Retrospective Analysis of Efficacy and Toxicity of Stereotactic Body Radiotherapy and Surgical Resection of Adrenal Metastases from Solid Tumors.

BACKGROUND: This single-center retrospective study aimed to evaluate the efficacy and toxicity profiles of stereotactic body radiotherapy (SBRT) and surgical resection in patients with adrenal metastases originating from solid tumors. METHODS/MATERIALS: Patients with advanced tumor conditions or comorbidities typically received SBRT, whereas those considered physically fit underwent standard surgical treatment. Endpoints included local control (LC), progression free survival (PFS), overall survival (OS), and complication rates (CR). RESULTS: 41 patients with 48 adrenal metastases were included, with 27 (65.9%) patients receiving SBRT and 14 (34.1%) patients undergoing adrenalectomy. One- and two-year LC values were 100% for both periods after adrenalectomy, and 70.0% and 52.5% after SBRT (p = 0.001). PFS showed values of 40.2% and 32.1% at one and two years after adrenalectomy and of 10.6% for both periods after SBRT (p = 0.223). OS was 83.3% both one and two years after surgery and 67.0% and 40.2% after SBRT (p = 0.031). There was no statistically significant difference between the two groups regarding acute complications (p = 0.123). CONCLUSION: Despite potential confounders, adrenalectomy exhibited statistically significant superior LC and OS compared to SBRT in managing adrenal metastases, while both treatment methods displayed acceptable toxicity profiles. However, patient selection bias must be taken into account when directly comparing the two therapy modalities. Nevertheless, the study provides new and important results for the scientific and medical communities regarding oncological outcomes after SBRT or surgical resection of adrenal metastases.

Re-irradiation to the prostate using stereotactic body radiotherapy (SBRT) after initial definitive radiotherapy - A systematic review and meta-analysis of recent trials.

Background: There is increasing data on re-irradiation to the prostate using stereotactic body radiotherapy (SBRT) after definitive radiotherapy for prostate cancer, with increasing evidence on prostate re-irradiation using a C-arm LINAC or an MR LINAC in recent years. We therefore conducted this systematic review and meta-analysis on prostate re-irradiation including studies published from 2020 to 2023, to serve as an update on existing meta-analysis. Methods: We searched the PubMed and Embase databases in October 2023 with queries including combinations of "repeat", "radiotherapy", "prostate", "re-irradiation", "reirradiation", "re treatment", "SBRT", "retreatment". Publication date was set to be from 2020 to 2023. There was no limitation regarding language. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. After data extraction, heterogeneity testing was done by calculating the I2. A random effects model with a restricted maximum likelihood estimator was used to estimate the combined effect. Funnel plot asymmetry was assessed visually and using Egger's test to estimate the presence of publication and/or small study bias. Results: 14 publications were included in the systematic review. The rates of acute ≥ grade 2 (G2) genitourinary (GU) and gastrointestinal (GI) toxicities reported in the included studies ranged from 0.0-30.0 % and 0.0-25.0 % respectively. For late ≥ G2 GU and GI toxicity, the ranges are 4.0-51.8 % and 0.0-25.0 %. The pooled rate of acute GU and GI toxicity ≥ G2 were 13 % (95 % CI: 7-18 %) and 2 % (95 % CI: 0-4 %). For late GU and GI toxicity ≥ G2 the pooled rates were 25 % (95 % CI: 14-35 %) and 5 % (95 % CI: 1-9 %). The pooled 2-year biochemical recurrence-free survival was 72 % (95 % CI: 64-92 %). Conclusions: SBRT in the re-irradiation of radiorecurrent prostate cancer is safe and effective. Further prospective data are warranted.

Discontinuation of Palliative Brain Radiotherapy in Patients with Brain Metastases: A Case-Control Study.

Background: Discontinuation of radiotherapy is rarely discussed in the scientific literature. The goal of this study was, therefore, to estimate the frequency of and reasons for treatment discontinuations in patients receiving radiotherapy for brain metastases from solid tumors and to identify factors predicting said discontinuations. Methods: All patients treated for brain metastases from solid tumors between 2010 and 2020 at our institution were retrospectively reviewed. In addition to collecting relevant patient characteristics, the Recursive Partitioning Analysis (RPA) and disease-specific Graded Prognostic Assessment (GPA) groups for each patient were calculated to assess the performance of these scores in predicting treatment discontinuations. Results: Out of 468 patients who underwent cranial radiotherapy, 35 treatments (7.5%) were discontinued. The most frequent reason was clinical deterioration, which was documented in 26 (74.3%) of discontinued treatments. Patients whose radiotherapy was discontinued had, on average, more leptomeningeal disease (20.0% vs. 12.6%), worse ECOG performance status (mean ECOG performance status 1.86 vs. 1.39), and more uncontrolled extracranial metastases (85.3% vs. 70.8%). The frequencies of treatment discontinuation increased with worse prognosis and differed significantly across RPA groups (p = 0.037) but not across GPA groups (p = 0.612). Conclusions: Treatment discontinuation occurred in 7.5% of cases, mostly due to clinical deterioration. Poor performance status, as well as more advanced disease and, in turn, poor prognosis, were associated with higher discontinuation rates.

Dose-intensified stereotactic body radiotherapy for painful vertebral metastases: A randomized phase 3 trial.

BACKGROUND: The purpose of this randomised study was to determine whether dose-intensified stereotactic body radiotherapy (SBRT) for painful vertebral metastases results in increased rates of pain improvement compared with conventional external beam radiotherapy (cEBRT) (control) 6 months after treatment. METHODS: This randomized, controlled phase 3 trial was conducted between November 2016 and January 2023, when it was stopped early. Patients were eligible if they were aged 18 years or older; had one or two painful, stable, or potentially unstable vertebral metastases; and had a life expectancy of 1 year or longer according to the investigator's estimates. Patients received 48.5 grays (Gy) in 10 fractions (with epidural involvement) or 40 Gy in five fractions (without epidural involvement) in the SBRT group and 30 Gy in 10 fractions or 20 Gy in five fractions in the cEBRT group, respectively. The primary end point was an improvement in the pain score at the treated site by at least 2 points (on a visual analog scale from 0 to 10 points) at 6-month follow-up. Data were analyzed on an intention-to-treat and per-protocol basis. RESULTS: Of 214 patients who were screened for eligibility, 63 were randomized 1:1 between SBRT (33 patients with 36 metastases) and cEBRT (30 patients with 31 metastases). The median age of all patients was 66 years, and 40 patients were men (63.5%). In the intention-to-treat analysis, the 6-month proportion of patients who had metastases with pain reduction by 2 or more points was significantly higher in the SBRT group versus the control group (69.4% vs. 41.9%, respectively; two-sided p = .02). Changes in opioid medication intake relative to baseline were nonsignificant between the groups. No differences were observed in vertebral compression fracture or adverse event rates between the groups. CONCLUSIONS: Dose-intensified SBRT improved pain score more effectively than cEBRT at 6 months.

HER2 Low Expression in Primary Male Breast Cancer.

Purpose: The introduction of HER2-targeting antibody drug conjugates (ADCs) offers new treatment options for female breast cancer patients (FBC) expressing low levels of HER2 (HER2 low). No evidence was found that HER2 low describes a new FBC subtype. There is a lack of studies determining the impact of HER2 low in male breast cancer (MBC). In this study, we evaluate the prevalence of HER2 low in primary MBC and correlate the results with patient characteristics. Patients and Methods: In this study, histological specimens were obtained from 120 male patients diagnosed and treated for primary invasive breast cancer from 1995 to 2022 at Breast Cancer Units in Bergisch Gladbach, Chemnitz, and Zwickau, Germany. HER2 immunostaining and in situ hybridization were performed by central pathology and evaluated based on the ASCO/CAP guidelines. The correlation of expression of HER2 low with tumor biological characteristics and patient outcomes was investigated. Results: Out of all cases, four patients (3.3%) showed HER2 positivity (3+), 39 (32.5%) patients were classified as HER2 low, 7 (5.8%) were HER2 2+ (no amplification), 32 (26.7%) were HER2 1+, and 77 (64.2%) were classified as HER2 zero. Out of 77 HER2 zero cases, 47 tumors (61.0%) showed incomplete staining, with <10% of tumor cells classified as HER2 ultralow. No statistical correlation between HER2 low and tumor biological characteristics and patients' survival was found. Conclusion: Our findings show a notable, albeit lower, prevalence of HER2 low expression in primary MBC. However, tumors expressing HER2 low do not show specific tumor biological features to define a new breast cancer subtype in MBC. Our results suggest that a significant number of MBC patients could benefit from ADCs, as shown in FBC. Further studies are required to better understand HER2 low breast cancer, both generally and in MBC.

Converting between the International Prostate Symptom Score (IPSS) and the Expanded Prostate Cancer Index Composite (EPIC) urinary subscales: modeling and external validation.

BACKGROUND: Prostate-related quality of life can be assessed with a variety of different questionnaires. The 50-item Expanded Prostate Cancer Index Composite (EPIC) and the International Prostate Symptom Score (IPSS) are two widely used options. The goal of this study was, therefore, to develop and validate a model that is able to convert between the EPIC and the IPSS to enable comparisons across different studies. METHODS: Three hundred forty-seven consecutive patients who had previously received radiotherapy and surgery for prostate cancer at two institutions in Switzerland and Germany were contacted via mail and instructed to complete both questionnaires. The Swiss cohort was used to train and internally validate different machine learning models using fourfold cross-validation. The German cohort was used for external validation. RESULTS: Converting between the EPIC Urinary Irritative/Obstructive subscale and the IPSS using linear regressions resulted in mean absolute errors (MAEs) of 3.88 and 6.12, which is below the respective previously published minimal important differences (MIDs) of 5.2 and 10 points. Converting between the EPIC Urinary Summary and the IPSS was less accurate with MAEs of 5.13 and 10.45, similar to the MIDs. More complex model architectures did not result in improved performance in this study. The study was limited to the German versions of the respective questionnaires. CONCLUSIONS: Linear regressions can be used to convert between the IPSS and the EPIC Urinary subscales. While the equations obtained in this study can be used to compare results across clinical trials, they should not be used to inform clinical decision-making in individual patients. TRIAL REGISTRATION: This study was retrospectively registered on clinicaltrials.gov on January 14th, 2022, under the registration number NCT05192876.

Mechanisms of SARS-CoV-2 Inactivation Using UVC Laser Radiation.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has had a tremendous impact on humanity. Prevention of transmission by disinfection of surfaces and aerosols through a chemical-free method is highly desirable. Ultraviolet C (UVC) light is uniquely positioned to achieve inactivation of pathogens. We report the inactivation of SARS-CoV-2 virus by UVC radiation and explore its mechanisms. A dose of 50 mJ/cm2 using a UVC laser at 266 nm achieved an inactivation efficiency of 99.89%, while infectious virions were undetectable at 75 mJ/cm2 indicating >99.99% inactivation. Infection by SARS-CoV-2 involves viral entry mediated by the spike glycoprotein (S), and viral reproduction, reliant on translation of its genome. We demonstrate that UVC radiation damages ribonucleic acid (RNA) and provide in-depth characterization of UVC-induced damage of the S protein. We find that UVC severely impacts SARS-CoV- 2 spike protein's ability to bind human angiotensin-converting enzyme 2 (hACE2) and this correlates with loss of native protein conformation and aromatic amino acid integrity. This report has important implications for the design and development of rapid and effective disinfection systems against the SARS-CoV-2 virus and other pathogens.

Five Fractions versus Seven Fractions SBRT for Intermediate- and High-Risk Prostate Cancer: A Propensity Score Matched Pair Analysis.

PURPOSE: To compare two stereotactic body radiotherapy (SBRT) regimens in patients with intermediate- or high-risk prostate cancer with regards toxicity and efficacy. METHODS/MATERIAL: We retrospectively collected data from 198 patients treated with SBRT for prostate cancer at two different institutions. Patients received either 35-36.25 Gy in five fractions (group A) using Cyberknife robotic platform or 42.7 Gy in seven fractions (group B) using a C-arm LINAC (image-guided). Propensity score matching was done (2:1 nearest neighbor matching without replacement), resulting in 120 patients (80 patients for group A, 40 patients for group B). Toxicity, PSA nadir, biochemical failure and disease-free survival (DFS) were analyzed. RESULTS: Median follow up of all patients was 13 months (range 1-91 months). Overall, 23.3% of patients had ≥G2 acute GU toxicity (21.1% group A versus 30% group B (p = 0.222)) and 6.6% of patients ≥G2 GI toxicity (2.5% versus 15% (p = 0.010)). There was one acute G3 GU toxicity in arm A and one acute G4 rectal bleeding in group B (anticoagulated patient). Regarding late toxicity, 14.1% of patients had ≥G2 late GU toxicity (17.4% versus 6.6% (p = 0.159)) and 5.0% of patients had ≥G2 late GI toxicity (1.4% versus 13.3% (p = 0.013)). There was one G3 late GU toxicity in arm B and two G3 late GI toxicities, one in each arm. Relative median PSA reduction was 92.4% (-53.9-99.9%) from baseline PSA (93.7% (-53.9-99.9%) in group A versus 87.7% (39.8-99.9%) in group B (p = 0.043). In total, 4.2% of patients had biochemical relapse, 5.0% in group A and 2.5% in group B (p = 0.518). One-year DFS in the overall cohort was 97.3%, 98.8% in group A and 94.3% in group B (p = 0.318). CONCLUSION: Both SBRT regimens have acceptable acute and late toxicity and good efficacy. There are significantly more GI toxicities in the seven-fraction regimen. Longer follow-up is warranted for better comparison of long-term efficacy.

Re-irradiation for head and neck cancer: outcome and toxicity analysis using a prospective single institution database.

Purpose: Re-irradiation (re-RT) in head and neck cancer is challenging. This study prospectively explored the feasibility of re-RT in patients with loco-regionally recurrent or second primary head and neck cancer (LRR/SP HNC). Methods: From 2004 to 2021, 61 LRR/SP HNC patients were treated with re-RT, defined as having a second course of RT with curative intent resulting in a cumulative dose of ≥100 Gy in an overlapping volume. Postoperative or definitive dynamic intensity-modulated and/or volumetric modulated re-RT was administered using twice daily hyperfractionation to 60 Gy combined with cisplatin or carboplatin/5-fluorouracil. Overall survival (OS), progression-free survival (PFS), locoregional control (LRC) and distant metastasis control (DMC) were analyzed and prognostic factors evaluated. Toxicity was prospectively recorded and graded. Results: The median follow-up was 9.8 months. In 41 patients (67.1%), complete administration of the intended treatment was not feasible. In 9 patients (15%) re-RT was interrupted prematurely and in other 9, the complete re-RT dose was lower than 60 Gy, and 37 patients (61%) could not receive or complete chemotherapy. Two-year OS, PFS and LRC rates were 19%, 18% and 30%, respectively. 20 patients (33%) received the complete intended treatment, and 1- and 2-year OS rates were 70% and 47%, respectively. Charlson comorbidity index was an important predictor for treatment completion. Multivariate analysis revealed recurrent N stage 0-1, age, chemotherapy administration and re-RT dose of 60 Gy as prognostic factors for clinical outcomes. No grade 5 re-RT-related toxicity was observed. The most common new grade ≥3 acute toxicities were dysphagia (52%) and mucositis (46%). Late toxicity included grade ≥3 dysphagia in 5% and osteoradionecrosis in 10% of evaluable patients, respectively. 6 patients (10%) were alive after 9 years without progression and no late toxicity grade ≥3, except for 2 patients presenting with osteoradionecrosis. Conclusion: Hyperfractionated re-RT with 60 Gy combined with platinum-based chemotherapy was a curative treatment option with acceptable toxicity in LRR/SP patients. Patients with higher comorbidity had a higher probability of failing to receive and complete the intended therapy. Consequently, they derived unsatisfactory benefits from re-RT, highlighting the importance of patient selection.

Dose-Volume Histogram Parameters and Quality of Life in Patients with Prostate Cancer Treated with Surgery and High-Dose Volumetric-Intensity-Modulated Arc Therapy to the Prostate Bed.

INTRODUCTION: Prostate bed radiotherapy (RT) is a major affecter of patients' long-term quality of life (QoL). To ensure the best possible outcome of these patients, dose constraints are key for optimal RT planning and delivery. However, establishing refined dose constraints requires access to patient-level data. Therefore, we aimed to provide such data on the relationship between OAR and gastrointestinal (GI) as well as genitourinary (GU) QoL outcomes of a homogenous patient cohort who received dose-intensified post-operative RT to the prostate bed. Furthermore, we aimed to conduct an exploratory analysis of the resulting data. METHODS: Patients who were treated with prostate bed RT between 2010 and 2020 were inquired about their QoL based on the Expanded Prostate Cancer Index Composite (EPIC). Those (n = 99) who received volumetric arc therapy (VMAT) of at least 70 Gy to the prostate bed were included. Dose-volume histogram (DVH) parameters were gathered and correlated with the EPIC scores. RESULTS: The median age at the time of prostate bed RT was 68.9 years, and patients were inquired about their QoL in the median 2.3 years after RT. The median pre-RT prostate-specific antigen (PSA) serum level was 0.35 ng/mL. The median duration between surgery and RT was 1.5 years. The median prescribed dose to the prostate bed was 72 Gy. A total of 61.6% received prostate bed RT only. For the bladder, the highest level of statistical correlation (p < 0.01) was seen for V10-20Gy, Dmean and Dmedian with urinary QoL. For bladder wall, the highest level of statistically significant correlation (p < 0.01) was seen for V5-25Gy, Dmean and Dmedian with urinary QoL. Penile bulb V70Gy was statistically significantly correlated with sexual QoL (p < 0.05). A larger rectal volume was significantly correlated with improved bowel QoL (p < 0.05). Sigmoid and urethral DVH parameters as well as the surgical approach were not statistically significantly correlated with QoL. CONCLUSION: Specific dose constraints for bladder volumes receiving low doses seem desirable for the further optimization of prostate bed RT. This may be particularly relevant in the context of the aspiration of establishing focal RT of prostate cancer and its local recurrences. Our comprehensive dataset may aid future researchers in achieving these goals.

Orally compensated short bowel patients are thin, potentially malnourished but rarely sarcopenic.

BACKGROUND AND AIM: In short bowel syndrome, insufficient absorptive capacity of the remnant bowel may lead to metabolic and nutritional consequences including electrolyte disturbances, severe diarrhea and malnutrition. While intestinal failure requires parenteral nutrition, short bowel patients with intestinal insufficiency (SB/II) have achieved oral autonomy. The aim of this exploratory study was to assess the nutritional, muscular and functional status of orally compensated SB/II patients. METHODS: 28 orally compensated SB/II patients with a mean of 46 months after termination of parenteral nutrition and 56 age- and sex-matched healthy controls (HC) were compared regarding anthropometric parameters, body composition using bioelectrical impedance analysis, handgrip strength and gait speed, blood parameters as well as nutritional intake and physical activity using validated questionnaires. Malnutrition and sarcopenia were diagnosed according to the criteria of the GLIM or EWGSOP2. RESULTS: SB/II patients had lower body mass index (BMI) and anthropometric parameters than HC but were within the normal weight range. The GLIM algorithm operationally diagnosed malnutrition in 39% (n = 11) of SB/II patients. Reduced skeletal muscle mass index and phase angle were rarely accompanied by a reduction of handgrip strength below cut-off values and the subsequent diagnosis of sarcopenia in SB/II patients (15%, n = 4). Compared to 11% of HC, 37% of SB/II patients had low physical activity level. Female SB/II patients had higher caloric and macronutrient intake. Caloric intake negatively correlated with body weight indicating compensatory hyperphagia in patients with lower body weight. Some of the SB/II patients showed signs of dehydration. CONCLUSIONS: Orally compensated SB/II patients are thinner than HC but have mostly normal BMI. Malnutrition is frequently diagnosed but may be overestimated due to the underlying malabsorption and its interplay with hyperphagia. Muscle mass is often reduced but is rarely accompanied by functional impairment leading to sarcopenia diagnosis. Thus, SB/II patients long term after termination of parenteral support may be malnourished but usually do not develop sarcopenia.

Applications of Machine Learning in Palliative Care: A Systematic Review.

Objective: To summarize the available literature on using machine learning (ML) for palliative care practice as well as research and to assess the adherence of the published studies to the most important ML best practices. Methods: The MEDLINE database was searched for the use of ML in palliative care practice or research, and the records were screened according to PRISMA guidelines. Results: In total, 22 publications using machine learning for mortality prediction (n = 15), data annotation (n = 5), predicting morbidity under palliative therapy (n = 1), and predicting response to palliative therapy (n = 1) were included. Publications used a variety of supervised or unsupervised models, but mostly tree-based classifiers and neural networks. Two publications had code uploaded to a public repository, and one publication uploaded the dataset. Conclusions: Machine learning in palliative care is mainly used to predict mortality. Similarly to other applications of ML, external test sets and prospective validations are the exception.

Label-free electrochemical immunosensor for picomolar detection of the cervical cancer biomarker MCM5.

An immunosensor for label-free electrochemical detection of MiniChromosome Maintenance Protein 5, MCM5, a protein overexpressed in cervical cancer, based on a gold electrode is reported. The electrode was first modified with a submonolayer (capture layer) of 11-mercaptoundecanoic acid (11-MUA) and then activated with N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) to immobilize the capture antibody. The change in electrode surface properties (wettability) during the formation of the 11-MUA layers was determined using the static water contact angle (WCA). The binding of MCM5 antigens to the capture antibody was monitored by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) using 5 mM [Fe(CN)6]3-/4- in 0.1 M LiClO4(aq) as an electroactive probe. AC Impedance was used to measure charge transfer resistance (Rct), which reflects impeded electron transfer when the antigen is bound to the antibody functionalized surface. After exposing the antibody-functionalized surface to MCM5 antigens, Rct increases linearly with the logarithmic value of MCM5 antigen concentration, with a linear dynamic range of 10-6 to 10-11 g/mL, a correlation coefficient of 0.99, and a detection limit of 2.9 pM (10-11 g/mL). This excellent sensitivity was achieved with simple preparation steps and minimal reagent consumption, without the need for complicated procedures such as enzymatic amplification, fluorescent labeling, or nanoparticle modification.

Correction: Kudura et al. Prediction of Early Response to Immune Checkpoint Inhibition Using FDG-PET/CT in Melanoma Patients. Cancers 2021, 13, 3830.

The authors wish to make the following corrections to this paper [...].

Machine Learning for the Detection and Segmentation of Benign Tumors of the Central Nervous System: A Systematic Review.

Objectives: To summarize the available literature on using machine learning (ML) for the detection and segmentation of benign tumors of the central nervous system (CNS) and to assess the adherence of published ML/diagnostic accuracy studies to best practice. Methods: The MEDLINE database was searched for the use of ML in patients with any benign tumor of the CNS, and the records were screened according to PRISMA guidelines. Results: Eleven retrospective studies focusing on meningioma (n = 4), vestibular schwannoma (n = 4), pituitary adenoma (n = 2) and spinal schwannoma (n = 1) were included. The majority of studies attempted segmentation. Links to repositories containing code were provided in two manuscripts, and no manuscripts shared imaging data. Only one study used an external test set, which raises the question as to whether some of the good performances that have been reported were caused by overfitting and may not generalize to data from other institutions. Conclusions: Using ML for detecting and segmenting benign brain tumors is still in its infancy. Stronger adherence to ML best practices could facilitate easier comparisons between studies and contribute to the development of models that are more likely to one day be used in clinical practice.

Cranial Radiotherapy for Prostate Cancer Patients With Brain Metastases Inaccessible to Stereotactic Radiotherapy.

BACKGROUND/AIM: To evaluate patients and treatment characteristics as well as clinical outcome in patients with intracranial metastases from prostate cancer (PCA) treated with palliative radiotherapy. PATIENTS AND METHODS: Fifteen patients treated for intracranial metastases of PCA were identified. The median age of patients was 69 years. 80% of patients received whole brain radiotherapy and 20% received partial brain radiotherapy. Clinical outcome was assessed. Univariate analysis was performed to analyze the impact of patient specific parameters on survival. RESULTS: There was no >G2 acute or any late toxicity. Median time from the first diagnosis of PCA to first diagnosis of intracranial metastases was 62 months (range=15-160 months). Median survival from first diagnosis of intracranial metastases was 14 weeks (range=0-126 weeks) and 6 weeks (range=0-47 weeks) from the start of radiotherapy. In univariate analysis, survival was significantly better for patients with an Eastern Cooperative Oncology Group (ECOG) performance status 1 compared to ECOG 2-3 [18 weeks (range=5-47 weeks) vs. 3 weeks (range=0-21 weeks), p=0.030] and Recursive Partitioning Analysis (RPA) class 2 compared to RPA class 3 [18 weeks (range=5-47 weeks) vs. 6 weeks (range=0-21 weeks), p=0.045]. CONCLUSION: Overall survival of the patients with wide-spread intracranial metastases from PCA was poor. The decision for a radiotherapy should be done on individual patient basis.

Convolutional Neural Networks to Detect Vestibular Schwannomas on Single MRI Slices: A Feasibility Study.

In this study. we aimed to detect vestibular schwannomas (VSs) in individual magnetic resonance imaging (MRI) slices by using a 2D-CNN. A pretrained CNN (ResNet-34) was retrained and internally validated using contrast-enhanced T1-weighted (T1c) MRI slices from one institution. In a second step, the model was externally validated using T1c- and T1-weighted (T1) slices from a different institution. As a substitute, bisected slices were used with and without tumors originating from whole transversal slices that contained part of the unilateral VS. The model predictions were assessed based on the categorical accuracy and confusion matrices. A total of 539, 94, and 74 patients were included for training, internal validation, and external T1c validation, respectively. This resulted in an accuracy of 0.949 (95% CI 0.935-0.963) for the internal validation and 0.912 (95% CI 0.866-0.958) for the external T1c validation. We suggest that 2D-CNNs might be a promising alternative to 2.5-/3D-CNNs for certain tasks thanks to the decreased demand for computational power and the fact that there is no need for segmentations. However, further research is needed on the difference between 2D-CNNs and more complex architectures.

Stereotactic Radiotherapy after Radical Prostatectomy in Patients with Prostate Cancer in the Adjuvant or Salvage Setting: A Systematic Review.

(1) Background: Prostate cancer is the most common cancer in men and can be treated with radical prostatectomy (RPE) or radiotherapy in the primary setting. Stereotactic radiotherapy (SBRT) has proven to be effective and well tolerated in this setting. However, if SBRT is an equally promising treatment option if applied in the adjuvant or salvage setting after RPE remains unknown. (2) Methods: We searched the PubMed and Embase databases with the following full-text queries in August 2021 for any combination of the terms "SBRT", "prostate", "adjuvant", "postoperative", "salvage", "stereotactic radiotherapy", "prostate bed". There were no limitations regarding publication date or language. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. (3) Results: We identified 11 individual studies that were included in this systematic review. Three publications included patients without prior radiotherapy and the remaining eight patients with prior radiotherapy. In all but two publications the radiation target was the macroscopic recurrence. SBRT was overall well tolerated with acceptable rates of acute and late gastrointestinal or genitourinary toxicity. Quality of life was published for two phase I trials with good results. There was a very heterogeneous reporting on biochemical control after SBRT. (4) Conclusions: At this point, ultra-hypofractionated RT using SBRT to the prostate bed remains experimental and its use should be restricted to clinical trials. Given the biological rationale for extreme hypofractionation in patients with prostate cancer and the acceptable toxicity rates that have been reported, further exploration of this field is warranted.

Deep inspiration breath-hold for patients with left-sided breast cancer - A one-fits-all approach? A prospective analysis of patient selection using dosimetrical and practical aspects.

OBJECTIVE: To prospectively analyze the feasibility of an algorithm for patient preparation, treatment planning, and selection for deep inspiration breath-hold (DIBH) treatment of left-sided breast cancer. METHODS: From February 2017 to July 2019, 135 patients with left-sided breast cancer were selected and prepared for radiotherapy in DIBH. 99 received radiotherapy for the breast alone and 36 for the breast including the lymphatic drainage (RNI). Treatment plans DIBH and free breathing (FB) were calculated. Dosimetrical analyses were performed, and criteria were defined to assess whether a patient would dosimetrically profit from DIBH. RESULTS: Of the 135 patients, 97 received a DIBH planning CT and 72 were selected for treatment in DIBH according to predefined criteria. When using DIBH, there was a mean reduction of the DmeanHeart of 2.8 Gy and DmeanLAD of 4.2 Gy. seven patients did not benefit from DIBH regarding DmeanHeart, 23 regarding DmeanLAD. For the left lung, the V20Gy was reduced by 4.9%, the V30Gy by 2.7% with 15 and 29 patients not benefiting from DIBH, respectively. In the 25 patients treated in FB, the benefit of DIBH would have been lower than for patients treated with DIBH (ΔDmeanHeart0.7 Gy vs 3.4 Gy). CONCLUSION: Dosimetrically, DIBH is no "one-fits-all" approach. However, there is a statistically significant benefit when looking at a larger patient population. DIBH should be used for treatment of left-sided breast cancer in patients fit for DIBH. ADVANCES IN KNOWLEDGE: This analysis offers a well-designed dosimetrical analysis in patients treated with DIBH radiotherapy in an "every day" cohort.

Prognostic relevance of Ki67 expression in primary male breast cancer: determination of cut-off points by different evaluation methods and statistical examinations.

PURPOSE: 1% of all breast cancer cases occur in men. There are significant differences regarding clinical behaviour and genetic profiles between female (FBC) and male breast cancer (MBC). Parameters for decision-making on treatment and prognosis are derived from FBC. Ki67 has a high value as a prognostic and predictive factor in FBC, but accurate Ki67 cut-off points for MBC are missing. In this study, we aimed to evaluate adequate examination methods and reliable cut-off points for Ki67 to assess the highest prognostic value for patient's overall survival (OS). METHODS: In this multicentric retrospective study, histological specimens were obtained from 104 male patients who were diagnosed and treated for primary invasive breast cancer. We applied three methods of Ki67 analysis: Tumor average scoring (TA), tumor border scoring (TB) and hot-spot scoring (HS). Calculated Ki67 cut-off points for each method were assessed as a threshold for patients' overall survival (OS). RESULTS: Ki67 cut-off points were 13.5 for the TA group, 22.5 for the HS group and 17.5 for the TB group. Only Ki67 TA cut-off calculations demonstrated statistical significance (p = 0.04). Ki67 expression analysis of TA showed that more than 90% of patients with low Ki67 levels (< 13.5) were alive after 5-year follow-up. CONCLUSION: Our findings demonstrate that determination of Ki67 expression in TA is the most reliable to define a cut-off point with high prognostic value. A Ki67 cut-off point of 13.5 shows highest statistical power to define luminal A subgroup and OS.