Definition of oligometastatic esophagogastric cancer and impact of local oligometastasis-directed treatment: A systematic review and meta-analysis

BACKGROUND Local treatment (metastasectomy or stereotactic radiotherapy) for oligometastatic disease (OMD) in patients with esophagogastric cancer may improve overall survival (OS). The primary aim was to identify definitions of esophagogastric OMD. A secondary aim was to perform a meta-analysis of OS after local treatment versus systemic therapy alone for OMD. METHODS Studies and study protocols reporting on definitions or OS after local treatment for esophagogastric OMD were included. The primary outcome was the maximum number of organs/lesions considered OMD and the maximum number of lesions per organ (i.e. 'organ-specific' OMD burden). Agreement was considered to be either absent/poor (< 50%), fair (50%-75%), or consensus (≥ 75%). The secondary outcome was the pooled adjusted hazard ratio (aHR) for OS after local treatment versus systemic therapy alone. The ROBINS tool was used for quality assessment. RESULTS A total of 97 studies, including 7 study protocols, and 2 prospective studies, were included. OMD was considered in 1 organ with ≤ 3 metastases (consensus). 'Organ-specific' OMD burden could involve bilobar ≤ 3 liver metastases, unilateral ≤ 2 lung metastases, 1 extra-regional lymph node station, ≤ 2 brain metastases, or bilateral adrenal gland metastases (consensus). Local treatment for OMD was associated with improved OS compared with systemic therapy alone based on 6 non-randomized studies (pooled aHR 0.47, 95% CI: 0.30-0.74) and for liver oligometastases based on 5 non-randomized studies (pooled aHR 0.39, 95% CI: 0.22-0.59). All studies scored serious risk of bias. CONCLUSIONS Current literature considers esophagogastric cancer spread limited to 1 organ with ≤ 3 metastases or 1 extra-regional lymph node station to be OMD. Local treatment for OMD appeared associated with improved OS compared with systemic therapy alone. Prospective randomized trials are warranted

Repeated use of rich pictures to explore changes in subjective experiences over time of patients with advanced cancer

BACKGROUND: The combination of verbal and visual tools may help unravel the experiences of advanced cancer patients. However, most previous studies have focused on a specific symptom, at only one moment in time. We recently found that a specific visual tool, originating from systems thinking, that is, rich pictures (RPs), could provide a more comprehensive view of the experiences of patients with advanced cancer. AIMS: To examine whether the repeated use of RPs can make changes in subjective experiences of patients living with advanced cancer visible over time. METHODS AND RESULTS: We performed a prospective study with a generic qualitative approach that was mostly informed by the process of grounded theory. We invited patients to make an RP twice, at the start of the study, and again after 2 months. Both RP drawing sessions were directly followed by a semi‐structured interview. Patients with all types of solid tumors, above the age of 18, and with a diagnosis of advanced, incurable cancer, were eligible. Eighteen patients participated and 15 patients were able to draw an RP twice. In eight RP‐sets, considerable differences between the first and second RP were noticeable. Two patterns were distinguished: (1) a change (decline or improvement) in physical health (five patients), and/or (2) a change in the way patients related to cancer (three patients). CONCLUSION: RPs are a valuable qualitative research method that can be used to explore the experiences of patients with advanced cancer, not only at a single point in time but also over time

Potential mechanisms of the fatigue-reducing effect of cognitive-behavioral therapy in cancer survivors:Three randomized controlled trials

OBJECTIVE: Fatigue is a common symptom among cancer survivors that can be successfully treated with cognitive‐behavioral therapy (CBT). Insights into the working mechanisms of CBT are currently limited. The aim of this study was to investigate whether improvements in targeted cognitive‐behavioral variables and reduced depressive symptoms mediate the fatigue‐reducing effect of CBT. METHODS: We pooled data from three randomized controlled trials that tested the efficacy of CBT to reduce severe fatigue. In all three trials, fatigue severity (checklist individual strength) decreased significantly following CBT. Assessments were conducted pre‐treatment and 6 months later. Classical mediation analysis testing a pre‐specified model was conducted and its results compared to those of causal discovery, an explorative data‐driven approach testing all possible causal associations and retaining the most likely model. RESULTS: Data from 250 cancer survivors (n = 129 CBT, n = 121 waitlist) were analyzed. Classical mediation analysis suggests that increased self‐efficacy and decreased fatigue catastrophizing, focusing on symptoms, perceived problems with activity and depressive symptoms mediate the reduction of fatigue brought by CBT. Conversely, causal discovery and post‐hoc analyses indicate that fatigue acts as mediator, not outcome, of changes in cognitions, sleep disturbance and depressive symptoms. CONCLUSIONS: Cognitions, sleep disturbance and depressive symptoms improve during CBT. When assessed pre‐ and post‐treatment, fatigue acts as a mediator, not outcome, of these improvements. It seems likely that the working mechanism of CBT is not a one‐way causal effect but a dynamic reciprocal process. Trials integrating intermittent assessments are needed to shed light on these mechanisms and inform optimization of CBT

Metabolic profiling of colorectal cancer organoids: A comparison between high-resolution magic angle spinning magnetic resonance spectroscopy and solution nuclear magnetic resonance spectroscopy of polar extracts

publishedVersio

Improved unsupervised physics-informed deep learning for intravoxel incoherent motion modeling and evaluation in pancreatic cancer patients

${\bf Purpose}$: Earlier work showed that IVIM-NET$_{orig}$, an unsupervised physics-informed deep neural network, was more accurate than other state-of-the-art intravoxel-incoherent motion (IVIM) fitting approaches to DWI. This study presents an improved version: IVIM-NET$_{optim}$, and characterizes its superior performance in pancreatic ductal adenocarcinoma (PDAC) patients. ${\bf Method}$: In simulations (SNR=20), the accuracy, independence and consistency of IVIM-NET were evaluated for combinations of hyperparameters (fit S0, constraints, network architecture, # hidden layers, dropout, batch normalization, learning rate), by calculating the NRMSE, Spearman's $\rho$, and the coefficient of variation (CV$_{NET}$), respectively. The best performing network, IVIM-NET$_{optim}$ was compared to least squares (LS) and a Bayesian approach at different SNRs. IVIM-NET$_{optim}$'s performance was evaluated in 23 PDAC patients. 14 of the patients received no treatment between scan sessions and 9 received chemoradiotherapy between sessions. Intersession within-subject standard deviations (wSD) and treatment-induced changes were assessed. ${\bf Results}$: In simulations, IVIM-NET$_{optim}$ outperformed IVIM-NET$_{orig}$ in accuracy (NRMSE(D)=0.18 vs 0.20; NMRSE(f)=0.22 vs 0.27; NMRSE(D*)=0.39 vs 0.39), independence ($\rho$(D*,f)=0.22 vs 0.74) and consistency (CV$_{NET}$ (D)=0.01 vs 0.10; CV$_{NET}$ (f)=0.02 vs 0.05; CV$_{NET}$ (D*)=0.04 vs 0.11). IVIM-NET$_{optim}$ showed superior performance to the LS and Bayesian approaches at SNRs<50. In vivo, IVIM-NET$_{optim}$ sshowed significantly less noisy parameter maps with lower wSD for D and f than the alternatives. In the treated cohort, IVIM-NET$_{optim}$ detected the most individual patients with significant parameter changes compared to day-to-day variations. ${\bf Conclusion}$: IVIM-NET$_{optim}$ is recommended for IVIM fitting to DWI data

Fecal Microbiota Transplantation from Overweight or Obese Donors in Cachectic Patients with Advanced Gastroesophageal Cancer : A Randomized, Double-blind, Placebo-Controlled, Phase II Study

Purpose Cachexia is a multifactorial syndrome, associated with poor survival in patients with cancer, and is influenced by the gut microbiota. We investigated the effects of fecal microbiota transplantation (FMT) on cachexia and treatment response in patients with advanced gastroesophageal cancer. Experimental Design: In a double-blind randomized placebo-controlled trial performed in the Amsterdam University Medical Center, we assigned 24 cachectic patients with metastatic HER2-negative gastroesophageal cancer to either allogenic FMT (healthy obese donor) or autologous FMT, prior to palliative chemotherapy (capecitabine and oxaliplatin). Primary objective was to assess the effect of allogenic FMT on satiety. Secondary outcomes were other features of cachexia, along with disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and toxicity. Finally, exploratory analyses were performed on the effect of FMT on gut microbiota composition (metagenomic sequencing) and metabolites (untargeted metabolomics). Results: Allogenic FMT did not improve any of the cachexia outcomes. Patients in the allogenic group (n = 12) had a higher DCR at 12 weeks (P = 0.035) compared with the autologous group (n = 12), longer median OS of 365 versus 227 days [ HR = 0.38; 95% confidence interval (CI), 0.14-1.05; P = 0.057] and PFS of 204 versus 93 days (HR = 0.50; 95% CI, 0.21-1.20; P = 0.092). Patients in the allogenic group showed a significant shift in fecal microbiota composition after FMT (P = 0.010) indicating proper engraftment of the donor microbiota. Conclusions: FMT from a healthy obese donor prior to first-line chemotherapy did not affect cachexia, but may have improved response and survival in patients with metastatic gastroesophageal cancer. These results provide a rational for larger FMT trials.Peer reviewe

Spiritual well-being and associated factors in Dutch patients with advanced cancer

CONTEXT: Palliative care aims to support patients' spiritual needs with the intention of promoting their spiritual well-being (SWB), an important dimension of quality of life. SWB is one of the less-studied dimensions of QoL, particularly in a secular country such as the Netherlands. OBJECTIVES: In this study we aimed to get a better understanding of SWB in Dutch patients with advanced cancer. We therefore examined its prominence and associated factors. METHODS: We used the baseline data of a cohort study on experienced quality of care and quality of life (eQuiPe study), which included 1,103 patients with advanced cancer. In addition to sociodemographic and religious/spiritual characteristics, study measures comprised the SWB subscales Meaning, Peace, and Faith of the revised FACIT-Sp-12, spiritual problems and needs (PNPCsv), quality of life (EORTC-QLQ-C30) and satisfaction with healthcare professionals' interpersonal skills (INPATSAT-32). RESULTS: On average, patients experienced quite a bit of Meaning (8.9, SD 2.3), a little bit to somewhat Peace (6.8, SD 2.7), and very low levels of Faith (2.9, SD 3.7). Two-thirds (71%) of patients reported one or more spiritual problems, for which the majority (54%) wanted to receive attention. In the final multivariable models, only a few factors were associated with SWB, such as greater spiritual needs with lower levels of Meaning and Peace. CONCLUSION: Dutch patients with advanced cancer experience medium to low levels of Meaning, Peace, and Faith. More attention for their SWB is warranted

Personalized versus standard cognitive behavioral therapy for fear of cancer recurrence, depressive symptoms or cancer-related fatigue in cancer survivors:study protocol of a randomized controlled trial (MATCH-study)

Abstract Background Fear of cancer recurrence, depressive symptoms, and cancer-related fatigue are prevalent symptoms among cancer survivors, adversely affecting patients’ quality of life and daily functioning. Effect sizes of interventions targeting these symptoms are mostly small to medium. Personalizing treatment is assumed to improve efficacy. However, thus far the empirical support for this approach is lacking. The aim of this study is to investigate if systematically personalized cognitive behavioral therapy is more efficacious than standard cognitive behavioral therapy in cancer survivors with moderate to severe fear of cancer recurrence, depressive symptoms, and/or cancer-related fatigue. Methods The study is designed as a non-blinded, multicenter randomized controlled trial with two treatment arms (ratio 1:1): (a) systematically personalized cognitive behavioral therapy and (b) standard cognitive behavioral therapy. In the standard treatment arm, patients receive an evidence-based diagnosis-specific treatment protocol for fear of cancer recurrence, depressive symptoms, or cancer-related fatigue. In the second arm, treatment is personalized on four dimensions: (a) the allocation of treatment modules based on ecological momentary assessments, (b) treatment delivery, (c) patients’ needs regarding the symptom for which they want to receive treatment, and (d) treatment duration. In total, 190 cancer survivors who experience one or more of the targeted symptoms and ended their medical treatment with curative intent at least 6 months to a maximum of 5 years ago will be included. Primary outcome is limitations in daily functioning. Secondary outcomes are level of fear of cancer recurrence, depressive symptoms, fatigue severity, quality of life, goal attainment, therapist time, and drop-out rates. Participants are assessed at baseline (T0), and after 6 months (T1) and 12 months (T2). Discussion To our knowledge, this is the first randomized controlled trial comparing the efficacy of personalized cognitive behavioral therapy to standard cognitive behavioral therapy in cancer survivors. The study has several innovative characteristics, among which is the personalization of interventions on several dimensions. If proven effective, the results of this study provide a first step in developing an evidence-based framework for personalizing therapies in a systematic and replicable way. Trial registration The Dutch Trial Register (NTR) NL7481 (NTR7723). Registered on 24 January 2019

Cyber Security: China and Russia\u27s Erosion of 21st Century United States\u27 Hegemony

With Russia and China emerging as challengers to U.S. hegemony, the use of cyber warfare could tilt the current balance of power in either of their favors. Using various methods, hackers can acquire sensitive information and destroy online infrastructures. In the development of cyber warfare, China has become a seasoned veteran with computer virus operations dating back to 199714. Russia has emerged as a cyber aggressor, as seen in Russia’s cyber attacks on several countries in the last decade. This paper argues that, with the growth of foreign cyber technology, the probability of cyberspace being used as a military front by state or non-state actors against the United States increases

Continuity of care for patients with de novo metastatic cancer during the COVID-19 pandemic:A population-based observational study

During the COVID-19 pandemic recommendations were made to adapt cancer care. This population-based study aimed to investigate possible differences between the treatment of patients with metastatic cancer before and during the pandemic by comparing the initial treatments in five COVID-19 periods (weeks 1–12 2020: pre-COVID-19, weeks 12–20 2020: 1st peak, weeks 21–41 2020: recovery, weeks 42–53 2020: 2nd peak, weeks 1–20 2021: prolonged 2nd peak) with reference data from 2017 to 2019. The proportion of patients receiving different treatment modalities (chemotherapy, hormonal therapy, immunotherapy or targeted therapy, radiotherapy primary tumor, resection primary tumor, resection metastases) within 6 weeks of diagnosis and the time between diagnosis and first treatment were compared by period. In total, 74,208 patients were included. Overall, patients were more likely to receive treatments in the COVID-19 periods than in previous years. This mainly holds for hormone therapy, immunotherapy or targeted therapy and resection of metastases. Lower odds were observed for resection of the primary tumor during the recovery period (OR 0.87; 95% CI 0.77–0.99) and for radiotherapy on the primary tumor during the prolonged 2nd peak (OR 0.84; 95% CI 0.72–0.98). The time from diagnosis to the start of first treatment was shorter, mainly during the 1st peak (average 5 days, p &lt;.001). These findings show that during the first 1.5 years of the COVID-19 pandemic, there were only minor changes in the initial treatment of metastatic cancer. Remarkably, time from diagnosis to first treatment was shorter. Overall, the results suggest continuity of care for patients with metastatic cancer during the pandemic.</p