Toxicity Of Cancer Treatment Research Articles

Toxicity and costs of cancer treatment reduced by deferring CDK4/6 inhibitor use

Toxicity and costs of cancer treatment reduced by deferring CDK4/6 inhibitor use

Chemical composition, cytotoxic potential and antioxidant properties of Punica granatum peel extract

Purpose: To evaluate the antioxidant activity of pomegranate peel extract and its effects on the survival of colorectal cancer cells (Caco-2) and kidney cells (HEK293). Methods: An ethanol extract was prepared from the outer layer of pomegranate peels. The chemical composition of the extract was examined using high-performance liquid chromatography with diodearray detection (HPLC-DAD) and liquid chromatography with tandem mass spectrometry (LC-MS-MS). Antioxidant activity was determined using DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'- azinobis(3-ethylbenzothiazoline-6-sulfonic acid)) assays. Cytotoxicity was tested against Caco-2 colorectal cancer cells and HEK293 normal kidney cells using MTT assay. Results: The pomegranate peel extract was rich in phenolic compounds and demonstrated significant antioxidant activity, with IC50 values comparable to Trolox in DPPH and ABTS assays. The extract exhibited selective and concentration-dependent cytotoxicity against Caco-2 cells, with an EC50 of 121.05 ± 13.12 µg/mL, while showing minimal toxicity towards HEK293 cells. Conclusion: Pomegranate peel extract's high phenolic content and potent antioxidant properties highlight its potential as a therapeutic agent against colorectal cancer. The findings suggest that this extract could serve as a viable, natural alternative with reduced toxicity for colorectal cancer treatment.

A combined treatment with Ursolic acid and Solasodine inhibits colorectal cancer progression through the AKT1/ERK1/2-GSK-3β-β-catenin axis

BackgroundConventional chemotherapy medications are inadequate for managing the primary or acquired drug resistance, high toxicity, and adverse effects of colorectal cancer (CRC) treatment. Ursolic acid (UA) and Solasodine (Sol) are natural compounds found in a wide variety of traditional medicinal plants, as well as in many fruits and vegetables, such as Actinidia arguta (Sieb. & Zucc) Planch and Solanum nigrum L.. These compounds exhibit significant anti-tumor activity. Recent investigations have demonstrated that a combination strategy using natural products exhibits greater potential in CRC treatment compared to a single-drug strategy. PurposeThis study aimed to elucidate the potential of UA-Sol synergy against CRC and to investigate the mechanism of action involved in inducing apoptosis and inhibiting metastasis through the AKT1/ERK1/2-GSK-3β-β-catenin axis. MethodsThe optimal ratio of UA-Sol and its synergistic effects were explored using an MTT assay combined with the technique of Chou Talalay. The effects of UA-Sol on the apoptosis, autophagy, and metastasis of CRC cells were assessed using Annexin V-FITC/PI, TUNEL, Immunofluorescence, Wound healing, Transwell migration, and western blotting. The core mechanism of action of UA-Sol against CRC was investigated employing network pharmacology prediction combined with CETSA and plasmid transfection. Finally, in vivo validation was conducted using mouse xenograft tumor and lung metastasis models. ResultsThe combination of UA and Sol synergistically inhibited CRC cell viability at a molar ratio of 6:24. UA-Sol induced the expression of pro-apoptotic and autophagy genes such as Bax/Bcl-2 and LC3, ultimately leading to apoptosis and autophagy in CRC cells in vitro. In addition, this combination inhibited MMP-9 and promoted the expression of the adhesion protein E-cadherin, thereby inhibiting CRC cell metastasis. Mechanistically, UA-Sol regulated the expression of a downstream protein GSK-3β by targeting AKT1 and ERK1/2 inhibition. This induced a cross-talk between the MAPK cascade pathway and the PI3K/AKT pathway, thereby inhibiting the nuclear translocation of β-catenin and participating in the regulation of CRC cell processes. ConclusionUA-Sol inhibited the AKT1/ERK1/2-GSK-3β-β-catenin axis to induce apoptosis, autophagy and anti-metastasis by targeting AKT1 and ERK1/2 inhibition. This dual-target drug combination strategy provides promising insights into the development of novel, safe, and efficient drugs for the treatment of CRC.

Recent advances in cancer therapy-associated oral mucositis.

Oral mucositis (OM) is a common and debilitating toxicity of cancer treatments - chemotherapy, radiotherapy, hematopoietic cell transplant, or combinations. OM is associated with severe oral pain and has negative impacts on patient function and quality of life. Additionally, OM has accompanying systemic complications that may have critical implications. These local and systemic consequences can alter cancer treatment, and add an economic burden. This review covers the clinical presentation and course of OM, differential diagnosis, clinical and economic impacts, pathogenesis, risk factors, assessment measures, biomarkers and prediction of OM, management, research advances in the development of new drugs and treatments, and big data.

A web-based, LLM-powered AI symptom summarization tool (ASST) for monitoring of breast cancer treatment toxicity.

e13622 Background: Traditional methods for capturing patient-reported outcomes (PROs) are often time-consuming and may lead to underreporting of symptoms by physicians. With advancements in artificial intelligence (AI), particularly large language models (LLMs) like GPT-4, there is potential to revolutionize this aspect of patient care. Methods: This study developed and tested a GPT-4-based web application for monitoring cancer treatment toxicity in breast cancer patients. The application utilized 35 items from the PRO-CTCAE scale to create an interactive form for patients to report treatment-related symptoms. Upon form completion, a natural language summary of the patient’s responses was generated using the GPT-4 API for physician review. Nine radiation oncologists (5 attendings, 4 residents) evaluated the summaries of virtual patients using the adapted Physician Documentation Quality Index (PDQI-9). PDQI-9 consists of 9 items scored using a 5-point Likert scale (1 -not at all- to 5. -extremely-). IRB approval was not required because this study did not use real patient data, in accordance with the 2018 Revised Common Rule Requirements of the NIH. All data used were researcher-generated and non-identifiable. Results: The mean time for textual summary generation was 7 (5.7-9.2) seconds. The AI-Symptom Summarization Tool (ASST) mean scores were 4.25 for accuracy and 4 for thoroughness. Usefulness, organization, comprehensibility, concision, synthesis quality and consistency were all rated between 3 and 4. Overall score was 42/50. No hallucinations (false information made up by the LLM) were found. Conclusions: The GPT-4-based application for cancer treatment toxicity monitoring demonstrates significant promise in enhancing the quality and efficiency of patient care. By automating the documentation of patient-reported symptoms, this tool could allow physicians to focus more time on patient interaction and individualized care. As AI technologies continue to evolve, their integration into clinical practice must be approached with caution, emphasizing augmentation over replacement and the importance of verification to maintain trust in these new tools.

Breast cancer outcomes and treatment toxicity in geriatric patients compared to other patients at the Cancer Disease Hospital in Zambia.

e13773 Background: Breast cancer is the second most common cancer in women in Zambia and the most common cancer in older women. Management of geriatric cancer patients can be challenging due to physiological changes and multiple comorbidities. Methods: Data was extracted from the CDH electronic database of breast cancer patients for November 2005 - November 2022. Geriatric patients were defined as those 65 years old or older. Data was analyzed using descriptive statistics. Clinical-pathologic characteristics and outcomes for geriatric (GP) and younger patients were compared using the Chi Squared Test/Fisher’s exact test for discrete and Student’s T-test for continuous variables. All p-values were two-sided. Results: Of 1981 patients, 493 (24.9%) were geriatric. 374 (18.9%) had Stage I/II cancer, 607 (30.6%) Stage III, 579 (29.2%) de novo Stage IV, with no differences between geriatric and younger patients. 441 (22.2%) had hormone receptor-positive (HR+) disease, 115 (5.8%) had HER2+ by IHC, 195 (9.3%) were triple-negative, 52 (2.6%) HR+HER2+. Geriatric patients were more likely to have invasive lobular carcinoma (4.6% v. 2.4%), less likely to have grade 3 (42.0% v 50.6%) or HER2+ (11.6% v 19.3%) cancer. 1889 (94.8%) received systemic treatment, 1188 (60.0%) surgery, and 844(42.6%) radiation (RT), with no differences in geriatric and younger patients. Geriatric patients were less likely to receive palliative RT (9.6% v 15.7%), to receive a lower total RT dose and had similar rates of RT dermatitis as younger patients. Geriatric patients were less likely to be treated with doxorubicin, docetaxel and more likely with methotrexate. After median follow-up of 1.1 years (st. dev 2.6), 301(15.2%) were alive without disease, 826 (41.7%) alive with cancer, 203 (10.2%) died from cancer, with no difference in local, distal recurrence, or survival for geriatric patients. Geriatric patients were less likely to be in good physical condition (33.9% v 39.4%) and more likely to have a worse ECOG (1.0% v 0.4% for ECOG 4, 4.1% v 2.4% for ECOG 3, 14.0% v 10.9% for ECOG 2, 73.4% v 75.8% for ECOG 1, 7.4% v 10.4% for ECOG 0). Geriatric patients had a lower number of total treatment toxicities (OR 0.95, 95% CI 0.91-0.98) and were less likely to have leukopenia (OR 0.89, 95% CI 0.83-0.94) and neutropenia (OR 0.88, 95% CI 0.82-0.95). (for similar outcomes p-value > 0.05; all where differences are noted p-value < 0.05). Conclusions: GPs were similar to other patients in terms of cancer stage and outcomes and had less aggressive disease. GPs had worse functional status, received less toxic chemotherapy, were less likely to receive surgery and RT. GPs had either a similar amount or less treatment toxicity compared to other patients. Results are limited by short follow-up of about 1.5 years. Results are limited by incomplete non-hematologic toxicity data.

Financial toxicity in the background of free health care: A cross-sectional survey in a tertiary care hospital in India.

e13685 Background: The financial toxicity of cancer treatment is a known fact in low to middle-income countries due to poverty, lack of health insurance and illiteracy. We tried to estimate the financial strain and its contributing factors in an Indian population with access to free cancer treatment. Methods: All government employees and their dependents are eligible to receive free treatment including inpatient management, investigations and medicines at our institute. All cancer patients ≥18 years were invited to participate in a survey. The survey included their demographic, cancer and therapy details, the COST-FACIT questionnaire, and information about increase in expenses since cancer diagnosis and source of additional finances. Results: 300 cancer patients completed the survey. 61.3% of the respondents were females and the mean patient age was 43.14 years. Breast cancer was the most common malignancy and stage IV was the most common stage. 44% were residents of a rural area. The average duration of treatment was 8.03 months. Prior to cancer diagnosis, 37.2% of the patients had average monthly expenses between INR 10-25,000 (USD 120 to 300). The approximate increase in monthly expenditures after cancer diagnosis was between INR 5-10,000 (USD 60 to 120) for 33.4% and between INR 10-25,000 (USD 120 to 300) for 31.4% of the population. The primary income source for 65.7% respondents was the salary of the government employee while 48% had two or more earning members in the family. Cancer treatment negatively affected the earning capacity of the patient alone in 40% of the population, while in 28% it affected the earning capacity of the patient and caregiver. 51% had to utilise their savings, 39% sold fixed assets, and 31% borrowed or took a loan to cope with the additional financial strain. Commonest expenses were travel, accommodation, and food (75.7%). 34.5% spent money on other therapy-related costs (second opinion or alternative therapy). The mean COST-FACIT score was 21.38,(20-24) demonstrating mild financial toxicity. Predictors of high financial toxicity were a single-earning member, familial discord and long duration of treatment (> 6 months). Conclusions: Though all participants had access to free cancer treatment, all experienced mild financial toxicity due to non-therapeutic expenses. Despite desperate financial measures to complete treatment, most participants did not express severe financial toxicity. This may be attributed to the stigma of expected high expenditure associated with cancer treatment in India. COST-FACIT scoring may not have suitably assessed the financial strain experienced by patients with free healthcare. Additional financial information collected by the survey, (monthly expenses, earning members, source of additional funds), helped us to better understand financial impact of cancer treatment and identify gaps in our healthcare.

Exercise adherence for patients with trismus after head and neck cancer treatment.

Head and neck cancer treatment often leads to trismus, a condition characterized by limited mouth opening. Exercise-based therapy is the most common intervention but there are no clear guidelines as to the optimal exercise regimen. Restorabite™ is a portable and force-regulated trismus device designed to enhance exercise adherence. This study explores the adherence to exercises using Restorabite™ in head and neck cancer patients with trismus and identifies facilitators and barriers to exercise therapy. Mixed-methods, prospective cohort study undertaken at a quaternary oncology hospital, in Sydney Australia involving participants diagnosed with head and neck cancer diagnosed with trismus (maximal incisal opening under 35 mm). Patients underwent a 10-week individualized trismus program using Restorabite™ with weekly speech pathology reviews. Exercise adherence was tracked through categorized descriptors. Data were collected prospectively at baseline, during 10 weeks of therapy with Restorabite™, and at 6- and 12-month post-trismus exercise. Participants described facilitators of trismus therapy, and barriers to completing the prescribed exercises. Clinical documentation of these responses was then analyzed using content analysis. One-hundred and thirty-five participants were recruited. During the intervention 69% (n = 93) exercised as recommended, 24% (n = 32) exercised less, and 7% (n = 10) exercised more than recommended. At 6 months post-intervention, 55.5% (n = 75) exercised as recommended, 38.5% (n = 52) exercised less, and 4% (n = 6) exercised more. At 12 months, 36% (n = 49) exercised as recommended, 48% (n = 62) exercised less, and 11% (n = 15) exercised more. MIO increased from a mean of 18.6 mm at baseline, to 30.1 mm at the end of the 10-week intervention. This was maintained at 6 and 12 months (31.7 and 32.1 mm, respectively). Adherence to the exercise program was associated with greater improvement in maximum interincisal opening (p < 0.001). Facilitators of adherence included intrinsic motivation, device portability, perceived functional change, and external support tools. Barriers included cancer treatment toxicities, competing priorities, and health challenges. Positive outcomes included functional improvements, while negative outcomes included increased pain. Seventy-six percent of patients prescribed Restorabite™ performed trismus exercises at or more than the recommended frequency. Facilitators and barriers identified provide insights into factors influencing adherence. Future research should involve comparative studies that compare the adherence and effectiveness of different exercise programs.

Cannabis and Cannabinoids in Adults With Cancer: ASCO Guideline.

To guide clinicians, adults with cancer, caregivers, researchers, and oncology institutions on the medical use of cannabis and cannabinoids, including synthetic cannabinoids and herbal cannabis derivatives; single, purified cannabinoids; combinations of cannabis ingredients; and full-spectrum cannabis. A systematic literature review identified systematic reviews, randomized controlled trials (RCTs), and cohort studies on the efficacy and safety of cannabis and cannabinoids when used by adults with cancer. Outcomes of interest included antineoplastic effects, cancer treatment toxicity, symptoms, and quality of life. PubMed and the Cochrane Library were searched from database inception to January 27, 2023. ASCO convened an Expert Panel to review the evidence and formulate recommendations. The evidence base consisted of 13 systematic reviews and five additional primary studies (four RCTs and one cohort study). The certainty of evidence for most outcomes was low or very low. Cannabis and/or cannabinoid access and use by adults with cancer has outpaced the science supporting their clinical use. This guideline provides strategies for open, nonjudgmental communication between clinicians and adults with cancer about the use of cannabis and/or cannabinoids. Clinicians should recommend against using cannabis or cannabinoids as a cancer-directed treatment unless within the context of a clinical trial. Cannabis and/or cannabinoids may improve refractory, chemotherapy-induced nausea and vomiting when added to guideline-concordant antiemetic regimens. Whether cannabis and/or cannabinoids can improve other supportive care outcomes remains uncertain. This guideline also highlights the critical need for more cannabis and/or cannabinoid research.Additional information is available at www.asco.org/supportive-care-guidelines.

Predictors of radiation-induced late rectal toxicity in prostate cancer treatment: a volumetric and dosimetric analysis.

Prostate cancer (PCa) is a prevalent malignancy in European men, often treated with radiotherapy (RT) for localized disease. While modern RT achieves high success rates, concerns about late gastrointestinal (GI) toxicities persist. This retrospective study aims to identify predictors for late GI toxicities following definitive conventionally fractionated external beam RT (EBRT) for PCa, specifically exploring the dose to the rectal wall. A cohort of 96 intermediate- to high-risk PCa patients underwent EBRT between 2008 and 2016. Rectum and rectum wall contours were delineated, and 3D dose matrices were extracted. Volumetric and dosimetric indices were computed, and statistical analyses were performed to identify predictors using the Mann-Whitney U-rank test, logistic regression, and recursive feature elimination. In our cohort, 15 out of 96 patients experienced grade II late proctitis. Our analysis reveals distinct optimal predictors for rectum and rectum wall (RW) structures varying with α/β values (3.0 and 2.3 Gy) across prescribed doses of 68 to 76 Gy. Despite variability, RW predictors demonstrate greater consistency, notably V68Gy[%] to V74Gy[%] for α/β 3.0 Gy, and V68Gy[%] to V70Gy[%] for α/β 2.3 Gy. The model with α/β 2.3 Gy, featuring RW volume receiving 70 Gy (V70Gy[%]), stands out with a BIC value of 62.92, indicating its superior predictive effectiveness. Finally, focusing solely on the rectum structure, the V74Gy[%] emerges the best predictor for α/β 3.0 Gy, with a BIC value of 66.73. This investigation highlights the critical role of V70Gy[%] in the rectum wall as a robust predictor for grade II late gastrointestinal (GI) toxicity following external beam radiation therapy (EBRT) for prostate cancer (PCa). Furthermore, our findings suggest that focusing on the rectum wall specifically, rather than the entire rectum, may offer improved accuracy in assessing proctitis development. A V70Gy (in EQD2 with α/β 2.3 Gy) of ≤5% and if possible ≤1% for the rectal wall should be achieved to minimize the risk of late grade II proctitis.

Impact of chrono-radiotherapy on the prognosis and treatment-related toxicity in patients with locally advanced nasopharyngeal carcinoma: A multicenter propensity-matched study

ABSTRACT The timing of radiotherapy (RT) delivery has been reported to affect both cancer survival and treatment toxicity. However, the association among the timing of RT delivery, survival, and toxicity in locally advanced nasopharyngeal carcinoma (LA-NPC) has not been investigated. We retrospectively reviewed patients diagnosed with LA-NPC who received definitive RT at multiple institutions. The median RT delivery daytime was categorized as morning (DAY) and night (NIGHT). Seasonal variations were classified into the darker half of the year (WINTER) and brighter half (SUMMER) according to the sunshine duration. Cohorts were balanced according to baseline characteristics using propensity score matching (PSM). Survival and toxicity outcomes were evaluated using Cox regression models. A total of 355 patients were included, with 194/161 in DAY/NIGHT and 187/168 in WINTER/SUMMER groups. RT delivered during the daytime prolonged the 5-year overall survival (OS) (90.6% vs. 80.0%, p = 0.009). However, the significance of the trend was lost after PSM (p = 0.068). After PSM analysis, the DAY cohort derived a greater benefit in 5-year progression-free survival (PFS) (85.6% vs. 73.4%, p = 0.021) and distant metastasis-free survival (DMFS) (89.2% vs. 80.8%, p = 0.051) in comparison with the NIGHT subgroup. Moreover, multivariate analysis showed that daytime RT was an independent prognostic factor for OS, PFS, and DMFS. Furthermore, daytime RT delivery was associated with an increase in the incidence of leukopenia and radiation dermatitis. RT delivery in SUMMER influenced only the OS significantly (before PSM: p = 0.051; after PSM: p = 0.034). There was no association between toxicity and the timing of RT delivery by season. In LA-NPC, the daytime of radical RT served as an independent prognostic factor. Furthermore, RT administered in the morning resulted in more severe toxic side effects than that at night, which needs to be confirmed in a future study.

Chronotherapy for Cancer Treatment: A Review of Timing Strategies

Chronotherapy, the delivery of drugs in accordance with the body's circadian cycle, has become a promising strategy to increase the effectiveness and lower the toxicity of cancer treatment. Cell division, DNA repair, and metabolism are three physiological functions regulated by the circadian clock that are known to affect how well anti-cancer treatments work. This study reviews the present status of research on timing techniques in order to offer a thorough overview of chronotherapy in the treatment of cancer. The review starts off by going over the basic ideas of circadian rhythms and how they relate to cancer biology. The justification for adopting chronotherapy to improve treatment results is then discussed, including the possibility of increasing therapeutic efficacy while reducing side effects. A full analysis of preclinical research is then provided, emphasizing the influence of treatment scheduling on drug metabolism, host-tumor interactions, and tumor growth inhibition. The significance of taking circadian rhythms into account while developing cancer treatment plans is emphasized in this study. The complicated interactions between circadian biology, tumor dynamics, and treatment effects are highlighted, underscoring the need for more study. In the end, utilizing the power of chronotherapy has the potential to transform cancer treatment by customizing regimens based on each patient's inherent rhythms.

Abstract 492: Investigating solute carrier SLC46A3 to enhance nanotherapeutic delivery for cancer

Abstract BACKGROUND: Nanoparticle therapeutics have multifaceted potential to improve efficacy and decrease toxicity of cancer treatments. Nanotherapeutics can encapsulate a range of cargos and have tunable surface chemistry that can enhance drug delivery to tumors. Cellular features also play a role in successful drug delivery, and predictive biomarkers may improve patient selection for clinical trials. In previous work, we identified SLC46A3, a poorly characterized lysosomal solute carrier, as a strong negative regulator of lipid-based nanoparticle uptake across many cancer models. We hypothesize that the expression of SLC46A3 will act as a predictive biomarker for therapeutic nanoparticles. METHODS: To test this hypothesis, we used two engineered model systems to probe the relationship between SLC46A3 expression and therapeutic response: lentiviral overexpression in a natively low-expressing melanoma model and genetic deactivation in a natively high-expressing breast cancer model. A library of FDA-approved and experimental therapeutic nanoparticles were screened in both models under a range of conditions. Liposomal formulations of chemotherapeutics were included with high and low surface functionalization of polyethylene glycol to investigate the impact of this ubiquitous ‘stealth’ polymer on our biomarker of interest. Solid lipid nanoparticles with nucleic acid cargo were also included. Orthogonal methods were used to probe these interactions and the therapeutic efficacy of nanotherapeutics, including pulsed dosing viability assays and label-free live-cell imaging. RESULTS: We found that SLC46A3 expression is a class-specific biomarker of lipid-based nanoparticle uptake and is predictive of distinctive patterns of response to therapy-loaded nanoparticles in both formulation and time-dependent manners. Additionally, we present a new technology for long-term, live cell imaging of nanoparticle uptake and trafficking that can discriminate mechanisms of cytotoxicity, accelerating the study of nano-bio interactions. These findings highlight a promising approach for the functional validation of nanoparticle-specific biomarkers using clinically relevant formulations that have the potential for rapid repurposing. Citation Format: Julianna Kenny-Serrano, Elizabeth B. Nelson, Gil Covarrubias, Namita Nabar, Joelle Straehla, Aanchal Gupta, Natalie Boehnke, Paula Hammond. Investigating solute carrier SLC46A3 to enhance nanotherapeutic delivery for cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 492.

Roadmap for Connecting Cancer Rehabilitation With Survivorship to Improve Patient Outcomes and Clinical Efficiency.

An evolved model of comprehensive cancer care is needed that begins at cancer diagnosis to proactively manage cancer treatment toxicities and optimize patient health, function, and well-being. Building new care models requires connecting oncology, primary care, and specialized clinicians from many disciplines including cancer rehabilitation. Having a vision for an evolved standard of comprehensive cancer care is a requirement, but it is not enough to bring an innovative clinical program to life and sustain it over the long term. To inform the development of new clinical programs, two example programs are presented that successfully integrate cancer rehabilitation services along with details of a three-step process these programs used to facilitate their success and build robust business models that ensure their sustainability. Following the roadmap for growth presented here, gaining input from stakeholders and ensuring their buy-in, leveraging existing programmatic priorities, as well as developing a strategic growth plan can help clinical innovators ensure that new programs anticipate and continually meet the needs of oncology, primary care, subspecialty care, and programs, while addressing the business needs of administrators and improving the experience for patients.

Harnessing Nanotechnology for Optimized Herbal Cancer Treatment: A Comprehensive Review of Nanoscale Drug Delivery Systems

Cancer is widely recognized as the second leading cause of death on a global scale. In recent years, nanotechnology has emerged as a promising strategy in the field of cancer therapy. Nanoscale drug delivery systems, a category of innovative technologies, harness the potential of various nanoparticles and nanomaterials to efficiently transport chemotherapeutic drugs, revolutionizing cancer treatment. The use of natural products has shown substantial promise in both the prevention and therapy of cancer. Herbal medicines, in particular, have gained widespread use due to their inherent therapeutic advantages and notably fewer adverse effects compared to modern drugs. However, their hydrophobic nature has presented a challenge, limiting their bioavailability and therapeutic efficacy. To overcome these limitations, researchers have developed nanocarriers tailored for the delivery of therapeutic agents to specific target cells. The combination of nanocarriers with herbal remedies results in improved bioavailability, enhanced pharmacological activity, and increased stability, all while minimizing systemic toxicity in cancer treatment. This review provides a comprehensive discussion of novel nanocarriers that find application in cancer treatment, with a specific focus on herbal medicine. The amalgamation of these innovative approaches offers promising prospects for the future of cancer therapy.

Exercise and the gut microbiome: implications for supportive care in cancer.

Growing recognition of the gut microbiome as an influential modulator of cancer treatment efficacy and toxicity has led to the emergence of clinical interventions targeting the microbiome to enhance cancer and health outcomes. The highly modifiable nature of microbiota to endogenous, exogenous, and environmental inputs enables interventions to promote resilience of the gut microbiome that have rapid effects on host health, or response to cancer treatment. While diet, probiotics, and faecal microbiota transplant are primary avenues of therapy focused on restoring or protecting gut function in people undergoing cancer treatment, the role of physical activity and exercise has scarcely been examined in this population. A narrative review was conducted to explore the nexus between cancer care and the gut microbiome in the context of physical activity and exercise as a widely available and clinically effective supportive care strategy used by cancer survivors. Exercise can facilitate a more diverse gut microbiome and functional metabolome in humans; however, most physical activity and exercise studies have been conducted in healthy or athletic populations, primarily using aerobic exercise modalities. A scarcity of exercise and microbiome studies in cancer exists. Exercise remains an attractive avenue to promote microbiome health in cancer survivors. Future research should elucidate the various influences of exercise modalities, intensities, frequencies, durations, and volumes to explore dose-response relationships between exercise and the gut microbiome among cancer survivors, as well as multifaceted approaches (such as diet and probiotics), and examine the influences of exercise on the gut microbiome and associated symptom burden prior to, during, and following cancer treatment.

A Study Evaluating Financial Toxicity Amongst Hematologic Malignancy Patients in the Bronx

Introduction Financial toxicity (FT) in cancer care is a growing public health problem faced by patients, caregivers, and oncologists . This burden is more pronounced in hematologic malignancies (HM), given the intense nature and novel but costly therapies in this patient population.Underserved communities face disproportionately higher financial toxicity of cancer treatment. This study aims to determine the impact of sociodemographic factors and clinical characteristics on the severity of FT in patients treated for HM, largely from underserved communities in a tertiary care hospital in the Bronx. Methods This prospective ongoing survey-based study is being carried out at the Montefiore Medical Center, Bronx, NY. All patients were adults categorized into newly diagnosed (ND) patients with HM and those receiving cellular therapy (CT): autologous/allogeneic stem cell transplantation and CAR-T cell therapy. Investigator designed questionnaire was used to obtain sociodemographic and clinical characteristics of the patients, while The Comprehensive Score for Financial Toxicity (COST-FACIT) questionnaire, a validated FT tool, was used to determine the severity of FT for each patient. Patients were given a score based on their answers for the COST-FACIT questionnaire: score 0 = Grade 3 - severe FT; 1-13 = Grade 2 - moderate FT; 14-26 = Grade 1 - mild FT and &amp;gt;26 = Grade 0 - no toxicity. Surveys were administered on day 0, day 30, and day 90. We looked at mean FT scores according to sociodemographic factors, disease type, and treatment arms. The student's t-test ANOVA was used for statistical analysis using SPSS software. This study was approved by the institutional IRB. Results We have recruited a total of 72 patients at the time of analysis to date (Table). At Day 0, there were 41 patients in the ND group and 31 patients in the CT group. In the ND group, 31 and 25 of them had completed the day 30 and day 90 survey respectively, while in the CT group, 20 and 9 patients completed the day 30 and day 90 survey, respectively. Seven patients (4 in ND, and 3 in CT cohort) died at the time of their first survey. The mean FT for various demographic and clinical characteristics is summarized in the table. We obtained further information using our questionnaire and correlated it to the COST-FACIT score. On day 0, 10 patients (24.4%) in the ND cohort and 5patients (16%) in the CT cohort reported having difficulty paying for food, shelter, and clothing often to most of the time. Over 90% of these patients reported moderate to severe FT on the COST-FACIT survey .On day 0, 10 patients (24.4%) of ND patients and 10 patients (32.3%) of CT patients reported delays in seeking medical care or missing medications due to inability to pay. Seventy percent of these patients had moderate to severe FT on day 0. On enquiring about emotional well-being over the last four weeks, 16% (6 in the ND cohort, 6 in the CT cohort) reported feeling depressed, anxious, depressed, and sad often to most of the time. 83% of those had moderate to severe FT. Comparing the mean FT longitudinally between the two arms, most patients experienced mild FT, but the CT group on Day 30, had a higher FT than on Day 0. Conclusion Our results show that a sizeable proportion of patients in the Bronx report financial strain at baseline that leads to emotional stress, difficulty in paying for food, basic necessities and leads to delay in seeking medical care or skipping medications. We also see that patients who are referred for CT potentially have worse financial toxicity over time. This group may be even more vulnerable given that CT is offered at select FACT-accredited centers and patients may have to travel longer distances. Our data is capturing only those patients who were able to make it to CT and there may be a selection bias introduced by the nature of this data. We will report further follow-up data at the meeting considering disease-specific treatments and aim to design specific interventions for this patient population.

Long-term cardiotoxicity in germ cell cancer survivors after platinum-based chemotherapy: cardiac MR shows impaired systolic function and tissue alterations

ObjectivesLong-term toxicities of germ cell cancer (GCC) treatment are of particular importance in young men with a life expectancy of several decades after curative treatment. This study aimed to investigate the long-term effects of platinum-based chemotherapy on cardiac function and myocardial tissue in GCC survivors by cardiac magnetic resonance (CMR) imaging.MethodsAsymptomatic GCC survivors ≥ 3 years after platinum-based chemotherapy and age-matched healthy controls underwent CMR assessment, including left ventricular (LV) and right ventricular (RV) ejection fraction (EF), strain analysis, late gadolinium enhancement (LGE) imaging, and T1/T2 mapping.ResultsForty-four survivors (age 44 [interquartile range, IQR 37–52] years; follow-up time 10 [IQR 5–15] years after chemotherapy) and 21 controls were evaluated. LV- and RVEF were lower in GCC survivors compared to controls (LVEF 56 ± 5% vs. 59 ± 5%, p = 0.017; RVEF 50 ± 7% vs. 55 ± 7%, p = 0.008). Seven percent (3/44) of survivors showed reduced LVEF (< 50%), and 41% (18/44) showed borderline LVEF (50–54%). The strain analysis revealed significantly reduced deformation compared to controls (LV global longitudinal strain [GLS] -13 ± 2% vs. -15 ± 1%, p < 0.001; RV GLS -15 ± 4% vs. -19 ± 4%, p = 0.005). Tissue characterization revealed focal myocardial fibrosis in 9 survivors (20%) and lower myocardial native T1 times in survivors compared to controls (1202 ± 25 ms vs. 1226 ± 37 ms, p = 0.016). Attenuated LVEF was observed after two cycles of platinum-based chemotherapy (54 ± 5% vs. 62 ± 5%, p < 0.001).ConclusionBased on CMR evaluation, combination chemotherapy with cumulative cisplatin ≥ 200 mg/m2 is associated with attenuated biventricular systolic function and myocardial tissue alterations in asymptomatic long-term GCC survivors.Clinical relevance statementPlatinum-based chemotherapy is associated with decreased systolic function, non-ischemic focal myocardial scar, and decreased T1 times in asymptomatic long-term germ cell cancer survivors. Clinicians should be particularly aware of the risk of cardiac toxicity after platinum-based chemotherapy.Key Points• Platinum-based chemotherapy is associated with attenuation of biventricular systolic function, lower myocardial T1 relaxation times, and non-ischemic late gadolinium enhancement.• Decreased systolic function and non-ischemic late gadolinium enhancement are associated with a cumulative cisplatin dose of ≥ 200 mg/m2.• Cardiac MRI can help to identify chemotherapy-associated changes in cardiac function and tissue in asymptomatic long-term germ cell cancer survivors.Graphical

Investigating the Properties and Cytotoxicity of Cisplatin-Loaded Nano-Polybutylcyanoacrylate on Breast Cancer Cells

Background: This study aimed to develop a novel drug formulation using polybutylcyanoacrylate (PBCA) nanoparticles to deliver cisplatin, a commonly used chemotherapeutic agent for breast cancer treatment.Materials and Methods: PBCA nanoparticles were synthesized using a mini-emulsion polymerization method, and the resulting NPs were comprehensively characterized for their physical properties, such as size, size distribution, zeta potential, drug loading, and encapsulation efficiency. In addition, the cytotoxicity of the NPs was assessed, along with their ability to release the entrapped drugs over time. Results: The results showed that the PBCA nanoparticles had a mean size of 457 ± 7.4 nm, a size distribution of 0.253±0.011 and a negative zeta potential of -12.3 ± 1.3 mV. The drug encapsulation efficiency and loading capacity of cisplatin-PBCA were found to be 45.6 ± 2.7% and 3.5 ±0.8%, respectively; The release of the drug from the PBCA was estimated to be approximately 12.2±1.1% after 45 hours. The cytotoxic effects of the nanoparticle formulation were significantly enhanced compared to the free drug. The cytotoxicity of cisplatin-PBCA was evaluated in the T-47D breast cancer cell line, showing promising results as a potential drug formulation for breast cancer therapy. Conclusions: These findings suggest that cisplatin-PBCA may offer advantages over traditional cisplatin formulations, potentially improving the efficacy and reducing the toxicity of breast cancer treatment.

PSY01-3 Financial toxicity of cancer treatment: From measurement to solutions

PSY01-3 Financial toxicity of cancer treatment: From measurement to solutions