Specific Cancer Types Research Articles

A Comparative Study on BRAFV600E Mutation, Sonographic Findings, and Pathologic Characteristics in Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP) and Invasive Follicular Variant of Papillary Thyroid Carcinoma (IFVPTC)

Objective: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) comprise a new subgroup of thyroid tumors of follicular origin with borderline histologic features that lack evidence of either capsular or vascular invasion. In contrast to the invasive follicular variant of papillary thyroid carcinoma (IFVPTC), adverse events such as cancer-related death, distant or regional metastases, and structural or biochemical recurrence do not occur in patients with NIFTP. Many studies have been done to elucidate these two specific types of papillary thyroid cancer (PTC) and reduce aggressive therapeutic actions. This study compares molecular, cytological, and radiologic features of NIFTP and IFVPTC. Materials and Methods: Two groups of patients with NIFTP and IFVPTC (n = 18 in each group) who were referred to the endocrine clinic, at Imam Reza Hospital, were enrolled in this crosssectional study. Molecular analysis for BRAFV600E mutation of thyroid tissue was evaluated for all cases. Patient data included: age, sex, type of surgery, thyroid sonographic findings, and prior cytological diagnosis with the Bethesda system for reporting thyroid cytopathology. Results: Only two cases in the IFVPTC group were positive for BRAFV600E mutation. The majority of NIFTP cases were diagnosed as benign lesions (8/18). In contrast, the majority of IFVPTC cases were diagnosed as suspicious for malignancy on cytology (7/18). The mean nodule size in ultrasound in the NIFTP group (41.81 ± 20.43 mm) was larger than the IFVPTC group (36.72 ± 20.73 mm) (p =0.47). Most cases in the IFVPTC group had significantly multiple nodules (72.2%), while most cases in the NIFTP group (81.3%) had solitary nodules. Nodule composition in both groups was solid and complex; however, no cystic nodules were detected in ultrasound examinations. Furthermore, no calcification or lymphadenopathy was seen in the majority of cases in ultrasound. In the IFVPTC group, 47.1% and 35.3% of nodules were hyperechoic and hypoechoic, respectively, while 23.1%, 38.5%, and 23.1% of nodules in the NIFTP group were heterogenic, hyperechoic, and hypoechoic, respectively. Conclusion: According to our findings, only 11.1% of IFVPTC cases were BRAFV600E-positive, while none of the patients in the NIFTP group showed this mutation. However, IFVPTC was predominantly associated with a preceding diagnosis of PTC on FNA, and NIFTP was associated with the preceding diagnosis of benign lesions and follicular neoplasm. Sonographic findings failed to distinguish NIFTP from IFVPTC.

Association between leisure-time physical activity and incident cancer risk: a nationwide population-based cohort study

BackgroundThe effects of physical activity on the development of different types of cancers have not been comprehensively studied. This nationwide, population-based cohort study investigated the effects of leisure-time physical activity (LTPA) on the development of different types of cancer in Taiwanese adults. A total of 67,890 adult participants (≥ 18 y old) from five rounds (2001, 2005, 2009, 2013, and 2017) of the Taiwan National Health Interview Survey were included. LTPA was measured as the metabolic equivalent of task (MET) expenditure per week and was classified as inactive (< 1 MET-h), low (1-7.49 MET-h), or high (≥ 7.5 MET-h). The LTPA and other covariates were collected through in-person interviews at baseline. New-onset cancer was ascertained from histopathological reports. The Fine-Gray sub-distribution method, with death as a competing risk, was used to determine the impact of LTPA on incident cancer risk.ResultsDuring the 844,337 person-years of follow-up, 4,435 individuals developed cancer. Compared to inactive adults, individuals engaging in high levels of LTPA (≥ 7.5 MET-h/week) were significantly associated with a reduced risk of developing cancer (adjusted hazard ratio [aHR] = 0.93; 95% confidence interval [CI] = 0.87–0.99). However, those with low levels of LTPA (1-7.49 MET-h/week) did not exhibit a significant association with a reduced risk of developing cancer (aHR = 1.00; 95% CI = 0.92–1.10). When considering specific types of cancers, participants with high levels of LTPA (≥ 7.5 MET-h/week) had a significantly lower risk of developing bladder cancer (aHR = 0.68; 95% CI = 0.47–0.99), cervical cancer (aHR = 0.48; 95% CI = 0.24–0.95), and thyroid cancer (aHR = 0.64; 95% CI = 0.44–0.93).ConclusionsOur findings suggest that high LTPA (≥ 7.5 MET-h/week) is significantly associated with a low risk of incident bladder, cervical, and thyroid cancers.

Association between gout and cancers: A systematic review and meta-analysis.

This study aimed to investigate the association between gout and cancer risk. This study was registered with the Prospective Registry for International Systematic Reviews (ID: CRD42023465587). We searched PubMed, Embase, Scopus, Cochrane, and Web of Science databases for studies related to gout and cancer risk, with a timeframe from the date the database was created to September 2023. We assessed the methodological quality of the included studies using the Newcastle-Ottawa scale and assessed heterogeneity between studies using the I2 statistic. Depending on the heterogeneity, we calculated pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) using fixed-effects or random-effects models. In addition, we performed sensitivity analyses and publication bias tests. In this study, we conducted a meta-analysis of 6 studies encompassing a total of 1279,804 participants. Our analysis revealed that individuals with gout are at a heightened risk of developing cancer in general (HR = 1.18, 95% CI = 1.04-1.34, P < .001). Moreover, specific types of cancer displayed a significant correlation with gout, including gastric cancer (HR = 1.31, 95% CI = 1.07-1.62, P = .012), liver cancer (HR = 1.24, 95% CI = 1.01-1.52, P < .001), lung cancer (HR = 1.26, 95% CI = 1.03-1.53, P = .001), and bladder cancer (HR = 1.57, 95% CI = 1.02-2.41, P < .001). Furthermore, gout exhibited a marginally increased risk for other cancer types, such as head and neck cancer and esophageal cancer, although these associations did not attain statistical significance. Our study suggests that gout is a risk factor for cancer, especially for stomach, liver, lung, and bladder cancers. Patients with gout have an increased risk of developing overall cancers, lung cancer, liver cancer, stomach cancer, and bladder cancer. However, more high-quality epidemiologic studies are needed to explore the association between gout and individual cancers more accurately.

Association between fish oil and glucosamine use and mortality in patients diagnosed with cancer: the role of the Life Essential 8 score and cancer prognosis

BackgroundThe effect of supplements on mortality risk in patients with cancer remains uncertain and has scarcely been investigated in subgroups of patients with varying characteristics. This study aimed to investigate the association between two popular supplements, fish oil and glucosamine, and mortality risk in a large population-based cohort and determine whether cardiovascular health and clinical prognosis influence these associations.MethodsThis prospective cohort study analyzed the data of UK Biobank participants who were diagnosed with cancer. The associations of fish oil and glucosamine consumption with mortality were analyzed using Cox proportional hazards models. Subgroup analyses were performed to assess the effects of Life Essential 8 [LE8] scores (a measure of cardiovascular health) and cancer prognosis (grouped according to the survival rates of specific cancer types) on the associations between supplement use and mortality.ResultsThis analysis included 14,920 participants (mean age = 59.9 years; 60.2% female). One third (34.1%) of the participants reported using fish oil, and one fifth (20.5%) reported using glucosamine. Over a median follow-up of 12.0 years, 2,708 all-cause deaths were registered. The use of fish oil was associated with reduced risks of all-cause mortality (adjusted hazard ratio [aHR] = 0.89, 95% Confidence Interval [CI] = 0.81–0.97) and cancer mortality (aHR = 0.89, 95% CI = 0.81–0.98). Similarly, glucosamine use was associated with reduced risks of all-cause mortality (aHR = 0.83, 95% CI = 0.74–0.92) and cancer mortality (aHR = 0.83, 95% CI = 0.74–0.93) in the fully adjusted model. Subgroup analyses revealed that the protective effects of fish oil and glucosamine against mortality risk were only observed in patients with LE8 scores lower than the mean score or a poor cancer prognosis. Additionally, the association between glucosamine use and a reduced risk of CVD-related mortality was only observed in patients with lower LE8 scores.ConclusionsThis large cohort study identified the potential differential impact of LE8 scores and cancer prognosis on the associations of fish oil and glucosamine supplementation with survival in patients with cancer. This suggests the importance of considering these factors in future research on supplements and in the provision of personalized integrative cancer care.

The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study.

The aim of this study was to determine the association between insulin glargine usage and the potential increase in cancer risk among the Lithuanian population diagnosed with type 2 diabetes mellitus (T2DM). A retrospective cohort study was conducted. The cohort of insulin users was established by identifying all male and female patients diagnosed with T2DM, as recorded in the National Health Insurance Fund database between 1 January 2000 and 31 December 2012. The risk of cancer among insulin glargine users was compared with the risk in non-glargine insulin users. Cox proportional hazard models were used to estimate hazard ratios (HR) and their 95% confidence intervals (CI). The overall cancer risk for all sites combined showed no significant difference (HR 0.84, 95% CI 0.67-1.05). Although a general decrease in the risk of cancers was observed at most sites for glargine users, the use of insulin glargine was associated with a non-significant increase in the risk of mouth and pharynx, stomach, non-melanoma skin, breast, cervical, ovarian, and central nervous system cancers. There was a tendency for a lower risk of colon, rectum, rectosigmoid, and anus cancer among glargine users (HR 0.45, 95% CI 0.18-1.12, p = 0.09). Our research contributes to the growing body of evidence showing that insulin glargine is not associated with an increased risk of all cancers or specific types of cancer.

Vanillin and Its Derivatives: A Critical Review of Their Anti-Inflammatory, Anti-Infective, Wound-Healing, Neuroprotective, and Anti-Cancer Health-Promoting Benefits

Inflammation and thrombosis are implicated in several non-communicable chronic disorders, including cardiovascular diseases, diabetes, renal and neurodegenerative disorders, skin diseases, and especially in cancer. Natural bioactives and especially phytochemicals like phenolic compounds have been proposed to reduce the inflammatory burden with several health benefits against these disorders. Vanillin is a phenolic compound found in the seeds of various species of vanilla plants. It has been known since ancient times for its aromatic and soothing properties; however, recent outcomes have outlined several other pleiotropic actions for this phenolic bioactive compound. Within this article, the potent anti-inflammatory activities of vanillin and its derivatives are thoroughly reviewed, with emphasis on their anti-cancer, anti-infective, wound-healing, and neuroprotective health-promoting properties. The mechanisms of their action(s), along with recent outcomes from in vitro and in vivo studies and clinical trials, on the benefits of these vanillin-based phenolic bioactives against each of these disorders, and especially against specific types of cancer, are also outlined. Limitations and future perspectives of their use solely as bioactive ingredients, as ingredients in several functional products—such as functional foods, supplements, nutraceuticals, or even cosmetics and drugs—and even as adjuvant therapies are also discussed.

Unveiling the pan-cancer landscape of S100A16: A comprehensive analysis of prognostic significance, drug sensitivity, and immunomodulatory roles.

Accumulating evidence supports the notion that S100A16 exhibits differential expression in many human cancers, affecting cellular functions associated with tumorigenesis through various signaling pathways. While extensive research has been conducted on S100A16 in specific cancer types, a comprehensive evaluation of its role across diverse cancers remains lacking. To explore the prognostic significance, drug sensitivity, and immunomodulatory roles of S100A16, a thorough analysis was conducted at a pan-cancer level using multiple databases. Our findings revealed high expression of S100A16 RNA in various human cancers. Importantly, this elevated expression was linked to disease prognosis and drug sensitivity across a spectrum of cancers. Genetic alterations in S100A16 were characterized across multiple cancer types, and a confirmed correlation was observed in the prognosis of skin cutaneous melanoma (SKCM). Furthermore, our study demonstrated a significant association between S100A16 expression and the infiltrating levels of diverse cell types in the tumor microenvironment (TME), suggesting its potential as a prognosis predictor for immunotherapy. Novel collections of miRNAs, such as has-miR-423-5p, has-miR-769-5p, has-miR-151a-3p, and has-miR-550a-5p, targeting S100A16 at a pan-cancer level were predicted through various databases. These findings contribute to a comprehensive understanding the role of S100A16 in prognosis prediction, chemotherapy, and immunotherapy, providing valuable insights for identifying novel targets in cancer treatment.

A genetically informed study reveals modifiable pathways in skin cancer

BackgroundIdentifying modifiable risk factors is essential for the prevention of skin cancer; however, establishing causality can be challenging in conventional epidemiological studies. This study aimed to determine the causal associations of potentially modifiable risk factors with skin cancer using Mendelian randomization (MR).MethodsGenetic instruments for 53 risk factors, including socioeconomic status, dietary and lifestyle factors, anthropometric measures, medication use, and comorbidities, were identified from previous genome-wide association studies. Two-sample MR analyses were performed using summary statistics for three major types of skin cancer: melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Findings were verified using multiple MR methods under different assumptions and replication datasets.ResultsGenetic liability to sunburn occasions, actinic keratosis, and prior skin cancers was associated with a higher risk of all three types of skin cancer, whereas genetic liability to vitiligo was associated with a lower risk. For specific skin cancer types, genetically predicted higher nevus counts and occupational class were associated with an increased risk of melanoma. Genetic liability to rheumatoid arthritis, type 2 diabetes, and increased physical activity were associated with a lower risk of BCC. Genetically predicated body mass index showed a negative association with BCC, and a positive association with SCC.ConclusionsOur study reaffirmed several previously established risk factors and identified novel potential risk factors for skin cancer. Further work is needed to unravel the biological pathways in different skin cancer types and translate our findings to inform public health policies.

8581 Unusual Case of Multifactorial Hyperthyroidism

Abstract Disclosure: D.D. Bagar: None. E. Meyers: None. M. Correia: None. Background: Nivolumab is an immune checkpoint inhibitor that is used to treat specific types of cancer, including melanoma, by increasing the ability of the immune system to detect cancer through activating cytotoxic T-cells. The side effects of immune checkpoint inhibitors are mainly through the overactivation of the immune system that can affect many organs with autoimmune diseases, including endocrine glands, which could be severe and irreversible, like hypothyroidism or immune thyroiditis. The uniqueness of this case is the presence of multifactorial causes of hyperthyroidism; in addition, it is one of the few cases of immune checkpoint inhibitor induced positive TSI thyroiditis.Clinical Case: An 82-year-old male with a known history of atrial fibrillation on amiodarone presented to his dermatologist with a left forearm lesion. A shave biopsy showed melanoma, and he underwent wide local excision with negative sentinel lymph node biopsy. However, he had significant melanoma in situ present within 5 mm of the margin and was deemed not a candidate for further excision. Tumor board recommended close surveillance. He then received two cycles of pembrolizumab for one year, followed by nivolumab. During his treatment course, he had CT scans with iodinated contrast every 8-12 weeks for the clinical trial. At his clinic visit, routine thyroid function tests were significant for hyperthyroidism with a TSH &amp;lt;0.01 and free T4 of 6.07 (0.8-1.8). He was asymptomatic except for unintentional weight loss. He denied using any biotin supplements. His labs also showed positive thyroid stimulating immunoglobulin (TSI) of 1.10 (&amp;lt;=0.54 IU/L). A thyroid US with doppler showed two nodules less than 1.1 cm and no increased vascularity. Amiodarone was discontinued, and prednisone and methimazole were started. His free T4 has since normalized and both prednisone and methimazole are being tapered down. Conclusion: This case is a multifactorial cause of hyperthyroidism. He had been using amiodarone for atrial fibrillation, had multiple imaging studies with iodinated contrast, and was on immune checkpoint inhibitor therapy with a positive TSI. The uniqueness of this case is not only that combined factors can affect thyroid function but also that he developed a positive TSI, which indicates either Graves’ disease or immune-induced thyroiditis by nivolumab, which has been reported only in a few cases. Presentation: 6/3/2024

8581 Unusual Case Of Multifactorial Hyperthyroidism

Abstract Disclosure: D.D. Bagar: None. E. Meyers: None. M. Correia: None. Background: Nivolumab is an immune checkpoint inhibitor that is used to treat specific types of cancer, including melanoma, by increasing the ability of the immune system to detect cancer through activating cytotoxic T-cells. The side effects of immune checkpoint inhibitors are mainly through the overactivation of the immune system that can affect many organs with autoimmune diseases, including endocrine glands, which could be severe and irreversible, like hypothyroidism or immune thyroiditis. The uniqueness of this case is the presence of multifactorial causes of hyperthyroidism; in addition, it is one of the few cases of immune checkpoint inhibitor induced positive TSI thyroiditis.Clinical Case: An 82-year-old male with a known history of atrial fibrillation on amiodarone presented to his dermatologist with a left forearm lesion. A shave biopsy showed melanoma, and he underwent wide local excision with negative sentinel lymph node biopsy. However, he had significant melanoma in situ present within 5 mm of the margin and was deemed not a candidate for further excision. Tumor board recommended close surveillance. He then received two cycles of pembrolizumab for one year, followed by nivolumab. During his treatment course, he had CT scans with iodinated contrast every 8-12 weeks for the clinical trial. At his clinic visit, routine thyroid function tests were significant for hyperthyroidism with a TSH &amp;lt;0.01 and free T4 of 6.07 (0.8-1.8). He was asymptomatic except for unintentional weight loss. He denied using any biotin supplements. His labs also showed positive thyroid stimulating immunoglobulin (TSI) of 1.10 (&amp;lt;=0.54 IU/L). A thyroid US with doppler showed two nodules less than 1.1 cm and no increased vascularity. Amiodarone was discontinued, and prednisone and methimazole were started. His free T4 has since normalized and both prednisone and methimazole are being tapered down. Conclusion: This case is a multifactorial cause of hyperthyroidism. He had been using amiodarone for atrial fibrillation, had multiple imaging studies with iodinated contrast, and was on immune checkpoint inhibitor therapy with a positive TSI. The uniqueness of this case is not only that combined factors can affect thyroid function but also that he developed a positive TSI, which indicates either Graves’ disease or immune-induced thyroiditis by nivolumab, which has been reported only in a few cases. Presentation: 6/3/2024

Network modeling links kidney developmental programs and the cancer type-specificity of VHL mutations

Elucidating the molecular dependencies behind the cancer-type specificity of driver mutations may reveal new therapeutic opportunities. We hypothesized that developmental programs would impact the transduction of oncogenic signaling activated by a driver mutation and shape its cancer-type specificity. Therefore, we designed a computational analysis framework by combining single-cell gene expression profiles during fetal organ development, latent factor discovery, and information theory-based differential network analysis to systematically identify transcription factors that selectively respond to driver mutations under the influence of organ-specific developmental programs. After applying this approach to VHL mutations, which are highly specific to clear cell renal cell carcinoma (ccRCC), we revealed important regulators downstream of VHL mutations in ccRCC and used their activities to cluster patients with ccRCC into three subtypes. This classification revealed a more significant difference in prognosis than the previous mRNA profile-based method and was validated in an independent cohort. Moreover, we found that EP300, a key epigenetic factor maintaining the regulatory network of the subtype with the worst prognosis, can be targeted by a small inhibitor, suggesting a potential treatment option for a subset of patients with ccRCC. This work demonstrated an intimate relationship between organ development and oncogenesis from the perspective of systems biology, and the method can be generalized to study the influence of other biological processes on cancer driver mutations.

Prescription predicament: Unveiling the financial fallout of drug shortages.

1 Background: Managing drug shortages has become a part of care delivery in oncology. Shortages have been reported to result in missed/delayed treatment, substitution of alternative therapy, increased costs, and significant administrative burden. A national shortage of cisplatin caused by manufacturing disruptions was reported by the Food and Drug Administration in the United States from February until August 2023 (shortage period). We assessed the effects of cisplatin shortage on the treatment of head and neck cancer (HNC) at practices in The US Oncology Network (The Network). Methods: Using drug administration data from medical records and claims for 26 practices in The Network prior to (July 2022 to January 2023), during, and after (September 2023 to March 2024) the shortage period, we assessed the utilization trends and financial impact (using Medicare average sale price (ASP)) of cisplatin and other anti-cancer drugs for HNC patients. Results: During the shortage period, cisplatin utilization for HNC decreased by 15% compared to pre-shortage levels. The lowest utilization occurred in June and July 2023, with a 60% decrease. Practices initially obtained supplies through an allocation model and fair-share utilization guidance from The Network Pharmacy &amp; Therapeutics Committee. During the shortage period, alternative chemotherapy drugs for HNC saw increased use: carboplatin by 40%, paclitaxel by 24%, 5-fluorouracil by 5.3%, and cetuximab by 15%. The increased use of alternative drugs corresponded to the decrease in cisplatin usage, with new starts shifting to carboplatin (with or without paclitaxel), cetuximab and 5-fluorouracil. Ten percent of existing cisplatin recipients were shifted to an alternative drug during the shortage period. Interestingly, 5-fluorouracil was also in short supply, albeit less acutely than cisplatin. After the shortage, cisplatin volumes rebounded by 8% of pre-shortage use, while carboplatin use dropped below pre-shortage levels. Cetuximab use remained consistently 12% higher. The average cost per administration was $18 for cisplatin, $14 for carboplatin, $16 for paclitaxel, $22 for 5-fluorouracil, and $2,607 for cetuximab, based on the ASP. The increased use of cetuximab instead of cisplatin resulted in a 16% total cost increase, leading to a 144-fold increase in costs at the administration level, impacting payer costs and patient cost-sharing amounts. Conclusions: Cisplatin shortage led to a shift in utilization to alternative therapies for HNC, resulting in significant cost increases for both payers and patients. These consequences may not be limited to specific cancer types or drugs and may have other undesirable effects. Even temporary shortages of drugs can lead to lasting utilization changes and have long-term financial implications. The impacts of drug shortages on treatment decisions, guideline concordance, costs, and patient outcomes are apt for further investigation.

Relationship between SGLT2 inhibitor use and specific cancer types: a systematic review and meta-analysis.

Aim: The study aimed to explore the incidence of cancer as an adverse event to SGLT2 inhibitors (SGLT2i) use in Type 2 diabetes.Materials & methods: The study followed PRISMA guidelines to pool RCTs conforming the inclusion criteria. Random effects model was used to pool risk ratios.Results & conclusion: After reviewing 19 studies, the analysis suggested a possible increased risk of reproductive, breast, thyroid, hematologic/lymphatic, urinary, skin and skeletal cancers with SGLT2i use. Conversely, lower incidences of respiratory and cardiovascular cancers were noted. However, these associations lacked statistical significance. Caution is advised in using SGLT2i due to potential cancer risks, especially in diabetic patients prone to cancer. More RCTs are essential due to limited research in this area.

Specific cancer types and prognosis in patients with variations in the KEAP1-NRF2 system: A retrospective cohort study.

The KEAP1-NRF2 system induces the expression of antioxidant genes in response to various types of oxidative stress. Some cancer cells activate this system, which increases their malignancy through genetic mutations. We performed a retrospective cohort study using the C-CAT database, which contains the gene-panel sequence data from 60,056 cases of diagnosed solid tumors. We analyzed somatic mutations in NRF2 and KEAP1 genes and their associations with clinical outcomes. Variants in the NRF2 gene were clustered in exon 2, which encodes the DLG and ETGE motifs essential for KEAP1 interaction. The NRF2 variants were frequently observed in esophageal and lung squamous cell carcinoma with frequencies of 35.9% and 19.6%, respectively. Among these mutations, the NRF2 variants in the ETGE motif were indicators of a worse prognosis. KEAP1 variants were found in 2.5% of all cases. The variants were frequent in lung cancer and showed a worse prognosis in lung and other types of adenocarcinomas. We then conducted gene expression analysis using TCGA data. While cancers with DLG and ETGE variants were similar in terms of gene expression profiles, there were significant differences between cancers with KEAP1 and NRF2 variants. Our results indicate that genetic alteration of the KEAP1-NRF2 pathway is a major factor in patient prognosis for each cancer type and its genetic variant. Variants in NRF2 and KEAP1 genes can characterize the biological basis of each cancer type and are involved in carcinogenesis, resistance to therapy, and other biological differences.

Abstract A081: Comprehensive examination of disparities in cancer incidences by race, gender, and age over 65 years in Alabama's Black belt counties, USA

Abstract In the United States, significant disparities persist in cancer incidence, mortality, and treatment outcomes, particularly among Black populations. Despite advances in medical care, disparities continue to challenge efforts to achieve health equity. Understanding and addressing these complex issues are imperative to ensure that all individuals, regardless of race or ethnicity, have equal access to effective cancer prevention, diagnosis, and treatment. Alabama stands out as the leading state among the top ten in terms of densely populated Black Belt counties in the United States. With 67 counties in total, Alabama is home to 24 designated Black Belt counties. Given this concentration, Alabama becomes a key focus for comprehending cancer disparities. The ongoing research seeks to examine the occurrence of various types of cancer among the predominant racial groups in the United States, focusing particularly on the Black Belt counties of Alabama. Data on cancer occurrences, obtained from the database of National Cancer Institute (NIH) and the Centers for Disease Control and Prevention (CDC), offer insights into cancer incidences among various demographic groups, age categories, and specific types of cancer spanning the last five years (2016-2020). Analysis of the data, focusing on patients aged 65 years and older, was performed using GraphPad Prism 5 software. Graphs were created to visually represent and interpret the data regarding incidences per 100,000 populations. We observe significantly elevated incidences of major cancer types such as prostate, colon, lung, stomach, pancreas, and liver among Black males, and similarly heightened rates of uterus, cervix, stomach, pancreas, and kidney cancers among Black females, when compared to white populations. Notably, within Alabama's Black Belt regions, only a small number of counties have reported incidences of cancer regardless of gender and cancer types, except for prostate cancer in males and breast cancer in females. Moreover, in certain Black Belt counties, rates of colon and lung cancer (in both males and females), as well as prostate cancer in males and breast cancer in females, are exceptionally elevated compared to both the statewide average in Alabama and even the national average in the United States. Generally, females tend to have lower rates of cancer across various types compared to males. In conclusion, factors contributing to these disparities include genetic predispositions, socioeconomic status, healthcare accessibility, systemic biases, and cultural influences. Further investigations, including molecular screening studies, are imperative to corroborate these health disparities and foster community-wide cancer awareness and public health initiatives. Citation Format: Faith Onomeh, Anathbandhu Chaudhuri. Comprehensive examination of disparities in cancer incidences by race, gender, and age over 65 years in Alabama's Black belt counties, USA [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A081.

Abstract B167: Genomics and cancer clinical trials navigator training: Results from a systematic review of the literature

Abstract Introduction: Trained cancer navigators have demonstrated success in improving outcomes for cancer patients. Trainings provided by the American Cancer Society and other organizations equip navigators with the knowledge, skills and experience to support patients and address barriers to cancer-related care and survivorship. Racial/ethnic minorities continue to be underrepresented in cancer clinical trials and are less likely to receive genomic counseling and testing. There is a notable gap in the availability of cancer navigator training in genomic and clinical trials. This study used a systematic review of the literature and consultations with Genomics and Cancer Clinical Trial (CCT) experts to inform the development of cancer navigation training curriculum. Methods: Two reviewers searched the PubMed database for peer-reviewed studies published through October 2022. Key MeSH terms included cancer, genetics, and training. An ancestor search of relevant articles was also conducted. Following title screening, eleven articles were selected for abstract and full-text review. Eight articles met all the inclusion criteria from which we extracted the 1) trainee population, 2) theoretical frameworks used, 3) program design and format, 4) curricular components, and 5) outcomes. New Data: Only seven articles on the topic of navigator training in genomics within the context of CCT were identified in the search. Training participants were diverse and were located within the United States and abroad. One training program was developed for bilingual (English/Spanish) navigators, one was tailored for cancer survivors who became navigators and two programs trained navigators for specific cancer types (e.g., colorectal cancer). Social cognitive theory (SCT) was used in two of the training programs. Other adult learning theories and intervention mapping for program development were also used in training development. The process for designing navigator trainings included: conducting discussion groups; interviews and surveys; engaging advisory boards; and adapting the National Human Genomics Research Institute modules and other resources. The curricula components included in-person and web-based; single semester or year-long sessions; formal coursework; lectures; role-playing; video viewing; tours of facilities; demonstrations; short writing assignments; action plans; case studies; story- telling; discussion and networking; assessment/evaluation; and refresher sessions. Modules addressed attitudes, barrier assessment and resolution, knowledge, self-efficacy, and communication. Conclusion: The peer-reviewed literature on navigator training describes some curricular elements that measure and address knowledge about genomics and CCT as well as the skills needed to increase self-efficacy to navigate for genetic studies and cancer clinical trials. However, the field of CCT lacks a consistent and widely used program aimed at training navigators in the integral role of genetics in precision medicine. These findings informed the design of our ACS-funded curriculum. Citation Format: Desiree Rivers, Robina Josiah Willock, Victoria Churchill. Genomics and cancer clinical trials navigator training: Results from a systematic review of the literature [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B167.

Evaluation of clinically significant miRNAs level by machine learning approaches utilizing total transcriptome data

Analysis of the mechanisms underlying the occurrence and progression of cancer represents a key objective in contemporary clinical bioinformatics and molecular biology. Utilizing omics data, particularly transcriptomes, enables a detailed characterization of expression patterns and post-transcriptional regulation across various RNA types relative to the entire transcriptome. Here, we assembled a dataset comprising transcriptomic data from approximately 16.000 patients encompassing over 160 types of cancer. We employed state-of-the-art gradient boosting algorithms to discern intricate correlations in the expression levels of four clinically significant microRNAs, specifically hsa-mir-21, hsa-let-7a-1, hsa-let-7b, and hsa-let-7i, with the expression levels of the remaining 60.660 unique RNAs. Our analysis revealed a dependence of the expression levels of the studied microRNAs on the concentrations of several small nucleolar RNAs and regulatory long non-coding RNAs. Notably, the roles of these RNAs in the development of specific cancer types had been previously established through experimental evidence. Subsequent evaluation of the created database will facilitate the identification of a broader spectrum of overarching dependencies related to changes in the expression levels of various RNA classes in diverse cancers. In future it will make possible discovery of unique alterations specific to certain types of malignant transformations.

Advancing Cancer Care in Colombia: Results of the First In Situ Implementation of Comprehensive Genomic Profiling.

Comprehensive genomic profiling (CGP) identifies genetic alterations and patterns that are crucial for therapy selection and precise treatment development. In Colombia, limited access to CGP tests underscores the necessity of documenting the prevalence of treatable genetic alterations. This study aimed to describe the somatic genetic profile of specific cancer types in Colombian patients and assess its impact on treatment selection. A retrospective cohort study was conducted at Clínica Colsanitas S.A. from March 2023 to June 2024. Sequencing was performed on the NextSeq2000 platform with the TruSight Oncology 500 (TSO500) assay, which simultaneously evaluates 523 genes for DNA analysis and 55 for RNA; additionally, analyses were performed with the SOPHiA DDM software. The tumor mutational burden (TMB), microsatellite instability (MSI), and programmed cell death ligand 1 (PDL1) were assessed. Among 111 patients, 103 were evaluated, with gastrointestinal (27.93%), respiratory (13.51%), and central nervous system cancers (10.81%) being the most prevalent. TP53 (37%), KMT2C (28%), and KRAS (21%) were frequent mutations. Actionable findings were detected in 76.7% of cases, notably in digestive (20 patients) and lung cancers (8 patients). MSI was stable at 82.52% and high at 2.91%, whilst TMB was predominantly low (91.26%). The test has facilitated access to targeted therapies, improving clinical outcomes in Colombian patients. This profiling test is expected to increase opportunities for personalized medicine in Colombia.

Epinephrine, Pregabalin, and Crizotinib as Three Medicines with Polish Implications over Three Last Centuries and in View of Three Different Drug Discovery Approaches.

The discovery of epinephrine (adrenaline) and its subsequent implications in medicine owes significant contributions to Cybulski across different centuries, who, in 1894, was pivotal in identifying the adrenal medulla's role in blood pressure regulation and naming the active substance "nadnerczyna", known today as adrenaline. His work demonstrated the adrenal glands' critical function in the body's regulatory mechanisms beyond the nervous system. Cybulski's groundbreaking research laid foundational knowledge for future endocrinological studies and pharmaceutical advancements. In the late 20th century, Andruszkiewicz collaborated with Silverman at Northwestern University to develop pregabalin, the active ingredient in Lyrica. Their innovative synthesis of gamma-aminobutyric acid derivatives led to a significant advancement in treating epilepsy, neuropathic pain, and fibromyalgia. Andruszkiewicz's expertise in organic chemistry and enzymology was crucial in this collaborative effort, resulting in the successful development and commercialization of Lyrica. Additionally, Mroczkowski's leadership at Pfizer contributed to the development of crizotinib, a notable anaplastic lymphoma kinase and proto-oncogene 1 tyrosine-protein kinase inhibitor used to treat specific types of non-small cell lung cancer. Her work exemplifies the continuing influence of Polish researchers in pioneering drug discovery and advancing therapeutic treatments over the past three centuries. These contributions highlight Poland's significant role in global pharmaceutical innovations and medical research.

Effectiveness of a Single Fixed Dose of 3 mg Rasburicase for the Prevention and Management of Hyperuricemia in Tumor Lysis Syndrome in Adults With Cancer.

Tumor lysis syndrome (TLS) is a critical and potentially fatal complication linked to specific types of cancer. Rasburicase stands as a crucial medication necessary for the prevention and treatment of hyperuricemia, a condition commonly associated with TLS. Due to a shortage of rasburicase during the COVID-19 pandemic, a fixed-dose strategy of 3 mg rasburicase was used in many adult cancer patients in our center. The objective of this study was to assess the effectiveness of a fixed dose of 3 mg rasburicase in preventing and managing hyperuricemia associated with TLS in adult cancer patients. We conducted a retrospective, observational cohort study between March 2020 and February 2022. The study included adult patients who received a fixed dose of 3 mg rasburicase. The primary outcome measure was the reduction in serum uric acid (UA) levels at 24 and 48 hours after treatment, with the aim of achieving and maintaining normal UA levels. Seventeen patients in the treatment group and 20 patients in the prevention group were included. In the treatment group, 15 (88%) patients had normalization of serum UA, which is considered to be <7 mg/dL (median: 4.48 mg/dL) at 24 hours, and 16 (94%) patients had achieved normal UA at 48 hours (median: 2.78 mg/dL) after receiving the rasburicase dose. In the prevention group, all 20 (100%) patients achieved normal UA at 24 hours after receiving the rasburicase dose. Based on these findings, a single fixed dose of 3 mg rasburicase is effective for preventing and managing hyperuricemia associated with TLS in high-risk patients.