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The proceedings contain 109 papers. The topics discussed include: dose intensity of palbociclib and initial body weight dosage: implications on progression free survival in 220 patients with ER+/HER2-negative metastatic breast cancer;characteristics of Nirmatrelvir/Ritonavir (Paxlovid) recipients and clinical interventions by oncology pharmacists at a tertiary outpatient cancer center;safe handling of non-carcinogenic drugs in the Ghent University Hospital: development, implementation and communication of hospital-specific guidelines;case series: use of olaparib in uncommon locations in patients with impaired homologous recombination;real-world data evaluation of medicines used in special situations in oncohematology: a retrospective study from a comprehensive cancer institution;Dostarlimab in the treatment of recurrent endometrial cancer: real life experience;medication-related osteonecrosis of the jaws and CDK4/6 inhibitors in breast cancer;and efficacy and safety outcomes of generic imatinib in adults with chronic myeloid leukemia (CML) following the switch from branded imatinib.
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Covid-19 virus variants identified so far are due to viral genetic diversity, genetic evolution, and variable infectivity, suggesting that high infection rates and high mortality rates may be contributed by these mutations. And it has been reported that the targeting strategies for innate immunity should be less vulnerable to viral evolution, variant emergence and resistance. Therefore, the most effective solution to Covid-19 infection has been proposed to prevent and treat severe exacerbation of patients with moderate disease by enhancing human immune responses such as NK cell and T cell. In previous studies, we demonstrated for the first time that gamma-PGA induced significant antitumor activity and antiviral activity by modulating NK cell-mediated cytotoxicity. Especially intranasal administration of gamma-PGA was found to effectively induce protective innate and CTL immune responses against viruses and we found out that gamma-PGA can be an effective treatment for cervical intraepithelial neoplasia 1 through phase 2b clinical trial. In this study, the possibility of gamma-PGA as a Covid-19 immune modulating agent was confirmed by animal experiments infected with Covid-19 viruses. After oral administration of gamma-PGA 300mug/mouse once a day for 5 days in a K18-hACE2 TG mouse model infected with SARS-CoV-2 (NCCP 43326;original strain) and SARS-CoV-2 (NCCP 43390;Delta variant), virus titer and clinical symptom improvement were confirmed. In the RjHan:AURA Syrian hamster model infected with SARS-CoV-2 (NCCP 49930;Delta variant), 350 or 550 mug/head of gamma-PGA was administered orally for 10 days once a day. The virus for infection was administered at 5 x 104 TCID50, and the titer of virus and the improvement of pneumonia lesions were measured to confirm the effectiveness in terms of prevention or treatment. In the mouse model infected with original Covid-19 virus stain, the weight loss was significantly reduced and the survival rate was also improved by the administration of gamma-PGA. And gamma-PGA alleviated the pneumonic lesions and reduced the virus titer of lung tissue in mice infected with delta variant. In the deltavariant virus infected hamster model, gamma-PGA showed statistically significant improvement of weight loss and lung inflammation during administration after infection. This is a promising result for possibility of Covid-19 therapeutics along with the efficacy results of mouse model, suggesting gammaPGA can be therapeutic candidate to modulate an innate immune response for Covid-19.
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CBD, an FDA approved drug for epilepsy, may have therapeutic potential for other diseases and is currently being tested for efficacy in cancer-related clinical trials. As the literature about CBD, especially in vitro reports, is often contradictory, increasing our understanding of its specific action on a molecular level will allow to determine whether CBD can become a useful therapy or exacerbates specific cancers in a context-dependent manner. Due to its relative lipophilicity, CBD is challenging to dispense at therapeutic concentrations;therefore, one goal is to identify cannabinoid congeners with greater efficacy and reduced drug delivery challenges. We recently showed that CBD activates interferons as a mechanism of inhibiting SARS-CoV-2 replication in lung carcinoma cells. As factors produced by the innate immune system, interferons have been implicated in both pro-survival and growth arrest and apoptosis signaling in cancer. Here we show that CBD induces interferon production and interferon stimulated genes (ISGs) through a mechanism involving NRF2 and MAVS in lung carcinoma cells. We also show that CBDV, which differs from CBD by 2 fewer aliphatic tail carbons, has limited potency, suggesting that CBD specifically interacts with one or more cellular proteins rather than having a non-specific effect. We also identified other CBD-related cannabinoids that are more effective at inducing ISGs. Taken together, these results characterize a novel mechanism by which CBD activates the innate immune system in lung cancer cells and identify related cannabinoids that have possible therapeutic potential in cancer treatment.
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Glioblastoma is an extremely aggressive and difficult cancer to treat, which may partly be due to its limited ability to induce T-cell responses. However, combining viral vector vaccines with other therapies to generate tumor-specific T cells may provide a meaningful benefit to patients. Here, we investigated whether heterologous prime-boost vaccination with chimpanzee-derived adenoviral vector ChAdOx1 and modified vaccinia Ankara (MVA) vaccines could generate therapeutically effective CD8+ T-cell responses against a model antigen P1A, a mouse homolog of human tumorassociated Melanoma Antigen GenE (MAGE)-type antigens, expressed by a BGL-1 mouse glioblastoma cell line. We demonstrated that heterologous prime-boost vaccination with ChAdOx1/MVA vaccines targeting P1A generated a high magnitude of CD8+ T cells specific for the P1A35-43 epitope presented by the MHC class I molecule H-2Ld . Prophylactic vaccination with ChAdOx1/MVA-P1A significantly prolonged the survival of syngeneic mice subcutaneously challenged with P1A-expressing BGL-1 tumors. Furthermore, different vaccination schedules significantly impact the magnitude of antigen-specific CD8+ T-cell responses and may impact protective efficacy. However, the substantial induction of myeloid-derived suppressor cells (MDSCs) by this tumor model presents a significant challenge in the therapeutic setting. Future work will investigate the efficacy of this vaccination strategy on intracranial P1A-expressing BGL-1 models.
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Objectives: COVID-19 had an impact on health care, including diagnostics. Early diagnosis of MM is a critical factor for prognosis. We examined the impact of COVID-19 on incidence of NDMM patients and on characteristics in NDMM patients in US and in Germany. Method(s): 44,164 NDMM patients were identified in TriNetX federated network across 55 healthcare organizations in US between January 2018 and December 2021. A bivariate analysis examined changes in patient characteristics in two cohorts before (Cohort 1;n=25513) and after (Cohort 2;n=18.651) the start of the COVID-19 pandemic in March 2020. 4172 NDMM patients were identified in the German database in a sample of across >100 healthcare organizations in the same time period. Similarly, bivariate analysis examined changes in patient characteristics before (Cohort 1;n=2252) and after (Cohort 2;n=1920) the start of pandemic. Result(s): Analysis of US data showed a significant decrease in incidence of NDMM. Bivariate analysis revealed that NDMM patients in Cohort 2 have a significantly higher risk profile compared with patients in Cohort 1, higher incidence of renal failure (13.5% v. 15.43%), heart failure (10.3% v 11.26%), bone lesions (12.6% v. 13.05%) and anemia (26.8% v. 29.75%). The German data indicated an increased risk profile in Cohort 2, with higher reporting of renal impairment (12.3% v. 15.5%) and cardiac impairment (8.3% v. 10.9%). The higher risk profile was reflected in a significant increase of all SLiM-CRAB criteria, notably hypercalcemia (24.1 % v. 36.9%), bone marrow plasma cell infiltration (28.1% v. 36.8%) and free light chain involvement (27.3% v. 41.3%). Conclusion(s): The results provide real-world evidence of a change in risk profile for patients with NDMM during COVID-19. This higher risk profile is observed in both the US and Germany, and may negatively impact outcomes such as progression-free and five-year overall survival.Copyright © 2023
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Background: Several pro- and anti-inflammatory cytokines involved in COVID-19 and it is reasonable to speculate that their removal from blood might limit organ damage. Hemoperfusion with CytoSorb is a technique developed to adsorb molecules in the middle molecular weight range (up to 55 kDa). Studies in vitro and in vivo have shown that HP is highly effective in clearing blood from a number of cytokines. Method(s): We report a case series of 9 consecutive COVID-patients admitted to our COVID Intensive Care Unit (ICU). Five of them were treated with HP using CytoSorb (T), due to the heavy emergency overload it was impossible to deliver blood purification in the other 4 patients (C), who were also considered as potential candidates by the attending medical team. All patients had pneumonia and respiratory failure requiring continuous positive airway pressure. Different antibacterial prophylaxes, antiviral, and anti-inflammatory therapies including steroids were delivered. Result(s): Our results show a better clinical course of T compared to control patients (C), in fact all T except 1 survived, and only 2 of them were intubated, while all C required intubation and died. CRP decreased in both groups, but to a greater extent after HP. Lymphocytopenia worsened in control patient but not in treated patient after HP. Procalcitonin increased in 2 of the not treated patients. In all survived patients (n = 4) HP reduced pro-inflammatory cytokines, as IL-6, TNF-alpha, and IL-8. Notably, a striking effect was observed on IL-6 levels that at the end of the second session were decreased by a 40% than before the first treatment. Serum levels of IL-8 and TNF-alpha were lowered within normal range. In all patients the treatment was safe and there were no complications. Conclusion(s): Our study suggests a potential efficacy of HP in an early phase of viral infection not only for improving survival in the treated patients but also by the remodeling treatment-associated cytokine levels.
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Introduction: Colorectal cancer is the third most common cause of cancer in the world, after lung and breast cancer, while in Croatia is the most common malignant disease. Among the EU members, Croatia ranks ninth in terms of the incidence of colon cancer and a high second place by mortality. Since 2007, Croatia has had a National Colon Cancer Early Detection Program, but the response rate is still very low - 36% (25-52% depending on county and year).2 Despite the prevention program, approximately 13% of patients in Croatia is initially diagnosed with metastatic disease.1 According to the results of the CONCORD 3 study3, Croatia is at the bottom of the five-year survival (48%) compared to some other western countries (up to 71%) in the world. Method(s): A retrospective analysis was conducted at the Clinic of Oncology and Radiotherapy, CHC Split. Patients with newly diagnosed colorectal adenocarcinoma enrolled in the clinic from January 1, 2020 to December 31, 2020 were processed. The data were analyzed using descriptive statistics methods, with the use of Microsoft Excel tools. Result(s): A retrospective analysis of the medical history identified 269 patients (compared to 387 in 2017) presented at the multidisciplinary team (MDT) of CHC Split who were diagnosed with colorectal adenocarcinoma in 2020. All patients were presented to the MDT before starting the treatment. The median age of patients was 66 years, and the youngest patient was 22 years old. Patients from other counties who did not undergo the entire treatment/monitoring in our institution were excluded from the analysis. 52 patients (19.3%) were diagnosed in the metastatic stage of the disease, in stage 0 4 patients (1.5%), in stage I 32 (12%), in stage II 91 (34%), and in stage III 88 (33%). In 2 patients, the stage couldn't be precisely determined. There is a significant decrease in the number (81 in 2017 and 52 in 2020) but no percentage wise (20.9% in 2017 and 19.3% in 2020) of patients diagnosed with de novo metastatic colorectal cancer compared to the previous analysis from 2017, when 81 of them were detected. Patients diagnosed with metastatic disease were mostly in good general condition: ECOG 0 status 21 patients (40.3%), ECOG 1 24 patients (46.2%), ECOG 2 7 patients (13.5%), while no patient was ECOG status 3 or 4. 32 (57.7%) patients had a left-sided tumor, while 20 (42.3%) patients had a right-sided tumor. Conclusion(s): The results of our retrospective analysis showed a significant decrease in the number of patients compared to previous years. The effect of the smaller number of newly diagnosed patients will be analyzed and the real consequences will be seen, however, the appearance of patients in the later stages of the disease is to be expected.
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Background & Aim: Immune checkpoint inhibitors (ICI) revolutionized solid tumor treatment, however, in many tumors only partial response is achieved. Allocetra-OTS has an immune modulating effect on macrophages and dendritic cells and showed an excellent safety profile in patients including patients with sepsis and Covid-19. Here we investigated the anti-tumoral effect of Allocetra-OTS cellular therapy, in peritoneal solid tumor animal models. Methods, Results & Conclusion(s): Allocetra-OTS is manufactured from enriched mononuclear fractions and induced to undergo early apoptosis. Balb/c mice were inoculated intraperitoneally (IP) with AB12 (mesothelioma) with pLenti-PGK-V5-Luc-Neo and treated with anti- CTLA4 with or without Allocetra-OTS. Mice were monitored daily for clinical score and weekly using IVIS (Fig.1). Kaplan-Meier log rank test was done for survival. For Allocetra-OTS preparation, enriched mononuclear fractions were collected by leukapheresis from healthy eligible human donors and induced to undergo early apoptosis. Anti- CTLA4 standalone therapy significantly improved survival (Fig.2) from mean 34+/-9 to 44.9 +/-20 days. However, OTS standalone therapy was non-inferior and improved survival to 52.3 +/-20 days. Anti-CTLA4 + Allocetra-OTS combination therapy, ameliorated survival to 86.7+/-20 days with complete cancer remission in 60-100% of mice. Similar anti- tumoral effects of Allocetra-OTS were seen in mesothelioma model in a combination therapy with either anti-PD1 or cisplatin and using anti-PD1 in ID8 ovary cancer model. Based on single cell analysis confirmed by flow cytometry and pathology, the mechanism of action seems to be related or at least associated with an increase in f/480high peritoneal macrophages and a decrease in recruited macrophages, and to f/480high infiltration of the tumor. However, further studies are needed to confirm these observations. During IP tumor progression, Allocetra-OTS as a standalone therapy or in combination with ICI, or cisplatin, significantly reduced tumor size and resulted in complete remission in up to 100% treated mice. Similar results were obtained in ID8 ovary cancer. Based on excellent safety profile in > 50 patients treated in prior clinical trials for sepsis and Covid-19, Phase I/II clinical trial of Allocetra-OTS plus chemotherapy has started and three patient already recruited. A second phase I/II clinical trial of Allocetra- OTS plus anti-PD1, as a second- and third-line therapy in various cancers, was initiated in Q1 2023. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy
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Background & Aim: The pro-angiogenic, immunoregulatory and anti- inflammatory properties of MSCs are being exploited for the development of cellular therapies, including the treatment of graft versus host disease (GvHD), inflammatory bowel disease and COVID-19. SNBTS have developed a GMP process to bank umbilical cord MSCs (UC-MSCs) whereby we can reliably bank 100 vials of 10 million P2 UC-MSCs per cord. Each of these vials can be extensively expanded and stored for specific applications. The ultimate aim of the bank is for off-the-shelf clinical use, e.g., in GvHD or as an adjuvant therapy in Islet transplantations. Methods, Results & Conclusion(s): During process development, different basal media and supplements were screened for proliferation and MSC marker expression. Cells grown in promising media combinations were then tested for tri-lineage differentiation (identity), their chemokine/cytokine expression and T-cell inhibition (function) assessed. Medium selected for further GMP development and scale up was ultimately determined by all round performance and regulatory compliance. GMP-like UC-MSCs were shown to have immune-modulatory activity in T-cell proliferation assays at 4:1 or 16:1 ratios. Co-culture of UC-MSCs and freshly isolated leukocytes, +/- the immune activating agent LPS, show a dose dependent survival effect on leukocytes. In particular, neutrophils, which are normally very short lived in vitro demonstrated increased viability when co-cultured with UCMSCs. The survival effect was partially reproduced when UC-MSC were replaced with conditioned medium or cell lysate indicating the involvement of soluble factors. This improved neutrophil survival also correlates with results from leukocyte migration studies that demonstrate neutrophils to be the main cell type attracted to MSCs in in vitro and in vivo. Genetic modification of UC-MSC may improve their therapeutic potential. We have tested gene editing by CRISPR/Cas9 technology in primary UC-MSCS. The CXCL8 gene, highly expressed in UC-MSC, was targeted in isolates from several different donors with editing efficiencies of 78-96% observed. This translated to significant knockdown of CXCL8 protein levels in resting cells, however after stimulation levels of CXCL8 were found to be very similar in edited and non-edited UC-MSCs. This observation requires further study, but overall the results show the potential to generate future banks of primary UC-MSCS with genetically enhanced pro-angiogenic, immunoregulatory and/or anti-inflammatory activities.Copyright © 2023 International Society for Cell & Gene Therapy
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Background: Breast cancer survivors often report their high needs for help during the transition to cancer survivorship. During the COVID-19 pandemic, technology-based programs are increasingly popular because of their high flexibility and accessibility in delivering information and coaching/support to address the current needs for help among cancer survivors. Yet, little is known about how socio-behavioral factors influence the effects of a technology-based intervention on the needs for help of racial/ethnic minority breast cancer survivors, especially Asian American breast cancer survivors. Purpose(s): The purpose of this secondary analysis was to examine the multiple socio-behavioral factors (including attitudes, self-efficacy, perceived barriers, and social influences related to breast cancer survivorship) mediated the effects of a technology-based intervention on the needs for help among Asian American breast cancer survivors. Method(s): This analysis was conducted with the data from 199 Asian American breast cancer survivor women who were recruited from January 2017 to June 2020 through online and offline communities/groups. The needs for help were measured using the Support Care Needs Survey-34 Short Form (SCNS) with five domains on psychological, information, physical, support, and communication needs. Mediation analysis was conducted using the PROCESS macro within SPSS. The analysis determined the mediating effects of four socio-behavioral mediators on the needs for help at pre-test [T0 ], post 1-month [T1 ], and post 3-months [T2 ] of a technology-based intervention. Result(s): Overall, all the mediators had statistically significant mediation effects on all types of needs for help (p < .05) at different points. Attitudes and social influence presented statistically significant mediation effects on the total needs for help score over 3 months (T0 , T1 , and T2 ). Perceived Barriers had mediation effects on all types of needs for help over 1 month (T0 , T1 ). Self-efficacy mediated the effects on all types of needs for help only at post 1 month (T1 ). Conclusion(s): The findings supported that all the socio-behavioral factors (attitudes, self-efficacy, perceived barriers, and social influences) mediated the effects of a technology-based intervention on the needs for help of Asian American breast cancer survivors. Future research and practice should consider socio-behavioral factors to reduce their needs for help during their survivorship process.
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Background: The COVID-19 pandemic impacted the delivery of cancer care and outcomes in the United States (US). We examined the association between time-varying state-level weekly COVID19 mortality and progression-free survival (rwPFS), time to progression (rwTTP), and survival (rwOS) among pts with advanced non-small cell lung cancer (advNSCLC). Method(s): This retrospective study used the nationwide Flatiron Health electronic health recordderived de-identified database. The cohort included community oncology pts diagnosed with advNSCLC between March 1, 2020 and December 31, 2021 (follow-up through March 30, 2022). We extracted US data on COVID-19 deaths from the COVID-19 Data Repository by the Center for Systems Science and Engineering at Johns Hopkins University. We calculated state-level weekly COVID-19 death rates as weekly COVID-19 deaths per state population size from the 2019 American Community Survey. We categorized rates into quintiles based on all weekly rates during the observation period. Analyses were restricted to treated pts and indexed to start of first-line therapy. For rwPFS analyses, first occurrence of progression or death was considered an event, and pts were censored at last clinic note date. For rwTTP, only progression (not death) was considered an event, and pts with no event were censored at last clinic note date. For rwOS analyses, pts who did not die were censored at last structured activity. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between weekly time-varying state-level COVID-19 mortality rates and outcomes of rwPFS, rwTTP, and rwOS, adjusted for age at diagnosis, race/ethnicity, and state. Result(s): Among 7,813 advNSCLC pts, the median age at diagnosis was 70 years, the majority of the cohort was non-Hispanic White (59%), had non-squamous cell histology (68%) and a history of smoking (87%). Compared to pts living in states with the lowest quintile of COVID-19 mortality rates (Q1), pts living in states with the highest COVID-19 mortality (Q5) had worse rwOS (Q5 vs. Q1: HR 1.46, 95% CI 1.26-1.69) and rwPFS (Q5 vs. Q1: HR 1.18, 95% CI 1.05-1.33). No association was observed with rwTTP (Q5 vs. Q1: HR 1.05, 95% CI 0.90-1.22). Conclusion(s): In this study of real-world oncology data, we demonstrated the use of publicly-available COVID-19 mortality data to measure the time-varying impact of COVID-19 severity on outcomes in pts with advNSCLC. Higher state-level COVID-19 mortality rates were associated with worse rwOS and rwPFS among advNSCLC pts. The association with increased mortality among pts with advNSCLC may be related to COVID-19-related mortality or other factors such as pre-existing comorbidities which were not explored in this study.
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Cancer remains one of the most prevalent diseases in the United States and a leading cause of death. Large prospective studies have found significant correlations between dietary intake and cancer. Chronic inflammation promotes pro-cancer inflammatory environments and nutrition can influence inflammation, with the intake of certain food items increasing inflammatory biomarkers. The objective of this research was to explore the relationship between inflammatory diet score measured by the Dietary Inflammatory index and all-cause mortality, cancer-specific mortality, and cancer recurrence among cancer survivors. Web of Science, Medline, CINHAL, and PsycINFO databases were searched to collect potentially eligible sources that focus on dietary inflammation and cancer outcomes. All sources were uploaded to Covidence software and screened by two independent blinded reviewers. The quality of the sources was assessed using the Newcastle Ottawa scale and relevant data was extracted and transferred to the Comprehensive Meta Analysis software and a random effects model was used to perform meta-analysis. Of the 1444 studies imported into the Covidence software, 13 passed all the screening stages and were included in the final analysis. Eight studies reported on pre-diagnosis diet while five others reported on postdiagnosis diet. Five studies reported on colorectal cancer, four on breast cancer, two on ovarian cancer, one on endometrial cancer and one on prostate cancer. Meta-analysis of the studies found that being in the highest postdiagnosis DII score indicating pro-inflammatory diet significantly increased the risk of all-cause death among cancer survivors by 33.5% (HR = 1.335, 95% CI = 1.049, 1.698, n = 6). Analysis did not show a statistically significant association between DII score and cancer mortality or recurrence (HR = 1.097, 95% CI = 0.939, 1.281, n = 6). Analysis by cancer subtype found a significant correlation between postdiagnosis DII score and all-cause mortality among the breast cancer survivors (HR = 1.335, 95% CI = 1.041, 1.711, n = 3) though there were no significant associations between DII and the outcomes of interest from the other cancer types. The meta-analysis concludes that being in the highest postdiagnosis DII score group significantly increased the risk of all-cause death among cancer survivors. This suggests that risk of all-cause mortality could be reduced for cancer survivors by consuming more anti-inflammatory food components and reducing consumption of pro-inflammatory foods. These findings also warrant more research in this field to clarify the relationship between dietary inflammation as measured by the DII and cancer outcomes, particularly cancer-specific mortality.
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Introduction: Active cancer increases the odds of death among patients with COVID-19.1 Cancer patients may be at increased risk of complications and mortality from COVID-19 owing to the systemic effects of malignancy, immune suppression after chemotherapy, treatment-related complications and presence of co-morbidities.2 They may develop serious complications necessitating ICU admission. In a meta-analysis, the pooled mortality in cancer patients with COVID-19 admitted to an ICU was 60.2%.3 Our hospital is a tertiary referral cancer centre, and the ICU admitted cancer patients with Covid-19 throughout the pandemic. Objective(s): To determine the 30-day in-hospital mortality of adult cancer patients with Covid-19 admitted to the ICU. We also aimed to determine the factors associated with mortality in cancer patients with Covid-19. Method(s): After approval from the Institutional Ethics Committee, data of all cancer patients (age = 16 years) with Covid-19 admitted to the ICU between March 2020 and March 2021 were retrieved from the hospital records. In case of multiple ICU admissions, data from the first admission was recorded. Data recorded included demographic details, type of cancer (solid, haematological), surgical status, APACHE-II and SOFA scores, C-reactive protein, and interventions in ICU. The primary outcome was 30-day in-hospital mortality. Data were analysed using Man-Whitney test and chi-square test. A multivariable regression analysis was carried out to determine factors associated with mortality. Result(s): Data of 127 cancer patients with Covid-19 was analysed. The median [interquartile range, IQR] age was 55 (43-62) years, and there were 50 females (39.3%). Comorbidities were present in 46 (36%) patients, the commonest being diabetes (29 patients) and hypertension (31 patients). The median [IQR] APACHE-II and SOFA scores were 15[8-20] and 4[2-7], respectively. Overall, 62/127 patients died, and 30-day hospital mortality was 49%. There were 30 patients with haematological malignancy and 97 with solid tumours with 30-day in-hospital mortality rates of 46.7% and 49.5%, respectively;p = 0.84). Amongst patients with solid tumours, there was no difference in mortality in surgical patients compared to non-surgical patients (43.3% vs. 52.2%;p = 0.42). Table 1 summarises the parameters and interventions in survivors and non-survivors. On multivariable analysis, only the change in SOFA score from Day 1 to Day 3 was independently associated with outcome (Odds ratio 1.36 (95% confidence interval 1.01-1.84, p-0.04). Conclusion(s): In patients with cancer and Covid-19 and age =16 years admitted to our ICU, the crude 30-day hospital mortality was 47%. There was no association of mortality with cancer type or surgical status. The only independent predictor of mortality was progression of organ failure. Cancer patients with Covid-19 have a reasonable outcome and should be given a trial of intensive care.
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It is known that inflammatory cytokines exacerbate the persistence and severity of various disease states. Breast cancer is the most frequently detected cancer among women worldwide and our recent studies suggest that the inflammatory state of breast (BrCa) cancer, a byproduct of elevated cytokine expression, induces epigenetic modifications leading to increased recurrence. Ongoing NCI clinical trial data (ClinicalTrials.gov, CCC19, NCT04354701) indicates that among patients with cancer and COVID-19, the mortality is high, and the most prevalent malignancies are of breast [21%] and prostate [16%] origin. Due to the risk of cytokine storm during SARS-CoV-2 infection, it is crucial to identify potential mechanisms of hyperinflammation in BrCa patients. In this study, we have evaluated the level of copy number alteration (CNA) of different inflammatory cytokines including IL-8, IL-1b, IL6, IL-8, GM-CSF, TNF-alpha and many others using cBioportal platform which includes over sixty-nine thousand tumor samples (n>69,000 from 213 different studies) from over 33 different cancers. We found that IL-8 has the highest level of amplification in different breast cancers subtypes. Besides, we also analyzed serum samples from BrCa patients, both recurrent and non-recurrent, by different proteomics methods to identify serum cytokines involved in prognosis and recurrence. Comparative data analysis between non-recurrent BrCa against recurrent BrCa patients identified several proteins with very high significance, mostly proteins associated with epigenetic pathways including HDAC9 (P = 0.0035), HDAC5 (P = 0.013), and HDAC7 (P = 0.020). Besides, we identified differential expression of several pro-inflammatory cytokines and immune regulators (IL-8, IL-4, IL-18, IL-12p70) that were present only in recurrent BrCa patient serum. Our data indicate that inflammatory processes contribute to epigenetic modifications that ultimately play a critical role in breast cancer recurrence. In terms of COVID-19 associated co-morbidity, the already dysregulated inflammatory state of BrCa patients may increase their susceptibility to cytokine-storm, leading to increased severity of COVID-related complications and increased mortality rate. Specifically, we hypothesize that the identified elevated level of IL-8 in BrCa patients may lead to a higher basal level of inflammation and contribute to the risk of attaining cytokine-storm during SARS-CoV-2 infection, making it a valuable target for future studies.
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Objectives: To present a series of immunosuppressed patients (oncohematological disease, congenital immunosuppression, hematopoietic stem cell (HSCT), and solid organ transplant) assisted on ECMO. Method(s): Descriptive, retrospective study (2011-2020) of a cohort of 9 immunosuppressed patients, supported on ECMO. Medical records were reviewed and demographic, clinical, and analytical variables were collected. Result(s): In our series of 9 patients, 5 were male, the median age was 8 years [RIC 3-11 years]. Considering the underlying disease, 6 were oncologic, 1 liver transplant and 2 with congenital immunodeficiency after HSCT. 4 were under active chemotherapy (median 6 days after the last cycle [RIC 5-188]). 6 were admitted due to acute respiratory failure, 3 due to hemodynamic instability (3/9), (one septic shock). The median PEEP was 12 [RIC 9-15] and FiO2 100% (81-100%). 78% (6) required vasoactive drugs (median inotropic score 35 [RIC 0-75]. 40%. 5 had severe neutropenia and/or plateletopenia in the 24 hours prior to ECMO, and alterations in acid-base balance (median pH 7. 1 [RIC 6.9-7.15]. 5 were on multiorgan failure. TPrimary ECMO transport was performed in 4 patients (44%). Cannulation was peripheral in 80% (57% cervical, 43% femoral) and central in 20%;70% VA-ECMO. Median time of assistance was 15 days [RIC 3.5-31.5] in cardiac ECMO (4), and 29 days [RIC 13.5-42] and in pulmonary ECMO (n=5). The median total time of admission was 45 days [RIC 27-59]. 9 had an infection, 2 COVID after HSCT, and 8 bleeding complications, but only one required surgical revision. Renal replacement therapy was used in 5 (median 9 days [RIC 5-34.5]). Other therapies used were polymyxin hemadsorption(2), intratracheal surfactant(2), plasma exchange(1), infusion of mesenchymal cells(1) and specific memory T lymphocytes(2). 4 patients died, 5 survived decannulation, 2 died later, with an overall survival rate to hospital discharge of 33% (3/9). Conclusion(s): Despite having a worse prognosis, ECMO can increase survival in immunosuppressed patients, in situations that are challenging and require a multidisciplinary approach.
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Introduction: Bruton's tyrosine kinase inhibitors (BTKi) are used extensively within the NHS to treat specific B-cell malignancies with patients stopping BTKi usually due to adverse events or disease progression. The objective of this study was to analyse effectiveness of BTKi therapy for chronic lymphocytic leukaemia (CLL) at our centre compared to previously published real-world data from the UKCLL Forum (Follows et al, Blood 2019). In addition, we investigated treatment-related adverse events (AE) and second malignancies. Method(s): This is a single-centre retrospective study of 112 CLL patients treated with a BTKi for a minimum of 4 weeks between 2014 and 2022 (ibrutinib n = 71, acalabrutinib n = 38, zanubrutinib n = 3). Treatment was first line (n = 39), second line (n = 44) and 3+ line (n = 29). Patient demographics, duration of BTKi therapy, Aes, discontinuation reasons and second malignancies were collected. Aes were compared with a parallel cohort of 53 non-CLL BTKi-treated patients. Result(s): Median age starting treatment was 73 years, and 71% were male. Primary outcomes were discontinuation-free survival (DFS) and overall survival (OS). With a median follow-up of 3.90 years, the median DFS was 4.18 years (95% CI: 3.52-4.91) with a median OS of 6.35 years (95% CI: 5.52-NA). These compare favourably with previous UKCLL forum data (median DFS = 2.79 years;median OS = 4.66 years), although our patients were more likely to receive BTKi earlier in treatment (3rd line or beyond: 26% of our patients vs. 78% in the UKCLL Forum). The most common Aes included bleeding, cytopenia, infection, cardiac events and mouth ulcers, with 21% stopping BTKi for CLL due to Aes whilst 15% of non-CLL BTKi patients stopped due to an AE. Second malignancies were reported in 49% of CLL patients, yet only 34% of non-CLL patients. Among patients with a confirmed cause of death, infection was the most common cause (39%), followed by CLL (33%), then second malignancy (18%). Of the 31 deaths in 2020 and 2021, 7/31 (23%) were due to, or in association with COVID-19 infection. No COVID-19 deaths were associated with BTKi in non-CLL patients. Conclusion(s): We demonstrate a favourable real-world DFS and OS for BTKi-treated CLL patients although a high number of patients still stop BTKi due to Aes. The very high incidence of second malignancies for all BTKi-treated patients and COVID-19 and infection-related deaths for CLL patients is concerning. As CLL is known to associate with high levels of second cancers, it remains unclear whether BTKi use increases this risk further.
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Background: The role of inflammatory cytokines is known in the pathogenesis of organ damage and is also confirmed in the context of COVID-19 disease. The modulation of the cytokine storm seems to determine endothelial protection, which can translate into a reduction of the "capillary leak syndrome", and, consequently, in a better control of the formation of edema and pulmonary infiltrates. CytoSorb stands in this context as a cartridge capable of adsorbing cytokines and allowing a better clinical course. Case Report: A 69 years-old woman with a history of arterial hypertension, diabetes mellitus and CKD, was admitted to ICU for SARS Cov 2 related critical illness staged with chest CT, blood gas analysis and PCR. At the admission, the patient presented with ubiquitous interstitial pneumonia, PaO2 60 mmHg with 90% Airvo2 and PCR 36.67. Therefore, in order to remove inflammatory cytokines, the patient underwent hemoperfusion treatment with the CytoSorb adsorbent cartridge. Method(s): The protocol used is approved by the FDA for the treatment of covid patients and consists of the use of 4 cartridges 12h, 12h, 24h, 24h with measurement for each cycle of PCR, PaO2 and chest CT control. Result(s): During the hemoperfusion whit CytoSorb, respiratory failure improved until the patient was discharged from the ICU on the tenth day, with oxygen support via simple facial mask. Below the progressive values of the PCR, PaO2 and the chest CT control on the twelfth day. Conclusion(s): The hemoperfusion treatment with the CytoSorb adsorbent cartridge proved to be a valid adjuvant therapy in determining a better clinical course both in terms of the need for invasive mechanical ventilation and survival.
ABSTRACT
Introduction: While elevated lipase is typically used to diagnose acute pancreatitis, it has also been associated with other critical disease states including sepsis, COVID-19, bowel obstruction, and trauma. In this study we compared outcomes of patients with elevated lipase who had pancreatitis and NPHL. Method(s): Retrospective analysis was performed on all patients who presented to the Emergency Department between February 2016 and August 2020 with lipase >= 3x the upper limit of normal. Patient demographics and past medical history, including active cancer, were noted. Patient outcomes were followed through November 2021. If applicable, dates of death were also documented. Result(s): 414 total patients were included in this study. Upon initial evaluation, 305/414 (74%) were diagnosed with acute pancreatitis (AP) and 109/414 had NPHL. The age (54 617 vs. 58 618, p=0.0220), Sex (male 164/305 vs. 49/109, p=0.1194), and BMI (28.9 67.4 vs. 25.8 64.6, p=0.0066) were compared between the AP and NPHL groups. The serum lipase in the AP and NPHL group were respectively 1471 61070 vs. 605 6555 (p< 0.0001). The most common causes of NPHL were sepsis (10/109;9%) renal failure (7/109;6%), GI bleed (5/109;4%), and bowel obstruction (5/109;4%). The NPHL group had higher rate of malignancy (29/105;28%) compared to those with AP (35/305;11%, p< 0.0001). NPHL patients without malignancy had a higher mortality rate (63/80;80%) compared to those without malignancy in the AP group (17/270;6.3%, p< 0.0001). The most common malignancy in patients with AP was breast (6/35;17%, vs. 3/29;10%, p=0.4943). In NPHL, the most common malignancies were pancreatic (4/29;14%, vs. 3/35;9%, p=0.6920) and bowel malignancies (4/29;14%, vs. 4/35, 11% p51.0000). Conclusion(s): Patients with NPHL without malignancy have higher mortality than those with pancreatitis despite lower serum lipase levels. A limitation of our study is the difference between age and BMI of AP versus NPHL patients. Whether this impacts the prognostic relevance of NPHL on survival need to be explored in future studies.
ABSTRACT
The proceedings contain 35 papers. The topics discussed include: germline variants and prognostic factors for cutaneous melanoma in children and adolescents;association between polygenic risk score and multiple primary melanoma;Porocarcinoma: an epidemiological, clinical, and dermoscopic 20-year study;primary cutaneous melanoma and COVID-19: a hospital-based study;atypical spitz tumors: an epidemiological, clinical and dermoscopic multicenter study with 16 years of follow-up;pediatric melanoma: an epidemiological, clinical and dermoscopic multicenter study;recurrence-free survival prediction in melanoma patients by exploiting artificial intelligence techniques on melanoma whole slide images;ultra-high frequency ultrasound and machine learning approaches for the differential diagnosis of melanocytic lesions;and genetic determinants of response to therapy in a real-world setting of advanced/metastatic melanoma patients: whole-exome sequencing and CFDNA analysis.