Treatment Of Cancer Research Articles

B-352 Effects of COVID-19 on Breast Cancer Positivity: A Retrospective and Predictive Study

Abstract Background The COVID-19 pandemic has had a significant impact on the healthcare system, resulting in overall reduction in access to healthcare services, including the suspension of screening programs and postponement of surgeries and medical treatments. The aim of this study was to evaluate the effects of the pandemic on breast cancer positivity from cases received at a laboratory in São Paulo, Brazil. Methods A retrospective analysis of a database from a pathology laboratory in São Paulo, Brazil, was performed during the 2017-2023 period and classified as following: pre-pandemic (January 2017-February 2020), pandemic (March 2020 - April-2022), and post-pandemic (May 2022-December 2023). Cases were classified as negative or positive for malignancies. Positive anatomopathological examinations (breast biopsies and surgical specimens) considered primary, metastatic mesenchymal or endothelial malignancies. The Mann-Kendall test was used to evaluate the trend, and the PACF (Partial Autocorrelation Function) correlogram was used to analyze historical memory for definition of the autoregressive model. The augmented Dickey-Fuller hypothesis test was applied to analyze whether the series is stationary or not, and the first differences test was applied. The ARIMA model was used for the estimates (1,1,1). Statistics were performed using the gretl software and pymannkendall library in the Python language. Results A total of 74,973 samples were evaluated during the 2017-2023 period. In the three-year pre-pandemic period, 32,644 tests were recorded, with an average of 29.34% positive cases. From the analysis of the pre-pandemic time series, there was a positive trend towards an increase in cases (p < 0.0001, z=6.1360, Tau=0.6955). In a non-pandemic scenario, from March 2020 to February 2021, the number of new tests expected would be 11,535; however, in the pandemic period, only 8,904 were observed, a 22.81% reduction on expected cases. According to the historical average positivity rate in the pre-pandemic period, the expected and observed total were, respectively, 3,384 and 2,566 positive cases for malignancy. Conclusions This study reveals a significant decrease of approximately 22.81% in new breast anatomopathological diagnoses during the COVID-19 pandemic in a laboratory in São Paulo, Brazil. For comparison purposes, we identified a 24.17% of missed opportunities on diagnoses of new malignancy-positive cases, compared to the pre-pandemic period. These findings highlight the need for strategies to mitigate the negative effects of the pandemic on the early detection and treatment of breast cancer.

Preparation and Formulation of a New Therapeutic Supplement by the Combination of Dendritic Cells and IPI-549 (Eganelisib) for the Treatment of Breast Cancer in BALB/c Mice

: Dendritic cell-based cancer immunotherapy is considered an innovative and promising approach aimed at enhancing the host's immune response to combat tumors. Additionally, IPI-549 has been identified as a first-line therapeutic option for breast cancer treatment. The objective of this research was to develop and formulate a novel therapeutic supplement by combining dendritic cells with IPI-549 (Eganelisib) for breast cancer treatment. The concurrent administration of dendritic cells and IPI-549 (DC-IPI) was utilized to treat mice and elicit immunological responses triggered by vaccination. Tumor regression and overall survival rates were evaluated across five distinct experimental groups. The administration of tumor cell lysate alongside DC-IPI resulted in a significant reduction in tumor growth and a two- to three-fold increase in the survival duration of treated mice. DC-IPI, whether decorated with mannan or not, elicited stronger responses in terms of delayed-type hypersensitivity, lymphocyte proliferation, and CD107a expression. Moreover, our findings demonstrated a reduction in IL-4 production in the supernatants of splenocyte cultures. A significant reduction in BRCA1 mRNA levels was also observed following treatment with DC-IPI. In conclusion, our results suggest that the DC-IPI antigen delivery system exhibited substantial anti-tumor efficacy in a breast cancer mouse model, representing a potential advancement in immunotherapy for human breast cancer.

Targeting the CSF1/CSF1R signaling pathway: an innovative strategy for ultrasound combined with macrophage exhaustion in pancreatic cancer therapy

Pancreatic cancer (PC) is a highly aggressive and lethal malignancy characterized by a complex tumor microenvironment (TME) and immunosuppressive features that limit the efficacy of existing treatments. This paper reviews the potential of combining ultrasound with macrophage exhaustion in the treatment of pancreatic cancer. Macrophages, particularly tumor-associated macrophages (TAMs), are crucial in pancreatic cancer progression and immune escape. Prolonged exposure to the immunosuppressive TME leads to macrophage exhaustion, reducing their anti-tumor ability and instead promoting tumor growth. The CSF1/CSF1R signaling pathway is key in macrophage recruitment and functional regulation, making it an effective target for combating macrophage exhaustion. Ultrasound technology not only plays a significant role in diagnosis and staging but also enhances therapeutic efficacy by guiding radiofrequency ablation (RFA) and percutaneous alcohol injection (PEI) in combination with immunomodulators. Additionally, ultrasound imaging can monitor the number and functional status of TAMs in real-time, providing a basis for optimizing treatment strategies. Future studies should further investigate the combined use of ultrasound and immunomodulators to refine treatment regimens, address challenges such as individual variability and long-term effects, and offer new hope for pancreatic cancer patients.

First-line treatment of EGFR-mutated non-small cell lung cancer with brain metastases: a systematic review and meta-analysis

This systematic review and network meta-analysis evaluates first-line treatment options for patients with EGFR-mutant non-small cell lung cancer (NSCLC) and brain metastases. We analyzed 24 randomized controlled trials (RCTs) involving 2,682 patients, comparing various EGFR tyrosine kinase inhibitors (TKIs) and combination therapies. Direct comparisons showed that the addition of bevacizumab or chemotherapy to first-generation (1G) EGFR-TKIs improved overall survival (OS) compared to 1G TKIs alone, with HRs of 0.704 (95% CI: 0.433–0.973) and 0.682 (95% CI: 0.464–0.899), respectively. However, third-generation (3G) TKI monotherapy did not significantly improve OS compared with 1G TKIs, with an HR of 0.855 (95% CI: 0.511–1.198). Indirect comparisons suggested that the combination of 3G TKIs with chemotherapy provided the most significant improvements in OS and progression-free survival (PFS), significantly outperforming 3G TKIs, with HRs of OS 1.69 (95% CI: 1.14–3.4) and PFS 2.13 (95% CI: 1.28–3.54). Intracranial PFS was best with 1G TKIs plus bevacizumab. Our findings suggest that 3G EGFR-TKIs in combination with chemotherapy may be the most effective strategy for patients with EGFR-mutant NSCLC and brain metastases, though further head-to-head trials are needed for validation.

Is an Electronic Nose Able to Predict Clinical Response following Neoadjuvant Treatment of Rectal Cancer? A Prospective Pilot Study

Introduction: A watch-and-wait strategy for patients with rectal cancer who achieve a clinical complete response after neoadjuvant (chemo) radiotherapy is a valuable alternative to rectal resection. In this pilot study, we explored the use of an electronic nose to predict response to neoadjuvant therapy by analyzing breath-derived volatile organic compounds. Materials and Methods: A pilot study was performed between 2020 and 2022 on patients diagnosed with intermediate- or high-risk rectal cancer who were scheduled for neoadjuvant therapy. Breath samples were collected before and after (chemo) radiotherapy. A machine-learning model was developed to predict clinical response using curatively treated rectal cancer patients as controls. Results: For developing the machine-learning model, a total of 99 patients were included: 45 patients with rectal cancer and 54 controls. In the training set, the model successfully discriminated between patients with and without rectal cancer, with a sensitivity and specificity of 0.80 and 0.65, respectively, and an accuracy of 0.72. In the test set, the model predicted partial or (near) complete response with a sensitivity and specificity of 0.64 and 0.47, respectively, and an accuracy of 0.58. The AUC of the ROC curve was 0.63. Conclusions: The prediction model developed in this pilot study lacks the ability to accurately differentiate between partial and (near) complete responders with an electronic nose. Machine-learning studies demand a substantial number of patients and operate in a rapidly evolving field. Therefore, the prevalence of disease and duration of a study are crucial considerations for future research.

The Frequency of Urination Dysfunction in Patients Operated on for Rectal Cancer: A Systematic Review with Meta-Analyses

The frequency of long-term urination dysfunction after surgery for rectal cancer remains unclear, yet it is essential to establish this to improve treatment strategies. Randomized controlled trials (RCTs), non-RCTs, and cohort studies were included with patients having undergone sphincter-preserving total (TME) or partial mesorectal excision (PME) for the treatment of primary rectal cancer in this review. The outcome was urination dysfunction reported at least three months postoperatively, both overall urination dysfunction and subdivided into specific symptoms. The online databases PubMed, Embase, and Cochrane CENTRAL were searched, bias was assessed using the Newcastle–Ottawa scale, and results were synthesized using one-group frequency meta-analyses. A total of 55 studies with 15,072 adults were included. The median follow-up was 29 months (range 3–180). The pooled overall urination dysfunction was 21% (95% confidence interval (CI) 12%–30%) 3–11 months postoperatively and 25% (95% CI 19%–32%) ≥12 months postoperatively. Retention and incontinence were common 3–11 months postoperatively, with pooled frequencies of 11% and 14%, respectively. Increased urinary frequency, retention, and incontinence seemed even more common ≥12 months postoperatively, with pooled frequencies of 37%, 20%, and 23%, respectively. In conclusion, one in five patients experienced urination dysfunction more than a year following an operation for rectal cancer.

Clinical Effects of Laparoscopic Radical Colon Cancer Treatment with Complete Mesocolic Resection for Colon Cancer

Objective: This paper aims to evaluate the effect of laparoscopic complete mesocolic resection on the efficacy and survival of patients with colon cancer. Methods: 80 colon cancer patients were included in this study, 40 of whom were treated with traditional radical colon cancer surgery as the control group, and the other 40 were treated with laparoscopic complete mesocolic resection radical colon cancer surgery as the observation group. The study period lasted from April 2022 to April 2023, and the surgical indexes, postoperative recovery, quality of life, and the occurrence of complications of the two groups were monitored throughout the whole process and compared and analyzed. Results: The therapeutic effect of the observation group was better than that of the control group (P < 0.05). The operation time, bleeding volume and postoperative hospitalization time of the observation group were significantly lower than those of the control group, and the number of lymph node dissection was significantly higher than that of the control group, with highly significant differences (all P < 0.001). The postoperative recovery of the observation group (time of first anal defecation, time of first solid food intake, and time of wound healing) was significantly better than that of the control group (all P < 0.001). The quality of life of the observation group was significantly improved with a highly significant correlation (P < 0.001), and the complication rate was significantly lower than that of the control group (P < 0.05). Conclusion: Laparoscopic radical colon cancer surgery with complete mesocolic resection for colon cancer shows better clinical effects and advantages in the treatment of colon cancer, which is worth further promotion and application in clinical practice.

Discovery of CZL-046 with an (S)-3-Fluoropyrrolidin-2-one Scaffold as a p300 Bromodomain Inhibitor for the Treatment of Multiple Myeloma.

E1A binding protein (p300) is a promising therapeutic target for the treatment of cancer. Herein, we report the discovery of a series of novel inhibitors with an (S)-3-fluoropyrrolidin-2-one scaffold targeting p300 bromodomain. The best compound 29 (CZL-046) shows potent inhibitory activity of p300 bromodomain (IC50 = 3.3 nM) and antiproliferative activity in the multiple myeloma (MM) cell line (OPM-2 IC50 = 51.5 nM). 29 suppressed the mRNA levels of c-Myc and IRF4 and downregulated the expression of c-Myc and H3K27Ac. Compared to the lead compound 5, 29 exhibits significantly improved in vitro and in vivo metabolic properties. Oral administration of 29 with 30 mg/kg achieved a TGI value of 44% in the OPM-2 xenograft model, accompanied by good tolerability. The cocrystal structure of CREB binding protein bromodomain with 29 provides an insight into the precise binding mode. The results demonstrate that 29 is a promising p300 bromodomain inhibitor for the treatment of MM.

Insights into the Molecular Structure, Stability, and Biological Significance of Non-Canonical DNA Forms, with a Focus on G-Quadruplexes and i-Motifs

This article provides a comprehensive examination of non-canonical DNA structures, particularly focusing on G-quadruplexes (G4s) and i-motifs. G-quadruplexes, four-stranded structures formed by guanine-rich sequences, are stabilized by Hoogsteen hydrogen bonds and monovalent cations like potassium. These structures exhibit diverse topologies and are implicated in critical genomic regions such as telomeres and promoter regions of oncogenes, playing significant roles in gene expression regulation, genome stability, and cellular aging. I-motifs, formed by cytosine-rich sequences under acidic conditions and stabilized by hemiprotonated cytosine–cytosine (C:C+) base pairs, also contribute to gene regulation despite being less prevalent than G4s. This review highlights the factors influencing the stability and dynamics of these structures, including sequence composition, ionic conditions, and environmental pH. Molecular dynamics simulations and high-resolution structural techniques have been pivotal in advancing our understanding of their folding and unfolding mechanisms. Additionally, the article discusses the therapeutic potential of small molecules designed to selectively bind and stabilize G4s and i-motifs, with promising implications for cancer treatment. Furthermore, the structural properties of these DNA forms are explored for applications in nanotechnology and molecular devices. Despite significant progress, challenges remain in observing these structures in vivo and fully elucidating their biological functions. The review underscores the importance of continued research to uncover new insights into the genomic roles of G4s and i-motifs and their potential applications in medicine and technology. This ongoing research promises exciting developments in both basic science and applied fields, emphasizing the relevance and future prospects of these intriguing DNA structures.

State of Geographic Access to Cancer Treatment Trials in the United States: Are Studies Located Where Patients Live?

In this study, we describe the geographic distribution of US cancer treatment trials to identify disparities and opportunities for targeted improvements in access to research for people with cancer. US-based phase I-III cancer treatment trials registered on ClinicalTrials.gov were tabulated for the years they were open to enrollment (2017-2022), overall and by county, and supplemented with data from the US Census Bureau, National Cancer Institute, Centers for Disease Control and Prevention, and US Department of Agriculture. We evaluated geographic differences in trial availability. We assessed 5-year trends in trials per capita and mapped 1-hour drive time areas around sites. A total of 6,710 trials were open to enrollment in 2022 across 1,836 sites. Trials increased by 4%, whereas sites decreased by 3% annually per capita from 2017. Seventy percent of US counties had no reported active trials in 2022 (2,211/3,143), representing 19% of people age ≥55 years. Eighty-six percent of nonmetropolitan counties had no trials versus 44% of metropolitan counties. Trial availability varied by county-level cancer mortality and social vulnerability (an index derived from demographic and socioeconomic data from the US Census). Eighteen percent of counties without trials had oncologist care sites (n = 618). Notably, 26% of people age ≥55 years lived beyond an hour drive of a site with ≥100 trials. Most US counties have limited to no trial offerings, a disparity magnified in counties that are nonmetropolitan, with high social vulnerability, and with high cancer mortality. Effort to facilitate diverse site participation is needed to promote equitable access to trials and to ensure patients participating in trials match the characteristics of patients who will receive interventions once approved. Counties with oncology care sites but no trials provide potential expansion areas.

TRLR-02 TARGETING GLIOBLASTOMA MICROENVIRONMENT TO UNLEASH IMMUNE FORCES

Abstract Brain cancer has persistently eluded therapeutic advances over the past three decades. Here, we aim to raise awareness of the potential differences between the cancer microenvironment within the brain vs. peripheral organ cancers, which may contribute to the therapeutic setbacks observed in brain cancer treatment. While the blood-brain barrier has long been implicated in drug impermeability, its impact on brain cancer may extend far beyond mere drug exclusion. Studies have shown that soluble factors such as VEGF are more concentrated in brain cancer than in any other malignancies. Moreover, recent studies revealed that VEGF, TWEAK, and others can also press on the immune brakes. Therefore, we hypothesize that normalizing the tumor microenvironment could pave the way for effective therapeutic interventions, especially immunotherapy. Our in vitro studies confirmed abundant production of VEGF by glioblastoma 1 (GBM1) cell line, which is exceptionally well scavenged by the anti-VEGF antibody – bevacizumab. Moreover, in vitro, co-culture of T cells and GBM1 cell line without vascular component demonstrated no therapeutic activity of bevacizumab or typical immunotherapeutic drug – anti-PD1 checkpoint inhibitor – nivolumab given in monotherapies. However, a combination of both antibodies revealed therapeutic efficacy in a dose-dependent manner in our experimental system. Currently, intravenous delivery of bevacizumab is the standard of care in patients with glioblastoma recurrence, but its effectiveness has not been proven in this group of patients. Intravenous nivolumab failed in clinical trials. Based on our observations and the negligible penetration of antibodies to the brain, we hypothesize that transiently opening the blood-brain barrier may be necessary to enhance antibody delivery to the tumor microenvironment, alleviate immune suppression, and unlock immune cell activity. Therefore, achieving high antibody concentrations in brain cancer tissue, coupled with a combination of classic checkpoint inhibitors with scavengers of soluble immunosuppressive molecules, could herald a new era of brain cancer therapy.

The branched N-glycan of PD-L1 predicts immunotherapy responses in patients with recurrent/metastatic HNSCC

Immunotherapy has revolutionized cancer treatment, but the lack of a reliable predictive biomarker for treatment response remains a challenge. Alpha-1,6-Mannosylglycoprotein 6-β-N-Acetylglucosaminyltransferase 5 (MGAT5) is a key regulator of complex N-glycan synthesis, and its dysregulation is associated with cancer progression. The lectin Phaseolus vulgaris leukoagglutinin (PHA-L) specifically binds to mature MGAT5 products. Previous studies have indicated elevated PHA-L staining in head and neck squamous cell carcinoma (HNSCC), which implies increased activity of MGAT5. However, the specific role of MGAT5 in HNSCC remains unclear. In this study, we found significantly higher PHA-L staining and MGAT5 expression in HNSCC tumors compared to adjacent non-tumor tissues. Using a mass spectrometry (MS)-based glycoproteomic approach, we identified 163 potential protein substrates of MGAT5. Functional analysis revealed that protein substrates of MGAT5 regulated pathways related to T cell proliferation and activation. We further discovered that PD-L1 was among the protein substrates of MGAT5, and the expression of MGAT5 protected tumor cells from cytotoxic T lymphocyte (CTL) killing. Treatment of nivolumab alleviated the protective effects of MGAT5 on CTL activity. Consistently, patients with MGAT5-positive tumors showed improved responses to immunotherapy compared to those with MGAT5-negative tumors. Using purified PD-L1 from HNSCC cells and a glycoproteomic approach, we further deciphered that the N35 and N200 sites carry the majority of complex N-glycans on PD-L1. Our findings highlight the critical role of MGAT5-mediated branched N-glycans on PD-L1 in modulating the interaction with the immune checkpoint receptor PD-1. Consequently, we propose that MGAT5 could serve as a biomarker to predict patients’ responses to anti-PD-1 therapy. Furthermore, targeting the branched N-glycans at N35 and N200 of PD-L1 may lead to the development of novel diagnostic and therapeutic approaches.

Doxorubicin-loaded methoxy-intercalated kaolinite as a repackaging of doxorubicin for an enhanced breast cancer treatment: in vitro and in vivo investigation.

Doxorubicin is one of the most common wide-spectrum chemotherapeutics. However, its efficacy is limited due to off-target accumulation and selectivity issues. In this study, we compared the anti-cancer effect and biocompatibility of KaoliniteMeOH-Dox, a doxorubicin repackaging, to doxorubicin monotherapy. The formulation was extensively tested using transmission electron microscopy, dynamic light scattering, zeta potential, Fourier transform infrared, x-ray diffraction, and in vitro drug release. The MTT assay measured MCF-7 cell growth inhibition in vitro. In vivo testing involved 20 naïve mice and 40 Ehrlich solid tumor-inoculated mice. The tumor size was monitored for 18 days. In all experimental groups, tumor and cardiac tissues were evaluated for cytotoxicity and genotoxicity by addressing oxidative stress, histopathology, and comet assay. We found that kaoliniteMeOH-Dox has many advantages in terms of size, charge, shape, high loading efficiency (90.16%), and pH-dependent release. The MTT assay showed that the formulation outperformed doxorubicin in growth inhibition and selectivity. In vivo, research showed that kaoliniteMeOH-Dox suppressed tumors by 86.075% compared to 60.379% for free doxorubicin. Histological analysis showed that kaoliniteMeOH-Dox reduced tumor size, metastasis, and carcinogenic oxidative stress and inflammation in mice without harming naive mice. Based on the obtained data, the kaoliniteMeOH-Dox formulation holds promise for breast cancer treatment and warrants further investigation.

Reshaped Local and Systemic Immune Responses Triggered by a Biomimetic Multifunctional Nanoplatform Coordinating Multi-Pathways for Cancer Therapy.

Immunotherapy has fundamentally transformed the clinical cancer treatment landscape; however, achieving intricate and multifaceted modulation of the immune systems remains challenging. Here, a multipathway coordination of immunogenic cell death (ICD), autophagy, and indoleamine 2,3-dioxygenase-1 (IDO1) was achieved by a biomimetic nano-immunomodulator assembled from a chemotherapeutic agent (doxorubicin, DOX), small interfering RNA (siRNA) molecules targeting IDO1 (siIDO1), and the zeolitic imidazolate framework-8 (ZIF-8). After being camouflaged with a macrophage membrane, the biomimetic nanosystem, named mRDZ, enriched in tumors, which allowed synergistic actions of its components within tumor cells. The chemotherapeutic intervention led to a compensatory upregulation in the expression of IDO1, consequently exerting an inhibitory effect on the reactive oxygen species (ROS) and autophagic responses triggered by DOX and ZIF-8. Precise gene silencing of IDO1 by siIDO1 alleviated its suppressive influence, thereby facilitating increased ROS production and improved autophagy, ultimately bolstering tumor immunogenicity. mRDZ exhibited strong capability to boost potent local and systemic antitumor immune responses with a feature of memory, which led to the effective suppression of the growth, lung metastasis, and recurrence of the tumor. Serving as an exemplary model for the straightforward and potent reshaping of the immune system against tumors, mRDZ offers valuable insights into the development of immunomodulatory nanomaterials for cancer therapy.

Single-component artificial urinary sphincter: Outcomes from one centre in Portugal.

Radical prostate cancer treatment is the predominant cause of iatrogenic stress urinary incontinence (SUI) in men, significantly impacting their quality of life (QoL). This prospective single-center study in Portugal aimed to evaluate the outcomes of men with moderate-to-severe SUI treated with a single-component artificial urinary sphincter (AUS). Male patients with iatrogenic moderate-to-severe SUI, determined by a 24-hour pad weight test, were included. The single-component device comprises a cuff linked to a pump unit through a kink-resistant tube. The implantation involved perineal incision for cuff placement and an inguinal incision for pump and tank positioning within the scrotum. Complications, pad usage, perioperative complications (Clavien-Dindo classification), and quality of life assessment using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) questionnaire were documented. Between May 2021 and March 2023, 20 consecutive single-component AUS insertions were conducted at a Portuguese urology department. Follow-up concluded in July 2023, with a mean follow-up duration of 15 months (range: 5-27). Four patients experienced complications necessitating device revision or removal (erosion = 2, infection = 1, mechanical failure = 1). Social continence (0/1 pad/day) was achieved in 70% (14/20 patients), while 30% (6/20 patients) experienced incontinence. Perioperatively, one patient was classified as grade 2, while the remaining were grade 0/1 in the Clavien-Dindo classification. The mean ICIQ-SF score reduction was 10.5 points. The single-component AUS shows promising efficacy in managing moderate-to-severe male SUI, offering a good success rate, acceptable complications, improved QoL, and a straightforward surgical procedure.

Localization and Tumor Growth Inhibition of I-131-Labeled Monoclonal Antibody ERIC1 in a Subcutaneous Xenograft Model of Small Cell Lung Cancer in SCID Mice

This study evaluates the efficacy of [131I]I-ERIC1 in targeting and inhibiting the growth of SCLC tumors in mice, focusing on tumor accumulation and regression and potential side effects. NCAM-positive NCI-H69 SCLC cells were implanted in CB 17 SCID mice, and [131I]I-ERIC1 biokinetics were measured in organs and tissues at four post-injection time points (24, 72, 96, and 120 h). The experimental series compared tumor growth, survival, and changes in blood counts among three treatment groups (1, 2, or 3 MBq) and a control group, with treatments initiated either two or five days post implantation. [131I]I-ERIC1 was synthesized with >95% radiochemical purity and a specific activity of 15 TBq/mmol. Tumor activity peaked at 31.5 ± 6.6% ID/g after four days, demonstrating significant antitumor efficacy, which resulted in sustained remission and extended survival. Hematological toxicity was observed, with the optimal dose identified as 2 MBq per animal administered two days post implantation. [131I]I-ERIC1 shows promise as a theranostic agent for personalized cancer treatment by effectively targeting SCLC tumors with manageable side effects. However, further studies are required to optimize dosing strategies and minimize toxicity.

CFD Simulations of a Loss of Heat Sink Experiment in the McMaster Nuclear Reactor

The McMaster nuclear reactor (MNR) is an important research facility that not only provides researchers with neutrons for fundamental science, but also supplies the medical industry with isotopes used for cancer treatment. To ensure the safety and performance of the MNR, modeling of the thermal hydraulics during nominal and accidental conditions is required. For such a task, system codes are customarily used. While system codes can assess the safety aspects of complex thermal–hydraulic systems, the question arises whether such systems can be modeled appropriately in a three-dimensional manner, such as computation fluid dynamics (CFD), while capturing the thermal mixing of the coolant. Modeling the thermal hydraulics of nuclear research reactors using CFD is relatively new. Therefore, validating such methods against experimental data is of utmost importance. The validation of CFD is the main focus of this work. More specifically, the influence of the loss of heat sink on the pool temperature is assessed using the CFD code Ansys CFX. The validation basis was provided by an experiment performed at the MNR in March 2023. In this experiment, the secondary heat removal system was intentionally shut down, and the pool temperature was measured in a few positions. The results obtained by modeling the loss of heat sink in the MNR using Ansys CFX agree well with the experiment.

Advancements of metallic nanoparticles: A promising frontier in cancer treatment.

The incidence of cancer is increasing and evolving as a major source of mortality. Nanotechnology has garnered considerable scientific interest in recent decades and can offer a promising solution to the challenges encountered with traditional chemotherapy. Nanoparticle utilization holds promise in combating cancer and other diseases, offering exciting prospects for drug delivery systems and medicinal applications. Metallic nanoparticles exhibit remarkable physical and chemical properties, such as their minute size, chemical composition, structure, and extensive surface area, rendering them versatile and cost-effective. Research has demonstrated their significant and beneficial impact on cancer treatment, characterized by enhanced targeting abilities, gene activity suppression, and improved drug delivery efficiency. By incorporating targeting ligands, functionalized metal nanoparticles ensure precise energy deposition within tumors, thereby augmenting treatment accuracy. Moreover, beyond their therapeutic efficacy, metal nanoparticles serve as valuable tools for cancer cell visualization, contributing to diagnostic techniques. Utilizing metal nanoparticles in therapeutic systems allows for simultaneous cancer diagnosis and treatment, while also facilitating controlled drug release, thus revolutionizing cancer care. This narrative review investigates the advancements of metal nanoparticles in cancer treatment, types and mechanisms in targeting cancer cells, application in clinical scenarios, and potential toxicity in medicine.

Counting the days: Exploring healthcare contact days during episodes of cancer care.

233 Background: Cancer diagnosis and treatment brings about not only emotional upheavals but also logistical hurdles of navigating a fragmented healthcare system. Little is known about the frequency of healthcare contact for cancer patients and its implications. Healthcare contact days, defined as the number of days a patient spends in direct contact with healthcare professionals outside of home, measures the patient’s interaction with the healthcare system. Methods: Using historical claims data (Part A institutional and Part B ambulatory claims) from the Enhancing Oncology Model (EOM) for 12 practices in The US Oncology Network covering the period between January 2019 to June 2022, we derived healthcare contact days per episode (6-month care periods initiating with the administration of chemotherapy), counting each unique date once. When patients encountered multiple care settings on a single date, the following hierarchy was used: inpatient (IP) > emergency room (ER) > skilled nursing facility (SNF)> hospice > ambulatory care. We further counted contact days for different services conducted during the ambulatory visits. Results: For the 75,246 episodes, an average of 31.9 days per episode (1 in every 6 days) were spent in healthcare contact. Cancer patients’ healthcare contact was predominantly within ambulatory care, and visits with oncology providers exceeded that with all other specialties. ER and IP visits, generally a representation of acute care events, accounted for <10% of the contact days. Conclusions: During cancer treatment, patients spend approximately one-sixth of their time in healthcare contact. The optimal frequency of contact, pattern of primary care support, care of comorbidities, and the interrelationship between acute care and clinician visits are apt for further exploration. Healthcare contact days can reflect different care delivery approaches between providers and may be a metric to assess both healthcare efficiency and accessibility. Understanding caregiver burden and social disparities associated with high contact days offers an opportunity to improve care coordination and streamline healthcare encounters while balancing patients’ care needs. CMMI Disclaimer: The statements contained in this document are solely those of the authors and do not necessarily reflect the views or policies of CMS. The authors assume responsibility for the accuracy and completeness of the information contained in this document. Healthcare contact days. Mean Percentiles 5 th -95 th Per Episode Healthcare Contact Days 31.9 10-65 Ambulatory Visits* 8-55 Chemotherapy 6.6 0-18 Imaging 2.7 0-7 Procedure 1.8 0-7 Radiation 2.4 0-23 Testing 11.8 3-25 Clinician Oncology 6 1-14 Other Specialties 3.4 0-10 Primary Care 2.8 0-8 Facility Visits ER 0.4 0-2 Hospice (Facility) 0.1 0-0 IP 2.7 0-16 SNF 0.8 0-0 *Ambulatory visits days are not mutually exclusive.

Cancer care delivery in prisons: From barriers to best practices.

49 Background: Cancer is the leading cause of death in US prisons. Incarcerated patients with cancer have 92% higher 5-year mortality than the general population with cancer, but little is known about how to improve cancer screening, diagnosis and treatment in this high-risk population. Methods: We conducted interviews with state prison medical directors and primary care clinicians, and medical, radiation and gynecologic oncologists who coordinate or provide cancer care for individuals incarcerated in prison. Participants were recruited via 1) email invitation to participants at a correctional health conference, 2) purposeful sampling using targeted emails to clinicians in prison systems selected for diversity in size, geography and correctional health model (e.g., contracted care), and 3) snowball sampling of individuals from research and participant networks. Participants were interviewed about 1) logistics of cancer care delivery from screening and treatment through end-of-life care, 2) barriers and facilitators to cancer care delivery, and 3) evidence-based strategies to facilitate cancer care in prisons, including best practices. Interview transcripts were analyzed using mixed inductive/deductive thematic content analysis to identify emerging themes. Results: 34 participants from 16 prison systems were interviewed (10 medical directors, 6 PCPs, 14 oncologists, 4 other). Participants reported prison clinicians coordinate most cancer care (e.g., screening, diagnosis and symptom management), while cancer treatment largely occurs in community or academic facilities outside of prison. Common barriers identified included underscreening / delays in diagnosis, complex logistical coordination, poor communication (between patients and oncologists, and prison clinicians and oncologists), inadequate symptom management, dehumanizing practices, loss-to-follow-up after release and that patients often come from marginalized populations. Common facilitators were better access to insurance, cancer screening, and general medical and cancer care than incarcerated patients might receive before/after incarceration. Participants identified multiple ways to improve cancer screening (creating enforceable standards, increasing continuing medical education, implementing electronic medical record reminders, reducing logistical barriers), cancer treatment (implementing navigators within prisons and cancer centers, prioritizing care with oncologist input, keeping care in prisons, decarceration), and transitions to the community (Medicaid activation prior to release, community partnerships to facilitate care transitions). Conclusions: Incarceration imposes multiple barriers to cancer care delivery, but clinicians identified numerous tools to improve cancer care in prison. Future studies should test and optimize these strategies to improve cancer outcomes for incarcerated patients.