Non-metastatic Patients Research Articles

Effect of race/ethnicity on survival in surgically treated intermediate/high risk non-metastatic clear cell renal carcinoma.

It is unknown to what extent 10-year overall survival of radical nephrectomy treated intermediate/high-risk non-metastatic clear cell renal carcinoma patients differs from age- and sex-matched population-based controls, especially when race/ethnicity is considered (Caucasian vs. African American vs. Hispanic vs. Asian/Pacific Islander). We relied on the SEER database (2004-2018) to identify newly diagnosed radical nephrectomy treated intermediate/high risk non-metastatic clear cell renal carcinoma patients. For each case, we simulated an age- and sex-matched control relying on Social Security Administration Life Tables with 10 years of follow-up. We compared overall survival between renal carcinoma cases and population-based controls. Multivariable competing risks regression models tested for predictors of cancer-specific mortality versus other-cause mortality. Of 6877 radical nephrectomy treated intermediate/high risk non-metastatic clear cell renal carcinoma patients, 5050 (73%) were Caucasian versus 433 (6%) African American versus 1002 (15%) Hispanic versus 392 (6%) Asian/Pacific Islanders. At 10 years, overall survival difference between radical nephrectomy treated intermediate/high risk non-metastatic clear cell renal carcinoma patients versus population-based controls was greatest in African Americans (51% vs. 81%, Δ = 30%), followed by Hispanics (54% vs. 80%, Δ = 26%), Asian/Pacific Islanders (56% vs. 80%, Δ = 24%) and Caucasians (52% vs. 74%, Δ = 22%). In competing risks regression, only African Americans exhibited significantly higher other cause mortality (hazard ratio = 1.3; 95% confidence interval = 1.1 - 1.6; p = 0.01) than others. Relative to Life Tables' derived sex- and age-matched controls, radical nephrectomy treated intermediate/high-risk non-metastatic clear cell renal carcinoma patients exhibit worse overall survival, with worst overall survival recorded in African Americans of all race/ethnicity groups.

Overexpression of microRNA-611 inhibits TGF-β-induced epithelial-mesenchymal transition and migration in lung cancer cells through MAPKAP1

Metastasis is a major cause of death in patients with lung cancer (LC). microRNA-611 (miR-611), a miRNA, has been little studied in cancer. Here, we aimed to further elucidate the roles of miR-611 in epithelial-mesenchymal transition (EMT) and migration induced by transforming growth factor-β (TGF-β) in LC cells and the possible underlying mechanisms. miR-611 and MAPKAP1 expression was first identified in LC tissues from metastatic and nonmetastatic patients, and their expression was associated with overall survival. Gain- and loss-of-function experiments were performed to verify the impacts of miR-611 and MAPKAP1 on pAKT expression, EMT, and migration in LC cells treated with TGF-β. The interaction between miR-611 and MAPKAP1 was also determined with a luciferase reporter assay. In our study, miR-611 was expressed at low levels, and MAPKAP1 was highly expressed in LC tissues, which was associated with metastasis and short overall survival. Functionally, miR-611 inhibition or MAPKAP1 overexpression accelerated EMT and migration and upregulated pAKT in TGF-β-treated A549 and H1299 cells; miR-611 overexpression or MAPKAP1 silencing exerted the opposite effects as miR-611 inhibition or MAPKAP1 overexpression. Mechanistically, miR-611 could target and downregulate MAPKAP1. MAPKAP1 expression was also negatively correlated with miR-611 expression in LC tissues. In addition, miR-611 overexpression reduced the EMT and migration of TGF-β-treated A549 and H1299 cells by targeting MAPKAP1. In conclusion, miR-611 overexpression attenuated EMT and migration by targeting MAPKAP1 in TGF-β-induced LC cells, indicating that miR-611 is a biological target for LC treatment.

Comparing the effects of warm footbath and foot reflexology on depression of patients undergoing radiotherapy: A randomized clinical trial

BackgroundCancer diagnosis not only impacts physical health but also mental well-being, often leading to significant stress, fear, and depression among patients.The utilization of CAM has shown a rising trend, influenced by the availability of different modalities offered by healthcare services, sometimes in an ad hoc fashion. This study seeks to examine and compare the respective impacts of warm foot baths and foot reflexology on depression in patients undergoing radiotherapy. MethodsA randomized clinical trial was conducted at Mashhad University of Medical Sciences in Iran in 2019, following CONSORT guidelines. Participants included non-metastatic cancer patients aged 18–60 undergoing a 28-day radiotherapy course. Patients were randomly assigned to receive either warm footbaths or foot reflexology as interventions, performed daily for 20 min over 21 days. The data were analyzed using appropriate statistical tests. ResultsStatistical analysis indicated no significant differences in demographic attributes between the two groups. Both interventions led to a significant reduction in depression scores post-treatment compared to pre-treatment assessments. Foot reflexology showed a greater reduction in depression scores compared to footbaths with warm water. ConclusionsBoth warm footbaths and foot reflexology are effective in alleviating depression in patients undergoing radiotherapy, with foot reflexology showing a greater impact on improving depression levels. The study recommends foot reflexology as a preferred intervention for managing depression in these patients if conditions and facilities permit.

Pre-Op Hydronephrosis Predicts Outcomes in Patients Receiving Robot-Assisted Radical Cystectomy.

Robot-assisted radical cystectomy (RARC) has gained momentum in the management of muscle invasive bladder cancer (MIBC). Predictors of RARC outcomes are not thoroughly studied. We aim to investigate the implications of preoperative hydronephrosis on oncological outcomes. This study analysed data from the Asian RARC consortium, a multicentre registry involving nine Asian centres. Cases were divided into two groups according to the presence or absence of pre-operative hydronephrosis. Background characteristics, operative details, perioperative outcomes, and oncological results were reviewed. Outcomes were (1) survival outcomes, including 10-year disease-free survival (DFS) and overall survival (OS), and (2) perioperative and pathological results. Multivariate regression analyses were performed on survival outcomes. From 2007 to 2020, 536 non-metastatic MIBC patients receiving RARC were analysed. 429 had no hydronephrosis (80.0%), and 107 (20.0%) had hydronephrosis. Hydronephrosis was found to be predictive of inferior DFS (HR = 1.701, p = 0.003, 95% CI = 1.196-2.418) and OS (HR = 1.834, p = 0.008, 95% CI = 1.173-2.866). Subgroup analysis demonstrated differences in the T2-or-above subgroup (HR = 1.65; p = 0.004 in DFS and HR = 1.888; p = 0.008 in OS) and the T3-or-above subgroup (HR = 1.757; p = 0.017 in DFS and HR = 1.807; p = 0.034 in OS). The presence of preoperative hydronephrosis among MIBC patients carries additional prognostic implications on top of tumour staging. Its importance in case selection needs to be highlighted.

Impact of acute therapeutic toxicities on anxiety during radiotherapy among Chinese patients with newly diagnosed nonmetastatic head and neck cancer: A cross-sectional study.

147 Background: Head and neck cancer (HNC) poses a significant threat to both psychological and physical health. This study aimed to depict the anxiety status of Chinese newly diagnosed nonmetastatic HNC patients during radiotherapy (RT) and to examine predictors of anxiety symptoms. Methods: Newly diagnosed nonmetastatic HNC patients who received RT at the Radiation Therapy Center of Sun Yat-sen University Cancer Center from August 23,2023 to August 24,2023 were recruited into this study. Using Zung Self-Rating Anxiety Scale (Zung SAS) to screen anxiety. Twenty-four common acute therapeutic toxicities (18 patient-reported and 6 clinician-rated) were assessed according to European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck 35 (EORTC QLQ-HN35) and Common Terminology Criteria for Adverse Events, fifth version (CTCAE V5.0). Chi-square ( χ2) test and multivariate binary logistic regression stepwise forward selection: likelihood ratio (LR) method were applied to identify factors associated with anxiety. Results: A total of 457 patients were included ultimately. Up to 29.10% of the patients showed varying degrees of anxiety and the average SAS standardized score was 45.66 ± 8.83. Chi-square test manifested that sex, annual household income, fatigue, anorexia, nausea, vomit, pain, dysphagia, sense problems (smell and taste), speech problems, trouble in social eating, trouble in social contact, sexual frustration, teeth problems, difficulty in opening mouth, xerostomia, sticky saliva, coughing, feeling ill, use of analgesics, use of nutritional supplements and weight loss were related to anxiety ( p < 0.05). But multivariate logistic regression only demonstrated fatigue (OR = 3.696, 95% CI = 2.096-6.519), speech problems (OR = 3.247, 95% CI = 1.554-6.783), sexual frustration (OR = 2.029, 95% CI = 1.232-3.341), nausea (OR = 3.075, 95% CI = 1.807-5.234), feeling ill (OR = 2.283, 95% CI = 1.215-4.291), use of nutritional supplements (OR = 1.930, 95% CI = 1.136-3.280) and difficulty in opening mouth (OR = 3.007, 95% CI = 1.081-8.363) as independent predictive factors of anxiety. Conclusions: The Chinese newly diagnosed nonmetastatic HNC patients suffered greatly from anxiety during RT. This study identified the predictive contribution of sociodemographic and clinical characteristics and 24 common acute therapeutic toxicities to the vulnerability to anxiety, which can provide evidence and reference for medical staff to carry out psychological intervention.

Evaluation of oral silymarin formulation efficacy in prevention of doxorubicin induced hepatotoxicity in patients with non-metastatic breast cancer.

Chemotherapy-induced hepatotoxicity is a common complication in breast cancer patients, especially with doxorubicin-containing regimens. Liver enzyme abnormality is reported in 34.8% of patients undergoing AC-T regimen and fatty liver is reported in 30% to 50% of cases. Antioxidant and anti-inflammatory properties of silymarin, a polyphenolic flavonoid extract derived from Silybum marianum, may be useful in preventing chemotherapy-induced hepatotoxicity. This study evaluated the effect of oral silymarin for preventing doxorubicin induced hepatotoxicity in non-metastatic breast cancer patients. In this triple-blind, placebo-controlled clinical trial, 50 patients with non-metastatic breast cancer were assigned to receive either 140 mg silymarin tablets or the placebo three times daily for 63 days and were evaluated for liver function test before the study and at the end of each chemotherapy cycle (every 3 weeks) for 4 cycles. In addition, an ultrasonography assessment was performed upon entry and the end of the study. Based on ultrasonography, the fatty liver grade was significantly higher in the placebo group at the end of the study. Moreover, the serum levels of aspartate aminotransferase (p = 0.015) and alkaline phosphatase (p = 0.004) at 6-week intervals, and the serum level of alkaline phosphatase (p = 0.002) at 9-week intervals were significantly lower in the silymarin group. Oral formulation of silymarin 420 mg/day for 63 days significantly prevented hepatotoxicity caused by doxorubicin in patients with non-metastatic breast cancer mostly based on liver ultrasonography but not laboratory parameters. Further investigations are suggested on different doses, durations and formulations of silymarin, particularly nano-formulations for increasing its oral bioavailability.

Treatment outcomes and prognostic factors in nonmetastatic metaplastic breast cancer patients: a multicenter retrospective cohort study.

Metaplastic breast carcinoma (BC-Mp) is an uncommon subtype that poses unique challenges. The limited information on patient prognosis and therapeutic strategies motivated our research initiative. We aimed to assess disease-free survival (DFS), overall survival (OS), and influential factors in patients with nonmetastatic BC-Mp. In this multicenter retrospective cohort study, clinicopathological data for nonmetastatic BC-Mp patients treated at four oncology units in Poland (2012-2022) were gathered. Among 115 women (median age 61, range: 28-91), the median tumor size was 40 mm (range 20-130); 30% of patients exhibited positive local lymph nodes. The majority of patients presented with stage II (46%) and triple-negative breast cancer (TNBC) (84%). Radiotherapy was administered to 61% of patients. Surgical procedures included breast-conserving surgery in 31% of patients and mastectomy in 68%. Eighty-three per cent of patients received chemotherapy. The median estimated DFS and OS were 59 and 68 months, respectively. Multivariable analysis revealed that tumor size influenced DFS and OS (Hazard ratios [HR] = 1.02, 95%CI 0.01-0.03 for both endpoints) and taxanes application improved DFS (HR = 0.47, 95%CI 0.24-0.93), but other factors did not. For patients receiving neoadjuvant systemic therapy (N = 51), taxanes improved DFS and OS according to univariable analysis. Our findings highlight poor DFS and OS regardless of receiving optimal treatment, emphasizing the need for tailored therapeutic strategies for BC-Mp patients. Taxanes appear promising in a neoadjuvant setting, particularly within the current standard of care for the TNBC subtype.

Non-adherence to recommended adjuvant radiation after total laryngectomy

ObjectivesInvestigate trends and associated factors in guideline adherence to adjuvant radiation therapy in locally advanced laryngeal and hypopharyngeal cancer after primary total laryngectomy (TL). MethodsPreviously untreated, non-metastatic patients who underwent TL for pathologic T4 larynx or hypopharynx squamous cell carcinoma (SCC) were queried using the National Cancer Database (NCDB). Patients were excluded if they had regional or distant metastasis or positive margins. Patient characteristics were evaluated for association with non-adherence to adjuvant radiation by logistic regression analysis. Association between non-adherence and overall survival (OS) was investigated by Cox proportional hazard analysis. ResultsAmong 2823 eligible T4 N0 patients, 841 (29.8 %) did not receive adjuvant radiation. Associated factors include increasing age, a Charlson Comorbidity Index of 2, greater per-mile distance to treatment center, and treatment at an academic cancer center. Delivery of adjuvant radiation was associated with improved OS on multivariable (HR 0.82, 95 % CI 0.72–0.93) analysis. ConclusionsWithin the NCDB, non-adherence to adjuvant radiation treatment after TL for pathologically T4 N0 larynx and hypopharynx SCC is common. Older patients with more comorbidities and greater travel distance may be at higher risk for non-adherence. Treatment at an academic cancer center is associated with non-adherence to recommended adjuvant radiation. Lack of adjuvant radiation is associated with worse overall survival.

Development and validation of competing risk nomograms for predicting cancer‑specific mortality in non-metastatic patients with non‑muscle invasive urothelial bladder cancer

We aimed to assess the cumulative incidences of cancer-specific mortality (CSM) in non-metastatic patients with non‑muscle invasive urothelial bladder cancer (NMIUBC) and establish competing risk nomograms to predict CSM. Patient data was sourced from the Surveillance, Epidemiology, and End Results database, as well as the electronic medical record system in our institution to form the external validation cohort. Sub-distribution proportional hazards model was utilized to determine independent risk factors influencing CSM in non-metastatic NMIUBC patients. Competitive risk nomograms were constructed to predict 3-year, 5-year, and 8-year cancer-specific survival (CSS) in all patients group, TURBT group and cystectomy group, respectively. The discrimination and accuracy of the model were validated through the concordance index (C-index), the area under the receiver operating characteristic curve (AUC), and calibration curves. Decision curve analysis (DCA) and a risk stratification system was employed to evaluate the clinical utility of the model. Race, age, marital status, surgery in other sites, tumor size, histological type, histological grade, T stage and N stage were identified as independent risk factors to predict CSS in all patients group. The C-index for 3-year CSS was 0.771, 0.770 and 0.846 in the training, testing and external validation sets, respectively. The ROC curves showed well discrimination and the calibration plots were well fitted and consistent. Moreover, DCA demonstrated well clinical effectiveness. Altogether, the competing risk nomogram displayed excellent discrimination and accuracy for predicting CSS in non-metastatic NMIUBC patients, which can be applied in clinical practice to help tailor treatment plans and make clinical decisions.

Assessing the role of prognostic nutritional index in predicting outcomes for rectal cancer surgery

Background & AimsThe association of Prognostic Nutritional Index (PNI) with prognosis has been established for various cancer types, including rectal cancer. However, the precise relationship between PNI and body composition characteristics in patients with non-metastatic rectal cancer remain unclear. This study aimed to investigate the impact of PNI on overall survival and disease-free survival in non-metastatic rectal cancer patients undergoing total surgical resection. Additionally, it sought to assess the inflammatory status and body composition in patients across different PNI levels. MethodsPatients with non-metastatic rectal cancer who underwent total surgical resection, were consecutively enrolled. PNI was calculated using the formula: PNI = (10 x serum albumin [g/dl]) + (0.005 x lymphocytes/μL). Body composition was assessed using CT-derived measurements and laboratory tests performed at diagnosis were used to calculate inflammatory indices. Univariate and multivariate logistic regression analyses as well as Kaplan-Meier curves were used to determine prognostic values. ResultsA total of 298 patients were included. Patients with low PNI demonstrated significantly reduced overall survival and disease-free survival compared to those with high PNI (Hazard ratio [HR] 1.85; Confidence interval [CI] 1.30-2 .62; p= 0.001). Moreover, patients with low PNI exhibited heightened systemic inflammatory status and reduced skeletal muscle index, increased muscle radiodensity, as well as a decrease in subcutaneous adipose tissue area, subcutaneous fat index, and low attenuation of both subcutaneous and visceral adipose tissue. ConclusionThe PNI, assessed prior to treatment initiation, serves as a prognostic biomarker for non-metastatic rectal cancer patients undergoing total surgical resection and is linked with both inflammation and alterations in body composition.

Impact of Pre-Operative Ureteroscopy on Bladder Recurrence Following Nephroureterectomy for UTUC.

(1) Introduction: Diagnostic ureteroscopy (URS) is an important component in the workup of upper tract urothelial carcinoma (UTUC). Whether URS was associated with increased recurrence in the bladder was not fully concluded. The current study aimed to evaluate the implication of URS on the incidences of intravesical recurrence following radical nephroureterectomy (RNU) in non-metastatic UTUC patients without prior history of bladder cancer via multi-institutional data. (2) Patients and Methods: Data were obtained from the Clinical Research Office of the Endourology Society Urothelial Carcinomas of the Upper Tract (CROES-UTUC) registry, a prospective, multicentre database. Patients with non-metastatic UTUC treated with RNU were divided into two groups: those undergoing upfront RNU and those having diagnostic URS prior to RNU. Intravesical recurrence-free survival (IVRS) was the primary endpoint, evaluated through Kaplan-Meier analysis and multivariate Cox regression. Cases with adequate follow-up data were included. (3) Results: The analysis included 269 patients. Of these, 137 (50.9%) received upfront RNU and 132 (49.1%) received pre-RNU URS. The URS group exhibited an inferior 24-month IVRS compared to the upfront RNU group (HR = 1.705, 95% CI = 1.082-2.688; p = 0.020). Multivariate analysis confirmed URS as the only significant predictor of IVR (p = 0.019). Ureteric access sheath usage, flexible ureteroscopy, ureteric biopsy, retrograde contrast studies, and the duration of URS did not significantly affect IVRS. (4) Conclusions: Diagnostic URS prior to RNU was found to be associated with an increased risk of IVR in patients with UTUC. The risk was not significantly influenced by auxiliary procedures during URS. Physicians were advised to meticulously evaluate the necessity of diagnostic URS.

Necroptosis enhances ‘don’t eat me’ signal and induces macrophage extracellular traps to promote pancreatic cancer liver metastasis

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 ‘don’t eat me’ signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial–mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.

The Prognostic Impact of HER2-Low and Menopausal Status in Triple-Negative Breast Cancer.

TNBC is noted for its aggressive behavior and poor prognosis. Recently developed HER2 target agents have shown potential benefit even in HER2-low expressing breast cancers. This study retrospectively analyzed 2542 non-metastatic TNBC patients from 2008 to 2020, revealing that 26.0% were HER2-low. Data on demographics, tumor characteristics, pathologic complete response (pCR) rates and disease-free survival (DFS), distant metastasis-free survival (DMFS), overall survival (OS), and breast cancer-specific survival (BCSS) were analyzed. The HER2-low group, compared to the HER2-0 group, showed significantly better DFS, DMFS, OS, BCSS (p = 0.0072, p = 0.0096, p = 0.0180, and p = 0.0001, respectively) with older age and higher rates of postmenopausal status (p < 0.0001). No significant differences in pCR rates were observed. Multivariate analyses identified HER2 status as a significant prognostic factor for DFS (p = 0.048), DMFS (p = 0.018), OS (p = 0.049), and BCSS (p = 0.008). Subgroup analysis revealed that these effects varied with menopausal status, showing more pronounced benefits in postmenopausal women. Our findings suggest that HER2-low TNBC patients exhibit a distinct clinical profile and improved survival compared to HER2-0 TNBC patients, especially in postmenopausal patients. Further research on estrogen and HER2 interaction is needed.

Survival benefits of propofol-based versus inhalational anesthesia in non-metastatic breast cancer patients: a comprehensive meta-analysis

Whether the anesthesia technique, inhalational general anesthesia (IGA) or propofol-based anesthesia (PBA), influences the long-term survival of non-metastatic breast cancer (eBC) remain unclear and controversial. We carried out a literature search on 16thJuly, 2022 for studies comparing IGA and PBA in eBC undergoing standard surgery, according to PRISMA 2020. The major endpoint in our study was overall survival (OS). Seventeen studies including four randomized clinical trials and thirteen retrospective cohort studies were included in the meta-analysis. Ten studies provided data for crude OS in unweighted eBC patients (imbalance in baseline characteristics). The summarized estimate HRs of the PBA group versus the IGA group (ten studies, N = 127,774, IGA group: 92,592, PBA group: 35,182.) was 0.83 (95%CI: 0.78–0.89). Compared with IGA, PBA was associated with both better 1-year OS (two studies, N = 104,083, IGA group: 84,074, PBA group: 20,009. Pooled HR = 0.80, 0.73–0.89) and 5-year OS (six studies, N = 121,580, IGA group: 89,472, PBA group: 32,108. HR = 0.80, 0.74–0.87). Ten studies applied PSM method to balance the baseline characteristics. In these weighted patients, PBA still showed a better OS (ten studies, N = 105,459, IGA group: 79,095, PBA group: 26,364. HR = 0.93, 0.87–1.00), a better 1-year OS (two studies, N = 83,007, IGA group: 67,609, PBA group: 15,398. HR = 0.88, 0.78–0.98) and a trend towards a better 5-year OS (nine studies, N = 121,580, IGA group: 76,797, PBA group: 24,066. HR = 0.95, 0.88–1.03). Loco-regional recurrence-free survival (LRRFS) was also better in PBA group (HR = 0.73, 0.61–0.86). The present study is the first comprehensive meta-analysis to demonstrate that propofol-based anesthesia could significantly improve OS and LRRFS in non-metastatic breast cancer patients, compared with inhalational anesthesia.

Sentinel Lymph Node Detection in Cutaneous Melanoma Using Indocyanine Green-Based Near-Infrared Fluorescence Imaging: A Systematic Review and Meta-Analysis.

The standard of care approach to identify sentinel lymph nodes (SLNs) in clinically non-metastatic cutaneous melanoma patients is technetium (Tc)-based lymphoscintigraphy. This technique is associated with radiation exposure, a long intervention time, high costs, and limited availability. Indocyanine green (ICG)-based near-infrared fluorescence imaging offers a potential alternative if proven to be of comparable diagnostic accuracy. While several clinical cohorts have compared these modalities, no systematic review exists that provides a quantitative analysis of their results. Hence, a systematic literature review was conducted in December 2023 considering clinical studies comparing the diagnostic accuracy of ICG and Tc for sentinel lymph node biopsy in cutaneous melanoma patients. Three hundred nineteen studies were identified and further screened in accordance with the PRISMA 2020 guidelines, resulting in seven studies being included in the final meta-analysis. Tc identified a significantly higher number of SLNs and metastatic SLNs in prospective studies only. However, in the overall meta-analysis of all included comparative studies, no significant differences were found regarding the identification of metastatic patients or the false negative rate (FNR). ICG may be a non-inferior alternative to Tc for intraoperative guidance in sentinel lymph node biopsy in cutaneous melanoma patients. Future randomized controlled trials are needed, especially regarding the preoperative, transcutaneous identification of the affected lymph node basin.

Short-term OS as a surrogate endpoint for 5-year OS in nasopharyngeal carcinoma in non-endemic area

PurposeTo address this evidence gap and validate short-term OS at less than 5 years as a reliable surrogate endpoint for 5-year OS.MethodsWe analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, focusing on non-metastatic NPC patients diagnosed between 2010 and 2015. Patients were categorized into radiotherapy and chemoradiotherapy groups.ResultsThis retrospective study examined 2,047 non-metastatic NPC patients. Among them, 217 received radiotherapy, and 1,830 received chemoradiotherapy. Our analysis results indicated that the 4-year OS may serve as a reliable surrogate endpoint for patients with AJCC clinical stage I (80 vs. 78%, P = 0.250), regardless of the treatment received. Specifically, in the radiotherapy group, patients with stage I, T0-T1, and N0 NPC showed similar OS rates at 4 and 5 years (83 vs. 82%, P = 1.000; 78 vs. 76%, P = 0.250; 78 vs. 77%, P = 0.500, respectively). Similarly, patients with stage II-IV, T2-T4, and N1-3 NPC showed no significant difference in OS rates between 3 and 5 years (57 vs. 51%, P = 0.063; 52 vs. 46%, P = 0.250; 54 vs. 46%, P = 0.125, respectively) in the radiotherapy group. In the chemoradiotherapy group, only the 3-year OS rate did not significantly differ from that at 5 years in stage I patients (79vs. 72%, P = 0.063).ConclusionsOur study suggests that short-term surrogate endpoints may be valuable for evaluating 5-year OS outcomes in NPC patients in non-endemic areas.

A powerful machine learning approach to identify interactions of differentially abundant gut microbial subsets in patients with metastatic and non-metastatic pancreatic cancer

ABSTRACT Pancreatic cancer has a dismal prognosis, as it is often diagnosed at stage IV of the disease and is characterized by metastatic spread. Gut microbiota and its metabolites have been suggested to influence the metastatic spread by modulating the host immune system or by promoting angiogenesis. To date, the gut microbial profiles of metastatic and non-metastatic patients need to be explored. Taking advantage of the 16S metagenomic sequencing and the PEnalized LOgistic Regression Analysis (PELORA) we identified clusters of bacteria with differential abundances between metastatic and non-metastatic patients. An overall increase in Gram-negative bacteria in metastatic patients compared to non-metastatic ones was identified using this method. Furthermore, to gain more insight into how gut microbes can predict metastases, a machine learning approach (iterative Random Forest) was performed. Iterative Random Forest analysis revealed which microorganisms were characterized by a different level of relative abundance between metastatic and non-metastatic patients and established a functional relationship between the relative abundance and the probability of having metastases. At the species level, the following bacteria were found to have the highest discriminatory power: Anaerostipes hadrus, Coprobacter secundus, Clostridium sp. 619, Roseburia inulinivorans, Porphyromonas and Odoribacter at the genus level, and Rhodospirillaceae, Clostridiaceae and Peptococcaceae at the family level. Finally, these data were intertwined with those from a metabolomics analysis on fecal samples of patients with or without metastasis to better understand the role of gut microbiota in the metastatic process. Artificial intelligence has been applied in different areas of the medical field. Translating its application in the field of gut microbiota analysis may help fully exploit the potential information contained in such a large amount of data aiming to open up new supportive areas of intervention in the management of cancer.

Real-world experiences in patients with Ewing sarcoma treated at a specialist centre in Turkey

ObjectivesThe present study evaluates the clinical outcomes of children, adolescents and adults with Ewing sarcoma and identifies the prognostic factors. MethodsIncluded in the study were 222 pediatric and adult patients diagnosed with Ewing sarcoma (EwS) who were followed up between 1992 and 2019, and whose data were analyzed retrospectively. ResultsThe median age of 131 male and 91 female patients included in the study was 13 (1–64). The median follow-up duration of the survivors was 79 months (range, 11–182 months). The 3-year EFS rate of the 222 patients was 34 % (Confidence Interval (CI) (0.158–0.242 %) and the OS rate was 54 % (CI, 0.289–0.590 %). For the non-metastatic patients, the 3-year EFS rate was 47 % and the OS was 68 %, while for the metastatic patients the 3-year EFS rate was 13 % and the OS was 30 %. Of the patient sample, 81 (36, 5 %) survived, of whom 72 were continuously free of disease while the disease persisted in nine, and three developed a secondary neoplasm (2 of whom subsequently died while one survived disease-free). Of the 129 patients who relapsed with metastases and/or local recurrence, eight survived and are disease-free, nine are alive with uncontrolled disease; five were lost to follow-up and 107 died. ConclusionThe findings of the present study suggest metastatic disease at presentation and positive margins after surgery to be of prognostic significance in EwS. Disruptions in aggressive local treatments may reduce the chances of cure in EwS.

A Plea for Monitoring Serum Selenium Levels in Breast Cancer Patients: Selenium Deficiency Is Rare during the First Year of Therapy, and Selenium Supplementation Is Associated with Elevated Risk of Overdosing.

(1) Background: The role of selenium in cancer biology remains poorly understood. Our aim was to study the course of selenium serum levels and the use of selenium supplements during breast cancer therapy. (2) Methods: Serum selenium levels, clinical-pathological data, selenium supplementation, and lifestyle factors were monitored quarterly over one year. (3) Results: A total of 110 non-metastatic breast cancer patients were enrolled in the prospective observational "BEGYN-1" study. At baseline, 2.9% of patients were selenium-deficient (<50 ng/mL), 1.9% were overdosed (>120 ng/mL), and 6.4% received substitution. The median selenium level was 81.5 ng/mL and ranged between 78.7 and 84.5 ng/mL within the year. A total of 25.3% of the patients received supplementation, resulting in significantly higher selenium levels (p < 0.05). A total of 8.7-28.6% of the patients using supplements were overdosed. Selenium levels strongly correlated with mushroom consumption (p = 0.003), but no association was found with therapy or clinical characteristics. (4) Conclusions: Although selenium deficiency is rare, serum selenium levels should be assessed in breast cancer patients. Mushrooms and nuts should be preferred over supplements to correct selenium deficiency. Ruling out selenium deficiency helps prevent the risk of selenosis and avoid unnecessary, costly supplementation in patients who are often financially burdened due to their disease.

327 Impact of Adjuvant Chemotherapy/Radiotherapy on the 5 Year Overall Survival of Patients with Non-Metastatic Rectal Cancer in Bulgaria - a Retrospective Population-Wide Observational Study

Abstract Introduction Survival rates of patients with non-metastatic rectal cancer (RC) have increased, due the use of adjuvant chemotherapy/radiotherapy post-surgery, recommended by the National Comprehensive Cancer Network (NCCN) [1–3]. The aim of the study was to analyse the impact of adjuvant chemotherapy/radiotherapy on the 5-year overall survival (OS) of patients diagnosed with non-metastatic RC patients in Bulgaria. Method This is a retrospective population wide observational study of 8968 cases registered with Colorectal cancer in the Bulgarian National Cancer Registry (BNCR) between 2015 and 2016. The mean and median age of patients with left colon (LCC) and right colon (RCC) along with rectal cancer (RC) was analysed. The impact of adjuvant chemotherapy and radiotherapy on the 5-Year OS for non-metastatic RC was analysed. Kaplan-Meier curve with log rank, ANOVA and chi-squared tests were used to estimate the statistical significance. Results The mean age at diagnosis for RCC, LCC and RC was 68.9, 67.41 and 66.4 respectively (p-Value=&amp;lt;0.001). The median age at diagnosis was 69, 68 and 67 for RCC, LCC and RC respectively. Our study showed that patients with non-metastatic RC that received both adjuvant chemotherapy and radiotherapy had a higher 5-year OS compared to patients who received either chemotherapy, radiotherapy or neither therapy (61.4%, 59.5%, 56.2%, 51.8%), p-Value=0.007. Less than 40% of patients received either adjuvant chemotherapy or radiotherapy. Conclusions Adjuvant chemotherapy/radiotherapy improves the 5-Year OS for patients with non-metastatic RC. NCCN guidelines should be implemented in Bulgaria [1–3]. Bulgaria will benefit by implementing an organised screening programme [4].