Bacillus Calmette-Guérin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial.

OBJECTIVES: To test whether Bacillus Calmette-Guérin (BCG) vaccination would reduce the incidence of COVID-19 and other respiratory tract infections (RTIs) in older adults with one or more comorbidities. METHODS: Community-dwelling adults aged 60 years or older with one or more underlying comorbidities and no contraindications to BCG vaccination were randomized 1:1 to BCG or placebo vaccination and followed for 6 months. The primary endpoint was a self-reported, test-confirmed COVID-19 incidence. Secondary endpoints included COVID-19 hospital admissions and clinically relevant RTIs (i.e. RTIs including but not limited to COVID-19 requiring medical intervention). COVID-19 and clinically relevant RTI episodes were adjudicated. Incidences were compared using Fine-Gray regression, accounting for competing events. RESULTS: A total of 6112 participants with a median age of 69 years (interquartile range, 65-74) and median of 2 (interquartile range, 1-3) comorbidities were randomized to BCG (n = 3058) or placebo (n = 3054) vaccination. COVID-19 infections were reported by 129 BCG recipients compared to 115 placebo recipients [hazard ratio (HR), 1.12; 95% CI, 0.87-1.44]. COVID-19-related hospitalization occurred in 18 BCG and 21 placebo recipients (HR, 0.86; 95% CI, 0.46-1.61). During the study period, 13 BCG recipients died compared with 18 placebo recipients (HR, 0.71; 95% CI, 0.35-1.43), of which 11 deaths (35%) were COVID-19-related: six in the placebo group and five in the BCG group. Clinically relevant RTI was reported by 66 BCG and 72 placebo recipients (HR, 0.92; 95% CI, 0.66-1.28). DISCUSSION: BCG vaccination does not protect older adults with comorbidities against COVID-19, COVID-19 hospitalization, or clinically relevant RTIs.

Clinical characteristics and risk factors of preventable hospital readmissions within 30 days.

Knowledge regarding preventable hospital readmissions is scarce. Our aim was to compare the clinical characteristics of potentially preventable readmissions (PPRs) with non-PPRs. Additionally, we aimed to identify risk factors for PPRs. Our study included readmissions within 30 days after discharge from 1 of 7 hospital departments. Preventability was assessed by multidisciplinary meetings. Characteristics of the readmissions were collected and 23 risk factors were analyzed. Of the 1120 readmissions, 125 (11%) were PPRs. PPRs occurred equally among different departments (p = 0.21). 29.6% of PPRs were readmitted by a practitioner of a different medical specialty than the initial admission (IA) specialist. The PPR group had more readmissions within 7 days (PPR 54% vs. non-PPR 44%, p = 0.03). The median LOS was 1 day longer for PPRs (p = 0.16). Factors associated with PPR were higher age (p = 0.004), higher socio-economic status (p = 0.049), fewer prior hospital admissions (p = 0.004), and no outpatient visit prior to readmission (p = 0.025). This study found that PPRs can occur at any department in the hospital. There is not a single type of patient that can easily be pinpointed to be at risk of a PPR, probably due to the multifactorial nature of PPRs.

Supplemental Breast MRI for Women with Extremely Dense Breasts: Results of the Second Screening Round of the DENSE Trial.

Background In the first (prevalent) supplemental MRI screening round of the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial, a considerable number of breast cancers were found at the cost of an increased false-positive rate (FPR). In incident screening rounds, a lower cancer detection rate (CDR) is expected due to a smaller pool of prevalent cancers, and a reduced FPR, due to the availability of prior MRI examinations. Purpose To investigate screening performance indicators of the second round (incidence round) of the DENSE trial. Materials and Methods The DENSE trial (ClinicalTrials.gov: NCT01315015) is embedded within the Dutch population-based biennial mammography screening program for women aged 50-75 years. MRI examinations were performed between December 2011 and January 2016. Women were eligible for the second round when they again had a negative screening mammogram 2 years after their first MRI. The recall rate, biopsy rate, CDR, FPR, positive predictive values, and distributions of tumor characteristics were calculated and compared with results of the first round using 95% CIs and χ2 tests. Results A total of 3436 women (median age, 56 years; interquartile range, 48-64 years) underwent a second MRI screening. The CDR was 5.8 per 1000 screening examinations (95% CI: 3.8, 9.0) compared with 16.5 per 1000 screening examinations (95% CI: 13.3, 20.5) in the first round. The FPR was 26.3 per 1000 screening examinations (95% CI: 21.5, 32.3) in the second round versus 79.8 per 1000 screening examinations (95% CI: 72.4, 87.9) in the first round. The positive predictive value for recall was 18% (20 of 110 participants recalled; 95% CI: 12.1, 26.4), and the positive predictive value for biopsy was 24% (20 of 84 participants who underwent biopsy; 95% CI: 16.0, 33.9), both comparable to that of the first round. All tumors in the second round were stage 0-I and node negative. Conclusion The incremental cancer detection rate in the second round was 5.8 per 1000 screening examinations-compared with 16.5 per 1000 screening examinations in the first round. This was accompanied by a strong reduction in the number of false-positive results. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Moy and Gao in this issue.

Quality of life in patients with liver tumors treated with holmium-166 radioembolization.

Holmium-166 radioembolization is a palliative treatment option for patients with unresectable hepatic malignancies. Its influence on quality of life has not been evaluated yet. Since quality of life is very important in the final stages of disease, the aim of this study was to evaluate the effect of holmium-166 radioembolization on quality of life. Patients with hepatic malignancies were treated with holmium-166 radioembolization in the HEPAR I and II studies. The European Organization for Research and Treatment of Cancer QLQ-C30 and LMC21 questionnaires were used to evaluate quality of life at baseline, 1 week, 6 weeks and at 6, 9 and 12 months after treatment. The course of the global health status and symptom and functioning scales were analyzed using a linear mixed model. Quality of life was studied in a total of 53 patients with a compliance of 94%. Role functioning was the most affected functioning scale. Fatigue and pain were the most affected symptom scales. Changes in almost all categories were most notable at 1 week after treatment. A higher WHO performance score at baseline decreased global health status, physical functioning, role functioning and social functioning and it increased symptoms of fatigue, dyspnea and diarrhea. Quality of life in salvage patients with liver metastases treated with holmium-166 radioembolization was not significantly affected over time, although a striking decline was seen during the first week post-treatment. A WHO performance score > 0 at baseline significantly influenced quality of life.

Supplemental MRI Screening for Women with Extremely Dense Breast Tissue.

BACKGROUND: Extremely dense breast tissue is a risk factor for breast cancer and limits the detection of cancer with mammography. Data are needed on the use of supplemental magnetic resonance imaging (MRI) to improve early detection and reduce interval breast cancers in such patients. METHODS: In this multicenter, randomized, controlled trial in the Netherlands, we assigned 40,373 women between the ages of 50 and 75 years with extremely dense breast tissue and normal results on screening mammography to a group that was invited to undergo supplemental MRI or to a group that received mammography screening only. The groups were assigned in a 1:4 ratio, with 8061 in the MRI-invitation group and 32,312 in the mammography-only group. The primary outcome was the between-group difference in the incidence of interval cancers during a 2-year screening period. RESULTS: The interval-cancer rate was 2.5 per 1000 screenings in the MRI-invitation group and 5.0 per 1000 screenings in the mammography-only group, for a difference of 2.5 per 1000 screenings (95% confidence interval [CI], 1.0 to 3.7; P<0.001). Of the women who were invited to undergo MRI, 59% accepted the invitation. Of the 20 interval cancers that were diagnosed in the MRI-invitation group, 4 were diagnosed in the women who actually underwent MRI (0.8 per 1000 screenings) and 16 in those who did not accept the invitation (4.9 per 1000 screenings). The MRI cancer-detection rate among the women who actually underwent MRI screening was 16.5 per 1000 screenings (95% CI, 13.3 to 20.5). The positive predictive value was 17.4% (95% CI, 14.2 to 21.2) for recall for additional testing and 26.3% (95% CI, 21.7 to 31.6) for biopsy. The false positive rate was 79.8 per 1000 screenings. Among the women who underwent MRI, 0.1% had either an adverse event or a serious adverse event during or immediately after the screening. CONCLUSIONS: The use of supplemental MRI screening in women with extremely dense breast tissue and normal results on mammography resulted in the diagnosis of significantly fewer interval cancers than mammography alone during a 2-year screening period. (Funded by the University Medical Center Utrecht and others; DENSE ClinicalTrials.gov number, NCT01315015.).

Contradiction between amide-CEST signal and pH in breast cancer explained with metabolic MRI.

PURPOSE: Metabolic MRI is a noninvasive technique that can give new insights into understanding cancer metabolism and finding biomarkers to evaluate or monitor treatment plans. Using this technique, a previous study has shown an increase in pH during neoadjuvant chemotherapy (NAC) treatment, while recent observation in a different study showed a reduced amide proton transfer (APT) signal during NAC treatment (negative relation). These findings are counterintuitive, given the known intrinsic positive relation of APT signal to pH. METHODS: In this study we combined APT MRI and 31 P-MRSI measurements to unravel the relation between the APT signal and pH in breast cancer. Twenty-two breast cancer patients were scanned with a 7 T MRI before and after the first cycle of NAC treatment. pH was determined by the chemical shift of inorganic phosphate (Pi). RESULTS: While APT signals have a positive relation to pH and amide content, we observed a direct negative linear correlation between APT signals and pH in breast tumors in vivo. CONCLUSIONS: As differentiation of cancer stages was confirmed by observation of a linear correlation between cell proliferation marker PE/Pi (phosphoethanolamine over inorganic phosphate) and pH in the tumor, our data demonstrates that the concentration of mobile proteins likely supersedes the contribution of the exchange rate to the APT signal.

MRI guided focal HDR brachytherapy for localized prostate cancer: Toxicity, biochemical outcome and quality of life.

PURPOSE: To describe toxicity, biochemical outcome and quality of life after MRI guided focal high dose rate brachytherapy (HDR-BT) in a single fraction of 19 Gy for localized prostate cancer. MATERIALS AND METHODS: Between May 2013 and April 2016, 30 patients were treated by MRI-guided focal HDR-BT. Patients with visible tumour on MRI were included. All patients were ≥65 years, T-stage

Additional hepatic 166Ho-radioembolization in patients with neuroendocrine tumours treated with 177Lu-DOTATATE; a single center, interventional, non-randomized, non-comparative, open label, phase II study (HEPAR PLUS trial).

BACKGROUND: Neuroendocrine tumours (NET) consist of a heterogeneous group of neoplasms with various organs of origin. At diagnosis 21% of the patients with a Grade 1 NET and 30% with a Grade 2 NET have distant metastases. Treatment with peptide receptor radionuclide therapy (PRRT) shows a high objective response rate and long median survival after treatment. However, complete remission is almost never achieved. The liver is the most commonly affected organ in metastatic disease and is the most incriminating factor for patient survival. Additional treatment of liver disease after PRRT may improve outcome in NET patients. Radioembolization is an established therapy for liver metastasis. To investigate this hypothesis, a phase 2 study was initiated to assess effectiveness and toxicity of holmium-166 radioembolization (166Ho-RE) after PRRT with lutetium-177 (177Lu)-DOTATATE. METHODS: The HEPAR PLUS trial ("Holmium Embolization Particles for Arterial Radiotherapy Plus 177 Lu-DOTATATE in Salvage NET patients") is a single centre, interventional, non-randomized, non-comparative, open label study. In this phase 2 study 30-48 patients with > 3 measurable liver metastases according to RECIST 1.1 will receive additional 166Ho-RE within 20 weeks after the 4th and last cycle of PRRT with 7.4 GBq 177Lu-DOTATATE. Primary objectives are to assess tumour response, complete and partial response according to RECIST 1.1, and toxicity, based on CTCAE v4.03, 3 months after 166Ho-RE. Secondary endpoints include biochemical response, quality of life, biodistribution and dosimetry. DISCUSSION: This is the first prospective study to combine PRRT with 177Lu-DOTATATE and additional 166Ho-RE in metastatic NET. A radiation boost on intrahepatic disease using 166Ho-RE may lead to an improved response rate without significant additional side-effects. TRIAL REGISTRATION: Clinicaltrials.gov NCT02067988 , 13 February 2014. Protocol version: 6, 30 november 2016.

Accuracy of SPECT/CT-based lung dose calculation for Holmium-166 hepatic radioembolization before OSEM convergence.

PURPOSE: In intra-arterial hepatic radioembolization using Holmium-166 (166 Ho) microspheres, a predicted lung-absorbed dose of more than 30 Gy is a contraindication for therapy. Therefore, scout imaging by means of quantitative SPECT of the lungs after a low-dose pretreatment session is essential. Earlier we showed the superiority of Monte Carlo-based iterative SPECT reconstructions over conventional reconstructions due to its quantitative nature, required for dosimetry, at the cost of substantial computation times. In clinical routine, however, the limited available time between scout imaging and therapy constrains its application. To reduce computation times, we investigated the minimum number of iterations required to guarantee a clinical acceptable accuracy in lung dose estimation using patient and phantom data. METHODS: 166 Ho scout SPECT data (range: 222-283 MBq) were used from 10 patients. SPECT images were Monte Carlo-based OSEM reconstructed (effective iterations: 240). Additionally, the 4D XCAT anthropomorphic phantom was used to mimic studies with an injected scout activity of 250 MBq and with varying lung-absorbed doses ranging from 0.9 to 225 Gy for a therapeutic dosage of 15 GBq. These studies were reconstructed in the same way as the patient data, and were also reconstructed using a clinically available, standard OSEM algorithm for comparison. Lung-absorbed dose was determined using VOI analysis as a function of iterations. RESULTS: The estimated lung-absorbed dose in nine patients ranged upon MC-based OSEM convergence from 0 to 0.26 Gy for a therapeutic dosage. One patient had an estimated lung absorbed-dose for a therapeutic dosage of 20.3 Gy upon MC-based OSEM convergence, or 18.4 Gy after 40 iterations (-9%). The phantom data showed that the lung-absorbed dose upon OSEM convergence was underestimated by 15% as compared to the actual simulated lung dose, and the dose after 40 iterations was underestimated by 9% as compared to the dose upon convergence. Both underestimations were irrespective of the magnitude of the lung-absorbed dose (0.9 to 225 Gy) and thus can be easily corrected for. The quantitative accuracy of the MC-based OSEM reconstructions (40 iterations, before convergence) outperformed the clinical OSEM reconstruction while estimating the lung dose. CONCLUSIONS: The number of effective iterations necessary for quantitative estimation of the lung dose using MC-based OSEM can be reduced from 240 to 40. The resulting sixfold reduction in calculation time enables processing of the scout images before therapy administration.

Radioembolisation in Europe: A Survey Amongst CIRSE Members.

INTRODUCTION: Radioembolisation of liver tumours demands many choices from the physician regarding planning of treatment and subsequent follow-up. METHODS: An online questionnaire was distributed amongst all members of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) to investigate the current state of radioembolisation practice. RESULTS: The survey was completed by 60 centres. The increasing number of radioembolisation procedures may reflect that radioembolisation is increasingly recognised as a valuable treatment option in European cancer guidelines. Imaging modalities play an important role in decision making. Furthermore, there seems to be a trend towards less coil-embolisation of non-target vessels. In addition, type of microsphere, model for dose calculation, complications and future developments are evaluated in this article. CONCLUSIONS: This survey provides insight into the current state of radioembolisation practice across Europe.

Efficacy of Radioembolization with 166Ho-Microspheres in Salvage Patients with Liver Metastases: A Phase 2 Study.

Radioembolization of liver malignancies with 166Ho-microspheres has been shown to be safe in a phase 1 dose-escalation study. The purpose of this study was to investigate the efficacy of 166Ho radioembolization. Methods: In this prospective single-arm study, 56 patients were enrolled, all with liver metastases refractory to systemic therapy and ineligible for surgical resection. The primary outcome was a response by 2 target lesions on triphasic liver CT scans 3 mo after therapy, as assessed using RECIST, version 1.1. Secondary outcomes included overall tumor response, time to imaging progression, overall survival, toxicity, quality of life, and quantification of the microspheres on SPECT and MRI. Results: Between May 2012 and March 2015, 38 eligible patients were treated, one of whom was not evaluable. In 27 (73%) of 37 patients, the target lesions showed complete response, partial response, or stable disease (disease control) at 3 mo (95% confidence interval [CI], 57%-85%). The median overall survival was 14.5 mo (95% CI, 8.6-22.8 mo). For colorectal cancer patients (n = 23), the median overall survival was 13.4 mo (95% CI, 8.2-15.7 mo). Grade 3 or 4 toxic events after treatment (according to the Common Terminology Criteria for Adverse Events, version 4.03) included abdominal pain (in 18% of patients), nausea (8%), ascites (3%), fatigue (3%), gastric stenosis (3%), hepatic failure (3%), liver abscesses (3%), paroxysmal atrial tachycardia (3%), thoracic pain (3%), upper gastrointestinal hemorrhage (3%), and vomiting (3%). On SPECT, 166Ho could be quantified with high accuracy and precision, with a mean overestimation of 9.3% ± 7.1% in the liver. Conclusion: Radioembolization with 166Ho-microspheres induced a tumor response with an acceptable toxicity profile in salvage patients with liver metastases.

Eligibility of patients for minimally invasive breast cancer therapy based on MRI analysis of tumor proximity to skin and pectoral muscle.

There is growing interest in minimally invasive breast cancer therapy. Eligibility of patients is, however, dependent on several factors related to the tumor and treatment technology. The aim of this study is to assess the proportion of patients eligible for minimally invasive breast cancer therapy for different safety and treatment margins based on breast tumor location. Patients with invasive ductal cancer were selected from the MARGINS cohort. Semiautomatic segmentation of tumor, skin, and pectoral muscle was performed in Magnetic Resonance images. Shortest distances of tumors to critical organs (ie, skin and pectoral muscle) were calculated. Proportions of eligible patients were determined for different safety and treatment margins. Three-hundred-forty-eight patients with 351 tumors were included. If a 10 mm safety margin to skin and pectoral muscle is required without treatment margin, 72.3% of patients would be eligible for minimally invasive treatment. This proportion decreases to 45.9% for an additional treatment margin of 5 mm. Shortest distances between tumors and critical organs are larger in older patients and in patients with less aggressive tumor subtypes. If a 10 mm safety margin to skin and pectoral muscle is required, more than two-thirds of patients would be eligible for minimally invasive breast cancer therapy.

Anatomic versus Metabolic Tumor Response Assessment after Radioembolization Treatment.

PURPOSE: To assess applicability of metabolic tumor response assessment on 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) after radioembolization (RE) in patients with colorectal liver metastases (CRLM) by comparison with one-dimensional size-based response assessment on MR imaging. MATERIALS AND METHODS: This prospective cohort study comprised 38 patients with CRLM undergoing RE. MR imaging and 18F-FDG PET/CT imaging were performed at baseline, 1 month (n = 38), and 3 months (n = 21). Longest tumor diameter (LTD) reduction on MR imaging at these time points was compared with reduction in total lesion glycolysis (TLG) on 18F-FDG PET/CT. Hepatic response was compared between RECIST and total liver TLG and correlated with overall survival (OS). RESULTS: TLG and LTD were positively correlated in 106 analyzed metastases (38 patients) at 1 month and 58 metastases (22 patients) at 3 months. Agreement was poor, with LTD underestimating TLG response. A significant association with prolonged OS was found in total liver TLG at 1 month (HR 0.64, P < .01) and 3 months (HR 0.43, P < .01). For LTD, a significant association with OS was found at 3 months (HR 0.10, P < .01). Important differences in liver response classification were found, with total liver TLG identifying more patients and situations where there appeared to be treatment benefit compared with RECIST. CONCLUSIONS: TLG response assessment on 18F-FDG PET/CT appears to be more sensitive and accurate, especially at early follow-up, than size-based response assessment on MR imaging in patients with CRLM treated by RE. Semiautomated liver response assessment with total liver TLG is objective, reproducible, rapid, and prognostic.

The effect of catheter displacement and anatomical variations on the dose distribution in MRI-guided focal HDR brachytherapy for prostate cancer.

PURPOSE: The aim of this study was to analyze the effect of catheter displacement and anatomical variations of prostate and organs at risk on dose distribution in MRI-guided 19 Gy single fraction focal high-dose-rate brachytherapy (HDR-BT) of the prostate. METHODS AND MATERIALS: Seventeen patients with localized prostate cancer were enrolled in a prospective trial investigating focal HDR-BT in a 1.5 T MRI-HDR-BT facility. The diagnostic MRI delineations were registered with intraoperative MR scan, and a single fraction of 19 Gy was applied to the visible tumor. Self-anchoring umbrella catheters were used for HDR-BT delivery. A 1.5 T MRI was performed directly after ultrasound (US)-guided catheter placement for treatment planning. After treatment and before removal of catheters, a posttreatment 1.5 T MRI was performed. Regions of interest were also delineated on the posttreatment MR images and the catheters of 17 patients were reconstructed. The dose plan was constructed for the posttreatment MRI scan to assess the influence of catheter migration and anatomical variation on the dose delivered to the target and the organs at risk. Also on the posttreatment MRI, the complete catheter reconstruction was reassessed, to correct for, for example, bending of the catheters. The displacement of catheters between the MRI scans was determined by comparing the catheter tip positions on the treatment planning and posttreatment 1.5 T MRI scans. RESULTS: The displacements of 241 catheters were investigated. Average (range) displacements of the umbrella catheters are 0.6 (0-2.9) mm in the x-direction, 0.5 (0-2.1) mm in the y-direction, and 0.9 (0-5.5) mm in the z-direction. In 3 patients, the displacement was >4 mm and up to 5.5 mm. This occurred in respectively 1/13, 1/16, and 1/18 catheters in these patients. The dosimetric differences between the intraoperative treatment and the posttreatment plans were in most patients less than 1.5 Gy. In 4 patients, a dose difference in clinical target volume D95 of >2 Gy up to 5.8 Gy was reported. No discrimination can be made between dose differences due to catheter displacement and/or organ movement/anatomy changes. CONCLUSIONS: In general, catheter displacements were in the order of a mm and differences in dose to the clinical target volume and the organs at risk between the treatment and posttreatment plans smaller than 1.5 Gy. In some patients, dose differences up to 5.8 Gy were determined, due to either individual larger catheter displacement and/or anatomy changes. A longer followup is necessary to assess the clinical implications of individual large dose differences.

Safety analysis of holmium-166 microsphere scout dose imaging during radioembolisation work-up: A cohort study.

OBJECTIVE: Radioembolisation is generally preceded by a scout dose of technetium-99m-macroaggregated albumin to estimate extrahepatic shunting of activity. Holmium-166 microspheres can be used as a scout dose (±250 MBq) and as a therapeutic dose. The general toxicity of a holmium-166 scout dose (166Ho-SD) and safety concerns of an accidental extrahepatic deposition of 166Ho-SD were investigated. METHODS: All patients who received a 166Ho-SD in our institute were reviewed for general toxicity and extrahepatic depositions. The absorbed dose in extrahepatic tissue was calculated on SPECT/CT and correlated to clinical toxicities. RESULTS: In total, 82 patients were included. No relevant clinical toxicity occurred. Six patients had an extrahepatic deposition of 166Ho-SD (median administered activity 270 MBq). The extrahepatic depositions (median activity 3.7 MBq) were located in the duodenum (3x), gastric fundus, falciform ligament and the lesser curvature of the stomach, and were deposited in a median volume of 15.3 ml, which resulted in an estimated median absorbed dose of 3.6 Gy (range 0.3-13.8 Gy). No adverse events related to the extrahepatic deposition of the 166Ho-SD occurred after a median follow-up of 4 months (range 1-12 months). CONCLUSION: These results support the safety of 250 MBq 166Ho-SD in a clinical setting. KEY POINTS: • A holmium-166 scout dose is safe in a clinical setting. • Holmium-166 scout dose is a safe alternative for 99m Tc-MAA for radioembolisation work-up. • Holmium-166 scout dose potentially has several benefits over 99m Tc-MAA for radioembolisation work-up.

Early health technology assessment of magnetic resonance-guided high intensity focused ultrasound ablation for the treatment of early-stage breast cancer.

BACKGROUND: Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) ablation is in development for minimally invasive treatment of breast cancer. Cost-effectiveness has not been assessed yet. An early health technology assessment was performed to estimate costs of MR-HIFU ablation, compared to breast conserving treatment (BCT). METHODS: An MR-HIFU treatment model using the dedicated MR-HIFU breast system (Sonalleve, Philips Healthcare) was developed. Input parameters (treatment steps and duration) were based on the analysis of questionnaire data from an expert panel. MR-HIFU experts assessed face validity of the model. Data collected by questionnaires were compared to published data of an MR-HIFU breast feasibility study. Treatment costs for tumours of 1 to 3 cm were calculated. RESULTS: The model structure was considered of acceptable face validity by consulted experts, and questionnaire data and published data were comparable. Costs of MR-HIFU ablation were higher than BCT costs. MR-HIFU best-case scenario costs exceeded BCT costs with approximately €1000. Cooling times and breathing correction contributed most to treatment costs. CONCLUSIONS: MR-HIFU ablation is currently not a cost-effective alternative for BCT. MR-HIFU experience is limited, increasing uncertainty of estimations. The potential for cost-effectiveness increases if future research reduces treatment durations and might substantiate equal or improved results.

Recommendations for radioembolisation after liver surgery using yttrium-90 resin microspheres based on a survey of an international expert panel.

INTRODUCTION: Guidelines on how to adjust activity in patients with a history of liver surgery who are undergoing yttrium-90 radioembolisation (90Y-RE) are lacking. The aim was to study the variability in activity prescription in these patients, between centres with extensive experience using resin microspheres 90Y-RE, and to draw recommendations on activity prescription based on an expert consensus. METHODS: The variability in activity prescription between centres was investigated by a survey of international experts in the field of 90Y-RE. Six representative post-surgical patients (i.e. comparable activity prescription, different outcome) were selected. Information on patients' disease characteristics and data needed for activity calculation was presented to the expert panel. Reported was the used method for activity prescription and whether, how and why activity reduction was found indicated. RESULTS: Ten experts took part in the survey. Recommendations on activity reduction were highly variable between the expert panel. The median intra-patient range was 44 Gy (range 18-55 Gy). Reductions in prescribed activity were recommended in 68% of the cases. In consensus, a maximum DTarget of 50 Gy was recommended. CONCLUSION: With a current lack of guidelines, large variability in activity prescription in post-surgical patients undergoing 90Y-RE exists. In consensus, DTarget ≤50 Gy is recommended. KEY POINTS: • BSA method does not account for a decreased remnant liver volume after surgery. • In post-surgical patients, a volume-based activity determination method is recommended. • In post-surgical patients, a mean D Target of ≤ 50Gy should be aimed for.

Second salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer.

PURPOSE: Salvage treatments for localized radiorecurrent prostate cancer can be performed safely when a focal and image guided approach is used. Due to the low toxicity, the opportunity exists to investigate a second salvage treatment when a second locally recurrent prostate cancer occurs. Here, we describe a second salvage treatment procedure of 4 patients. MATERIAL AND METHODS: Four patients with a pathologically proven second local recurrence were treated in an outpatient magnetic resonance imaging (MRI)-guided setting with a single fraction of 19 Gy focal high-dose-rate brachytherapy (HDR-BT). Delineation was performed using choline-PET-CT or a 68Ga-PSMA PET in combination with multiparametric 3 Tesla MRI in all four patients. Toxicity was measured using common toxicity criteria for adverse events (CTCAE) version 4.0. RESULTS: With a median follow-up of 12 months (range, 6-15), there were 2 patients with biochemical recurrence as defined by the Phoenix-definition. There were no patients with grade 3 or more toxicity. In all second salvage HDR-BT treatments, the constraints for rectum, bladder, and urethra were met. Median treatment volume (GTV) was 4.8 cc (range, 1.9-6.6 cc). A median of 8 catheters (range, 6-9) were used, and the median dose to the treatment volume (GTV) was a D95: 19.3 Gy (SD 15.5-19.4 Gy). CONCLUSIONS: Second focal salvage MRI-guided HDR-BT for a select group of patients with a second locally recurrent prostate cancer is feasible. There was no grade 3 or more acute toxicity for these four patients.

Patient Preferences for Minimally Invasive and Open Locoregional Treatment for Early-Stage Breast Cancer.

BACKGROUND: Noninvasive or minimally invasive treatments are being developed as alternatives to surgery for patients with early-stage breast cancer. Patients' preferences with regard to these new treatments have not been investigated. OBJECTIVES: To assess preferences of patients with breast cancer and of healthy women regarding these new techniques, compared with conventional surgical treatments. METHODS: Six hypothetical breast cancer treatment-outcome scenarios were developed: three standard surgical scenarios (mastectomy, mastectomy with immediate implant-based reconstruction, and breast-conserving therapy [BCT]) and three minimally invasive or noninvasive scenarios (radiofrequency ablation, magnetic resonance-guided high-intensity focused ultrasound ablation, and single-dose ablative radiotherapy). Participants rated treatment-outcome scenarios by visual analogue scale (VAS) and time trade-off (TTO). The Friedman and post hoc Wilcoxon signed-rank tests were used to test whether scores were significantly different from BCT. RESULTS: Seventy-one patients with breast cancer and 50 healthy volunteers participated. Overall, BCT was rated the highest in terms of VAS (0.80) and TTO (0.90) scores. After stratification, BCT ranked the highest in most subgroups, with the exception of healthy individuals, who had given the highest score to ablative boost (VAS, 0.80; TTO, 0.88). Mastectomy with immediate reconstruction was the least preferred in most subgroups. CONCLUSIONS: This study showed no significant preference for minimally invasive treatment for breast cancer. Using hypothetical scenarios, breast cancer survivors attributed the highest scores to BCT, whereas healthy volunteers showed a slight preference for minimally invasive treatments.