Clinical and inflammation marker features of cancer patients with COVID-19: data of Istanbul, Turkey multicenter cancer patients (2020-2022).

OBJECTIVE: We aimed to identify a rapid, accurate, and accessible biomarker in the early stages of COVID-19 that can determine the prognosis of the disease in cancer patients. METHODS: A total number of 241 patients with solid cancers who had a COVID-19 diagnosis between March 2020 and February 2022 were included in the study. Factors and ten different markers of inflammation were analyzed by year of diagnosis of COVID-19 and grouped by severity of infection. RESULTS: Hospitalization, referral to the intensive care unit (ICU), mechanical ventilation, and death were more frequent in 2020 than in 2021 and 2022 (mortality rates, respectively, were 18.8%, 3.8%, and 2.5%). Bilateral lung involvement and chronic lung disease were independent risk factors for severe disease in 2020. In 2021-2022, only bilateral lung involvement was found as an independent risk factor for severe disease. The neutrophil-to-lymphocyte platelet ratio (NLPR) with the highest area under the curve (AUC) value in 2020 had a sensitivity of 71.4% and specificity of 73.3% in detecting severe disease (cut-off > 0.0241, Area Under the Curve (AUC) = 0.842, p <.001). In 2021-2022, the sensitivity of the C-reactive protein-to-lymphocyte ratio (CRP/L) with the highest AUC value was 70.0%, and the specificity was 73.3% (cut-off > 36.7, AUC = 0.829, p = .001). CONCLUSIONS: This is the first study to investigate the distribution and characteristics of cancer patients, with a focus on the years of their COVID-19 diagnosis. Based on the data from our study, bilateral lung involvement is an independent factor for severe disease, and the CRP/L inflammation index appears to be the most reliable prognostic marker.

Severe SARS-CoV-2 infection as a marker of undiagnosed cancer: a population-based study.

No study has yet investigated if a severe SARS-CoV-2 infection represents a marker of an undiagnosed cancer. This population-based study, using the SNDS database, identified from 02/15/2020 to 08/31/2021, 41,302 individuals hospitalized in intensive care unit due to SARS-CoV-2 (ICU-gr) and 713,670 control individuals not hospitalized for SARS-CoV-2 (C-gr). Individuals were matched according to year of birth, sex and French department. The cancer incidence was compared in the two groups during the follow-up period (index date-12/31/2021), using Cox proportional hazards models adjusted on matching variables, socioeconomic characteristics and comorbidities. In the ICU-gr, 2.2% (n = 897) was diagnosed with a cancer in the following months, compared to 1.5% (n = 10,944) in the C-gr. The ICU-gr had a 1.31 higher risk of being diagnosed with a cancer following hospital discharge compared to the C-gr (aHR 1.31, 95% CI 1.22-1.41). A global similar trend was found when competing risk of death was taken into account (aHR 1.25, 95% CI 1.16-1.34). A significant higher risk was found concerning renal (aHR 3.16, 95% CI 2.33-4.27), hematological (aHR 2.54, 95% CI 2.07-3.12), colon (aHR 1.72, 95% CI 1.34-2.21), and lung (aHR 1.70, 95% CI 1.39-2.08) cancers. This suggests that a severe SARS-CoV-2 infection may represent a marker of an undiagnosed cancer.

Comparison of two frailty screening tools in older patients with colorectal cancer.

INTRODUCTION: Geriatric assessment (GA) is widely used to detect vulnerability in older patients. As this process is time-consuming, prescreening tools have been developed to identify patients at risk for frailty. We aimed to assess whether the Geriatric 8 (G8) or the Korean Cancer Study Group Geriatric Score (KG-7) shows better performance in identifying patients who are in need of full GA. MATERIALS AND METHODS: A consecutive series of patients aged ≥ 60 years with colorectal cancer were included. The sensitivity, specificity, predictive value, and 95% confidence intervals (95% CI) were calculated for the G8 and the KG-7 using the results of GA as the reference standard. ROC(Receiver Operating Characteristic) was used to evaluate the accuracy of the G8 and the KG-7. RESULTS: One hundred four patients were enrolled. A total of 40.4% of patients were frail according to GA, and 42.3% and 50.0% of patients were frail based on the G8 and the KG-7, respectively. The sensitivity and specificity of the G8 were 90.5% (95% CI: 77.4-97.3%) and 90.3% (95% CI: 80.1-96.4%), respectively. For the KG-7, the sensitivity and specificity were 83.3% (95% CI: 68.6-93.0%) and 72.6% (95% CI: 59.8-83.1%), respectively. Compared to the KG-7, the G8 had a higher predictive accuracy (AUC: (95% CI): 0.90 (0.83-0.95) vs. 0.78 (0.69-0.85); p < 0.01). By applying the G8 and the KG-7, 60 and 52 patients would not need a GA assessment, respectively. CONCLUSION: Both the G8 and the KG-7 showed a great ability to detect frailty in older patients with colorectal cancer. In this population, compared to the KG-7, the G8 had a better performance in identifying those in need of a full Geriatric Assessment.

The Cancer Financial Experience (CAFÉ) study: randomized controlled trial of a financial navigation intervention to address cancer-related financial hardship.

BACKGROUND: There is an urgent need for evidence on how interventions can prevent or mitigate cancer-related financial hardship. Our objectives are to compare self-reported financial hardship, quality of life, and health services use between patients receiving a financial navigation intervention versus a comparison group at 12 months follow-up, and to assess patient-level factors associated with dose received of a financial navigation intervention. METHODS: The Cancer Financial Experience (CAFÉ) study is a multi-site randomized controlled trial (RCT) with individual-level randomization. Participants will be offered either brief (one financial navigation cycle, Arm 2) or extended (three financial navigation cycles, Arm 3) financial navigation. The intervention period for both Arms 2 and 3 is 6 months. The comparison group (Arm 1) will receive enhanced usual care. The setting for the CAFÉ study is the medical oncology and radiation oncology clinics at two integrated health systems in the Pacific Northwest. Inclusion criteria includes age 18 or older with a recent cancer diagnosis and visit to a study clinic as identified through administrative data. Outcomes will be assessed at 12-month follow-up. Primary outcomes are self-reported financial distress and health-related quality of life. Secondary outcomes are delayed or foregone care; receipt of medical financial assistance; and account delinquency. A mixed methods exploratory analysis will investigate factors associated with total intervention dose received. DISCUSSION: The CAFÉ study will provide much-needed early trial evidence on the impact of financial navigation in reducing cancer-related financial hardship. It is theory-informed, clinic-based, aligned with patient preferences, and has been developed following preliminary qualitative studies and stakeholder input. By design, it will provide prospective evidence on the potential benefits of financial navigation on patient-relevant cancer outcomes. The CAFÉ trial's strengths include its broad inclusion criteria, its equity-focused sampling plan, its novel intervention developed in partnership with clinical and operations stakeholders, and mixed methods secondary analyses related to intervention dose offered and dose received. The resulting analytic dataset will allow for rich mixed methods analysis and provide critical information related to implementation of the intervention should it prove effective. TRIAL REGISTRATION: ClinicalTrials.gov NCT05018000 . August 23, 2021.

Web-based tool for cancer family history collection: A prospective randomized controlled trial.

OBJECTIVES: Approximately 1% of individuals have a hereditary cancer predisposition syndrome, however, the majority are not aware. Collecting a cancer family history (CFH) can triage patients to receive genetic testing. To rigorously assess different methods of CFH collection, we compared a web-based tool (WBT) to usual care (clinician collects CFH) in a randomized controlled trial. METHODS: New gynecologic oncology patients (seen 9/2019-9/2021) were randomized to one of three arms in a 2:2:1 allocation ratio: 1) usual care clinician CFH collection, 2) WBT completed at home, or 3) WBT completed in office. The WBT generated a cancer-focused pedigree and scores on eight validated cancer risk models. The primary outcome was collection of an adequate CFH (based on established guidelines) with usual care versus the WBT. RESULTS: We enrolled 250 participants (usual care - 110; WBT home - 105; WBT office - 35 [closed early due to COVID-19]). Within WBT arms, 109 (78%) participants completed the tool, with higher completion for office versus home (33 [94%] vs. 76 [72%], P = 0.008). Among participants completing the WBT, 63 (58%) had an adequate CFH versus 5 (5%) for usual care (P < 0.001). Participants completing the WBT were significantly more likely to complete genetic counseling (34 [31%] vs. 15 [14%], P = 0.002) and genetic testing (20 [18%] vs. 9 [8%], P = 0.029). Participant and provider WBT experience was favorable. CONCLUSIONS: WBTs for CFH collection are a promising application of health information technology, resulting in more comprehensive CFH and a significantly greater percentage of participants completing genetic counseling and testing.

Antigen rapid diagnostic test monitoring for SARS-CoV-2 in asymptomatic and fully vaccinated cancer patients: Is it cost-effective?

BACKGROUND: Routine testing for cancer patients not presenting COVID-19-related symptoms and fully vaccinated for SARS-CoV-2 prior to cancer treatment is controversial. METHODS: In this retrospective study we evaluated whether antigen-rapid-diagnostic-test (Ag-RDT) monitoring for SARS-CoV-2 in a large cohort of consecutive asymptomatic (absence of SARS-CoV-2-related symptoms such as fever, cough, sore throat or nasal congestion) and fully vaccinated cancer patients enrolled in a short period during cancer treatment has an impact on the therapeutic path of cancer patients. RESULTS: From December 27, 2021, to February 11, 2022, 2439 cancer patients were screened through Ag-RDT for SARS-CoV-2 before entering the hospital for systemic treatment. Fifty-three patients (2.17%) tested positive, of whom 7 (13.2%) subsequently developed COVID-related symptoms, generally mild. Cancer treatment was discontinued, as a precaution, in 49 patients (92.5%) due to the test positivity. CONCLUSION: SARS-CoV-2 screening in asymptomatic and fully vaccinated cancer patients during systemic treatment appeared to be not cost-effective: the low rate of SARS-CoV-2 positive patients and the low percentage of overt associated infection do not seem proportional to the direct costs (nursing work for swabs, costs of materials and patient monitoring) and indirect costs (dedicated rooms, extension of waiting times for patients and oncologists in delivering therapy as well as its discontinuation in the positive ones). It can, on the other hand, be detrimental when systemic cancer treatment is suspended as a precaution. Given the small number of patients testing positive and the rapid and favorable trend of the infection, it is recommended to always consider continuing systemic oncological treatment, especially when this impacts patient survival as in the adjuvant or neoadjuvant setting.

Chemistry and biology of ferritin.

Iron is an essential element required by cells and has been described as a key player in ferroptosis. Ferritin operates as a fundamental iron storage protein in cells forming multimeric assemblies with crystalline iron cores. We discuss the latest findings on ferritin structure and activity and its link to cell metabolism and ferroptosis. The chemistry of iron, including its oxidation states, is important for its biological functions, its reactivity, and the biology of ferritin. Ferritin can be localized in different cellular compartments and secreted by cells with a variety of functions depending on its spatial context. Here, we discuss how cellular ferritin localization is tightly linked to its function in a tissue-specific manner, and how impairment of iron homeostasis is implicated in diseases, including cancer and coronavirus disease 2019. Ferritin is a potential biomarker and we discuss latest research where it has been employed for imaging purposes and drug delivery.

The emerging role of exosomes in innate immunity, diagnosis and therapy.

Exosomes, which are nano-sized transport bio-vehicles, play a pivotal role in maintaining homeostasis by exchanging genetic or metabolic information between different cells. Exosomes can also play a vital role in transferring virulent factors between the host and parasite, thereby regulating host gene expression and the immune interphase. The association of inflammation with disease development and the potential of exosomes to enhance or mitigate inflammatory pathways support the notion that exosomes have the potential to alter the course of a disease. Clinical trials exploring the role of exosomes in cancer, osteoporosis, and renal, neurological, and pulmonary disorders are currently underway. Notably, the information available on the signatory efficacy of exosomes in immune-related disorders remains elusive and sporadic. In this review, we discuss immune cell-derived exosomes and their application in immunotherapy, including those against autoimmune connective tissue diseases. Further, we have elucidated our views on the major issues in immune-related pathophysiological processes. Therefore, the information presented in this review highlights the role of exosomes as promising strategies and clinical tools for immune regulation.

Early survival for patients newly diagnosed with cancer during COVID-19 in Ontario, Canada: A population-based cohort study.

BACKGROUND: Little is known about the association between the COVID-19 pandemic and early survival among newly diagnosed cancer patients. METHODS: This retrospective population-based cohort study used linked administrative datasets from Ontario, Canada. Adults (≥18 years) who received a cancer diagnosis between March 15 and December 31, 2020, were included in a pandemic cohort, while those diagnosed during the same dates in 2018/2019 were included in a pre-pandemic cohort. All patients were followed for one full year after the date of diagnosis. Cox proportional hazards regression models were used to assess survival in relation to the pandemic, patient characteristics at diagnosis, and the modality of first cancer treatment as a time-varying covariate. Interaction terms were explored to measure the pandemic association with survival for each cancer type. RESULTS: Among 179,746 patients, 53,387 (29.7%) were in the pandemic cohort and 37,741 (21.0%) died over the first post-diagnosis year. No association between the pandemic and survival was found when adjusting for patient characteristics at diagnosis (HR 0.99 [95% CI 0.96-1.01]), while marginally better survival was found for the pandemic cohort when the modality of treatment was additionally considered (HR 0.97 [95% CI 0.95-0.99]). When examining each cancer type, only a new melanoma diagnosis was associated with a worse survival in the pandemic cohort (HR 1.25 [95% CI 1.05-1.49]). CONCLUSIONS: Among patients able to receive a cancer diagnosis during the pandemic, one-year overall survival was not different than those diagnosed in the previous 2 years. This study highlights the complex nature of the COVID-19 pandemic impact on cancer care.

Impact of BSG/CD147 gene expression on diagnostic, prognostic and therapeutic strategies towards malignant cancers and possible susceptibility to SARS-CoV-2.

BACKGROUND: BSG (CD147) is a member of the immunoglobulin superfamily that shows roles for potential prognostics and therapeutics for metastatic cancers and SARS-CoV-2 invasion for COVID-19. The susceptibility of malignant cancers to SARS-CoV-2 as well as the correlations between disease outcome and BSG expression in tumor tissues have not been studied in depth. METHODS: In this study, we explored the BSG expression profile, survival correlation, DNA methylation, mutation, diagnostics, prognostics, and tumor-infiltrating lymphocytes (TILs) from different types of cancer tissues with corresponding healthy tissues. In vitro studies for cordycepin (CD), N6-(2-hydroxyethyl) adenosine (HEA), N6, N6-dimethyladenosine (m62A) and 5'-uridylic acid (UMP) on BSG expression were also conducted. RESULTS: We revealed that BSG is conserved among different species, and significantly upregulated in seven tumor types, including ACC, ESCA, KICH, LIHC, PAAD, SKCM and THYM, compared with matched normal tissues, highlighting the susceptibility of these cancer patients to SARS-CoV-2 invasion, COVID-19 severity and progression of malignant cancers. High expression in BSG was significantly correlated with a short OS in LGG, LIHC and OV patients, but a long OS in KIRP patients. Methylation statuses in the BSG promoter were significantly higher in BRCA, HNSC, KIRC, KIRP, LUSC, PAAD, and PRAD tumor tissues, but lower in READ. Four CpGs in the BSG genome were identified as potential DNA methylation biomarkers which could be used to predict malignant cancers from normal individuals. Furthermore, a total of 65 mutation types were found, in which SARC showed the highest mutation frequency (7.84%) and THYM the lowest (0.2%). Surprisingly, both for disease-free and progression-free survival in pan-cancers were significantly reduced after BSG mutations. Additionally, a correlation between BSG expression and immune lymphocytes of CD56bright natural killer cell, CD56dim natural killer cell and monocytes, MHC molecules of HLA-A, HLA-B, HLA-C and TAPBP, immunoinhibitor of PVR, PVRL2, and immunostimulators of TNFRSF14, TNFRSF18, TNFRSF25, and TNFSF9, was revealed in most cancer types. Moreover, BSG expression was downregulated by CD, HEA, m62A or UMP in cancer cell lines, suggesting therapeutic potentials for interfering entry of SARS-CoV-2. CONCLUSIONS: Altogether, our study highlights the values of targeting BSG for diagnostic, prognostic and therapeutic strategies to fight malignant cancers and COVID-19. Small molecules CD, HEA, m62A and UMP imply therapeutic potentials in interfering with entry of SARS-CoV-2 and progression of malignant cancers.

Machine Learning Models Using Routinely Collected Clinical Data Offer Robust and Interpretable Predictions of 90-Day Unplanned Acute Care Use for Cancer Immunotherapy Patients.

PURPOSE: Clinical management of patients receiving immune checkpoint inhibitors (ICIs) could be informed using accurate predictive tools to identify patients at risk of short-term acute care utilization (ACU). We used routinely collected data to develop and assess machine learning (ML) algorithms to predict unplanned ACU within 90 days of ICI treatment initiation. METHODS: We used aggregated electronic health record data from 7,960 patients receiving ICI treatments to train and assess eight ML algorithms. We developed the models using pre-SARS-COV-19 COVID-19 data generated between January 2016 and February 2020. We validated our algorithms using data collected between March 2020 and June 2022 (peri-COVID-19 sample). We assessed performance using area under the receiver operating characteristic curves (AUROC), sensitivity, specificity, and calibration plots. We derived intuitive explanations of predictions using variable importance and Shapley additive explanation analyses. We assessed the marginal performance of ML models compared with that of univariate and multivariate logistic regression (LR) models. RESULTS: Most algorithms significantly outperformed the univariate and multivariate LR models. The extreme gradient boosting trees (XGBT) algorithm demonstrated the best overall performance (AUROC, 0.70; sensitivity, 0.53; specificity, 0.74) on the peri-COVID-19 sample. The algorithm performance was stable across both pre- and peri-COVID-19 samples, as well as ICI regimen and cancer groups. Type of ICI agents, oxygen saturation, diastolic blood pressure, albumin level, platelet count, immature granulocytes, absolute monocyte, chloride level, red cell distribution width, and alcohol intake were the top 10 key predictors used by the XGBT algorithm. CONCLUSION: Machine learning algorithms trained using routinely collected data outperformed traditional statistical models when predicting 90-day ACU. The XGBT algorithm has the potential to identify high-ACU risk patients and enable preventive interventions to avoid ACU.

Remote Medical Scent Detection of Cancer and Infectious Diseases With Dogs and Rats: A Systematic Review.

BACKGROUND: Remote medical scent detection of cancer and infectious diseases with dogs and rats has been an increasing field of research these last 20 years. If validated, the possibility of implementing such a technique in the clinic raises many hopes. This systematic review was performed to determine the evidence and performance of such methods and assess their potential relevance in the clinic. METHODS: Pubmed and Web of Science databases were independently searched based on PRISMA standards between 01/01/2000 and 01/05/2021. We included studies aiming at detecting cancers and infectious diseases affecting humans with dogs or rats. We excluded studies using other animals, studies aiming to detect agricultural diseases, diseases affecting animals, and others such as diabetes and neurodegenerative diseases. Only original articles were included. Data about patients' selection, samples, animal characteristics, animal training, testing configurations, and performances were recorded. RESULTS: A total of 62 studies were included. Sensitivity and specificity varied a lot among studies: While some publications report low sensitivities of 0.17 and specificities around 0.29, others achieve rates of 1 sensitivity and specificity. Only 6 studies were evaluated in a double-blind screening-like situation. In general, the risk of performance bias was high in most evaluated studies, and the quality of the evidence found was low. CONCLUSIONS: Medical detection using animals' sense of smell lacks evidence and performances so far to be applied in the clinic. What odors the animals detect is not well understood. Further research should be conducted, focusing on patient selection, samples (choice of materials, standardization), and testing conditions. Interpolations of such results to free running detection (direct contact with humans) should be taken with extreme caution. Considering this synthesis, we discuss the challenges and highlight the excellent odor detection threshold exhibited by animals which represents a potential opportunity to develop an accessible and non-invasive method for disease detection.

[Diagnosis and treatment of adult tumor patients with COVID-19].

After the first outbreak of corona virus disease 2019 (COVID-19) at the end of 2019, it has caused multiple rounds of transmission in many countries around the world. Cancer patients are mainly elderly people, and the immunosuppression state caused by the tumor itself and anti-tumor treatment, more accompanying underlying diseases, and more hospital environmental exposure leading to a higher incidence of COVID-19 infection. The proportion of severe cases after infection is high, and the mortality is high. Therefore, based on the domestic and foreign research and clinical practice, the Expert Committee of Geriatric Cancer Prevention and Treatment of Chinese Society of Clinical Oncology launched a discussion based on the characteristics of cancer patients, including the epidemiology, clinical manifestations, differential diagnosis, definition and risk factors of severe cases, diagnosis and treatment recommendations, recovery of anti-tumor treatment and vaccination recommendations. To provide the corresponding suggestions for the clinical diagnosis and treatment of such patients.

Liquid biopsies in blood donors: Issues in implementing cell-free DNA cancer screening tests in the blood donor population.

Issues in implementing cell-free DNA cancer screening tests in blood donors.

Factors Affecting Presentation and Treatment of Pediatric/Adolescent Cancer Patients Diagnosed With SARS-CoV-2.

BACKGROUND: It is thought that the clinical course of actively treated pediatric/adolescent cancer patients diagnosed with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is more severe than experienced by the general pediatric population. We describe the clinical course, risk factors affecting presentation, and management of coronavirus disease 2019 (COVID-19) infection for these patients. METHODS: Patients at a single institution receiving cancer therapy while diagnosed with SARS-CoV-2 between January 2020 and June 2021 were retrospectively reviewed. Data collected included age at SARS-CoV-2 diagnosis, sex, ethno-race, adjusted body mass index, and active therapies. RESULTS: Twenty-nine patients met inclusion criteria, with 16 (55.2%) experiencing symptoms. Twenty-three (79.3%) patients required no institutional support; 10 (34.4%) required hospitalization, of which 80.0% required oxygen, 30.0% required intensive care, and 10.0% required intubation. Three (10.3%) patients developed MIS-C. Obesity increased odds of hospitalization (odds ratio=25.5; P =0.002) and oxygenation (odds ratio=14.88; P =0.012). CONCLUSIONS: Hospitalization and MIS-C rates were significantly higher than, whereas mortality rates and symptom presentations were consistent with, rates in the general pediatric population. Obesity was the only risk factor predictive of clinical severity. Cancer treatment modifications and pre-emptive administration of COVID-19 treatment did not modify clinical course.