Publications by authors named "Thibodeau S"

Purpose: Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease, with a spectrum of anatomic extent, health status, and treatment approaches. Receipt of treatment and its intent should be independent of health system factors where care quality is optimal. We investigated the degree that modifiable health system factors are associated with receipt of treatment and treatment intent in stage III NSCLC in a large, universal health system.

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  • Heart failure with preserved ejection fraction (HFpEF) is influenced by various risk factors that affect organs beyond the heart, and a study used a mouse model to explore the effects of metabolic-hypertensive stress and exercise on heart health.
  • After a period of stress, the study found that stopping the stresses and introducing voluntary exercise led to significant cardiac improvements, especially in female mice who experienced loss of cardiac hypertrophy and remodeling.
  • The research also revealed changes in plasma microRNA levels (miRs), which changed in response to stress; however, while plasma levels normalized after recovery, the heart tissue showed persistent abnormalities, indicating that circulatory markers alone may not provide a complete picture of heart health recovery.
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Single nucleotide polymorphism (SNP) interactions are the key to improving polygenic risk scores. Previous studies reported several significant SNP-SNP interaction pairs that shared a common SNP to form a cluster, but some identified pairs might be false positives. This study aims to identify factors associated with the cluster effect of false positivity and develop strategies to enhance the accuracy of SNP-SNP interactions.

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We propose a new mouse (C57Bl6/J) model combining several features of heart failure with preserved ejection fraction encountered in older women, including hypertension from Angiotensin II infusion (AngII), menopause, and advanced age. To mimic menopause, we delayed ovariectomy (Ovx) at 12 months of age. We also studied the effects of AngII infusion for 28 days in younger animals and the impact of losing gonadal steroids earlier in life.

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After menopause, the incidence of cardiovascular disease rapidly rises in women. The disappearing protection provided by sex steroids is a consequence of the development of many risk factors. Preclinical studies are necessary to understand better the effects of ovarian hormones loss cardiac aging.

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  • Menopausal hormone therapy (MHT) may lower the risk of colorectal cancer (CRC), especially in women with a higher genetic predisposition to the disease.
  • In a study of nearly 30,000 postmenopausal women, those in the highest genetic risk quartile saw a significantly greater reduction in CRC risk when using MHT compared to those in the lowest quartile.
  • The findings suggest that integrating genetic risk information could improve CRC risk predictions and inform the assessment of MHT benefits in postmenopausal women.
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Multiple factors cause heart failure with preserved ejection fraction (HFpEF) and involve various systems. HFpEF prevalence is rapidly rising, and its prognosis remains poor after the first hospitalization. Adopting a more active lifestyle has been shown to provide beneficial clinical outcomes for patients with HFpEF.

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  • Obesity is linked to various types of colorectal cancer (CRC), but the strength and cause of these links are not fully understood.
  • By using Mendelian randomization, researchers studied how body size traits like BMI, waist circumference, and body fat percentage affect risks for different CRC subtypes.
  • Results showed that higher BMI and body fat significantly increased the risks for serrated and alternate CRC pathways (Jass types 1, 2, and 3), while associations with the traditional pathway (Jass type 4) were weaker.
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The global cancer burden, especially in low- and middle-income countries (LMICs), worsens existing disparities, amplified by the rising costs of advanced treatments. The shortage of radiation therapy (RT) services is a significant issue in LMICs. Extended conventional treatment regimens pose significant challenges, especially in resource-limited settings.

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•SABR has shown survival benefits in oligometastatic cases, particularly in low-volume metastatic disease states.•Spine SABR offers potential improvements in local control, and pain response for metastatic spine tumors.•Technical requirements for SABR, like advanced image guidance and immobilization systems, are increasingly available.

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Radiotherapy is an integral part of the multidisciplinary management of breast cancer (BC). There have been multiple recent advances in the delivery of radiotherapy, reviewed with a critical discussion of the evidence from trials investigating adjuvant ultra-hypofractionation and partial breast irradiation for early-stage BC, and the locoregional management of lymph nodes in locally advanced BC. Multiple precision medicine-based approaches have been developed as prognostic and/or predictive for BC patients and identifying biomarkers of radioresistance could help identify patients that may benefit from dose-escalated radiotherapy or radiosensitizers.

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  • A recent study analyzed genetic data from over 156,000 prostate cancer cases and 788,000 controls from diverse populations, significantly increasing the representation of non-European participants.
  • Researchers identified 187 new genetic risk variants for prostate cancer, bringing the total to 451, enhancing understanding of genetic factors across different ancestries.
  • The developed genetic risk score (GRS) showed varying risk levels for prostate cancer among different ancestry groups, highlighting its potential for better risk assessment, especially in men of African descent.
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Purpose: To determine cardiac dose received by patients treated with high dose rate interstitial brachytherapy. Patients with early-stage, node negative breast cancer can be treated using multi-catheter interstitial brachytherapy accelerated partial breast irradiation (MIB-APBI), with the benefit of reduced treatment volumes and favorable toxicity.

Methods And Materials: We conducted a retrospective review of left-sided breast cancer patients treated using MIB-APBI at our institution since 2014.

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  • About 30% of people with non-small cell lung cancers (NSCLC) have stage III cancer when they find out they're sick, and half of them get treated with special chemotherapy and radiation.
  • A study looked at 195 patients treated from 2010 to 2021 to see what factors affect their chances of getting brain cancer after treatment.
  • Out of these patients, many had complications; 43% got any kind of cancer spread and 17% developed brain cancer, especially if they had more severe disease or certain treatment-related factors.
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  • Diabetes is linked to a higher risk of colorectal cancer, but the mechanisms behind this link and the influence of genetic variants need further exploration.!* -
  • Researchers conducted a genome-wide analysis using data from over 31,000 colorectal cancer cases and nearly 41,500 controls to investigate gene-environment interactions involving genetics and diabetes.!* -
  • Findings revealed that specific genes on chromosomes 8q24.11 (SLC30A8) and 13q14.13 (LRCH1) may affect how diabetes increases colorectal cancer risk, highlighting potential biological pathways related to insulin signaling and immune functions.!*
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Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS.

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  • Genome-wide polygenic risk scores (GW-PRS) were analyzed for their predictive ability regarding prostate cancer risk, compared to an established multi-ancestry polygenic risk score (PRS).
  • The GW-PRS models utilized data from a large and diverse group of nearly 235,000 participants, including individuals from both African and European ancestries.
  • Results showed that while GW-PRS had varying predictive abilities, the multi-ancestry PRS performed equally well or better in predicting prostate cancer risk for both ancestry groups, indicating GW-PRS may not offer significant improvements in risk prediction.
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  • This study explores how genetics and body mass index (BMI) interact to influence colorectal cancer risk, analyzing data from over 84,000 participants.
  • The research identifies a significant genetic marker (rs58349661) in the FMN1/GREM1 gene region that shows a strong connection with increased cancer risk in individuals with higher BMI, particularly among those with a specific genotype.
  • Findings suggest that understanding this gene-environment interaction could help develop more tailored prevention strategies for colorectal cancer related to obesity.
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  • The Prospective Lynch Syndrome Database (PLSD) gathers data on individuals with MMR variants to study cancer diagnosis and treatment outcomes, focusing on a newly expanded cohort.
  • The study includes over 8,500 patients from 25 countries, analyzing cancer incidence, mortality rates up to age 75, and survival rates after diagnosis.
  • Findings reveal that while gynecological cancers have high incidence rates among carriers, non-colorectal cancers lead to more deaths, highlighting the need for improved care for these patients.
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  • Early-onset colorectal cancer (diagnosed before 50) is increasing, and understanding its molecular features across different tumor locations is crucial for personalized treatment.
  • A study of 14,004 colorectal cancer cases identified distinct molecular characteristics like microsatellite instability (MSI), CIMP, and mutations in KRAS and BRAF, comparing early-onset and later-onset tumors.
  • Results showed that early-onset tumors had a higher prevalence of MSI-high status but lower rates of CIMP-high status and BRAF mutations, highlighting the biological differences and potential treatment implications based on age and tumor location.
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  • The study investigates how the location of colorectal tumors affects survival rates, particularly in relation to their molecular characteristics like microsatellite instability (MSI) and methylation patterns (CIMP).
  • A large dataset of over 13,000 colorectal cancer cases revealed significant survival trends based on tumor location, with non-MSI-high tumors showing better outcomes as they moved from the cecum to the sigmoid colon, while MSI-high tumors had worse outcomes in the same locations.
  • The findings emphasize the need for considering both tumor location and molecular features for more accurate prognostication in colon cancer, highlighting the potential of precision medicine in improving patient outcomes.
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Background: Obesity is an established risk factor for colorectal cancer (CRC), but the evidence for the association is inconsistent across molecular subtypes of the disease.

Methods: We pooled data on body mass index (BMI), tumor microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, and Jass classification types for 11 872 CRC cases and 11 013 controls from 11 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for covariables.

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  • - The study aims to compare colorectal cancer (CRC) incidences between two groups: one group receiving mandatory colonoscopy surveillance (PLSD) and another group with retrospective data (IMRC) that did not have the same follow-up.
  • - Results from the PLSD showed higher CRC rates in carriers of MMR gene variants, particularly for path_MLH1 and path_MSH2, compared to the IMRC cohort, challenging previous expectations about cancer rates in these groups.
  • - The study concludes that while colonoscopy did reduce CRC incidences in paths_MPS2 carriers prior to age 50, it did not have the same effect for path_MLH1 and path_MSH2, suggesting the need for reevaluation of
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Age, hypertension, and the female sex are among the risk factors in the development of heart failure with preserved ejection fraction. We studied by standard and speckle-tracking echocardiography (STE), the response of the left ventricle (LV) to aging and angiotensin II continuous infusion (ANG II; 1.5 mg/kg/day for 28 days) in 2- and 12-mo-old male and female C57Bl6/J mice.

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  • * The study involved two main approaches: one examined links between specific germline variants and somatic mutations in 1,375 CRC cases, while the other investigated the relationship between germline variants and overall CRC risk using data from a large-scale genetic study.
  • * Key findings included a specific variant (rs78963230) linked to mutations in the FBXW7 gene, and another variant (rs2302274) associated with overall CRC risk, highlighting the importance of studying both types of genetic variations for deeper understanding of CRC
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