Development of Cancer Immunotherapies.

Cancer immunotherapy, or the utilization of components of the immune system to target and eliminate cancer, has become a highly active area of research in the past several decades and a common treatment strategy for several cancer types. The concept of harnessing the immune system for this purpose originated over 100 years ago when a physician by the name of William Coley successfully treated several of his cancer patients with a combination of live and attenuated bacteria, later known as "Coley's Toxins", after observing a subset of prior patients enter remission following their diagnosis with the common bacterial infection, erysipelas. However, it was not until late in the twentieth century that cancer immunotherapies were developed for widespread use, thereby transforming the treatment landscape of numerous cancer types. Pivotal studies elucidating molecular and cellular functions of immune cells, such as the discovery of IL-2 and production of monoclonal antibodies, fostered the development of novel techniques for studying the immune system and ultimately the development and approval of several cancer immunotherapies by the United States Food and Drug Association in the 1980s and 1990s, including the tuberculosis vaccine-Bacillus Calmette-Guérin, IL-2, and the CD20-targeting monoclonal antibody. Approval of the first therapeutic cancer vaccine, Sipuleucel-T, for the treatment of metastatic castration-resistant prostate cancer and the groundbreaking success and approval of immune checkpoint inhibitors and chimeric antigen receptor T cell therapy in the last decade, have driven an explosion of interest in and pursuit of novel cancer immunotherapy strategies. A broad range of modalities ranging from antibodies to adoptive T cell therapies is under investigation for the generalized treatment of a broad spectrum of cancers as well as personalized medicine. This chapter will focus on the recent advances, current strategies, and future outlook of immunotherapy development for the treatment of cancer.

Glycosylated phospholipid-coated upconversion nanoparticles for bioimaging of non-muscle invasive bladder cancers.

Detection of non-muscle invasive bladder cancer (NMIBC) is crucial to facilitate complete tumor resection, thus improving the survival rate as well as reducing the recurrence frequency and treatment expense. Fluorescence imaging cystoscopy is an effective method for the detection of NMIBC. However, its application is limited as the commonly applied fluorescent agents such as dyes and photosensitizers usually lack specific tumor accumulation and are vulnerable to photobleaching. Furthermore, the broad emission band of conventional fluorescent agents limits their imaging and detection efficacy. To overcome these limitations, upconversion nanoparticles (UCNPs) have been selected as the fluorescent agent, due to their resistance to photobleaching, less background auto-fluorescence, and narrow emission bands. In order to achieve active tumor targeting, the UCNPs are coated with a glycosylated phospholipid layer. The glycosylated phospholipid-coated UCNPs exhibited high selective accumulation in cancer cells over normal cells and enhanced the upconversion luminescence (UCL) (at 540 nm and 660 nm) from bladder cancer cells under 980 nm laser irradiation. Glycosylated phospholipid coating that promotes uptake of UCNPs by cancer cells, and UCL emitted from UCNPs under NIR (980 nm) laser irradiation for cancer cell imaging.

Cancer and COVID-19: analysis of patient outcomes.

Background: We sought to investigate the outcomes associated with COVID-19 disease in cancer patients. Methods: We conducted a retrospective cohort study of laboratory-confirmed COVID-19 patients. Results: Of the 206 patients included, 57 had at least one preexisting malignancy. Cancer patients were older than noncancer patients. Of the 185 discharged cases, cancer patients had a significantly higher frequency of unplanned reintubation (7.1% vs 0.9%, p < 0.049), and required longer hospital stay (8.58 ± 6.50 days versus 12.83 ± 11.44 days, p < 0.002). Regression analysis revealed that obesity and active smoking were associated with an increased risk of mortality. Conclusion: Outcomes in COVID-19 appear to be driven by obesity as well as active smoking, with no difference in mortality between cancer and noncancer patients.

In this study, we aimed to investigate how COVID-19 affected cancer patients and whether this altered their survival outcomes. To do this, we examined data from a database of patients who have passed through our institution ­ a retrospective cohort analysis. Of the 206 patients we included in the study from this database, 57 had at least one preexisting cancer. Cancer patients tended to be older than noncancer patients. Of the 185 discharged patients, cancer patients required longer hospital stays, but there was no difference in mortality. Disease complications and intensive care unit admission with obesity and active smoking put patients in our cohort at increased risk of death. To conclude, outcomes in COVID-19 patients appear to be driven by obesity as well as active smoking, with no difference in mortality between cancer and noncancer patients.

Diabetes care management patterns before and after a cancer diagnosis: A SEER-Medicare matched cohort study.

BACKGROUND: Diabetes places patients with cancer at an increased risk of infections, hospitalizations, and mortality. The objective of the current study was to characterize diabetes care management patterns among patients with cancer in the year before and, separately, after cancer diagnosis. The authors hypothesized that diabetes care declines after a diagnosis of cancer. METHODS: The Surveillance, Epidemiology, and End Results (SEER) cancer registry linked to Medicare claims data was used. The authors included diabetic beneficiaries aged ≥65 years who were diagnosed with incident, nonmetastatic breast, prostate, or colorectal cancer between 2008 and 2013. Controls were diabetic Medicare beneficiaries in SEER regions who did not have cancer. Cases were matched to controls based on age, sex, Charlson Comorbidity Index, and diabetes severity. Primary outcomes were diabetes care received over 12 months: 1) hemoglobin A1c testing; 2) eye examination; and 3) low-density lipoprotein testing. Using a difference-in-difference (DID) approach, the authors examined use differences 12 months before to after diagnosis for patients with cancer and controls. To avoid capturing testing related to diagnosis and not diabetes management, the authors implemented a 90-day washout period (45 days before and/or after diagnosis). RESULTS: A total of 32,728 diabetic patients with cancer and 32,728 matched noncancer controls were included. After diagnosis, patients with cancer were found to have modest, but significantly lower, rates of diabetes care use compared with controls. Patients with cancer had greater declines in hemoglobin A1c testing (DID, 2.4%; 95% CI, 1.7%-3.0%), low-density lipoprotein testing (DID, 4.3%; 95% CI, 3.6%-5.0%), and receipt of all diabetes indicators (DID, 2.7%; 95% CI, 1.8%-3.5%) 12 months before to after diagnosis. CONCLUSIONS: Compared with controls, less diabetes care use was observed among patients with cancer in the year after diagnosis. Understanding and addressing the reasons for this may improve outcomes in this population.

A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer.

CV9201 is an RNActive®-based cancer immunotherapy encoding five non-small cell lung cancer-antigens: New York esophageal squamous cell carcinoma-1, melanoma antigen family C1/C2, survivin, and trophoblast glycoprotein. In a phase I/IIa dose-escalation trial, 46 patients with locally advanced (n = 7) or metastatic (n = 39) NSCLC and at least stable disease after first-line treatment received five intradermal CV9201 injections (400-1600 µg of mRNA). The primary objective of the trial was to assess safety. Secondary objectives included assessment of antibody and ex vivo T cell responses against the five antigens, and changes in immune cell populations. All CV9201 dose levels were well-tolerated and the recommended dose for phase IIa was 1600 µg. Most AEs were mild-to-moderate injection site reactions and flu-like symptoms. Three (7%) patients had grade 3 related AEs. No related grade 4/5 or related serious AEs occurred. In phase IIa, antigen-specific immune responses against ≥ 1 antigen were detected in 63% of evaluable patients after treatment. The frequency of activated IgD+CD38hi B cells increased > twofold in 18/30 (60%) evaluable patients. 9/29 (31%) evaluable patients in phase IIa had stable disease and 20/29 (69%) had progressive disease. Median progression-free and overall survival were 5.0 months (95% CI 1.8-6.3) and 10.8 months (8.1-16.7) from first administration, respectively. Two- and 3-year survival rates were 26.7% and 20.7%, respectively. CV9201 was well-tolerated and immune responses could be detected after treatment supporting further clinical investigation.

Low-molecular-weight-heparin versus a coumarin for the prevention of recurrent venous thromboembolism in high- and low-risk patients with active cancer: a post hoc analysis of the CLOT Study.

In patients with active cancer and acute venous thromboembolism (VTE), the low-molecular-weight-heparin (LMWH) dalteparin is more effective than vitamin K antagonist (VKA) in reducing the risk of recurrent venous thromboembolism (rVTE) without increasing the risk of bleeding. However, the relative benefit of LMWH versus VKA in patients with active cancer at high or low risk of rVTE and bleeding is unclear. This post hoc analysis used data from the CLOT study to explore the efficacy and safety of LMWH versus VKA in preventing recurrent thrombosis in high- and low-risk patients with active cancer. High-risk patients were defined by metastatic disease and/or antineoplastic treatment at baseline; low-risk patients presented with neither. Among high-risk patients, rVTE occurred in 25/318 (8%) (LMWH) versus 53/314 (17%) (VKA) (hazard ratio, 0.44; p = 0.001). No significant difference was detected in the rate of major or any bleeding. The 6-month mortality rate was 40% (LMWH) versus 41% (VKA). In low-risk patients, 2/20 (10%) (LMWH) had rVTE versus 0/24 (0%) (VKA) (hazard ratio, not estimable; p = 0.998). No significant difference was detected in the rate of major or any bleeding. The 6-month mortality rate was 20% (LMWH) versus 29% (VKA). In patients with cancer-associated thrombosis at high risk of rVTE and bleeding, the LMWH dalteparin was more effective than VKA in reducing the risk of rVTE without increasing the risk of bleeding. No difference in rate of rVTE or bleeding was observed between LMWH and VKA among low-risk patients.

COSIMO - patients with active cancer changing to rivaroxaban for the treatment and prevention of recurrent venous thromboembolism: a non-interventional study.

BACKGROUND: Around 20% of venous thromboembolism (VTE) cases occur in patients with cancer. Current guidelines recommend low molecular weight heparin (LMWH) as the preferred anticoagulant for VTE treatment. However, some guidelines state that vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) are acceptable alternatives for long-term therapy in some patients if LMWHs are not available. LMWHs and VKAs have a number of drawbacks that can increase the burden on patients. DOACs, such as rivaroxaban, can ameliorate some burdens and may offer an opportunity to increase patient satisfaction and health-related quality of life (HRQoL). The Cancer-associated thrOmboSIs - patient-reported outcoMes with rivarOxaban (COSIMO) study is designed to provide real-world information on treatment satisfaction in patients with active cancer who switch from LMWH or VKA to rivaroxaban for the treatment of acute VTE or to prevent recurrent VTE. METHODS: COSIMO is a prospective, non-interventional, single-arm cohort study that aims to recruit 500 patients in Europe, Canada and Australia. Adults with active cancer who are switching to rivaroxaban having received LMWH/VKA for the treatment and secondary prevention of recurrent VTE for at least the previous 4 weeks are eligible. Patients will be followed for 6 months. The primary outcome is treatment satisfaction assessed as change in the Anti-Clot Treatment Scale (ACTS) Burdens score at week 4 after enrolment compared with baseline. Secondary outcomes include treatment preferences, measured using a discrete choice experiment, change in ACTS Burdens score at months 3 and 6, and change in HRQoL (assessed using the Functional Assessment of Chronic Illness Therapy - Fatigue questionnaire). COSIMO will collect data on patients' medical history, patterns of anticoagulant use and incidence of bleeding and thromboembolic events. Study recruitment started in autumn 2016. CONCLUSIONS: COSIMO will provide information on outcomes associated with switching from LMWH or VKA therapy to rivaroxaban for the treatment or secondary prevention of cancer-associated thrombosis in a real-life setting. The key goal is to assess whether there is a change in patient-reported treatment satisfaction. In addition, COSIMO will facilitate the evaluation of the safety and effectiveness of rivaroxaban in preventing recurrent VTE in this patient population. TRIAL REGISTRATION: NCT02742623. Registered 19 April 2016.

Through our eyes: A photovoice intervention for adolescents on active cancer treatment.

RESEARCH APPROACH: Photovoice, a participatory action research methodology, is a novel and promising intervention for adolescents with cancer. Photovoice was used as an intervention for eliciting and addressing the psychosocial needs of adolescents on active cancer treatment. PARTICIPANTS: Six adolescents, aged thirteen to seventeen years old, who were on active treatment or had completed treatment in the three months prior to recruitment participated in a seven-week photovoice group that took place from March to May 2017. Methodological Approach: Each of the seven sessions was recorded and later transcribed. A content analysis was used to identify themes that were analyzed using an integrated framework developed earlier. The framework broadly categorized the themes into six domains: (i) physical changes, (ii) psychosocial impacts, (iii) short-term social impacts, (iv) long-term social impacts, (v) impacts on holistic well-being, and (vi) informational needs. INTERPRETATION: Photovoice is an effective intervention for eliciting and addressing the psychosocial needs of adolescents on active cancer treatment.

Association between the controlling nutritional status score and outcomes in ischemic stroke patients with active cancer.

BACKGROUND: The effect of nutritional status on survival in ischemic stroke patients with active cancer remains unclear. METHODS: This study retrospectively evaluated ischemic stroke patients with active cancer admitted to a university hospital in Japan between 2006 and 2016. Patients were followed for 2 years after stroke. The controlling nutritional status (CONUT) score was used to classify undernutrition degree into 4 groups: normal, light, moderate, and severe. Survival rates were compared using the Kaplan-Meier method. Hazard ratio (HR) and 95 % confidence intervals (CIs) for mortality were calculated using Cox regression models. RESULTS: A total of 158 patients (31 % women; median age: 71 years) were analyzed. Of these, 47 % had distant metastasis. The median (interquartile range) National Institute of Health Stroke Scale and CONUT scores were 4 (1-10) and 5 (3-7), respectively. Kaplan-Meier curve indicated that patients with poorer nutritional status had worse outcomes (overall log-rank test, p < 0.001). The univariable Cox regression analysis showed that the HR (95 % CI) for the light, moderate, and severe groups were 1.14 (0.45-2.86), 3.01 (1.27-7.12), and 2.94 (1.10-7.84), respectively. This statistical significance did not persist after adjustment for potential confounders (HR [95 % CI] for the light, moderate, and severe groups were 0.95 [0.36-2.49], 1.56 [0.57-4.28], and 1.34 [0.37-4.92], respectively). Past stroke, distant metastasis, and plasma D-dimer levels on admission were independent predictors of prognosis. CONCLUSIONS: This single-center, retrospective study suggests that nutritional status serves as a prognostic indicator for ischemic stroke patients with active cancer. However, the effect is not statistically independent.

COVID-19 in Patients with Active Cancer: Higher Inflammatory Activity Predicts Poor Outcome.

INTRODUCTION: Active malignancies have been identified as an independent risk factor for severity and mortality in COVID-19. However, direct comparisons between SARS-CoV-2-infected patients with active (acP) and non-active cancers (n-acP) remain scarce. PATIENTS AND METHODS: We retrospectively analyzed a cohort of cancer patients with PCR-confirmed SARS-CoV-2 infection, enrolled from March 16, 2020, to July 31, 2021. Data on demographics, cancer, and laboratory findings were collected. Descriptive and subsequent regression analyses were performed. Endpoints were "deterioration to severe COVID-19" and "infection-associated mortality." RESULTS: In total, 987 cancer patients (510 acP vs. 477 n-acP) were included in our analysis. The majority was >55 years old, more men than women were included. At detection of SARS-CoV-2, 65.5% of patients had mild/moderate symptoms, while deterioration to severe COVID-19 was slightly more common in acP (19 vs. 16%; p = 0.284). COVID-19-associated mortality was significantly higher in acP (24 vs. 17.5%, p < 0.001). In terms of laboratory tests, severe cytopenia and elevated levels of inflammatory markers were common findings in acP at baseline, particularly in those who developed a severe infection or died. Multivariate analysis revealed that ferritin (HR 14.24 [2.1-96], p = 0.006) and CRP (HR 2.85 [1.02-8.02], p = 0.046) were associated with severity and mortality. In n-acP, association was seen for ferritin only (HR 4.1 [1.51-11.17], p = 0.006). CONCLUSION: Comparing patients with active and non-active cancer, the former showed higher mortality rates. Also, inflammatory markers were significantly increased, assuming higher levels of inflammation may play a role in the adverse outcome of COVID-19 in aCP.

Association of Transcranial Doppler Microembolic Signal With Short-Term Mortality in Acute Ischemic Stroke and Active Cancer.

BACKGROUND: This study aimed to clarify the characteristics and survival prediction value of transcranial Doppler microembolic signals (MES) in patients with acute cerebral infarction and active cancer. METHODS AND RESULTS: Between 2017 and 2022, 1089 cases of acute cerebral infarction were recorded within 7 days of disease onset. Among them, transcranial Doppler was successful in 33 patients who had active cancer, and these data were analyzed in this study. The primary outcomes were stroke recurrence and mortality at 3 months. The study population had the following characteristics [median (interquartile range)]: age, 70 years (63-78); body mass index, 21.6 (20-24), National Institutes of Health Stroke Scale 3 (1-6), and modified Rankin Scale score at discharge 1 (1-4). The most common cancer types were lung (24%), pancreatic (24%), and intestinal (18%). MES was present in 16 of 33 patients (48.5%). The presence and number of MES were significantly associated with the levels of D-dimer (P <0.001) and C-reactive protein (P=0.012). Moreover, the presence of MES was associated with multiple ischemic lesions and the 3-territory sign on magnetic resonance imaging. Of the 33 patients, 9 died at 3 months, and 1 had stroke recurrence. On Cox multivariate analysis, using the MES-negative group as a reference, the presence of MES was significantly associated with all-cause death (adjusted hazard ratio, 12.19 [95% CI, 1.45-216.85]; P=0.020). CONCLUSIONS: In patients with acute ischemic stroke and active cancer, the presence of MES was associated with D-dimer and C-reactive protein levels and multiple and 3-territory ischemic lesions, and was predictive of short-term survival.

Von Willebrand Factor Antigen Levels Predict Poor Outcomes in Patients With Stroke and Cancer: Findings From the Multicenter, Prospective, Observational SCAN Study.

BACKGROUND: Patients with acute ischemic stroke and active cancer have more severe neurological symptoms, elevated risks of stroke recurrence, and death compared with the general population. We examined whether von Willebrand factor (vWF) antigen levels at stroke onset were associated with the poor outcomes of patients with stroke and cancer. METHODS AND RESULTS: Using data from 90 patients with acute ischemic stroke and active cancer who were registered in the SCAN (Ischemic Stroke in Patients With Cancer and Neoplasia) study, a prospective multicenter, observational study in Japan, we divided patients into 2 groups according to their median vWF antigen levels (high, n=46; or low, n=44). The high-vWF group had a significantly higher initial National Institutes of Health Stroke Scale score (median, 7 [interquartile range, 3-11.25] versus 3 [interquartile range, 1-8.5]; P<0.05) and a significantly higher incidence of cryptogenic stroke (32 [70%] versus 16 [36%]; P<0.01) and venous thromboembolism (7 [15%] versus 0 [0%]; P<0.01), as well as multiple lesions (28 [62%] versus 12 [27%]; P<0.001), than the low-vWF group. We observed no significant difference in the rate of stroke recurrence within 1 year between the groups. However, increased vWF levels were an independent predictor of death within 1 year of stroke onset, after adjusting for potential confounders (odds ratio, 6.77 [95% CI, 1.49-30.78]; P<0.05). CONCLUSIONS: Elevated vWF antigen levels were associated with adverse outcomes in patients with cancer-associated stroke and may represent a useful biomarker to guide future therapeutic interventions.

A Rare Case of Right Atrial Thrombus in a Patient With Recurrent Classical Hodgkin Lymphoma.

Patients with cancer are at risk for thrombotic complications due to a hypercoagulable state. However, the benefit of prophylactic anticoagulation is unclear in many subsets of these patients. For the first episode of acute thromboembolic disease (VTE) in patients with active cancer, anticoagulant therapy is administered for at least three to six months. Herein, we present a 31-year-old female with active, recurrent stage IIIa classical Hodgkin lymphoma (CHL) (nodular sclerosis), previously treated for proximal upper extremity deep vein thrombosis (DVT), presenting for evaluation of shortness of breath and eventually diagnosed with bilateral pulmonary embolism (PE) secondary to a right atrial thrombus. The patient was successfully treated with surgical resection of the thrombus. With this case report, we hope to encourage physicians to use prophylactic indefinite anticoagulation in patients with active cancer and previous DVT, including patients with upper extremity DVT.

The Validity of a New Procedure-Based Definition of Cancer Status in Patients with Breast-, Lung- and Colorectal Cancer in the Danish National Patient Registry.

Background/Aim: The Danish National Patient Registry (DNPR) provides unique epidemiological insight, but often lacks granular data. We propose a procedure-based definition of cancer status in patients with breast-, lung- and colorectal cancer, which can be applied to administrative health databases. New definitions of cancer status are needed as mortality and morbidity are closely linked to cancer status, yet most studies only use duration since cancer diagnosis as a severity marker. The aim of the study was to validate a new pragmatic definition. Methods: Medical journals of 600 patients, with breast-, lung- and colorectal cancer from the Department of Oncology at Herlev-Gentofte Hospital were retrospectively reviewed. We defined active cancer as a cancer diagnosis, not followed by a potentially curative procedure within 6 months of the diagnosis. The remaining patients were characterized as having non-active cancer. This dichotomization was then compared to a cancer status assessment based on treatment received and paraclinical test such as their first post-procedural control scan. Based on this comparison, we calculated the positive predictive value (PPV) of our definitions of active and non-active cancer. Results: The calculated PPVs for active breast-, lung- and colorectal cancer were 87% (CI 95%: 0.74-0.99), 91% (CI 95%: 0.87-0.96) and 82% (CI 95%: 0.73-0.91). The PPVs for non-active breast-, lung- and colorectal cancer were 95% (CI 95%: 0.92-0.99), 91% (CI 95%: 0.82-0.99) and 73% (CI 95%: 0.66-0.81), respectively. Conclusion: We found an overall high PPV for both active and non-active cancer across all three types of cancer.

Transcatheter Aortic Valve Replacement in Patients With or Without Active Cancer.

Background Data on clinical outcomes after transcatheter aortic valve replacement (TAVR) in specific cancer types or the presence of metastatic disease remain sparse. This study aimed to investigate the impact of active cancer on short-term mortality, complications, and readmission rates after TAVR across different cancer types. Methods and Results The authors assessed the Nationwide Readmissions Database for TAVR cases from 2012 to 2019. Patients were stratified by specific cancer types. Primary outcome was in-hospital mortality. Secondary outcomes included bleeding requiring blood transfusion and readmissions at 30, 90, and 180 days after TAVR. Overall, 122 573 patients undergoing TAVR were included in the analysis, of whom 8013 (6.5%) had active cancer. After adjusting for potential confounders, the presence of active cancer was not associated with increased in-hospital mortality (adjusted odds ratio [aOR], 1.06 [95% CI, 0.89-1.27]; P=0.523). However, active cancer was associated with an increased risk of readmission at 30, 90, and 180 days after TAVR and increased risk of bleeding requiring transfusion at 30 days. Active colon and any type of metastatic cancer were individually associated with readmissions at 30, 90, and 180 days after TAVR. At 30 days after TAVR, colon (aOR, 2.51 [95% CI, 1.68-3.76]; P<0.001), prostate (aOR, 1.40 [95% CI, 1.05-1.86]; P=0.021), and any type of metastatic cancer (aOR, 1.65 [95% CI, 1.23-2.22]; P=0.001) were individually associated with an increased risk of bleeding requiring transfusion. Conclusions Patients with active cancer had similar in-hospital mortality after TAVR but higher risk of readmission and bleeding requiring transfusion, the latter depending on certain types of cancer.

Heterogeneous distributions in clinical events preceding anticoagulant treatment nonpersistence in patients with venous thromboembolism stratified by active cancer: A nationwide cohort study.

BACKGROUND: Nonpersistence in anticoagulation therapy is common and associated with undesirable clinical outcomes in patients with venous thromboembolism (VTE). METHODS: We investigated preceding clinical events of treatment nonpersistence (e.g., switching, discontinuing, or restarting) in VTE patients with and without active cancer using Korean claims database. RESULTS: Clinically significant events including thromboembolic events, hepatic function change and surgery preceded treatment nonpersistence, but heterogeneous distributions of clinical events were observed in the presence of active cancer. Patients with active cancer had a low rate of clinical events preceding treatment nonpersistence, and new active cancer diagnosis in the nonactive cancer group was most common before the switch to parenteral anticoagulants from warfarin or non-vitamin K antagonist oral anticoagulants (NOACs). CONCLUSION: These findings suggest that clinically significant events can precede treatment nonpersistence and largely paralleled current guidelines for patients with VTE, whereas heterogeneous distributions of clinical events were observed in the presence of active cancer.

Aptamer-Based Strategies to Boost Immunotherapy in TNBC.

The immune system (IS) may play a crucial role in preventing tumor development and progression, leading, over the last years, to the development of effective cancer immunotherapies. Nevertheless, immune evasion, the capability of tumors to circumvent destructive host immunity, remains one of the main obstacles to overcome for maximizing treatment success. In this context, promising strategies aimed at reshaping the tumor immune microenvironment and promoting antitumor immunity are rapidly emerging. Triple-negative breast cancer (TNBC), an aggressive breast cancer subtype with poor outcomes, is highly immunogenic, suggesting immunotherapy is a viable strategy. As evidence of this, already, two immunotherapies have recently become the standard of care for patients with PD-L1 expressing tumors, which, however, represent a low percentage of patients, making more active immunotherapeutic approaches necessary. Aptamers are short, highly structured, single-stranded oligonucleotides that bind to their protein targets at high affinity and specificity. They are used for therapeutic purposes in the same way as monoclonal antibodies; thus, various aptamer-based strategies are being actively explored to stimulate the IS's response against cancer cells. The aim of this review is to discuss the potential of the recently reported aptamer-based approaches to boost the IS to fight TNBC.

Predictors of Survival in Patients With Ischemic Stroke and Active Cancer: A Prospective, Multicenter, Observational Study.

Background Limited data exist on the prognostic factors for patients with ischemic stroke and active cancer. Methods and Results We conducted a prospective, multicenter, observational study in Japan, including patients with acute ischemic stroke and active cancer, to investigate the prognostic factors. We followed up the patients for 1 year after stroke onset. The patients were divided into 2 groups according to cryptogenic stroke and known causes (small-vessel occlusion, large-artery atherosclerosis, cardioembolism, and other determined cause), and survival was compared. The hazard ratios (HRs) and 95% CIs for mortality were calculated using Cox regression models. We identified 135 eligible patients (39% women; median age, 75 years). Of these patients, 51% had distant metastasis. A total of 65 (48%) and 70 (52%) patients had cryptogenic stroke and known causes, respectively. Patients with cryptogenic stroke had significantly shorter survival than those with known causes (HR [95% CI], 3.11 [1.82-5.32]). The multivariable Cox regression analysis revealed that distant metastasis, plasma D-dimer levels, venous thromboembolism (either deep venous thrombosis or pulmonary embolism) complications at stroke onset were independent predictors of mortality after adjusting for potential confounders. Cryptogenic stroke was associated with prognosis in univariable analysis but was not significant in multivariable analysis. The plasma D-dimer levels stratified the prognosis of patients with ischemic stroke and active cancer. Conclusions The prognosis of patients with acute ischemic stroke and active cancer varied considerably depending on stroke mechanism, distant metastasis, and coagulation abnormalities. The present study confirmed that coagulation abnormalities were crucial in determining the prognosis of such patients.

Active cancer as the main predictor of mortality for COVID-19 in oncology patients in a specialized center.

Introduction: The role of the type, stage and status of cancer in the outcome of COVID-19 remains unclear. Moreover, the characteristic pathological changes of severe COVID-19 reveled by laboratory and radiological findings are similar to those due to the development of cancer itself and antineoplastic therapies. Objective: To identify potential predictors of mortality of COVID-19 in cancer patients. Materials and methods: A retrospective and cross-sectional study was carried out in patients with clinical suspicion of COVID-19 who were confirmed for COVID-19 diagnosis by RT-PCR testing at the National Institute of Neoplastic Diseases between April and December 2020. Demographic, clinical, laboratory and radiological data were analyzed. Statistical analyses included area under the curve and univariate and multivariate logistic regression analyses. Results: A total of 226 patients had clinical suspicion of COVID-19, the diagnosis was confirmed in 177 (78.3%), and 70/177 (39.5%) died. Age, active cancer, leukocyte count ≥12.8 × 109/L, urea ≥7.4 mmol/L, ferritin ≥1,640, lactate ≥2.0 mmol/L, and lung involvement ≥35% were found to be independent predictors of COVID-19 mortality. Conclusion: Active cancer represents the main prognosis factor of death, while the role of cancer stage and type is unclear. Chest CT is a useful tool in the prognosis of death from COVID-19 in cancer patients. It is a challenge to establish the prognostic utility of laboratory markers as their altered values it could have either oncological or pandemic origins.

Effectiveness and safety of rivaroxaban in patients with venous thromboembolism and active cancer: A subanalysis of the J'xactly study.

BACKGROUND: Data on the effectiveness and safety of rivaroxaban for the treatment of patients with venous thromboembolism (VTE) and active cancer are limited in the Japanese real-world setting. METHODS: In this subanalysis of the J'xactly study, which was a multicenter, prospective, observational study, we evaluated the effectiveness and safety of rivaroxaban in patients with acute VTE and active cancer (n = 193) versus those without active cancer (n = 823). RESULTS: Compared with patients without active cancer, those with active cancer demonstrated a significantly different age distribution, with fewer aged <65 and ≥75 years; a lower proportion of women; a lower mean body mass index; and a lower proportion of physical inactivity, injury, thrombophilia, and heart failure. There was no difference in the initial dose distribution of rivaroxaban between patients with and without active cancer. The incidences of recurrence or aggravation of symptomatic VTE and major bleeding were not significantly different [VTE: 1.44 % vs. 2.80 % per patient-year, hazard ratio (HR) 0.50, 95 % confidence interval (CI) 0.18-1.39, p = 0.172; major bleeding: 4.49 % vs. 2.55 % per patient-year, HR 1.80, 95 % CI 0.82-3.95, p = 0.137]. Approximately 10 % of patients with active cancer died at 6 months, with a significantly higher cumulative all-cause mortality rate than those without active cancer (23.29 % vs. 2.03 % per patient-year, HR 11.31, 95 % CI 7.30-17.53, p < 0.001). CONCLUSIONS: In patients with VTE and active cancer, rivaroxaban showed acceptable effectiveness, although clinically significant bleeding remains a concern. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry number, UMIN000025072.