Common Cancer Research Articles

Photodynamic Therapy against Colorectal Cancer Using Porphin-Loaded Arene Ruthenium Cages

Colorectal cancer (CRC) is the third most common cancer in the world, with an ongoing rising incidence. Despite secure advancements in CRC treatments, challenges such as side effects and therapy resistance remain to be addressed. Photodynamic therapy (PDT) emerges as a promising modality, clinically used in treating different diseases, including cancer. Among the main challenges with current photosensitizers (PS), hydrophobicity and low selective uptake by the tumor remain prominent. Thus, developing an optimal design for PS to improve their solubility and enhance their selective accumulation in cancer cells is crucial for enhancing the efficacy of PDT. Targeted photoactivation triggers the production of reactive oxygen species (ROS), which promote oxidative stress within cancer cells and ultimately lead to their death. Ruthenium (Ru)-based compounds, known for their selective toxicity towards cancer cells, hold potential as anticancer agents. In this study, we investigated the effect of two distinct arene-Ru assemblies, which lodge porphin PS in their inner cavity, and tested them as PDT agents on the HCT116 and HT-29 human CRC cell lines. The cellular internalization of the porphin-loaded assemblies was confirmed by fluorescence microscopy. Additionally, significant photocytotoxicity was observed in both cell lines after photoactivation of the porphin in the cage systems, inducing apoptosis through caspase activation and cell cycle progression disruptions. These findings suggest that arene-Ru assemblies lodging porphin PS are potent candidates for PDT of CRC.

Time to death from cervical cancer and its predictors in hospitalized patients: a survival approach study in Mato Grosso, Brazil

BackgroundCervical cancer (CC) is a serious public health concern, being the fourth most common cancer among women and a leading cause of cancer mortality. In Brazil, many women are diagnosed late, and in Mato Grosso, with its geographical diversity, there are specific challenges. This study analyzed hospital survival and its predictors using data from the Hospital Information System (SIH) of the Unified Health System (SUS) in Mato Grosso from 2011 to 2023.MethodsCox regression and Kaplan-Meier models were applied to determine survival time and identify mortality predictors. The adjusted Hazard Ratio (AHR) with a 95% Confidence Interval (CI) was used to measure the association between the factors analyzed.ResultsThe hospital mortality rate was 9.88%. The median duration of hospitalization was 33 days (interquartile range [IQR]: 12–36), with a median survival of 43.7%. Patients were followed up for up to 70 days. In the multivariable Cox model, after adjusting for potential confounders, the risk of death during hospitalization was higher in patients aged 40–59 years (AHR = 1.39, p = 0.027) and 60–74 years (AHR = 1.54, p = 0.007), in the absence of surgical procedures (AHR = 4.48, p < 0.001), in patients with medium service complexity (AHR = 2.40, p = 0.037), and in the use of ICU (AHR = 4.97, p < 0.001). On the other hand, patients with hospital expenses above the median (152.971 USD) showed a reduced risk of death (AHR = 0.21, p < 0.001).ConclusionThis study highlights that hospitalized CC patients have reduced survival, underscoring the need for interventions to improve care, including strategies for early diagnosis and expanded access to adequately resourced health services.

The Diagnostic Value of bpMRI in Prostate Cancer: Benefits and Limitations Compared to mpMRI.

Prostate cancer is the second most common cancer in men and a leading cause of death worldwide. Early detection is vital, as it often presents with vague symptoms such as nocturia and poor urinary stream. Diagnostic tools like PSA tests, ultrasound, PET-CT, and mpMRI are essential for prostate cancer management. The PI-RADS system helps assess malignancy risk based on imaging. While mpMRI, which includes T1, T2, DWI, and dynamic contrast-enhanced imaging (DCE), is the standard, bpMRI offers a contrast-free alternative using only T2 and DWI. This reduces costs, acquisition time, and the risk of contrast-related side effects but has limitations in detecting higher-risk PI-RADS 3 and 4 lesions. This study compared bpMRI's diagnostic accuracy to mpMRI, focusing on prostate volume and PI-RADS scoring. Both methods showed strong inter-rater agreement for prostate volume (ICC 0.9963), confirming bpMRI's reliability in this aspect. However, mpMRI detected more complex conditions, such as periprostatic fat infiltration and iliac lymphadenopathy, which bpMRI missed. While bpMRI offers advantages like reduced cost and no contrast use, it is less effective for higher-risk lesions, making mpMRI more comprehensive.

Plasma metabolomics profiles and breast cancer risk

BackgroundBreast cancer (BC) is the most common cancer in women and incidence rates are increasing; metabolomics may be a promising approach for identifying the drivers of the increasing trends that cannot be explained by changes in known BC risk factors.MethodsWe conducted a nested case–control study (median followup 6.3 years) within the New York site of the Breast Cancer Family Registry (BCFR) (n = 40 cases and 70 age-matched controls). We conducted a metabolome-wide association study using untargeted metabolomics coupling hydrophilic interaction liquid chromatography (HILIC) and C18 chromatography with high-resolution mass spectrometry (LC-HRMS) to identify BC-related metabolic features.ResultsWe found eight metabolic features associated with BC risk. For the four metabolites negatively associated with risk, the adjusted odds ratios (ORs) ranged from 0.31 (95% confidence interval (CI): 0.14, 0.66) (L-Histidine) to 0.65 (95% CI: 0.43, 0.98) (N-Acetylgalactosamine), and for the four metabolites positively associated with risk, ORs ranged from 1.61 (95% CI: 1.04, 2.51, (m/z: 101.5813, RT: 90.4, 1,3-dibutyl-1-nitrosourea, a potential carcinogen)) to 2.20 (95% CI: 1.15, 4.23) (11-cis-Eicosenic acid). These results were no longer statistically significant after adjusting for multiple comparisons. Adding the BC-related metabolic features to a model, including age, the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk score improved the accuracy of BC prediction from an area under the curve (AUC) of 66% to 83%.ConclusionsIf replicated in larger prospective cohorts, these findings offer promising new ways to identify exposures related to BC and improve BC risk prediction.

Hypofractionated Gamma Knife Radiosurgery in Big Tumors

Objective: This research aimed to determine the most effective dosages and achieve improved outcomes without surgical intervention, discomfort, or blood loss. Its objective was also to regulate the formation of both benign and malignant tumours and reduce tumour size. Patients and Methods: A study involving 50 patients at Dr. Saad Al-Witry Hospital for Neurosciences and Al-Altaj Hospital examined brain tumours using MRI models, CBCT, and a gamma knife device. Patients with large tumours were included, while those receiving single fractions of treatment and pregnant women were excluded. Patients were prepared using Leksell frames, thermoplastic masks, and personalised stereotactic masks. Gamma Knife radiosurgery sessions were administered based on tumour size, location, and patient tolerance. Results: This study analysed the use of hypofractionation gamma knife treatment for six brain tumours: Meningioma, Glioma, Schwannoma, Arteriovenous Malformations (AVM), Pituitary Adenoma, and Metastasis. The mean dose distribution was higher in metastasis, followed by AVM, meningioma, glioma, schwannoma, and pituitary adenoma. The maximum dose was found in metastasis, followed by meningioma, glioma, pituitary adenoma, AVM, and schwannoma. The coverage of the target reached excellent value for metastasis, followed by AVM and pituitary adenoma. The beam on time for the treatment was highest in meningioma. Following six months of treatment, the study found a significant difference in tumour volume before and after six months. The highest reduction was observed in meningioma cases, followed by glioma and vestibular schwannoma. A study involving ten patients showed a significant reduction in tumours after a year of gamma knife treatment, with meningioma cases showing the highest reduction. Conclusion: The study found that metastasis was the most common cancer, followed by meningioma, glioma, schwannoma, AVM, and schwannoma. After six months, meningioma showed the highest reduction, and meningioma showed a better response to hypofractionation, followed by AVM.

Role of Sodium-Dependent Vitamin C Transporter-2 and Ascorbate in Regulating the Hypoxic Pathway in Cultured Glioblastoma Cells.

The most common and aggressive brain cancer, glioblastoma, is characterized by hypoxia and poor survival. The pro-tumour transcription factor, hypoxia-inducible factor (HIF), is regulated via HIF-hydroxylases that require ascorbate as cofactor. Decreased HIF-hydroxylase activity triggers the hypoxic pathway driving cancer progression. Tissue ascorbate accumulates via the sodium-dependent vitamin C transporter-2 (SVCT2). We hypothesize that glioblastoma cells rely on SVCT2 for ascorbate accumulation, and that knockout of this transporter would disrupt the regulation of the hypoxic pathway by ascorbate. Ascorbate uptake was measured in glioblastoma cell lines (U87MG, U251MG, T98G) by high-performance liquid chromatography. CRISPR/Cas9 was used to knockout SVCT2. Cells were treated with cobalt chloride, desferrioxamine or 5% oxygen, with/without ascorbate, and key hypoxic pathway proteins were measured using Western blot analysis. Ascorbate uptake was cell line dependent, ranging from 1.7 to 11.0 nmol/106 cells. SVCT2-knockout cells accumulated 90%-95% less intracellular ascorbate than parental cells. The hypoxic pathway was induced by all three stimuli, and ascorbate reduced this induction. In the SVCT2-knockout cells, ascorbate had limited effect on the hypoxic pathway. This study verifies that intracellular ascorbate is required to suppress the hypoxic pathway. As patient survival is related to an activated hypoxic pathway, increasing intra-tumoral ascorbate may be of clinical interest.

Proanthocyanidin Regulates NETosis and Inhibits the Growth and Proliferation of Liver Cancer Cells - In Vivo, In Vitro and In Silico Investigation.

Liver cancer ranks third in global cancer-related mortality, with about 700,000 deaths recorded yearly, making it one of the most common cancers worldwide. Even though prognoses differ according to the severity of the diseases, many patients now exhibit an increased life cycle since the implementation of chemotherapy. In the current study, we investigated the effect of proanthocyanidin ‒a polyphenol molecule found in many plants‒ on the proliferation and invasion of liver cancer cells. In particular, we determined the effect of proanthocyanidin on the serum levels of four strategic liver cancer target, TNFα, IL-6, cfDNA, and IL-1β. Further molecular insight on the inhibitory mechanism of proanthocyanidin against TNFα, IL-6, and IL-1β was obtained via molecular docking, molecular dynamics simulations and binding free energy calculations. Results showed that proanthocyanidin inhibited the growth of HepG2 and HEP3B cells, and effectively reduced clonogenic survival and invasion potential when compared to control cells. Proanthocyanidin was also found to suppress the expression of Bcl-2 (26 kDa) protein in HepG2 cells, while increasing the expression of Bax (21 kDa). Molecular dynamics (MD) and thermodynamic binding free energy calculations showed that proanthocyanidin maintained stable binding within the active site of target proteins across the entire 100 ns MD simulation period, and its binding affinity outscored respective control molecules.In conclusion, the multifaceted analysis showcased in this study demonstrated promising anti-cancer effect of proanthocyanidin on HepG2 and HEP3B cancer cells, highlighting its potential as a viable liver cancer therapeutic alternative.

The Prospective role of lapatinib as an adjuvant therapy in prevalent cancers: Insights from in silico analysis targeting EGFR and HER2

IntroductionVarious pieces of evidence suggest an elevation in the levels of EGFR and HER2 in different cancers leading to the proliferation, invasion, and metastasis of cancer cells. In this study, we conducted a comprehensive investigation into the expression alterations of these two receptors in various cancers using in silico data. In addition, we investigated the therapeutic potential of lapatinib as an inhibitor of these receptors in various cancer types. MethodsRNAseq data for prevalent cancers were downloaded from The Cancer Genome Atlas (TCGA). After initial preprocessing, expression changes of HER2, EGFR, and candidate genes—identified based on their association with EGFR and HER2 signaling pathways—were examined. Human protein atlas data were utilized to assess the protein expression of HER2 and EGFR. GSE129254 was employed to identify molecular pathways and candidate genes associated with lapatinib. The protein-protein interaction network was used to identify lapatinib-influenced hub genes. Clinical data for common cancers were used to investigate the correlation between the expression of candidate genes and patients' mortality rates by Cox regression test. ResultsThe findings clearly indicated a significant increase in the expression levels of HER2 and EGFR in cancers such as kidney, lung, breast, bladder, pancreas, head and neck, stomach, and endometrial, both at the mRNA and protein levels (p-value <0.01). Additionally, more than 30 % of samples in some cancers showed a twofold increase in HER2 or EGFR expression. The analysis of GSE129254 data revealed that lapatinib reduces the expression of numerous genes associated with cell proliferation. METTL1, LYAR, LTV1, CCND1, NOP2, and DDX21 were identified as hub genes related to the effect of lapatinib. Our results demonstrated that many hub genes exhibited elevated expression in candidate cancers, and the upregulation of some of them was correlated with poor prognosis. ConclusionOur results indicate an upregulation in the expression levels of HER2 and EGFR in certain common cancers, suggesting that lapatinib, in addition to breast cancer, could be considered for the treatment of these cancers. Furthermore, we demonstrated that some genes with increased expression in prevalent cancers and associated with poor prognosis have the potential to be modulated by lapatinib.

Anti-Proliferative and Anti-Migratory Activity of Licorice Extract and Glycyrrhetinic Acid on Papillary Thyroid Cancer Cell Cultures

Papillary thyroid cancer (PTC) is the 8th most common cancer among women overall. Licorice contains over 300 active compounds, many of them with anti-cancer properties. Glycyrrhetinic acid (GA) is a major component of licorice. The aim of this study was to investigate the potential anti-proliferative effects of licorice and GA on PTC cell cultures. Licorice extract (LE) was produced from the root and tested on BCPAP and K1 cell lines, as well as GA and aldosterone. We used the MTT test to investigate the anti-proliferative activity, the wound healing test for the migratory activity, and finally, we analyzed cell cycle distribution, apoptosis, and oxidative stress after LE, GA, or aldosterone incubation. Both LE and GA reduced cell viability at 48 h and cell migration at 24 h in both PTC cultures. Aldosterone reduced cell migration only in K1 cells. LE and GA induced cell cycle arrest in the G0/G1 phase in the BCPAP cell line, while LE and aldosterone induced it in the K1 culture. GA but not LE increased the apoptosis rate in both cell lines, whereas LE but not GA increased oxidative stress in both cultures. This study presents the first evidence of the in vitro anti-proliferative and anti-migratory activity of LE and GA on PTC.

A review on optimization of Wilms tumour management using radiomics

Abstract Background Wilms tumour, a common paediatric cancer, is difficult to treat in low- and middle-income countries due to limited access to imaging. Artificial intelligence has been introduced for staging, detecting, and classifying tumours, aiding physicians in decision-making. However, challenges include algorithm accuracy, translation into conventional diagnosis, reproducibility, and reliability. As AI technology advances, radiomics, an AI tool, emerges to extract tumor morphology and stage information. Objectives This review explores the application of radiomics in Wilms tumour management, including its potential in diagnosis, prognosis, and treatment. Additionally, it discusses the future prospects of artificial intelligence (AI) in this field and potential directions for automation-aided Wilms tumour treatment. Methods The review analyses various research studies and articles on the use of radiomics in Wilms tumour management. This includes studies on automated deep learning-based classification, interobserver variability in histopathological analysis, and the application of AI in staging, detecting, and classifying Wilms tumours. Results The review finds that radiomics offers several promising applications in Wilms tumour management, including: improved diagnosis: it helps in classifying Wilms tumours from other paediatric kidney tumours, Prognosis prediction: radiomic features can be used to predict both staging and response to preoperative chemotherapy. Treatment response assessment: Radiomics can be used to monitor the response of Wilms and to predict the feasibility of nephron-sparing surgery. Conclusions This review concludes that radiomics has the potential to significantly improve the diagnosis, prognosis, and treatment of Wilms tumours. Despite some challenges, such as the need for further research and validation, AI integration in Wilms tumour management offers promising opportunities for improved patient care. Advances in knowledge This review provides a comprehensive overview of the potential applications of radiomics in Wilms tumour management and highlights the significant role AI can play in improving patient outcomes. It contributes to the growing body of knowledge on AI-assisted diagnosis and treatment of paediatric cancers.

A Review on Nanotechnologically Derived Phytomedicines for the Treatment of Hepatocellular Carcinoma: Recent Advances in Molecular Mechanism and Drug Targeting.

The second largest cause of cancer-related death worldwide, Hepatocellular Carcinoma (HCC) is also the most common primary liver cancer. HCC typically arises in patients with liver cirrhosis. Existing synthetic medicines for treating chronic liver disease are ineffective and come with undesirable side effects. Although herbal remedies have widespread popularity, there is still a long road ahead before they are fully accepted by the scientific community. Secondary metabolites and phytochemicals found in plants are abundant in both the human diet and the non-human environment. Natural plant chemicals have been shown to be beneficial as therapeutic and chemopreventive treatments for a wide variety of chronic disorders. Many diseases, including HCC, can be effectively treated with the help of phytochemicals found in food. Resveratrol, curcumin, urolithin A, silibinin, quercetin, N-trans-feruloyl octopamine, emodin, lycopene, caffeine, and phloretin are all examples. Approximately, 60% of all anticancer medications are determined to be derived from natural substances, according to recent studies. Plant derivatives have played an important role in cancer due to their capacity to scavenge free radicals, limit cell proliferation, and set off apoptosis. The progression of HCC is linked to inflammatory signaling pathways, and this study sought to look at how novel approaches, such as phytomedicines, are being used to fight cancer. Recent advancements in molecular mechanisms and drug targeting for HCC have been discussed in this review.

The Metabolic Effects and Effectiveness of the Different Reconstruction Methods used in Gastric Cancer Surgery: A Systematic Review and Meta-Analysis.

Gastric Cancer (GC) is the fifth most common cancer worldwide. Early stages of GC began being detected, giving rise to a new concern, Quality of Life. This study aimed to systematically assess the effects of different GC reconstruction techniques on postoperative type 2 diabetes mellitus (T2DM), hypertension (HBP), and body mass index (BMI) reduction rate and to provide an overview of recent research on oncometabolic surgery (OS). We performed a systematic review and meta-analysis by searching three databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We performed a meta-analysis of risk ratios and mean differences to estimate the impact of duodenal bypass, Roux-en-Y reconstruction, and residual stomach on T2DM, HBP, and BMI reduction rate. Heterogeneity was assessed using the I2 statistics. At the end of the follow-up, the duodenal bypass group compared to Billroth I had a significantly higher postoperative remission of T2DM and HBP, with a relative risk (RR) of 1.43 (95% confidence interval (95% CI) [1.27; 1.62]) and 1.3 (95% CI [1.00; 1.69]), respectively. Compared with the Billroth II group, Roux-en-Y reconstruction had significantly greater T2DM remission after gastrectomy (RR = 1.19; 95% CI [1.08; 1.31]), while HBP showed no significant differences. Regarding the improvement of HBP, total gastrectomy was significantly superior to subtotal gastrectomy (95% CI [1.01; 2.64]). A trend towards Roux-en-Y Esophagojejunostomy as the best option for T2DM remission was observed (95% CI [0.98; 2.77]; p = 0.06). Gastrectomy with Roux-en-Y reconstruction appears to be the most effective treatment for T2DM remission. Further research is needed to assess the impact of OS on metabolic diseases.

Prostate Cancer and Obesity: Current Hypotheses and Challenges

Prostate cancer is the most common cancer diagnosed in males in the United States. Known prostate cancer risk factors include age, ethnicity, and genetic factors. There is some data suggesting that obesity is a risk factor for numerous aspects related to prostate cancer including prostate cancer development, biochemical recurrence, and prostate cancer mortality. Moreover, there may be potential therapeutic complications in the obese patient. Weight loss has also been shown to benefit the patient with prostate cancer. Finally, obesity may affect the microbiome and other molecular pathways such alterations in adipokine signaling, insulin and the insulin-like growth factor 1 pathway, and effects on the tumor microenvironment (e.g.: ectopic/periprostatic fat). The purpose of this review is to discuss the most current hypotheses on the relationship between obesity and prostate cancer across this broad spectrum of potential relationships.

Temporal trends in pediatric cancer mortality: rare cancers lag behind more common cancers

Temporal trends demonstrate improved survival for many types of common pediatric cancer. Studies have not examined improvement in very rare pediatric cancers or compared these improvements to more common cancers. In this cohort study of the Surveillance, Epidemiology, and End Results (SEER) registry, we examined patients from 1975 to 2016 who were 0–19 years of age at the time of diagnosis. Cancers were grouped by decade of diagnosis and 3 cancer frequency groups: Common, Intermediate, and Rare. Trends in mortality across decades and by cancer frequency were compared using Kaplan–Meier curves and adjusted Cox proportional hazards models. A total of 50,222 patients were available for analysis, with the top 10 cancers grouped as Common (67%), 13 cancers grouped with Intermediate (24%), and 37 cancers as Rare (9%). Rare cancers had higher rates of children who were older and Black. 5-year survival increased from 63% to 86% across all cancers from the 1970s to the 2010s. The hazard ratio (HR) for mortality decreased from the reference point of 1 in the 1970s to 0.27 (95% CI: 0.25-0.30) in the 2010s in Common cancers, while the HR only dropped to 0.60 (0.49–0.73) over that same period for rare cancers. Pediatric oncology patients have experienced dramatic improvement in mortality since the 1970s, with mortality falling by nearly 75% in common cancers. Unfortunately, rare pediatric cancers continue to lag behind more common and therefore better studied cancers, highlighting the need for a renewed focus on research efforts for children with these rare diseases.

Role of Imaging in Screening for Hepatocellular Carcinoma.

Primary liver cancer is among the most common cancers globally. It is the sixth-most common malignancy encountered and the third-most common cause of cancer-related death. Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, accounting for about 90% of primary liver cancers. The majority of HCCs occur in patients with underlying cirrhosis, which results from chronic liver diseases such as fatty liver, hepatitis B and hepatitis C infections, and chronic alcohol use, which are the leading causes. The obesity pandemic has led to an increased prevalence of nonalcoholic fatty liver disease (NAFLD), which leads to nonalcoholic steatohepatitis and could progress to cirrhosis. As HCC is among the most common cancers and occurs in the setting of chronic liver disease in most patients, screening the population at risk could help in early diagnosis and management, leading to improved survival. Screening for HCC is performed using biochemical marker testing such as α-fetoprotein (AFP) and cross-sectional imaging. It is critical to emphasize that HCC could potentially occur in patients without cirrhosis (non-cirrhotic HCC), which can account for almost 20% of all HCCs. The lack of cirrhosis can cause a delay in surveillance, which could potentially lead to diagnosis at a later stage, worsening the prognosis for such patients. In this article, we discuss the diagnosis of cirrhosis in at-risk populations with details on the different modalities available for screening HCC in patients with cirrhosis, emphasizing the role of abdominal ultrasounds, the primary imaging modality in HCC screening.

6931 Weight Trends and Predictors of Weight Gain in Breast Cancer Survivors

Abstract Disclosure: M.D. Hurtado: None. E. Tama: None. D. Hodge: None. A. Weston: None. S. Fahad: None. K. Ruddy: None. J. Olson: None. F. Coach: None. R. Carter: None. S. D'Andre: None. A. Acosta: Consulting Fee; Self; Amgen Inc. Grant Recipient; Self; Vivus USA, Novo Nordisk. C. Shufelt: None. Background: Breast cancer (BC) is the most common cancer in women. Weight gain after treatment for early-stage BC is associated with a higher risk of recurrence. Excess adiposity is also a major risk factor for cardiovascular disease, the leading cause of non-BC related death in BC survivors. This study aimed to describe weight trends in a large cohort of BC survivors and to identify predictors of weight gain after BC diagnosis. Methods: This was a retrospective study of BC survivors from the prospectively consented Mayo Clinic Breast Cancer Registry, which has enrolled &amp;gt;10,000 patients seen at least once at Mayo Clinic Rochester for a BC diagnosed within the prior year. We extracted data on weights at baseline, and years 1, 4, and 6 after BC diagnosis to generate longitudinal weight trajectory curves on the change from baseline. Weights were either reported by patients in the registry questionnaires or extracted from the electronic health records. We identified BC survivors with weight gain &amp;gt;10% from baseline weight at years 1, 4, and 6. We then conducted univariable logistic regression analyses to identify predictors of &amp;gt;10% weight gain. Variables considered included: demographics, anthropometrics, BC clinical and pathologic characteristics, BRCA 1 and 2 genetic mutation status, and treatment (surgery, neoadjuvant or adjuvant chemotherapy, and/or radiotherapy). Results: We included 4744 BC survivors, mostly white (95%) and non-Hispanic (91%), with a mean age and weight at BC diagnosis of 58 ± 13 years and 76 ± 18 kg. Most patients had clinical stage I (43%) and ER+ and PR+ BC (83% and 76%, respectively). Most patients underwent breast preserving surgery (62%), half received radiation (54%), one third (36%) received systemic chemotherapy, and two thirds (61%) received endocrine therapy. At one year after BC diagnosis the average weight change was negligible compared to baseline (mean difference -0.2 ± 8 kg), but there were small but significant average increases by years 4 and 6 (0.5 ± 9 kg, p=0.002; and 0.8 ± 10 kg, p&amp;lt;0.001; respectively). At years 1, 4, and 6, the percentage of BC survivors gaining &amp;gt;10% of their baseline weight was 10%, 15%, and 18%, respectively. Baseline characteristics associated with &amp;gt;10% weight gain at 6 years included lower baseline weight (p&amp;lt;0.001), younger age at BC diagnosis (p&amp;lt;0.001), more advanced clinical and pathologic BC stage (p=0.008), ER+ and PR+ tumor biology (p=0.02 for both), BRCA2 mutation (p&amp;lt;0.001), mastectomy (compared to breast preserving surgeries, p=0.008), the use of systemic chemotherapy treatment (p&amp;lt;0.001), and the use of endocrine therapy (p=0.03). Conclusion: While most BC survivors do not experience weight gain after survivorship, 1 out 5 may experience excessive weight gain of more than 10%. Baseline anthropometric and BC-related variables are associated with excessive weight gain and could be used as predictors of weight gain in this population. Presentation: 6/3/2024

7323 Prostatic Acid Phosphatase Is Negatively Regulated by Androgens and Persists in Castration-resistant Prostate Cancer

Abstract Disclosure: A. Kirschenbaum: None. P. Cheung: None. S. Yao: None. P. Cheung: None. Background: Prostate cancer (PCa) is the most common cancer and second leading cause of cancer death in American men. Most patients with metastatic PCa respond initially to androgen deprivation therapy (ADT) but the majority will progress to lethal, metastatic, castrate-resistant PCa (mCRPC). The identification of markers of mCRPC that are not regulated or negatively regulated by androgens can serve as markers and therapeutic targets in mCRPC. We hypothesized that prostatic acid phosphatase (PAP), a protein phosphatase and 5’ectonucleotidase that is expressed in both the cytoplasm and transmembrane (TM-PAP) of PCa cells, is negatively regulated by androgen signaling and can serve as a therapeutic target. Methods: PAP protein expression was assessed by immunohistochemistry (IHC) in PCa cell line spheroids (VCaP, 22Rv1, LNCaP, C42B) +/- androgen addition as well as in LNCaP s.c. xenografts +/- castration. Protein expression of PAP was assessed with western blotting in PCa cell lines after treatment with androgens (DHT) and anti-androgen (enzalutamide). Results: In spheroids derived from PCa cell lines, there is some IHC expression of PAP with the strongest staining in VCaP and 22Rv1 spheroids. DHT decreased PAP IHC expression in all spheroids. LNCaP and VCaP s.c. xenografts demonstrated that castration decreased tumor growth rates but that in castrate as well as control tumors PAP expression persisted. All forms of PAP including TM-PAP are expressed in VCaP cell line and were negatively regulated by androgen addition. Conclusions: The identification of markers of mCRPC that are not regulated or are negatively regulated by androgen could help identify recalcitrant tumor cells and mount targeted delivery of therapeutic agents. In several androgen sensitive PCa cell lines, DHT addition decreased PAP expression in spheroids. In vivo, PAP expression persists after castration in spite of decreases in tumor growth rates. Finally, DHT decreases and enzalutamide restores PAP expression in vitro. These data demonstrate that PAP is a more progenitor cell marker in PCa that persists after castration and may be targeted in castration-resistant disease. Presentation: 6/3/2024

6925 A Rare Case of Metastatic Papillary Thyroid Carcinoma Confined to Cervical Lymph Node with No Identifiable Primary Tumor In The Thyroid Gland. A Diagnostic Conundrum

Abstract Disclosure: R. Abdelmasih: None. W. Pan: None. Introduction: Papillary thyroid carcinoma (PTC) is the most common treatable thyroid cancer (TC) with very good prognosis. Metastatic PTC either in the lymph node LN or extra-nodal with no primary thyroid lesion identified is a rare phenomenon referred to as occult thyroid carcinoma (OTC). Despite its rarity, it is reported and constitute a diagnostic conundrum. herein we present a case of metastatic PTC identified in cervical lymph nodes (LN) without a primary tumor in the thyroid gland confirmed with surgical pathology. Case Presentation: A 43-year-old female with history of post-ablative hypothyroidism after treatment of toxic nodular goiter for 10 years, with no family history of thyroid cancer presented with incidentally found left 1.8 Heterogeneous hypoechoic solid nodule with lobulated borders and internal calcifications along with left-sided 0.8 LN without normal fatty hilum on Ultrasound Head and Neck. Fine needle aspiration of the left thyroid nodule and suspicious LN revealed PTC in the left LN though the thyroid nodule sample was non-diagnostic. CT of head and neck showed partially calcified thyroid nodule, Hyperattenuating 8 mm left III LN without fatty hilum, and 9 mm left II calcified LN. Patient underwent total thyroidectomy, central neck, and left lateral neck dissection. Surgical pathology showed no malignancy in thyroid gland or central LNs and 1 out 5 LN of the left neck dissection showed PTC with tumor grading of pT0 pN1b pMNA. patient underwent whole-body thyrogen-stimulated thyroid scan which showed iodine avid tissue in the thyroid bed followed by high-dose I-131 radioactive iodine ablation (RAI). Discussion: OTC refers to impalpable incidental TC less than 10 mm per the WHO. Boucek et al classify OTC into four categories, recently a fifth category was added, in which metastasis is confirmed either in regional LN or distant metastasis though thyroid tissue is confirmed to be benign per pathology and imaging evaluation, our patient falls in the fifth category. Hypothesis of this phenomenon is not well understood, one suggested explanation is missed diagnosis due to not enough sample or if lesion is less than 3 mm. another hypothesis is tumor spontaneous regression, or regression secondary to treatment that was inadequate to treat the systemic process of the tumor, which we believe our patient fits in this hypothesis, given that she underwent RAI ablation many years ago. Tumor regression is very rare and reported to be 1 in 140,000 cases. Another theory suggests that PTC can arise in ectopic thyroid tissue. This case is to shed light on a rare clinical and pathological entity to avoid missed diagnoses. Prognosis depends on the extent of metastasis, with favorable one when it is limited to regional LN and worse with distant metastasis. More cases reports are warranted to help guide further management of such cases due to the lack of available guidance in use of RAI surveillance and ablation. Presentation: 6/1/2024

General context and relevant public datasets available for improving pathways in Paediatric Cancer applying Artificial Intelligence. A review

Due to the promise of transforming healthcare and medicine that Artificial Intelligence (AI) has posed, the number of applications has increased exponentially. These applications range from screening and disease diagnosis to prognosis, treatment planning, and follow-up. In complex topics such as childhood cancer, these techniques are being expanded with the ambition of improving the quality of care by allowing healthcare professionals to make more informed decisions. However, the adequate application of such techniques heavily depends on the data, which creates a set of challenges including collection, bias, and scarcity among others. Furthermore, ethical, legal, and regulatory frameworks increase even more the difficulties to develop AI-powered solutions. In this paper, we present an exhaustive literature review to identify and analyse public datasets targeting two common childhood cancer types, such as neuroblastoma and nephroblastoma. Moreover, the complex context for the development of AI- based software solutions is outlined. It includes the description of the most relevant techniques to address problems associated with data sharing and training. Finally, a set of code snippets is provided to perform exploratory analysis for the available data.

8788 Implications of NTRK gene fusion in Papillary thyroid cancer

Abstract Disclosure: W. Medina-Torres: None. L. El Musa Penna: None. J. Segarra-Villafane: None. L.R. Sepulveda-Garcia: None. Z. Maisonet -Feliciano: None. I.C. Arroyo: None. M. Ramirez: None. M. Alvarado: None. L.A. Gonzalez-Rodriguez: None. V.J. Carlo: None. Thyroid cancer (TC) is the most common endocrine cancer. Papillary thyroid carcinoma (PTC) is the predominant contributor of this occurrence, comprising approximately 80% of all thyroid carcinomas. PTC has a good prognosis with a 5-year survival rate of more than 90% after resection. Nonetheless, factors such as tumor size, multifocality, nodal and distant metastases, characterize more aggressive cases including tall cell variant, columnar cell variant, and hobnail variant Aside from staging parameters, PTC behavior is mostly determined by morphologic variant. This is the case of 31 y/o female without known past medical history who was evaluated at endocrinology clinic due to a fine needle thyroid aspiration (FNA) positive for PTC, tall cell variant. Total thyroidectomy with central compartment dissection was performed. Pathology report presented a main tumoral mass of 3 cm but permeating multinodular pattern involving the entire gland with focal extrathyroidal extension, positive margins and six level VI positive lymph nodes. As per report, the tumor presented both papillary and follicular patterns of growth and other findings including oncocytic change, foci of clear cell change, low mitotic rate, and most notably "reverse polarization”. This pattern has the pathological features suggestive of the novel NTRK gene fusion mutation. The patient was treated with radioactive iodine (RAI) and one year post treatment there was evidence of elevated Thyroglobulin level at 904 ng/mLand thyroglobulin Ab at 2.48 IU/mL. A WBS +SPECT was done resulting in small uptake at left posterior thyroid bed and pulmonary intake. A chest CT revealed multiple bilateral sub centimeter nodules. Based on this result, a second course of RAI was given. Follow up neck ultrasound and chest CT presented persistent left level VI lymph nodes, increased amount of bilateral sub-centimeter pulmonary nodules and new thoracic(T11) lesion. FNA of left neck lymph nodes were positive for metastatic PTC for which left neck dissection was performed. Evaluation for actionable somatic mutations was requested based on resistance behavior, remarkable for TRIM33-NTRK1 chromosomal rearrangement. Patient was evaluated by Oncology service who started Larotrectinib treatment since it was approved for NTRK driven malignancies. Six-month post therapy patient achieved clinical and biochemical improvement. In the thyroid, NTRK-driven malignancies are rare and aggressive but treatable, in the evolving genomic era. As reviewed in the literature, NTRK fusion-positive TC exhibits distinctive clinicopathological features that could aid in identifying potential patients. Thus, in such patients who have PTC with non-classic pathologic patterns, specific molecular profile of the main tumor may have significant prognostic value that must be integrated into stratification system in order to provide target therapy on time. Presentation: 6/3/2024