Therapy For Treatment Of Cancer Research Articles

Validation on selected breast cancer drugs of physicochemical features by using machine learning models

Breast cancer is one of the leading causes of death among females today. The elbow approach determines the ideal number of clusters after determining that the Dataset is highly cluster able with the Hopkins statistic. Three distinct groups with distinct differences were produced using the dataset's proposed expectation maximization fuzzy k-means clustering algorithm (PEMFKM). Different fuzzy clustering techniques, such as fuzzy k-means (FKM), fuzzy k-means with entropy (FKM.ENT), fuzzy k-means with entropy and noise (FKM.ENT.NOISE), Gustafson and Kessel - like fuzzy k-means (FKM.GK), Gustafson and Kessel - like fuzzy k-means with entropy regularization (FKM.GK.ENT), Gustafson and Kessel - like fuzzy kmeans with entropy regularization and noise (FKM.GK.ENT.NOISE), and PEMFKM, are evaluated. The partition coefficient (PC), partition entropy (PE), and Modified partition coefficient index (MPC) index values are better for FKM.GK than the suggested PEMFKM method. When compared to the FKM.GK method, the index values for the proposed PEMFKM algorithm have superior results for the parameters Silhouette (SIL), Xie and Beni index (XB), and fuzzy silhouette index (SIL.F). The results shows that the PEMFKM algorithm will provide better clusters and that the drugs in a given cluster may be combined for use in combination therapy for breast cancer treatment.

Drug Repurposing: Exploring Potential Anti-Cancer Strategies by Targeting Cancer Signalling Pathways

The repurposing of previously clinically approved drugs as an alternative therapeutic approach to treating disease has gained significant attention in recent years. A multitude of studies have demonstrated various and successful therapeutic interventions with these drugs in a wide range of neoplastic diseases, including multiple myeloma, leukaemia, glioblastoma, and colon cancer. Drug repurposing has been widely encouraged due to the known efficacy, safety, and convenience of already established drugs, allowing the bypass of the long and difficult road of lead optimization and drug development. Repurposing drugs in cancer therapy is an exciting prospect due to the ability of these drugs to successfully target cancer-associated genes, often dysregulated in oncogenic signalling pathways, amongst which are the classical cancer signalling pathways; WNT (wingless-related integration type) and Hippo signalling. These pathways play a fundamental role in controlling organ size, tissue homeostasis, cell proliferation, and apoptosis, all hallmarks of cancer initiation and progression. Prolonged dysregulation of these pathways has been found to promote uncontrolled cellular growth and malignant transformation, contributing to carcinogenesis and ultimately leading to malignancy. However, the translation of cancer signalling pathways and potential targeted therapies in cancer treatment faces ongoing challenges due to the pleiotropic nature of cancer cells, contributing to resistance and an increased rate of incomplete remission in patients. This review provides analyses of a range of potential anti-cancer compounds in drug repurposing. It unravels the current understanding of the molecular rationale for repurposing these drugs and their potential for targeting key oncogenic signalling pathways.

An Overview of Emerging Trends in Gene Therapy for Cancer Treatment

An Overview of Emerging Trends in Gene Therapy for Cancer Treatment

Advancements in CAR-T Therapy: A Comprehensive Review

Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as a ground-breaking approach in cancer treatment, offering new hope to patients with refractory or relapsed malignancies. By genetically modifying T lymphocytes, this potent method allows for the targeted eradication of infectious cells. The efficient production of CAR-T cells is essential for the effective use of these treatments to treat malignancies, as it affects not just the product's efficacy as well as safety but also its general availability to patients who require it. This article's primary goal is to provide a comprehensive overview of CAR-T therapy, encompassing its historical evolution, mechanistic insights, clinical applications, challenges, and future directions. By synthesizing existing literature and realworld evidence, this review seeks to elucidate the significance of CAR-T therapy in the landscape of cancer treatment and its potential to redefine the standard of care for patients with refractory or relapsed malignancies. The methodology involved a comprehensive literature search conducted using various databases, including PubMed, Google Scholar, and clinical trial registries such as Clinical- Trials.gov. The search strategy incorporated a combination of relevant keywords and Medical Subject Headings (MeSH) terms, including but not limited to "CAR-T therapy," "chimeric antigen receptor T-cell therapy," "cancer immunotherapy," "clinical trials," "pharmaceutical companies," "regulatory approvals," "pipeline molecules," and "cancer types." Boolean operators (AND, OR) were utilized to refine the search and capture relevant articles and studies. In addition to database searches, manual screening of reference lists from relevant review articles and primary studies was performed to identify additional relevant publications. The inclusion criteria encompassed original research articles, clinical trials, systematic reviews, meta-analyses, and regulatory documents related to CAR-T cell therapy and its applications in cancer treatment and the review included studies published in English between January 2010 and March 2024. Exclusion criteria comprised studies not relevant to the scope of the review, such as those focusing on non-CAR-T cell therapies or non-cancer-related topics. This review underscores the transformative potential of CAR-T therapy in cancer treatment, highlighting its efficacy, safety, and clinical relevance across various malignancies. By synthesizing findings from preclinical studies, clinical trials, and real-world data from patients, CAR-T therapy has consistently exhibited remarkable therapeutic outcomes. These include high response rates, durable remissions, and significant improvements in survival outcomes among patients with refractory or relapsed cancers. Additionally, the inclusion of practical research with big data from real patients further supports the robustness and applicability of CAR-T therapy in clinical practice. In conclusion, CAR-T therapy represents a paradigm shift in cancer treatment, offering new avenues for personalized and precisiondriven oncology. By addressing current gaps, optimizing treatment protocols, and exploring novel strategies, CAR-T therapy holds immense promise in reshaping the landscape of oncology and providing hope to patients with advanced malignancies.

Better together: nanoscale co-delivery systems of therapeutic agents for high-performance cancer therapy

Combination therapies can enhance the sensitivity of cancer to drugs, lower drug doses, and reduce side effects in cancer treatment. However, differences in the physicochemical properties and pharmacokinetics of different therapeutic agents limit their application. To avoid the above dilemma and achieve accurate control of the synergetic ratio, a nanoscale co-delivery system (NCDS) has emerged as a prospective tool for combined therapy in cancer treatment, which is increasingly being used to co-load different therapeutic agents. In this study, we have summarized the mechanisms of therapeutic agents in combination for cancer therapy, nanoscale carriers for co-delivery, drug-loading strategies, and controlled/targeted co-delivery systems, aiming to give a general picture of these powerful approaches for future NCDS research studies.

Advances in preclinical approaches for intravesical therapy of bladder cancer.

The purpose of this review is to explore new strategies to treat bladder cancer. This article addresses challenges and opportunities in intravesical therapy of bladder cancer. The review examines the latest advances in the development of preclinical approaches for intravesical therapy of bladder cancer. It discusses strategies to improve drug delivery efficiency by using synthesized diverse carriers. Immunotherapy with protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride has been shown to be more effective than intravesical Bacillus Calmette-Guerin. Novel drug delivery systems such the urinary drug-disposing strategy and intravesical nanoparticle formulations improve the drug delivery efficiency while minimizing adverse reactions. Innovative imaging techniques using near-infrared fluorescence probes and multifunctional nano-transformers enable real-time detection and targeted therapy in bladder cancer treatment. Treatment of bladder cancer is clinically challenging. However, recent progress in drug delivery technologies shows promise. Optimizing these technologies helps improve patient outcomes, and facilitates clinical translation of different treatment modalities.

Travel-Time Disparities in Access to Proton Beam Therapy for Cancer Treatment

Proton beam therapy is an emerging radiotherapy treatment for patients with cancer that may produce similar outcomes as traditional photon-based therapy for many cancers while delivering lower amounts of toxic radiation to surrounding tissue. Geographic proximity to a proton facility is a critical component of ensuring equitable access both for indicated diagnoses and ongoing clinical trials. To characterize the distribution of proton facilities in the US, quantify drive-time access for the population, and investigate the likelihood of long commutes for certain population subgroups. This population-based cross-sectional study analyzed travel times to proton facilities in the US. Census tract variables in the contiguous US were measured between January 1, 2017, and December 31, 2021. Statistical analysis was performed from September to November 2023. Drive time in minutes to nearest proton facility. Population totals and prevalence of specific factors measured from the American Community Survey: age; race and ethnicity; insurance, disability, and income status; vehicle availability; broadband access; and urbanicity. Poor access to proton facilities was defined as having a drive-time commute of at least 4 hours to the nearest location. Median drive time and percentage of population with poor access were calculated for the entire population and by population subgroups. Univariable and multivariable odds of poor access were also calculated for certain population subgroups. Geographic access was considered for 327 536 032 residents of the contiguous US (60 594 624 [18.5%] Hispanic, 17 974 186 [5.5%] non-Hispanic Asian, 40 146 994 [12.3%] non-Hispanic Black, and 195 265 639 [59.6%] non-Hispanic White; 282 031 819 [86.1%] resided in urban counties). The median (IQR) drive time to the nearest proton facility was 96.1 (39.6-195.3) minutes; 119.8 million US residents (36.6%) lived within a 1-hour drive of the nearest proton facility, and 53.6 million (16.4%) required a commute of at least 4 hours. Persons identifying as non-Hispanic White had the longest median (IQR) commute time at 109.8 (48.0-197.6) minutes. Multivariable analysis identified rurality (odds ratio [OR], 2.45 [95% CI, 2.27-2.64]), age 65 years or older (OR, 1.09 [95% CI, 1.06-1.11]), and living below the federal poverty line (OR, 1.22 [1.20-1.25]) as factors associated with commute times of at least 4 hours. This cross-sectional study of drive-time access to proton beam therapy found that disparities in access existed among certain populations in the US. These results suggest that such disparities present a barrier to an emerging technology in cancer treatment and inhibit equitable access to ongoing clinical trials.

Dual therapy of cancer using optimal control supported by swarm intelligence.

The scientific revolution in the treatment of many illnesses has been significantly aided by stem cells. This paper presents an optimal control on a mathematical model of chemotherapy and stem cell therapy for cancer treatment. To develop effective hybrid techniques that combine the optimal control theory (OCT) with the evolutionary algorithm and multi-objective swarm algorithm. The developed technique is aimed to reduce the number of cancerous cells while utilizing the minimum necessary chemotherapy medications and minimizing toxicity to protect patients' health. Two hybrid techniques are proposed in this paper. Both techniques combined OCT with the evolutionary algorithm and multi-objective swarm algorithm which included MOEA/D, MOPSO, SPEA II and PESA II. This study evaluates the performance of two hybrid techniques in terms of reducing cancer cells and drug concentrations, as well as computational time consumption. In both techniques, MOEA/D emerges as the most effective algorithm due to its superior capability in minimizing tumour size and cancer drug concentration. This study highlights the importance of integrating OCT and evolutionary algorithms as a robust approach for optimizing cancer chemotherapy treatment.

Concepts of lines of therapy in cancer treatment: findings from an expert interview-based study

ObjectiveThe concept of lines of therapy (LOT) in cancer treatment is often considered for decision making in tumor boards and clinical management, but lacks a common definition across medical specialties. The complexity and heterogeneity of malignancies and treatment modalities contribute to an inconsistent understanding of LOT among physicians. This study assesses the heterogeneity of understandings of the LOT concept, its major dimensions, and criteria from the perspective of physicians of different specialties with an oncological focus in Germany. Semi-structured expert interviews with nine physicians were conducted and evaluated using qualitative content analysis.ResultsMost interviewees agreed that there is no single definition for LOT and found it difficult to explicate their understanding. A majority of experts stated that they had already encountered misunderstandings with colleagues regarding LOT and that they had problems with deciphering LOT from the medical records of their patients. Disagreement emerged about the roles of the following within the LOT concept: maintenance therapy, treatment intention, different therapy modalities, changing pharmaceutical agents, and therapy breaks. Respondents predominantly considered the same criteria as decisive for the definition of LOT as for a change in LOT (e.g., the occurrence of a progression event or tumor recurrence).

Construction of BaTiO3-TiO2 hollow sphere heterojunctions for enhanced microwave dynamic therapy in cancer treatment.

Cancer is one of the primary health concerns among humans due to its high incidence rate and lack of effective treatment. Currently, medical techniques to achieve the precise elimination of local cancer lesions with negligible damage to normal tissues are still intensely desired. Herein, we synthesized BaTiO3-TiO2 hollow spheres (BTHSs) for use in microwave dynamic therapy (MWDT) for cancer. Under UV irradiation, BTHSs can mediate the production of multiple reactive oxygen species (ROS), mainly 1O2, which results in a rapid photocatalytic degradation rate (97%), 1.6-fold that of commercial P25. Importantly, the ROS production process can be triggered by microwaves to effectively execute MWDT for cancer. Under microwave irradiation, BTHSs exhibit a remarkable therapeutic effect and slight cytotoxicity. In terms of mechanism, the enhanced ROS production efficiency of BTHSs can be attributed to their unique hollow structure and the formation of a type-II heterojunction by the incorporation of BaTiO3. The hollow structure increases the availability of active sites and enhances light scattering, while the BaTiO3-TiO2 heterojunction enhances the photocatalytic activity of TiO2 through charge transfer and electron-hole separation. Overall, this study provides important insights into the design and optimization of sensitizers for MWDT applications.

Potent antitumor activity of a bispecific T-cell engager antibody targeting the intracellular antigen KRAS G12V.

Kirsten Rat Sarcoma viral oncogene homolog (KRAS) is one of the most frequent oncogenes. However, there are limited treatment options due to its intracellular expression. To address this, we developed a novel bispecific T-cell engager (BiTE) antibody targeting HLA-A2/KRAS G12V complex and CD3 (HLA-G12V/CD3 BiTE). We examined its specific binding to tumor cells and T cells, as well as its anti-tumor effects in vivo. HLA-G12V/CD3 BiTE was expressed in Escherichia coli and its binding affinities to CD3 and HLA-A2/KRAS G12V were measured by flow cytometry, along with T-cell activation. In a xenograft pancreatic tumor model, the HLA-G12V/CD3 BiTE's anti-tumor effects were assessed through tumor growth, survival time, and safety. Our results demonstrated specific binding of HLA-G12V/CD3 BiTE to tumor cells with an HLA-A2/KRAS G12V mutation and T cells. The HLA-G12V/CD3 BiTE also activated T-cells in the presence of tumor cells in vitro. HLA-G12V/CD3 BiTE in vivo testing showed delayed tumor growth without severe toxicity to major organs and prolonged mouse survival. This study highlights the potential of constructing BiTEs recognizing an HLA-peptide complex and providing a novel therapy for cancer treatment targeting the intracellular tumor antigen.

Long-Term Follow-Up of Phase I Trial of Oncolytic Adenovirus-Mediated Cytotoxic and Interleukin-12 Gene Therapy for Treatment of Metastatic Pancreatic Cancer.

The long-term follow-up findings of the phase I trial evaluating the efficacy of oncolytic adenovirus-mediated cytotoxic and interleukin-12 gene therapy in metastatic pancreatic cancer (mPC) seem very promising. The study employed a replication-competent Adenovector in combination with chemotherapy in a dose-escalation format. The trial demonstrated a clinically meaningful median overall survival (OS) benefit, with patients in the highest dose cohort exhibiting an impressive median OS of 18.4 months. This contrasts starkly with patients receiving lower doses who experienced a median OS of 4.8 and 3.5 months, respectively. Remarkably, subject number 10, who received the highest dose, demonstrated an extraordinary survival of 59.1 months, presenting a compelling case for further exploration. Additionally, this patient displayed complete responses in lung and liver metastases, a rare occurrence in mPC treatment. Statistical analyses supported the observed survival benefit. The unprecedented OS results emphasize the potential of this treatment strategy and pave the way for future investigations into this promising gene therapy approach.

Evaluation of KRAS inhibitor-directed therapies for pancreatic cancer treatment.

Despite significant advancements in the treatment of other cancers, pancreatic ductal adenocarcinoma (PDAC) remains one of the world's deadliest cancers. More than 90% of PDAC patients harbor a Kirsten rat sarcoma (KRAS) gene mutation. Although the clinical potential of anti-KRAS therapies has long been realized, all initial efforts to target KRAS were unsuccessful. However, with the recent development of a new generation of KRAS-targeting drugs, multiple KRAS-targeted treatment options for patients with PDAC have entered clinical trials. In this review, we provide an overview of current standard of care treatment, describe RAS signaling and the relevance of KRAS mutations, and discuss RAS isoform- and mutation-specific differences. We also evaluate the clinical efficacy and safety of mutation-selective and multi-selective inhibitors, in the context of PDAC. We then provide a comparison of clinically relevant KRAS inhibitors to second-line PDAC treatment options. Finally, we discuss putative resistance mechanisms that may limit the clinical effectiveness of KRAS-targeted therapies and provide a brief overview of promising therapeutic approaches in development that are focused on mitigating these resistance mechanisms.

A BRD4‐Targeting Photothermal Agent for Controlled Protein Degradation

BRD4 protein plays a pivotal role in cell cycle regulation and differentiation. Disrupting the activity of BRD4 has emerged as a promising strategy for inhibiting the growth and proliferation of cancer cells. Herein, we introduced a BRD4‐targeting photothermal agent for controlled protein degradation, aiming to enhance low‐temperature photothermal therapy (PTT) for cancer treatment. By incorporating a BRD4 protein inhibitor into a cyanine dye scaffold, the photothermal agent specifically bond to the bromodomain of BRD4. Upon low power density laser irradiation, the agent induced protein degradation, directly destroying the BRD4 structure and inhibiting its transcriptional regulatory function. This strategy not only prolonged the retention time of the photothermal agent in cancer cells but also confined the targeted protein degradation process solely to the tumor tissue, minimizing side effects on normal tissues through the aid of exogenous signals. This work established a simple and feasible platform for future PTT agent design in clinical cancer treatment.

A BRD4-Targeting Photothermal Agent for Controlled Protein Degradation.

BRD4 protein plays a pivotal role in cell cycle regulation and differentiation. Disrupting the activity of BRD4 has emerged as a promising strategy for inhibiting the growth and proliferation of cancer cells. Herein, we introduced a BRD4-targeting photothermal agent for controlled protein degradation, aiming to enhance low-temperature photothermal therapy (PTT) for cancer treatment. By incorporating a BRD4 protein inhibitor into a cyanine dye scaffold, the photothermal agent specifically bond to the bromodomain of BRD4. Upon low power density laser irradiation, the agent induced protein degradation, directly destroying the BRD4 structure and inhibiting its transcriptional regulatory function. This strategy not only prolonged the retention time of the photothermal agent in cancer cells but also confined the targeted protein degradation process solely to the tumor tissue, minimizing side effects on normal tissues through the aid of exogenous signals. This work established a simple and feasible platform for future PTT agent design in clinical cancer treatment.

Current status, challenges and prospects of antifouling materials for oncology applications.

Targeted therapy has become crucial to modern translational science, offering a remedy to conventional drug delivery challenges. Conventional drug delivery systems encountered challenges related to solubility, prolonged release, and inadequate drug penetration at the target region, such as a tumor. Several formulations, such as liposomes, polymers, and dendrimers, have been successful in advancing to clinical trials with the goal of improving the drug's pharmacokinetics and biodistribution. Various stealth coatings, including hydrophilic polymers such as PEG, chitosan, and polyacrylamides, can form a protective layer over nanoparticles, preventing aggregation, opsonization, and immune system detection. As a result, they are classified under the Generally Recognized as Safe (GRAS) category. Serum, a biological sample, has a complex composition. Non-specific adsorption of chemicals onto an electrode can lead to fouling, impacting the sensitivity and accuracy of focused diagnostics and therapies. Various anti-fouling materials and procedures have been developed to minimize the impact of fouling on specific diagnoses and therapies, leading to significant advancements in recent decades. This study provides a detailed analysis of current methodologies using surface modifications that leverage the antifouling properties of polymers, peptides, proteins, and cell membranes for advanced targeted diagnostics and therapy in cancer treatment. In conclusion, we examine the significant obstacles encountered by present technologies and the possible avenues for future study and development.

Fabrication of Carbon Dots with Singlet Oxygen Generation and Their Potential Photodynamic Therapy Applications.

Due to the unique chemical and biomedical properties of carbon dots (CDs), they have increasingly obtained the attention in many research fields, for example, bioimaging, fluorescence sensing, and drug delivery, etc. Recently, it was found that, under light excitation, CDs can also be exploited as a novel photosensitizer to prepare reactive oxygen species (ROS), which expand their applications in the field of photodynamic therapy for cancer treatment. Nevertheless, the high cost and complex fabrication approach of CDs significantly limit their applications. To address this issue, bottom-up routes usually utilize sustainable and inexpensive carbon precursor as starting materials, employed N,N-dimethylformamide (DMF) or ethanol as an environmental-friendly solvent. Bottom-up approach was energy efficient, and the purification process was relatively simple by dialysis. Therefore, carbon dots (CDs) were facilely fabricated in a one-pot solvothermal process using 1-aminoanthraquinone as a precursor, and their application as photosensitizers for in vitro antitumor cells, especially photodynamic therapy (PDT) was established. Then the photophysical and nanoscale dimensions properties of the fabricated CDs were characterized via TEM, UV-visible, fluorescence, and FT-IR spectroscopy. The synthesized N-doped CDs can easily dissolve in water, possess very low biotoxicity, yellow-light emission (maximum peak at 587nm). More importantly, PDT studies demonstrated that the obtained CDs possess a high singlet oxygen yield of 35%, and exhibit significant phototoxicity to cancer cells upon 635nm laser irradiation. These studies highlight that N-doped CDs can be facilely synthesized from only one precursor, and are a potentially novel theranostic agent for in vivo PDT.

Abstract PO3-09-09: Interventions to improve adherence to oral endocrine therapy for prevention or treatment of breast cancer in African American women of low socioeconomic status

Abstract Introduction: Adherence to oral endocrine therapy (OET) for the prevention and treatment of hormone receptor-positive breast cancer (BC) is important as they reduce the risk of new or recurrent BC. OET adherence is greatly compromised in women of lower socioeconomic status (SES). We have recently reported that patients belonging to the African American race, with longer time on OET, and using OET in the prevention setting are more likely to be non-adherent to OET. Therefore, our study aims to design unique patient-centered interventions and pilot test their feasibility, acceptability, and effectiveness in improving OET adherence in African American women of low SES. Patients and Methods: This prospective study includes adult, African American women on OET for either the prevention or treatment of BC at Harris Health System in Houston, Texas, serving the underserved patient population with low SES. The first intervention is a motivational interviewing (MI) based telephone intervention consisting of an initial phone call followed by five monthly follow-up calls with an MI-trained pharmacy student. The second intervention is a theatre-based educational video with a script developed by a local African American playwright, featuring African American women. Three African American BC survivors with experience in taking OET consulted with the study team to convey their BC journey and explain challenges with taking OET. They provided feedback on the script and production of the educational video. Informed consent was obtained verbally via phone in the MI intervention and electronically for the educational video intervention. Individuals in both intervention groups were compensated with Walmart eGift cards. Pre- and post-intervention adherence was measured using the proportion of days covered (PDC) over 6-12 months and compared using a paired t-test. Participants also complete a survey at the end of the interventions to determine their acceptability. The survey responses were summarized descriptively. Results: For the MI intervention initiated in 20 patients, the median age and BMI of study participants was 61 years (range: 49-71) and 30.8 (range: 22.3-57.8) respectively. All participants identified their ethnicity as non-Hispanic or Latino. The majority of participants had hypertension (n=13, 65%) and/or hyperlipidemia (n=11, 55%) with depression (n=3, 15%) and diabetes (n=8, 40%) being less common. The most common stage of BC cancer was stage I (n=9, 45%), followed by stage II (n=4, 20%), stage 0 (n=3, 15%) and then stage III (n=2, 10%) and IV (n=2, 10%). Letrozole was the most common OET (n=13, 65%), followed by tamoxifen (n=3, 15%), anastrozole (n=2, 10%) and exemestane (n=2, 10%). Most participants were not on a CDK 4/6 inhibitor (n=18, 90%). The median number of years on therapy was 2.8 (0.6-4.5). The median pre-intervention PDC for OET was 0.7 (range: 0.2-0.9). The MI intervention is expected to be complete by October 2023 for all patients. For the educational video intervention, 7 out of the anticipated 25 participants have been enrolled in the intervention. All patients were taking OET for BC treatment and not prevention. Letrozole (n=3, 43%) and anastrozole (n=3, 43%) were the most utilized OET, followed by exemestane (n=1, 14%). While 5 participants (71%) in this intervention reported not missing any OET doses in the past week, 2 patients (29%) reported missing all 7 doses within the past week. After watching the educational video, most participants (n=6, 86%) reported that they strongly agreed to take their OET regularly. The recruitment of study participants for this intervention is ongoing. Conclusion: In this study, we report that MI and educational video interventions are feasible. The interventions and analysis of their effectiveness and acceptability are ongoing. Citation Format: Camille Johnson, Ann Adigwe, Nicole Ekezie, Bilqees Fatima, Zahra Majd, Keith Houk, Tejal Patel, Rob Shimko, Onyebuchi Ononogbu, Susan Abughosh, Meghana Trivedi. Interventions to improve adherence to oral endocrine therapy for prevention or treatment of breast cancer in African American women of low socioeconomic status [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-09-09.

Abstract PO5-12-07: Analyzing Patient Experiences with Adjuvant Hormone Therapy for Early Breast Cancer Treatment via NLP/ML on Social Media: Symptoms and Their Mitigation

Abstract Understanding the early breast cancer (eBC) patient experience of disease and treatment is critical to addressing unmet patient needs, improving outcomes, and informing the next wave of drug development. Traditional approaches, such as interviews or focus group studies, are resource intensive and have limitations in reflecting the diverse experiences of patients with different disease characteristics, treatments, and sociodemographic backgrounds, and in detecting rare severe events that could potentially lead to therapy discontinuation. To overcome these limitations, we have developed a semi-automated approach utilizing Natural Language Processing (NLP) and Machine Learning (ML) methods in application to public patient forums to extract patient insights. Specifically, we analyzed 500,000 anonymized posts from the BreastCancer.org forum, utilizing Transformer-based methods to identify posts related to eBC patient experiences treated with standard hormonal therapies (HT). First, a novel ML-based model identified posts related to eBC adjuvant HT. For those, patient demographics, symptoms and their severity, and symptom management strategies such as exercise and yoga were subject to further analysis. Out of 362,074 relevant eBC posts, 32 symptoms and 9 impacts were significantly associated with at least one of the six hormonal therapies we considered. Hot flushes (relative risk [RR]: 6.70; 95% CI: 3.36–13.36), arthralgia (RR: 6.67; 95% CI: 3.53–12.59), weight increase (RR: 4.83; 95% CI: 3.20–7.28), mood swings (RR: 7.36; 95% CI: 5.75–9.42), insomnia (RR: 4.76; 95% CI: 3.14–7.22), and depression (RR: 3.05; 95% CI: 1.71–5.44) demonstrated the strongest associations. Severe headache, dizziness, back pain, and muscle spasms showed significant associations with ≥1 HT despite their low overall prevalence in eBC posts. Notably, posts contained a wide range of symptoms severity, including rarely seen symptoms in smaller patient pools, such as severe night hot flashes leading to treatment discontinuation. Symptoms/impacts mentioned in association with exercise and yoga as a way for symptom mitigation included hot flashes, arthralgia, fatigue, anxiety, depression, and pain. Of those posts, 53.3% to 82.5% reported positive or neutral sentiments for exercise, and 22.2% to 100.0% for yoga. For posts specifically mentioning the management of side effects of HT, between 50.0% and 63.5% had a positive sentiment associated with exercise concerning each of the symptoms/impacts with a lower positive impact related to yoga (between 11.1% and 43.0% of posts). Posts discussing pain management and exercise included a higher proportion of negative feedback, versus positive sentiment for depression. Posts related to yoga as an HT symptom mitigation strategy had a higher prevalence of negative sentiments for anxiety and depression. Our proposed ML/NLP-based approach to collecting patient feedback from publicly available forums complements standard qualitative methods by enabling the scalable extraction of insights from hundreds of thousands of online conversations that could span a broad diversity of symptoms and well-being reflections. Furthermore, our findings suggest the potential value of informing clinical outcome assessment (COA) measurement for clinical trials, alone and in combination with standard qualitative research approaches to guide the next clinical development. Overall, our study highlights the significant potential of NLP and ML to address the critical need to better understand the eBC patient experience of disease and treatment to improve outcomes for patients. Citation Format: Sameet Sreenivasan, Chao Fang, Emuella Flood, Natasha Markuzon, Jasmine Sze. Analyzing Patient Experiences with Adjuvant Hormone Therapy for Early Breast Cancer Treatment via NLP/ML on Social Media: Symptoms and Their Mitigation [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-12-07.

Abstract PO5-18-05: Assessment of the Potential of Photon mini-GRID Therapy for Pre-operative Partial Breast Cancer Treatment

Abstract Purpose We propose a new spatially fractionated radiation therapy (SFRT) technique, called mini-GRID therapy, to reduce normal tissue toxicities in pre-operative partial breast cancer radiotherapy. Mini-GRID therapy, an optimized implementation of GRID therapy, utilizes very narrow beams (widths ~ 1-2 mm) which significantly increase normal tissue tolerances. The concept, proposed by our team in 2017 [1], has been successfully implemented at Hospital de Santiago de Compostela (Spain) showing excellent results in terms of brain toxicity reduction [2]. Profiting from this remarkable increase in tolerance, this study aims to evaluate the feasibility and efficacy of photon mini-GRID therapy for pre-operative partial breast cancer treatment. Methods Ten unbiased clinical cases were selected for the study, comparing photon mini-GRID therapy with conventional broad beam radiotherapy. Monte Carlo simulations (TOPAS v.3.6) were performed based on the mini-GRID therapy implementation (megavoltage X-rays, Varian flattening-filter-free LINAC) realized at the University Hospital in Santiago de Compostela. A mean dose of 24 Gy was delivered in the PTV using three photon mini-GRID arrays with mini beams of approximately 1.8x1.8 mm² at the isocenter. The study aimed to achieve better tumor coverage than conventional pre-operative radiotherapy while ensuring comparable skin toxicity. Valley doses, determining tissue-sparing effects, were compared against organs-at-risk (OARs) tolerance limits. Results The mini-GRID therapy treatments ensured partial tumor coverage and met the dose tolerance limits for all the considered OARs, the most challenging of all being the skin [3]. Peak-to-valley dose ratio (PVDR) in the skin was higher than 3.5 for all the considered patients. Compared to standard radiotherapy (SRT) plans, mini-GRID therapy significantly reduced mean doses to the lungs, heart, and chest wall in the studied cases. Conclusion In this proof-of-concept study, we evaluated photon mini-GRID therapy with megavoltage X-rays as an alternative treatment approach for pre-operative partial breast cancer irradiation, demonstrating its feasibility and straightforward implementation. Because of its high skin and normal tissue-sparing capacities, photon mini-GRID therapy has great potential to improve pre-operative treatment outcomes. Complementary studies and clinical validation are needed to fully establish the optimal protocols and assess long-term effects, but the results encourage the integration of photon mini-GRID therapy as a promising modality for breast cancer therapy.