatic tumor volume (GTV-Exp). Spearman´s correlation coefficients (ρ) were assessed between RF derived from the different GTVs. We additionally analyzed the differences in RF values for PCa and non-PCa tissues. Furthermore, areas under receiver-operating characteristics curves (AUC) were calculated and uni- and multivariate analyses were performed to evaluate the RF based discrimination of GS 7 and ≥8 disease and of patients with nodal spread (pN1) and non-nodal spread (pN0) in surgical specimen. The results found in the latter analyses were validated by a retrospective cohort of 40 patients. Results: Most RF from GTV-Exp showed strong correlations with RF from GTV-Histo (86% with ρ>0.7). 81% and 76% of RF from GTV-Exp and GTV-Histo significantly discriminated between PCa and non-PCa tissue. The texture feature QSZHGE discriminated between GS 7 and ≥8 considering GTV-Histo (AUC=0.93) and GTV-Exp (prospective cohort: AUC=0.91 / validation cohort: AUC=0.84). QSZHGE also discriminated between pN1 and pN0 disease considering GTV-Histo (AUC=0.85) and GTV-Exp (prospective cohort: AUC=0.87 / validation cohort: AUC=0.85). In uni- and multivariate analyses including patients of both cohorts QSZHGE was a statistically significant (p<0.01) predictor for PCa patients with GS ≥8 tumors and pN1 status. Conclusion: RF derived from PSMA PET discriminated between PCa and non-PCa tissue within the prostate. Additionally, the texture feature QSZHGE discriminated between GS 7 and GS ≥8 tumors and between patients with pN1 and pN0 disease. Our results support the role of RF in PSMA PET as a new tool for non-invasive PCa discrimination and characterization of its biological properties.

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A multiobjective gradient-based algorithm has been developed for the purpose of dose distribution optimization in external beam conformal radiotherapy. This algorithm is based on the concept of gathering the values of all objectives into a single value. The weighting factors of the composite objective values are varied in different steps, allowing the reconstruction of the trade-off surfaces (three or more objectives) or curves (two objectives) which define the boundary between the feasible and non-feasible domain regions. The analysis of these curves allows the decision-maker to select the solution that best fits the clinical goals. In contrast to all the other algorithms, our method provides not a single solution but a sample of solutions representing all possible clinical importance factors (weights) for the objectives used. The application of this algorithm to two test cases shows that a correct selection for the importance factors to multiply the individual objectives in the global objective value is not trivial and that the location and shape of the boundary region between the feasible and non-feasible solution regions are case dependent. Provided that the individual objective functions are analytically differentiable and that the number of objectives is the range of two to three, the computation times are acceptable for clinical use. Furthermore, the optimization for a unique combination of importance factors within the aggregate objective function is performed in less than 1 min.

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This work provides full dosimetric data for the new selectSeed 125I prostate seed source to be distributed by Nucletron B.V. The AAPM TG-43 dosimetric formalism and the new 1999 NIST air kerma strength calibration standard have been followed. Air kerma strength, dose rate constant, radial dose functions, anisotropy functions, and anisotropy factors were calculated using Monte Carlo simulation. Corresponding calculations were also performed for the commercially available 6711 seed source, which is of similar design, for reasons of comparison. The calculated dose rate constant of the selectSeed was 0.954+/-0.005 cGy h(-1) U(-1) compared to 0.953+/-0.005 cGy h(-1) U(-1) for the 6711 source design. The latter value for the 6711 source suggests that the correction factor proposed by NIST for conversion of dose rate constants to the new 1999 NIST calibration standard may be overestimated by 2-3%. Radial dose functions of the two sources were found in good agreement for radial distances up to 4 cm, the selectSeed being less penetrating at greater radial distances (approximately 4% at 10 cm). The selectSeed source presents similar anisotropy characteristics with the 6711 source design. For both source designs, a distance and polar angle dependent discontinuity of anisotropy function values was observed owing to the dose contribution of radioactivity distributed on the ends of the cylindrical source cores. Variation of dosimetric parameters with possible variation in radioactive silver halide coating thickness of the silver source core of the new source was also investigated.

3-D conformal HDR brachytherapy as monotherapy using intraoperative real-time planning is a feasible and highly conformal treatment for localized prostate cancer associated with minimal acute toxicity. Longer follow-up is needed to evaluate late toxicity and biochemical control.