BACKGROUND: Patients with cancer have a higher risk of coronavirus disease 2019 (COVID-19) than noncancer patients. The authors conducted a multicenter retrospective study to investigate the clinical manifestations and outcomes of patients with cancer who are diagnosed with COVID-19. METHODS: The authors reviewed the medical records of hospitalized patients who were treated at 5 hospitals in Wuhan City, China, between January 5 and March 18, 2020. Clinical parameters relating to cancer history (type and treatment) and COVID-19 were collected. The primary outcome was overall survival (OS). Secondary analyses were the association between clinical factors and severe COVID-19 and OS. RESULTS: A total of 107 patients with cancer were diagnosed with COVID-19, with a median age of 66 years (range, 37-98 years). Lung (21 patients; 19.6%), gastrointestinal (20 patients; 18.7%), and genitourinary (20 patients; 18.7%) cancers were the most common cancer diagnoses. A total of 37 patients (34.6%) were receiving active anticancer treatment when diagnosed with COVID-19, whereas 70 patients (65.4%) were on follow-up. Overall, 52.3% of patients (56 patients) developed severe COVID-19; this rate was found to be higher among patients receiving anticancer treatment than those on follow-up (64.9% vs 45.7%), which corresponded to an inferior OS in the former subgroup of patients (hazard ratio, 3.365; 95% CI, 1.455-7.782 [P = .005]). The detrimental effect of anticancer treatment on OS was found to be independent of exposure to systemic therapy (case fatality rate of 33.3% [systemic therapy] vs 43.8% [nonsystemic therapy]). CONCLUSIONS: The results of the current study demonstrated that >50.0% of infected patients with cancer are susceptible to severe COVID-19. This risk is aggravated by simultaneous anticancer treatment and portends for a worse survival, despite treatment for COVID-19. Cancer 2020;126:4023-4031.

The outbreak of 2019 novel coronavirus disease (COVID-19) caused not only extraordinary public health concerns but also tremendous psychological distress. 1 Soon after the COVID-19 outbreak, the Chinese government has activated level 1 health emergency responses and Wuhan was locked down on January 23, 2020. During the quarantine period, cancer patients represented a significant vulnerable population confronting with high risk of infection and poorer outcomes after infection. 2-4 Public emotional impacts and psychological response have drawn increasing attention of researchers during the COVID-19 epidemic. However, most studies have focused on the mental health situations of general population or medical staff. 5,6 No study has yet specifically examined the psychological influence of COVID-19 in cancer patients, particularly cancer patients in the initial epicenter of this pandemic. Therefore, we conducted a survey to study the psychological impacts of COVID-19 epidemic on cancer patients in Wuhan, the epicenter of the epidemic in China. Fear of disease progression and psychological stress were investigated by analyzing the data on selfreport questionnaires of Fear of Progression Questionnaire-Short Form (FoP-Q-SF), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) from cancer patients, and correlated factors were also explored to help us set up potential appropriate interventions. 2 | METHODS 2.1 | Procedure and data collection Cancer patients from our cancer institute were contacted by their doctors-in-charge and were asked to respond to an Internet-based survey. Demographic data (gender, age, marriage status, reproductive history, educational level, income, concern degree about COVID-19 outbreak, cancer type, co-morbidity, living style, and impact of COVID-19 outbreak on cancer treatment), scores of FoP-Q-SF, SAS, and SDS were collected from April 15 to 17, 2020. A basic description of the three questionnaires was provided in the Supplementary Information. 2.2 | Statistical analyses Mann-Whitney U test or Kruskal-Wallis H test was used to compare quantitative variables between groups. Factors with univariate P < .05 or clinical factors that may have significance were included in the multiple linear regression model. The statistical analyses were undertaken using SPSS Statistics Version 25. All tests were two-tailed, and a P < .05 was considered statistically significant. 2.3 | Ethical issues The study was approved by the Ethics Committee of Zhongnan Hospital of Wuhan University (2020089K). Informed consent was Gaili Chen, Qiuji Wu, and Huangang Jiang are co-first authors.

Radiation therapy is one of the cornerstones of cancer treatment. In tumor cells, exposure to ionizing radiation (IR) provokes DNA damages that trigger various forms of cell death such as apoptosis, necrosis, autophagic cell death, and mitotic catastrophe. IR can also induce cellular senescence that could serve as an additional antitumor barrier in a context-dependent manner. Moreover, accumulating evidence has demonstrated that IR interacts profoundly with tumor-infiltrating immune cells, which cooperatively drive treatment outcomes. Recent preclinical and clinical successes due to the combination of radiation therapy and immune checkpoint blockade have underscored the need for a better understanding of the interplay between radiation therapy and the immune system. In this review, we will present an overview of cell death modalities induced by IR, summarize the immunogenic properties of irradiated cancer cells, and discuss the biological consequences of IR on innate immune cell functions, with a particular attention on dendritic cells, macrophages, and NK cells. Finally, we will discuss their potential applications in cancer treatment.

Radiation therapy is one of the major therapeutic modalities for most solid tumors. The anti-tumor effect of radiation therapy consists of the direct tumor cell killing, as well as the modulation of tumor microenvironment and the activation of immune response against tumors. Radiation therapy has been shown to promote immunogenic cells death, activate dendritic cells and enhance tumor antigen presentation and anti-tumor T cell activation. Radiation therapy also programs innate immune cells such as macrophages that leads to either radiosensitization or radioresistance, according to different tumors and different radiation regimen studied. The mechanisms underlying radiation-induced macrophage activation remain largely elusive. Various molecular players such as NF-κB, MAPKs, p53, reactive oxygen species, inflammasomes have been involved in these processes. The skewing to a pro-inflammatory phenotype thus results in the activation of anti-tumor immune response and enhanced radiotherapy effect. Therefore, a comprehensive understanding of the mechanism of radiation-induced macrophage activation and its role in tumor response to radiation therapy is crucial for the development of new therapeutic strategies to enhance radiation therapy efficacy.

No abstract

Background: At present, there is a global pandemic of coronavirus disease 2019 (COVID-19) pneumonia. Two previous case series from China have suggested that cancer patients are at a higher risk of COVID-19 pneumonia, but the reports were limited by small numbers and few clinical information. Objective: To study clinical characteristics and outcomes of cancer patients infected with COVID-19. Design: Retrospective study. Setting: Four designated COVID-16 hospitals in Wuhan, Hubei province, China. Participants: Medical records of 67 cancer patients admitted to hospitals between Jan 5, 2020 to Feb 18, 2020 were included. Measurements: Demographic, clinical, laboratory, radiological and treatment data were collected. Survival data of the cohort was cut-off on Mar 10, 2020. Results: Of the 67 patients (median age: 66 years), the median age of patients who had severe illness was older than that of patients who had mild symptoms (P<0.001). Forty-three (64.2%) patients had other concurrent chronic diseases, and the proportion of severe patients had co-morbidities was higher than patients with mild disease (P=0.004). Twenty-three (34.3%) patients were still at the anticancer treatment phase, but no tumour progression and recurrence was observed for all the patients during the treatment of COVID-19 pneumonia. About 70% of these patients had fever (n=53, 79.1%) and/or cough (n=50, 74.6%). Lymphocytopenia was the main laboratory finding accompanying increased C-reactive protein and procalcitonin in cancer patients, especially in severe cases. By Mar 10, 2020, 18 (26.9%) patients died from COVID-19, and 39 (58.2%) patients have been discharged. The median age of survivors was younger than that of deaths (P=0.014). Lung cancer (n=15, 22.4%) with COVID-19 was the most common cancer type and accounted for the highest proportion COVID-19 resulted deaths (33.3%, 5/15). We observed a tendency that patients at the follow-up phase had a better prognosis than that at anticancer treatment phase (P=0.095). Limitation: This is a retrospective study with only 67 cases from four hospitals. And some specific clinical information was insufficient. Conclusion: This study showed COVID-19 patients with cancer seem to have a higher proportion of severe cases and poorer prognosis. The tendency of poor prognosis was more obvious in patients at anticancer treatment phase. We should pay more intensive attentions to cancer patients infected with COVID-19.

Although tumor-associated macrophages have been extensively studied in the control of response to radiotherapy, the molecular mechanisms involved in the ionizing radiation-mediated activation of macrophages remain elusive. Here we show that ionizing radiation induces the expression of interferon regulatory factor 5 (IRF5) promoting thus macrophage activation toward a pro-inflammatory phenotype. We reveal that the activation of the ataxia telangiectasia mutated (ATM) kinase is required for ionizing radiation-elicited macrophage activation, but also for macrophage reprogramming after treatments with γ-interferon, lipopolysaccharide or chemotherapeutic agent (such as cisplatin), underscoring the fact that the kinase ATM plays a central role during macrophage phenotypic switching toward a pro-inflammatory phenotype through the regulation of mRNA level and post-translational modifications of IRF5. We further demonstrate that NADPH oxidase 2 (NOX2)-dependent ROS production is upstream to ATM activation and is essential during this process. We also report that the inhibition of any component of this signaling pathway (NOX2, ROS and ATM) impairs pro-inflammatory activation of macrophages and predicts a poor tumor response to preoperative radiotherapy in locally advanced rectal cancer. Altogether, our results identify a novel signaling pathway involved in macrophage activation that may enhance the effectiveness of radiotherapy through the reprogramming of tumor-infiltrating macrophages.

COVID-19 has become a global health concern. HIV-infected patients are particularly vulnerable to COVID-19 due to their immune-compromised status.