SYMBA: An end-to-end VLBI synthetic data generation pipeline: Simulating Event Horizon Telescope observations of M 87

Context. Realistic synthetic observations of theoretical source models are essential for our understanding of real observational data. In using synthetic data, one can verify the extent to which source parameters can be recovered and evaluate how various data corruption effects can be calibrated. These studies are the most important when proposing observations of new sources, in the characterization of the capabilities of new or upgraded instruments, and when verifying model-based theoretical predictions in a direct comparison with observational data. Aims. We present the SYnthetic Measurement creator for long Baseline Arrays (SYMBA), a novel synthetic data generation pipeline for Very Long Baseline Interferometry (VLBI) observations. SYMBA takes into account several realistic atmospheric, instrumental, and calibration effects. Methods. We used SYMBA to create synthetic observations for the Event Horizon Telescope (EHT), a millimetre VLBI array, which has recently captured the first image of a black hole shadow. After testing SYMBA with simple source and corruption models, we study the importance of including all corruption and calibration effects, compared to the addition of thermal noise only. Using synthetic data based on two example general relativistic magnetohydrodynamics (GRMHD) model images of M 87, we performed case studies to assess the image quality that can be obtained with the current and future EHT array for different weather conditions. Results. Our synthetic observations show that the effects of atmospheric and instrumental corruptions on the measured visibilities are significant. Despite these effects, we demonstrate how the overall structure of our GRMHD source models can be recovered robustly with the EHT2017 array after performing calibration steps, which include fringe fitting, a priori amplitude and network calibration, and self-calibration. With the planned addition of new stations to the EHT array in the coming years, images could be reconstructed with higher angular resolution and dynamic range. In our case study, these improvements allowed for a distinction between a thermal and a non-thermal GRMHD model based on salient features in reconstructed images

The impact of schizophrenia spectrum disorder, bipolar disorder and borderline personality disorder on radiotherapy treatment and overall survival in cancer patients: A matched pair analysis

Introduction: The effect of a psychiatric disorder (PD) on the choice of radiotherapy regimens and subsequent cancer control outcomes is largely unknown. In this study, we evaluated differences in radiotherapy regimens and overall survival (OS) between cancer patients with a PD in comparison with a control population of patients without a PD. Methods: Referred patients with a PD (i.e. schizophrenia spectrum disorder, bipolar disorder or borderline personality disorder) were included through a text-based search of the electronic patient database of all the patients that received radiotherapy between 2015 and 2019 at a single centre. Each patient was matched to a patient without a PD. Matching was based on cancer type, staging, performance score (WHO/KPS), non-radiotherapeutic cancer treatment, gender and age. Outcomes were the amount of fractions received, total dose, and OS. Results: 88 patients with PD were identified; 44 patients with schizophrenia spectrum disorder, 34 with bipolar disorder, and 10 with borderline personality disorder. Matched patients without a PD showed similar baseline characteristics. No statistically significant difference was observed regarding the number of fractions with a median of 16 (interquartile range [IQR] 3–23) versus 16 (IQR 3–25), respectively (p = 0.47). Additionally, no difference in total dose was found. Kaplan-Meier curves showed a statistically significant difference in OS between the patients with a PD versus those without a PD, with 3-year OS rates of 47 % versus 61 %, respectively (hazard ratio 1.57, 95 % confidence interval 1.05–2.35, p = 0.03). No clear differences in causes of death were observed. Conclusion: Cancer patients referred for radiotherapy with schizophrenia spectrum disorder, bipolar disorder or borderline personality disorder receive similar radiotherapy schedules for a variety of tumour types but attain worse survival

Cervical ultrasonography has no additional value over negative 18F-FDG PET/CT scans for diagnosing cervical lymph node metastases in patients with oesophageal cancer

Objectives: To investigate the additional value of cervical ultrasonography over 18F-FDG PET/CT for diagnosing cervical lymph node metastases in patients with newly diagnosed oesophageal cancer. Methods: Between January 2013 and January 2016, 163 patients with newly diagnosed oesophageal cancer underwent both cervical ultrasonography and 18F-FDG PET/CT at a tertiary referral centre in the Netherlands. Retrospective clinical data analysis was performed to assess the diagnostic value of cervical ultrasonography and 18F-FDG PET/CT for the detection of cervical lymph node metastases. Fine needle aspiration or clinical follow-up was used as reference standard. Results: The overall incidence of patients with cervical lymph node metastases was 14%. The sensitivity of 18F-FDG PET/CT to detect cervical lymph node metastases was 82% (95% CI 59–94%) and specificity was 91% (95% CI 85–95%). The sensitivity and specificity of cervical ultrasonography were 73% (95% CI 50–88%) and 84% (95% CI 77–90%), respectively. In patients with a negative 18F-FDG PET/CT, 12 of 133 (9%) patients had suspicious nodes on cervical ultrasonography. In all these 12 patients the nodes were confirmed benign. Conclusions: Cervical ultrasonography has no additional diagnostic value to a negative integrated 18F-FDG PET/CT for the detection of cervical lymph node metastases in patients with newly diagnosed oesophageal cancer. Key Points: • Cervical ultrasonography has no value over PET/CT in evaluating cervical node metastases.• PET/CT provides greater diagnostic confidence compared to cervical ultrasonography.• Cervical ultrasonography during standard diagnostic work-up may be considered unnecessary.• Cervical lesions on PET/CT require cytopathological confirmation by FNA

The relationship of lymphocyte recovery and prognosis of esophageal cancer patients with severe radiation-induced lymphopenia after chemoradiation therapy

Introduction: Radiation-induced lymphopenia (RIL) during therapy is associated with poor prognosis but is often temporary and resolves after treatment completion in esophageal cancer. How lymphocyte recovery contributes to prognosis is unknown. Methods: We reviewed 755 patients with stage I-III esophageal carcinoma who received concurrent chemoradiation therapy (CRT) with or without surgery in 2004–2015. Complete blood counts were obtained before, during, and at first follow-up after CRT. Lymphopenia was graded per the Common Terminology Criteria for Adverse Events v4.03 during CRT (G) and as recovery after CRT (Gr). Clinical factors and lymphopenia grade were tested for association with survival in univariable and multivariable Cox proportional hazard regression analyses. Results: During CRT, 294 patients (38.9%) had G4 lymphopenia; by the first follow-up, 406 patients (53.8%) had recovered (Gr0-1). Relative to patients with G0-3 lymphopenia during CRT, G4 lymphopenia independently predicted worse OS in multivariable analyses. However, lymphocyte recovery was not associated with a better prognosis. Patients with G4 lymphopenia during CRT and recovery (Gr0-1) afterward still had poorer 5-year OS rate than patients with G0-3 during CRT without recovery (Gr2-4) afterward (36.6% vs. 51.9%, HR = 1.40, 95% CI 1.04–1.89, P = 0.027). Moreover, the lymphocyte recovery ability (post-CRT ALC divided by pre-CRT ALC) was not affected by lymphopenia grade during CRT (0.66 in G0-3 vs. 0.65 in G4, p = 0.473). Among patients with G4 lymphopenia during treatment, lymphocyte recovery was only associated with pre-CRT lymphocyte counts. Conclusion: Lymphocyte count recovery after CRT does not alter the poor long-term outcomes brought about by high-grade lymphopenia during CRT

Liver oligometastatic disease in synchronous metastatic gastric cancer patients: a nationwide population-based cohort study

Introduction: This population-based cohort study analysed treatment, overall survival (OS), and independent prognostic factors for OS in gastric cancer patients with liver metastases. Methods: Between 2015 and 2017, patients with synchronous metastatic gastric or gastroesophageal junction adenocarcinoma limited to the liver were included from the prospectively maintained population-based Netherlands Cancer Registry. Liver oligometastatic disease (OMD) was defined as ≤3 liver metastases. The primary outcome was OS. Independent prognostic factors for OS were analysed using multivariable Cox regression analysis. Results: A total 295 patients with metastases limited to the liver were included. The primary tumour was resected in four patients (1.4%). Treatment for liver metastases consisted of chemotherapy alone (28.1%), trastuzumab plus chemotherapy (4.7%), surgery (1.0%), or best supportive care (67.5%). Median OS across all included patients was 4.0 months (95% confidence interval [CI]: 3.1–4.5). Liver OMD was detected in 77 patients (26%). Treatment for liver OMD consisted of chemotherapy alone (24.6%), trastuzumab plus chemotherapy (5.2%), surgery (3.9%), or best supportive care (67.5%). Median OS among patients with liver OMD was 5.7 months (95% CI: 4.8–7.5). Across all patients, better OS was independently associated with liver OMD (hazard ratio [HR] 0.66, 95% CI: 0.50–0.87), trastuzumab (HR 0.41, 95% CI: 0.23–0.72) but not with triplet compared with doublet chemotherapy (HR 0.94, 95% CI: 0.57–2.87). Worse OS was independently associated with unknown nodal stage versus cN0 (HR 1.74, 95% CI: 1.17–2.60), diffuse-type versus intestinal-type adenocarcinoma (HR 2.06, 95% CI: 1.32–3.20), and monotherapy or best supportive care versus doublet chemotherapy (HR 1.72, 95% CI: 1.03–2.87, and HR 3.61, 95% CI: 2.55–5.10, respectively). Conclusion: In this population-based cohort study, liver OMD was detected in 26% of patients. Liver OMD and trastuzumab treatment were independently associated with better OS while triplet as compared with doublet chemotherapy was not. OS among patients with liver OMD nevertheless remained poor. The concept of OMD and the benefit of resection of liver OMD may still have been relatively unknown in this disease type during the study inclusion years

Correlation between functional imaging markers derived from diffusion-weighted MRI and F-18-FDG PET/CT in esophageal cancer

Objective Both the apparent diffusion coefficient (ADC) acquired by diffusion-weighted magnetic resonance imaging (DW-MRI) and the standardized uptake value (SUV), acquired by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT), are well-established functional parameters in cancer imaging. Currently, it is unclear whether these two markers provide complementary prognostic and predictive information in esophageal cancer. The aim of this study was to evaluate the correlation between ADC and SUV in patients with esophageal cancer. Materials and methods This prospective study included 76 patients with histologically proven esophageal cancer who underwent both DW-MRI and 18 F-FDG PET/CT examinations before treatment. The minimum and mean ADC values (ADC min and ADC mean) of the primary tumor were assessed on MRI. Similarly, the glucose metabolism was evaluated by the maximum and mean SUV (SUV max and SUV mean) in the same lesions on 18 F-FDG PET/CT images. Spearman's rank correlation coefficients were used to assess the correlation between tumor ADC and SUV values. Results The tumor ADC and SUV values as measures of cell density and glucose metabolism, respectively, showed negligible nonsignificant correlations (ADC min vs. SUV max: r=-0.087, P=0.457; ADC min vs. SUV mean: r=-0.105, P=0.369; ADC mean vs. SUV max: r=-0.099, P=0.349; ADC mean vs. SUV mean: r=-0.111, P=0.340). No differences in tumor ADC and SUV values were observed between the different histologic tumor types, stages, and differentiation grades. Conclusion This study indicates that tumor cellularity derived from DW-MRI and tumor metabolism measured by 18 F-FDG PET/CT are independent cellular phenomena in newly diagnosed esophageal cancer. Therefore, tumor ADC and SUV values may play complementary roles as imaging markers in the prediction of survival and evaluation of response to treatment in esophageal cancer

European clinical practice guidelines for the definition, diagnosis, and treatment of oligometastatic esophagogastric cancer (OMEC-4)

Introduction: The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD). Methods: Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD. Results: Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI &gt; 2 years, upfront local treatment is additionally recommended. Discussion: These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment.</p