Cancer Surveillance Research Articles

Editorial: Endogenous danger signals in cancer immunology and immunotherapy

Editorial: Endogenous danger signals in cancer immunology and immunotherapy

Systematic analysis of IGF2BP family members in non-small-cell lung cancer

BackgroundThe insulin-like growth factor-2 mRNA-binding proteins 1, 2, and 3 (IGF2BP1, IGF2BP2, and IGF2BP3) are known to be involved in tumorigenesis, metastasis, prognosis, and cancer immunity in various human cancers, including non-small cell lung cancer (NSCLC). However, the literature on NSCLC largely omits the specific context of lung squamous cell carcinoma (LUSC), an oversight we aim to address.MethodsOur study evaluated the differential expression of IGF2BP family members in tumors and normal tissues. Meta-analyses were conducted to assess the prognostic value of IGF2BPs in lung adenocarcinoma (LUAD) and LUSC. Additionally, correlations between IGF2BPs and tumor immune cell infiltration, mutation characteristics, chemotherapy sensitivity, and tumor mutation burden (TMB) were investigated. GSEA was utilized to delineate biological processes and pathways associated with IGF2BPs.ResultsIGF2BP2 and IGF2BP3 expression were found to be upregulated in LUSC patients. IGF2BP2 mRNA levels were correlated with cancer immunity in both LUSC and LUAD patients. A higher frequency of gene mutations was observed in different IGF2BP1/2/3 expression groups in LUAD compared to LUSC. Meta-analyses revealed a significant negative correlation between overall survival (OS) and IGF2BP2/3 expression in LUAD patients but not in LUSC patients. GSEA indicated a positive association between VEGF and IGF2BP family genes in LUAD, while matrix metallopeptidase activity was inversely correlated with IGF2BP family genes in LUSC. Several chemotherapy drugs showed significantly lower IC50 values in high IGF2BP expression groups in both LUAD and LUSC.ConclusionOur findings indicated that IGF2BPs play different roles in LUAD and LUSC. This divergence highlights the need for tailored therapeutic strategies and prognostic tools, cognizant of the unique molecular profiles of LUAD and LUSC.

PDL1 targeting by miR-138-5p amplifies anti-tumor immunity and Jurkat cells survival in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) has constituted over 80% of the lung cancer population with a poor prognosis. Over the past decade, immunotherapy has been constructed in the enlargement of immune checkpoint inhibitors as a promising approach for NSCLC treatment. Evading the immune system using the PD-1/PD-L1 axis is an intelligent way for cancers, and T cells cannot respond fully and confront cancer. Recently, the miR-138 was reported as a PD-L1 regulator in NSCLC. However, its inhibitory impact on T-cell exhaustion has not been characterized. The present study aims to impair PD-L1 (B7-H1) expression in Adenocarcinoma cell lines using miR-138-5p and determines how it prevents Jurak cell exhaustion. To gain the purpose, first, 18 highly significant dysregulated miRNAs containing hsa-miR-138 and CD274-mRNA network were detected in NSCLC based on bioinformatics analysis. Moreover, our study revealed a high level of miR-138-5p could make significant changes like PDL1 downregulation, proliferation, and mortality rate in A549/Calu6 cells. We also simulate cancer environmental conditions by culturing Jurak cells and NSCLC cell lines under the influence of stimulator cytokines to show how miR-138-5p survives Jurak cells by targeting PD-L1/PD-1pathway.

USPSTF Recommendations and Overdiagnosis.

Overdiagnosis is the concept that some cancers detected at screening would never have become clinically apparent during a woman's lifetime in the absence of screening. This could occur if a woman dies of a cause other than breast cancer in the interval between mammographic detection and clinical detection (obligate overdiagnosis) or if a mammographically detected breast cancer fails to progress to clinical presentation. Overdiagnosis cannot be measured directly. Indirect methods of estimating overdiagnosis include use of data from randomized controlled trials (RCTs) designed to evaluate breast cancer mortality, population-based screening studies, or modeling. In each case, estimates of overdiagnosis must consider lead time, breast cancer incidence trends in the absence of screening, and accurate and predictable rates of tumor progression. Failure to do so has led to widely varying estimates of overdiagnosis. The U.S. Preventive Services Task Force (USPSTF) considers overdiagnosis a major harm of mammography screening. Their 2024 report estimated overdiagnosis using summary evaluations of 3 RCTs that did not provide screening to their control groups at the end of the screening period, along with Cancer Intervention and Surveillance Network modeling. However, there are major flaws in their evidence sources and modeling estimates, limiting the USPSTF assessment. The most plausible estimates remain those based on observational studies that suggest overdiagnosis in breast cancer screening is 10% or less and can be attributed primarily to obligate overdiagnosis and nonprogressive ductal carcinoma in situ.

Peripheral Blood CD8+ T-Lymphocyte Immune Response in Benign and Subpopulations of Breast Cancer Patients.

Peripheral blood CD8+ T lymphocytes play a crucial role in cell-mediated immunity and tumor-related immune responses in breast cancer. In this study, label-free quantification analysis and gene set enrichment analysis (GSEA) of CD8+ T lymphocytes in the peripheral blood of benign patients and patients with different breast cancer (BC) subtypes, i.e., luminal A, luminal B, and triple-negative breast cancer (TNBC), were performed using nano-UHPLC and Orbitrap mass spectrometry. Differential protein expression in CD8+ T lymphocytes revealed significant downregulation (log2 FC ≥ 0.38 or ≤-0.38, adj. p < 0.05), particularly in proteins involved in cytotoxicity, cytolysis, and proteolysis, such as granzymes (GZMs) and perforin 1 (PRF1). This downregulation was observed in the benign group (GZMH, GZMM, and PRF1) and luminal B (GZMA, GZMH) subtypes, whereas granzyme K (GZMK) was upregulated in TNBC in comparison to healthy controls. The RNA degradation pathway was significantly downregulated (p < 0.05, normalized enrichment score (NES) from -1.47 to -1.80) across all BC subtypes, suggesting a potential mechanism for regulating gene expression during T cell activation. Also, the Sm-like proteins (LSM2, LSM3, and LSM5) were significantly downregulated in the RNA degradation pathway. Proteomic analysis of CD8+ T lymphocytes in peripheral blood across different breast cancer subtypes provides a comprehensive view of the molecular mechanisms of the systemic immune response that can significantly contribute to advancements in the diagnosis, treatment, and prognosis of this disease.

Mechanoimmunology in the solid tumor microenvironment.

The tumor microenvironment (TME) is a complex and dynamic ecosystem that adjoins the cancer cells within solid tumors and comprises distinct components such as extracellular matrix, stromal and immune cells, blood vessels, and an abundance of signaling molecules. In recent years, the mechanical properties of the TME have emerged as critical determinants of tumor progression and therapeutic response. Aberrant mechanical cues, including altered tissue architecture and stiffness, contribute to tumor progression, metastasis, and resistance to treatment. Moreover, burgeoning immunotherapies hold great promise for harnessing the immune system to target and eliminate solid malignancies; however, their success is hindered by the hostile mechanical landscape of the TME, which can impede immune cell infiltration, function, and persistence. Consequently, understanding TME mechanoimmunology - the interplay between mechanical forces and immune cell behavior - is essential for developing effective solid cancer therapies. Here, we review the role of TME mechanics in tumor immunology, focusing on recent therapeutic interventions aimed at modulating the mechanical properties of the TME to potentiate T cell immunotherapies, and innovative assays tailored to evaluate their clinical efficacy.

Exploring immune status in peripheral blood and tumor tissue in association with survival in patients with multi-organ metastatic colorectal cancer

ABSTRACT Colorectal cancer (CRC) raises considerable clinical challenges, including a high mortality rate once the tumor spreads to distant sites. At this advanced stage, more accurate prediction of prognosis and treatment outcome is urgently needed. The role of cancer immunity in metastatic CRC (mCRC) is poorly understood. Here, we explore cellular immune cell status in patients with multi-organ mCRC. We analyzed T cell infiltration in primary tumor sections, surveyed the lymphocytic landscape of liver metastases, and assessed circulating mononuclear immune cells. Besides asking whether immune cells are associated with survival at this stage of the disease, we investigated correlations between the different tissue types; as this could indicate a dominant immune phenotype. Taken together, our analyses corroborate previous observations that higher levels of CD8+ T lymphocytes link to better survival outcomes. Our findings therefore extend evidence from earlier stages of CRC to indicate an important role for cancer immunity in disease control even after metastatic spreading to multiple organs. This finding may help to improve predicting outcome of patients with mCRC and suggests a future role for immunotherapeutic strategies.

Emulator-Based Bayesian Calibration of the CISNET Colorectal Cancer Models.

To calibrate Cancer Intervention and Surveillance Modeling Network (CISNET)'s SimCRC, MISCAN-Colon, and CRC-SPIN simulation models of the natural history colorectal cancer (CRC) with an emulator-based Bayesian algorithm and internally validate the model-predicted outcomes to calibration targets. We used Latin hypercube sampling to sample up to 50,000 parameter sets for each CISNET-CRC model and generated the corresponding outputs. We trained multilayer perceptron artificial neural networks (ANNs) as emulators using the input and output samples for each CISNET-CRC model. We selected ANN structures with corresponding hyperparameters (i.e., number of hidden layers, nodes, activation functions, epochs, and optimizer) that minimize the predicted mean square error on the validation sample. We implemented the ANN emulators in a probabilistic programming language and calibrated the input parameters with Hamiltonian Monte Carlo-based algorithms to obtain the joint posterior distributions of the CISNET-CRC models' parameters. We internally validated each calibrated emulator by comparing the model-predicted posterior outputs against the calibration targets. The optimal ANN for SimCRC had 4 hidden layers and 360 hidden nodes, MISCAN-Colon had 4 hidden layers and 114 hidden nodes, and CRC-SPIN had 1 hidden layer and 140 hidden nodes. The total time for training and calibrating the emulators was 7.3, 4.0, and 0.66 h for SimCRC, MISCAN-Colon, and CRC-SPIN, respectively. The mean of the model-predicted outputs fell within the 95% confidence intervals of the calibration targets in 98 of 110 for SimCRC, 65 of 93 for MISCAN, and 31 of 41 targets for CRC-SPIN. Using ANN emulators is a practical solution to reduce the computational burden and complexity for Bayesian calibration of individual-level simulation models used for policy analysis, such as the CISNET CRC models. In this work, we present a step-by-step guide to constructing emulators for calibrating 3 realistic CRC individual-level models using a Bayesian approach. We use artificial neural networks (ANNs) to build emulators that surrogate complex individual-based models to reduce the computational burden in the Bayesian calibration process.ANNs showed good performance in emulating the CISNET-CRC microsimulation models, despite having many input parameters and outputs.Using ANN emulators is a practical solution to reduce the computational burden and complexity for Bayesian calibration of individual-level simulation models used for policy analysis.This work aims to support health decision scientists who want to quantify the uncertainty of calibrated parameters of computationally intensive simulation models under a Bayesian framework.

Co-Culture In Vitro Systems to Reproduce the Cancer-Immunity Cycle.

Fundamental cancer research and the development of effective counterattack therapies both rely on experimental studies detailing the interactions between cancer and immune cells, the so-called cancer-immunity cycle. In vitro co-culture systems combined with multiparametric flow cytometry (mFC) and tumor-on-a-chip microfluidic devices (ToCs) enable simple, fast, and reliable monitoring and characterization of each step of the cancer-immunity cycle and lead to the identification of the mechanisms responsible for tipping the balance between cancer immunosurveillance and immunoevasion. A thorough understanding of the dynamic interplays between cancer and immune cells provides critical insights to outsmart tumors and will accelerate the pace of therapeutic personalization and optimization in patients. Specifically, here we detail a straightforward mFC- and ToC-assisted protocol for unraveling the dynamic complexities of each step of the cancer-immunity cycle in murine cancer cell lines and mouse-derived immune cells and focus on immunosurveillance. Considering the time- and cost-related features of this protocol, it is certainly feasible on a large scale. Moreover, with minor variations, this protocol can be both adapted to human cancer cell lines and human peripheral-blood-derived immune cells and combined with genetic and/or pharmacologic inhibition of specific pathways in order to identify biomarkers of immune response.

Factor of time in dendritic cell (DC) maturation: short-term activation of DCs significantly improves type 1 cytokine production and T cell responses

Dendritic cells (DCs) have been intensively studied in correlation to tumor immunology and for the development DC-based cancer vaccines. Here, we present the significance of the temporal aspect of DC maturation for the most essential subsequent timepoint, namely at interaction with responding T cells or after CD40-Ligand restimulation. Mostly, DC maturation is still being achieved by activation processes which lasts 24 h to 48 h. We hypothesized this amount of time is excessive from a biological standpoint and could be the underlying cause for functional exhaustion. Indeed, shorter maturation periods resulted in extensive capacity of monocyte-derived DCs to produce inflammatory cytokines after re-stimulation with CD40-Ligand. This effect was most evident for the primary type 1 polarizing cytokine, IL-12p70. This capacity reached peak at 6 h and dropped sharply with longer exposure to initial maturation stimuli (up to 48 h). The 6 h maturation protocol reflected superiority in subsequent functionality tests. Namely, DCs displayed twice the allostimulatory capacity of 24 h- and 48 h-matured DCs. Similarly, type 1 T cell response measured by IFN-γ production was 3-fold higher when CD4+ T cells had been stimulated with shortly matured DC and over 8-fold greater in case of CD8+ T cells, compared to longer matured DCs. The extent of melanoma-specific CD8+ cytotoxic T cell induction was also greater in case of 6 h DC maturation. The major limitation of the study is that it lacks in vivo evidence, which we aim to examine in the future. Our findings show an unexpectedly significant impact of temporal exposure to activation signals for subsequent DC functionality, which we believe can be readily integrated into existing knowledge on in vitro/ex vivo DC manipulation for various uses. We also believe this has important implications for DC vaccine design for future clinical trials.

Toll-like receptors in breast cancer immunity and immunotherapy.

Toll-like receptors (TLRs) are a key family of pattern recognition receptors (PRRs) in the innate immune system. The activation of TLRs will not only prevent pathogen infection but also respond to damage-induced danger signaling. Increasing evidence suggests that TLRs play a critical role in breast cancer development and treatment. However, the activation of TLRs is a double-edged sword that can induce either pro-tumor activity or anti-tumor effect. The underlying mechanisms of these opposite effects of TLR signaling in cancer are not fully understood. Targeting TLRs is a promising strategy for improving breast cancer treatment, either as monotherapies or by improving other current therapies. Here we provide an update on the role of TLRs in breast cancer immunity and immunotherapy.

Effects of exercise during active surveillance for prostate cancer: A systematic review and meta-analysis.

The efficacy of exercise in men with prostate cancer (PCa) on active surveillance (AS) remains unclear. In this meta-analysis, we aimed to examine the effects of exercise in PCa patients on AS. A literature search was conducted in PubMed, EMBASE, and the Cochrane Library using search terms, including exercise, PCa, AS, and randomized controlled trials (RCTs). The means and standard deviations for peak oxygen consumption (VO2peak), prostate-specific antigen (PSA) levels, and quality of life (QoL) were extracted for the intervention and control groups. A random-effects model was used to summarize the effects of exercise. Of the 158 identified studies, six RCTs with 332 patients were included. The interventions included lifestyle modifications (aerobic exercise + diet) in three studies and different exercise modalities in three studies. The intervention duration was 2-12 months; three interventions were supervised and three were self-directed. The pooled weighted mean difference between exercise and usual care for VO2peak was 1.42 mL/kg/min (95% confidence interval [CI]: 0.30 to 2.54, P ≤ 0.001). A non-significant effect was observed for QoL (pooled standardized mean difference [SMD]: 0.24, 95% CI: - 0.03 to 0.51, P = 0.08) which became statistically significant and stronger after excluding one outlier study (P < 0.001). Exercise also had a positive effect on PSA levels (pooled SMD: - 0.43, 95% CI: - 0.87 to 0.01, P = 0.05). Exercise improves cardiorespiratory fitness and may improve QoL and PSA levels in men with PCa on AS. Further studies with larger sample sizes are warranted to obtain more reliable results.

Deciphering Natural Killer Cell Cytotoxicity Against Medulloblastoma in vitro and in vivo: Implications for Immunotherapy.

Medulloblastoma (MB) is the most prevalent paediatric brain tumour. Despite improvements in patient survival with current treatment strategies, the quality of life of these patients remains poor owing to the sequelae and relapse risk. An alternative, or, in addition to the current standard treatment, could be considered immunotherapy, such as Natural Killer cells (NK). NK cells are cytotoxic innate lymphoid cells that play a major role in cancer immunosurveillance. To date, the mechanism of cytotoxicity of NK cells, especially regarding the steps of adhesion, conjugation, cytotoxic granule polarisation in the cell contact area, perforin and granzyme release in two and three dimensions, and therapeutic efficacy in vivo have not been precisely described. Each step of NK cytotoxicity against the three MB cell lines was explored using confocal microscopy for conjugation, Elispot for degranulation, flow cytometry, and luminescence assays for target cell necrosis and lysis and mediators released by cytokine array, and then confirmed in a 3D spheroid model. Medulloblastoma-xenografted mice were treated with NK cells. Their persistence was evaluated by flow cytometry, and their efficacy in tumour growth and survival was determined. In addition, their effects on the tumour transcriptome were evaluated. NK cells showed variable affinities for conjugation with MB target cells depending on their subgroup and cytokine activation. Chemokines secreted during NK and MB cell co-culture are mainly associated with angiogenesis and immune cell recruitment. NK cell cytotoxicity induces MB cell death in both 2D and 3D co-culture models. NK cells initiated an inflammatory response in a human MB murine model by modulating the MB cell transcriptome. Our study confirmed that NK cells possess both in vitro and in vivo cytotoxic activity against MB cells and are of interest for the development of immunotherapy.

Effect of tumorspheres cultured from circulating cancer stem cells on the innate checkpoint CD47 in patients with breast cancer.

e13113 Background: Circulating cancer cells, and in particular their very rare subpopulation, circulating cancer stem cells (cCSCs), are responsible for recurrence and metastasis. The exact role of cCSCs in escape of cancer from immunosurveillance is still unknown, but recent studies reported that increased expression of CD47 enable cancer cells to evade phagocytosis by macrophages and promote the cancer stem cell phenotype. Understanding the mechanisms behind this CD47 overexpression in cancer stem cells is critical for developing more effective immunotherapy. Therefore, in the current study, we evaluated the incidence and clinical relevance of tumorspheres cultured from cCSCs expressing CD47 in breast cancer patients. Methods: 110 patients with breast cancer in different stages of disease were included in this study. The determination of cCSCs was performed using the sphere-forming assay. Additionally, anti-CD47 antibody staining was applied to examine CD47 expression on breast tumorspheres. Results: We have developed an innovative in vitro platform for detection of cCSCs from peripheral blood of cancer patients. The number of tumorspheres was associated with disease progression and aggressiveness of primary tumor. Patients with metastatic disease had statistically more tumorspheres as compared to patients without metastasis (30 vs 10/100µl blood, p&lt;0.05). Patients with multiple metastasis had more tumorspheres compared to patients with single metastases (60 vs 30/100µl blood, p&lt;0.05). CD47 was highly expressed in tumorspheres, which are enriched from circulating cancer stem cells and associated with triple-negative tumors. We also observed high heterogeneity of CD47 expression between the tumorspheres of a patient and between the patients. Conclusions: The number of tumorspheres cultured from peripheral blood directly reflects aggressiveness and proliferation capacity of primary tumor. The presence of tumorspheres with high expression of CD47 might suggest their immunoregulatory potential. Better understanding of the interaction between cCSCs and tumor immunology may improve outcome especially in high-risk patients in part by attacking cCSCs and disinhibiting innate immunity.

KANSURVIVE: Testing a telementoring model for improving cancer survivorship care in rural practice.

e13791 Background: Cancer survivors require long-term, coordinated care to address the physical, emotional, and psychosocial effects of cancer and its treatment. KanSurvive, a single arm feasibility trial, evaluated the effectiveness of the KanSurvive ECHO intervention combined with practice facilitation (PF) to promote better adoption of evidence-based practice (EBP) survivorship care guidelines for breast, colorectal, lung, and prostate cancer among rural survivors. Methods: Fifteen primary care clinics in Kansas (80% in RUCA codes 4-10), including 62 healthcare professionals, were invited to participate in four, 1-hour Project ECHO telementoring program held in 2021. Real-time videoconferencing sessions covered EBP survivorship guidelines for breast, colorectal, lung, and prostate cancer. Clinics used brief plan-do-study-act cycles with PF supporting implementation of the quality improvement process. Utilizing the National Quality Forum framework, a performance indicator booklet with established measures in preventive health and cancer survivorship was developed as a data collection and quality improvement resource. Performance indicators included EBP screening actions related to cancer surveillance, lifestyle factors, distress, evidence of a review of family history of cancer, and the patient’s cancer diagnosis documented in the EHR. Results: Three clinics (7 = healthcare professionals) withdrew from the project citing competing demands and a provider leaving the practice. The COVID-19 pandemic delayed project initiation and prevented clinic visits. Recruitment and study procedures were implemented remotely. Clinic staff identified 138 cancer survivors (M = 13, IQR [6-16] per practice) seen in the year pre-intervention, and 129 survivors in the year prior to post-intervention. Pre-intervention, overall tumor surveillance was 91%, but lung cancer surveillance was lower than other tumor types at 70%. Other than surveillance, measures of baseline performance were similar across tumor types: screening for distress 84%, assessment of BMI 97%, screening for tobacco use 83% and documentation of family history 70%. Post-intervention performance indicators were similar except for documentation of family history which increased to 89% (p &lt; 0.01). Conclusions: Standardized survivorship metrics can facilitate quality assessment as part of an ECHO-based cancer survivorship program. Although there are modest opportunities for improvement, PCPs in this study caring for rural patients perform reasonably well across a variety of cancer survivorship performance metrics comparable to national primary care quality measures. Documented assessment of family history of cancer lags other metrics and improved after participation in the KanSurvive telementoring program.

Temporal trends of cancer incidence rates for the most frequent cancer sites in Cyprus (2004-2017).

Cancer is one of the leading causes of morbidity and mortality, worldwide. Little information is available for the temporal trends of cancer in the Mediterranean region, including Cyprus. We aimed to analyze cancer incidence trends overall and by sex for the period 2004-2017 regarding the five most common cancer sites for the population of Cyprus. Data were obtained from the nationwide cancer registry dataset that included 27 017 total cancer cases in Cyprus (2004-2017). We estimated the crude, sex-, and age-specific, as well as age-standardized (ASR) cancer incidence rates and we analyzed the time trends of ASR using the joinpoint regression program. For the general population (0-85+ years of age), the most common cancer sites in descending order, were breast, prostate, lung, colorectal, and thyroid cancer. During the study period, breast and thyroid cancer ASR presented a significant (p < .05) increasing temporal trend. Lung cancer ASRs seemed to stabilize (no increase or decrease) during the more recent years (2009 onwards) for both sexes; a similar pattern was observed for colorectal cancer in males. The ASRs of prostate cancer in men were in steady decline from 2012 onwards and the same was observed for the female ASRs of colorectal cancer from 2007 onwards. The colorectal cancer ASR temporal patterns overall, during the whole study period appeared unchanged. This temporal analysis would feed into cancer surveillance and control programs that focus on prevention, early detection, and treatment, particularly for cancer sites of higher mortality rates or those with temporally increasing trends.

Impact of COVID-19 on post-treatment breast cancer surveillance and outcomes.

e23114 Background: Little is known about the impact of the COVID-19 pandemic on post-treatment surveillance for patients diagnosed with breast cancer. Disruptions in recommended cancer surveillance screening to detect progression or recurrence could impact long-term outcomes. In this study, we compared use of recommended surveillance screening in pre- and post-COVID time periods for patients diagnosed with breast cancer within a large integrated healthcare system, Kaiser Permanente Southern California (KPSC). We also evaluated detection of breast cancer recurrence or progression. Methods: We identified patients in post-treatment surveillance for early-stage breast cancer in two time periods, pre-COVID and post-COVID. Pre-COVID included patients diagnosed 01/01/2015-12/31/2016 with 2 years of follow-up time through 12/31/2019; post-COVID included patients diagnosed 06/01/2018-05/31/2020 with 2 years of follow-up time through 05/31/2023. Eligible patients were diagnosed with stage 0-II breast cancer and received curative surgery. We excluded patients with multiple cancers, and those who disenrolled from the health plan, died, or were referred to hospice within the 2-year surveillance period. Based on NCCN guidelines, we identified the proportion of patients who underwent annual breast imaging during each year of the surveillance period. A log Poisson model examined the association between imaging and COVID period; covariates included patient age, race/ethnicity, cancer stage, treatment, and comorbidity score. We identified cancer recurrence or progression using diagnostic, treatment, and imaging codes. Results: We identified 3,369 pre-COVID patients and 3,925 post-COVID patients; groups were similar (Table 1). A significantly smaller proportion of post-COVID patients received surveillance screening (first surveillance year: 85% in the pre-COVID group vs. 77% post-COVID, p = 0.001; second year: 83% vs. 80%, p = 0.01). Patients were 4% less likely to receive imaging post-COVID compared to pre-COVID (adjusted OR 0.96, 95% CI: 0.94-0.98). Similar percentages of patients had breast cancer recurrence or progression in the pre-COVID (2.7%) and post-COVID (2.5%) periods (p-value = 0.44). Conclusions: Fewer post-treatment breast cancer patients received recommended annual breast cancer screening for surveillance in the post-COVID period compared to pre-COVID, but breast cancer recurrence or progression was similar between groups. Given the less frequent surveillance in the post-COVID period, cancer recurrence and progression should be evaluated over 5- and 10-year periods as data become available. [Table: see text]

Addressing cancer survivorship needs in geriatric survivors: Feasibility of a primary care–based survivorship clinic.

e13797 Background: The largest segment of the growing population of cancer survivors is at least 65 years of age, a population that is likely to have comorbidities and requires co-management between primary care and specialist physicians. The goal of this study was to characterize care for this patient population in a specialized primary care for cancer survivorship clinic that manages survivorship issues and ongoing primary care in one place. Methods: This study collected demographic and clinical data via electronic chart review of patients aged 65 and over who established care in the Primary Care for Cancer Survivorship clinic at an academic center from November 1, 2021 through November 30, 2023. Results: Out of 228 total patients who established primary care in the clinic, 63 patients were over the age of 65. The mean age of the group was 73, with the range 65 to 90. Seventy-three percent of patients were female, and 27% were male. The most common cancers were breast (38%), lung (10%), leukemia (13%), lymphoma (8%), prostate (8%), and multiple myeloma (6%). Twenty-five patients (40%) had active disease, 37 patients (58%) were post-treatment, and 1 patient was a “previvor” with Li-Fraumeni syndrome. Cancer surveillance was discussed with 81% of patients, and 2 patients (5% of post-treatment patients) were diagnosed with recurrent cancer. Secondary cancer screening was performed in 86% of patients, with no secondary cancers diagnosed. The most common referral sources were medical oncology from the same institution (40%), self-referrals (25%), and hematology (13%). The average number of visits per year was 2.8 with 61% in person and 29% via video. Cardiovascular risk was addressed in 98% of patients; 32% had at least one cardiovascular medication started and 17% were referred to a cardiologist for management. Long term and late effects were addressed in 84% of patients, including mental health (70%), bone health (65%), cognitive function (21%), cancer-related fatigue (13%), and sexual health (11%). Ten percent had end-of-life issues or goals of care addressed. Conclusions: This study demonstrates the feasibility of a primary care-based cancer survivorship clinic to address the ongoing needs of geriatric cancer survivors. Quality review of these patient encounters can identify gaps in care delivery and inform new models of comprehensive care for the growing geriatric cancer survivor population. [Table: see text]

Machine learning‐based identification of a cell death‐related signature associated with prognosis and immune infiltration in glioma

AbstractAccumulating evidence suggests that a wide variety of cell deaths are deeply involved in cancer immunity. However, their roles in glioma have not been explored. We employed a logistic regression model with the shrinkage regularization operator (LASSO) Cox combined with seven machine learning algorithms to analyse the patterns of cell death (including cuproptosis, ferroptosis, pyroptosis, apoptosis and necrosis) in The Cancer Genome Atlas (TCGA) cohort. The performance of the nomogram was assessed through the use of receiver operating characteristic (ROC) curves and calibration curves. Cell‐type identification was estimated by using the cell‐type identification by estimating relative subsets of known RNA transcripts (CIBERSORT) and single sample gene set enrichment analysis methods. Hub genes associated with the prognostic model were screened through machine learning techniques. The expression pattern and clinical significance of MYD88 were investigated via immunohistochemistry (IHC). The cell death score represents an independent prognostic factor for poor outcomes in glioma patients and has a distinctly superior accuracy to that of 10 published signatures. The nomogram performed well in predicting outcomes according to time‐dependent ROC and calibration plots. In addition, a high‐risk score was significantly related to high expression of immune checkpoint molecules and dense infiltration of protumor cells, these findings were associated with a cell death‐based prognostic model. Upregulated MYD88 expression was associated with malignant phenotypes and undesirable prognoses according to the IHC. Furthermore, high MYD88 expression was associated with poor clinical outcomes and was positively related to CD163, PD‐L1 and vimentin expression in the in‐horse cohort. The cell death score provides a precise stratification and immune status for glioma. MYD88 was found to be an outstanding representative that might play an important role in glioma.

The effect of distance reiki on patient reported quality of life, correlated with changes in immune repertoires among patients with multiple myeloma: A pilot study.

e23199 Background: Psychological distress and diminished health related quality of life (HRQOL) is associated with multiple myeloma (MM). Complementary and alternative medicine (CAM) is an adjunct to traditional medicine. T-cells are essential to the adaptive immune system. The complementarity determining region (CDR3) of the T cell receptor formed by combination of the V,D,J regions is highly variable and critical for antigen specificity. PCR is used to analyze the TCR-CDR3 to monitor T-cell clonotypes as a measure of antigen specific T cell responses and thereby cancer immunity. Reiki is a Japanese energy healing technique involving noninvasive light touch to modulate energy fields. The primary aim was feasibility and acceptability of Reiki within a structured medical paradigm. Secondary aims were changes in HRQOL and T-cell receptor repertoires with Reiki. Methods: Adult MM patients (pts) on a stable regimen were eligible. Pts randomized in a 1:1:1 to weekly True Reiki (Treiki), Simulated Reiki (Sreiki) or no intervention (NI). The PROMIS-29® assessed HRQOL. A “Was it Worth it” (WIWI) questionnaire was administered post intervention to assess the experience. TCR-CDR3 sequencing was performed on PBMCs at enrollment and end of therapy to determine immune repertoire changes. Samples underwent library preparation and next generation sequencing for TCR repertoire analysis by iRepertoire® Results: Thirty pts were randomized into 3 arms between 12/2020 to 4/2022. Median age 62.5 (range 27-76), 18/30 (60%) female, median time to diagnosis was 48 mo (Range 7-221), 50% had high risk FISH,(90%) had prior ASCT and received median 2 (range 1-13) lines of therapy prior to enrollment. No pts relapsed or progressed during study period. Using WIWI 100% of pts in Treiki and 75% in Sreiki arms found the therapy useful and would do it again; 100% Treiki pts and 87.5% in the Sreiki arm would recommend the study to others. No statistical difference between groups in any HRQOL domains. Among TCR repertoires, no statistically significant difference was observed between groups with respect to Richness, Shannon entropy, Clonality, Diversity 50 (D50) and Inverse Simpson indexes. Each pt showed substantial variability in certain TCR-CDR3 clones and clonal diversity. Conclusions: We successfully demonstrated acceptability and feasibility of Reiki among MM pts, although no impact on HRQOL was shown. Reiki intervention is an easy non-invasive additional option for pts’ to their conventional therapies. The TCR-CDR3 repertoires showed no difference with the reiki intervention but had significant variability. Further research comparing TCR repertoires between MM and age/sex matched healthy controls is ongoing. T-cell directed therapies are evolving in MM, we plan to analyze if changing diversity of TCR-CDR3 repertoires could define how best to sequence these treatments. Clinical trial information: NCT04783038 .