Identify Cancer Patients Research Articles

Long-Term Risk of Medication-Related Osteonecrosis of the Jaw (MRONJ) After Bisphosphonates and/or Denosumab in Metastatic Breast Cancer Patients

Recently published data identified cancer patients with bone metastases receiving continuous monthly antiresorptive drugs (bisphosphonates and/or denosumab) as patients at high risk for Medication-Related Osteonecrosis of the Jaw (MRONJ), even with late onset. A retrospective multicenter study was conducted between 2000 and 2020 at all breast centers across Tyrol (Austria), screening all patients with breast cancer and bone metastases receiving antiresorptive therapy. The MRONJ incidence was found to be considerably high in patients receiving denosumab (11.6%-16.3%), with an elevated cumulative incidence at 6 years. This commentary underlines some important results of the study and proposes further evaluation of the group of patients receiving a sequence of bisphosphonates and denosumab. Furthermore, other interesting data could come from patients treated in the last decade, receiving more effective anticancer treatments but also more frequently denosumab, in comparison with patients treated in previous years.

MicroRNAs are enriched at COVID-19 genomic risk regions, and their blood levels correlate with the COVID-19 prognosis of cancer patients infected by SARS-CoV-2

BackgroundCancer patients are more susceptible to an aggressive course of COVID-19. Developing biomarkers identifying cancer patients at high risk of COVID-19-related death could help determine who needs early clinical intervention. The miRNAs hosted in the genomic regions associated with the risk of aggressive COVID-19 could represent potential biomarkers for clinical outcomes.Patients and methodsPlasma samples were collected at The University of Texas MD Anderson Cancer Center from cancer patients (N = 128) affected by COVID-19. Serum samples were collected from vaccinated healthy individuals (n = 23) at the Municipal Clinical Emergency Teaching Hospital in Timisoara, Romania. An in silico positional cloning approach was used to identify the presence of miRNAs at COVID-19 risk-associated genomic regions: CORSAIRs (COvid-19 RiSk AssocIated genomic Regions). The miRNA levels were measured by RT-qPCR.ResultsWe found that miRNAs were enriched in CORSAIR. Low plasma levels of hsa-miR-150-5p and hsa-miR-93-5p were associated with higher COVID-19-related death. The levels of hsa-miR-92b-3p were associated with SARS-CoV-2 test positivity. Peripheral blood mononuclear cells (PBMC) increased secretion of hsa-miR-150-5p, hsa-miR-93-5p, and hsa-miR-92b-3p after in vitro TLR7/8- and T cell receptor (TCR)-mediated activation. Increased levels of these three miRNAs were measured in the serum samples of healthy individuals between one and nine months after the second dose of the Pfizer-BioNTech COVID-19 vaccine. SARS-CoV-2 infection of human airway epithelial cells influenced the miRNA levels inside their secreted extracellular vesicles.ConclusionsMiRNAs are enriched at CORSAIR. Plasma miRNA levels can represent a potential blood biomarker for predicting COVID-19-related death in cancer patients.

Alcohol consumption in cancer patients receiving psycho-oncologic care analysis of socio-demographic, health-related and cancer-related factors.

The carcinogenic effects of alcoholic beverages and the negative impact of alcohol consumption on cancer progression and treatment outcomes are well established in oncology research. Many cancer patients experience significant psychological distress, often manifesting as elevated levels of depression and anxiety. In the general population, alcohol consumption is commonly used as a coping mechanism for such distress. For cancer patients facing substantial psychological challenges, psycho-oncology care is available to help manage their symptoms and the overall impact of their condition. However, there is limited understanding of the alcohol consumption patterns in this particularly vulnerable group of patients, as well as the disease-related factors that may influence their drinking behavior. This study aims to examine the prevalence of potentially risky alcohol consumption in cancer patients receiving psycho-oncology care and to identify sociodemographic, health-related, and psychosocial factors associated with alcohol consumption after cancer diagnosis. By understanding drinking patterns and the factors associated with them, we aim to promote healthier behaviors and enhance treatment outcomes for cancer patients receiving psycho-oncology care. A consecutive sample of 1.225 patients from the psycho-oncology outpatient clinic of the University Medical Center Hamburg Eppendorf (UKE) was analyzed with regard to their alcohol consumption behavior using the Alcohol Use Disorders Identification Test-Consumption Items (AUDIT-C). Self-report questionnaires were employed to assess sociodemographic, health-related, and cancer-specific information. For statistical analysis, multiple linear regression was utilized. In the sample of cancer patients receiving psycho-oncology support one in six of both female and male patients showed risky alcohol drinking behavior (e.g. AUDIT-C above three for women and four for men). In the analysis (R-Square: 0.056) male gender (regression coefficient B 0.686, 95% CI: 0.453-0.919) and patientsreporting a higher physical health-related quality of life (SF8-PCS) (B 0.021, 95% CI: 0.011-0.032) were associated with higher levels of alcohol consumption, whereas having children (B -0.481, 95%CI: -0.700- -0.262) was associated with lower alcohol consumption. With regard to cancer type, a single-factor analysis of variance with gender as the centered covariate showed that patients with gastrointestinal cancer had had lower average consumption levels compared to the groups of patients with breast cancer, melanoma, genitourinary cancer, and lymphoma. Also, patients with sarcoma had lower average consumption levels than patients with lymphoma. The results allow to identify patient characteristics and cancer types associated with higher or lower alcohol consumption levels and higher likelihood of risky consumption behavior in this sample of cancer patients receiving psycho-oncological support. Cancer patients are particularly susceptible to the hazardous effects of alcohol consumption. The results of this study help to identify cancer patients at risk of worsening prognosis due to alcohol consumption and to develop intervention programs to minimize alcohol consumption in this group.

Construction and preclinical evaluation of a 124I-labelled bispecific antibody targeting PD-L1 and PD-L2.

NB12 is a bispecific antibody that consists of two anti-programmed cell death-ligand 1 (PD-L1) nanobodies and two anti-programmed cell death-ligand 2 (PD-L2) nanobodies. The aim of this study was to design a novel tracer, [124I]I-NB12, targeting PD-L1/2 and perform preclinical evaluations to dynamically monitor PD-L1/2 expression for determining cancer patient responsiveness to ICI therapy. NB12 was labelled with the radionuclide 124I at room temperature (RT). An in vitro binding assay was performed to assess the affinity of [124I]I-NB12 for PD-L1 and PD-L2. Cellular uptake, pharmacokinetic, and biodistribution experiments were performed to evaluate the biological properties. Micro-PET/CT imaging with [124I]I-NB12 was conducted at different time points. Immunohistochemical and haematoxylin and eosin (HE) staining experiments were carried out using tumour tissues. Routine blood, biochemical indices and major organ pathology were used to evaluate the biosafety of the tracers. The radiochemical yield of [124I]I-NB12 was 84.62 ± 3.90%, and the radiochemical purity (RCP) was greater than 99%. [124I]I-NB12 had a high affinity for the PD-L1 (Kd = 19.82 nM) and PD-L2 (Kd = 2.93 nM). Cellular uptake experiments confirmed that the uptake of [124I]I-NB12 by A549-PDL1/2 cells was greater than that by A549 cells. The half-lives of the distribution phase and elimination phase were 0.26h and 4.08h, respectively. Micro-PET/CT showed significant [124I]I-NB12 uptake in the tumour region of A549-PDL1/2 tumour-bearing mice compared with A549 tumour-bearing mice 24h postinjection. Immunohistochemical and HE staining experiments confirmed that tumour-bearing mice was successfully constructed. We constructed a bispecific antibody that targets PD-L1 and PD-L2, namely, [124I]I-NB12. Biological evaluation revealed its specificity and affinity for PD-L1/2, and micro-PET/CT confirmed the feasibility of visualizing tumour PD-L1/2 in vivo. Using [124I]I-NB12 may be a promising strategy for identifying cancer patients that can potentially benefit from ICI therapy.

Evaluation of the incidence, predictors, risk assessment scores and outcomes of thromboembolism in a cohort of Egyptian NHL patients - Real World Experience

Non-Hodgkin’s Lymphoma (NHL) is the most common subtype of lymphoma. The incidence of venous thromboembolism (VTE) in aggressive NHL was estimated recently to be 11%. Several risk assessment scores and factors are available to help identify cancer patients at risk for developing VTE. Patients with a pathologically confirmed diagnosis of NHL were identified at the Oncology Center of Mansoura University. The study included 777 patients: 719 with DLBCL-NOS, 26 with Anaplastic-B-cell, and 32 with T-cell-rich-NHL. Data were retrospectively collected from electronic medical records, including clinical, radiological, and laboratory information related to VTE and NHL. The median age at NHL diagnosis was 53 years, (range: 18–98). There was a male predominance, 51.4% of the cases. At initial lymphoma diagnosis, VTE was identified in 46 (5.9%) patients, and 61 (7.9%) patients experienced VTE while undergoing chemotherapy. According to logistic regression analysis, a PS (performance status) ≥ 2, bulky lesions, and mediastinal masses were significant predictors of VTE at presentation, with P-values of 0.022, 0.002, and < 0.001, respectively. Meanwhile, NHL patients who developed VTE during chemotherapy had significantly poorer PS, higher absolute neutrophilic counts (ANC), neutrophil/lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lactate dehydrogenase (LDH) levels than lymphoma patients without VTE, with P-values of 0.003, 0.034, 0.049, 0.01 and 0.007, respectively, as determined by multivariate analysis. The ROC curve identified the cut-off values of 4.875 × 109/L for ANC, 2.985 for NLR, 144.85 for PLR, and 417.5 U/L for LDH as potential markers for predicting VTE in NHL patients. Patients with a PS ≥ 2 and values exceeding these cut-offs for ANC, NLR, and PLR experienced significantly higher incidences of VTE than other groups, with P-values of 0.003, < 0.001, < 0.001, and < 0.001, respectively. At the end of the follow-up, the overall survival was significantly shortened by VTE occurring during chemotherapy, hypoalbuminemia, intermediate-high and high international prognostic index (IPI) scores (intermediate-high and high), responses other than CR and relapse, all with P-values < 0.05. ECOG PS and Inflammatory markers such as NLR, PLR, and neutrophilic count could serve as predictors of the development of thrombotic events in patients with NHL-DLBCL. Additionally, the occurrence of VTE during chemotherapy is an independent poor prognostic marker for overall survival (OS).

Imaging Recommendations for Diagnosis, Staging, and Management of Central Nervous System Neoplasms in Adults: CNS Metastases.

To identify cancer patients at a higher risk of developing CNS metastases and to evaluate associated prognostic factors. Review of imaging referral guidelines, response criteria, interval imaging assessment, modality of choice, as well as the association of clinical, serological, and imaging findings as per various cancer societies. Quantitative response assessment of target and non-target brain metastases as well as an interval imaging protocol set up based on primary histological diagnosis and therapy status are discussed as per various cancer societies and imaging programs. Predictive factors in the primary tumor as well as independent variables of brain metastases like size, number, and response to therapy are necessary in management. The location of CNS metastases, symptomatic disease, as well as follow up imaging findings form a skeletal plan to prognosticate the disease, keeping in mind all the available new advanced therapy options of surgery, radiation, and immunotherapy that improve patient outcome significantly.

The clinical prognostic significance of miR-140–5p expression in patients with cancer: A Meta and Bioinformatic analysis

The prognostic value of microRNA-140–5p (miR-140–5p) expression in cancer patients has been investigated, but with inconsistent results. This meta-analysis aims to determine the prognostic significance of miR-140–5p expression in patients with various malignancies. A comprehensive literature search was conducted using PubMed, Web of Science, ProQuest, Cochrane, and Google Scholar to identify relevant studies published before June 2023. Pooled hazard ratios (HR) and odds ratios (OR) with 95 % confidence intervals (CI) were calculated to assess the prognostic importance and clinicopathological features of miR-140–5p in overall survival (OS) and disease-free survival (DFS) of cancer patients, respectively. The CancerMIRNome database and other OS analysis webservers were utilized to explore the prognostic value and expression profile of miR-140–5p. A total of 17 studies were included in the final analysis. The results demonstrated that decreased miR-140–5p expression was significantly associated with inferior OS (pooled HR 0.63; 95 % CI, 0.51–0.79; p < 0.001) and DFS (pooled HR 0.40; 95 % CI, 0.25–0.64; p < 0.001). Pooled ORs indicated a significant correlation between reduced miR-140–5p expression and positive lymph node metastasis (LNM; OR = 3.42; 95 % CI, 2.36–4.94; p < 0.001), advanced tumor stage (OR = 2.80; 95 % CI, 2.07–3.78; p < 0.001), and positive distant metastasis (DM; OR = 10.81; 95 % CI, 3.31–35.30; p < 0.001). No significant associations were observed between miR-140–5p expression and gender (OR = 0.94; 95 % CI, 0.70–1.28; p = 0.70), age (OR = 1.31; 95 % CI, 0.99–1.74; p = 0.06), tumor size (OR = 1.55; 95 % CI, 0.77–3.10; p = 0.22), and histological grade (OR = 1.20; 95 % CI, 0.46–3.10; p = 0.71). Subgroup analyses revealed that decreased miR-140–5p expression was associated with shorter OS in subgroups based on sample size (<100 or >100), tumor origin (GI or non-GI), and cancer type (GC/CRC). Bioinformatic analysis supported the finding that miR-140–5p was downregulated in most tumor tissues, and its reduced expression was linked to poor prognosis in patients with multiple malignancies. The prognostic significance of miR-140–5p in predicting reduced OS and DFS suggests that measuring miR-140–5p expression levels before treatment could serve as a valuable biomarker for identifying cancer patients with an unfavorable prognosis and improving clinical management.

The association between malnutrition risk and revised Edmonton Symptom Assessment System (ESAS-r) scores in an adult outpatient oncology population: a cross-sectional study

BackgroundCancer-associated malnutrition is associated with worse symptom severity, functional status, quality of life, and overall survival. Malnutrition in cancer patients is often under-recognized and undertreated, emphasizing the need for standardized pathways for nutritional management in this population. The objectives of this study were to (1) investigate the relationship between malnutrition risk and self-reported symptom severity scores in an adult oncology outpatient population and (2) to identify whether a secondary screening tool for malnutrition risk (abPG-SGA) should be recommended for patients with a specific ESAS-r cut-off score or group of ESAS-r cut-off scores.MethodsA single-institution retrospective cross-sectional study was conducted. Malnutrition risk was measured using the Abridged Patient-Generated Subjective Global Assessment (abPG-SGA). Cancer symptom severity was measured using the Revised Edmonton Symptom Assessment System (ESAS-r). In accordance with standard institutional practice, patients completed both tools at first consult at the cancer centre. Adult patients who completed the ESAS-r and abPG-SGA on the same day between February 2017 and January 2020 were included. Spearman’s correlation, Mann Whitney U tests, receiver operating characteristic curves, and binary logistic regression models were used for statistical analyses.Results2071 oncology outpatients met inclusion criteria (mean age 65.7), of which 33.6% were identified to be at risk for malnutrition. For all ESAS-r parameters (pain, tiredness, drowsiness, nausea, lack of appetite, shortness of breath, depression, anxiety, and wellbeing), patients at risk for malnutrition had significantly higher scores (P < 0.001). All ESAS-r parameters were positively correlated with abPG-SGA score (P < 0.01). The ESAS-r parameters that best predicted malnutrition risk status were total ESAS-r score, lack of appetite, tiredness, and wellbeing (area under the curve = 0.824, 0.812, 0.764, 0.761 respectively). Lack of appetite score ≥ 1 demonstrated a sensitivity of 77.4% and specificity of 77.0%. Combining lack of appetite score ≥ 1 with total ESAS score > 14 yielded a sensitivity of 87.9% and specificity of 62.8%.ConclusionMalnutrition risk as measured by the abPG-SGA and symptom severity scores as measured by the ESAS-r are positively and significantly correlated. Given the widespread use of the ESAS-r in cancer care, utilizing specific ESAS-r cut-offs to trigger malnutrition screening could be a viable way to identify cancer patients at risk for malnutrition.

Development of a nomogram for predicting malnutrition in elderly hospitalized cancer patients: a cross-sectional study in China.

The Patient-Generated Subjective Global Assessment (PG-SGA) serves as a specialized nutritional assessment instrument designed for cancer patients. Despite its specificity, the complexity and time requirements of this tool, along with the necessity for administration by trained professionals, limit its practicality in clinical settings. Our objective is to identify a straightforward, efficient, and dependable nutritional assessment tool to promote broader adoption in clinical practice. This study encompassed a total of 450 patients diagnosed with cancer. Of these, 315 individuals constituted the training set, and the remaining 135 were allocated to the external validation set. The model variables were identified through the Least Absolute Shrinkage and Selection Operator (LASSO) regression method. Binary logistic regression outcomes facilitated the development of a nomogram, offering a visual depiction of the predicted probabilities. The predictive accuracy of the nomogram model was evaluated by calculating the area under the Receiver Operating Characteristic (ROC) curve. The LASSO method detected four variables that were included in the final prediction model: age, serum albumin levels (ALB), body mass index (BMI), and activities of daily living (ADL). The area under the curve (AUC) for this prediction model was 0.905. Both the internal and external calibration curves for malnutrition showed that the predictive nomogram model was highly accurate. The study has developed a prediction model that demonstrates remarkable accuracy in forecasting malnutrition. Furthermore, it presents a streamlined nutritional assessment tool aimed at swiftly identifying cancer patients at nutritional risk, thereby facilitating oncologists in delivering targeted nutritional support to these individuals.

Increased stress burden and electrodermal reactivity in bladder cancer patients in comparison to healthy controls

The purpose of our study was to assess specific physiological parameters associated with stress responses in bladder cancer (BCa) patients compared to healthy individuals. By examining the transition from a supine to a sitting position, representing a mild physiological load, we investigated the changes in autonomic nervous system (ANS) activity as reflected by alterations in these parameters, indicating shifts in ANS regulation, using non-linear heart rate variability (HRV) parameters (0V%, 2UV%, parasympathetic and sympathetic nervous system – PNS and SNS indices), modified heart rate acceleration (ACmod) and deceleration capacities (DCmod), heart rate (HR), electrodermal activity (EDA), and also their correlations with perceived stress score. Our findings showed that BCa patients (n = 38) exhibited elevated resting HR, heightened SNS index, and increased EDA compared to their healthy counterparts (n = 47), indicating a notable physiological stress burden. The 0V% parameter showed a positive association with the SNS index, ACmod, HR, and EDA parameters, while displaying a negative correlation with the PNS index, DCmod and 2UV%. These non-linear HRV parameters, such as 0V% and 2UV%, offer nuanced insights into the complexities of heartbeat dynamics and autonomic regulation. After the transition from supine to sitting positions, BCa patients displayed higher EDA responses, indicating heightened stress reactivity and ANS sensitivity. These physiological distinctions persisted even when we did not prove differences in the levels of perceived stress between the studied groups. In conclusion, our study emphasizes the significance of identifying cancer patients at risk of ANS dysregulation, paving the way for tailored stress management strategies.

Risk of Atrial Fibrillation in Patients with Different Cancer Types in Taiwan.

Atrial fibrillation (AF) commonly occurs in approximately 2% of cancer patients, and the incidence of AF among cancer patients is greater than in the general population. This observational study presented the incidence risk of AF among cancer patients, including specific cancer types, using a population database. The Taiwan Cancer Registry was used to identify cancer patients between 2008 and 2017. The diagnosis of AF was based on the International Classification of Diseases codes (ICD-9-CM: 427.31 or ICD-10-CM: I48.0, I48.1, I48.2, and I48.91) in Taiwan national health insurance research datasets. The incidence of developing AF in the cancer population was calculated as the number of new-onset AF cases per person-year of follow-up during the study period. The overall incidence of AF among cancer patients was 50.99 per 100,000 person-years. Patients aged older than 65 years and males had higher AF incidence rates. Lung cancer males and esophageal cancer females showed the highest AF incidence risk (185.02 and 150.30 per 100,000 person-years, respectively). Our findings identified esophageal, lung, and gallbladder cancers as the top three cancers associated with a higher incidence of AF. Careful monitoring and management of patients with these cancers are crucial for early detection and intervention of AF.

Identifying cancer patients who received palliative care using the SPICT-LIS in medical records: a rule-based algorithm and text-mining technique

BackgroundDue to limited numbers of palliative care specialists and/or resources, accessing palliative care remains limited in many low and middle-income countries. Data science methods, such as rule-based algorithms and text mining, have potential to improve palliative care by facilitating analysis of electronic healthcare records. This study aimed to develop and evaluate a rule-based algorithm for identifying cancer patients who may benefit from palliative care based on the Thai version of the Supportive and Palliative Care Indicators for a Low-Income Setting (SPICT-LIS) criteria.MethodsThe medical records of 14,363 cancer patients aged 18 years and older, diagnosed between 2016 and 2020 at Songklanagarind Hospital, were analyzed. Two rule-based algorithms, strict and relaxed, were designed to identify key SPICT-LIS indicators in the electronic medical records using tokenization and sentiment analysis. The inter-rater reliability between these two algorithms and palliative care physicians was assessed using percentage agreement and Cohen’s kappa coefficient. Additionally, factors associated with patients might be given palliative care as they will benefit from it were examined.ResultsThe strict rule-based algorithm demonstrated a high degree of accuracy, with 95% agreement and Cohen’s kappa coefficient of 0.83. In contrast, the relaxed rule-based algorithm demonstrated a lower agreement (71% agreement and Cohen’s kappa of 0.16). Advanced-stage cancer with symptoms such as pain, dyspnea, edema, delirium, xerostomia, and anorexia were identified as significant predictors of potentially benefiting from palliative care.ConclusionThe integration of rule-based algorithms with electronic medical records offers a promising method for enhancing the timely and accurate identification of patients with cancer might benefit from palliative care.

Abstract 5198: Non-invasive biomarkers of ECM turnover are prognostic for combinations of checkpoint inhibition immunotherapy in solid tumors

Abstract Background: Immune checkpoint inhibitors (ICIs) are investigated in many different combinations (Table 1). As only a fraction of patients responds to ICIs, prognostic biomarkers are needed to assess the likelihood of benefit. High collagen turnover in the tumor microenvironment are closely related to response to ICIs and survival outcomes. In this study, we explored the clinical utility of non-invasive biomarkers of type I collagen (reC1M), type III collagen (PRO-C3), type IV collagen (C4M), type XIX collagen (PRO-C19), type XX collagen (PRO-C20), TGF-β activity in metastatic cancer patients treated with ICIs. Methods: PRO-C3, PRO-C19, PRO-C20, TGF-β, reC1M and C4M were measured with ELISAs in pre-treatment serum from 33 patients with metastatic disease in a basket trial comprising 14 different tumor types, treated with 8 different checkpoint inhibition regimens (Table 1). The association between biomarker levels and overall survival (OS) outcome was evaluated by Kaplan-Meier analysis and Cox regression analysis after dichotomizing patients at the 75th percentile (Q4). Results: When evaluating the combined group of cancer patients, high levels (Q4) of PRO-C3 (HR=3.00, 95%CI=1.21-7.44, p=0.018), PRO-C19 (HR=2.49, 95%CI=1.04-5.99, p=0.041), PRO-C20 (HR=2.49, 95%CI=1.04-5.99, p=0.041), TGF-β (HR=2.52, 95%CI=1.05-6.04, p=0.039), reC1M (HR=2.79, 95%CI=1.16-6.67, p=0.021) and C4M (HR=2.52, 95%CI=1.05-6.04, p=0.039) were all associated with poor OS compared to low levels (Q1-Q3). The median OS was 4.7-6.1 months in biomarker-high patients compared to 8.7-11.4 in biomarker-low patients. Conclusion: Across a diverse cohort of metastatic cancer patients treated with different checkpoint inhibition regimens, non-invasive biomarkers associated with tumor fibrosis and collagen turnover (PRO-C3, PRO-C19, PRO-C20, TGF-β, reC1M and C4M) could identify cancer patients with poor prognosis. Table 1. Cancer type Number of patients Treatment Esophageal 1 Nivolumab (Nivo) +Anti-LAG3 Breast 2 Carboplatine+Gemciabine+Pembrolizumab (Pembro) Ovarian 4 Atezolizumab+BET inhibitor Parotid 1 Nivo Gastric 2 Nivo+Anti-LAG3 or Atezolizumab+CD40-agonist Bladder 3 Pembro Colorectal 5 Nivo, Pembro, Atezolizumab++bispecific antibody targeting CEA and CD3 or Atezolizumab+CD40-agonist Hepatocellular carcinoma 3 Nivo+Anti-LAG3 Colorectal 1 Atezolizumab+bispecific antibody targeting CEA and CD3 Mesothelioma 2 Pembro or Atezolizumab+CD40-agonist Neuroendocrine tumor 1 Pembro non-small cell 5 Nivo, Pembro or ipilumumab+Nivolumab Pancreas 1 Atezolizumab+CD40-agonist Unknown primary 2 Atezolizumab++bispecific antibody targeting CEA and CD3 or Pembro Citation Format: Caroline N. Bistrup, Vinicius Araujo Barbosa de Lima, Christina Jensen, Morten A. Karsdal, Inge Marie Svane, Ulrik Lassen, Nicholas Willumsen. Non-invasive biomarkers of ECM turnover are prognostic for combinations of checkpoint inhibition immunotherapy in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5198.

Sonographic Measurements of Rectus Femoris Muscle Thickness Strongly Predict Neutropenia in Cancer Patients Receiving Chemotherapy.

The objective of this study was to explore the possible association between low skeletal muscle mass (SMM)-assessed by computed tomography (CT) and ultrasound (US)-and hematologic toxicity in cancer patients. A prospective cohort study was conducted in cancer patients who received anthracycline-based chemotherapy between 2018 and 2020 and who had baseline abdominal CT including L3 level for measuring SMM. Regional muscle measurements were carried out using US. A total of 65 patients (14 males, 51 females) were included. ROC (receiver operating characteristic) analysis identified threshold values of 18.0 mm [AUC (area under the curve) = 0.765] for females and 20.0 mm (AUC = 0.813) for males, predicting severe neutropenia. Using these cut-offs, females with low rectus femoris (RF) thickness (<18.0 mm) had a significantly higher incidence of grade ≥3 neutropenia (50.0% vs. 10.8%, p = 0.005), and males with low RF values (<20.0 mm) had a higher incidence (80.0% vs. 22.2%, p = 0.063). A regression analysis, irrespective of age, gender, and body mass index, revealed that only low RF muscle thickness increased the risk of grade 3-4 neutropenia by 9.210 times (95% CI = 2.401-35.326, p = 0.001). Utilizing US to measure RF muscle thickness aids in identifying cancer patients at an elevated risk of developing neutropenia. Needless to say, US can serve as a convenient and easily accessible tool for assessing low SMM, providing repeat point-of-care evaluations in clinical practice.

Elevated levels of citrullinated fibrinogen in patients with cancer.

Neutrophil released peptidyl arginine deiminase 4 (PAD4) converts arginine residues on plasma proteins into citrulline. Here, we developed an assay to quantify citrullinated fibrinogen. We employed a biotin-conjugated phenylglyoxal (biotin-phenylglyoxal (PG)) compound that selectively labels citrulline. Patient samples were derived from a multicenter prospective cohort study that aimed to identify cancer patients at high risk for venous thromboembolism (VTE). Our data show that cancer patients have higher (median 2-fold increased) citrullinated fibrinogen levels when compared to normal human plasma and a cohort of healthy donors. Our results show that citrullination of fibrinogen is a common posttranslational modification in patients with cancer.

Predictive Models for Palliative Care Needs of Advanced Cancer Patients Receiving Chemotherapy

ContextEarly palliative care is recommended within eight-week of diagnosing advanced cancer. Although guidelines suggest routine screening to identify cancer patients who could benefit from palliative care, implementing screening can be challenging due to understaffing and time constraints. ObjectivesTo develop and evaluate machine learning models for predicting specialist palliative care needs in advanced cancer patients undergoing chemotherapy, and to investigate if predictive models could substitute screening tools. MethodsWe conducted a retrospective cohort study using supervised machine learning. The study included patients aged 18 or older, diagnosed with metastatic or stage IV cancer, who underwent chemotherapy and distress screening at a designated cancer hospital in Japan from April 1, 2018, to March 31, 2023. Specialist palliative care needs were assessed based on distress screening scores and expert evaluations. Data sources were hospital's cancer registry, health claims database, and nursing admission records. The predictive model was developed using XGBoost, a machine learning algorithm. ResultsOut of the 1878 included patients, 561 were analyzed. Among them, 114 (20.3%) exhibited needs for specialist palliative care. After under-sampling to address data imbalance, the models achieved an Area Under the Curve (AUC) of 0.89 with 95.8% sensitivity and a specificity of 71.9%. After feature selection, the model retained five variables, including the patient-reported pain score, and showcased an 0.82 AUC. ConclusionOur models could forecast specialist palliative care needs for advanced cancer patients on chemotherapy. Using five variables as predictors could replace screening tools and has the potential to contribute to earlier palliative care.

Impact of Mutations in Subunit Genes of the Mammalian SWI/SNF Complex on Immunological Tumor Microenvironment.

Recently, inactivating somatic mutations of SWI/SNF chromatin-remodeling genes in cancers have been reported. However, few studies have been performed regarding the immunological analysis of the tumor microenvironment (TME) in chromatin remodeling complex gene-mutated tumors. In the present study, we identified cancer patients harboring various mammalian SWI/SNF complex mutations and investigated the immunological features in those mutated cancers. Cancer patients harboring any type of chromatin remodeling complex gene mutation were selected and clinicopathological features were compared between chromatin remodeling complex gene expression-low and expression-high groups. Specifically, expression levels of immune response-associated genes and cancer-associated genes were compared between the SMARCA4 expression-low and expression-high groups using volcano plot analysis. Among cancers harboring PBRM1, SAMRACA4 and ARID2 gene mutations, T-cell marker and mature B-cell marker genes were up-regulated in the tumor. Specifically, T-cell effector genes (CD8B, CD40LG), central memory marker genes (CD27, CCR7) and mature B-cell marker genes (CD20, CD38, CD79 and IRF4) were up-regulated, and cancer-associated genes including MYB, MYC and AURKB genes were down-regulated in the SMARCA4 expression-low group. Remarkably, heatmap of gene expression and immunohistochemistry (IHC) data demonstrated that the tertiary lymphoid structure (TLS) gene signature of mature B cells was up-regulated in SMACA4 gene-mutated stomach cancers. These results suggest that immune tumor microenvironment status, such as mature B cell recruitment featuring the TLS gene signature and immune activation mediated by cancer signal down-regulation, might contribute to the classification of SMARCA4 gene-mutated tumors as immune checkpoint blockade therapy-sensitive target tumors.

Abstract A022: Assessing, understanding, and addressing social determinants of cancer health disparities through patient navigation among rural Arkansans

Abstract The Winthrop P. Rockefeller Cancer Institute at the University of Arkansas for Medical Sciences (UAMS), Office of Community Outreach and Engagement has developed a Cancer Patient Navigation Program dedicated to improving cancer care for everyone in Arkansas. The team includes nurse navigators and community health workers that help bridge the gap between cancer patients, and financial resources in the community, and health care providers. The Cancer Patient Navigation Program emphasizes patient empowerment through prevention, screening, and treatment for rural and underserved populations across the state. The aim of the program is to help eliminate barriers to health care by providing resources for cancer treatment to rural and underserved populations across Arkansas. Navigators and community health works are located throughout every geographic region of Arkansas and are representative of the diversity in the communities they serve. Navigators and community health workers use the Protocol for Responding to and Assessing Patients’ Assets, Risks, and Experiences (PRAPARE®) to identify cancer patients’ barriers to care. PRAPARE® is a standardized patient risk assessment tool consisting of a set of national core measures as well as a process for addressing the social drivers at both the patient and population levels. Since May 2022, the Cancer Patient Navigation program has assessed and addressed the needs of 350 cancer patients. The data collected by navigators and community health workers has improved care coordination services, increased collaborations with local community partners with similar goals, and provided a unique opportunity for UAMS to better understand challenges of cancer patients and provide more appropriate services and care that is needed on a community level. The PRAPRE data has allowed the Office of Community Outreach and Engagement to understand the number of social determinants risks as well as the most common social determinant risks in our patient population. The risk tally score established a baseline to determine who might be more “at risk” by both geographic location and cancer diagnosis. To date, the data collected has been analyzed to track referrals and interventions. The data will further be used to ensure community-engagement priorities and resources are integrated into all Winthrop P. Rockefeller Cancer Institute research cores and clinical enterprises. Addressing the adverse social drivers of health will ultimately allow UAMS to improve patient well-being, facilitate access to prevention, screening, and treatment. Citation Format: Valandra L. German. Assessing, understanding, and addressing social determinants of cancer health disparities through patient navigation among rural Arkansans [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A022.

Negotiating cancer alone: A qualitative study exploring care experiences of racially and ethnically diverse women diagnosed with breast cancer during COVID-19.

COVID-19 has critically impacted cancer care services including reduced screenings, diagnoses, and surgeries; particularly among Black and Latina/x women who already suffer worse outcomes. This qualitative study explored the care experiences of a diverse sample of breast cancer survivors (N = 21; 7 Black, 4 Hispanic, 10 White) undergoing treatment during the pandemic via online semi-structured interviews. Grounded theory analysis yielded the core category "negotiating cancer alone," that included: (1) psychological distress, negotiating the cancer trajectory in isolation; (2) provider/healthcare system diagnostic and treatment delays; (3) heightened anxiety about treatment delays causing cancer progression; (4) supportive care limitations; and (5) disparate experiences of cancer care disruptions. Black and Latina/x women described greater delays in care, financial challenges, treatment complications, and insurance limitations than White women. The study identifies cancer patients' pandemic-related psychological, healthcare system, and health equity challenges and suggests recommendations to support their increased psychological needs during oncologic care disruptions.

Abstract 18300: Do Current Cardiovascular Risk Models Predict the Development of Cardiotoxicity in Lymphoma Patients Treated With Anthracycline?

Introduction: Assessing baseline cardiovascular (CV) risk factors is crucial for identifying cancer patients at higher risk of cardiotoxicity (CT). While both CT specific scores, including Heart Failure Association-International Cardio Oncology Society (HFA-ICOS) and our institutional score, as well as general CV scores like Atherosclerotic cardiovascular disease (ASCVD), have been used to assess CT risk; in lymphoma patients undergoing anthracycline therapy, their utility remains unknown. Aim: Evaluate the performance of each risk score to predict CT in a cohort of newly diagnosed lymphoma patients undergoing anthracycline treatment, followed for a median of 5.4 years. Methods: 326 Hodgkin and non-Hodgkin lymphoma patients treated and followed from 2013 to 2021 were prospectively assessed. Baseline measurements of the three risk scores were obtained. ASCVD score was not assessed in patients &gt;80 or &lt;40 years old or without baseline cholesterol. CT was defined during or after one year of chemotherapy as severe, moderate, or mild according to 2022 ESC guidelines. Logistic regression and AUC were used to assess the association of each score and compare the models. Results: Among 326 patients, 78 developed CT (8 severe, 21 moderate, 49 mild). A high-risk score from HFA-ICOS was significantly associated with severe and moderate CT(OR: 6.1, p=0.001), sensitivity 37%, and specificity 88%. A very high-risk classification of the institutional score was associated with severe and moderate CT (OR: 8.4, p=0.006), sensitivity 44%, and specificity 81%. No association was found between the ASCVD score stratification and CT. When mild CT was included in the analysis, the AUC values were lower (see Table 1). Conclusions: Cardio-oncology risk scores were associated with severe and moderate CT, outperforming ASCVD, but their predictive capacity was weak. Incorporating other serum or imaging biomarkers into the models may improve the predictive accuracy of CT risk assessment.