Oncological Therapy Research Articles

Histology Agnostic Drug Development: An Updated Review.

Recent advancements in oncology have led to the development of histology-agnostic therapies, which target genetic alterations irrespective of the tumor's tissue of origin. This review aimed to provide a comprehensive update on the current state of histology-agnostic drug development, focusing on key therapies, including pembrolizumab, larotrectinib, entrectinib, dostarlimab, dabrafenib plus trametinib, selpercatinib, trastuzumab deruxtecan, and reprotrectinib. We performed a detailed analysis of each therapy's mechanism of action, clinical trial outcomes, and associated biomarkers. The review further explores challenges in drug resistance, such as adaptive signaling pathways and neoantigen variability, as well as diagnostic limitations in identifying optimal patient populations. While these therapies have demonstrated efficacy in various malignancies, significant hurdles remain, including intratumoral heterogeneity and resistance mechanisms that diminish treatment effectiveness. We propose considerations for refining trial designs and emerging biomarkers, such as tumor neoantigen burden, to enhance patient selection. These findings illustrate the transformative potential of histology-agnostic therapies in precision oncology but highlight the need for continued research to optimize their use and overcome existing barriers.

Characteristics and outcomes of patients with a history of cancer enrolled in our prospective HFpEF registry

Abstract Background Along with the aging population, the incidence of concomitant heart failure with preserved ejection fraction (HFpEF) and cancer, is increasing. However, little is known about the typical characteristics of patients with both HFpEF and a history of oncologic disease. Aim We aimed to characterize the distinctive characteristics and outcomes of patients with a history of cancer within a prospective HFpEF registry. Methods We analyzed data from 491 unselected HFpEF patients from our tertiary university center between 2010 and 2022 and followed the patients until 2023. Laboratory parameters and comorbidities were assessed. Patients were categorized into those with and without a history of cancer, including various malignancies, survivors of childhood cancer, radiation therapy, with or without chemotherapy. Kaplan-Meier estimates were used to explore the association between cancer history, as well as previous radiotherapy, and a combined endpoint of heart failure hospitalization and/or all-cause death. Results In this analysis of 491 HFpEF patients, a total of 101 patients (21%); had a history of cancer [mean age 74±7 years; female 72 (72%), male 29 (29%)]. The median time from cancer diagnosis to the initial HFpEF visit was 7.0 years (IQR 13-0.5 years). The most prevalent primary cancer sites included the chest wall (32%) comprising 4 adenocarcinomas of the lung and 28 cases of breast cancer, followed by the gastric (28%), urogenital system (18%), hematologic and lymphatic system (16%), cancers located at the head and neck (5%) and endocrine malignancies (1%). Radiotherapy (39%) and chemotherapy (26%) were common. Notably, no significant differences were observed, between patients with or without a history of cancer, in terms of median NT-proBNP levels [1037 (IQR 416-2075) vs. 1060 pg/ml (IQR 462-2013)] and the frequency of key cardiovascular comorbidities (all p>0.05, see Table 1). Over the study period [median follow-up 50 months (IQR 18-76)], 64 (64%) of cancer patients met the combined endpoint, with no statistically significant difference in outcomes between HFpEF patients with and without a cancer history (log-rank p=0.222, see Figure 1). Furthermore, there was no significant difference in the combined endpoint between patients who had undergone radiotherapy and those without (log-rank p=0.162). Conclusion Our findings highlight a high coexistence of cancer and HFpEF, which can frequently occur after oncology therapies. The data suggest that the presence of a history of cancer or previous radiotherapy did not significantly impact overall outcomes in HFpEF patients compared to those without cancer during the study period. Further research is needed to characterize patients with both disease entities in detail. Due to modern cardiovascular therapy in a university and cardio-oncology clinic setting, outcomes for cancer patients appear better than expected.

Redefining Available Therapy in Oncology Accelerated Approval Decisions.

When weighing rapid approval for follow-on drugs, should @FDAOncology recognize the drugs that came before?

Porphyrin-engineered nanoscale metal-organic frameworks: enhancing photodynamic therapy and ferroptosis in oncology.

Photodynamic therapy and ferroptosis induction have risen as vanguard oncological interventions, distinguished by their precision and ability to target vulnerabilities in cancer cells. Photodynamic therapy's non-invasive profile and selective cytotoxicity complement ferroptosis' unique mode of action, which exploits iron-dependent lipid peroxidation, offering a pathway to overcome chemoresistance with lower systemic impact. The synergism between photodynamic therapy and ferroptosis is underscored by the depletion of glutathione and glutathione peroxidase four inhibitions by photodynamic therapy-induced reactive oxygen species, amplifying lipid peroxidation and enhancing ferroptotic cell death. This synergy presents an opportunity to refine cancer treatment by modulating redox homeostasis. Porphyrin-based nanoscale metal-organic frameworks have unique hybrid structures and exceptional properties. These frameworks can serve as a platform for integrating photodynamic therapy and ferroptosis through carefully designed structures and functions. These nanostructures can be engineered to deliver multiple therapeutic modalities simultaneously, marking a pivotal advance in multimodal cancer therapy. This review synthesizes recent progress in porphyrin-modified nanoscale metal-organic frameworks for combined photodynamic therapy and ferroptosis, delineating the mechanisms that underlie their synergistic effects in a multimodal context. It underscores the potential of porphyrin-based nanoscale metal-organic frameworks as advanced nanocarriers in oncology, propelling the field toward more efficacious and tailored cancer treatments.

Towards verifiable cancer digital twins: tissue level modeling protocol for precision medicine.

Cancer exhibits substantial heterogeneity, manifesting as distinct morphological and molecular variations across tumors, which frequently undermines the efficacy of conventional oncological treatments. Developments in multiomics and sequencing technologies have paved the way for unraveling this heterogeneity. Nevertheless, the complexity of the data gathered from these methods cannot be fully interpreted through multimodal data analysis alone. Mathematical modeling plays a crucial role in delineating the underlying mechanisms to explain sources of heterogeneity using patient-specific data. Intra-tumoral diversity necessitates the development of precision oncology therapies utilizing multiphysics, multiscale mathematical models for cancer. This review discusses recent advancements in computational methodologies for precision oncology, highlighting the potential of cancer digital twins to enhance patient-specific decision-making in clinical settings. We review computational efforts in building patient-informed cellular and tissue-level models for cancer and propose a computational framework that utilizes agent-based modeling as an effective conduit to integrate cancer systems models that encode signaling at the cellular scale with digital twin models that predict tissue-level response in a tumor microenvironment customized to patient information. Furthermore, we discuss machine learning approaches to building surrogates for these complex mathematical models. These surrogates can potentially be used to conduct sensitivity analysis, verification, validation, and uncertainty quantification, which is especially important for tumor studies due to their dynamic nature.

Perspectives on non-genetic optoelectronic modulation biointerfaces for advancing healthcare

AbstractAdvancements in optoelectronic biointerfaces have revolutionized healthcare by enabling targeted stimulation and monitoring of cells, tissues, and organs. Photostimulation, a key application, offers precise control over biological processes, surpassing traditional modulation methods with increased spatial resolution and reduced invasiveness. This perspective highlights three approaches in non-genetic optoelectronic photostimulation: nanostructured phototransducers for cellular stimulation, micropatterned photoelectrode arrays for tissue stimulation, and thin-film flexible photoelectrodes for multiscale stimulation. Nanostructured phototransducers provide localized stimulation at the cellular or subcellular level, facilitating cellular therapy and regenerative medicine. Micropatterned photoelectrode arrays offer precise tissue stimulation, critical for targeted therapeutic interventions. Thin-film flexible photoelectrodes combine flexibility and biocompatibility for scalable medical applications. Beyond neuromodulation, optoelectronic biointerfaces hold promise in cardiology, oncology, wound healing, and endocrine and respiratory therapies. Future directions include integrating these devices with advanced imaging and feedback systems, developing wireless and biocompatible devices for long-term use, and creating multifunctional devices that combine photostimulation with other therapies. The integration of light and electronics through these biointerfaces paves the way for innovative, less invasive, and more accurate medical treatments, promising a transformative impact on patient care across various medical fields.

Curcumin as a complementary treatment in oncological therapy: a systematic review.

Curcumin, the active ingredient in turmeric, is employed by numerous cancer patients to support conventional cancer therapy. This systematic review aims to summarize the existing clinical evidence and to provide an overview of the potential benefits and risks associated with curcumin supplementation. In January 2024, we conducted a systematic search of five electronic databases (Embase, Cochrane, PsycInfo, CINAHL, and Medline) using a complex search strategy. We included randomized controlled trials on the use, effectiveness, and potential harm of additional curcumin therapy in adult patients under cancer treatment. The risk of bias was assessed using Cochrane revised Risk of Bias Tool 2.0. This systematic review included 34 randomized controlled trials involving 2580 patients out of 11143 search results. Included patients were primarily diagnosed with head and neck cancer, followed by breast, prostate, and colorectal cancer. Therapy concepts encompassed topical or systemic curcumin administration. The studies reported heterogeneous results concerning oral and skin symptoms, pain, weight alteration and changes in body composition, survival, and disease progression. Significant findings were reported for oral mucositis and weight loss. Considering risk of bias, all studies had moderate to high risk of bias. Regarding side effects, one study reported significantly more vomiting in the curcumin group. Although the results suggest promise in reducing mucositis and weight loss, a clear statement regarding the effectiveness of curcumin therapy on cancer patients cannot be made due to heterogeneous results and methodological limitations of the involved studies. Further investigations of higher quality are necessary to derive a definite recommendation for action.

Interactive Structural Analysis of KH3-4 Didomains of IGF2BPs with Preferred RNA Motif Having m6A Through Dynamics Simulation Studies.

m6A modification is the most common internal modification of messenger RNA in eukaryotes, and the disorder of m6A can trigger cancer progression. The GGACU is considered the most frequent consensus sequence of target transcripts which have a GGAC m6A core motif. Newly identified m6A 'readers' insulin-like growth factor 2 mRNA-binding proteins modulate gene expression by binding to the m6A binding sites of target mRNAs, thereby affecting various cancer-related processes. The dynamic impact of the methylation at m6A within the GGAC motif on human IGF2BPs has not been investigated at the structural level. In this study, through in silico analysis, we mapped IGF2BPs binding sites for the GGm6AC RNA core motif of target mRNAs. Subsequent molecular dynamics simulation analysis at 400 ns revealed that only the KH4 domain of IGF2BP1, containing the 503GKGG506 motif and its periphery residues, was involved in the interaction with the GGm6AC backbone. Meanwhile, the methyl group of m6A is accommodated by a shallow hydrophobic cradle formed by hydrophobic residues. Interestingly, in IGF2BP2 and IGF2BP3 complexes, the RNA was observed to shift from the KH4 domain to the KH3 domain in the simulation at 400 ns, indicating a distinct dynamic behavior. This suggests a conformational stabilization upon binding, likely essential for the functional interactions involving the KH3-4 domains. These findings highlight the potential of targeting IGF2BPs' interactions with m6A modifications for the development of novel oncological therapies.

Optimization of Exocrine Pancreatic Insufficiency in Pancreatic Adenocarcinoma Patients.

This study explores the optimization of exocrine pancreatic insufficiency (EPI) management in pancreatic adenocarcinoma patients, focusing on the scientific advancements and technological interventions available to improve patient outcomes, including oral pancreatic enzyme replacement therapy (PERT) and immobilized lipase cartridge (RELiZORB®). This was a prospective Institutional Review Board (IRB)-approved study from October 2019 through to August 2021 at the Louisville Medical Center in collaboration with Norton Healthcare and the University of Louisville Division of Surgical Oncology. Patients with a diagnosis of pancreatic adenocarcinoma (Stage 2 or 3) who underwent oncologic surgical resection were included in this study. Patients were contacted at pre-defined intervals (prior to surgery, before hospital discharge, and 2, 4, 6, and 12 weeks after surgery) to complete nutrition evaluation, EPI assessment, and quality of life questionnaires to identify the severity and frequency of gastrointestinal (GI) symptoms. EPI symptoms were reported in 28 of the 35 total patients studied (80%). Jejunostomy tubes were placed during oncologic surgery in 25 of the 35 total patients studied (71%), and 12 of the 25 patients with a jejunostomy tube utilized enzyme cartridges to manage EPI symptoms while on supplemental tube feeding (48%). EPI symptoms were reported in 8 of the 10 patients without a feeding tube (80%), and their EPI symptoms were managed with PERT alone. EPI interventions, both oral PERT and immobilized cartridges, were associated with a decrease in EPI symptoms after surgery and improved quality of life (QOL). Overall, early optimization of EPI is crucial to enhance overall patient care, return to oncology therapy after surgery, and improve quality of life in pancreatic adenocarcinoma patients.

Gastrointestinal adverse events associated with immune checkpoint inhibitors: a pharmacovigilance analysis of the EudraVigilance and VigiAccess databases

ABSTRACT Background This study aimed to provide an overview of gastrointestinal (GI) adverse events associated with immune checkpoint inhibitors (ICIs) using two pharmacovigilance databases, EudraVigilance and VigiAccess. Research design and methods Data was collected from the date of ICI’s marketing authorization until 30 November 2023. Reporting odds ratio (ROR) was used as a measure of ADR reporting disproportionality for signal detection. Results Overall, across both databases, EudraVigilance and VigiAccess, a total of 76,606 ADR reports were analyzed. In EudraVigilance, colitis (12,581) and diarrhea (12,108) were the most reported GI adverse events, with similar findings in VigiAccess. Furthermore, in both databases, the most ADR reports were associated with nivolumab and pembrolizumab. Durvalumab (ROR: 3.96, 95%CI :3.65–4.28), ipilimumab (ROR: 1.95, 95%CI: 1.89–2.01), nivolumab (ROR: 1.05, 95%CI: 1.02–1.07), and atezolizumab (ROR: 1.04, 95%CI: 1.01–1.07) demonstrated higher risks of GI events compared to other ICIs. EudraVigilance analysis identified dysphagia, ascites, hematochezia, and gastroesophageal reflux disease as potential signals associated with ICI therapy. Majority of ADR reports (87.2%) comprised serious GI adverse events, a portion of which was associated with fatal outcomes (14.5%). Atezolizumab (14.9%) and pembrolizumab (11.9%) were linked to a higher incidence of fatal outcomes compared to other ICIs. Conclusion The differential risk profiles of ICIs-associated-GI adverse events underscore the importance of personalized therapy in oncology.

Red Blood Cell Transfusions in Patients with Advanced Cancer Receiving Home Palliative Care.

Background: Red blood cell (RBC) transfusion is the standard treatment for anemia in advanced cancer. Nevertheless, guidelines for managing this condition are still not exhaustive. Objective: To investigate frequency, timing, and clinical characteristics associated with RBC transfusions in patients with advanced cancer assisted by at-home oncological care service and to evaluate the association between parameters at the entry and the possibility of receiving RBC transfusions during homecare. Design: Retrospective observational study without medication. Setting/Subjects: Patients with advanced cancer entered in homecare during 2021 living in Bologna (Italy). Measurements: Gender, tumor primary site, oncological therapy, and symptoms at the entry were considered as possible factors in a binary logistic regression for the possibility of receiving at least one RBC transfusion during assistance. Data about transfusions were analyzed, and the transfusion history for each patient from the entry to death was traced. Results: Among the 1108 patients admitted, 179 (16.2%) were given at least one RBC transfusion during homecare. Genitourinary, hematological malignancies, and being still in therapy for advanced cancer are associated with a higher probability of receiving RBC transfusion during assistance (p = 0.017, p < 0.001, and p = 0.032, respectively). Half of the patients (52%) underwent RBC transfusions less than a month before death. Duration of the assistance was correlated with the period from last transfusion to death (p < 0.001). Conclusion: Hematological and genitourinary cancer and being in simultaneous care at the entry were associated with transfusion. Although the appropriateness of this treatment remains to be defined in this population, transfused patients frequently received "late in life" transfusions.

Analysis of Risk Factors with Assessment of the Impact of the Microbiome on the Risk of Squamous Cell Carcinoma of the Larynx.

Introduction: Head and neck squamous cell carcinoma (HNSCC) ranks sixth among cancers in the world, and the 5-year survival rate ranges from 25% to 60%. The risk factors for HNSCC are primarily smoking, alcohol consumption and human papillomavirus (HPV). Data indicate that 15-20% of cancers are caused by infectious agents, 20-30% by smoking and 30-35% by unhealthy lifestyles, diet, lack of physical activity and obesity. Dysbiosis is a microbiome imbalance, which promotes oncogenesis by intensifying inflammatory processes and affecting the host's metabolism. Profiling the microbiome in various types of cancer is currently the subject of research and analysis. However, there is still little information on the correlation of the microbiome with HNSCC and its impact on oncogenesis, the course of the disease and its treatment. Objective: The aim of the study was to prospectively assess risk factors with assessment of the impact of the microbiome on the risk of squamous cell carcinoma of the larynx. The study included a group of 44 patients diagnosed with squamous cell carcinoma of the larynx and 30 patients from the control group. Results: In the control group, bacteria of the normal microbiome dominated-the genus Streptococcus, Gemella, Neisseria and Kingella. In the group of patients with laryngeal cancer, Prevotella, Clostridiales and Stomatobaculum were found significantly more often. Porphyromonas, Fusobacterium, Lactobacillus, Actinobacteria, Actinomyces and Shaalia odontolytica were also found at a higher percentage in the study group. Analyzing the phylum, Firmicutes dominated in the control group; there were statistically significantly more of them than in patients from the study group. Bacteroides and Bacillota were found significantly more often in patients with laryngeal cancer. Conclusions: The importance of the microbiome in oncology has been confirmed in many studies. Independent risk factors for laryngeal cancer were primarily a lower number of Firmicutes in the microbiome, but also an increased leukocyte level above 6.52 × 103/mm and a decreased total protein level below 6.9 g/dL. Prevotella, Clostridiales, Stomatobaculum, Porphyromonas, Fusobacterium, Lactobacillus, Actinobacteria, Actinomyces and Shaalia were considered to be the bacteria contributing to the development of laryngeal cancer. Streptococcus, Gemella, Neisserie and Kingella were considered to be protective bacteria. Moreover, the study confirmed the significant impact of smoking, alcohol consumption and poor oral hygiene on the development of laryngeal cancer. The microbiome, its identification and manipulation may constitute a breakthrough discovery for improving the diagnosis and oncological therapy of laryngeal cancer, and also of the entire group of HNSCC. Profiling the microbiome may allow for personalized therapy related to its modification. Assessing the microbiome of patients diagnosed with cancer may provide an opportunity to predict treatment response and effectiveness.

Clinical advances and challenges associated with TCR-T cell therapy for cancer treatment.

T cell receptor (TCR)-T cell therapy is an innovative form of cancer immunotherapy that genetically modifies patients' T cells to target and destroy cancer cells. However, the current status of clinical trials of TCR-T cell therapy for the treatment of cancer remains unclear. This study aimed to comprehensively analyze the registration trials related to TCR-T cell therapy for the treatment of cancer. A comprehensive search was conducted in the Trialtrove database for all clinical trials related to TCR-T cell therapy registered by August 1, 2024. Inclusion criteria focused on trials targeting TCR-T cell therapy for oncology, and excluded observational studies and incomplete data. Statistical analysis was performed on key trial characteristics, with between-group comparisons utilizing chi-square or Fisher's exact tests. Analysis of 174 eligible clinical trials revealed that TCR-T cell therapy exhibits significant efficacy across various tumor types, particularly in refractory hematologic malignancies and certain solid tumors. Additionally, combining TCR-T cell therapy with other immunotherapies enhanced these anti-tumor effects. TCR-T cell therapy holds substantial promise for cancer treatment. Future research should focus on optimizing treatment protocols, enhancing efficacy, and minimizing prices to fully realize the potential of this therapy.

Total body irradiation is associated with long-term deficits in femoral bone structure but not mechanical properties in male rhesus macaques.

Exposure to ionizing radiation for oncological therapy increases the risk for late-onset fractures in survivors. However, the effects of total body irradiation (TBI) on adult bone are not well-characterized. The primary aim of this study was to quantify the long-term effects of TBI on bone microstructure, material composition, and mechanical behavior in skeletally mature rhesus macaque (Macaca mulatta) non-human primates. Femora were obtained post-mortem from animals exposed to an acute dose of TBI (6.0-6.75Gy) nearly a decade earlier, age-matched non-irradiated controls, and non-irradiated young animals. The microstructure of femoral trabecular and cortical bone was assessed via micro-computed tomography. Material composition was evaluated by measuring total fluorescent advanced glycation end products (fAGEs). Cortical bone mechanical behavior was quantified via four-point bending and cyclic reference point indentation (cRPI). Animals exposed to TBI had slightly worse cortical microstructure, including lower cortical thickness (-11%, p = 0.037) and cortical area (-24%, p = 0.049), but similar fAGE content and mechanical properties as age-matched controls. Aging did not influence cortical microstructure, fAGE content, or cRPI measures but diminished femoral cortical post-yield properties, including toughness to fracture (-32%, p = 0.032). Because TBI was administered after the acquisition of peak bone mass, these results suggest that the skeletons of long-term survivors of adulthood TBI may be resilient, retaining or recovering their mechanical integrity during the post-treatment period, despite radiation-induced architectural deficits. Further investigation is necessary to better understand radiation-induced skeletal fragility in mature and immature bone to improve care for radiation patients of all ages.

Three‐Pronged Induction of Tumor Calcification Synergistic Calcium Immunotherapy Enables Diagnosis and Cure of Cancer

AbstractTumor calcification is considered to have the superiority of integrating tumor diagnosis and treatment, and it also has been found to be a predictor of favorable prognosis. However, selecting suitable nanocarriers and therapeutic drugs to maximize the tumor calcification efficiency are key factors for improving calcification‐medicated theranostics. This study performs a multi‐channel calcification nanoinitiator (CalNI, i.e., BP‐Cur‐Ca@PKLAK) by loading curcumin (Cur) and depositing Ca2+ on black phosphorus (BP) and combined carrying mitochondria‐targeting cytotoxic peptide KLAK to boost a triple‐induced tumor calcification. CalNI preferentially accumulates inside tumor mitochondria and induces multilevel calcification promotion by the three combined effects of (i) the degradation of BP into PO43− provides the phosphorus source required for calcification; (ii) burst of calcium ions can directly induce cellular calcium overload; (iii) Cur can inhibit calcium efflux thus further aggravate intracellular calcium stress. Moreover, KLAK exhibited enhanced mitochondrial synergistic toxic effects. Notably, the potential function of CalNI on the regulation of macrophage polarization could completely reverse the immunosuppressive microenvironment, and activate the initiation of T cell‐mediated immune response. Therefore, this three‐pronged CalNI showed a huge promise to be an alternative to conventional oncology therapy, which presents a more satisfactory therapeutic efficiency than any kind of single induction mode.

7437 Harnessing Diabetes Technology for Management of Immune Checkpoint Inhibitor Associated Diabetes

Abstract Disclosure: A. Knape: None. A. Kotwal: None. D. Rohlfsen: None. A. Patel: None. W. Goldner: None. Background: Immune checkpoint inhibitors (ICIs) are a key treatment modality for many cancers. One percent of patients who receive ICIs can develop insulin deficient ICI associated diabetes (ICI-DM). These patients often have complex oncologic therapy plans making treatment of newly diagnosed insulin deficient diabetes challenging which often results in additional healthcare-related burden for the patient. Methods: This is a retrospective case series of five adults who developed ICI-DM after receiving either PD-1, CTLA-4 or PDL-1 inhibitors or a combination. Data on demographics, medical history and labs were collected in addition to mode of glucose monitoring and treatment after diagnosis of ICI-DM. Results: Patients were age 44-72 at diagnosis of ICI-DM, three were female. Two were admitted to the hospital in DKA, one was diagnosed in the ER with severe hyperglycemia without DKA, two had outpatient hyperglycemia without DKA. Glucose at diagnosis ranged from 215-510 mg/dL. C-peptide was low for all patients. Fingerstick blood sugar (FSBS) monitoring and basal/bolus insulin was immediately initiated for all patients. All were transitioned from FSBS to continuous glucose monitor (CGM) and 2/5 ultimately transitioned to sensor-augmented insulin pump therapy (AID). Time in range on CGM improved in four patients with percent time in range improving between 10-48%. In two patients, hypoglycemia frequency declined by 6% and 3%. Hyperglycemia frequency declined by 13% and 48% in patients on AID therapy and by 14% and 25% in two of those on basal/bolus insulin therapy. All patients preferred CGM over FSBS and remained on CGM therapy. Those who chose AID preferred it over basal/bolus insulin therapy stating it was less complicated than basal/bolus insulin with CGM. Conclusions: We report successful treatment of five cases of ICI-DM with CGM + basal/bolus insulin or AID. 80% demonstrated improved time in range and decreased overall frequency of hyperglycemia. 40% had decreased frequency of hypoglycemia. CGM allows for dynamic adjustment of insulin therapy in a population with complex medical regimens resulting in fluctuating glucose levels. The integrated pump and sensor technology in AID was less burdensome than basal/bolus in those who chose it. Managing ICI-DM is complicated. The burden of this entity can be lessened by harnessing the power of diabetes technology. Presentation: 6/2/2024

Resistance Management for Cancer: Lessons from Farmers.

One of the main reasons we have not been able to cure cancers is that treatments select for drug-resistant cells. Pest managers face similar challenges with pesticides selecting for pesticide-resistant insects, resulting in similar mechanisms of resistance. Pest managers have developed ten principles that could be translated to controlling cancers: (1) prevent onset, (2) monitor continuously, (3) identify thresholds below which there will be no intervention, (4) change interventions in response to burden, (5) preferentially select non-chemical control methods, (6) use target-specific drugs, (7) use the lowest effective dose, (8) reduce cross-resistance, (9) evaluate success based on long-term management, and (10) forecast growth and response. These principles are general to all cancers and cancer drugs and so could be employed broadly to improve oncology. Here, we review the parallel difficulties in controlling drug resistance in pests and cancer cells. We show how the principles of resistance management in pests might be applied to cancer. Integrated pest management inspired the development of adaptive therapy in oncology to increase progression-free survival and quality of life in patients with cancers where cures are unlikely. These pest management principles have the potential to inform clinical trial design.

Biological Therapies in Oncology: Balancing Efficacy and Safety in the Context of Latent Tuberculosis.

Biological Therapies in Oncology: Balancing Efficacy and Safety in the Context of Latent Tuberculosis.

Frequency and Natural History of Emergency General Surgery Conditions in Cancer Patients: A SEER-Medicare Population Analysis.

To determine if cancer patients experience variability in incidence or management of emergency general surgery (EGS) conditions compared to non-cancer patients. The true frequency, and natural history of EGS conditions among cancer patients has not been characterized. We utilized SEER-Medicare data from January 2006-December 2015 to compare patients with breast, prostate, and lung cancer to a non-cancer cohort. Patients were followed from date of cancer diagnosis, or an index date for non-cancer patients, to the development of an EGS condition, death or last follow up. We assessed the cumulative incidence of EGS conditions over time, and fit multivariable Cox proportional hazards models to evaluate the impact of time-dependent surgical intervention on mortality. We identified 322,756 patients with breast (N=82,147), lung (N=128,618), and prostate cancer (N=111,991) and 210,429 non-cancer patients.. Cancer patients had a higher incidence of an EGS condition within the first year after diagnosis (4.8% vs. 3.2%), with lung (6.8%) and breast cancer (4.0%) showing consistent rends. Cancer patients were less likely to undergo surgery for (13% vs. 14%, P=0.005), though this varied by cancer type and EGS conditions. Patients with breast (HR 1.27, 95%CI 1.17-1.39) and lung cancer (HR 3.27, 95%CI 3.07-3.48) were more likely to die within 30-days of an EGS diagnosis. Cancer patients experience a higher incidence of EGS conditions within the first year following diagnosis, but are less likely to undergo surgery. Future research is needed to explore the interplay between EGS conditions, their management, and receipt of intended oncologic therapy, and resulting outcomes.

Race/ethnicity and human epidermal growth hormone receptor 2–targeted therapy for breast cancer.

91 Background: Breast cancer is the most common cancer in the US. Up to 25% of breast cancers are classified as human epidermal growth factor receptor 2 (HER2)-positive and associated with an aggressive tumor burden. HER2-targeting monoclonal antibodies improves survival in patients with HER2-positive breast cancer. Prior work has demonstrated disparities in access to oncologic therapies among older women. Our study seeks to examine racial/ethnic disparities in receiving HER2-targeted therapies for patients with HER2-positive breast cancer and trends in use over time. Methods: In the Surveillance, Epidemiology and End Results (SEER) Medicare-linked database we identified women diagnosed with breast cancer from 2010 to 2019. We included those &gt;66 years old who survived 12 months after diagnosis, were enrolled in Medicare Parts A/B for 12 months pre and post-diagnosis, and had local or regional stage HER2-positive cancer. Our primary outcome was receipt of HER2-targeted therapies in the 12 months after diagnosis. Our independent variable was race/ethnicity as measured by the validated Research Triangle Institute race/ethnicity codes in Medicare. Due to small sample sizes, we focus our analysis on White, Black, or Hispanic women. We used multivariable Modified Poisson regression to evaluate changes in the probability of HER2-targeted therapy receipt by race/ethnicity over time, adjusted for sociodemographics, cancer factors, and medical comorbidities. Results: Our cohort comprised 13,887 patients including 8.7% Black, 7.5% Hispanic, and 83.8% White (mean age 74.9). Overall, 7,351 (52.9%) received HER2-targeted therapies in the 12 months post-diagnosis, with use increasing over time in all racial/ethnic groups (Table). Compared with White patients, Black and Hispanic patients had a 19% (adjusted risk ratio [aRR] 0.81, 95% CI:0.69-0.96) and 27% (aRR 0.73, 95% CI 0.61-0.89) lower likelihood, respectively, of receiving HER2-targeted therapies from 2010-2011 (Table). By 2018-2019, no significant differences in receiving HER2-targeted therapies were observed across racial/ethnic groups. Conclusions: In a national cohort of Medicare enrollees with HER2-positive breast cancer, we observed significant racial/ethnic disparities which narrowed over time. Overall utilization rates were low. Future work is needed to understand how improved access to breast cancer treatments impact downstream outcomes. Use of human epidermal growth hormone receptor 2–targeted therapy from 2010-2011 and 2018-2019 by race/ethnicity. Race and Ethnicity Unadjusted Rates Adjusted Risk Ratios (95% CI)* 2010-2011 2018-2019 2010-2011 2018-2019 Black 36% 62% 0.81 (0.69-0.96) 0.97 (0.87-1.08) Hispanic 31% 68% 0.73 (0.61-0.89) 1.01 (0.92-1.12) White 42% 64% Reference Reference *Adjusted for age, marital status, region, breast cancer stage and year of diagnosis, and medical comorbidities.