Institute Of Cancer Research Research Articles

Vitisin B, a resveratrol tetramer from Vitis thunbergii var. taiwaniana, ameliorates impaired glucose regulations in nicotinamide/streptozotocin-induced type 2 diabetic mice.

In Taiwan, Vitis thunbergii var. taiwaniana (VTT) is used in traditional medicine and as a local tea. VTT rich in resveratrol and resveratrol oligomers have been reported to exhibit anti-obesity and anti-hypertensive activities in animal models; however, no studies have investigated type 2 diabetes mellitus (T2DM) treatments. This study aimed to investigate the anti-T2DM effects of resveratrol tetramers isolated from the VTT in nicotinamide/streptozotocin (STZ)-induced Institute of Cancer Research (ICR) mice. The oral glucose tolerance test (OGTT) was used to imitate postprandial blood glucose (BG) regulations in mice by pre-treatment with VTT extracts, resveratrol tetramers of vitisin A, vitisin B, and hopeaphenol 30min before glucose loads. Vitisin B (50mg/kg) was administered to treat T2DM-ICR mice once daily for 28 days to investigate its hypoglycemic activity. Mice pre-treated with VTT-S-95EE, or vitisin B (100mg/kg) 30-min before glucose loading showed significant reductions (P<0.001) in the area under the curve at 120-min (BG-AUC0-120) than those without pre-treatment with VTT-S-95EE or vitisin B. Vitisin B-treated T2DM mice showed hypoglycemic activities via a reduction in plasma dipeptidyl peptidase (DPP)-IV activities to maintain insulin actions and differed significantly than those of untreated T2DM mice (P<0.05), and also reduced BG-AUC0-120 and insulin-AUC0-120 in the OGTT.These invivo results showed that VTT containing vitisin B would be beneficial for developing nutraceuticals and/or functional foods for glycemic control in patients with T2DM, which should be investigated further.

Associations of Adherence to the 2018 World Cancer Research Fund and the American Institute for Cancer Research Dietary Recommendations with Gut Microbiota and Inflammation Levels.

Whether the World Cancer Research Fund and the American Institute for Cancer Research (WCRF/AICR) dietary recommendations affect the gut microbiota and inflammatory status remains unclear. We examined the association of dietary adherence scores to the WCRF/AICR with gut microbiota and inflammation in a cross-sectional setting. The WCRF/AICR diet adherence scores were calculated for 151 participants (adenoma 97, non-adenoma 54) from 7-day dietary records. The gut microbiota was analyzed by 16S rRNA gene sequencing of fecal samples. The levels of inflammatory biomarkers in both blood (i.e., IL-6, IL-8, IgA, IgM, and IgG) and fecal samples (i.e., FCP) were evaluated in 97 colorectal adenoma patients who had blood samples available. Multivariable linear regression analyses were conducted to examine the association of individual and total dietary adherence scores with gut microbiota and inflammatory biomarker levels. Participants with higher adherence had lower relative abundance of Proteobacteria (β = -0.041, 95%CI: -0.073, -0.009), Enterobacteriaceae (β = -0.035, 95%CI: -0.067, -0.003), and unidentified Enterobacteriaceae at the genus level (β = -0.029, 95%CI: -0.055, -0.003) compared to those with lower adherence. Plant-based food intake was positively correlated with increased abundance of Phascolarctobacterium (β = 0.013, 95%CI: 0.001, 0.026). Restricting fast food was linked to high abundance of Bacteroidaceae (β = 0.149, 95%CI: 0.040, 0.257) and Bacteroides (β = 0.149, 95%CI: 0.040, 0.257). Limiting sugary drinks was associated with reduced abundance of Lachnospiraceae (β = -0.155, 95%CI: -0.292, -0.018). Plant-based food intake (β = -0.251, 95%CI: -0.450, -0.052) and restriction of fast food (β = -0.226, 95%CI: -0.443, -0.008) were associated with reduced IGG levels in men. Alcohol restriction was linked to lower IL-6 (β = -7.095, 95%CI: -11.286, -2.903) and IL-8 (β = -7.965, 95%CI: -14.700, -1.230) levels in women, but with higher IL-6 (β = 0.918, 95%CI: 0.161, 1.675) levels in men. Our findings support the association of adherence to the WCRF/AICR diet with gut microbiota and inflammation. These results need to be validated in additional prospective or interventional studies.

Supplementing maternal diet with milk oligosaccharides and probiotics helps develop the immune system and intestinal flora of offsprings.

Intestinal flora is very important for improving the development of the immune system in newborns. Maternal diet during pregnancy and lactation is one of the key factors affecting the growth and development of offspring. The objective of the present study was to examine whether supplementation of maternal diet with milk oligosaccharides and Bifidobacterium could influence the development of the intestinal flora and immune system of neonatal mice. In total, 30 pregnant Institute of Cancer Research (ICR) mice were randomly divided into six groups: a control group (basal diet) and five intervention groups (basal diet supplemented with different doses of 2'-fucosyllactose [2'-FL] and Bifidobacterium Bb12) during the pregnancy period. All female mice were monitored for physical health during gavage. After delivery, the number of mice in each litter, any deformity, and the development of the offspring were recorded. The spleen, blood, and fecal samples of six groups of 10-12 day-old offspring were collected. The results demonstrated that maternal milk oligosaccharides and probiotics conferred protective effects against lipopolysaccharide (LPS)-induced immunosuppression in mice offspring by significantly enhancing the immune organ indexes, splenocyte proliferation, immunoglobulin (immunoglobulin G, A, M) production as well as improving the macrophage phagocytosis (p < .05). The abundance of Lactobacilli and Bifidobacteria in the feces of offspring mice in the intervention groups was significantly higher than that of the offspring mice in the control group (p < .05). These findings suggest that the combination of 2'-FL and Bifidobacterium Bb12 displayed synergistic interactions between the two components that could promote the development of the immune system of the offsprings and improve their microbiota through maternal ingestion.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research and Korean Cancer Prevention Guidelines and cancer risk: a prospective cohort study from the Health Examinees-Gem study.

The purpose of this study was to explore the association between adherence to 2 cancer prevention recommendations and cancer risk. In total, 104,386 individuals aged 40-69 years old who were recruited between 2004 and 2013 in the Health Examinees-Gem study were included. Adherence scores were constructed based on 8 items from the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations, including body weight, physical activity, diet, alcohol consumption and breastfeeding, and on 6 items from the Korean cancer prevention guidelines (smoking status, eating vegetables and fruits, salty foods, alcohol intake, physical activity, and body weight). A Cox proportional hazards model was used to estimate the associations between adherence scores and the risk of total and 5 major cancers. The multivariable hazard ratio (HR) for total cancer with the high adherence score versus the lowest score (4.25-7.00 vs. 0.00-3.25) for the WCRF/AICR guidelines was 0.91 (95% confidence interval [CI], 0.82 to 1.00) in men. A reduced breast cancer risk was observed among women with the highest score. Men within the highest category of the Korean cancer prevention guideline score (3.25-6.00) had an HR of 0.80 (95% CI, 0.73 to 0.88) for developing total cancer compared to men within the lowest score (0.00-2.50). The higher adherence group among men showed lower risks of developing stomach, colorectal, and lung cancers. Adhering to guidelines for cancer prevention can help to reduce the risk of developing cancer in Korean men. The association might differ by cancer type and gender.

Electrogenic Staphylococcus epidermidis colonizes nasal cavities and alleviates IL-6 progression induced by the SARS2-CoV nucleocapsid protein.

Certain probiotic bacteria have been shown to possess an immunomodulatory effect and a protective effect on influenza infections. Using the Staphylococcus epidermidis K1 colonized mice model, we assessed the effect of nasal administration of glycerol or flavin mononucleotide (FMN) on the production of interleukin (IL)-6 mediated by the severe acute respiratory syndrome coronavirus 2 (SARS2-CoV) nucleocapsid protein (NPP). FMN, one of the key electron donors for the generation of electricity facilitated by S. epidermidis ATCC 12228, was detected in the glycerol fermentation medium. Compared to the S. epidermidis ATCC 12228, the S. epidermidis K1 isolate showed significant expression of the electron transfer genes, including pyruvate dehydrogenase (pdh), riboflavin kinase (rk), 1,4-dihydroxy-2-naphthoate octaprenyltransferase (menA), and type II NADH quinone oxidoreductase (ndh2). Institute of cancer research (ICR) mice were intranasally administered with S. epidermidis K1 with or without pretreatment with riboflavin kinase inhibitors, then nasally treated with glycerol or FMN before inoculating the NPP. Furthermore, J774A.1 macrophages were exposed to NPP serum and then treated with NPP of SARS2-CoV. The IL-6 levels in the bronchoalveolar lavage fluid (BALF) of mice and macrophages were quantified using a mouse IL-6 enzyme-linked immunosorbent assay kit. Here, we report that nasal administration of NPP strongly elevates IL-6 levels in both BALF and J774A.1 macrophages. It is worth noting that NPP-neutralizing antibodies can decrease IL-6 levels in macrophages. The nasal administration of glycerol or FMN to S. epidermidis K1-colonized mice results in a reduction of NPP-induced IL-6 production.

Research on the anti-ageing mechanism of Prunella vulgaris L.

Prunella vulgaris L. (P. vulgaris) has long been considered to have antipyretic, analgesic and anti-inflammatory effects, lowering blood lipids and pressure. Many studies show that in addition to the traditional telomere attrition, DNA damage and epigenetic changes, immunosenescence is also a new possibility to explore the mechanism of ageing. Therefore, this herb may have potential anti-ageing effects. Typically, there are a series of markers that identify senescent cells, such as superoxide dismutase (SOD)2, an inhibitor of CDK4 (p16INK4A), tumor necrosis factor (TNF)-α, immune cells number, proliferation, and nuclear abnormalities. These changes rarely present in young tissues, while greatly increasing in response to ageing. Firstly, the ageing model of the Institute of Cancer Research (ICR) mouse was established by d-galactose subcutaneous injection. Then, SOD2, p16INK4A and TNF-α were detected by quantitative Real-time PCR (qPCR), Western Blot (WB) and Enzyme-Linked Immunosorbent Assay (ELISA). Simultaneously, senescent cells in livers were stained by hematoxylin and eosin (HE). The viability of splenocytes was detected by Cell Counting Kit-8(CCK-8). The difference in specific immune cells (NK cells, B lymphocytes and T lymphocytes) was detected by flow cytometry. Both low (100 mg/kg) and high (300 mg/kg) concentrations of P. vulgaris treated ageing ICR mice show anti-ageing alterations, such as p16INK4A decreased approximately 1/2 and SOD2 tripled in livers, TNF-α decreased from 1 to 0.6 in plasma, and T cells increased from 0.09 to 0.19%. Compared with the ageing group, the spleen cells in the Prunella-treated group had stronger proliferation ability. Thus, P. vulgaris could have an anti-ageing effect. This is the first study to demonstrate the anti-ageing effect of P. vulgaris. It may also be capable of preventing a variety of age-related diseases.

Different operationalizations of the 2018 WCRF/AICR cancer prevention recommendations and risk of cancer.

The standardized scoring system assessing adherence to the 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) cancer prevention recommendations assigns equal weight for each recommendation, thereby giving higher weight to dietary factors collectively (5 points) than adiposity (1 point) and physical activity (1 point). An alternative score assigning equal weights to the adiposity, physical activity, alcohol, and other dietary (composite) recommendations may better predict cancer associations. We examined associations between standardized and alternative scores with cancer risk in two US prospective cohorts. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. During 28 years of follow-up, 16,342 incident cancer cases in women and 8729 cases in men occurred. Individuals in the highest versus lowest quintile of the standardized score had a reduced overall cancer risk (women: HR = 0.89, 95% CI: 0.85, 0.94; men: HR = 0.87, 95% CI: 0.81, 0.94). Results were slightly stronger for the alternative score (women: HR = 0.83, 95% CI: 0.79, 0.87; men: HR = 0.81, 95% CI: 0.75, 0.86). Similar patterns were observed for obesity-related, alcohol-related, smoking-related, and digestive system cancers. Greater adherence to the WCRF/AICR cancer prevention recommendations was associated with lower cancer risk. A score assigning equal weights to the adiposity, physical activity, alcohol, and all remaining diet components yielded stronger associations than the standardized score.

Developing novel treatments for childhood solid cancers

Developing novel treatments for childhood solid cancers With a particular focus on glioma, Dr Peter J Houghton from Greehey Children’s Cancer Research Institute outlines the barriers that have hindered the development of effective therapies for childhood solid cancers. Childhood cancer represents less than 1% of human cancers, thus, is not a priority for drug development in the pharmaceutical industry. However, the consequences of having a child diagnosed with a malignant disease can be devastating for families. Developing new therapies for childhood solid cancers presents certain constraints that are seldom encountered with neoplastic diseases diagnosed in adults. Childhood tumours are rare, which has therefore restricted large-scale drug evaluations or randomised clinical trials. For example, of the new Phase I agents evaluated in adult malignancies, less than 30% receive an adequate assessment in children.

Editorial introductions.

Editorial introductions.

Exogenous lactate intake immediately after endurance exercise increases time to exhaustion in VO2max measurements in mice.

The purpose of the study was to investigate the effects of 4 weeks of lactate intake immediately after endurance exercise on maximal oxygen uptake (VO2max) in exercise performance. Seven-week-old mice from the Institute of Cancer Research (ICR) were randomly divided into four groups: vehicle intake (SE/CON), lactate intake (SE/LAC), endurance exercise with vehicle intake (EX/ CON), and lactate intake with endurance exercise (EX/ LAC). Mice were subjected to 60-70% VO2max endurance exercise with or without oral lactate intake 5 days/ week for 4 weeks. VO2max measurements (VO2max, time to exhaustion (TTE), respiratory exchange rate, fat oxidation, and carbohydrate oxidation) were recorded at the end of the study period. After 48 h of VO2max measurement, the mice were sacrificed, and three different abdominal fat samples (epididymal, perirenal, and mesenteric) were collected. Body weight and abdominal fat mass did not differ between the groups. When measuring VO2max, endurance exercise raised VO2max, and lactate intake after endurance exercise increased TTE. The change in energy substrate utilization during VO2max measurement demonstrated that although the respiratory exchange rate and fat oxidation were enhanced by lactate intake, there were no synergistic effects of lactate intake and endurance exercise. Lactate intake immediately after endurance exercises can improve exercise performance, indicating the benefit of long-term exogenous lactate intake as an exercise supplement.

Meet the First Authors.

Meet the First Authors.

Construction and validation of a survival prognostic model for stage III hepatocellular carcinoma: a real-world, multicenter clinical study

ObjectiveTo construct a survival prediction model for patients with TNM stage III hepatocellular carcinoma (HCC) to guide the clinical diagnosis and treatment of HCC patients and improve prognosis.MethodsBased on data from patients with stage III (AJCC 7th TNM stage) recorded by the American Institute of Cancer Research from 2010 to 2013, risk factors affecting the prognosis were screened by Cox univariate and multivariate regression, line plots was constructed, and the credibility of the model was verified by Boostrap method. ROC operating curves, calibration curves and DCA clinical decision curves were used to evaluate the model, and Kaplan–Meier was used for survival analysis was used to evaluate the efficacy of the model. External survival data from patients newly diagnosed with stage III hepatocellular carcinoma during 2014–2015 were used to validate and fit the model and to optimize the model.ResultsAge > 75 years vs.18-53 years [HR = 1.502; 95%CI(1.134–1.990)], stage IIIC vs. Stage IIIA [HR = 1.930; 95%CI(1.509–2.470)], lobotomy vs. non-surgery [HR = 0.295; 95%CI(0.228–0.383)], radiotherapy vs. non-radiotherapy [HR = 0.481; 95%CI(0.373–0.619)], chemotherapy vs. Non-chemotherapy [HR = 0.443; 95%CI(0.381–0.515)], positive serum AFP before treatment vs. negative [HR = 1.667; 95%CI(1.356–2.049)], the above indicators are independent prognostic factors for patients with stage III hepatocellular carcinoma, and the P values for the above results were less than 0.05. A joint prediction model was constructed based on age, TNM stage, whether and how to operate, whether to receive radiotherapy, whether to receive chemotherapy, pre-treatment serum AFP status and liver fibrosis score. The consistency index of the improved prognosis model was 0.725.ConclusionsThe traditional TNM staging has limitations for clinical diagnosis and treatment, while the Nomogram model modified by TNM staging has good predictive efficacy and clinical significance.

Determinants and changes in adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer-prevention recommendations over the past 25 years in Switzerland.

The World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) established 10 lifestyle recommendations for cancer prevention. The current study examines the proportion and changes over 25 years of adherence to these recommendations and their determinants in Switzerland. On the basis of six Swiss Health Surveys (1992-2017, N = 110 478), an index reflecting adherence to the 2018 WCRF/AICR cancer-prevention recommendations was created. Multinomial logistic regression models were fitted to investigate changes over time and determinants of a cancer-protective lifestyle. Adherence to cancer-prevention recommendations was moderate and higher in the years 1997-2017 compared to 1992. Higher adherence was observed among women (odds ratio [OR]high vs. low adherence ranging from 3.31 to 3.74) and participants with a tertiary education level (ORhigh vs. low adherence ranging from 1.71 to 2.18), and lower adherence among participants of the oldest age group (ORhigh vs. low adherence ranging from 0.28 to 0.44) and participants of the Switzerland (lat.: Confoederatio helvetica)-French language regions (ORhigh vs. low adherence ranging from 0.53 to 0.73). Our results showed that cancer-prevention recommendations are not well followed by the general Swiss population, as the adherence to a cancer-protective lifestyle was generally moderate; however, adherence to cancer-prevention recommendations improved over the past 25 years. Sex, age group, education level, and language regions were significant determinants of adherence to a cancer-protective lifestyle. Further actions at the governmental and individual levels promoting the adoption of a cancer-protective lifestyle are needed.

A Clinicopathological Study of Hepatocellular Carcinoma: A Cross Sectional Study

The purpose of the present study was to find out the clinicopathological characteristics of Hepatocellular Carcinoma (HCC) patients. All the clinically suspected patients were recruited as per inclusion and exclusion criteria. The relevant socio-demographic characteristics, clinical findings as well as the physical examination were performed after talking written consent from all the study subjects. The ultrasonography was performed to all the patients. After that, the patients were sent to the department of pathology for histopathological examination. The descriptive cross-sectional study was carried out in the Department of Oncology of National Institute of Cancer Research and Hospital (NICRH), Dhaka, Bangladesh from July 2014 to June 2015 for a period of 12 months. Total sample size was 52 in this study and age distribution of HCC was found from 25 years to 97 years to with the mean age 50.57 ± 12.09 years. Males were predominant (78.0%), male and female ratio was 3.72:1. The common presenting features of HCC were abdominal pain and swelling, fever and jaundice; viral marker was positive in 86.5% of patients (HBsAg-67.3%, Anti HCV-19.2%) with normal tumor marker alpha-fetoprotein (AFP) in 69% of the patients. Okuda staging shows 82.7% patients within stage I and Stage II and performance status, 38.5% patients were unable to carry out normal activity. Sonological findings revealed 69.2% patients had ≤2 cm tumor size, 88.4% had ascites lastly splenomegaly was present among 86.5% respondents.

Interferon-γ induces salivary gland epithelial cell ferroptosis in Sjogren's syndrome via JAK/STAT1-mediated inhibition of system Xc-

The elevated level of interferon-γ (IFN-γ) in Sjogren's syndrome (SS) triggers salivary gland epithelial cells (SGEC) death. However, the underlying mechanisms of IFN-γ-induced SGEC death modes are still not fully elucidated. We found that IFN-γ triggers SGEC ferroptosis via Janus kinase/signal transducer and activator of transcription 1 (JAK/STAT1)-mediated inhibition of cystine-glutamate exchanger (System Xc−). Transcriptome analysis revealed that ferroptosis-related markers are differentially expressed in SS human and mouse salivary glands with distinct upregulation of IFN-γ and downregulation of glutathione peroxidase 4 (GPX4) and aquaporin 5 (AQP5). Inducing ferroptosis or IFN-γ treatment in the Institute of cancer research (ICR) mice aggravated and inhibition of ferroptosis or IFN-γ signaling in SS model non-obese diabetic (NOD) mice alleviated ferroptosis in the salivary gland and SS symptoms. IFN-γ activated STAT1 phosphorylation and downregulated system Xc− components solute carrier family 3 member 2 (SLC3A2), glutathione, and GPX4 thereby triggering ferroptosis in SGEC. JAK or STAT1 inhibition in SGEC rescued IFN-γ-downregulated SLC3A2 and GPX4 as well as IFN-γ-induced cell death. Our results indicate the role of ferroptosis in SS-related death of SGEC and SS pathogenicity.

Effects of 3 Weeks Home Based Exercise on HRQOL and Functional Capacity in Advanced Lung Cancer Subjects After First Chemotherapy

Aims and objectives: The aim of the study was to find out the effect of home based exercise on functional capacity and health related quality of life (HRQOL) of individuals having Advanced Lung Cancer &amp; undergoing their first Chemotherapy session. Methodology: 12 subjects were recruited from Cancer Research Institute, Himalayan Hospital, Dehradun. The subjects were randomly divided into two groups. Group A was provided with Home based exercise protocol whereas Group B was kept as Control group. Home based exercise protocol was given in a printed manner (as a leaflet) and was followed on every alternate day for 3 weeks. EORTC QLQ 30, QLQ LC 13 and 6MWD were recorded prior to the 1st Chemotherapy session and 3 weeks post- 1st chemotherapy session. Results: The results of this study showed that, there was significant increase in the functional capacity in both the groups (Group A &amp; B: Pre &amp; Post, value of p : 0.014 &amp; 0.003 respectively). But it was highly significant in the experimental group when compared with control group (p=0.003). Conclusion: The study concluded that the Home Based Exercise Protocol should be established as a treatment strategy to improve Health Related Quality of Life and Functional Capacity for Advanced Lung Cancer individuals undergoing their 1st Chemotherapy session.

Incomplete HPV vaccination among individuals aged 27-45 years in the United States: A mixed effect analysis of individual and contextual factors.

10546 Background: In the United States, the Human papillomavirus (HPV) vaccine is approved for use up to age 45. Incomplete HPV vaccination rates among those over age 26, however, remain high. The aim of this study was to examine the independent effects of individual- and neighborhood-level factors on incomplete HPV vaccine series in the United States (US) among those aged 27-45 years. Methods: This retrospective cohort study used administrative data from Optum’s Clinformatics DataMart Database to identify individuals aged 27-45 years who received 1 or more doses of HPV vaccine between July 2019 and June 2022. Multilevel multivariable logistic regression models were applied to the data on 7,662 individuals aged 27-45 years who were fully vaccinated against HPV or not, nested within 3839 neighborhoods across the US. Results: More than half of the participants in this study (52.93%) were not completely vaccinated against HPV. About 64% of the eligible participants aged 27-30 years did not complete their HPV vaccine series. After adjusting for all other covariates in the final model, being older than 30 years old decreased the odds of incomplete HPV vaccine series. Participants living in neighborhoods of South region of the US had enhanced odds of incomplete HPV vaccine series compared to those residing in Northeast region (aOR 1.21; 95% CrI 1.03–1.42). There was significant clustering of incomplete HPV vaccine series at the neighborhood level. Conclusions: This study revealed that individual- and neighborhood-level factors significantly influence HPV vaccination incompleteness in the US. Interventions to improve HPV vaccination uptake and completion should take into consideration both individual- and contextual-level characteristics during design, planning and implementation of policies and programs to improve HPV vaccination coverage and completion in the US and other similar countries. Acknowledgement Dr. Adekanmbi is supported by a research career development award (K12HD052023: Building Interdisciplinary Research Careers in Women’s Health Program-BIRCWH; Berenson, PI) from the National Institutes of Health/Office of the Director (OD), National Institute of Allergy and Infectious Diseases (NIAID), and Eunice Kennedy Shriver National Institute of Child Health &amp; Human Development (NICHD). Dr. Guo is currently supported by an award (K07CA222343) from the National Institutes of Health, National Cancer Institute (NIH/NCI). Dr. Berenson is supported by an award (PP200048) from the Cancer Prevention and Research Institute of Texas (CPRIT). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or CPRIT. Conflict of Interest: All authors report no conflicts of interest.

Does adherence to cancer prevention guidelines before diagnosis associate with improved cancer survival?

10582 Background: The American Institute for Cancer Research and American Cancer Society regularly publish cancer prevention recommendations for decreasing cancer risk. Which lifestyles, or whether they work together to impact cancer survival is not well established. We examined associations of adherence to cancer prevention recommendations with mortality in 5,766 patients enrolled in the Data Bank and BioRepository at Roswell Park. Methods: Patients were newly diagnosed between 2003 and 2016 with a variety of pathologically confirmed invasive malignancies. Detailed epidemiological data including lifestyles one year prior to diagnosis were linked with Tumor Registry data. The primary analytic exposure was a composite Lifestyle Index Score (LIS) created in accordance with previously published standardization guidance; the primary analytic outcome was all-cause mortality. The LIS comprised seven lifestyles including: physical activity (PA); body mass index (BMI); fruit and vegetable (FV) intake; red and processed meat (RPM) intake; sugar sweetened beverage (SSB) consumption; alcohol consumption; and smoking status. Kaplan Meier analyses were used to compare survival experience according to LIS tertiles. Multivariable Cox proportional hazard models adjusted for age, tumor type, stage, and sex were used to estimate the associations of the LIS and each lifestyle factor with mortality in the overall study population and according to tumor stage. Results: During follow-up through April 2022, we observed 2,316 deaths (median follow-up 6.9 years). Patients reporting strongest adherence to prevention recommendations (highest LIS tertile) had significantly improved survival compared to patients with the lowest LIS (93.0 vs. 75.0 months, respectively; log-rank p &lt; 0.0001). In multivariable analyses, the highest versus lowest LIS tertile was associated with a 17% reduction in mortality in the overall study population (HR = 0.83, 95% CI: 0.74-0.93). Significant mortality reductions were observed in patients diagnosed with both early- and late-stage disease (HR = 0.73, 95% CI: 0.59-0.90 and HR = 0.85, 95% CI: 0.73-0.99, respectively). Being a never smoker (HR = 0.54, 95% CI: 0.47-0.62), meeting the PA Guidelines (HR = 0.74, 95% CI: 0.66-0.83), and highest FV intake (HR = 0.82, 95% CI: 0.73-0.91) were the only independent factors associated with significant reductions in mortality. Conclusions: Strongest adherence to the cancer prevention recommendations before diagnosis was associated with significant reductions in mortality. These findings provide additional evidence that modifiable lifestyle factors can impact cancer survival, even among patients diagnosed with advanced-stage disease. Confirmatory studies examining post-diagnosis lifestyles are needed so that lifestyle assessment tools, education, and intervention can be clinically leveraged to improve patient outcomes.

Comprehensive genomic profiling and individual therapeutic planning in high-risk/refractory pediatric solid tumors: A single-center real-world study.

10035 Background: Despite major improvements in the survival of pediatric cancer patients that were achieved through the intensification of chemotherapy and the perfection of supportive care in the past decades, treatment outcomes for high-risk, relapsed, and refractory solid cancers remain unsatisfactory. Accelerating the progress of pediatric oncology requires both therapeutic advances and attention to reducing the long-term cytotoxic treatment-related side effects. This could be achieved by targeting specific molecular changes that drive pediatric malignancies. Methods: From September 2016 to August 2020, a total of 192 patients with pediatric high-risk solid tumors successfully underwent comprehensive genomic profiling. Since more than thirty patients had two or more biopsies from recurrent relapses, the total number of samples examined was 295. In the cohort, there were 78 cases of central nervous system tumors, 68 sarcomas, 14 neuroblastomas, 10 lymphomas, and 22 tumors of other histology. Whole-exome sequencing was performed in all patients, fusion gene analysis in 96% of patients, whole-transcriptome profiling in 84% of patients, and CNV analysis in 63% of patients. Results: The diagnostic yield of therapeutically actionable findings was 40%, with single-nucleotide variants and small insertions/deletions being the most common actionable alteration types. In 23% of patients, a clinically relevant gene fusion was identified. The majority of the identified fusions were of diagnostic significance, and 18% of those were therapeutically targetable gene fusions involving BRAF, RAF1, ALK, FGFR1, or NTRK2. Four patients were eligible for immunotherapy based on high tumor mutational burden ( &gt; 10 mut/Mb). Lymphomas and CNS tumors showed the highest rate of patients with therapeutically actionable findings (60% and 56%, respectively), followed by neuroblastomas (36%), sarcomas (25%), and other solid tumors (23%). All results and individual treatment plans were discussed and approved at multidisciplinary molecular tumor boards. Conclusions: Precision medicine in pediatric oncology has rapidly developed over the last decade and resulted in new therapeutic options based on molecular biomarkers and increased our understanding of the complexity of pediatric malignancies. Supported by the Ministry of Health of the Czech Republic, grant nr. NU20-03-00240 and the project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102) - Funded by the European Union - Next Generation EU.

Efficacy of Neoadjuvant Chemotherapy on Locally Advanced Gastric Adenocarcinoma in Terms of Downstaging and Resectability in a Tertiary Cancer Hospital

Background: Neoadjuvant chemotherapy (NACT) in carcinoma stomach was introduced in an effort to eliminate micro-metastasis and to improve resectablity before surgery which improves R0 resection rates. The aim of the current study was to evaluate the effect of neoadjuvant chemotherapy on downstaging and resectability rate in locally advanced gastric cancer. Material &amp; Methods: This was a single-center quasi-experimental study conducted in the Department of Surgical Oncology in collaboration with the Departments of Medical Oncology, Radiation oncology, and Pathology at the National Institute of Cancer Research and hospital, Dhaka, which is a tertiary care cancer hospital in Bangladesh, between January 2021 and June 2022.Patients with locally advanced adenocarcinoma stomach staged by contrast-enhanced computed tomography (CECT) were randomly included in this study by purposive sampling. Patients in Group I underwent upfront surgery Patients in Group II were started on neoadjuvant chemotherapy, either XELOX or FLOT regimen. Surgery was done following the response assessment CECT. We assessed R0 resection rate, age, sex, comorbidities, tumour size, TNM stage and complications were compared between the two groups. Response to NACT was assessed in Group II. Results: The mean age of patients in groups 1 &amp; 2 was 56 ± 11.06 and 55.70 ± 10.46 years of age respectively (p &gt; 0.05). Majority of the respondents (55/74) were male and 19 patients (26%) were female. Male to female ratio was (24/37 &amp;31/37) in group 1 and (31/37 &amp; 6/37) groups respectively (p &gt; 0.05). Out of 37 patients who received NACT, in 9 patients (24.32%) complete response was noted. Partial response was found in 20 cases (54.05%), p-value (&lt;.0001) while a stable disease was reported in three (8.1%) cases. 5 patients (13.51%) had progressive disease. In the upfront surgery group, R0 resection was feasible in 16 (43.2%) cases, and in the NACT plus surgery group, R0 resection was done in 29 (78.4%) cases. In group 1, R1 resection was done in considerable numbers (19/37) compared to group 2 (5/37), P=0.001. Three patients (8.1%) in group 2 and one (2.7) in group 1 had irresectable lesions. Conclusion: In this study it can be concluded that neoadjuvant chemotherapy could downstage tumour and increase tumor resectability rate in patients with locally-advanced gastric adenocarcinoma. However, further studies are necessary to confirm the effect of this modality on patients’ overall survival. We await survival analysis to further validate the role of NACT.