Cancer Treatment Protocols Research Articles

Diosmin: A promising phytochemical for functional foods, nutraceuticals and cancer therapy

AbstractDiosmin, a potent bioflavonoid derived from citrus fruits, has gained significant attention for its anticancer potential, reflecting a critical need in the ongoing battle against cancer. Amidst increasing cancer incidence, the quest for safer and more effective treatments has brought diosmin to the forefront, given its unique pharmacological profile distinct from other flavonoids. Diosmin's anticancer mechanisms are multifaceted, involving apoptosis induction, angiogenesis inhibition, and metastasis prevention. Extensive research encompassing cellular studies, animal models, and limited clinical trials underscores its efficacy not only against cancer but also in managing chronic venous insufficiency and hemorrhoids, attributing to its anti‐inflammatory properties. Furthermore, diosmin exhibits low toxicity and complements conventional chemotherapy, proposing its utility as an adjunct therapy in cancer treatment protocols. The review delves into the specific anticancer advantages of diosmin, distinguishing it from the broader flavonoid category. It provides a detailed analysis of its implications in preclinical and clinical settings, advocating for its consideration in the oncological therapeutic arsenal. By juxtaposing diosmin with other herbal medicines, the review offers a nuanced perspective on its role within the wider context of natural anticancer agents, emphasizing the need for further clinical research to substantiate its efficacy and safety in oncology.

ОЦЕНКА БЕЗОПАСНОСТИ И ЭФФЕКТИВНОСТИ МЕТОДИКИ МОБИЛИЗАЦИИ И СБОРА ГЕМОПОЭТИЧЕСКИХ СТВОЛОВЫХ КЛЕТОК У ДЕТЕЙ РАЗНЫХ ВОЗРАСТНЫХ ГРУПП СО ЗЛОКАЧЕСТВЕННЫМИ НОВООБРАЗОВАНИЯМИ: ОПЫТ ОДНОГО ЦЕНТРА

High dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) is used currently as a consolidating stage in cancer treatment protocols for children from different age groups with various malignant neoplasms. Auto-HSCT can improve both progression-free survival and overall survival of such patients. At the same time the optimization of the collection of autologous hematopoietic stem cells (HSCs) seems to be an important factor in the successful implementation of auto-HSCT. The purpose of this research was to evaluate the safety and effectiveness of the HSCs mobilization and collection method in children from different age groups with various malignancies. Materials and methods used: a single-center retrospective cohort study of 258 pediatric patients (median body weight 20.0 [13.8; 42.0] (7.0-95.0) kg and median height 116 [97; 155] (55.0-189) cm) with various cancers aged 1 to 18 y/o (median 78.0 [36; 144] (3-215) months old) who received treatment in Jan. 2020-Jan. 2023 at the Research Institute of Pediatric Oncology and Hematology named after Academician L.A. Durnov with the N.N. Blokhin Russian Cancer Research Center (Moscow, Russia). Patients were divided into 3 age groups: younger than 1 y/o, 1 to 10 y/o and 11 to 18 y/o. Results: 242 (93.8%) of HSC apheresis procedures were successful on the first attempt, 16 patients underwent repeated apheresis (a total of 274 procedures were performed). The median number of CD34+ cells obtained was 110.95 [45.6; 276.4] (0.70-2338.2) cells/µl, median apheresis duration was 253.5 [189; 338] (82-575) min. No serious complications were observed during the HSCs mobilization and collection in any patient. None of the patients developed hemodynamic disturbances. The main criteria for effectiveness was the CD34+/kg level, the median of which was 5.1 [2.4; 12.7] (0.01-95.6)•106. One of the safety criteria for the patients from all the three age groups was the absence of hemodynamic disorders and citrate reactions in the form of numbness, cyanosis of the skin and respiratory disorders. Another important safety criteria were the absence of a significant decrease in both platelet and hemoglobin levels. The median platelet levels prior to the procedure was 125.5 [68; 210] (14.0-815)•109/l and 129 [73; 210] (17.0-823)•109/l at the end of the procedure (p<0.001). Hemoglobin levels before and after the procedure were 100 [94; 110] (75-242) g/l and 99 [93; 109] (70-142) g/l, respectively (p<0.001). Considering it safe to reduce hemoglobin (g/l) and/or platelets (•109/l) by no more than 10 units in each measurement, in 87.6±4.1% (83.0-91.1) of observed cases the procedure was safe without statistically significant differences in all age groups. The effectiveness of the HSCs mobilization and collection method proposed by the Authors in children of the older age group (11 to 18 y/o) was the lowest and was statistically significantly different from the effectiveness in the group of children aged 1 to 10 y/o (p<0.001) with cancer and amounted to 84.5±4.4% (79.6-88.4). Conclusion: with the multidisciplinary team of practitioners, HSC apheresis in children is a safe and effective technique used as part of the complex cancer treatment in patients from poor prognosis groups. The apheresis algorithm that the Authors have proposed allows high-quality collection of CD34+ positive cells in amounts sufficient for further auto-HSCT.

Correlation of distinct circulating cytokine/chemokine profiles with clinical benefits of Pexa-Vec (thymidine kinase-deactivated vaccinia virus plus GM-CSF) and cemiplimab (REGN2810; anti-PD-1) in metastatic or unresectable renal cell carcinoma (mRCC).

e14539 Background: This study explores the transformation of 'cold' tumour microenvironments into 'hot' ones in mRCC, focusing on the potential of Oncolytic Viruses (OVs) for personalized immunotherapy. Recognizing the variability in patient responses, the research underscores the necessity for reliable biomarkers. The objective is to examine the correlation between plasma cytokine/chemokine levels and the efficacy of Pexa-Vec and cemiplimab, proposing that these biomarkers could predict treatment outcomes and contribute to more personalized cancer treatment protocols. Methods: In this study, mRCC patients from the REN026 trial were categorized into three treatment groups: Pexa-Vec (Intratumoral and intravenous) and cemiplimab combination therapy (N=65), intravenous Pexa-Vec and cemiplimab combination therapy (N=54), and cemiplimab monotherapy (N=14). Blood samples were collected at baseline, during treatment, and at end of treatment (EOT) for analysis. Subsequently, the plasma samples underwent analysis using the Human Cytokine 96-Plex Discovery Assay through the Luminex 200 system. The statistical approach included the Mann–Whitney U-test or Wilcoxon signed-rank test, along with a Cox proportional hazards model. The False Discovery Rate (FDR) method was employed to control type I error. Results: During the follow-up period from June 2018 to February 2023, key outcomes were observed as follows (Table): In the Pexa-Vec and cemiplimab cohort, a lower baseline of MCP-3 or an increased rate of change in post-treatment levels of IFNβ, Eotaxin, IL-1α, and sFasL were associated with improved Progression-Free Survival (PFS). Specifically, a low baseline of MCP-3 or an increased level of Eotaxin and sFasL post-treatment correlated with enhanced Overall Survival (OS). In the intravenous Pexa-Vec and cemiplimab group, a rise in post-treatment levels of IFNβ, Eotaxin, IL-17F, and sFasL were indicative of better PFS, with elevated Eotaxin also suggesting improved OS. Within the cemiplimab monotherapy group, an increase in post-treatment IP-10 was linked to favourable PFS. Conclusions: Our findings suggest the potential utility of plasma cytokine and chemokine profiles in clinical benefits of mRCC patient to the combination of Pexa-Vec and cemiplimab, thereby aiding in future personalized treatment approaches.

Abstract PO2-12-11: Ocular Toxicity of Tamoxifen in Patients with Breast Cancer

Abstract Background: The latest recommendations in breast cancer treatment protocols with tamoxifen indicate that it should be used from five to 10 years. It depends mainly on the cumulative dose of the drug in the body. Despite its multiplicity, the various studies conducted on this subject did not reach conclusive results. Objectives: This research aims to study retinopathy associated with hormonal treatment of breast cancer using tamoxifen. Methods: A cross-sectional study was conducted at Al-Mouwasat University Hospital on a sample of 130 eyes according to (G-Power) with a statistical power of 95%. The participants were briefed on the research and consented on the ethical considerations. Then, the patients who entered the study were interrogated, clinically examined, and were asked about their medical history, the time of breast cancer diagnosis along with the details about the treatment protocols they underwent or currently undergoing. The refractive errors were measured with an automatic refractive device, then they were examined on the slit lamp to investigate the refractory media, then the corrected and uncorrected visual acuity were taken. Finally, after ensuring that the inclusion criteria were met and excluding those who fulfil one or more of the exclusion criteria, optical coherence tomography was performed using SD-OCT technique to measure and review the retinal thickness map in circles of 1-3-6 mm, respectively, to notice possible changes on it. Results: We found that the use of tamoxifen irrespective to cumulative dose leads to increase in the macula thickness values in the upper and lower sectors within the 3 mm circle, and to significant decrease in the macula thickness values in the upper and lower sectors within the 6 mm circle, in addition to decrease in nasal sector thickness within the circles of 3 and 6 mm. Conclusion: We conclude that the difference between people treated with tamoxifen and those not treated with it is not limited to the occurrence of crystals deposition in the macular area or the presence of a cavity in the central macula (with or without typical cystic macular edema), but rather to existence of macula thickness differences unrelated to the cumulative dose of the drug, whether by increase or decrease in thickness of the upper, lower and nasal segments. Citation Format: Husain Alhouz, Arwa Azmeh, Maher Saifo. Ocular Toxicity of Tamoxifen in Patients with Breast Cancer [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 PO2-12-11.

Neoadjuvant radiotherapy in ER+, HER2+, and triple-negative -specific breast cancer based humanized tumor mice enhances anti-PD-L1 treatment efficacy.

Pre-operative radiation therapy is not currently integrated into the treatment protocols for breast cancer. However, transforming immunological "cold" breast cancers by neoadjuvant irradiation into their "hot" variants is supposed to elicit an endogenous tumor immune defense and, thus, enhance immunotherapy efficiency. We investigated cellular and immunological effects of sub-lethal, neoadjuvant irradiation of ER pos., HER2 pos., and triple-negative breast cancer subtypes in-vitro and in-vivo in humanized tumor mice (HTM). This mouse model is characterized by a human-like immune system and therefore facilitates detailed analysis of the mechanisms and efficiency of neoadjuvant, irradiation-induced "in-situ vaccination", especially in the context of concurrently applied checkpoint therapy. Similar to clinical appearances, we observed a gradually increased immunogenicity from the luminal over the HER2-pos. to the triple negative subtype in HTM indicated by an increasing immune cell infiltration into the tumor tissue. Anti-PD-L1 therapy divided the HER2-pos. and triple negative HTM groups into responder and non-responder, while the luminal HTMs were basically irresponsive. Irradiation alone was effective in the HER2-pos. and luminal subtype-specific HTM and was supportive for overcoming irresponsiveness to single anti-PD-L1 treatment. The treatment success correlated with a significantly increased T cell proportion and PD-1 expression in the spleen. In all subtype-specific HTM combination therapy proved most effective in diminishing tumor growth, enhancing the immune response, and converted non-responder into responder during anti-PD-L1 therapy. In HTM, neoadjuvant irradiation reinforced anti-PD-L1 checkpoint treatment of breast cancer in a subtype -specific manner. According to the "bench to bedside" principle, this study offers a vital foundation for clinical translating the use of neoadjuvant irradiation in the context of checkpoint therapy.

Machine learning analysis of breast cancer treatment protocols and cycle counts: A case study at Mohammed vi hospital, Morocco

This paper presents a new study of predicting patients' breast cancer treatment protocol and the corresponding treatment cycle based on machine learning algorithms. The data used were collected at Mohammed VI Hospital in Morocco, and it contains patient information with two targets (protocol and treatment cycle).After preparing the data and testing several machine learning algorithms, two models were developed: The first one, based on Gradient Boosting Classifier algorithm, successfully classified patient treatment protocols with an overall accuracy of 64 % across all categories and an impressive 94 % accuracy for the mode category, widely adopted in the hospital. The second model, based on Random Forest Regressor algorithm, which integrates the results of the first model during the training, predicted the treatment cycle of patients with a Root Mean Square Error (RMSE) score of 0.050 and a Mean Absolute Percentage Error (MAPE) score of 0.020. Furthermore, feature importance analysis was performed to highlight the importance of variables, and show the positive influence of some variables on the models.Finally, this study can help doctors quickly make decisions about the treatment needed for each patient and also gives an idea of which molecules should exist in the hospital stock based on the patient's treatment cycle predicted.

EviQ Cancer Treatments Online: Providing evidence-based information to improve cancer patient outcomes.

To understand the current usage of eviQ Cancer Treatments Online (www.eviQ.org.au), an Australian, open-access website providing evidence-based and consensus-driven cancer treatment protocols and information, and the extent to which it is meeting its intended outcomes and providing value to its users. A mixed-method evaluation was conducted in 2020-2022 which included a review of key program documentation and website usage data, and delivery of a focused online survey to its users. In 2022, 329 clinicians representing all Australian states and territories contributed to eviQ content development and review. eviQ content continues to grow with a 15.2% increase in total content from 2019 to 2022. eviQ website users continue to grow with 90,000 total monthly users in 2022, representing a 166% increase from 2018. The proportion of international users compared to Australian users continues to grow with 57% of total users in Australia and 43% international in 2022. Of 466 survey responses, the most cited reason for eviQ use was for information on side effects/toxicity (67%). Ninety-three percent (93%) of respondents either agreed or strongly agreed that eviQ contributed to both health professionals providing the best evidence-based treatment and care and improving the standardization of treatment and care provided. eviQ is embedded in Australian clinical practice, highly valued, and relied upon by users. Users agree that eviQ has a positive impact on patients by supporting the delivery of evidence-based treatment and that eviQ contributed to patients' improved health outcomes and quality of life. eviQ's increasing international usage should be explored.

Abstract 7503: Non-clinical study of circulating tumor cells in humanized mice: Post-xenograft effects in immunodeficient mice

Abstract Circulating tumor cells (CTCs) possess the potential to serve as innovative markers in clinical trials, contributing to the understanding of cancer metastasis mechanisms, diagnosis, prognosis, the development of personalized treatment strategies, and enabling the monitoring of treatment efficacy. NSG mice, which are a strain of immunodeficient mice frequently utilized as a non-clinical model for cancer research, exhibit diminished levels of natural killer (NK) cells and abnormal monocytes in their bloodstream. In a previous study, a positive correlation was observed between the duration of injection and the levels of white blood cells (WBC) in mice that were injected with various cancer cell lines derived from humans. To evaluate the correlation among the primary tumor and circulating tumor cells (CTCs), as well as the impact on immune cells, we assessed changes in immune cell composition, primary tumor size, and enumeration of CTCs in xenografted mice over a period of time. This investigation was carried out using CytoGen's Smart Biopsy™ systems. The results, which were obtained using equipment including CytoGen's Smart Biopsy™ Systems, showed that the distribution of white blood cell (WBC) components exhibited variations based on age, primary tumor burden, and circulating tumor cell (CTC) count following injection. A notable association was observed between the augmentation of immune cells and the quantity of circulating tumor cells (CTCs) present in the bloodstream. Therefore, alterations in immune cells may potentially impact the potential to affect the ability to influence the efficacy of cancer immunotherapy, metabolic therapy, and anti-metastatic therapy. When conducting non-clinical investigations with the objective of developing cancer treatment protocols, it is crucial to meticulously select humanized or immunodeficient mice that are appropriate for the study. Therefore, it is advisable to perform regular monitoring of murine blood samples in order to observe any variations in the counts of circulating tumor cells (CTCs), while considering a standardized blood volume per individual. In the immunodeficient mouse model, the existence of circulating tumor cells (CTCs) results in an increase in the quantity of cells present in the bloodstream. The observed rise in circulating tumor cells (CTCs) is found to be concurrent with the progression and development of the primary tumor. The consideration of this aspect is of utmost importance in the formulation of non-clinical studies aimed at the development of cancer treatment protocols. Citation Format: Sehyung Pak, Hajin Pak, Hee Jin Yoo, Sra Min, Hui Ji Kim, JaeYoon Lee, Min-Ji Song, Jaesung Choi, Aejin Jeong, Hanbyeol Kim, Jung Won Kim, Hai-Chon Lee. Non-clinical study of circulating tumor cells in humanized mice: Post-xenograft effects in immunodeficient mice [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 7503.

Abstract 6378: Systems-level immunomonitoring in children with solid tumors

Abstract Background: Cancer is the leading cause of death from disease in children. Curing cancer requires cytostatic drugs and radiation, as well as systemic immune responses to clear malignant cells. Determinants of such responses in children of different ages and with different tumors are unknown. Novel immunotherapies can potentiate anti-tumor immune responses, but so far, very few children with solid tumors have benefitted and markers of productive anti-tumor immune responses in children are lacking. Methods: 119 children at the Section for Pediatric Oncology, Astrid Lindgren Children’s Hospital, Karolinska University Hospital in Stockholm, Sweden, diagnosed with solid tumors were recruited to Immune Systems Against Cancer in Children (ISAC) cohort from March 2018 to April 2021. Whole blood samples were collected for immune cell composition (Mass cytometry), plasma protein abundances (Olink assays), transcriptomics, and clonality analysis. Whole genome sequencing data from tumor tissue of children included in the ISAC cohort was obtained from the Swedish Childhood Tumor Biobank and was used for mutational load and signatures analysis. Results: We find that the variation among systemic immune system states is determined predominantly by tumor type, and not age or sex as is the case among healthy children. We also show that specific groups of tumors elicit similar immune response states, which could inspire future updates to treatment protocols for such cancers. This illustrates the potential of this unbiased approach and inclusion of children with diverse solid tumors, whereby shared patterns can lead to novel hypotheses regarding underlying mechanisms among groups of patients, rarely considered together in more reductionist studies of individual tumor types. We also report that general, as well as specific, mutational profiles of neuroblastomas are associated with specific differences in immune responses and finally, we show that clonally expanded T cell responses are rarely observed at baseline in children but can be elicited by successful treatments and monitored as biosensors of therapeutic responses enabling precision oncology in the future. Such monitoring should be considered a complement to the already established precision medicine approaches based on tumor genetics. Conclusions: Our findings suggest the importance of systemic immunity in coordinating and sustaining immune responses against tumors, but also that the developmental changes in human immune systems must be considered when developing and applying new immunotherapeutic interventions for children of different ages with various tumors. Our findings could also inspire the development of future strategies to trigger more productive immune responses against tumors in children. Citation Format: Qi Chen, Binbin Zhao, Ziyang Tan, Gustav Hedberg, Jun Wang, Laura Gonzalez, Constantin Mugabo, Anette Johnsson, Laura Páez, Lucie Rodriguez, Anna James, Yang Chen, Jaromir Mikes, Hugo Barcenilla, Chunlin Wang, Mark M. Davis, Lena-Maria Carlson, Niklas Pal, Nikolas Herold, Klas Blomgren, Dirk Repsilber, Tadepally Lakshmikanth, Per Kogner, Linda Ljungblad, Petter Brodin. Systems-level immunomonitoring in children with solid tumors [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 6378.

A Multiomics Assessment of Preoperative Exercise in Pancreatic Cancer Survivors Receiving Neoadjuvant Therapy: A Case Series.

To molecularly characterize the impact of exercise on mitigating neoadjuvant treatment (NAT)-induced physical decline in pancreatic ductal adenocarcinoma (PDAC) patients, a multi-omics approach was employed for the analysis of plasma samples before and after a personalized exercise intervention. Consisting of personalized aerobic and resistance exercises, this intervention was associated with significant molecular changes that correlated with improvements in lean mass, appendicular skeletal muscle index (ASMI), and performance in the 400-m walk test (MWT) and sit-to-stand test. These alterations indicated exercise-induced modulation of inflammation and mitochondrial function markers. This case study provides proof-of-principal application for multiomics-based assessments of supervised exercise, thereby supporting this intervention as a feasible and beneficial intervention for PDAC patients to potentially enhance treatment response and patient quality of life. The molecular changes observed here underscore the importance of physical activity in cancer treatment protocols, advocating for the development of accessible multiomics-guided exercise programs for cancer patients.

Evaluation of the Gonadotoxicity of Cancer Therapies to Improve Counseling of Patients About Fertility and Fertility Preservation Measures: Protocol for a Retrospective Systematic Data Analysis and a Prospective Cohort Study.

Cytotoxic treatments such as chemo- and radiotherapy and immune therapies are required in cancer diseases. These therapies have the potential to cure patients but may also have an impact on gonadal function and, therefore, on fertility. Consequently, fertility preservation treatments such as freezing of gametes and gonadal tissue might be required. However, as detailed data about the necessity to perform fertility preservation treatment are very limited, this study was designed to fill this data gap. Primary objective of this study is to analyze the impact of cancer therapies and chemotherapies on the ovarian reserve and sperm quality. Secondary objectives are to analyze the (1) impact of cancer therapies and chemotherapies on other fertility parameters and (2) probability of undergoing fertility preservation treatments in relation to specific cancer diseases and treatment protocols and the probability to use the frozen gametes and gonadal tissue to achieve pregnancies. First, previously published studies on the gonadotoxicity of chemo- and radiotherapies among patients with cancer will be systematically analyzed. Second, a prospective cohort study set up by approximately 70 centers in Germany, Switzerland, and Austria will collect the following data: ovarian function by analyzing anti-Müllerian hormone (AMH) concentrations and testicular function by analyzing sperm parameters and total testosterone immediately before and around 1 year after gonadotoxic therapies (short-term fertility). A follow-up of these fertility parameters, including history of conceptions, will be performed 5 and 10 years after gonadotoxic therapies (long-term fertility). Additionally, the proportion of patients undergoing fertility-preserving procedures, their satisfaction with these procedures, and the amount of gametes and gonadal tissue and the children achieved by using the frozen material will be analyzed. Third, the data will be merged to create the internet-based data platform FertiTOX. The platform will be structured in accordance with the ICD (International Classification of Diseases) classification of cancer diseases and will be easily be accessible using a specific App. Several funding bodies have funded this study. Ten systematic reviews are in progress and the first one has been accepted for publication. All Swiss and many German and Austrian ethics committees have provided their approval for the prospective cohort study. The study registry has been set up, and a study website has been created. In total, 50 infertility centers have already been prepared for data collection, which started on December 1, 2023. The study can be expected to bridge the data gap regarding the gonadotoxicity of cancer therapies to better counsel patients about their infertility risk and their need to undergo fertility preservation procedures. Initial data are expected to be uploaded on the FertiTOX platform in 2026. ClinicalTrials.gov NCT05885048; https://clinicaltrials.gov/study/NCT05885048. DERR1-10.2196/51145.

Dermoscopy of Chronic Radiation-Induced Dermatitis in Patients with Head and Neck Cancers Treated with Radiotherapy.

Radiotherapy (RT) is an integral part of many cancer treatment protocols. Chronic radiation-induced dermatitis (CRD) is a cutaneous toxicity that occurs in one-third of all patients treated with this method. CRD is usually observed several months after completion of treatment. Typical symptoms of CRD are telangiectasia, skin discoloration, atrophy, thickening, and cutaneous fibrosis. There are currently no data in the literature on the evaluation of the dermoscopic features of CRD. The aim of this prospective study was the identification of clinical and dermoscopic features in a group of 32 patients with head and neck cancer (HNC) in whom CRD developed after RT. CRD was assessed at 3, 6, and 12 months after RT in 16, 10, and 10 patients, respectively. CRD was assessed at one time point and two time points in 28 and 4 patients, respectively. The control included skin areas of the same patient not exposed to RT. The dataset consisted of 36 clinical and 216 dermoscopic photos. Clinical evaluation was performed according to the RTOG/EORTC radiation-induced dermatitis scale. The highest score was grade 2 observed in 21 patients. Clinical observations revealed the presence of slight and patchy atrophy, pigmentation change, moderate telangiectasias, and some and total hair loss. Dotted vessels, clustered vessel distribution, white patchy scale, perifollicular white color, white structureless areas, brown dots and globules, and white lines were the most frequently noted features in dermoscopy. Three independent risk factors for chronic toxicity, such as age, gender, and surgery before RT, were identified. The dermoscopic features that had been shown in our study reflect the biological reaction of the skin towards radiation and may be used for the parametrization of CRD regarding its intensity and any other clinical consequences in the future.

Establishment of Twinning Partnership to Improve Pediatric Radiotherapy Outcomes Globally.

Pediatric radiotherapy is a necessary and challenging component of oncologic care for children in low- and middle-income countries (LMICs). Collaboration between institutions in LMICs and high-income countries (HICs) has been shown to be effective in improving oncologic treatment outcomes; however, literature regarding pediatric radiotherapy twinning partnerships is limited. Emory University has a long-standing twinning collaboration with Tikur Anbessa Specialized Hospital (TASH) for certain medical specialties. After securing institutional funding, a faculty member and a resident from the Emory University Department of Radiation Oncology set out to establish a twinning program with TASH for pediatric radiotherapy. Emory and TASH faculty and residents established initial communications virtually via email and video correspondence. TASH residents and faculty completed surveys regarding pediatric radiotherapy institutional and educational needs to outline goals of collaboration. Five lectures and case-based practicums were identified focused on Wilms tumor, medulloblastoma, rhabdomyosarcoma, Hodgkin lymphoma, and palliative radiotherapy. The Emory team then conducted a visit to TASH during which lectures and practicums were delivered. The Emory team directly observed and guided simulation and treatment planning procedures. TASH residents practiced decision making, simulation, contouring, and field placement for Wilms tumor cases on the basis of didactics and feedback provided by the Emory team. Additionally, a needs assessment regarding pediatric oncologic resources was completed. Clinical care pathways and standard operating procedures were drafted by collaborators. Virtual peer-review sessions were established to continue collaborations abroad and plan for next in-person visit. Collaborative efforts by global experts have helped to establish and improve treatment protocols for childhood cancer. The presented twinning experience may serve as a model for other LMIC and HIC centers for establishing similar partnerships.

MRI-Based Kinetic Heterogeneity Evaluation in the Accurate Access of Axillary Lymph Node Status in Breast Cancer Using a Hybrid CNN-RNN Model.

Accurate evaluation of the axillary lymph node (ALN) status is needed for determining the treatment protocol for breast cancer (BC). The value of magnetic resonance imaging (MRI)-based tumor heterogeneity in assessing ALN metastasis in BC is unclear. To assess the value of deep learning (DL)-derived kinetic heterogeneity parameters based on BC dynamic contrast-enhanced (DCE)-MRI to infer the ALN status. Retrospective. 1256/539/153/115 patients in the training cohort, internal validation cohort, and external validation cohorts I and II, respectively. 1.5 T/3.0 T, non-contrast T1-weighted spin-echo sequence imaging (T1WI), DCE-T1WI, and diffusion-weighted imaging. Clinical pathological and MRI semantic features were obtained by reviewing histopathology and MRI reports. The segmentation of the tumor lesion on the first phase of T1WI DCE-MRI images was applied to other phases after registration. A DL architecture termed convolutional recurrent neural network (ConvRNN) was developed to generate the KHimage (kinetic heterogeneity of DCE-MRI image) score that indicated the ALN status in patients with BC. The model was trained and optimized on training and internal validation cohorts, tested on two external validation cohorts. We compared ConvRNN model with other 10 models and the subgroup analyses of tumor size, magnetic field strength, and molecular subtype were also evaluated. Chi-squared, Fisher's exact, Student's t, Mann-Whitney U tests, and receiver operating characteristics (ROC) analysis were performed. P < 0.05 was considered significant. The ConvRNN model achieved area under the curve (AUC) of 0.802 in the internal validation cohort and 0.785-0.806 in the external validation cohorts. The ConvRNN model could well evaluate the ALN status of the four molecular subtypes (AUC = 0.685-0.868). The patients with larger tumor sizes (>5 cm) were more susceptible to ALN metastasis with KHimage scores of 0.527-0.827. A ConvRNN model outperformed traditional models for determining the ALN status in patients with BC. 3 TECHNICAL EFFICACY: Stage 2.

TARDBP is a candidate diagnostic biomarker promoting tumor progression via impacting tumor immunity and tumor microenvironment.

In the realm of cancer research, particularly hepatocellular carcinoma (HCC), TAR DNA-binding protein (TARDBP) has transitioned from being associated with neurodegenerative diseases to emerging as a significant molecule in oncology due to its aberrant expression in HCC and other malignancies. This shift underlines the versatility of TARDBP and its critical role in tumorigenesis. Our study illuminates TARDBP's universal upregulation across various cancers, indicating its involvement in fundamental oncogenic processes and potential impact on genomic instability. The relationship between TARDBP expression and tumor mutational burden (TMB) across several cancers highlights its influence on a key hallmark of cancer progression. Additionally, TARDBP's interaction with immune and inflammatory factors within the tumor microenvironment, including its association with immune-stimulatory factors and inverse relationship with immune inhibitors, suggests its role in modulating immune evasion. Clinically, TARDBP's aberrant expression correlates with adverse patient outcomes in HCC, making it a promising candidate for therapeutic targeting. The study concludes that TARDBP holds significant potential as a novel therapeutic target in HCC and possibly other malignancies, meriting further exploration to integrate TARDBP-targeted therapies into cancer treatment protocols, thereby advancing the field of precision medicine.

Physiotherapy Interventions for the Management of Treatment-related Complications in Breast Cancer: Systematic Literature Review

Introduction: The prevalence of treatment-related complications remains high throughout the course of cancer treatment resulting a decline in quality of life. Physiotherapy can have a positive influence on various domains of Quality of Life (QoL), potentially alleviating the severity of perceived complications. Aim: To evaluate the physiotherapy interventions used for managing treatment-related complications among breast cancer patients. Materials and Methods: Databases including Medical Literature Analysis and Retrieval System Online (MEDLINE), Science Direct, Cochrane Library, and Scopus from year 2000 to 2022 was searched with Mesh terms for trials with breast cancer patients &gt;18 years of age participating in physiotherapy program. The primary outcome measure of interest was a significant improvement in treatment-related complications from pre- to post intervention. Change in quality of life was evaluated as secondary outcome measure. Cochrane risk of bias tool was used to assess the risk of bias and quality of included studies. Results: A total of 20 randomised controlled trials with 2019 patients incorporated various physiotherapy interventions to manage and alleviate treatment-related complications. For physical functioning (p=0.04) and the pain-sleep-fatigue cluster (p=0.006 to 0.044) different types of exercises were included. Complex Decongestive Therapy (CDT) combined with other electrotherapy modalities was embraced to manage lymphedema (p&lt;0.05). For shoulder and arm dysfunction (p&lt;0.05) passive stretching, mobilisation and strengthening exercises were incorporated. Furthermore, regular practice of exercise and physiotherapy exhibited positive impacts on overall health-related quality of life (p=0.0001 to 0.01) along with improvements in anxiety, depression, self-esteem and emotional function. Conclusion: Physiotherapy interventions are exceedingly effective in managing and providing relief from breast cancer treatment-related complications. Consequently, the integration of physiotherapy into cancer treatment protocols has the potential to enhance the overall QoL of patients.

In Vivo and Clinical Studies of Natural Products Targeting the Hallmarks of Cancer.

Despite more than 200 approved anticancer agents, cancer remains a leading cause of death worldwide due to disease complexity, tumour heterogeneity, drug toxicity, and the emergence of drug resistance. Accordingly, the development of chemotherapeutic agents with higher efficacy, a better safety profile, and the capability of bypassing drug resistance would be a cornerstone in cancer therapy. Natural products have played a pivotal role in the field of drug discovery, especially for the pharmacotherapy of cancer, infectious, and chronic diseases. Owing to their distinctive structures and multiple mechanistic activities, natural products and their derivatives have been utilized for decades in cancer treatment protocols. In this review, we delve into the potential of natural products as anticancer agents by targeting cancer's hallmarks, including sustained proliferative signalling, evading growth suppression, resisting apoptosis and cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. We highlight the molecular mechanisms of some natural products, in vivo studies, and promising clinical trials. This review emphasizes the significance of natural products in fighting cancer and the need for further studies to uncover their fully therapeutic potential.

Use of Antibody-Drug Conjugates in the Early Setting of Breast Cancer.

Antibody-drug conjugates (ADCs) are anticancer agents with the capacity to selectively deliver their payloads to cancer cells. Antibody-drug conjugates consist of a monoclonal antibody backbone connected by a linker to cytotoxic payloads. Antibody-drug conjugate effect occurs either by directly targeting cancer cells via membrane antigen or through "bystander effect." Antibody-drug conjugates have demonstrated efficacy against various types of tumors, including breast cancer. Ado-trastuzumab emtansine is presently the only approved ADC for the treatment of breast cancer in the early setting, while several ADCs are now approved for metastatic breast cancer. Due to the transformative impact that several ADCs have reported in the setting of advanced breast cancer, researchers are now testing more of such compounds in the early setting, to portend benefits to patients through highly potent anticancer drugs. Ongoing trials hold the potential to transform treatment protocols for early breast cancer in the near future. These trials are aiming at evaluating different treatment modulation approaches, as informed by breast cancer risk of recurrence, including toward treatment de-escalation. Efforts are provided in ongoing clinical trials to identify the patients who will benefit most, to pursue paradigms of precision medicine with the novel ADCs. This review focuses on the potential role of ADCs in early breast cancer, providing an overview of the latest progress in their development and how they are implemented in ongoing clinical trials.

Cancer Risk in Nepal: An Analysis from Population‐Based Cancer Registry of Urban, Suburban, and Rural Regions

Background. Cancer is one of the leading causes of death globally. The low and middle‐income countries (LMICs) cover a major share of the global cancer burden; however, most of the LMICs including Nepal still lack national cancer control and prevention strategies. Since 1st January 2018, the Nepal Health Research Council (NHRC) started the population‐based cancer registry (PBCR) in urban, suburban, and rural regions to support evidence‐based cancer control intervention in each geographical region. Methods. Data regarding incidence and mortality was collected by the PBCR in Nepal. Indirect and direct methods were used to collect data from health facilities and communities, respectively. Registered cases of incidence and mortality from 1st January 2019 to 31st December 2019 were used. Each case was verified for correctness and duplication followed by residence confirmation via phone call. Guidelines and principles of the International Association of Cancer Registry were followed for the overall registration process including data quality control. Ethical approval was taken from the Ethical Review Board of the NHRC. Result. Age‐adjusted incidence (AAR) and mortality rates in Nepal were found 65.6 and 29 per 100,000 people, respectively. Every 1 in 14 men and 1 in 13 women were at risk of getting, and 1 in 28 men and 1 in 33 women were dying of cancer before age 75 in Nepal. The highest risk was found for lung cancer (1 in 80) followed by stomach and mouth among men, and in women, breast cancer (1 in 76) was the commonest among all followed by lung and cervix. Conclusion. Cancer has been growing as one of the major public health burdens in Nepal. Screening with cost‐effective technology, awareness, and vaccination against HPV should be a government priority including revision of treatment protocols for cancers that have higher mortality to prevent further preventable life loss from malignancies.

Nurses' Perceptions of Support in Cancer Pharmacotherapy at a University Hospital: A Descriptive Quantitative Study.

Advances in treatment have transformed cancer from a fatal to a chronic illness. This requires healthcare professionals, particularly nurses, to have advanced knowledge and collaborative skills. However, challenges persist in implementing patient-centered care in the context of evolving treatment complexity. This study aimed to clarify nurses' support practices in providing cancer pharmacotherapy at a university hospital in Japan and compare these practices based on nurses' years of experience. A questionnaire survey was conducted from February to April 2023 among 430 nurses involved in provision of cancer pharmacotherapy at a Japanese university hospital. Nurses were asked about the types of support they provided during care for patients undergoing cancer pharmacotherapy. Nurses' cancer pharmacotherapy support practices were extracted using factor analysis, and differences in support scores by years of experience were examined. Responses were received from 184 nurses (42.8% response rate). Three support factors were identified: "Providing patient-centered cancer pharmacotherapy," "Management of continued cancer pharmacotherapy treatment," and "Assessment of and response to physical symptoms." Scores for "Providing patient-centered cancer pharmacotherapy" were significantly lower than those for the other two factors (p < .001). The group with ≥10 years of nursing experience had statistically significantly lower practice scores than those with 4-9 years of experience. Enhancing nursing education and interprofessional collaboration are crucial to overcome barriers to patient-centered cancer care. Continuous learning opportunities are essential to adapt to evolving cancer treatment protocols and ensure delivery of patient-centered care, particularly for experienced nurses.