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Background and Introduction: Increasing evidence suggests that a subgroup of patients with oligometastatic cancer might achieve a prolonged disease-free survival through local therapy for all active cancer lesions. Our aims are to investigate the impact of brain metastases on the classification, treatment, and outcome in these patients., Materials and Methods: We analyzed a total of 7,000 oncological positron emission tomography scans to identify patients with extracranial oligometastatic disease (defined as ≤ 5 intra- or extra-cranial metastases). Concurrent magnetic resonance imaging brain was assessed to quantify intracranial tumor burden. We investigated the impact of brain metastases on oligometastatic disease state, therapeutic approaches, and outcome. Predictors for transitioning from oligo- to polymetastatic states were evaluated using regression analysis., Results: A total of 106 patients with extracranial oligometastases and simultaneous brain metastases were identified, primarily originating from skin or lung/pleura cancers (90%, n = 96). Brain metastases caused a transition from an extracranial oligometastatic to a whole-body polymetastatic state in 45% (n = 48) of patients. While oligometastatic patients received systemic therapy (55% vs. 35%) more frequently and radiotherapy for brain metastases was more often prescribed to polymetastatic patients (44% vs. 26%), the therapeutic approach did not differ systematically between both sub-groups. The oligometastatic sub-group had a median overall survival of 28 months compared to 10 months in the polymetastatic sub-group (p < 0.01)., Conclusion: In patients with brain metastases, a low total tumor burden with an oligometastatic disease state remained a significant prognostic factor for overall survival. Presence of brain metastases should therefore not serve as exclusion criterion for clinical trials in the field of oligometastatic disease. Moreover, it underscores the importance of considering a multimodality treatment strategy in oligometastatic cancer patients., (© 2024. The Author(s).)

Aims: Multidisciplinary tumor boards (MDTs) are an integral part of ensuring high-quality, evidence-based and personalized cancer care. In this study, we aimed to evaluate the adherence to and implementation of MDT recommendations in patients with oligometastatic disease (OMD)., Methods: We screened all oncologic positron emission tomography (PET) scans conducted at a single comprehensive cancer center in 2020. Patients were included if they had evidence of imaging-based OMD from a solid organ malignancy on the index scans, had their OMD case discussed at an MDT, and were treated and followed up at the same center. A switch away from the MDT-recommended treatment modalities was classified as a major deviation ; non-MDT-mandated adjustments to a recommended treatment modality were coded as minor deviation . Clinical data was obtained via chart review; statistical calculations were computed using the R software., Results: After review of PET and/or concurrent brain scans, 787 cases of OMD were identified. Thereof, 347 (44.1 %) cases were discussed at MDT, of which 331 (42.1 %) were therapeutically managed and subsequently followed. The three most commonly recommended therapies were systemic therapy (35.6 %), multimodality treatment including definitive local therapy (17.8 %), and radiotherapy (13.9 %). A major deviation was recorded in 16.3 % of cases (most commonly: none of the MDT-recommended treatment modalities were performed: 19 (35.2 %); not all MDT-planned treatment modalities were performed: 12 (22.2 %); and additional treatment modality was performed: 11 (20.3 %). A minor deviation was found in 1.5 % of cases. On multivariable regression, number of distant metastases (n > 1) was associated with a major deviation (OR: 1.85; 95 % CI, 1.0-3.52). Major deviations were associated with a significantly worse OS (p = 0.0034)., Conclusions: Adherence to and implementation of MDT recommendations in OMD patients was generally high (83.7%). Major deviations might be further reduced by more careful and elaborate discussions of OMD patient characteristics s and patient preferences., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AW received research grants through a research collaboration (“POP”) of the University of Zurich with Hoffmann-La Roche Ltd. MAH received research grants from Immune-Sensor, Inc. and ViewRay, Inc., as well as speaking honoraria for presenting at the Harvard Medical School Breast Cancer Symposium. M.H. received grants and speaker honoraria from GE Healthcare, a fund by the Alfred and Annemarie von Sick legacy and a grant from the clinical research priority program (CRPP) Artificial Intelligence in Oncological Imaging Network of the University of Zurich. NA has received grants from ViewRay Inc. and BrainLab and personal fees from AstraZeneca, Debiopharm, ViewRay and BrainLab, and non-financial support from ViewRay, all outside of the submitted work. MG has received grants from AstraZeneca and Varian and personal fees from AstraZeneca, all outside of the submitted work. Moreover, the USZ Department of Radiation Oncology has research and teaching agreements with Siemens/Varian, ViewRay and VisionRT. PB cited research grants to the institution from ViewRay Inc. (Mountain View, CA, USA)., (© 2024 The Author(s).)

Background: Oligoprogression is defined as cancer progression of a limited number of metastases under active systemic therapy. The role of metastasis-directed therapy, using stereotactic body radiotherapy (SBRT), is controversial as is the continuation versus switch of systemic therapy. We report outcomes of oligoprogressive patients after SBRT, and compare those patients that continued or switched their current line of systemic therapy., Material/methods: We included patients who developed up to 5 progressive extracranial metastases under systemic therapy for any solid organ malignancy and were treated with SBRT to all lesions at our institution between 01/2014 and 12/2019. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method, and the interval to the next systemic therapy line determined using cumulative incidence functions. Multivariable Cox regression models were used to analyze the influence of baseline and post-progression variables on OS, PFS and survival with the next systemic therapy after SBRT., Results: Among 135 patients with oligoprogressive disease of which the most common primary tumor was lung cancer (n = 46, 34.1 %), 96 continued their current line of systemic therapy after oligoprogression. Among 39 who switched systemic therapy, 28 (71.8 %) paused or discontinued, while 11 (28.2 %) immediately started another systemic treatment. After a median follow-up of 27.2 months, patients that switched and those who continued systemic therapy after oligoprogression had comparable median OS (32.1 vs. 38.2 months, p = 0.47) and PFS (4.3 vs. 3.4 months, p = 0.6). The intervals to the next systemic therapy line were comparable between both cohorts (p = 0.6). An ECOG performance status of 2 and immediately starting a new systemic therapy after oligoprogression were associated with a poorer survival without next systemic therapy, while the de-novo OMD state was associated with better survival without next systemic therapy compared to the induced state., Conclusion: Oncological outcomes of patients that continued or switched systemic therapy after SBRT for oligoprogression were comparable, potentially indicating that further lines of treatment may be safely delayed in selected cases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Introduction and Background: Metastatic disease has been proposed as a continuum, with no clear cut-off between oligometastatic and polymetastatic disease. This study aims to quantify tumor burden and patterns of spread in unselected metastatic cancer patients referred for PET-based staging, response assessment of restaging., Materials and Methods: All oncological fluorodeoxyglucose (FDG-) and prostate-specific membrane antigen (PSMA-) positron emission tomography (PET) scans conducted at a single academic center in 2020 were analyzed. Imaging reports of all patients with metastatic disease were reviewed and assessed., Results: For this study, 7,000 PET scans were screened. One third of PET scans (n = 1,754; 33 %) from 1,155 unique patients showed presence of metastatic disease from solid malignancies, of which 601 (52 %) and 554 (48 %) were classified as oligometastatic (maximum 5 metastases) and polymetastatic (>5 metastases), respectively. Lung and pleural cancer, skin cancer, and breast cancer were the most common primary tumor histologies with 132 (23.8 %), 88 (15.9 %), and 72 (13.0 %) cases, respectively. Analysis of the number of distant metastases showed a strong bimodal distribution of the metastatic burden with 26 % of patients having one solitary metastasis and 43 % of patients harboring >10 metastases. Yet, despite 43 % of polymetastatic patients having >10 distant metastases, their pattern of distribution was restricted to one or two organs in about two thirds of patients, and there was no association between the number of distant metastases and the number of involved organs., Conclusion: The majority of metastatic cancer patients are characterized by either a solitary metastasis or a high tumor burden with >10 metastases, the latter was often associated with affecting a limited number of organs. These findings support both the spectrum theory of metastasis and the seed and soil hypothesis and can support in designing the next generation of clinical trials in the field of oligometastatic disease., Competing Interests: PB cited research grants to the institution from ViewRay Inc. (Mountain View, CA, USA). NA has received grants from ViewRay Inc. and BrainLab and personal fees from AstraZeneca, Debiopharm, ViewRay and BrainLab, and non-financial support from ViewRay, all outside of the submitted work. MH has received research support from GE Healthcare, a fund by the Alfred and Annemarie von Sick legacy for translational and clinical cardiac and oncological research, and a grant by the Clinical Research Priority Program (CRRP) “Artificial Intelligence in oncological Imaging” of the University Zurich, all outside of the submitted work., (© 2024 The Authors.)

•Stereotactic body radiation therapy (SBRT) for ultra-central lung tumors is associated with high toxicity rates.•To evaluate differences in radiosensitivity within the proximal bronchial tree (PBT), the PBT was sub-segmented into seven anatomical sections.•A risk-adapted SBRT regimen of EQD2&#95;10 = 54.4 Gy in 8 or 10 fractions results in excellent local control and low rates of severe toxicity.•Data from a recent meta -analysis, the NORDIC Hilus trial and dosimetric data from this study were combined to create a NTCP model.•A dose threshold of EQD2&#95;3 = 100 Gy to the PBT or any of its subsegments is expected to result in low rates of severe bronchial toxicity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background and Introduction: Brain metastasis velocity (BMV) has been proposed as a prognostic factor for overall survival (OS) in patients with brain metastases (BMs). In this study, we conducted an external validation and comparative assessment of the performance of all three BMV scores., Materials and Methods: Patients treated with intracranial stereotactic radiotherapy (SRT) for BM at a single center between 2014 and 2018 were identified. Where possible, all three BMV scores were calculated. Log-rank tests and linear, logistic and Cox regression analysis were used for validation and predictor identification of OS., Results: For 333 of 384 brain metastasis patients, at least one BMV score could be calculated. In a sub-group of 187 patients, "classic" BMV was validated as categorical (p < 0.0001) and continuous variable (HR 1.02; 95% CI 1.02-1.03; p < 0.0001). In a sub-group of 284 patients, "initial" BMV was validated as categorical variable (high-risk vs. low-risk; p < 0.01), but not as continuous variable (HR 1.02; 95% CI 0.99-1.04; p = 0.224). "Volume-based" BMV could not be validated in a sub-group of 104 patients. On multivariable Cox regression analysis, iBMV (HR 1.85; 95% CI 1.01-3.38; p < 0.05) and cBMV (HR 2.32; 95% CI 1.15 4.68; p < 0.05) were predictors for OS for intermediate-risk patients after first SRT and first DBFs, respectively. cBMV proved to be the dominant predictor for OS for high-risk patients (HR 2.99; 95% CI 1.30-6.91; p < 0.05)., Conclusion: This study externally validated cBMV and iBMV as prognostic scores for OS in patients treated with SRT for BMs whereas validation of vBMV was not achieved., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Stereotactic arrhythmia radioablation (STAR) is delivered with a planning target volume (PTV) prescription dose of 25 Gy, mostly to the surrounding 75-85% isodose line. This means that the average and maximum dose received by the target is less than 35 Gy, which is the minimum threshold required to create a homogenous transmural fibrosis. Similar to catheter ablation, the primary objective of STAR should be transmural fibrosis to prevent heterogenous intracardiac conduction velocities and the occurrence of sustained ventricular arrhythmias (sVA) caused by reentry. We hypothesize that the current dose prescription used in STAR is inadequate for the long-term prevention of sVA and that a significant increase in dose is necessary to induce transmural scar formation., Objective: A single arm, multi-center, phase II, dose escalation prospective clinical trial employing the i3 + 3 design is being conducted to examine the safety of a radiation dose-escalation strategy aimed at inducing transmural scar formation. The ultimate objective of this trial is to decrease the likelihood of sVA recurrence in patients at risk., Methods: Patients with ischemic or non-ischemic cardiomyopathy and recurrent sVA, with an ICD and history of ≥ 1 catheter ablation for sVA will be included. This is a prospective, multicenter, one-arm, dose-escalation trial utilizing the i3 + 3 design, a modified 3 + 3 specifically created to overcome limitations in traditional dose-finding studies. A total of 15 patients will be recruited. The trial aims to escalate the ITV dose from 27.0 Gy to an ITV prescription dose-equivalent level of maximum 35.1 Gy by keeping the PTV prescription dose constant at 25 Gy while increasing the dose to the target (i.e. the VT substrate without PTV margin) by step-wise reduction of the prescribing isodose line (85% down to 65%). The primary outcome of this trial is safety measured by registered radiation associated adverse events (AE) up to 90 days after study intervention including radiation associated serious adverse events graded as at least 4 or 5 according to CTCAE v5, radiation pneumonitis or pericarditis requiring hospitalization and decrease in LVEF ≥ 10% as assessed by echocardiography or cardiac MRI at 90 days after STAR. The sample size was determined assuming an acceptable primary outcome event rate of 20%. Secondary outcomes include sVA burden at 6 months after STAR, time to first sVA recurrence, reduction in appropriate ICD therapies, the need for escalation of antiarrhythmic drugs, non-radiation associated safety and patient reported outcome measures such as SF-36 and EQ5D., Discussion: DEFT-STAR is an innovative prospective phase II trial that aims to evaluate the optimal radiation dose for STAR in patients with therapy-refractory sVA. The trial has obtained IRB approval and focuses on determining the safe and effective radiation dose to be employed in the STAR procedure., Trial Registration: NCT05594368., (© 2023. The Author(s).)

Purpose: To evaluate the potential of the artificial intelligence (AI) chatbot ChatGPT in supporting young clinical scientists with scientific tasks in radio oncological research., Materials and Methods: Seven scientific tasks were to be completed in 3 h by 8 radiation oncologists with different scientific experience working at a university hospital: creation of a scientific synopsis, creation of a research question and corresponding clinical trial hypotheses, writing of the first paragraph of a manuscript introduction, clinical trial sample size calculation, and clinical data analyses (multivariate analysis, boxplot and survival curve). No participant had prior experience with an AI chatbot. All participants were instructed in ChatGPT v3.5 and its use was provided for all tasks. Answers were scored independently by two blinded experts. The subjective value of ChatGPT was rated by each participant. Data were analyzed with regression-, t-test and Spearman correlation (p < 0.05)., Results: Participants completed tasks 1-3 with an average score of 50% and 4-7 with 56%. Scientific experience, number of original publications and of first/last authorships showed a positive correlation with overall scoring (p = 0.01-0.04). Participants with little to moderate scientific experience scored ChatGPT to be more helpful in solving tasks 4-7 compared to more experienced participants (p = 0.04), with simultaneously presenting lower scorings (p = 0.03)., Conclusions: ChatGPT did not compensate for differences in scientific experience of young clinical scientists, with less experienced researchers believing false AI-generated scientific results., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr. Andratschke reports personal fees from AstraZeneca, personal fees from Debiopharm, grants, personal fees and nonfinancial support from ViewRay, grants and personal fees from Brainlab, outside the submitted work. Dr. Tanadini-Lang reports that her husband works at Varian Medical Systems. The other authors report no conflicts of interest.]., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: To analyze clinical trial activities and patient recruitment numbers into prospective clinical studies for solid malignancies during the COVID-19 pandemic in a tertiary cancer center., Materials and Methods: Patient recruitment numbers in prospective clinical studies of solid malignancies were retrospectively analyzed for the years 2019 - 2021 at the Comprehensive Cancer Center Zurich (CCCZ). Changes in recruitment numbers were tested for association with organ-specific subunits, as well as organizational and treatment-related trial characteristics. To assess differences between categorical variables, Chi-squared test was used. For uni- and multivariate analysis, Cox proportional hazards were calculated., Results: In 2019, there were a total of 107 studies (registry trials, clinical phase I-III trials, and translational studies) recruiting 304 patients at the CCCZ. During the COVID-19 pandemic in 2020 and 2021, there were 120 and 125 active trials with a total recruitment of 355 and 666 patients, respectively. No significant differences between the subunits and study characteristics in changes of patient recruitment in clinical phase I-III trials were identified when the year prior to the COVID-19 pandemic (2019) was compared to the first year of the pandemic (2020) and to 2020-2021., Conclusions: Despite healthcare systems around the world have experienced significant disruption due to the COVID-19 pandemic, data from our tertiary cancer center showed that clinical trial activities were maintained at a high level during the pandemic., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CB reported consulting or advisory roles for AstraZeneca, Pfizer, Roche, Takeda, Janssen-Cilag, Boehringer Ingelheim, Merck KGaA, and Sanofi; research funding from Bayer; and travel accommodations and expenses from AstraZeneca, Takeda and Roche; all over the last five years. MW has received research grants from Quercis and Versameb, and honoraria for lectures or advisory board participation or consulting from Bayer, Curevac, Medac, Novartis, Novocure, Orbus, Philogen, Roche and Sandoz. IO reported the following disclosures: Roche (Institutional Grant and Speakers Bureau), AstraZeneca (Advisory Board and Speakers Bureau), MSD (Advisory Board), BMS (Advisory Board), Medtronic (Institutional Grant), Intuitive (Proctorship). PR has received honoraria for lectures or advisory board participation from Alexion, Bristol-Myers Squibb, Boehringer Ingelheim, Debiopharm, Midatech Pharma, Novocure, QED, and Roche and research support from Merck Sharp and Dohme and Novocure. JM has intermittent project focused consultant or advisory relationships with Merck/Pfizer, Merck Sharp & Dohme, Amgen, Novartis, Roche, Bristol Myers Squibb and Pierre Fabre and has received travel support from Ultrasun, L’ Oreal, Merck Sharp & Dohme, Bristol Myers and Squibb und Pierre Fabre outside of the submitted work. ER received research funding by Amgen; consulting or advisory roles for Sanofi/Regeneron and Amgen; honoraria from Pierre Fabre, Lilly, Galderma, MSD, Sanofi, and BMS GmbH & Co KG; Travel expenses from Amgen and Sanofi. All other authors reported no potential conflicts of interest, (Copyright © 2023. Published by Elsevier Inc.)

Background and Purpose: Due to advances in oncology, a growing proportion of patients is treated with repetitive courses of radiotherapy. The aim of this study is to analyze whether radiotherapy maintains its safety and efficacy profile in patients treated with multiple repeat courses of irradiation., Material and Methods: All patients treated between 2011 and 2019 at our institution were screened for a minimum of five repeat irradiation courses, to analyze treatment characteristics, survival, safety and efficacy. The type of re-irradiation was classified according to ESTRO-EORTC consensus guidelines., Results: A total of n = 112 patients receiving n = 660 radiotherapy courses were included in this retrospective cohort study. The most frequent primary tumors were lung cancer in 41.9 % (n = 47) and malignant melanoma in 8.9 % (n = 10). The most frequent re-irradiation types were repeat irradiation and Type 2 re-irradiation in 309 (46.8 %) and 113 (17.1 %) cases, respectively. Median survival after the first course of radiotherapy was 3.6 (0.3-13.4) years. Response to radiotherapy was observed in 548 (83.0 %) cases and CTCAE toxicity grade ≥ 3 was observed in 21 (3.2 %) cases. An increasing number of RT courses (HR: 1.30, p=<0.0001), Type 1 re-irradiation (HR 3.50, p = 0.008) and KPS ≤ 80 % (HR: 2.02, p = 0.002) were associated with significantly worse treatment responses. Toxicity rates remained stable with increasing numbers of RT courses., Conclusion: Multiple courses of repeat radiotherapy maintain a favorable therapeutic ratio of high response combined with reasonable safety profile., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

•Data on cardiac toxicity after SBRT for ultra-central lung tumors remains limited.•We analyzed the dose to 18 cardiac sub-structures and cardiovascular toxicity.•A SBRT regimen of 45 Gy in 8-10 fractions yields good local control and low toxicity.•The highest cardiac doses were observed in the pulmonary artery and left atrium.•Higher doses to the base of the heart seem to be associated with non-cancer deaths., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background and Introduction: The place of last care carries importance for patients at the end of life. It is influenced by the realities of the social welfare and healthcare systems, cultural aspects, and symptom burden. This study aims to investigate the place of care trajectories of patients admitted to an acute palliative care unit., Materials and Methods: The medical records of all patients hospitalized on our acute palliative care unit in 2019 were assessed. Demographic, socio-economic and disease characteristics were recorded. Descriptive and inferential statistics were used to identify determinants for place of last care., Results: A total of 377 patients were included in this study. Median age was 71 (IQR, 59-81) years. Of these patients, 56% (n = 210) were male. The majority of patients was Swiss (80%; n = 300); about 60% (n = 226) reported a Christian confession; and 77% had completed high school or tertiary education. Most patients (80%, n = 300) had a cancer diagnosis. The acute palliative care unit was the place of last care for 54% of patients. Gender, nationality, religion, health insurance, and highest level of completed education were no predictors for place of last care, yet previous outpatient palliative care involvement decreased the odds of dying in a hospital (OR, 0.301; 95% CI, 0.180-0.505; p-value < 0.001)., Conclusion: More than half of patients admitted for end-of-life care died on the acute palliative care unit. While socio-economic factors did not determine place of last care, previous involvement of outpatient palliative care is a lever to facilitate dying at home., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Patients with oligometastatic disease (OMD) treated with metastasis-directed definitive local therapy such as stereotactic body radiotherapy (SBRT) are at risk of developing new metastases. Here, we compare characteristics and outcomes of patients treated with a single course and repeat SBRT., Materials/methods: OMD patients treated with SBRT to 1-5 metastases were included in this retrospective study, and classified as single course or repeat SBRT. Progression-free survival (PFS), widespread failure-free survival (WFFS), overall survival (OS), systemic therapy-free survival (STFS) and cumulative incidence of different first failures were analyzed. Patient and treatment characteristics predicting the use of repeat SBRT were investigated using univariable and multivariable logistic regression., Results: Among the 385 patients included, 129 and 256 received repeat or single course SBRT, respectively. The most common primary tumor and OMD state in both groups were lung cancer and metachronous oligorecurrence. Patients treated with repeat SBRT had shorter PFS (p < 0.0001), while WFFS (p = 0.47) and STFS (p = 0.22) were comparable. Distant failure, particularly with a single metastasis, was more frequently observed in repeat SBRT patients. Repeat SBRT patients had longer median OS (p = 0.01). On multivariable logistic regression, low distant metastases velocity and more previous lines of systemic therapy significantly predicted the use of repeat SBRT., Conclusion: Despite shorter PFS and comparable WFFS and STFS, repeat SBRT patients had longer OS. The role of repeat SBRT for OMD patients warrants further prospective investigation, focussing on predictive factors to select patients that might derive a benefit., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Introduction: Definitive surgical, oncological and radio-oncological treatment may result in significant morbidity and acute mortality. Mortality during or shortly after treatment in patients undergoing curative radio-(chemo)-therapy has not been studied systematically. We reviewed all curative radio-(chemo-)therapies at a large comprehensive cancer center over the last decade., Materials and Methods: The institutional record was screened for patients who received curative-intent radio-(chemo-)therapy and deceased during or within 30 days after radiotherapy. Curative therapy was defined as prescribed dosage of EQD2 ≥ 50 Gy for radiotherapy alone and EQD2 ≥ 40 Gy for radiochemotherapies. Data on demographics, disease and treatment were assembled and assessed., Results: Of 15,255 radiotherapy courses delivered at our center, 8,515 (56%) were performed with curative-intent. During or within 30 days after radio-(chemo-)therapy, 78 patients died (0.9% of all curative-intent courses). Median age of the deceased patients was 70 (IQR, 62-78) years, and 36% (28/78) were female. Median pre-therapeutic ECOG-PS was 1 (IQR, 0-2) and Charlson-Comorbidity-Index was 3+ (IQR, 2-3+). The most common primary malignancies were head and neck cancer (33/78; 42%) and central nervous system tumors (13/78; 17%). Peritherapeutic mortality varied by primary tumor, with the highest prevalence observed in head and neck and gastrointestinal cancer patients with 2.9% (33/1,144) and 2.4% (8/332), respectively. Among patients with known cause of death (34/78; 44%), tumor progression (12/34; 35%) and pulmonary complications/causes (11/34; 35%) were most common. On multivariable regression analysis, a worse ECOG-PS was associated with a relatively earlier peri -radiotherapeutic death (p = 0.014)., Conclusion: Mortality during or within 30 days of curative-intent radio-(chemo-)therapy was low, yet highest for head and neck (2.9%) and gastrointestinal tumor (2.4%) patients. Reasons for these findings include rapid tumor progression in some cancers, good patient selection, with ECOG-PS being most useful and predictive for avoiding early mortality. Future research should help refine predictors for peri -RT mortality., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: STL received a research grant from Varian, honoraria from Varian, and her husband is employed at Varian. PB cited research grants to the institution from ViewRay Inc. (Mountain View, CA, USA). NA has received grants from ViewRay Inc. and BrainLab and personal fees from AstraZeneca, Debiopharm, ViewRay and BrainLab, and non-financial support from ViewRay, all outside of the submitted work. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Purpose: In patients with extracranial oligometastatic disease, distant failure (DF) after local ablative therapies is common. Prognostic scores to guide salvage treatment decision making are currently lacking. Analogous to brain metastasis velocity, we propose distant metastasis velocity (DMV) as a prognostic score for overall survival (OS) and widespread failure-free survival (WFFS) after DF following metastasis-directed stereotactic body radiation therapy (SBRT)., Methods and Materials: Patients with ≤5 metastases from solid organ malignancies treated with SBRT to all lesions at our institution from 2014 to 2019 were screened, and patients who developed DF were included in this retrospective analysis. DMV was defined as metastases per month, determined at DF, and transformed into a 3-level categorical variable with cut points that minimized the log-rank P value for OS. Simple and multiple linear regression was used to predict DMV based on different patient and treatment variables. The association of DMV and other variables with OS was studied by univariable and multivariable Cox regression., Results: Three hundred eighty-five patients were screened, of which 303 developed DF and were included. The median DMV was 0.7 metastases per month. Patients with <0.5, 0.5 to 1.5, and >1.5 metastases per month were classified as low, intermediate, and high DMV, and had a median OS of 37.1, 26.7, and 16.8 months, respectively (P < .0001). On multivariable analysis, DMV was a strong independent predictor of OS, with a hazard ratio of 0.31 for low (P < .001) compared with high DMV. Lower DMV was significantly associated with longer WFFS (P = .04). The cumulative metastases volume at baseline (regression coefficient β = 0.03, P = .04) and oligoprogressive/-persistent disease (β = 1.91, P = .10) predicted higher DMV., Conclusions: DMV is a novel metric strongly associated with OS and WFFS after DF following SBRT in patients with oligometastatic disease and should be evaluated for decision making about the optimal multimodality salvage treatment strategy. The prognostic value of DMV should be validated in prospective studies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Introduction: Growing evidence supports a combined modality treatment strategy for patients with oligometastatic disease. However, lack of phase III trial data and uncertainties around patient selection highlight the importance of multidisciplinary tumor boards (MDT) in therapeutic decision-making. This study aimed to analyze the recognition of and treatment recommendations for oligometastatic patients by MDTs at a large comprehensive cancer center in order to better understand current treatment patterns of oligometastasis., Materials and Methods: For this retrospective single-center cross-sectional study, oligometastatic patients were identified by screening oncological PET and concurrent brain MRI scans conducted at our center in 2020. MDT discussions and recommendations within four weeks of the imaging diagnosis of oligometastasis were analyzed. Logistic regression analysis was used to identify predictors for the addition of local therapy to standard-of-care., Results: A total of 787 oligometastatic cases were identified. Lung cancer and mesothelioma, skin cancer, and prostate cancer were the most common histologies with 231 (29 %), 160 (20 %), and 84 (11 %) cases, respectively. Almost half of the cases (46 %) had one distant metastasis on imaging only. More than half (56 %) of all oligometastatic cases were discussed at an MDT. In 47 % of cases, for which a therapeutic recommendation was reached in an MDT, local therapy was part of the therapeutic strategy. On logistic regression analysis, oligometastatic skin cancer was significantly associated with a recommendation for local therapy (p < 0.05), whereas the number of oligometastases was not (p = 0.202)., Conclusion: More than half of oligometastatic cases were discussed in MDTs, of which more than every second received a recommendation including the addition of local therapy. This frequency of MDT use underscores the importance of multidisciplinary decision-making, yet efforts should be increased to standardize reporting and use standard nomenclature on oligometastasis in MDTs to better frame multidisciplinary discussion., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. PB cited research grants to the institution from ViewRay Inc. (Mountain View, CA, USA). NA has received grants from ViewRay Inc. and BrainLab and personal fees from AstraZeneca, Debiopharm, ViewRay and BrainLab, and non-financial support from ViewRay, all outside of the submitted work. MH has received research support from GE Healthcare, a fund by the Alfred and Annemarie von Sick legacy for translational and clinical cardiac and oncological research, and a grant by the Clinical Research Priority Program (CRRP) “Artificial Intelligence in oncological Imaging” of the University Zurich, all outside of the submitted work., (© 2022 The Author(s).)

Purpose: Oligometastatic disease refers to a distinct state in patients with cancer characterized by a low metastatic burden, with diagnosis being informed by a limited number of distant metastases in radiologic imaging. However, oligometastasis remains poorly understood in terms of its biology and prevalence in the metastatic cascade. In the absence of clinically viable molecular biomarkers, this study examined the prevalence of oligometastasis using oncological imaging., Methods and Materials: This study is based on all consecutive [fluorine-18]-fluorodeoxyglucose (FDG)- and [gallium-68]-prostate specific membrane antigen (PSMA)-positron emission tomography (PET) scans conducted at our cancer center between January and December 2020. We identified and analyzed all PET scans from patients with a maximum of 5 distant metastases from a solid malignancy and also reviewed concurrent cranial magnetic resonance imaging (cMRI) imaging in all candidate patients. Data on the number and sites of metastases were extracted from the imaging reports and verified on imaging studies in case of uncertainties., Results: In total, 7000 PET scans were analyzed, of which 1155 were performed in unique metastatic patients, and 637 patients showed extracranial oligometastatic disease (55%). Concurrent cMRI scans were available for 20% (130/637) of extracranial oligometastatic patients, 36 of which proved to be polymetastatic after combined PET and cMRI analysis. Prevalence of oligometastatic disease was influenced by primary tumor histology and was most frequent in pancreatic, liver and gallbladder cancers (59%), but was least frequent in cancer of unknown primary (26%). In 72% of oligometastatic cases, only 1 or 2 metastases were detected. Bone/soft tissue metastases were the most common sites of distant metastasis (41%). About 75% of patients had metachronous oligometastatic disease., Conclusions: Our analysis suggests that about half of patients with metastatic cancer are characterized by a limited tumor burden detectable on PET and cMRI imaging. This finding warrants intensified research efforts to better understand the biology of oligometastatic disease and to optimize multidisciplinary treatment strategies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Patients who develop oligorecurrent disease may be treated with metastasis-directed stereotactic body radiotherapy (SBRT) to defer the start of systemic therapy and delay its potential side effects. We report oncological outcomes and patterns of failure in patients with oligorecurrent disease treated with SBRT and determine which factors impact the interval to initiation of systemic therapy., Material/methods: This retrospective study included patients with oligorecurrent disease (≤5 lesions) from any solid organ malignancy, treated with SBRT to all metastases and no systemic therapy for a minimum one month after SBRT between 01/2014 and 12/2019. The Kaplan-Meier method was used to analyze overall survival (OS) and progression-free survival (PFS), and the cumulative incidence of initiation of systemic therapy was analyzed assuming death without systemic therapy as a competing risk. Univariable and multivariable analyses are used to assess predictors of the systemic therapy-free interval., Results: Among 545 patients treated with SBRT for oligometastatic disease, 142 patients were treated with SBRT only for oligorecurrent disease. The most common primary tumors were lung and gastrointestinal cancer in 47 (33.1 %) and 28 (19.7 %) patients, respectively. After a median follow-up of 25 months, the median PFS and OS was 6.1 months and 48.9 months, respectively. Distant metastases were the most common first failure, and oligometastatic distant failure occured in 86 patients (60.6 %). New metastases were treated with repeat SBRT in 48 patients (33.8 %). The 1- and 2-year cumulative incidence of initiation of systemic therapy was 24.6 % and 36.8 %, respectively. In multivariable analysis, the number of previous lines of systemic therapy and the cumulative volume of metastases were significantly associated with the interval to initiation of systemic therapy., Conclusion: Selected patients with oligorecurrence achieved favorable OS and low cumulative incidence of initiation of systemic therapy. Prospective studies are warranted to determine how the deferral of systemic therapy impacts OS compared with immediate systemic therapy in combination with SBRT., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Andratschke reports personal fees from AstraZeneca, personal fees from Debiopharm, grants, personal fees and non-financial support from ViewRay, grants and personal fees from Brainlab, outside the submitted work The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Purpose: Accurate prediction of survival is important to facilitate clinical decision-making and improve quality of care at the end of life. While it is well documented that survival prediction poses a challenge for treating physicians, the need for clinically valuable predictive factors has not been met. This study aims to quantify the prevalence of patient transfer 72 h before death onto the acute palliative care unit in a tertiary care center in Switzerland, and to identify factors predictive of 72-h mortality., Methods: All patients hospitalized between January and December 2020 on the acute palliative care unit of the Competence Center Palliative Care of the Department of Radiation Oncology at the University Hospital Zurich were assessed. Variables were retrieved from the electronic medical records. Univariable and multivariable logistic regressions were used to identify predictors of mortality., Results: A total of 398 patients were screened, of which 188 were assessed. Every fifth patient spent less than 72 h on the acute palliative care unit before death. In multivariable logistic regression analysis, predictors for 72-h mortality after transfer were no prior palliative care consult (p = 0.011), no advance care directive (p = 0.044), lower performance status (p = 0.035), lower self-care index (p = 0.003), and lower blood albumin level (p = 0.026)., Conclusion: Late transfer to the acute palliative care unit is not uncommon, which can cause additional distress to patients and caretakers. Though clinically practical short-term survival predictors remain largely unidentified, early integration of palliative care should be practiced more regularly in patients with life-limiting illness., (© 2022. The Author(s).)

Introduction and Background: Choosing the right treatment for the right patient in a setting of metastatic cancer disease remains a challenge. To facilitate clinical decision-making, predictive tools have been developed to personalize treatment. Here, we aim to assess the use of the recently proposed "METSSS score" as a prognostic tool for overall survival of cancer patients after palliative radiotherapy in the last phase of life., Methods: All patients treated with palliative radiotherapy at the end-of-life at the Department of Radiation Oncology of the University Hospital Zurich between January 2010 and December 2019 were included in this study. Data on demographics, diagnosis, treatment and comorbidities was extracted from the treatment planning and the electronical medical records system. To statistically assess the validity of the "METSSS score", the mortality risk score was calculated, followed by stratification of all patients to prognostic risk groups. The prediction of the 1-year overall survival estimates was subsequently calculated., Results: Over the past decade, 274 patients have received palliative radiotherapy during the end-of-life period. One third of patients was female (34%, n = 93). The most frequent primary tumor was lung cancer (n = 121, 44%), and 55% of patients (n = 152) had no comorbidities according to the Charlson-Deyo comorbidity index. The most common radiotherapy site was the brain and eye region (42%, n = 115). The median actual overall survival of all patients was 40 days from the start of radiotherapy. The "METSSS score" survival model predicted that 269 patients (98.1%) belong into the high-risk, four patients (1.5%) into the medium-risk, and one patient (0.4%) into the low-risk group. The predicted median 1-year overall survival was 10%., Discussion: The METSSS score correctly predicted the survival of our end-of-life patient cohort by assigning them into the highest risk category, and it can therefore serve as a decision-making tool when assigning patient to symptomatic radiotherapy., Competing Interests: NA received research support from ViewRay, BrainLab, SNF, the Swiss Cancer League, the Staffanini Foundation, and received honoraria from ViewRay, AstraZeneca, BrainLab, and Debiopharm., (© 2022 The Authors.)

Background: Treatment of metastatic cancer patients with multiple repeat courses of radiotherapy has become more frequent due to their improved overall survival. However, very little is known about their long-term outcome. This analysis reports on the quality-of-life, hematologic toxicity, patient-reported experiences and satisfaction, and psychological distress of cancer patients treated with multiple repeat radiotherapy., Methods: All patients treated with ≥5 courses of radiotherapy between 2011 and 2019 at the Department of Radiation Oncology, University Hospital Zurich (USZ) were screened for this study. A course of radiotherapy was defined as all treatment sessions to one anatomical site under one medical indication. All patients completed two questionnaires: EORTC QLQ-C30 questionnaire for quality-of-life and a questionnaire evaluating psychological distress and patient-reported experiences. Hematologic toxicities were assessed via a recent blood sample., Results: Of n = 33 patients treated with ≥5 radiotherapy courses and being alive, 20 (60.6%) participated in this study. The most common primary tumor was non-small cell lung cancer (n = 14, 42.4%). The most common sites of irradiation were brain (n = 78, 37.1%) and bone metastases (n = 59, 28.1%). All participating patients reported that they had experienced a subjective benefit from multiple repeat radiotherapy and denied increased side effects in later radiotherapy courses. Yet, 45% (n = 9) of the patients reported an increase of psychological distress with increasing numbers of radiotherapy treatments. While global health status was stable, patients having received multiple repeat radiotherapy reported increased fatigue (p = <0.006). Blood analysis showed significantly reduced hemoglobin and lymphocyte levels compared to the healthy population (p = <0.03)., Discussion and Conclusion: Patient-reported experiences and satisfaction of long-term cancer patients treated with multiple repeat radiotherapy are positive. However, increased levels of fatigue and significantly reduced hemoglobin and lymphocyte levels were observed. These data indicate the need to further investigate the effects of multiple courses of radiotherapy in chronic cancer patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Purpose: To explore the prognostic value of the oligometastatic disease (OMD) states as proposed by the European Society for Radiotherapy and Oncology (ESTRO) European Organisation for Research and Treatment of Cancer (EORTC) classification system., Materials and Methods: This retrospective single-institution study included patients with 1-5 extracranial metastases from any solid malignancy treated with SBRT to all metastases. OMD states were defined according to the ESTRO EORTC classification. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Discriminatory strength of the classification was assessed by Gönen & Heller's concordance probability estimate (CPE). Univariable and multivariable Cox regression models were used to assess predictors of OS and PFS., Results: In total, 385 patients were included. The median follow-up was 24.1 months. The most frequent OMD states were metachronous oligorecurrence (23.6%) and induced oligoprogression (18.7%). Induced OMD patients had significantly shorter median OS (28.1 months) compared with de-novo (46.3 months, p = 0.002) and repeat OMD (50.3 months, p = 0.002). Median PFS in de-novo OMD patients (8.8 months) was significantly longer than in repeat (5.4 months, p = 0.002) and induced OMD patients (4.3 months, p < 0.001). The classification system had moderate discriminatory strength for OS and PFS. Multivariable analyses confirmed that compared with induced OMD, de-novo OMD was associated with longer PFS and repeat with longer OS., Conclusion: All patients were successfully categorized according to the ESTRO EORTC classification system. The discriminatory strength of the classification was confirmed for OMD patients treated with metastases-directed SBRT. Larger multicenter trials are needed to validate the prognostic power for OMD patients irrespective of primary tumor and treatment approach., Competing Interests: Conflicts of Interest Statement Dr. Andratschke reports grants from SPHN Imaging - Swiss National Funds, from Clinical Research Priority Program University of Zurich, during the conduct of the study; personal fees from Debiopharm, personal fees from Astrazeneca, grants, personal fees and non-financial support from ViewRay, grants from Brainlab, outside the submitted work. Dr. Willmann, Dr. Vlaskou Badra, Mrs. Adilovic, Dr. Ahmadsei, Dr. Christ, Dr. van Timmeren, Dr. Kroeze, Dr. Mayinger and Dr. Guckenberger report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction and Background: As cancer is developing into a chronic disease due to longer survival, continuity and coordination of oncological care are becoming more important for patients. As radiation oncology departments are an integral part of cancer care and as repeat irradiation becomes more commonplace, the relevance of continuity and coordination of care in operating procedures is increasing. This study aims to perform a single-institution analysis of cancer patients in which continuity and coordination of care matters most, namely the highly selected group with multiple repeat course radiotherapy throughout their chronic disease., Materials and Methods: All patients who received at least five courses of radiotherapy at the Department of Radiation Oncology at the University Hospital Zurich from 2011 to 2019 and who were alive at the time of the initiation of this project were included into this study. Patient and treatment characteristics were extracted from the hospital information and treatment planning systems. All patients completed two questionnaires on continuity of care, one of which was designed in-house and one of which was taken from the literature., Results: Of the 33 patients identified at baseline, 20 (60.6%) participated in this study. A median of 6 years (range 3-13) elapsed between the first and the last visit at the cancer center. The median number of involved primary oncologists at the radiation oncology department was two (range 1-5). Fifty-seven percent of radiation therapy courses were preceded by a tumor board discussion. Both questionnaires showed high levels of experienced continuity of care. No statistically significant differences in experienced continuity of care between groups with more or less than two primary oncologists was found., Discussion and Conclusion: Patients treated with multiple repeat radiation therapy at our department over the past decade experienced high levels of continuity of care, yet further efforts should be undertaken to coordinate care among oncological disciplines in large cancer centers through better and increased use of interdisciplinary tumor boards., (© 2021. The Author(s).)

Introduction and Background: Through recent advances in cancer care, the number of long-term survivors has continuously increased. As a result, repetitive use of local radiotherapy for curative or palliative indications might have increased as well. This analysis aims to describe patterns of care and outcome of patients treated with multiple courses of repeat radiotherapy., Materials and Methods: All patients treated with radiotherapy between 2011 and 2019 at our department of Radiation Oncology were included into this analysis. A course of radiotherapy was defined as all treatment sessions to one anatomical site under one medical indication. Demographics, cancer and treatment characteristics and overall survival of patients having undergone multiple radiotherapy courses (minimum n = 5) were evaluated., Results: The proportion of cancer patients treated with a minimum five courses of radiotherapy increased continuously from 0.9% in 2011 to 6.5% in 2019. In the 112 patients treated with a minimum of five radiotherapy courses, the primary tumor was lung in 41.9% (n = 47), malignant melanoma in 8.9% (n = 10) and breast in 8.0% (n = 9) of cases. A median interval of 3 years (maximum 8 years) elapsed between the first and the last radiotherapy course. The maximum number of courses in a single patient were n = 10. Treatment intent was curative or palliative in 46.4% and 53.6% for the first radiotherapy, respectively. The proportion of curative intent decreased to 11.6% at the 5th, and the last radiotherapy course was following a palliative intent in all patients. Five-year overall survival measured from the 1st radiotherapy course was 32.7%. Median overall survival was 3.3, 2.4, 1.3, and 0.6 years when measured from the 1st, the 1st palliative, the 5th and last course of radiotherapy, respectively., Discussion and Conclusion: A continuously increasing number of patients is treated with multiple courses of radiotherapy throughout their long-term cancer survivorship., (© 2021. The Author(s).)

Atherosclerosis is a major underlying cause of cardiovascular disease. Previous studies showed that inhibition of the co-stimulatory CD40 ligand (CD40L)-CD40 signaling axis profoundly attenuates atherosclerosis. As CD40L exerts multiple functions depending on the cell-cell interactions involved, we sought to investigate the function of the most relevant CD40L-expressing cell types in atherosclerosis: T cells and platelets. Atherosclerosis-prone mice with a CD40L-deficiency in CD4 + T cells display impaired Th1 polarization, as reflected by reduced interferon-γ production, and smaller atherosclerotic plaques containing fewer T-cells, smaller necrotic cores, an increased number of smooth muscle cells and thicker fibrous caps. Mice with a corresponding CD40-deficiency in CD11c + dendritic cells phenocopy these findings, suggesting that the T cell-dendritic cell CD40L-CD40 axis is crucial in atherogenesis. Accordingly, sCD40L/sCD40 and interferon-γ concentrations in carotid plaques and plasma are positively correlated in patients with cerebrovascular disease. Platelet-specific deficiency of CD40L does not affect atherogenesis but ameliorates atherothrombosis. Our results establish divergent and cell-specific roles of CD40L-CD40 in atherosclerosis, which has implications for therapeutic strategies targeting this pathway.

Aims: The co-stimulatory receptor CD27 modulates responses of T cells, B cells, and NK cells. Various T cell subsets participate in atherogenesis. However, the role of CD27 in atherosclerosis remains unexplored., Methods and Results: Here we investigated the effect of bone marrow-derived and systemic CD27 deficiency in Apolipoprotein E-deficient (Apoe-/-) mice in early and advanced stages of atherosclerosis. Lethally-irradiated Apoe-/- mice reconstituted with Cd27-/-Apoe-/- bone marrow and consuming an atherogenic diet displayed a markedly increased plaque size and lesional inflammation compared to mice receiving Cd27+/+Apoe-/- bone marrow. Accordingly, chow diet-fed Cd27-/-Apoe-/- mice showed exacerbated lesion development and increased inflammation at the age of 18 weeks. At a more advanced stage of atherosclerosis (28 weeks), lesion size and phenotype did not differ between the two groups. Systemic and bone marrow-derived CD27 deficiency reduced the abundance of regulatory T cells (Treg) in blood, lymphoid organs, and the aorta. Numbers of other immune cells were not affected while expression of inflammatory cytokine genes (e.g. IL-1β and IL-6) was increased in the aorta when haematopoietic CD27 was lacking. In vitro, Tregs of CD27-deficient mice showed similar suppressive capacity compared with their wild-type controls and migrated equally towards CCL19 and CCL21. However, thymic Cd27-/- Tregs underwent increased apoptosis and expressed fewer markers of proliferation in vivo. Reconstitution of Cd27-/-Apoe-/- mice with Cd27+/+Apoe-/- Tregs reversed the increase in atherosclerosis., Conclusion: We demonstrate that CD27 co-stimulation increases the number of Tregs and limits lesion development and inflammation in experimental atherosclerosis, particularly during early stages of disease. Thus, our study suggests that promotion of CD27 function may mitigate atherosclerosis., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

The co-stimulatory molecule CD70 is expressed on activated immune cells and is known to modulate responses of T, B, and NK cells via its receptor CD27. Until now, there is only limited data describing the role of CD70 in atherosclerosis. We observed that ruptured human carotid atherosclerotic plaques displayed higher CD70 expression than stable carotid atherosclerotic plaques, and that CD70 expression in murine atheroma localized to macrophages. Lack of CD70 impaired the inflammatory capacity (e. g. reactive oxygen species and nitric oxide production) of bone marrow-derived macrophages, increased both M1-like and M2-like macrophage markers, and rendered macrophages metabolically inactive and prone to apoptosis. Moreover, CD70-deficient macrophages expressed diminished levels of scavenger receptors and ABC-transporters, impairing uptake of oxidised low-density lipoprotein (oxLDL) and cholesterol efflux, respectively. Hyperlipidaemic Apoe -/- mice reconstituted with CD70-deficient bone marrow displayed a profound increase in necrotic core size, plaque area, and number of lesional macrophages as compared to mice receiving control bone marrow. Accordingly, 18 week-old, chow diet-fed CD70-deficient Apoe -/- mice displayed larger atheroma characterised by lower cellularity and more advanced plaque phenotype than Apoe -/- mice. In conclusion, CD70 promotes macrophage function and viability and is crucial for effective phagocytosis and efflux of oxLDL. Deficiency in CD70 results in more advanced atheroma. Our data suggest that CD70 mitigates atherosclerosis at least in part by modulating macrophage function.

Purpose of Review: Cardiovascular disease (CVD) is the leading cause of death and morbidity worldwide. Detailed knowledge of the mechanisms of atherosclerosis, the main underlying disease of CVD, will enable improved preventive and therapeutic options, thus potentially limiting the burden of vascular disease in aging societies. A large body of evidence illustrates the contribution of platelets to processes beyond their traditionally recognized role as mediators in thrombosis and hemostasis. Recent advances in molecular biology help to understand the complexity of atherosclerosis., Recent Findings: This article outlines the role of platelets as modulators of immune responses in the context of atherosclerosis. It provides a short overview of interactions between platelets and endothelial cells or immune cells via direct cell contact or soluble factors during atherogenesis. By means of some well examined, exemplary pathways (e.g. CD40/CD40L dyad), this article will discuss recent discoveries in immune-related function of platelets. We also focus on the relationship between platelets and the lipid metabolism highlighting potential consequences to atherosclerosis and dyslipidemia., Summary: A better understanding of the molecular mechanisms of platelet-related immune activity allows their utilization as powerful diagnostic tools or targets of therapeutic intervention. Those findings might help to develop new classes of drugs which may supplement or replace classical anticoagulants and help clinicians to tackle CVD more efficiently.