Strategies For Management Of Cancer Research Articles

Abstract A001: Urine-based liquid biopsy test for the detection of residual bladder cancer in radical cystectomy patients

Abstract One commonly employed management strategy for muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy followed by radical cystectomy (RC) and urinary diversion. Approximately 35% of patients achieve a pathologic complete response (pCR) when evaluated from RC specimens. RC with urinary diversion is a life-altering operation with high complication rates and therefore determining who are complete responders would improve quality of life and could decrease costs and still achieve a high cure rate via RC avoidance. Unfortunately, current methods cannot accurately identify complete responders. Our lab has developed a urine-based liquid biopsy test in which DNA isolated from urine and germline is isolated and subjected to panel exome sequencing for enumeration of somatic variants. This occurs under the premise that tumor DNA identified (as mutant alleles) is a marker of residual disease while the absence of tumor DNA (meaning the absence of mutant alleles) can indicate a pCR. A 60 gene panel was designed to be used for exonic sequencing of urinary DNA (uDNA) to identify mutations indicative of bladder cancer or therapeutic targets. We have shown that most mutations in tumor tissue (Mt) are detectable as mutations in urine (Mu). We also showed that the presence or absence of residual Mu after completion of chemotherapy strongly associates with residual disease or pCR at the time of RC, respectively. Therefore, this test could be used after neoadjuvant therapy to better identify patients for RC avoidance. We optimized this test by studying pre-analytical factors affecting the yield, purity, and integrity of uDNA and the quality of sequencing data using prospectively collected samples from patients with MIBC. We are also in the process of testing commercial and novel preservatives to optimize DNA integrity, yield, and mutation detection accuracy to enable temporary ambient temperature storage without compromising mutation detection, permitting shipping/centralized testing. Lastly, we are comparing two library preparation approaches. Study of these preanalytical factors has increased the number of Mu that can be detected and were applied to a cohort of patients who underwent bladder sparing curative-intent treatment in a prospective clinical trial. Studies described herein will enable liquid biopsy tests to accurately identify patients with pCR after neoadjuvant therapy and might safely avoid radical cystectomy. Citation Format: Philip H. Abbosh, Henkel Valentine, Rhea Arya. Urine-based liquid biopsy test for the detection of residual bladder cancer in radical cystectomy patients [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A001.

Integrating MDT Tumor Board Shadowing into the Undergraduate Medical Curriculum: Perspective of Medical Students.

Site-specific multidisciplinary team (MDT) tumor boards are valuable resources for medical students, enabling them to familiarize themselves with the latest evidence-based cancer management strategies and observe effective teamwork in action. In this study, we looked at the awareness and perceptions of medical students about incorporating MDT tumor boards in the medical curriculum. A cross-sectional study was conducted among medical students from year 1 to year 5 at the Aga Khan University after exemption from ethical review committee. A 20-item self-administered questionnaire was used to evaluate the awareness and perceptions of medical students regarding MDT tumor boards. A total of 285 medical students participated in this study, with their mean age (± standard deviation) being 21.91 ± 1.67years. A majority of 183 (64.2%) had no prior knowledge of the existence of a site-specific MDT tumor board for cancer management. Of the 285 students, 252 (88.4%) demonstrated sufficient awareness of the effectiveness of MDT tumor boards; similarly, 232 (81.4%) responded positively to the idea of mandatory tumor board rotations being incorporated into the undergraduate curriculum. No significant association was found between the student's year of study (χ2 = 6.03, p = 0.20) or gender (χ2 = 35, p = 0.84) and their perceptions of the effectiveness of MDT tumor boards. However, it was found that students who had prior knowledge of their existence had a stronger association with sufficient awareness (χ2 = 4.2, p = 0.04). The results indicate that while the majority of the medical students have no prior attendance or knowledge regarding MDT tumor boards, there is an overwhelming willingness among students to incorporate them into the medical curriculum.

Phase-Separated Biomolecular Condensation in Cancer: New Horizons and Next Frontiers.

Beyond lipid membrane compartments, cells including cancer cells utilize various membraneless compartments, often termed biomolecular condensates, to regulate or organize key cellular processes underlying physiologic or pathologic phenotypes. In this commentary, the emergence of biomolecular condensation in cancer biology is highlighted, with a focus on key unanswered questions and with implications for improving the understanding of cancer pathogenesis and developing innovative cancer management strategies.

Comprehensive Review on Recent Strategies for Management of Prostate Cancer: Therapeutic Targets and SAR.

Prostate cancer is a disease that is affecting a large population worldwide. Androgen deprivation therapy (ADT) has become a foundation for the treatment of advanced prostate cancer, as used in most clinical settings from neo-adjuvant to metastatic stage. In spite of the success of ADT in managing the disease in the majority of men, hormonal manipulation fails eventually. New molecules are developed for patients with various hormone-refractory diseases. Advancements in molecular oncology have increased understanding of numerous cellular mechanisms which control cell death in the prostate and these insights can lead to the development of more efficacious and tolerable therapies for carcinoma of the prostate. This review is focused on numerous therapies that might be a boon for prostate therapy like signaling inhibitors, vaccines, and inhibitors of androgen receptors. Along with these, various bioactive molecules and their derivatives are highlighted, which act as potential antiprostate cancer agents. This article also emphasized the recent advances in the field of medicinal chemistry of prostate cancer agents.

Cross-platform gene expression profiling of breast cancer: Exploring the relationship between breast cancer grades and gene expression pattern

Gene expression profiling is a powerful tool that has been extensively used to investigate the underlying biology and etiology of diseases, including cancer. Microarray gene expression analysis enables simultaneous measurement of thousands of mRNA levels. Sophisticated computational approaches have evolved in parallel with the rapid progress in bioassay technologies, enabling more effective analysis of the large and complex datasets that these technologies produce.In this study, we utilized systems biology approaches to examine gene expression profiles across different grades of breast cancer progression. We conducted a meta-analysis of publicly available microarray data to elucidate the molecular mechanisms underlying breast cancer grade classification.Our results suggest that while grade index is commonly used for evaluating cancer progression status in the clinic, the complexity of molecular mechanisms, histological characteristics, and other factors related to patient outcomes raises doubts about the utility of breast cancer grades as a foundation for formulating treatment protocols.Our study underscores the importance of advancing personalized strategies for breast cancer classification and management. More research is crucial to refine diagnostic tools and treatment modalities, aiming for greater precision and tailored care in patient outcomes.

Importance of 3β-hydroxysteroid dehydrogenases and their clinical use in prostate cancer.

Androgen receptor signaling is crucial for the development of treatment resistance in prostate cancer. Among steroidogenic enzymes, 3β-hydroxysteroid dehydrogenases (3βHSDs) play critical roles in extragonadal androgen synthesis, especially 3βHSD1. Increased expression of 3βHSDs is observed in castration-resistant prostate cancer tumors compared with primary prostate tumors, indicating their involvement in castration resistance. Recent studies link 3βHSD1 to resistance to androgen receptor signaling inhibitors. The regulation of 3βHSD1 expression involves various factors, including transcription factors, microenvironmental influences, and post-transcriptional modifications. Additionally, the clinical significance of HSD3B1 genotypes, particularly the rs1047303 variant has been extensively studied. The impact of HSD3B1 genotypes on treatment outcomes varies according to the therapy administered, suggesting the potential of HSD3B1 genotyping for personalized medicine. Targeting 3βHSDs may be a promising strategy for prostate cancer management. Overall, understanding the roles of 3βHSDs and their genetic variations may enable the development and optimization of novel treatments for prostate cancer.

106 Transforming Health Equity with an Innovative Social Determinants of Health Platform: Application of HOUSES Index to Colorectal Cancer Screening

OBJECTIVES/GOALS: To tackle population-level health disparities, quality dashboards can leverage individual socioeconomic status (SES) measures, which are not always readily accessible. This study aimed to assess the feasibility of a population health management strategy for colorectal cancer (CRC) screening rates using the HOUSES index and heatmap analysis. METHODS/STUDY POPULATION: We applied the 2019 Minnesota Community Measurement data for optimal CRC screening to eligible Mayo Clinic Midwest panel patients. SES was defined by HOUSES index, a validated SES measure based on publicly available property data for the U.S. population. We first assessed the association of suboptimal CRC screening rate with HOUSES index adjusting for age, sex, race/ethnicity, comorbidity, and Zip-code level deprivation by using a mixed effects logistic regression model. We then assessed changes in ranking for performance of individual clinics (i.e., % of patients with optimal CRC screening rate) before and after adjusting for HOUSES index. Geographical hotspots of high proportions of low SES AND high proportions of suboptimal CRC screening were superimposed to identify target population for outreach. RESULTS/ANTICIPATED RESULTS: A total of 58,382 adults from 41 clinics were eligible for CRC screening assessment in 2019 (53% Female). Patients with lower SES defined by HOUSES quartile 1-3 have significantly lower CRC screening compared to those with highest SES (HOUSES quartile 4) (adj. OR [95% CI]: 0.52 [0.50-0.56] for Q1, 0.66 [0.62-0.70] for Q2, and 0.81 [0.76-0.85]) for Q3). Ranking of 26 out of 41 (63%) clinics went down after adjusting for HOUSES index suggesting disproportionately higher proportion of underserved patients with suboptimal CRC screening. We were able to successfully identify hotspots of suboptimal CRC (area with greater than 130% of expected value) and overlay with higher proportion of underserved population (HOUSES Q1), which can be used for data-driven targeted interventions such as mobile health clinics. DISCUSSION/SIGNIFICANCE: HOUSES index and associated heatmap analysis can contribute to advancing health equity. This approach can aid health care organizations in meeting the newly established standards by The Joint Commission, which have elevated health equity to a national safety priority.

Proximity labeling-assisted click conjugation for electrochemical analysis of specific subpopulations in circulating extracellular vesicles

Sensitive and accurate analysis of specific subpopulations in circulating extracellular vesicles (EVs) can provide a wealth of information for cancer diagnosis and management. Thus, we propose herein a new electrochemical biosensing method based on a proximity labeling-assisted click conjugation strategy. The method's core design is use of antibody-guided proximity labeling to equip target EVs with a large amount of alkyne groups, so that azide-tagged silver nanoparticles can be accurately loaded onto target EV surfaces, via click conjugation, to generate significant electrochemical responses. Adopting CD44-positive EVs as the model, the electrochemical method was demonstrated by analyzing target EVs across a wide linear range (103–109 particles/mL) with acceptable sensitivity and specificity. Satisfactory utility in clinical blood samples, and versatility with human epidermal growth factor receptor-2-positive EVs as alternative targets, were also shown. This method may thus provide a novel approach to specific subgroup analyses of circulating EVs, and is expected to offer reliable guidance for cancer diagnoses and management strategies.

Targeting Peroxisome Proliferator-Activated Receptor-β/δ, Reactive Oxygen Species and Redox Signaling with Phytocompounds for Cancer Therapy.

Significance: Peroxisome proliferator-activated receptors (PPARs) have a moderately preserved amino-terminal domain, an extremely preserved DNA-binding domain, an integral hinge region, and a distinct ligand-binding domain that are frequently encountered with the other nuclear receptors. PPAR-β/δ is among the three nuclear receptor superfamily members in the PPAR group. Recent Advances: Emerging studies provide an insight on natural compounds that have gained increasing attention as potential anticancer agents due to their ability to target multiple pathways involved in cancer development and progression. Critical Issues: Modulation of PPAR-β/δ activity has been suggested as a potential therapeutic strategy for cancer management. This review focuses on the ability of bioactive phytocompounds to impact reactive oxygen species (ROS) and redox signaling by targeting PPAR-β/δ for cancer therapy. The rise of ROS in cancer cells may play an important part in the initiation and progression of cancer. However, excessive levels of ROS stress can also be toxic to the cells and cancer cells with increased oxidative stress are likely to be more vulnerable to damage by further ROS insults induced by exogenous agents, such as phytocompounds and therapeutic agents. Therefore, redox modulation is a way to selectively kill cancer cells without causing significant toxicity to normal cells. However, use of antioxidants together with cancer drugs may risk the effect of treatment as both act through opposite mechanisms. Future Directions: It is advisable to employ more thorough and detailed methodologies to undertake mechanistic explorations of numerous phytocompounds. Moreover, conducting additional clinical studies is recommended to establish optimal dosages, efficacy, and the impact of different phytochemicals on PPAR-β/δ.

Abstract 2769: Long non coding RNA H19/cell adhesion molecules circuitry as novel target and diagnostic tool for metastatic prostate cancer

Abstract In the complex tumor biology of prostate cancer (PCa), we previously contributed by demonstrating that estrogen receptor and hypoxia signaling promoted transcription of progression-associated genes. Notably, combined treatment, estrogens plus hypoxia, caused a significant down regulation of the long noncoding RNA H19, one of the most sensitive to these pro-tumoral stimuli. Mechanistically, H19 acts as transcriptional repressor: H19 over-expression decreases E-cadherin (CDH1) level causing epithelial-to-mesenchymal transition whereas H19 reduction promotes the expression of E-cadherin and β4 integrin (ITGB4) switching the tumor dissemination program toward an alternative mechanism, specifically the cohesive metastatic phenotype. We focused on this H19/cell adhesion molecules circuitry by investigating its role as: 1.Novel prognostic biomarker at the time of biopsies. eNOS, HIF2a and β4 integrin expression was evaluated by immunohistochemistry, H19 and CDH1 transcripts by Droplet Digital PCR on FFPE-biopsies in a retrospective cohort of PCa patients [n = 30; Gleason score GS≤ 7(3+4) n= 17, GS ≥7(4+3) n= 13; biochemical, local, or metastatic recurrence defining disease progression (n=8/30; time of recurrence: range 2-6 years)]. Importantly, multivariate analysis of combined biomarkers, named “Bioscore”, defined by the presence of at least 3 among HIF-2α, eNOS, CDH1, β4 integrin ≥cut off or H19≤cut off revealed its prognostic value for progression and Progression-Free Survival determined using the ROC analysis (p=0.003) and Kaplan Meier curve (p= 0.005), respectively. 2.Master regulator of metastatic program in vivo and ex vivo PCa experimental models. Upon H19 silencing, mimicking combined estrogens plus hypoxia treatment, luciferase-positive PC-3 and 22Rv1 cells led to increased E-cadherin and β4 integrin expression, enhanced tumor growth and metastasis formation at bone, lung, and liver in PCa mouse models. Further, treatment with H3K27 demethylase inhibitor, GSK-J4, rescued cell adhesion molecules expression by modulating H3K27me3 level at gene promoters, reduced metastasis number and size, and induced cell death in PCa-derived Organotypic Slice Cultures. Additionally, treatment with JQ1 and dBET6 BET protein family inhibitors) markedly reduced both E-cadherin and β4 integrin levels, cell proliferation and in vivo tumor growth. Intriguingly, H19 silencing increased BRD3 and BRD4 levels, implicating H19 in BRD transcription. Overall, this research enhances our understanding of the molecular mechanisms driving aggressive prostate cancer phenotypes, providing a foundation for new diagnostic and therapeutic strategies in prostate cancer management. Citation Format: Valeria Pecci, Aurora Aiello, Sara De Martino, Cristian Ripoli, Dante Rotili, Francesco Pierconti, Francesco Pinto, Claudio Grassi, Carlo Gaetano, Alfredo Pontecorvi, Lidia Strigari, Antonella Farsetti, Simona Nanni. Long non coding RNA H19/cell adhesion molecules circuitry as novel target and diagnostic tool for metastatic prostate 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 2769.

Oncotype DX in Breast Cancer Management: Insights and Outcomes From the United Arab Emirates.

Introduction Breast cancer remains the most significant cancer affecting women worldwide, with an increasing incidence, especially in developing regions. The introduction of genomic tests like Oncotype DX has revolutionized personalized treatment, allowing for more tailored approaches to therapy. This study focuses on the United Arab Emirates (UAE), where breast cancer is the leading cause of cancer-related deaths among women, aiming to assess the predictive accuracy of the Oncotype DX test in categorizing patients based on recurrence risk. Materials and methods A retrospective cohort study was conducted on 95 breast cancer patients diagnosed at Tawam Hospital between 2013 and 2017 who underwent Oncotype DX testing. Data on patient demographics, tumor characteristics, treatment details, and Oncotype DX scores were collected. Survival analysis was performed using the Kaplan-Meier method, with the chi-square goodness of fit test assessing the model's adequacy. Results The cohort's age range was 27-71 years, with a mean age of 50, indicating a significant concentration of cases in the early post-menopausal period. The Oncotype DX analysis classified 55 patients (57.9%) as low risk, 29 (30.5%) as medium risk, and 11 (11.6%) as high risk of recurrence. The majority, 73 patients (76.8%), did not receive chemotherapy, highlighting the test's impact on treatment decisions. The survival analysis revealed no statistically significant difference in recurrence rates across the Oncotype DX risk categories (p = 0.268231). Conclusion The Oncotype DX test provides a valuable genomic approach to categorizing breast cancer patients by recurrence risk in the UAE. While the test influences treatment decisions, particularly the use of chemotherapy, this study did not find a significant correlation between Oncotype DX risk categories and actual recurrence events. These findings underscore the need for further research to optimize the use of genomic testing in the UAE's diverse patient population and enhance personalized treatment strategies in breast cancer management.

Comparison of prognostic outcomes between endoscopic submucosal dissection and surgical treatment for early gastric cancer: a retrospective cohort study

Background and aimThe optimal management strategy for early gastric cancer (EGC) a topic of contention. This study aims to compare the prognostic outcomes of endoscopic submucosal dissection (ESD) and surgical treatment in patients diagnosed with EGC.MethodsIn thisretrospective cohort study, we analyzed data from539 patients diagnosed with EGC between January 2012 and December 2020 from two centers. We compared Clinicopathological features, procedure-related complications, recurrence rate, overall survival, and disease specific survival between the 262 patients who underwent ESD and the 277 patients who underwent surgical treatment. ESD procedures were conducted using a dual knife by experienced endoscopists, while surgical treatments included laparoscopic or open gastrectomy. Regular ollow-up examinations were conducted post-treatment.ResultsThe two groups exhibited comparable baseline characteristics. Multivariable Cox regression analysis identified vascular invasion as a risk factor for worse recurrence-free survival (RFS), and overall survival (OS) in patients with early gastric cancer. The ESD group experienced fewer overall postoperative complications compared to the surgical treatment group. Kaplan-Meier curves demonstrated no significant differences in recurrence rate or overall survival between the two groups.ConclusionsBoth ESD and surgical treatment emerged as safe and effective approaches for managing EGC. The choice of treatment should be tailored to individual patient factors. ESD can be considered an alternative treatment option for selected patients who are not suitable candidates for surgery. Further studies are warranted to determine the long-term outcomes of ESD and surgical treatment for EGC.

The Role of Tumor and Host Microbiome on Immunotherapy Response in Urologic Cancers

Introduction & Objective: The role of the microbiome in the development and treatment of genitourinary malignancies is just starting to be appreciated. Accumulating evidence suggests that the microbiome can modulate immunotherapy through signaling in the highly dynamic tumor microenvironment. Nevertheless, much is still unknown about the immuno-oncology-microbiome axis, especially in urologic oncology. The objective of this review is to synthesize our current understanding of the microbiome’s role in modulating and predicting immunotherapy response to genitourinary malignancies. Methods: A literature search for peer-reviewed publications about the microbiome and immunotherapy response in bladder, kidney, and prostate cancer was conducted. All research available in PubMed, Google Scholar, clinicaltrials.gov, and bioRxiv up to September 2023 was analyzed. Results: Significant differences in urinary microbiota composition have been found in patients with genitourinary cancers compared to healthy controls. Lactic acid-producing bacteria, such as Bifidobacterium and Lactobacillus genera, may have value in augmenting BCG responsiveness to bladder cancer. BCG may also be a dynamic regulator of PD-L1. Thus, the combination of BCG and immune checkpoint inhibitors may be an effective strategy for bladder cancer management. In advanced renal cell carcinoma, studies show that recent antibiotic administration negatively impacts survival outcomes in patients undergoing immunotherapy, while administration of CBM588, a live bacterial product, is associated with improved progression-free survival. Specific bacterial taxa, such as Streptococcus salivarius, have been linked with response to pembrolizumab in metastatic castrate-resistant prostate cancer. Fecal microbiota transplant has been shown to overcome resistance and reduce toxicity to immunotherapy; it is currently being investigated for both kidney and prostate cancers. Conclusions: Although the exact mechanism is unclear, several studies identify a symbiotic relationship between microbiota-centered interventions and immunotherapy efficacy. It is possible to improve immunotherapy responsiveness in genitourinary malignancies using the microbiome, but further research with more standardized methodology is warranted.

Comprehensive review of Bcl-2 family proteins in cancer apoptosis: Therapeutic strategies and promising updates of natural bioactive compounds and small molecules.

Cancer has a considerably higher fatality rate than other diseases globally and is one of the most lethal and profoundly disruptive ailments. The increasing incidence of cancer among humans is one of the greatest challenges in the field of healthcare. A significant factor in the initiation and progression of tumorigenesis is the dysregulation of physiological processes governing cell death, which results in the survival of cancerous cells. B-cell lymphoma 2 (Bcl-2) family members play important roles in several cancer-related processes. Drug research and development have identified various promising natural compounds that demonstrate potent anticancer effects by specifically targeting Bcl-2 family proteins and their associated signaling pathways. This comprehensive review highlights the substantial roles of Bcl-2 family proteins in regulating apoptosis, including the intricate signaling pathways governing the activity of these proteins, the impact of reactive oxygen species, and the crucial involvement of proteasome degradation and the stress response. Furthermore, this review discusses advances in the exploration and potential therapeutic applications of natural compounds and small molecules targeting Bcl-2 family proteins and thus provides substantial scientific information and therapeutic strategies for cancer management.

Role of Plant derived-medicine for controlling Cancer

This review paper has highlighted a list of plants containing active phytochemicals with anticancer potential, as well as data supporting their use in cancer therapy, animal models, and their pharmacological properties. Cancer is among the leading causes of morbidity and mortality worldwide. Cancer is a disease characterized by abnormal cell division and proliferation that result from disruption of molecular signals that control these processes. Cancer is the abnormal, uncontrolled division of cells in the body. The cancer cells when malignant, invade various parts of the body through the bloodstream. The spread of cancer from its cells or tissue of origin to another healthy part of tissues or organs is called metastasis. Some of the regular characteristics of cancers are apoptosis, angiogenesis, multiple replication, growth signal production, insensitivity to signals of anti-growth and metastasis. These features make cancer cells to have continuous growth, long time survival and the potential to invade normal cells. Moreover, if these activities are not blocked, cancer cells will continue to increase, overwhelm and finally kill the patient with cancer. Oncology is the study of cancer. An oncologist is a doctor who treats cancer and provides medical care for a person diagnosed with cancer. An oncologist may also be called a cancer specialist. Today, despite considerable efforts, cancer still remains an aggressive killer worldwide. The success rate of these therapies is diminished by toxicities, drug resistance, recurrence and treatment failure. A significant challenge associated with cancer is that treatment is as much an art as it is a science. Therefore, there is a constant demand to develop new, effective, and affordable anticancer drugs. Several factors, such as environmental factors, habitual activities, genetic factors, etc., are responsible for cancer. Many cancer patients seek alternative and/or complementary treatments because of the high death rate linked with cancer and the adverse side effects of chemotherapy, radiation therapy, immunotherapy, surgery, and stem cell therapy. Medicinal plants could also possess effective anticancer compounds that may be used as adjuvants to existing chemotherapy to improve efficacy and/or reduce drug-induced toxicity; such as chemotherapy-induced nausea and vomiting to improve patients’ quality of life. Cell death is caused by the whole plant extracts via apoptosis. However, majority of plant extracts have been researched for cancer prevention rather than treatment, resulting in low efficacy and uptake in practice. Prevention is certainly an attractive cancer management strategy. Thus it might be possible to reduce the process of carcinogenesis with regular use of these plants along with a healthy lifestyle.

An Observational Study On Cervical Cancer In Sri Lanka And Its Prevention And Management

Background: Cervical cancer is a major health concern worldwide, with significant prevalence in Sri Lanka. Despite being preventable through early detection and vaccination, the disease continues to cause high morbidity and mortality among Sri Lankan women, primarily due to late diagnosis and inadequate access to treatment and preventive measures. Methods and Materials: This observational study employs a cross-sectional design to collect data from a representative sample of Sri Lankan women, using structured questionnaires and interviews. The study aims to determine the prevalence of cervical cancer, identify risk factors, assess awareness and preventive practices, and explore challenges in treatment and prevention. Statistical analysis will be performed on the collected data to achieve these objectives. Results: The study is expected to provide detailed insights into the prevalence and risk factors of cervical cancer in Sri Lanka, along with the current state of awareness and preventive measures among women. It will also highlight the barriers to effective treatment and prevention, guiding future strategies. Conclusion: The findings of this study will significantly contribute to understanding the impact of cervical cancer in Sri Lanka, offering evidence-based recommendations for healthcare providers, policymakers, and the community to improve cervical cancer prevention and management strategies, with the ultimate goal of reducing the incidence and mortality rates of the disease in the country.

Exploring the impact of stage and tumor site on colorectal cancer survival: Bayesian survival modeling.

Colorectal cancer is a prevalent malignancy with global significance. This retrospective study aimed to investigate the influence of stage and tumor site on survival outcomes in 284 colorectal cancer patients diagnosed between 2001 and 2017. Patients were categorized into four groups based on tumor site (colon and rectum) and disease stage (early stage and advanced stage). Demographic characteristics, treatment modalities, and survival outcomes were recorded. Bayesian survival modeling was performed using semi-competing risks illness-death models with an accelerated failure time (AFT) approach, utilizing R 4.1 software. Results demonstrated significantly higher time ratios for disease recurrence (TR = 1.712, 95% CI 1.489-2.197), mortality without recurrence (TR = 1.933, 1.480-2.510), and mortality after recurrence (TR = 1.847, 1.147-2.178) in early-stage colon cancer compared to early-stage rectal cancer. Furthermore, patients with advanced-stage rectal cancer exhibited shorter survival times for disease recurrence than patients with early-stage colon cancer. The interaction effect between the disease site and cancer stage was not significant. These findings, derived from the optimal Bayesian log-normal model for terminal and non-terminal events, highlight the importance of early detection and effective management strategies for colon cancer. Early-stage colon cancer demonstrated improved survival rates for disease recurrence, mortality without recurrence, and mortality after recurrence compared to other stages. Early intervention and comprehensive care are crucial to enhance prognosis and minimize adverse events in colon cancer patients.

A Meta-Analysis and Review of Radiation Dose Escalation in Definitive Radiation Therapy between Squamous Cell Carcinoma and Adenocarcinoma of Esophageal Cancer

Esophageal cancer, ranked as the eighth most prevalent cancer globally, is characterized by a low survival rate and poor prognosis. Concurrent chemoradiation therapy (CCRT) is the standard therapy in the non-surgical treatment of localized carcinoma of the esophagus. Nevertheless, the radiation doses employed in CCRT remain notably lower compared to the curative definite chemoradiation therapy utilized in the management of other carcinomas. In order to increase the local control rates and enhance the treatment outcomes, several clinical trials have used high-dose radiation to analyze the effect of dose escalation. Despite the integration of technically advanced RT schemes such as intensity-modulated radiation therapy (IMRT), the results of these trials have failed to demonstrate a significant improvement in overall survival or local progression-free survival. In this review, we investigated previous clinical trials to determine the ineffectiveness of radiation dose escalation in the context of CCRT for esophageal cancer. We aim to clarify the factors contributing to the limited efficacy of escalated radiation doses in improving patient outcomes. Furthermore, we delve into recent research endeavors, exploring prospective radiation dose modifications being altered based on the histological characteristics of the carcinoma. The exploration of these recent studies not only sheds light on potential refinements to the existing treatment protocols but also seeks to identify novel approaches that may pave the way for more efficacious and personalized therapeutic strategies for esophageal cancer management.

Causes of death in patients operated for colorectal cancer

BackgroundColorectal cancer remains the third leading cause of cancer-related mortality in the United States. This study evaluates the causes of death in patients operated on for colorectal cancer and their determinants. MethodsAn Instructional Review Board-approved database containing patients who underwent surgical resection for colorectal cancer from 2004 to 2018 (last followed up in December 2020) in a tertiary care institution. Data on the underlying cause of death was extracted from the Registry of Vital Records and Statistics in Massachusetts. ResultsA total of 576 deaths were recorded in the database, of which 290 (50.35%) patients died of colorectal cancer. Deaths from colorectal cancer gradually decreased over time, whereas deaths from other cancers increased, and deaths from cardiovascular diseases remained stable. Patients who died from colorectal cancer were younger, died earlier in the disease course, had fewer comorbidities, higher rates of stage IV disease, rectal cancer, neoadjuvant therapy, extramural vascular invasion, perineural invasion, R0 resection, and preserved mismatch repair protein status. On multivariate analysis, age (adjusted odds ratio for 10-year increase = 0.79, 95% confidence interval 0.65–0.95), American Society of Anesthesiologists score (adjusted odds ratio = 0.64, confidence interval 0.42–0.98), stage IV disease (adjusted odds ratio = 3.02, confidence interval 1.59–5.9), neoadjuvant therapy (adjusted odds ratio = 7.91, confidence interval 2.64–28.13), extramural vascular invasion (adjusted odds ratio = 2.3, confidence interval 1.36–3.91) & time from diagnosis to death (adjusted odds ratio = 0.76, confidence interval 0.68–0.83) predicted death due to colorectal cancer versus other causes, whereas tumor location, perineural invasion, R0 resection, and mismatch repair protein status did not. ConclusionThere is a declining trend of deaths from colorectal cancer, presumably reflecting advances in colorectal cancer management strategies and better screening over time. However, younger patients disproportionately contribute to death due to colorectal cancer and need aggressive screening and management strategies.

Anticancer Potential of β-Carboline Alkaloids: An Updated Mechanistic Overview.

his comprehensive review is designed to evaluate the anticancer properties of β-carbolines derived from medicinal plants, with the ultimate goal of assessing their suitability and potential in cancer treatment, management, and prevention. An exhaustive literature survey was conducted on a wide array of β-carbolines including, but not limited to, harmaline, harmine, harmicine, harman, harmol, harmalol, pinoline, tetrahydroharmine, tryptoline, cordysinin C, cordysinin D, norharmane, and perlolyrine. Various analytical techniques were employed to identify and screen these compounds, followed by a detailed analysis of their anticancer mechanisms. Natural β-carbolines such as harmaline and harmine have shown promising inhibitory effects on the growth of cancer cells, as evidenced by multiple in vitro and in vivo studies. Synthetically derived β-carbolines also displayed noteworthy anticancer, neuroprotective, and cognitive-enhancing effects. The current body of research emphasizes the potential of β-carbolines as a unique source of bioactive compounds for cancer treatment. The diverse range of β-carbolines derived from medicinal plants can offer valuable insights into the development of new therapeutic strategies for cancer management and prevention.