The impact of the COVID-19 pandemic on short-term cancer survival in the United Kingdom: a cohort analysis (preprint)

Objectives: The COVID-19 pandemic profoundly affected healthcare systems and patients. There is a pressing need to comprehend the collateral effects of the pandemic on non-communicable diseases. Here we examined the impact of the COVID-19 pandemic on short-term cancer survival in the United Kingdom (UK). We hypothesised that short-term survival from nine cancers would be reduced during the pandemic, particularly cancers that benefit from screening and early detection (e.g., breast and colorectal cancer). Design: Population-based cohort study. Setting: Electronic health records from UK primary care Clinical Practice Research Datalink (CPRD) GOLD database. Participants: There were 12,259,744 eligible patients aged [≥]18 years with [≥]one year of prior history identified from January 2000 to December 2021. Main outcome measures: We estimated age-standardised incidence rates (IR) and short-term (one- and two-year) survival of several common cancers (breast, colorectal, head and neck, liver, lung, oesophagus, pancreatic, prostate, and stomach cancer) from 2000 to 2019 (in five-year strata) compared to 2020 to 2021 using the Kaplan-Meier method. Results: Apart from pancreatic cancer, IRs decreased for all cancers in 2020 and recovered to different extents in 2021. Short-term survival improved for most cancers between 2000 to 2019, but then declined for those diagnosed in 2020 to 2021.This was most pronounced for colorectal cancer, with one-year survival falling from 79.3% [95% confidence interval: 78.5%-80.1%] in 2015 to 2019 to 76.3% [74.6%-78.1%] for those diagnosed in 2020 to 2021. Conclusion: Short-term survival for many cancers was impacted by the management of the COVID-19 pandemic in the UK. This decline was most prominent for colorectal cancer, with reductions in survivorship equivalent to returning to mortality seen in the first decade of the 2000s. These results illustrate the need for an immediate and well-funded investment in resolving the current backlog in cancer screening and diagnostic procedures in the UK National Health Service to improve patient outcomes.

Host factor PLAC8 is required for pancreas infection by SARS-CoV-2 (preprint)

Although mounting evidence demonstrated that pancreas is infected by SARS-CoV-2 the severity and pathophysiology of pancreatic COVID-19 disease are still unclear. Here we investigated the consequences of SARS-CoV-2 infection of the pancreas and the role of Placenta-associated protein-8 (PLAC8). Our data showed pancreatic damage in patients who died from COVID-19. Notably, circulating pancreatic enzymes stratified patients according to COVID-19 severity and outcome. PLAC8 expression was associated with SARS-CoV-2 infection in postmortem analysis of COVID-19 patients and functional assays demonstrated the requirement of PLAC8 in SARS-CoV-2 pancreatic infection. Full SARS-CoV-2 infectious virus revealed a requirement of PLAC8 for efficient viral infection of pancreatic cell lines. Finally, we observed colocalization of PLAC8 and SARS-CoV-2 in the pancreas of deceased patients. In conclusion, our data confirm the human pancreas as a SARS-CoV-2 target and demonstrate the requirement of PLAC8 for SARS-CoV-2 pancreatic infection thereby opening new target opportunities for COVID-19-associated pancreatic pathogenesis.

Unleashing the Power of Artificial Intelligence: Unraveling the Intricate Dynamics between Viral and Bacterial Infections, Immune Factors, COVID-19, and Cancer in Women's Health (preprint)

The intricate interplay between viral and bacterial infections, immune factors, COVID-19, and cancer in women's health has garnered significant attention in recent research. This comprehensive study aimed to unravel the complex dynamics between these factors and provide valuable insights into their implications for women's health. Through meticulous analysis of available data, this study elucidated the prevalence of viral and bacterial infections in women, encompassing influential pathogens such as influenza, human papillomavirus, Staphylococcus aureus, Escherichia coli, and Streptococcus pneumoniae. Additionally, it explored the relationship between specific cytokine types, including Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), Interferon-gamma (IFN-γ), and Interleukin-10 (IL-10), and viral infections. The prevalence of various cancer types, such as breast cancer, lung cancer, colorectal cancer, ovarian cancer, and cervical cancer, was also assessed. Furthermore, this study examined the correlations between immune factors and viral infections, uncovering significant associations that shed light on the intricate interplay between immune responses and viral infections. Immune markers such as IL-6, TNF-α, IFN-γ, Interleukin-1beta (IL-1β), and Interleukin-12 (IL-12) exhibited diverse levels of correlation with specific viral infections. These findings hold promise for disease prognosis and treatment optimization. Additionally, the association between bacterial infections and women's health conditions was explored, revealing the impact of pathogens like Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecalis on gynecological infections, reproductive disorders, and other relevant conditions. This highlights the need for effective strategies to prevent and manage bacterial infections, aiming to mitigate their adverse effects on women's health. In the context of COVID-19, this study investigated immune factors as predictors of disease outcomes in women. Various cytokines, including IL-6, TNF-α, IL-1β, IFN-γ, IL-10, IL-8, IL-4, IL-2, IL-12, and IL-17, demonstrated associations with disease severity, offering potential prognostic markers for identifying individuals at higher risk of severe illness. Furthermore, the relationship between viral and bacterial infections and cancer incidence in women was explored. Viral infections, such as human papillomavirus and influenza, showed associations with specific cancer types, including breast cancer, cervical cancer, lung cancer, skin cancer, and stomach cancer. Bacterial infections, such as Staphylococcus aureus and Escherichia coli, were linked to ovarian cancer, colorectal cancer, pancreatic cancer, bladder cancer, kidney cancer, and esophageal cancer. These findings provide valuable insights into the potential role of infectious etiologies in cancer development among women. In conclusion, this comprehensive study unveils the intricate dynamics between viral and bacterial infections, immune factors, COVID-19, and cancer in women's health. The findings emphasize the importance of considering the interconnectedness of these factors to enhance disease prevention, diagnosis, and treatment strategies in women. Further research is warranted to unravel the underlying mechanisms and translate these findings into clinical applications.

Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is lethal in 88% of patients1, yet harbours mutation-derived T cell neoantigens that are suitable for vaccines 2,3. Here in a phase I trial of adjuvant autogene cevumeran, an individualized neoantigen vaccine based on uridine mRNA-lipoplex nanoparticles, we synthesized mRNA neoantigen vaccines in real time from surgically resected PDAC tumours. After surgery, we sequentially administered atezolizumab (an anti-PD-L1 immunotherapy), autogene cevumeran (a maximum of 20 neoantigens per patient) and a modified version of a four-drug chemotherapy regimen (mFOLFIRINOX, comprising folinic acid, fluorouracil, irinotecan and oxaliplatin). The end points included vaccine-induced neoantigen-specific T cells by high-threshold assays, 18-month recurrence-free survival and oncologic feasibility. We treated 16 patients with atezolizumab and autogene cevumeran, then 15 patients with mFOLFIRINOX. Autogene cevumeran was administered within 3 days of benchmarked times, was tolerable and induced de novo high-magnitude neoantigen-specific T cells in 8 out of 16 patients, with half targeting more than one vaccine neoantigen. Using a new mathematical strategy to track T cell clones (CloneTrack) and functional assays, we found that vaccine-expanded T cells comprised up to 10% of all blood T cells, re-expanded with a vaccine booster and included long-lived polyfunctional neoantigen-specific effector CD8+ T cells. At 18-month median follow-up, patients with vaccine-expanded T cells (responders) had a longer median recurrence-free survival (not reached) compared with patients without vaccine-expanded T cells (non-responders; 13.4 months, P = 0.003). Differences in the immune fitness of the patients did not confound this correlation, as responders and non-responders mounted equivalent immunity to a concurrent unrelated mRNA vaccine against SARS-CoV-2. Thus, adjuvant atezolizumab, autogene cevumeran and mFOLFIRINOX induces substantial T cell activity that may correlate with delayed PDAC recurrence.

Clinical trial-identified inflammatory biomarkers in breast and pancreatic cancers.

Breast cancer and pancreatic cancer are two common cancer types characterized by high prevalence and high mortality rates, respectively. However, breast cancer has been more well-studied than pancreatic cancer. This narrative review curated inflammation-associated biomarkers from clinical studies that were systematically selected for both breast and pancreatic cancers and discusses some of the common and unique elements between the two endocrine-regulated malignant diseases. Finding common ground between the two cancer types and specifically analyzing breast cancer study results, we hoped to explore potential feasible methods and biomarkers that may be useful also in diagnosing and treating pancreatic cancer. A PubMed MEDLINE search was used to identify articles that were published between 2015-2022 of different kinds of clinical trials that measured immune-modulatory biomarkers and biomarker changes of inflammation defined in diagnosis and treatment of breast cancer and pancreatic cancer patients. A total of 105 papers (pancreatic cancer 23, breast cancer 82) were input into Covidence for the title and abstract screening. The final number of articles included in this review was 73 (pancreatic cancer 19, breast cancer 54). The results showed some of the frequently cited inflammatory biomarkers for breast and pancreatic cancers included IL-6, IL-8, CCL2, CD8+ T cells and VEGF. Regarding unique markers, CA15-3 and TNF-alpha were two of several breast cancer-specific, and CA19 and IL-18 were pancreatic cancer-specific. Moreover, we discussed leptin and MMPs as emerging biomarker targets with potential use for managing pancreatic cancer based on breast cancer studies in the future, based on inflammatory mechanisms. Overall, the similarity in how both types of cancers respond to or result in further disruptive inflammatory signaling, and that point to a list of markers that have been shown useful in diagnosis and/or treatment method response or efficacy in managing breast cancer could potentially provide insights into developing the same or more useful diagnostic and treatment measurement inflammatory biomarkers for pancreatic cancer. More research is needed to investigate the relationship and associated inflammatory markers between the similar immune-associated biological mechanisms that contribute to breast and pancreatic cancer etiology, drive disease progression or that impact treatment response and reflect survival outcomes.

A National Audit of Pancreatic Enzyme Prescribing in Pancreatic Cancer from 2015 to 2023 in England Using OpenSAFELY-TPP.

OBJECTIVES: Cancer treatments were variably disrupted during the coronavirus disease 2019 (COVID-19) pandemic. UK guidelines recommend pancreatic enzyme replacement therapy (PERT) to all people with unresectable pancreatic cancer. The aim was to investigate the impact of the COVID-19 pandemic on PERT prescribing to people with unresectable pancreatic cancer and to investigate the national and regional rates from January 2015 to January 2023. DATA SOURCES: With the approval of NHS England, we conducted this study using 24 million electronic health records of people within the OpenSAFELY-TPP research platform. There were 22,860 people diagnosed with pancreatic cancer in the study cohort. We visualized the trends over time and modeled the effect of the COVID-19 pandemic with the interrupted time-series analysis. CONCLUSION: In contrast to many other treatments, prescribing of PERT was not affected during the pandemic. Overall, since 2015, the rates increased steadily over time by 1% every year. The national rates ranged from 41% in 2015 to 48% in early 2023. There was substantial regional variation, with the highest rates of 50% to 60% in West Midlands. IMPLICATIONS FOR NURSING PRACTICE: In pancreatic cancer, if PERT is prescribed, it is usually initiated in hospitals by clinical nurse specialists and continued after discharge by primary care practitioners. At just under 50% in early 2023, the rates were still below the recommended 100% standard. More research is needed to understand barriers to prescribing of PERT and geographic variation to improve quality of care. Prior work relied on manual audits. With OpenSAFELY, we developed an automated audit that allows for regular updates (https://doi.org/10.53764/rpt.a0b1b51c7a).

Infection with COVID-19 promotes the progression of pancreatic cancer through the PI3K-AKT signaling pathway (preprint)

Objective To investigate the effect of COVID-19 infection on pancreatic cancer . Methods Based on the mRNA-Seq data of COVID-19 patients and pancreatic cancer (PC) patients in the GEO database, we used support vector machine (SVM), LASSO-Cox regression analysis and random forest tree (RF) to screen the common signature genes of the two diseases and further investigate their effects and functional characteristics on PC, respectively. And the above procedures were performed in R software. Results The proteins COL10A1/FAP/FN1 were found to be common signature genes for COVID-19 and PC, were significantly up-regulated in both diseases, and showed good diagnostic efficacy for PC. The risk model based on COL10A1/FAP/FN1 showed good PC risk prediction ability and clinical application potential. Tumor typing based on COL10A1/FAP/FN1 expression levels effectively classified PC into different subtypes, and showed significant differences between the two subtypes in terms of survival prognosis, immune levels, immune checkpoint expression levels, mutation status of common tumor mutation sites, and drug sensitivity analysis. While pathway analysis also revealed that FN1 as an extracellular matrix component may be involved in the biological process of PC by regulating the PI3K-AKT signaling axis. Conclusion The upregulated expression of COL10A1/FAP/FN1, the characteristic genes of COVID-19, are potential diagnostic targets for PC, and the upregulated expression of FN1 may promotes the progression of PC by activating the PI3K-AKT signaling pathway. The COL10A1/FAP/FN1-based typing provides a new typing approach for PC, also provides a good reference and idea for the refinement of PC treatment and subsequent clinical research.

Challenges in Recruitment and Retention: Leveraging Health-Related Antecedents and Information Carrier Factors to Improve Patient Participation in Pancreatic Cancer Research-A Review Article.

ABSTRACT: Advancements in pancreatic ductal adenocarcinoma (PDAC) prevention, diagnosis, and treatment rely on representative and robust clinical trial participation. Given the severity of PDAC, along with the lack of effective early detection approaches, the need for accessible screening tools and new treatments is dire. Unfortunately, enrollment barriers often result in low participant accrual rates for PDAC studies and illustrate the challenging terrain researchers are facing. Research participation along with access to preventative care has been further impacted by the coronavirus disease 2019 pandemic. In this review, we use the Comprehensive Model for Information Seeking to discuss underexplored factors that influence patient participation in clinical studies. Adequate staffing, flexible scheduling, effective patient and physician communication, and culturally responsive messaging, along with the use of telehealth, can support enrollment objectives. Clinical research studies are a key component of health care, informing medical advancements, and improving outcomes. By leveraging health-related antecedents and information carrier factors, researchers can more effectively address barriers to participation and implement potential evidence-based mitigating strategies. While this work focuses on the PDAC research context, the lessons delineated here are applicable to the wider cancer research setting.

The impact of the COVID-19 pandemic upon pancreatic cancer treatment (CONTACT Study): a UK national observational cohort study.

INTRODUCTION: CONTACT is a national multidisciplinary study assessing the impact of the COVID-19 pandemic upon diagnostic and treatment pathways among patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: The treatment of consecutive patients with newly diagnosed PDAC from a pre-COVID-19 pandemic cohort (07/01/2019-03/03/2019) were compared to a cohort diagnosed during the first wave of the UK pandemic ('COVID' cohort, 16/03/2020-10/05/2020), with 12-month follow-up. RESULTS: Among 984 patients (pre-COVID: n = 483, COVID: n = 501), the COVID cohort was less likely to receive staging investigations other than CT scanning (29.5% vs. 37.2%, p = 0.010). Among patients treated with curative intent, there was a reduction in the proportion of patients recommended surgery (54.5% vs. 76.6%, p = 0.001) and increase in the proportion recommended upfront chemotherapy (45.5% vs. 23.4%, p = 0.002). Among patients on a non-curative pathway, fewer patients were recommended (47.4% vs. 57.3%, p = 0.004) or received palliative anti-cancer therapy (20.5% vs. 26.5%, p = 0.045). Ultimately, fewer patients in the COVID cohort underwent surgical resection (6.4% vs. 9.3%, p = 0.036), whilst more patients received no anti-cancer treatment (69.3% vs. 59.2% p = 0.009). Despite these differences, there was no difference in median overall survival between the COVID and pre-COVID cohorts, (3.5 (IQR 2.8-4.1) vs. 4.4 (IQR 3.6-5.2) months, p = 0.093). CONCLUSION: Pathways for patients with PDAC were significantly disrupted during the first wave of the COVID-19 pandemic, with fewer patients receiving standard treatments. However, no significant impact on survival was discerned.

Travel patterns of patients seeking cancer care during the COVID-19 pandemic: Multi-centre cohort study in Osaka, Japan.

BACKGROUND: In Japan, provision of equal access to cancer care is intended to be achieved via secondary medical areas (SMAs). However, the percentage of patients receiving care within the residential area varies by SMA in Osaka Prefecture. We aimed to assess the effect size of factors associated with patient mobility, and whether patient mobility was affected by the COVID-19 pandemic. METHODS: Records of patients diagnosed with stomach, colorectal, lung, breast, cervical, oesophageal, liver or pancreatic cancer during 2019-2020 were extracted from multi-centre hospital-based cancer registry data. Odds ratios of whether a patient received care within the SMA of residence were set as the outcome. A multivariable model was built using generalised estimating equations with multiple imputation for missing data. Change in patient mobility after the pandemic was examined by deriving age- and SMA-specific adjusted ORs (aORs). RESULTS: A total of 78,839 records were included. Older age, more advanced stage and palliative care had up to 1.69 times higher aORs of receiving care within their own area. Patients with oesophageal, liver or pancreatic cancer tended to travel outside their area with aORs ranging from 0.71 to 0.90. Patients aged ≤ 79 and living in the East and South SMAs tended to remain in their area with aORs ranging from 1.05 to 1.11 after the pandemic. CONCLUSION: Patient mobility decreased for higher age and stage. It also varied by SMA, cancer site and treatment type. POLICY SUMMARY: Our results need to be linked with resource inputs to help policymakers decide whether to intervene to address current efficiency or equity issues.

Effect of DPP4/CD26 expression on SARS­CoV­2 susceptibility, immune response, adenosine (derivatives m62A and CD) regulations on patients with cancer and healthy individuals.

The worldwide COVID­19 pandemic was brought on by a new coronavirus (SARS Cov­2). A marker/receptor called Dipeptidyl peptidase 4/CD26(DPP4/CD26) may be crucial in determining susceptibility to tumors and coronaviruses. However, the regulation of DPP4 in COVID­invaded cancer patients and its role on small molecule compounds remain unclear. The present study used the Human Protein Atlas, Monaco, and Schmiedel databases to analyze the expression of DPP4 in human tissues and immune cells. The association between DPP4 expression and survival in various tumor tissues was compared using GEPIA 2. The DNMIVD database was used to analyze the correlation between DPP4 expression and promoter methylation in various tumors. On the cBioPortal network, the frequency of DPP4 DNA mutations in various cancers was analyzed. The correlation between DPP4 expression and immunomodulators was analyzed by TISIDB database. The inhibitory effects of cordycepin (CD), N6, N6­dimethyladenosine (m62A) and adenosine (AD) on DPP4 in cancer cells were evaluated. DPP4 was mainly expressed in endocrine tissue, followed by gastrointestinal tract, female tissue (mainly in placenta), male tissue (mainly in prostate and seminal vesicle), proximal digestive tract, kidney, bladder, liver, gallbladder and respiratory system. In immune cells, DPP4 mRNA was mainly expressed in T cells, and its expression was upregulated in esophageal carcinoma, kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma, pancreatic adenocarcinoma, prostate adenocarcinoma, stomach adenocarcinoma, thyroid carcinoma and thymoma. However, it was downregulated in breast invasive carcinoma, kidney chromophobe, lung squamous cell carcinoma and skin cutaneous melanoma. Thus, DPP4 is involved in viral invasion in most types of cancer. The expression of DPP4 could be inhibited by CD, m62A and AD in different tumor cells. Moreover, CD significantly inhibited the formation of GFP­positive syncytial cells. In vivo experiments with AD injection further showed that AD significantly inhibited lymphocyte activating factor 3 expression. These drugs may have potential to treat COVID­19 by targeting DPP4. Thus, DPP4 may be medically significant for SARS­CoV­2­infected cancer patients, providing prospective novel targets and concepts for the creation of drugs against COVID­19.

The Pancreas in Coronavirus Disease 2019 Infection.

An association between acute pancreatitis (AP) and coronavirus disease 2019 (COVID-19) has been proposed but the mechanisms of pancreatic injury of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the implicative role on the development of AP are not yet fully understood. COVID-19 also imposed major challenges on pancreatic cancer management. We conducted an analysis on the mechanisms of pancreatic injury by SARS-CoV-2 and reviewed published case reports of AP attributed to COVID-19. We also examined the pandemic effect on pancreatic cancer diagnosis and management, including pancreatic surgery.

European cancer mortality predictions for the year 2023 with focus on lung cancer.

BACKGROUND: We predicted cancer mortality figures for 2023 for the European Union (EU-27), its five most populous countries, and the UK. We also focused on mortality from lung cancer. MATERIALS AND METHODS: Using cancer death certification and population data from the World Health Organization and Eurostat databases for 1970-2018, we predicted numbers of deaths and age-standardized rates (ASRs) for 2023 for all cancers combined and the 10 most common cancer sites. We investigated the changes in trends over the observed period. The number of avoided deaths over the period 1989-2023 were estimated for all cancers as well as lung cancer. RESULTS: We predicted 1 261 990 cancer deaths for 2023 in the EU-27, corresponding to ASRs of 123.8/100 000 men (-6.5% versus 2018) and 79.3 for women (-3.7%). Over 1989-2023, ∼5 862 600 cancer deaths were avoided in the EU-27 compared with peak rates in 1988. Most cancers displayed favorable predicted rates, with the exceptions of pancreatic cancer, which was stable in EU men (8.2/100 000) and rose by 3.4% in EU women (5.9/100 000), and female lung cancer, which, however, tends to level off (13.6/100 000). Steady declines are predicted for colorectal, breast, prostate, leukemia, stomach in both sexes, and male bladder cancers. The focus on lung cancer showed falls in mortality for all age groups in men. Female lung cancer mortality declined in the young (-35.8%, ASR: 0.8/100 000) and middle-aged (-7%, ASR: 31.2/100 000) but still increased by 10% in the elderly (age 65+ years). CONCLUSIONS: The advancements in tobacco control are reflected in favorable lung cancer trends, and should be pushed further. Greater efforts on the control of overweight and obesity, alcohol consumption, infection and related neoplasms, together with improvements in screening, early diagnosis, and treatments may achieve a further 35% reduction in cancer mortality in the EU by 2035.

Expanding role of CXCR2 and therapeutic potential of CXCR2 antagonists in inflammatory diseases and cancers.

C-X-C motif chemokine receptor 2 (CXCR2) is G protein-coupled receptor (GPCR) and plays important roles in various inflammatory diseases and cancers, including chronic obstructive pulmonary disease (COPD), atherosclerosis, asthma, and pancreatic cancer. Upregulation of CXCR2 is closely associated with the migration of neutrophils and monocytes. To date, many small-molecule CXCR2 antagonists have entered clinical trials, showing favorable safety and therapeutic effects. Hence, we provide an overview containing the discovery history, protein structure, signaling pathways, biological functions, structure-activity relationships and clinical significance of CXCR2 antagonists in inflammatory diseases and cancers. According to the latest development and recent clinical progress of CXCR2 small molecule antagonists, we speculated that CXCR2 can be used as a biomarker and a new target for diabetes and that CXCR2 antagonists may also attenuate lung injury in coronavirus disease 2019 (COVID-19).

The COVID - AGICT study: COVID-19 and advanced gastro-intestinal cancer surgical treatment. A multicentric Italian study on the SARS-CoV-2 pandemic impact on gastro-intestinal cancers surgical treatment during the 2020. Analysis of perioperative and short-term oncological outcomes.

BACKGROUND: This Italian multicentric retrospective study aimed to investigate the possible changes in outcomes of patients undergoing surgery for gastrointestinal cancers during the COVID-19 pandemic. METHOD: Our primary endpoint was to determine whether the pandemic scenario increased the rate of patients with colorectal, gastroesophageal, and pancreatic cancers resected at an advanced stage in 2020 compared to 2019. Considering different cancer staging systems, we divided tumors into early stages and advanced stages, using pathological outcomes. Furthermore, to assess the impact of the COVID-19 pandemic on surgical outcomes, perioperative data of both 2020 and 2019 were also examined. RESULTS: Overall, a total of 8250 patients, 4370 (53%) and 3880 (47%) were surgically treated during 2019 and 2020 respectively, in 62 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (P = 0.25). Nevertheless, the analysis of quarters revealed that in the second half of 2020 the rate of advanced cancer resected, tented to be higher compared with the same months of 2019 (P = 0.05). During the pandemic year 'Charlson Comorbidity Index score of cancer patients (5.38 ± 2.08 vs 5.28 ± 2.22, P = 0.036), neoadjuvant treatments (23.9% vs. 19.5%, P < 0.001), rate of urgent diagnosis (24.2% vs 20.3%, P < 0.001), colorectal cancer urgent resection (9.4% vs. 7.37, P < 0.001), and the rate of positive nodes on the total nodes resected per surgery increased significantly (7 vs 9% - 2.02 ± 4.21 vs 2.39 ± 5.23, P < 0.001). CONCLUSIONS: Although the SARS-CoV-2 pandemic did not influence the pathological stage of colorectal, gastroesophageal, and pancreatic cancers at the time of surgery, our study revealed that the pandemic scenario negatively impacted on several perioperative and post-operative outcomes.

Observational study on antibody response to COVID-19 Vaccines in pAtients with gastro-entero-panCreatic Cancers and neuroendocrIne NeoplAsms on systemic TreatmEnts (VACCINATE). (preprint)

The Coronavirus disease-19 (COVID-19) pandemic dramatically impacted on oncologic patients' care. Since the introduction of vaccines and the demonstration of their benefit on frail patients, COVID-19 vaccinations were indicated also for oncologic population. However, data about the impact of anticancer-treatments and the timing between vaccinations and systemic therapy de-livery were not available. We aimed to evaluate potential factors influencing the outcome of COVID-19 vaccination in cancer patients. We prospectively collected data of patients undergoing COVID-19 vaccination with gas-tro-entero-pancreatic and neuroendocrine neoplasms, treated at our Institute, between 03/2021 and 12/2021. We enrolled 46 patients, 63.1% males; at the time of data collection 86.9% received two-doses of Pfizer-BioNTech and the remains Moderna vaccine. All patients obtained a subsequent im-mune-response. A significantly lower values of IgG for patients treated with chemotherapy versus other anti-cancer agents (p=0.004). No significant effect on immune-response was reported for both vaccinations performed ≤7 vs >7 days from the last systemic treatment (p=0.77) and lymphocytes count (p=0.11). The findings suggest that the optimal timing for COVID-19 vaccination and lymphocytes count are not the issue but rather the quality of the subset of lymphocytes before the vaccination to deter-mine the efficacy level of immune-response in this population.

Circulating tissue factor-positive extracellular vesicles and their association with thrombosis in different diseases.

Tissue factor (TF) is a procoagulant protein released from activated host cells, such as monocytes, and tumor cells on extracellular vesicles (EVs). TF + EVs are observed in the circulation of patients with various types of diseases. In this review, we will summarize the association between TF + EVs and activation of coagulation and survival in different types of diseases, including cancer, sepsis, and infections with different viruses, such as human immunodeficiency virus (HIV), influenza A virus (IAV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We will also discuss the source of TF + EVs in various diseases. EVTF activity is associated with thrombosis in pancreatic cancer patients and coronavirus disease 2019 patients (COVID-19) and with disseminated intravascular coagulation in cancer patients. EVTF activity is also associated with worse survival in patients with cancer and COVID-19. Monocytes are the major sources of TF + EVs in sepsis, and viral infections, such as HIV, Ebola virus, and SARS-CoV-2. In contrast, alveolar epithelial cells are the major source of TF + EVs in bronchoalveolar lavage fluid in COVID-19 and influenza A patients. These studies indicate that EVTF activity could be used as a biomarker to identify patients that have an increased risk of coagulopathy and mortality.

A Modified Regimen of 21-day Nab-Paclitaxel Plus Gemcitabine in Locally Advanced or Metastatic Pancreatic Cancer: A Retrospective Real-World Study.

BACKGROUND: It is 1 of the standard treatment options for metastasis pancreatic cancer to receive nab-paclitaxel (125 mg/m2) plus gemcitabine (1000 mg/m2) on days 1, 8 and 15 every 28 days. Some patients showed intolerance and inconvenience to this therapeutic regimen. Thus, we conducted this retrospective real-world study to determine the efficacy and tolerability of a modified 21-day nab-paclitaxel plus gemcitabine (nab-P/Gem) regimen for the first-line treatment of locally advanced or metastatic pancreatic cancer. METHODS: Patients with locally advanced and metastatic pancreatic cancer treated with nab-paclitaxel (125 mg/m2) plus gemcitabine (1000 mg/m2) on days 1 and 8 every 21-day at West China Hospital and Shang Jin Hospital of Sichuan University from Mar 2018 to Dec 2021 were reviewed retrospectively. Clinical characteristics of patients were collected. The progression-free survival, overall survival, objective response rate, disease control rate, and toxicity were evaluated. RESULTS: A total of 113 patients who received the modified regimen of 21-day nab-P/Gem chemotherapy were included. The median overall survival was 9.3 months and the median progression-free survival was 4.4 months. The objective response rate and disease control rate were 18.6% and 56.7%, respectively. The median relative dose intensity for this modified regimen was 65%. The adverse events were mild to moderate, and the most common grade 3 or 4 treatment-related adverse events were neutropenia (21%) and leukopenia (16%). CONCLUSIONS: Our study showed that this modified regimen of 21-day nab-P/Gem for locally advanced and metastatic pancreatic cancer had comparable efficacy and tolerable toxicity. This treatment may provide a considerable option for pancreatic cancer patients who desire a modified schedule. The modified regimen of 21-day nab-P/Gem is also an option worth considering during the coronavirus disease 2019 pandemic for minimizing the number of visits and limiting the risk of exposure.

Healthcare in England was affected by the COVID-19 pandemic across the pancreatic cancer pathway: a cohort study using OpenSAFELY-TPP (preprint)

Background Healthcare across all sectors, in the UK and globally, was negatively affected by the COVID-19 pandemic. We investigated the effect of the COVID-19 pandemic on the quantity of healthcare services delivered to people with pancreatic cancer. Methods With the approval of NHS England, and drawing from a nationally representative OpenSAFELY-TPP dataset of 24 million patients (over 40% of the English population), we undertook a cohort study of people diagnosed with pancreatic cancer. We queried electronic healthcare records for information on the provision of healthcare services across the pancreatic cancer pathway. To estimate the effect of the COVID-19 pandemic, we predicted the rates of healthcare services if the pandemic had not happened. We used generalised linear models (GLM) and the pre-pandemic data from January 2015 to February 2020 to predict rates in March 2020 to September 2022. The 95% confidence intervals of the predicted values were used to estimate the significance of the difference between the predicted and observed rates. Results The rate of pancreatic cancer and diabetes diagnoses in the cohort was not affected by the pandemic. There were 24,500 people diagnosed with pancreatic cancer from January 2015 to September 2022. The mean age at diagnosis was 72 (SD 11), 48% of people were female, 95% were of White ethnicity and 39% were diagnosed with diabetes. We found a reduction in surgical resections by nearly 25% during the pandemic. In addition, 20%, 10% and 5% fewer people received BMI, HbA1c and liver function tests respectively before they were diagnosed with pancreatic cancer. There was no impact of the pandemic on the number of people making contact with primary care, but the number of contacts increased on average by 1 to 2 per person amongst those who made contact. Abdominal scans decreased by 7% and reporting of jaundice decreased by 20%, but recovered within six months into the pandemic. Emergency department visits, hospital admissions and deaths were not affected. Conclusions The pandemic affected healthcare in England across the pancreatic cancer pathway. Positive lessons could be learnt from services that recovered quickly. The reductions in healthcare experienced by people with cancer have the potential to lead to worse outcomes. Current efforts should focus on addressing the unmet needs of people with cancer.