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Rationale and Objectives: This study investigates the dose burden of photon-counting detector (PCD) lung CT with ultra-high-resolution (UHR) and standard mode using organ-based tube current modulation (OBTCM)., Materials and Methods: An anthropomorphic Alderson-Rando phantom was scanned in UHR and standard mode with and without OBTCM on three dose levels (IQ 5, 20, 50). Effective radiation dose was determined by thermoluminescent dosimetry in 13 measurement sites and compared with the calculated effective dose derived from the dose-length product. Image quality was evaluated subjectively by six radiologists using an equidistant 7-point scale and objectively by means of modulation transfer function analysis., Results: Measured effective radiation exposure was lower in UHR and OBTCM studies than in standard mode (IQ 5: 0.34-0.36, IQ 20: 1.57-1.70, IQ 50: 3.76-3.99 mSv). Compared with the calculated effective dose, the radiation exposure measured with thermoluminescence dosimetry was 131-170% higher. Noise in UHR mode was rated lower than in standard (all p ≤ 0.042) and OBTCM images (all p ≤ 0.028) for all dose levels, while image sharpness was deemed highest for UHR protocols (all p ≤ 0.042). The use of OBTCM had no significant effect on either dimension of subjective image quality (all p ≥ 0.999). Modulation transfer function analysis confirmed the highest spatial frequency in UHR datasets (all p ≤ 0.016)., Conclusion: In PCD-CT of the lung, full field-of-view UHR imaging entails no dose disadvantage over standard mode despite superior image quality. OBTCM possesses moderate dose saving potential. Thermoluminescence dosimetry yielded considerably higher effective doses than those calculated from dose-length products., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jan-Peter Grunz [grant number Z-3BC/02] and Philipp Gruschwitz [Z-02CSP/18] are financially supported by the Interdisciplinary Center of Clinical Research Würzburg. Andreas Kunz, Thorsten Bley, and Jan-Peter Grunz report a relationship with Siemens Healthineers that includes consulting or advisory and paid expert testimony. The Department of Diagnostic and Interventional Radiology receives ongoing research funding by Siemens Healthineers outside of the presented work., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

We present the rare case of a 42-year-old woman with oligometastatic lung adenocarcinoma in her first trimester of pregnancy who was treated for brain metastases with metastasectomy and intraoperative radiation therapy (IORT) using the INTRABEAM® system (Zeiss AG, Jena, Germany). This case underscores the potential of IORT in optimizing cancer treatment while safeguarding fetal health in pregnant patients., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

This work investigates the proposed enhanced efficacy of photodynamic therapy (PDT) by activating photosensitizers (PSs) with Cherenkov light (CL). The approaches of Yoon et al. to test the effect of CL with external radiation were taken up and refined. The results were used to transfer the applied scheme from external radiation therapy to radionuclide therapy in nuclear medicine. Here, the CL for the activation of the PSs (psoralen and trioxsalen) is generated by the ionizing radiation from rhenium-188 (a high-energy beta-emitter, Re-188). In vitro cell survival studies were performed on FaDu, B16 and 4T1 cells. A characterization of the PSs (absorbance measurement and gel electrophoresis) and the CL produced by Re-188 (luminescence measurement) was performed as well as a comparison of clonogenic assays with and without PSs. The methods of Yoon et al. were reproduced with a beam line at our facility to validate their results. In our studies with different concentrations of PS and considering the negative controls without PS, the statements of Yoon et al. regarding the positive effect of CL could not be confirmed. There are slight differences in survival fractions, but they are not significant when considering the differences in the controls. Gel electrophoresis showed a dominance of trioxsalen over psoralen in conclusion of single and double strand breaks in plasmid DNA, suggesting a superiority of trioxsalen as a PS (when irradiated with UVA). In addition, absorption measurements showed that these PSs do not need to be shielded from ambient light during the experiment. An observational test setup for a PDT nuclear medicine approach was found. The CL spectrum of Re-188 was measured. Fluctuating inconclusive results from clonogenic assays were found.

High-grade gliomas (HGGs) and glioblastoma multiforme (GBM) are characterized by a heterogeneous and aggressive population of tissue-infiltrating cells that promote both destructive tissue remodeling and aberrant vascularization of the brain. The formation of defective and permeable blood vessels and microchannels and destructive tissue remodeling prevent efficient vascular delivery of pharmacological agents to tumor cells and are the significant reason why therapeutic chemotherapy and immunotherapy intervention are primarily ineffective. Vessel-forming endothelial cells and microchannel-forming glial cells that recapitulate vascular mimicry have both infiltration and destructive remodeling tissue capacities. The transmembrane protein TMEM230 (C20orf30) is a master regulator of infiltration, sprouting of endothelial cells, and microchannel formation of glial and phagocytic cells. A high level of TMEM230 expression was identified in patients with HGG, GBM, and U87-MG cells. In this study, we identified candidate genes and molecular pathways that support that aberrantly elevated levels of TMEM230 play an important role in regulating genes associated with the initial stages of cell infiltration and blood vessel and microchannel (also referred to as tumor microtubule) formation in the progression from low-grade to high-grade gliomas. As TMEM230 regulates infiltration, vascularization, and tissue destruction capacities of diverse cell types in the brain, TMEM230 is a promising cancer target for heterogeneous HGG tumors.

TMEM230 promotes antigen processing, trafficking, and presentation by regulating the endomembrane system of membrane bound organelles (lysosomes, proteosomes and mitochondria) and phagosomes. Activation of the immune system requires trafficking of various cargos between the endomembrane system and cell plasma membrane. The Golgi apparatus is the hub of the endomembrane system and essential for the generation, maintenance, recycling, and trafficking of the components of the endomembrane system itself and immune system. Intracellular trafficking and secretion of immune system components depend on mitochondrial metalloproteins for ATP synthesis that powers motor protein transport of endomembrane cargo. Glycan modifying enzyme genes and motor proteins are essential for the activation of the immune system and trafficking of antigens between the endomembrane system and the plasma membrane. Recently, TMEM230 was identified as co-regulated with RNASET2 in lysosomes and with metalloproteins in various cell types and organelles, including mitochondria in autoimmune diseases. Aberrant metalloproteinase secretion by motor proteins is a major contributor to tissue remodeling of synovial membrane and joint tissue destruction in rheumatoid arthritis (RA) by promoting infiltration of blood vessels, bone erosion, and loss of cartilage by phagocytes. In this study, we identified that specific glycan processing enzymes are upregulated in certain cell types (fibroblast or endothelial cells) that function in destructive tissue remodeling in rheumatoid arthritis compared to osteoarthritis (OA). TMEM230 was identified as a regulator in the secretion of metaloproteinases and heparanase necessary tissue remodeling in OA and RA. In dendritic (DC), natural killer and T cells, TMEM230 was expressed at low or no levels in RA compared to OA. TMEM230 expression in DC likely is necessary for regulatory or helper T cells to maintain tolerance to self-antigens and prevent susceptibility to autoimmune disease. To identify how TMEM230 and the endomembrane system contribute to autoimmunity we investigated, glycan modifying enzymes, metalloproteinases and motor protein genes co-regulated with or regulated by TMEM230 in synovial tissue by analyzing published single cell transcriptomic datasets from RA patient derived synovial tissue., (Copyright © 2024. Published by Elsevier Inc.)

Glial cells provide physical and chemical support and protection for neurons and for the extracellular compartments of neural tissue through secretion of soluble factors, insoluble scaffolds, and vesicles. Additionally, glial cells have regenerative capacity by remodeling their physical microenvironment and changing physiological properties of diverse cell types in their proximity. Various types of aberrant glial and macrophage cells are associated with human diseases, disorders, and malignancy. We previously demonstrated that transmembrane protein, TMEM230 has tissue revascularization and regenerating capacity by its ability to secrete pro-angiogenic factors and metalloproteinases, inducing endothelial cell sprouting and channel formation. In healthy normal neural tissue, TMEM230 is predominantly expressed in glial and marcophate cells, suggesting a prominent role in neural tissue homeostasis. TMEM230 regulation of the endomembrane system was supported by co-expression with RNASET2 (lysosome, mitochondria, and vesicles) and STEAP family members (Golgi complex). Intracellular trafficking and extracellular secretion of glial cellular components are associated with endocytosis, exocytosis and phagocytosis mediated by motor proteins. Trafficked components include metalloproteins, metalloproteinases, glycans, and glycoconjugate processing and digesting enzymes that function in phagosomes and vesicles to regulate normal neural tissue microenvironment, homeostasis, stress response, and repair following neural tissue injury or degeneration. Aberrantly high sustained levels TMEM230 promotes metalloprotein expression, trafficking and secretion which contribute to tumor associated infiltration and hypervascularization of high tumor grade gliomas. Following injury of the central nervous or peripheral systems, transcient regulated upregulation of TMEM230 promotes tissue wound healing, remodeling and revascularization by activating glial and macrophage generated microchannels/microtubules (referred to as vascular mimicry) and blood vessel sprouting and branching. Our results support that TMEM230 may act as a master regulator of motor protein mediated trafficking and compartmentalization of a large class of metalloproteins in gliomas and gliosis., (Copyright © 2024. Published by Elsevier Inc.)

Intraoperative radiation therapy (IORT) is a radiation technique applying a single fraction with a high dose during surgery. We report the first abdomino-pelvic application of an image-guided intraoperative electron radiation therapy with intraoperative real time dose calculation based on the individual intraoperative patient anatomy. A patient suffering from locoregionally recurrent rectal cancer after treatment with neoadjuvant re-chemoradiation was chosen for this approach. After surgical removal of the recurrence, an adequate IORT applicator was placed as usual. A novel mobile imaging device (ImagingRing, MedPhoton) was positioned around the patient covering the region to be treated with the IORT-applicator in place. It allowed the acquisition of three-dimensional intraoperative cone-beam computed tomography images suitable for dose calculation using an automated scaling (heuristic object and head scatter as well as hardening corrections) of Hounsfield units. After image acquisition confirmed the correct applicator position, the images were transferred to our treatment planning system for intraoperative dose calculation. Treatment could be accomplished using the calculated dose distribution. We herein describe the details of the procedure including necessary adjustments in the typically used IORT equipment and work flow. We further discuss the pros and cons of this new approach generally overcoming a decade long limitation of IORT procedures as well as future perspectives regarding IORT treatments., (© 2023. The Author(s).)

Acute lymphoblastic leukemia (ALL) is the most common cause of cancer-related death in children. Despite significantly increased chances of cure, especially for high-risk ALL patients, it still represents a poor prognosis for a substantial fraction of patients. Misregulated proteins in central switching points of the cellular signaling pathways represent potentially important therapeutic targets. Recently, the inositol phosphatase SHIP1 (SH2-containing inositol 5-phosphatase) has been considered as a tumor suppressor in leukemia. SHIP1 serves as an important negative regulator of the PI3K/AKT signaling pathway, which is frequently constitutively activated in primary T-ALL. In contrast to other reports, we show for the first time that SHIP1 has not been lost in T-ALL cells, but is strongly downregulated. Reduced expression of SHIP1 leads to an increased activation of the PI3K/AKT signaling pathway. SHIP1-mRNA expression is frequently reduced in primary T-ALL samples, which is recapitulated by the decrease in SHIP1 expression at the protein level in seven out of eight available T-ALL patient samples. In addition, we investigated the change in the activity profile of tyrosine and serine/threonine kinases after the restoration of SHIP1 expression in Jurkat T-ALL cells. The tyrosine kinase receptor subfamilies of NTRK and PDGFR, which are upregulated in T-ALL subgroups with low SHIP1 expression, are significantly disabled after SHIP1 reconstitution. Lentiviral-mediated reconstitution of SHIP1 expression in Jurkat cells points to a decreased cellular proliferation upon transplantation into NSG mice in comparison to the control cohort. Together, our findings will help to elucidate the complex network of cell signaling proteins, further support a functional role for SHIP1 as tumor suppressor in T-ALL and, much more importantly, show that full-length SHIP1 is expressed in T-ALL samples.

A large amount of published research points to the interesting concept (hypothesis) that magnesium (Mg) status may have relevance for the outcome of COVID-19 and that Mg could be protective during the COVID disease course. As an essential element, Mg plays basic biochemical, cellular, and physiological roles required for cardiovascular, immunological, respiratory, and neurological functions. Both low serum and dietary Mg have been associated with the severity of COVID-19 outcomes, including mortality; both are also associated with COVID-19 risk factors such as older age, obesity, type 2 diabetes, kidney disease, cardiovascular disease, hypertension, and asthma. In addition, populations with high rates of COVID-19 mortality and hospitalization tend to consume diets high in modern processed foods, which are generally low in Mg. In this review, we review the research to describe and consider the possible impact of Mg and Mg status on COVID-19 showing that (1) serum Mg between 2.19 and 2.26 mg/dL and dietary Mg intakes > 329 mg/day could be protective during the disease course and (2) inhaled Mg may improve oxygenation of hypoxic COVID-19 patients. In spite of such promise, oral Mg for COVID-19 has thus far been studied only in combination with other nutrients. Mg deficiency is involved in the occurrence and aggravation of neuropsychiatric complications of COVID-19, including memory loss, cognition, loss of taste and smell, ataxia, confusion, dizziness, and headache. Potential of zinc and/or Mg as useful for increasing drug therapy effectiveness or reducing adverse effect of anti-COVID-19 drugs is reviewed. Oral Mg trials of patients with COVID-19 are warranted.

Elderly patients represent a growing subgroup of cancer patients for whom the role of radiation therapy is poorly defined. Older patients are still clearly underrepresented in clinical trials, resulting in very limited high-level evidence. Moreover, elderly patients are less likely to receive radiation therapy in similar clinical scenarios compared to younger patients. However, there is no clear evidence for a generally reduced radiation tolerance with increasing age. Modern radiation techniques have clearly reduced acute and late side effects, thus extending the boundaries of the possible regarding treatment intensity in elderly or frail patients. Hypofractionated regimens have further decreased the socioeconomic burden of radiation treatments by reducing the overall treatment time. The current review aims at summarizing the existing data for the use of radiation therapy or chemoradiation in elderly patients focusing on the main cancer types. It provides an overview of treatment tolerability and outcomes with current standard radiation therapy regimens, including possible predictive factors in the elderly population. Strategies for patient selection for standard or tailored radiation therapy approaches based on age, performance score or comorbidity, including the use of prediction tests or geriatric assessments, are discussed. Current and future possibilities for improvements of routine care and creation of high-level evidence in elderly patients receiving radiation therapy are highlighted., Competing Interests: Falk Roeder received travel grants and lecture honoraria from Intraop Medical and PharmaMar. All other authors reported no competing interests., (© 2023 Roeder et al.)

Objective: Malnutrition is often underestimated in the context of cancer therapy: the dietary trends initiated by patients after diagnosis are usually neither known to nor evaluated by the medical staff. Here, we propose a combined screening instrument evaluating malnutrition and dietary trends., Methods: The validated screening tool NRS-2002 was combined with a four-item questionnaire assessing whether (1) patients preferred certain foods, (2) avoided certain foods, (3) used dietary supplements or followed a special diet since the time of cancer diagnosis. The screening tool was routinely used by cancer patients in the daily practice of three oncological departments. The presented analysis was performed retrospectively and anonymized., Results: Overall, 102 cancer patients undergoing systemic therapy (CP), 97 undergoing radiation therapy (RP), and 36 head-neck cancer patients (HNP) were screened. The CP cohort showed a higher rate of malnutrition (50.00%) than the HNP (28.13%) or RP (26.80%) cohort. Overall, diet changes were observed in 33.63% of all patients. Avoiding meat, stimulants, or hard and edgy food was often mentioned in free text answers, while patients reported a preference for fruit and vegetables. Nutritional supplements were used by 28.76% of the patients. While dietary changes were common, only 6.64% of the patients mentioned adhering to a specific cancer diet., Conclusion: Malnutrition is still underestimated nowadays. Diet trends, especially avoiding certain foods, are common in cancer patients, while adhering to a specific cancer diet is an exception. Diet trends should be assessed and addressed to avoid or aggravate malnutrition.

Objective. CT-mesh hybrid phantoms (or 'hybrid(s)') made from integrated patient CT data and mesh-type reference computational phantoms (MRCPs) can be beneficial for patient-specific whole-body dose evaluation, but this benefit has yet to be evaluated for second cancer risk prediction. The purpose of this study is to compare the hybrid's ability to predict risk throughout the body with a patient-scaled MRCP against ground truth whole-body CTs (WBCTs). Approach. Head and neck active scanning proton treatment plans were created for and simulated on seven hybrids and the corresponding scaled MRCPs and WBCTs. Equivalent dose throughout the body was calculated and input into five second cancer risk models for both excess absolute and excess relative risk (EAR and ERR). The hybrid phantom was evaluated by comparing equivalent dose and risk predictions against the WBCT. Main results. The hybrid most frequently provides whole-body second cancer risk predictions which are closer to the ground truth when compared to a scaled MRCP alone. The performance of the hybrid relative to the scaled MRCP was consistent across ERR, EAR, and all risk models. For all in-field organs, where the hybrid shares the WBCT anatomy, the hybrid was better than or equal to the scaled MRCP for both equivalent dose and risk prediction. For out-of-field organs across all patients, the hybrid's equivalent dose prediction was superior than the scaled MRCP in 48% of all comparisons, equivalent for 34%, and inferior for 18%. For risk assessment in the same organs, the hybrid's prediction was superior than the scaled MRCP in 51.8% of all comparisons, equivalent in 28.6%, and inferior in 19.6%. Significance. Whole-body risk predictions from the CT-mesh hybrid have shown to be more accurate than those from a reference phantom alone. These hybrids could aid in risk-optimized treatment planning and individual risk assessment to minimize second cancer incidence., (Creative Commons Attribution license.)

The general topic of this year's 17th St. Gallen (SG) International Consensus Conference on the treatment of patients with early breast cancer (SG-BCC) was "Customizing local and systemic therapies for women with early breast cancer." This topic considers that each treatment decision must also consider the cancer-specific situation of the individual patient. This year, the votes of the SG-BCC were again discussed taking into account the multidisciplinary German S3 Guidelines and the recommendations of the Breast Cancer Working Group of the AGO (Arbeitsgemeinschaft Gynäkologische Onkologie; AGO Mamma). As the international panel of the SG-BCC consists of experts from different countries, the votes do represent an international cross-section of opinions. Therefore, it is useful to discuss the voting results with respect to the German evidence-based treatment guidelines. This publication focuses mainly on systemic treatment., Competing Interests: Prof. Cornelia Kolberg-Liedtke received honoraria from Roche, AstraZeneca, Celgene, Novartis, Pfizer, Lilly, Hexal, Amgen, Eisai, and SonoScape as well as honoraria for consultancy work from Phaon Scientific, Novartis, Pfizer, and Celgene as well as research assistance from Roche, Novartis, and Pfizer. Travel grant from Novartis and Roche, employment at Palleos Healthcare, and Managing Director and partner at Phaon Scientific. Prof. Diana Lüftner received honoraria from Amgen, AstraZeneca, Celgene, Pfizer, Novartis, Roche, L'Oréal, Teva, GSK, and Eli Lilly. Prof. Dr. med. Sara Y. Brucker received honoraria from Roche, Novartis, Pfizer, AstraZeneca, and Teva. Prof. Dr. med. Wilfried Budach has no conflict of interest. Prof. Dr. med. Carsten Denkert received honoraria from Novartis, Roche, MSD Oncology, Daiichi Sankyo, Molecular Health, AstraZeneca, and Merck as well as research funding (for the Pathology Institute) from Myriad Genetics and Roche. He was co-founder and (until 2016) shareholder of Sividon Diagnostics. He is a co-inventor of the VMscope software for identifying Ki-67. Prof. Peter A. Fasching received grants from BioNtech and Cepheid as well as honoraria from Novartis, Pfizer, Daiichi-Sankyo, AstraZeneca, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, SeaGen, Roche, Hexal, and Agendia. Renate Haidinger has no conflict of interest. Prof. Nadia Harbeck received honoraria from AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, and Seattle Genetics. Prof. Jens Huober received honoraria from Celgene, Roche, Novartis, Hexal, Pfizer, AstraZeneca, Lilly, Amgen, Eisai, and MSD as well as research assistance from Celgene, Hexal, and Novartis and travel grants from Roche, Novartis, Daiichi Sankyo, and Celgene. Prof. Christian Jackisch received honoraria from AstraZeneca, Lilly, Celgene, Novartis, Pfizer, AstraZeneca, Pierre Fabre, and Roche as well as research assistance from Exact Sciences. Prof. Wolfgang Janni received honoraria from Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Genomic Health, Hexal, Lilly, MSD, Novartis, Pfizer, Roche, Tesaro, and Teva. Dr. med. David Krug received honoraria from Merck Sharp & Dohme. Prof. Thorsten Kühn received honoraria from Celgene, Roche, and Pfizer as well as research assistance from Mammotome, Merit Medical, and Pfizer. Prof. Dr. med. Sibylle Loibl received honoraria from AbbVie, Amgen, AstraZeneca, Bayer, BMS, Celgene, Chugai, Daiichi Sankyo, EirGenix, GSK, Immunomedics, Ipsen, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Prime/Medscape, Puma, Roche, Samsung, Seagen, Teva, and Vifor and has a patent application (EP14153692.0) under review. Prof. Volkmar Müller received honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, and Seattle Genetics as well as honoraria for consultancy work from Genomic Health, Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Tesaro, Seattle Genetics, and Neltar as well as funding for travel expenses from Roche, Pfizer, and Daiichi Sankyo and research assistance for the employer from Novartis, Roche, Seattle Genetics, and Genentech. Prof. Andreas Schneeweiss received honoraria from Celgene, Roche, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, and Lilly as well as research assistance from Celgene, Roche, AbbVie, and Molecular Partner [sic: Molecular Partners] as well as travel grants from Celgene, Roche, and Pfizer. Prof. Christoph Thomssen received honoraria from Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Lilly, MSD, Mylan, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Roche, and Vifor and research assistance from American Diagnostica, Affymetrix, and Nanostring. Prof. Michael Untch: honoraria to the employer (for AdBoard participation, presentations) as well as travel assistance from Amgen, AstraZeneca, BMS, Celgene, Daiichi Sankyo, Eisai, Janssen Cilag, Johnson & Johnson, Lilly Deutschland, Lilly International, MSD Merck, Mundipharma, Myriad Genetics, Odonate, Pfizer, PUMA Biotechnology, Riemser, Roche, Pierre Fabre, Novartis, Abbie [sic: AbbVie], Molecular Health, Agendia, and GSK. Prof. Dr. Marc Thill received honoraria and travel assistance from Amgen, AstraZeneca, Aurikamed, Becton and Dickinson, Biom'Up, Celgene, Clearcut, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Grünenthal, Hexal, I-Med Institute, Lilly, MCI, Medtronic, MSD, Neodynamics, Norgine, Novartis, OnkoLive, OmniaMed, Organon, pfm medical, Pfizer, Roche, Seagen, Sysmex, Tesaro, Teva, RTI Surgical, and Vifor and research assistance from Endomagnetics and Exact Sciences., (Copyright © 2022 by S. Karger AG, Basel.)

Purpose: To evaluate the results of the radiation therapy (RT) quality assurance (QA) program of the phase 3 randomized SAKK 09/10 trial in patients with biochemically recurrent prostate cancer after prostatectomy., Methods and Materials: Within the Schweizerische Arbeitsgemeinschaft für Klinische Krebsforschung (SAKK) 09/10 trial testing 64-Gy versus 70-Gy salvage RT, a central collection of treatment plans was performed and thoroughly reviewed by a dedicated medical physicist and radiation oncologist. Adherence to the treatment protocol and specifically to the European Organization for the Research and Treatment of Cancer (EORTC) guidelines for target volume definition (classified as deviation observed yes vs no) and its potential correlation with acute and late toxicity (Common Terminology Criteria for Adverse Events version 4.0) and freedom from biochemical progression (FFBP) were investigated., Results: The treatment plans for 344 patients treated between February 2011 and April 2014 depicted important deviations from the EORTC guidelines and the recommendations per trial protocol. For example, in up to half of the cases, the delineated structures deviated from the protocol (eg, prostate bed in 48.8%, rectal wall [RW] in 41%). In addition, variations in clinical target volume (CTV) and planning target volume (PTV) occurred frequently (eg, CTV and PTV deviations in up to 42.4% and 25.9%, respectively). The detected deviations showed a significant association with a lower risk of grade ≥2 gastrointestinal acute toxicity when the CTV did not overlap the RW versus when the CTV overlapped the RW (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.22-0.85; P = .014), and a higher rate of grade ≥2 late genitourinary (GU) toxicity when the CTV overlapped the RW (OR, 2.58; 95% CI, 1.17-5.72; P = .019). A marginally significant lower risk of grade ≥2 late GU toxicity was observed when the prostate bed did not overlap versus did overlap the RW (OR, 0.51; 95% CI, 0.25-1.03; P = .06). In addition, a marginally significant decrease in FFBP was observed in patients with PTV not including surgical clips as potential markers of the limits of the prostate bed (hazard ratio, 1.44; 95% CI, 0.96-2.17; P = .07)., Conclusions: Despite a thorough QA program, the central review of a phase 3 trial showed limited adherence to treatment protocol recommendations, which was associated with a higher risk of toxicity by means of acute or late gastrointestinal or GU toxicity and showed a trend toward worse FFBP. Data from this QA review might help to refine future QA programs and prostate bed delineation guidelines., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Glioblastomas (GBM) are the most aggressive tumors originating in the brain. Histopathologic features include circuitous, disorganized, and highly permeable blood vessels with intermittent blood flow. These features contribute to the inability to direct therapeutic agents to tumor cells. Known targets for anti-angiogenic therapies provide minimal or no effect in overall survival of 12-15 months following diagnosis. Identification of novel targets therefore remains an important goal for effective treatment of highly vascularized tumors such as GBM. We previously demonstrated in zebrafish that a balanced level of expression of the transmembrane protein TMEM230/C20ORF30 was required to maintain normal blood vessel structural integrity and promote proper vessel network formation. To investigate whether TMEM230 has a role in the pathogenesis of GBM, we analyzed its prognostic value in patient tumor gene expression datasets and performed cell functional analysis. TMEM230 was found necessary for growth of U87-MG cells, a model of human GBM. Downregulation of TMEM230 resulted in loss of U87 migration, substratum adhesion, and re-passaging capacity. Conditioned media from U87 expressing endogenous TMEM230 induced sprouting and tubule-like structure formation of HUVECs. Moreover, TMEM230 promoted vascular mimicry-like behavior of U87 cells. Gene expression analysis of 702 patients identified that TMEM230 expression levels distinguished high from low grade gliomas. Transcriptomic analysis of patients with gliomas revealed molecular pathways consistent with properties observed in U87 cell assays. Within low grade gliomas, elevated TMEM230 expression levels correlated with reduced overall survival independent from tumor subtype. Highest level of TMEM230 correlated with glioblastoma and ATP-dependent microtubule kinesin motor activity, providing a direction for future therapeutic intervention. Our studies support that TMEM230 has both glial tumor and endothelial cell intracellular and extracellular functions. Elevated levels of TMEM230 promote glial tumor cell migration, extracellular scaffold remodeling, and hypervascularization and abnormal formation of blood vessels. Downregulation of TMEM230 expression may inhibit both low grade glioma and glioblastoma tumor progression and promote normalization of abnormally formed blood vessels. TMEM230 therefore is both a promising anticancer and antiangiogenic therapeutic target for inhibiting GBM tumor cells and tumor-driven angiogenesis., Competing Interests: IZ and RR have a patent accepted concerning the use of Agents that modulate TMEM230 in tumor associated angiogenesis. Patent Application International Publication number: 20200247882. Agents that modulate TMEM230 as angiogenesis regulators and that detect TMEM230 AS markers of metastasis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cocola, Magnaghi, Abeni, Pelucchi, Martino, Vilardo, Piscitelli, Consiglio, Grillo, Mosca, Gualtierotti, Mazzaccaro, La Sala, Di Pietro, Palizban, Liuni, DePedro, Morara, Nano, Kehler, Greve, Noghero, Marazziti, Bussolino, Bellipanni, D’Agnano, Götte, Zucchi and Reinbold.)

The paper "Combating COVID-19 and Building Immune Resilience: A Potential Role for Magnesium Nutrition?" by TC Wallace, which was published in the Journal of the American College of Nutrition highlights the importance of adequate magnesium (Mg) supply in relation to COVID-19. Wallace notes that Mg deficiency is associated with low-grade chronic inflammation. Furthermore, hypokalemia and a lack of active Vitamin D are consequences of a Mg deficit. In this way, Mg deficiency may exacerbate the course of COVID-19. Therefore, in patients with Covid-19 permanent monitoring of the Mg status and, if necessary, supplementation should be carried out. The possible importance of Mg in COVID-19 was only recently discussed also by Iotti et al. and the German Society for Magnesium Research e.V. Considering the meaningful connections between Mg and COVID-19 there are relevant research topics that should be addressed: Does Mg deficiency increase the risk of infection with COVID-19 or the risk of a severe course of the disease? Is there an increased prevalence of Mg deficiency in COVID-19 patients? Could Mg supplementation alleviate the course of the disease in COVID-19 or reduce complications? Does pharmacological induction of hypermagnesemia via intravenous Mg provide clinical benefits for COVID-19 patients in the intensive care unit (for example with regard to lung function or thromboembolism)?