Improving plan quality and consistency by standardization of dose constraints in prostate cancer patients treated with CyberKnife.

Treatment plans for prostate cancer patients undergoing stereotactic body radiation therapy (SBRT) are often challenging due to the proximity of organs at risk. Today, there are no objective criteria to determine whether an optimal treatment plan has been achieved, and physicians rely on their personal experience to evaluate the plan's quality. In this study, we propose a method for determining rectal and bladder dose constraints achievable for a given patient's anatomy. We expect that this method will improve the overall plan quality and consistency, and facilitate comparison of clinical outcomes across different institutions. The 3D proximity of the organs at risk to the target is quantified by means of the expansion-intersection volume (EIV), which is defined as the intersection volume between the target and the organ at risk expanded by 5 mm. We determine a relationship between EIV and relevant dosimetric parameters, such as the volume of bladder and rectum receiving 75% of the prescription dose (V75%). This relationship can be used to establish institution-specific criteria to guide the treatment planning and evaluation process. A database of 25 prostate patients treated with CyberKnife SBRT is used to validate this approach. There is a linear correlation between EIV and V75% of bladder and rectum, confirming that the dose delivered to rectum and bladder increases with increasing extension and proximity of these organs to the target. This information can be used during the planning stage to facilitate the plan optimization process, and to standardize plan quality and consistency. We have developed a method for determining customized dose constraints for prostate patients treated with robotic SBRT. Although the results are technology specific and based on the experience of a single institution, we expect that the application of this method by other institutions will result in improved standardization of clinical practice

What is the effect of MRI with targeted biopsies on the rate of patients discontinuing active surveillance? A reflection of the use of MRI in the PRIAS study

Background The reduction of overtreatment by active surveillance (AS) is limited in patients with low-risk prostate cancer (PCa) due to high rates of patients switching to radical treatment. MRI improves biopsy accuracy and could therewith affect inclusion in or continuation of AS. We aim to assess the effect of MRI with target biopsies on the total rate of patients discontinuing AS, and in particular discontinuation due to Grade Group (GG) reclassification. Methods Three subpopulations included in the prospective PRIAS study with GG 1 were studied. Group A consists of patients diagnosed before 2009 without MRI before or during AS. Group B consists of patients diagnosed without MRI, but all patients underwent MRI within 6 months after diagnosis. Group C consists of patients who underwent MRI before diagnosis and during follow-up. We used cumulative incidence curves to estimate the rates of discontinuation. Results In Group A (n = 500), the cumulative probability of discontinuing AS at 2 years is 27.5%; GG reclassification solely accounted for 6.9% of the discontinuation. In Group B (n = 351) these numbers are 30.9 and 22.8%, and for Group C (n = 435) 24.2 and 13.4%. The three groups were not randomized, however, baseline characteristics are highly comparable. Conclusions Performing an MRI before starting AS reduces the cumulative probability of discontinuing AS at 2 years. Performing an MRI after already being on AS increases the cumulative probability of discontinuing AS in comparison to not performing an MRI, especially because of an increase in GG reclassification. These results suggest that the use of MRI could lead to more patients being considered unsuitable for AS. Considering the excellent long-term cancer-specific survival of AS before the MRI era, the increased diagnostic accuracy of MRI could potentially lead to more overtreatment if definitions and treatment options of significant PCa are not adapted.Peer reviewe

Predictive models of toxicity with external radiotherapy for prostate cancer: Clinical issues

The objective of the current study was to analyze the state of the art and present limitations of available predictive clinical models (when available) estimating the risk of genitourinary tract and small bowel complications, erectile dysfunction, and acute and late symptoms of the rectal syndrome caused by prostate cancer external irradiation. An analysis of the literature indicated that very limited attention has been devoted to the development of "integrated," patient-tailored, user-friendly, and clinically usable tools for the prediction of external beam radiotoxicity. In this article, the authors reported on the multivariate correlation between late genitourinary and gastrointestinal toxicities and clinical/dosimetric risk factors, as well as on the first set of nomograms developed to predict acute and late rectal side effects. At the present state of knowledge, the use of nomograms as predictive instruments of radiotoxicity appears to be particularly attractive for several main reasons. They are "user friendly" and easily developed using the results of multivariate analyses, as they weigh the combined effects of multiple independent factors found to be correlated with the selected clinical endpoint. The integrated evaluation of clinical and dosimetric parameters in the single patient can help to provide a tailored probability of the specific outcome considered. Predicting a high probability of toxicity could avoid unnecessary daily costs for the individual patient in terms of quality of life modification during and after treatment, helping patients in the decision-making process of choosing the best individual, quality of life-related treatment, and clinicians in better tailoring the treatment to patient's characteristics

PD-0498: Use of STAT in prostate cancer: correlation with risk factors and identification of residual cohort

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How Does Active Surveillance for Prostate Cancer Affect Quality of Life?:A Systematic Review

The optimal management of screen-detected, localised prostate cancer remains controversial, related to overtreatment issues of screening and the nonrandomised evidence base. Active surveillance (AS) aims to delay or avoid curative therapy but may potentially harm patients' well-being through living with untreated prostate cancer

Erratum to 'Core Biopsies from Prostate Cancer Patients in Active Surveillance Protocols Harbor PTEN and MYC Alterations'[European Urology Oncology 2 (2019) 277-285].

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'Act on oncology' as a new comprehensive approach to assess prostate cancer centres : Method description and results of a pilot study

Background: Multidisciplinary care of prostate cancer is increasingly offered in specialised cancer centres. It requires the optimisation of medical and operational processes and the integration of the different medical and non-medical stakeholders.Objective: To develop a standardised operational process assessment tool basing on the capability maturity model integration (CMMI) able to implement multidisciplinary care and improve process quality and efficiency.Design, Setting, and Participants: Information for model development was derived from medical experts, clinical guidelines, best practice elements of renowned cancer centres, and scientific literature. Data were organised in a hierarchically structured model, consisting of 5 categories, 30 key process areas, 172 requirements, and more than 1500 criteria. Compliance with requirements was assessed through structured on-site surveys covering all relevant clinical and management processes. Comparison with best practice standards allowed to recommend improvements. 'Act On Oncology'(AoO) was applied in a pilot study on a prostate cancer unit in Europe.Results and Limitations: Several best practice elements such as multidisciplinary clinics or advanced organisational measures for patient scheduling were observed. Substantial opportunities were found in other areas such as centre management and infrastructure. As first improvements the evaluated centre administration described and formalised the organisation of the prostate cancer unit with defined personnel assignments and clinical activities and a formal agreement is being worked on to have structured access to First-Aid Posts.Conclusions: In the pilot study, the AoO approach was feasible to identify opportunities for process improvements. Measures were derived that might increase the operational process quality and efficiency

Interim analysis of the REASSURE (Radium-223 alpha Emitter Agent in non-intervention Safety Study in mCRPC popUlation for long-teRm Evaluation) study: patient characteristics and safety according to prior use of chemotherapy in routine clinical practice

Purpose: REASSURE is a global, prospective, non-interventional study to assess long-term safety of radium-223 in patients with bone metastatic castration-resistant prostate cancer. Here we report an interim analysis of patients according to previous use of chemotherapy. Methods: Radium-223 was administered in routine clinical practice. Interim safety analysis was planned after enrolment of the first 600 patients. Patient characteristics and safety data by previous administration of chemotherapy (docetaxel and/or cabazitaxel) were investigated. Results: This interim analysis included 583 patients. Median duration of observation was 7 months (range, 0–20). Nineteen patients treated with concomitant chemotherapy were excluded, 564 (97%) were eligible for exploratory analysis according to prior use of chemotherapy; 190 (34%) had previously received and completed chemotherapy, and 374 (66%) had not. In the prior versus no prior chemotherapy group, a higher proportion of patients had an Eastern Cooperative Oncology Group performance status of ≥2 (22% vs 11%) and > 20 metastatic lesions (26% vs 15%), median alkaline phosphatase (162.0 vs 115.0 U/L) and prostate-specific antigen (132.0 vs 40.2 ng/mL) levels were higher, and a lower proportion completed 6 radium-223 injections (45% vs 63%). Drug-related treatment-emergent adverse events (TEAEs) occurred in 63 and 48%, and haematological drug-related TEAEs in 21 and 9% of patients who had or had not previously received chemotherapy. Four drug-related deaths were reported, all in the prior chemotherapy group. Conclusions: The short-term safety profile of radium-223 in routine clinical practice was comparable to other clinical studies, irrespective of prior chemotherapy use. Haematological TEAEs occurred more frequently in the prior chemotherapy group, presumably due to decreased bone marrow function as a consequence of more advanced disease and prior exposure to cytotoxic therapy. Patients who had not previously received chemotherapy appeared to have a lower burden of disease at baseline, and a lower proportion discontinued radium-223 treatment.Purpose: REASSURE is a global, prospective, non-interventional study to assess long-term safety of radium-223 in patients with bone metastatic castration-resistant prostate cancer. Here we report an interim analysis of patients according to previous use of chemotherapy. Methods: Radium-223 was administered in routine clinical practice. Interim safety analysis was planned after enrolment of the first 600 patients. Patient characteristics and safety data by previous administration of chemotherapy (docetaxel and/or cabazitaxel) were investigated. Results: This interim analysis included 583 patients. Median duration of observation was 7 months (range, 0–20). Nineteen patients treated with concomitant chemotherapy were excluded, 564 (97%) were eligible for exploratory analysis according to prior use of chemotherapy; 190 (34%) had previously received and completed chemotherapy, and 374 (66%) had not. In the prior versus no prior chemotherapy group, a higher proportion of patients had an Eastern Cooperative Oncology Group performance status of ≥2 (22% vs 11%) and > 20 metastatic lesions (26% vs 15%), median alkaline phosphatase (162.0 vs 115.0 U/L) and prostate-specific antigen (132.0 vs 40.2 ng/mL) levels were higher, and a lower proportion completed 6 radium-223 injections (45% vs 63%). Drug-related treatment-emergent adverse events (TEAEs) occurred in 63 and 48%, and haematological drug-related TEAEs in 21 and 9% of patients who had or had not previously received chemotherapy. Four drug-related deaths were reported, all in the prior chemotherapy group. Conclusions: The short-term safety profile of radium-223 in routine clinical practice was comparable to other clinical studies, irrespective of prior chemotherapy use. Haematological TEAEs occurred more frequently in the prior chemotherapy group, presumably due to decreased bone marrow function as a consequence of more advanced disease and prior exposure to cytotoxic therapy. Patients who had not previously received chemotherapy appeared to have a lower burden of disease at baseline, and a lower proportion discontinued radium-223 treatment

A systematic review of methods to immobilise breast tissue during adjuvant breast irradiation

Greater use of 3D conformal, Intensity Modulated Radiotherapy (IMRT) and external beam partial breast irradiation following local excision (LE) for breast cancer has necessitated a review of the effectiveness of immobilisation methods to stabilise breast tissue. To identify the suitability of currently available breast (rather than thorax) immobilisation techniques an appraisal of the literature was undertaken. The aim was to identify and evaluate the benefit of additional or novel immobilisation approaches (beyond the standard supine, single arm abducted and angled breast board technique adopted in most radiotherapy departments). A database search was supplemented with an individual search of key radiotherapy peer-reviewed journals, author searching, and searching of the grey literature. A total of 27 articles met the inclusion criteria. The review identified good reproducibility of the thorax using the standard supine arm-pole technique. Reproducibility with the prone technique appears inferior to supine methods (based on data from existing randomised controlled trials). Assessing the effectiveness of additional breast support devices (such as rings or thermoplastic material) is hampered by small sample sizes and a lack of randomised data for comparison. Attention to breast immobilisation is recommended, as well as agreement on how breast stability should be measured using volumetric imaging. Keywords: Breast, immobilisation, positioning, reproducibility, review.</p