Clinical Outcomes In Cancer Patients Research Articles

PB0945 Effect of Drug Interactions with Apixaban on Clinical Outcomes in Cancer Patients with Venous Thromboembolism

PB0945 Effect of Drug Interactions with Apixaban on Clinical Outcomes in Cancer Patients with Venous Thromboembolism

Effects of Nanosecond Pulsed Electric Field on Immune Checkpoint Receptors in Melanoma Cells.

Checkpoint molecules such as PD-1, LAG-3, and TIM-3 are currently under extensive investigation for their roles in the attenuation of the immune response in cancer. Various methods have been applied to overcome the challenges in this field. This study investigated the effects of nanosecond pulsed electric field (nsPEF) treatment on the expression of immune checkpoint molecules in A375 and C32 melanoma cells. The researchers found that the nsPEF treatment was able to enhance membrane permeabilization and morphological changes in the cell membrane without being cytotoxic. We found that the effects of nsPEFs on melanoma included (1) the transport of vesicles from the inside to the outside of the cells, (2) cell contraction, and (3) the migration of lipids from inside the cells to their peripheries. The treatment increased the expression of PD-1 checkpoint receptors. Furthermore, we also observed potential co-localization or clustering of MHC class II and PD-1 molecules on the cell surface and the secretion of cytokines such as TNF-α and IL-6. These findings suggest that nsPEF treatment could be a viable approach to enhance the delivery of therapeutic agents to cancer cells and to modulate the tumor microenvironment to promote an antitumor immune response. Further studies are needed to explore the mechanisms underlying these effects and their impacts on the antitumor immune response, and to investigate the potential of nsPEF treatment in combination with immune checkpoint inhibitors to improve clinical outcomes for cancer patients.

Dual-targeted transferrin and AS1411 aptamer conjugated micelles for improved therapeutic efficacy and imaging of brain cancer

Brain tumors represent an aggressive form of cancer, posing significant challenges in achieving complete remission. Development of advanced therapies is crucial for improving clinical outcomes in cancer patients. This study aimed to create a novel treatment approach using dual-targeted transferrin (TF) and AS1411 conjugated micelles, designed to enhance therapeutic effectiveness of docetaxel (DTX) and facilitate gadolinium (Gd) based imaging in brain cancer. Micelles were prepared using a slightly modified solvent-casting method, and the dual-targeting ligands were attached to the micelle’s surface through a physical adsorption process. Average particle size of micelles ranged from 117.49 ± 3.90–170.38 ± 3.39 nm, with a low polydispersity index. Zeta potential ranged from − 1.5 ± 0.02 to − 18.7 ± 0.04 mV. Encapsulation efficiency of DTX in micelles varied from 92.64 ± 4.22–79.77 ± 4.13 %. Simultaneously, encapsulation of Gd in micelles was found to be 48.27 ± 3.18–58.52 ± 3.17, respectively. In-vitro drug release studies showed a biphasic sustained release profile, with DTX and Gd release continuing up to 72 h with their t50 % at 4.95, 11.29, and 24.14 h for GDTP, GDTP-TF and GDTP-TF-AS1411 micelles, respectively. Cytotoxicity effect of GDTP-TF-AS1411 micelles has shown significant improvement (P < 0.001) and reduced IC50 value up to 0.19 ± 0.14 μg/ml compared to Taxotere® (2.73 ± 0.73 μg/ml). Theranostic study revealed higher accumulation of GDTP-TF and GDTP-TF-AS1411 micelles free GD treated animal brains. The AUC of GDTP-TF-AS1411 micelles exhibited 23.79 ± 17.82 μg.h/ml higher than Taxotere® (14.14 ± 10.59 μg.h/ml). These findings direct enhanced effectiveness in brain cancer therapy leading to improved therapeutics in brain cancer patients. The combined targeted ligands and therapeutic agents strategy can direct advancement in brain cancer therapy and offer improved therapy for patients.

Assessment of plasma D-dimer level for prognosis, disease progression, and survival in solid malignancies

ABSTRACT Background: D-dimer is a fibrin degradation product (FDP), a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. Aim: To evaluate the association of D-dimer level with prognosis, disease progression and survival of patients in cases of solid malignancies. Setting and Design: Analytical cross sectional study conducted from February 2021 to February 2023. Materials and Methods: Data regarding 100 solid malignancy cases including their preintervention D-dimer levels and its value at follow up, grading, TNM [Tumor size (T), node (N), and metastases (M)] staging of tumor, disease progression and patient status were recorded. Statistical Analysis: Kaplan–Meier curve and Log Rank. Results: Amplified D-dimer level was noted in 85% cancer cases. 76.3% of oral cancer, 82% of breast cancer, 100% cases of digestive tract and ovarian cancer were presented with high D-dimer level. D-dimer in T1 + T2 stage was statistically lower than the D-dimer level of T3 + T4 stage. (χ 2 = 5.40, P = 0.002). Comparison of Lymph node in N0 versus N1 + N2 stage (χ 2 = 5.82, P = 0.0001) as well as no metastases stage (Mo) versus M1 stages (χ 2 = 3.02, P = 0.003) of solid malignancies had significant difference in D-dimer level. D-dimer increased significantly and linearly with recurrence and advancement of solid malignancy. Dead patient had higher D-dimer than alive patients (t = 3.75, P = 0.0001). Increased D-dimer was associated with elevated mortality (P = 0.023, odd ratio = 3.73, survival coefficient = 1.31 with standard error = 0.578). Conclusion: D-dimer is a promising prognostic biomarker which can predict poor clinical outcomes in cancer patients, cancer recurrence, progression, metastases, poor survival.

Tertiary lymphoid structures and B lymphocytes: a promising therapeutic strategy to fight cancer.

Tertiary lymphoid structures (TLSs) are clusters of lymphoid cells with an organization that resembles that of secondary lymphoid organs. Both structures share common developmental characteristics, although TLSs usually appear in chronically inflamed non-lymphoid tissues, such as tumors. TLSs contain diverse types of immune cells, with varying degrees of spatial organization that represent different stages of maturation. These structures support both humoral and cellular immune responses, thus the correlation between the existence of TLS and clinical outcomes in cancer patients has been extensively studied. The finding that TLSs are associated with better prognosis in some types of cancer has led to the design of therapeutic strategies based on promoting the formation of these structures. Agents such as chemokines, cytokines, antibodies and cancer vaccines have been used in combination with traditional antitumor treatments to enhance TLS generation, with good results. The induction of TLS formation therefore represents a novel and promising avenue for the treatment of a number of tumor types.

Crosstalk of Mast Cells and Natural Killer Cells with Neurons in Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major comorbidity of cancer. Multiple clinical interventions have been studied to effectively treat CIPN, but the results have been disappointing, with no or little efficacy. Hence, understanding the pathophysiology of CIPN is critical to improving the quality of life and clinical outcomes of cancer patients. Although various mechanisms of CIPN have been described in neuropathic anti-cancer agents, the neuroinflammatory process involving cytotoxic/proinflammatory immune cells remains underexamined. While mast cells (MCs) and natural killer (NK) cells are the key innate immune compartments implicated in the pathogenesis of peripheral neuropathy, their role in CIPN has remained under-appreciated. Moreover, the biology of proinflammatory cytokines associated with MCs and NK cells in CIPN is particularly under-evaluated. In this review, we will focus on the interactions between MCs, NK cells, and neuronal structure and their communications via proinflammatory cytokines, including TNFα, IL-1β, and IL-6, in peripheral neuropathy in association with tumor immunology. This review will help lay the foundation to investigate MCs, NK cells, and cytokines to advance future therapeutic strategies for CIPN.

Molecular Mechanisms of Cutaneous Immune-Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitors.

Over the past few decades, immune checkpoint inhibitors (ICIs) have emerged as promising therapeutic options for the treatment of various cancers. These novel treatments effectively target key mediators of immune checkpoint pathways. Currently, ICIs primarily consist of monoclonal antibodies that specifically block cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and lymphocyte activation gene 3 protein (LAG-3). Despite the notable efficacy of ICIs in cancer treatment, they can also trigger immune-related adverse events (irAEs), which present as autoimmune-like or inflammatory conditions. IrAEs have the potential to affect multiple organ systems, with cutaneous toxicities being the most commonly observed. Although cutaneous irAEs are typically of low-grade severity and can usually be managed effectively, there are cases where severe irAEs can become life-threatening. Therefore, early recognition and a comprehensive understanding of the mechanisms underlying cutaneous irAEs are crucial for improving clinical outcomes in cancer patients. However, the precise pathogenesis of cutaneous irAEs remains unclear. This review focuses on the skin manifestations induced by ICIs, the prognosis related to cutaneous irAEs, and the exploration of potential mechanisms involved in cutaneous irAEs.

Impact of type of anticoagulant on clinical outcomes in cancer patients who had atrial fibrillation

To date, evidence on optimal anticoagulant options in patients with AF who concurrently have active cancer remains elusive. To describe anticoagulant patterns and clinical outcomes among patients with a concomitant diagnosis of AF and cancer. Data were obtained from the University of Utah and Huntsman Cancer Institute (HCI) Hospitals. Patients were included if they had diagnosis of AF and cancer. Outcome was type and pattern of anticoagulant. Clinical outcomes were stroke, bleeding and all-cause mortality. From October 1999 to December 2020, there were 566 AF patients who concurrently had active cancer. Mean age ± standard deviation was 76.2 ± 10.7 and 57.6% were males. Comparing to warfarin, patients who received direct oral anticoagulant (DOACs) were associated with similar risk of stroke (adjusted hazard ratio, aHR 0.8, 95% confidence interval [CI] 0.2–2.7, P = 0.67). On contrary, those who received low-molecular-weight heparin (LMWH) were associated with significantly higher risk of stroke comparing to warfarin (aHR 2.4, 95% CI 1.0–5.6, P = 0.04). Comparing to warfarin, DOACs and LMWH was associated with similar risk of overall bleeding with aHR 1.1 (95% CI 0.7–1.6, P = 0.73) and aHR 1.1 (95% CI 0.6–1.7, P = 0.83), respectively. Patients who received LMWH but not DOACs were associated with increased risk of death as compared to warfarin, aHR 4.5 (95% CI 2.8–7.2, P < 0.001) and 1.2 (95% CI 0.7–2.2, P = 0.47). In patients with active cancer and AF, LMWH, compared to warfarin, was associated with an increased risk of stroke and all-cause mortality. Furthermore, DOACs was associated with similar risk of stroke, bleeding and death as compared to warfarin.

Adenosine receptor A2b confers ovarian cancer survival and PARP inhibitor resistance through IL-6-STAT3 signalling.

Ovarian cancer is the deadliest gynecologic cancer worldwide, and the therapeutic options are limited. PARP inhibitor (PARPi) represents an effective therapeutic strategy and has been approved for maintenance therapy. However, the intrinsic or acquired resistance to PARPi becomes a big challenge. To investigate the mechanisms for PARPi resistance, we analysed public databases and established Olaparib-resistant ovarian cancer cells for exploration. Our results showed that the inflammatory pathway and adenosine receptor A2b (Adora2b/A2B ) expression were significantly increased in Olaparib-resistant cells. A2B was highly expressed in recurrent ovarian tumours and negatively correlated with the clinical outcomes in cancer patients. Olaparib treatment enhanced A2B expression through NF-κB activation. The elevated A2B contributed to Olaparib resistance by sensing adenosine signal and promoting tumour cell survival, growth and migration via IL-6-STAT3 signalling. Therefore, inhibition of A2B -IL-6-STAT3 axis could overcome Olaparib resistance and synergize with Olaparib to reduce cancer cell growth and lead to cell death. Our findings reveal a critical role of A2B signalling in mediating PARPi resistance independent of DNA damage repair, providing insights into developing novel therapies in ovarian cancers.

Clinical outcomes of patients with cancer before the SARS COV2 pandemic vs during the pandemic: A nationwide analysis.

e18569 Background: The novel SARS COV2 pandemic has disrupted cancer treatment, both preventive as well as treatment services. We aimed to study the clinical outcomes of cancer patients who were hospitalised before and during the pandemic. Methods: Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS) 2016-2020 was queried to identify adult patients (Age &gt; 18 years) with a diagnosis of cancer using the ICD-10 (International Classification of Diseases) codes. Study population was stratified based on the year of admission- 2016 to 2019 vs 2020 (the pandemic year). Primary outcomes included mortality, length of stay (LOS), and total hospitalization charges (THC). Secondary outcomes included prevalence of pulmonary embolism (PE), ICU admission, acute respiratory failure (ARF), blood transfusion, and sepsis. Statistics were performed using multivariate linear and logistic regression using STATA v17. Results: There were 18 million admissions in adults with cancer from 2016-2020. Among them 14.6 million (81.1%) were hospitalised during 2016-2019 (pre pandemic) whereas 3.4 million (18.9%) were hospitalized in 2020 (pandemic). There was no significant difference in the mean age of both groups, pandemic group had higher charlson comorbidity burden (66.4 vs 63.7%, p &lt; 0.01). Pandemic group had higher rates of DM (26 vs 24%), CHF (15 vs 13.8%), CKD (18 vs 16.5%), dyslipidemia (36.4 vs 33%), PEM (15 vs 13%), anemia (44 vs 42) all p &lt; 0.01. A total of 835,065 cancer patients died during the study period, the mortality rate in the pre-pandemic and pandemic years was 4.5% and 5% respectively (p &lt; 0.05). After adjusting for confounders, the all-cause mortality was increased in the pandemic group (aOR 1.10, 95% CI 1.05-1.12, p &lt; 0.01). The adjusted LOS was decreased by 0.1 days (95% CI: 0.06- 0.20, p &lt; 0.01)). The adjusted total hospitalization charges was increased by $12,891 (95% CI: 9745-16,035, p &lt; 0.01). Pandemic group had higher odds of sepsis (7.8 vs 6.5%), mechanical ventilation (4 vs 3%), pressor requirements (1.5 vs 1%), acute kidney injury (10 vs 7%) and acute respiratory failure (10 vs 7%), all p &lt; 0.01. Conclusions: During the COVID-19 pandemic, cancer patients with a high prevalence of medical comorbidities were more likely to be admitted to the hospital with COVID infection. The higher mortality in these patients was likely the result of higher secondary complications, also likely leading to earlier death explaining the lower LOS and higher hospitalization charges. Cancer patients with medical comorbidities should take higher preventive measures from COVID including encouraging continued primary vaccinations and regular boosters.

Cost savings and clinical outcomes in cancer patients enrolled in clinical trials from a national public health system perspective.

e18813 Background: Clinical research has led to great advances that have an impact on improving the survival and quality of life of cancer patients and should be part of the standard of care. However, there is no clear evidence on whether participation in clinical trials (CTs) is cost-efficient for the national health system. For this reason, in the present study I have tried to analyse the direct impact of participation in CTs in terms of improvement in clinical results and costs. Particularly, I have looked into CT subjects diagnosed with metastatic renal cell carcinoma (mRCC) or G1-G2 metastatic neuroendocrine tumors (mNET). In addition, the potential influence of different prognostic and demographic factors on these variables has also been evaluated. Methods: Retrospectively, clinical data of the patients related to their baseline characteristics and the efficacy of the different lines of treatment they had received for their tumor were collected, as well as the direct healthcare costs derived from the clinical approach of all patients diagnosed with mRCC or mNET and clinically followed by the Ramón y Cajal University Hospital Medical Oncology Service, in Madrid, Spain, between January 2010 and February 2017. Subsequently, a comparative statistical analysis was performed of the results obtained in patients included in a clinical trial versus those who never participated in one but instead received therapy according to the standard of care (SOC). Results: Of the 104 patients (65 mRCC and 39 mNET) who were eventually included, 39 participated in a clinical trial. Overall, the 39 CT patients presented a higher overall survival (OS) than SOC patients (52 vs. 15 months. HR: 0.41; 95% CI: [0.23; 0.71]; p &lt; 0.01), a finding that carried through in all subgroups, including age, sex and prognostic factors. Regarding healthcare costs, patients who participated in CT yielded a mean annual savings of €46,109.56 per patient (p &lt; 0.01) compared to patients treated according to SOC, mainly due to pharmacological savings (€27,406.42). Furthermore, the savings were generalized in all subgroups regardless of age, sex and prognostic factors. Additionally, CT patients required 75.81% fewer hospitalisations (p &lt; 0.01) with a lower associated mean cost (p = 0.02), and the mean annual cost corresponding to the use of the Emergency Service was lower (p &lt; 0.01). Finally, the unadjusted incremental cost-effectiveness ratio (ICER) was -€14,970.64 per year of life gained (YLG) and the adjusted ICER was -€42,656.11 per life saved. Conclusions: From the national health system perspective, the participation of patients in CTs is related to an improvement in OS and savings in clinical costs in patients diagnosed with mRCC and mNET. In short, the participation of cancer patients in CTs represents a cost-efficient therapeutic option.

Association between severe adverse event management and overall survival in patients treated with immune checkpoint inhibitor with advanced non–small-cell lung cancer.

6604 Background: The impact of severe adverse event (sAE) management (mgmt) on clinical outcomes in cancer patients (pts) receiving immune checkpoint inhibitor (ICI) therapy has not been fully examined. We aimed to evaluate the association between mgmt of sAEs and overall survival (OS) in pts receiving ICIs for advanced non-small cell lung cancer (aNSCLC). Methods: Data were drawn from the ConcertAI Patient360 dataset, a curated EMR-based US oncology database representing 19,000+ NSCLC patients. aNSCLC pts who initiated ICI in the first 3 lines of anti-cancer therapy from 1/1/15 - 8/31/21 with no record of clinical trial enrollment or diagnosis of a second primary cancer were included. sAEs (dermatologic, gastrointestinal, endocrine, hepatic, respiratory, rheumatic, renal, and cardiac) and mgmt actions were curated from unstructured data from ICI initiation through the earliest of: 100 days after ICI discontinuation, start of a non-ICI regimen, end of study period, or death. Cox regression was used to evaluate the association between sAE mgmt actions (as time-varying covariate) and OS adjusting for baseline characteristics including line of therapy. The earliest sAE and mgmt action per patient were examined in OS analysis. Results: 3,211 pts were identified (median [IQR] age 67 [13] years, 55.1% male). Median [Q1-Q3] duration of follow-up from ICI initiation was 8.2 [3.3-17.5] months. Most pts had advanced disease at initial diagnosis (82.0%) and started ICI in first line (61.6%). The most common ICI regimens in the first 3 lines were nivolumab (29.5%) and pembrolizumab + carboplatin + pemetrexed (29.1%). 8.6% of pts had at least one sAE, most often diarrhea (3.5%). Median [Q1-Q3] time from ICI initiation to first sAE was 84 [34-211] days. Mgmt actions any time after first sAE included anti-cancer treatment interruptions [dose reduction (4.0%), hold (20.6%), discontinuation (2.2%)], sAE treatment [corticosteroids (71.8%), immunosuppressive drugs (2.5%)], hospital admission [hospitalization (57.4%), emergency department visit (24.6%)], and other/unknown (4.3%). Overall, median [95% CI] OS was 13.6 [12.6-14.6] months. Compared with pts with no sAEs, pts with sAEs whose earliest mgmt action was hospital admission (N=155) or sAE treatment (N=71) had a higher risk of all-cause mortality (adjusted HR [95% CI] 1.61 [1.38-1.88] and 1.53 [1.22-1.91], respectively). Pts with sAEs first managed with anti-cancer treatment interruptions (N=39) had similar risk of all-cause mortality (0.91 [0.66-1.25]) compared with pts with no sAEs. Conclusions: Pts with sAEs first managed with hospital admission or sAE treatment had shorter OS than those with no sAEs. No difference was observed for sAEs first managed with anti-cancer treatment interruptions. Findings suggest early treatment interruption for sAEs does not impact OS.

Abstract 68: Preparing for the Next Pandemic: An Asian National Cancer Centers Alliance (ANCCA) Initiative

Abstract Purpose: The COVID-pandemic has shown significant impact on cancer care from early detection, management plan to clinical outcomes of cancer patients. The devastating effects of COVID-19 seen worldwide have underscored the need for better preparation of the next pandemic. Methods: Based on the experiences and lessons learnt from the COVID-19 pandemic, the Asian National Cancer Centers Alliance (ANCCA) has put together the 9 “Ps” as guidelines for cancer programs to better prepare for the next pandemic. Results: The 9 “Ps” are Priority, Protocols and Processes, Patients, People, Personal Protective Equipments (PPEs), Pharmaceuticals, Places, Preparedness, and Politics. Priority: to maintain cancer care as a key priority in the health system response even during a global infectious disease pandemic. Protocols and processes: to develop a set of Standard Operating Procedures (SOPs) and have relevant expertise to man the Disease Outbreak Response (DORS) Taskforce before an outbreak. Patients: to prioritize patient safety in the event of an outbreak and the need to reschedule cancer management plan, supported by tele-consultation and use of artificial intelligence technology. People: to have business continuity planning to support surge capacity. PPEs and Pharmaceuticals: to develop plan for stockpiles management, build local manufacturing capacity and disseminate information on proper use and reduce wastage. Places: to design and build cancer care facilities to cater for the need of triaging, infection control, isolation and segregation. Preparedness: to invest early on manpower building and technology innovations through multisectoral and international collaborations. Politics: to ensure leadership which bring trust, cohesion and solidarity for successful response to pandemic and mitigate negative impact on the healthcare system. Conclusion: It is important to evaluate the lessons learnt, leverage on the silver linings arising from the crisis and re-examine our strategies, processes, and guidelines on cancer control from research and evidence related to the impact of COVID-19 on cancer prevention and control as well as the escalation in healthcare cost from delayed diagnosis of cancer and late stage cancer treatments are also urgently needed. This “9 Ps” guide put together by ANCCA aims to serve as a summary guide or reminders for cancer centres or programme to better prepare for the next pandemic. Citation Format: Sok King Ong, Laureline Gatellier, Tomohiro Matsuda. Preparing for the Next Pandemic: An Asian National Cancer Centers Alliance (ANCCA) Initiative [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 68.

Liquid biopsy-informed precision oncology study to evaluate utility of plasma genomic profiling for therapy selection.

TPS1616 Background: Liquid biopsies have enabled a transformation in the management of patients with cancer as they have the potential to detect, characterize, and monitor tumor burden. However, the increasing complexity involved in the integration of genomic data into clinical practice has presented challenges with the practical implementation of liquid biopsies in clinical cancer care. To address these challenges, multidisciplinary teams comprised of experts within oncology, genetics, pathology, and informatics have created Molecular Tumor Boards (MTBs), which can improve clinical outcomes for cancer patients by efficiently utilizing the technologies created by the rapidly expanding precision oncology industry. Nevertheless, there remains a gap in the optimal implementation and interpretation of these diagnostic findings to maximize patient outcomes and access to standard of care therapies and clinical trials. Methods: We instigated a prospective observational liquid biopsy-informed precision oncology study, in which patients with metastatic solid tumors will be matched with genotype-driven therapies via serial liquid biopsies (NCT05585684). Liquid biopsy-derived genotypes will be generated through a clinical NGS assay (PGDX Plasma Focus) and will be annotated by an automated ensemble approach for variant actionability assessment, developed by the Johns Hopkins MTB, followed by a treatment recommendation. Key eligibility criteria include patients ≥18 years old, with ECOG performance status of 0-1 and with metastatic disease that have relapsed or progressed after standard of care first-line therapies or patients for which first-line standard of care therapeutic options are not expected to yield a clinical response. The primary objectives of the trial focus on feasibility of the approach and evaluating the fraction of patients with actionable mutations, for which the MTB recommendation is enacted upon. Unique to this study, a recommendation to not pursue genotype-targeted therapy is equally considered for personalized clinical decision making. Secondary objectives are to investigate whether enacting upon MTB recommendations improves progression-free and overall survival and perform a comparative analysis with tumor-based NGS. Exploratory objectives are to determine if serial molecular profiling after initiation of systemic treatment is sufficient to determine therapeutic response, compare with RECIST radiographic response and determine whether changes in liquid biopsy dynamics correlate with progression-free and overall survival. This study will enroll 150 patients with solid tumors, including lung, esophageal, breast, and head and neck cancer and mesothelioma to evaluate the clinical utility of liquid biopsy genomic profiling. Patient accrual for this study initiated in February 2023. Clinical trial information: NCT05585684 .

Racial disparities and clinical outcomes among cancer patients admitted with SARS-CoV-2 infection: A nationwide analysis.

e18568 Background: The novel SARS COV2 pandemic highlighted existing racial disparities in US healthcare. The impact was further amplified in the cancer community. We studied the racial disparities in the clinical outcomes of cancer patients who were hospitalised with COVID-19 infection. Methods: Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS) 2020 was queried to identify adult patients (Age &gt; 18 years) admitted for COVID with underlying cancer using the ICD-10 codes. Study population was stratified based on race (White vs African Americans vs Hispanics). Primary outcomes included mortality, length of stay (LOS), and total hospitalization charges (THC). Secondary outcomes included prevalence of pulmonary embolism (PE), ICU admission, acute respiratory failure (ARF), blood transfusion, and sepsis. Statistics were performed using multivariate linear and logistic regression using STATA v17. Results: There were 53,465 adult admissions for COVID in cancer patients. Among them 30,605 (58.8%) were White (WH), 9580 (18.4%) were African Americans (AA), 8225 (15.8%) were Hispanics (HISP). HISP and AA were significantly younger compared to WH (61.7 vs 65.8 vs 72.4, p &lt; 0.001). HISP had lowest Charlson comorbidity index (CCI) compared to whites (50.4% vs 67.7%, p &lt; 0.001). AA had highest rates of all medical comorbidities except dyslipidemia and COPD which was higher in WH. Of the 8135 (15.2%) patients that died during the admission, 60% (N = 4880) were WH, 17.1% (N = 1390) were AA whereas 13.5% (N = 1100) were HISP. Compared to WH, HISP had a higher odds of mortality (aOR 1.24, 95% CI 1.03-1.48; p = 0.022), there was no difference in the odds of mortality between WH and AA. The LOS was increased for AA and HISP compared to WH (9.1 vs 9.44 vs 7.78 days, p &lt; 0.001). The total hospitalization charges was also higher for AA and HISP compared to WH ($90,680 vs $123,894 vs $74,126, p &lt; 0.001). HISP patients had higher odds of requiring intubation, blood transfusion, shock and sepsis than WH. Conclusions: Despite being significantly younger with lower comorbidity burden, HISP, had an increased odds of mortality compared to WH patients. Contrary to reported literature (PMID: 35344045), there was no significant difference in the odds of mortality between WH and AA. Further studies are needed to explore the reasons for high mortality in HISP patients. [Table: see text]

Mutation hot spots in MICA/MICB extracellular domains

MICA and MICB are non-classical MHC molecules that indicate cellular stress. They act as ligands for NKG2D receptors found on NK cells, thereby triggering a cytotoxic response against damaged, infected, or transformed cells. The production of soluble forms of MICA/MICB occurs via the cleavage of their extracellular domains (ECDs). The expression of MICA/MICB molecules in tumor sections or the levels of their soluble forms in blood have potential as diagnostic tools for cancer. They can predict important clinical outcomes for cancer patients, such as overall and recurrence-free survival. However, their extensive molecular polymorphism complicates the development of monoclonal antibodies (mAbs) for diagnostic use. Therefore, the diagnostic value of mAb-based assays may vary depending on the frequencies of allelic variants in local human populations. We examined the ECD amino acid sequences of more than 280 MICA and 50 MICB allelic variants. Additionally, we identified 172 and 58 single nucleotide polymorphisms (SNPs) located in the coding regions of the respective genes and resulting in amino acid replacements. The most frequent amino acid replacements (&gt; 10%) in the ECD occur at 11 and 4 sites of MICA and MICB, respectively. We found that the frequencies of SNPs in the identified hot spots strongly correlate with each other in different human populations, despite the diversity of allelic variant frequencies. The functional role of only one site is known. The replacement of valine with methionine at position 152 enhances the affinity of MICA to NKG2D receptor. As the hot spots are dispersed throughout the entire ECD sequences, they may play a role other than modulating affinity with the NKG2D receptor interaction. We recommend that Ag sets used to validate anti-MICA/MICB mAbs meet two criteria. First, they should include both MICA and MICB alleles, as these genes have highly similar sequences. Second, the alleles should cover the variability observed in the identified hot spots.

An Inflection Point in Cancer Protein Biomarkers: What was and What's Next

Biomarkers remain the highest value proposition in cancer medicine today—especially protein biomarkers. Despite decades of evolving regulatory frameworks to facilitate the review of emerging technologies, biomarkers have been mostly about promise with very little to show for improvements in human health. Cancer is an emergent property of a complex system, and deconvoluting the integrative and dynamic nature of the overall system through biomarkers is a daunting proposition. The last 2 decades have seen an explosion of multiomics profiling and a range of advanced technologies for precision medicine, including the emergence of liquid biopsy, exciting advances in single-cell analysis, artificial intelligence (machine and deep learning) for data analysis, and many other advanced technologies that promise to transform biomarker discovery. Combining multiple omics modalities to acquire a more comprehensive landscape of the disease state, we are increasingly developing biomarkers to support therapy selection and patient monitoring. Furthering precision medicine, especially in oncology, necessitates moving away from the lens of reductionist thinking toward viewing and understanding that complex diseases are, in fact, complex adaptive systems. As such, we believe it is necessary to redefine biomarkers as representations of biological system states at different hierarchical levels of biological order. This definition could include traditional molecular, histologic, radiographic, or physiological characteristics, as well as emerging classes of digital markers and complex algorithms. To succeed in the future, we must move past purely observational individual studies and instead start building a mechanistic framework to enable integrative analysis of new studies within the context of prior studies. Identifying information in complex systems and applying theoretical constructs, such as information theory, to study cancer as a disease of dysregulated communication could prove to be “game changing” for the clinical outcome of cancer patients.

Emergency department imaging utilization of cancer patients treated with bevacizumab: single-institution 8-year experience.

This study aims to highlight the presentations, imaging, and clinical outcomes of cancer patients presenting to the emergency department (ED) while receiving bevacizumab (Avastin) therapy. Our retrospective study was based on data from a single institution to identify cancer patients who presented acutely to the ED between 2014 and 2021 within 3months of beginning bevacizumab who subsequently received diagnostic imaging with CT, MRI, ultrasound, and/or nuclear medicine ventilation/perfusion (VQ) scans. Data gathered included presenting symptoms grouped by body system, imaging impressions, and clinical outcomes, including hospitalization and discontinuation of bevacizumab after each ED visit. Imaging examinations and patient charts were reviewed by a team of fellowship-trained radiologists, radiology residents, and medical students. A total of 84 patients who presented to the ED were included for analysis. This included 32 (38.1%) males and 52 (61.9%) females, with a mean age of 61.2years and an age range of 29-91years. Neurological symptoms were the most common presenting symptoms, followed by abdominal symptoms and respiratory symptoms. Head imaging with CT and MRI was the most common imaging ordered with 55 total examinations, followed by abdominal imaging with 37 CT abdomen/pelvis (A/P) examinations, and then CT chest imaging with 22 examinations. Imaging revealed a serious adverse drug reaction in 21 (25.0%) patients, disease progression in 19 (22.6%), and no acute imaging findings in 44 (52.4%) patients. Imaging diagnoses were significantly associated with treatment planning, with a positive determination of bevacizumab-related serious adverse reaction on imaging leading to discontinuation of bevacizumab (p = 0.001). Multimodality imaging was a commonly used assessment tool for cancer patients receiving bevacizumab who presented to the ED. Imaging played a crucial role in diagnosis in these patients, especially of treatment-related serious adverse reactions and disease progression. Positive imaging findings of serious adverse reactions affected patient management including discontinuation of bevacizumab.

Transcriptome mapping of renal clear cell carcinoma revealed by machine learning algorithm based on enhanced computed tomography images.

A growing number of studies have shown that inflammation-related components of the tumor microenvironment (TME) affect the clinical outcomes of cancer patients, and advances in radiomics may help predict survival and prognosis. We performed a systematic analysis of inflammation-related genes (IRGs) in clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus and mapped their interaction network to assess the specific relationship between these differentially expressed inflammation-related genes (DEIRGs) and inflammation. The association between DEIRGs and prognosis was discussed and further validated using consensus cluster analysis. Next, we constructed IRGs-related risk score from the collected information and validated the prognostic value of the model using Kaplan-Meier survival analysis and receiver operating characteristic analysis. Computed tomographic images corresponding to the TCGA-ccRCC cohort were obtained from the Cancer Imaging Archive database for radiomics signature extraction. We screened for prognostic IRGs and found that they were positively correlated with inflammatory cells in the tumor microenvironment associated with tumor progression and metastasis, such as activated CD8+ cells, myeloid-derived suppressor cells and neutrophils. The impact of IRGs on the prognosis of ccRCC patients was also verified. Using these differentially expressed genes, we successfully constructed a risk signature and validated its good prognosis assessment for patients. Furthermore, radiomics-based prognostic models performed better than those using risk signatures or clinical characteristics. IRG-related risk scores play an important role in assessing the prognosis and improving the management of patients with ccRCC. Through this feature, the infiltration of immune cells in the TME can be predicted. Furthermore, non-invasive radiomics signatures showed satisfactory performance in predicting ccRCC prognosis.

Measurement of sarcopenia in lung cancer inpatients and its association with frailty, nutritional risk, and malnutrition.

Sarcopenia, frailty, and malnutrition are associated with undesirable clinical outcomes in cancer patients. Sarcopenia-related measurements may be promising fast biomarkers for frailty. Our objectives were to assess the prevalence of nutritional risk, malnutrition, frailty, and sarcopenia in lung cancer inpatients, and describe the relationship of them. Stage III and IV lung cancer inpatients were recruited before chemotherapy. The skeletal muscle index (SMI) was assessed by multi-frequency bioelectric impedance analysis (m-BIA). Sarcopenia, frailty, nutritional risk, and malnutrition were diagnosed according to the Asian Working Group for Sarcopenia 2019 (AWGS 2019), Fried Frailty Phenotype (FFP), nutritional risk screening-2002 (NRS-2002), and Global Leadership Initiative on Malnutrition criteria (GLIM), and correlation analysis was performed between them with Pearson's r correlation coefficients. A univariate and multivariate logistic regression analysis was conducted for all patients, gender and age-stratified subgroups to obtain odds ratios (ORs) and 95% confidence intervals (95%CIs). The cohort included 97 men (77%) and 29 women (23%), with mean age of 64.8 ± 8.7 years. Among the 126 patients, 32 (25.4%) and 41 (32.5%) had sarcopenia and frailty, and the prevalence of nutritional risk and malnutrition was 31.0% (n = 39) and 25.4% (n = 32). Adjusted for age and gender, SMI was correlated with FFP (r = -0.204, p = 0.027), and did not remain significantly when stratified by gender. Stratification according to age revealed in ≥65-years-old population, SMI and FFP were significantly correlated (r = -0.297, p = 0.016), which is not seen in <65-years-old group (r = 0.048, p = 0.748). The multivariate regression analysis showed FFP, BMI, and ECOG were the independent variables associated with sarcopenia (OR 1.536, 95%CI 1.062-2.452, p = 0.042; OR 0.625, 95%CI 0.479-0.815, p = 0.001; OR 7.286, 95%CI 1.779-29.838, p = 0.004). Comprehensively assessed sarcopenia is independently associated with frailty based on FFP questionnaire, BMI, and ECOG. Therefore, sarcopenia assessment including m-BIA based SMI, and muscle strength and function could be used to indicate frailty to help select the targeting patients for care. Moreover, in addition to muscle mass, muscle quality should not be ignored in clinical practice.