Colorectal Cancer Outcomes Research Articles

Sarcopenia Predicts Postoperative Complications and Survival of Colorectal Cancer Patients Undergoing Radical Surgery.

Aims/Background Previous literature has indicated that sarcopenia is related to poor outcomes after radical resection for colorectal cancer (CRC). However, its effect on the postoperative clinical outcomes of CRC remains controversial. This study aimed to elucidate the predictive value of sarcopenia for postoperative complications and survival in CRC patients. Methods This investigation retrospectively assessed the clinical data of 226 CRC patients who underwent radical resection at the Department of Gastrointestinal Surgery, Affiliated Hospital of Zunyi Medical University from January 2018 to December 2020. Sarcopenia was diagnosed according to the recommendations of the Asian Working Group for Sarcopenia in 2019, and patients were categorized into sarcopenia and non-sarcopenia groups. Multivariate and univariate analyses were employed to assess the risk factors for postoperative complications. The Kaplan-Meier method and survival curve were used to analyze postoperative survival time. Cox proportional hazards regression models were used to evaluate risk factors affecting the prognosis of CRC patients. Results This investigation included 226 patients, of which 68 were diagnosed with sarcopenia. Furthermore, it was revealed that sarcopenia was linked with older age (p < 0.001), low body mass index (p < 0.001), high prevalence of diabetes (p = 0.002), high cystatin level (p = 0.017), and low 3rd lumbar spine (L3) planar skeletal muscle index (p < 0.001), but was not related to the tumour stage or the gender. Moreover, sarcopenia was also correlated with increased occurrence of all postoperative complications (p = 0.050). The results of the multivariate analysis indicated that sarcopenia was an independent risk factor for postoperative complications (odds ratio (OR): 7.154; 95% confidence interval (CI): 2.261-22.633; p = 0.017). The Kaplan-Meier analysis revealed that sarcopenia patients had significantly lower 5-year disease-free survival (DFS) (48.5% vs 59.5%; log-rank p = 0.033) and 5-year overall survival (OS) (57.4% vs 77.2%; log-rank p < 0.001) rates. Sarcopenia was an independent risk factor for poor DFS (hazard ratio (HR) = 1.404; p = 0.016) and OS (HR = 1.290; p = 0.021). Conclusion In CRC patients undergoing radical surgery, sarcopenia is an independent risk factor for postoperative complications. Sarcopenia may be a predictive factor for the prognosis and survival of CRC patients undergoing radical resection.

Exploring prognostic biomarkers in pathological images of colorectal cancer patients via deep learning.

Hematoxylin and eosin (H&E) whole slide images provide valuable information for predicting prognostic outcomes in colorectal cancer (CRC) patients. However, extracting prognostic indicators from pathological images is challenging due to the subtle complexities of phenotypic information. We trained a weakly supervised deep learning model on data from 640 CRC patients in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial dataset and validated it using data from 522 CRC patients in the cancer genome atlas (TCGA) dataset. We created the colorectal cancer risk score (CRCRS) to assess patient prognosis, visualized the pathological phenotype of the risk score using Grad-CAM, and employed multiomics data from the TCGA CRC cohort to investigate the potential biological mechanisms underlying the risk score. The overall survival analysis revealed that the CRCRS served as an independent prognostic indicator for both the PLCO cohort (p < 0.001) and the TCGA cohort (p < 0.001), with its predictive efficacy remaining unaffected by the clinical staging system. Additionally, satisfactory chemotherapeutic benefits were observed in stage II/III CRC patients with high CRCRS but not in those with low CRCRS. A pathomics nomogram constructed by integrating the CRCRS with the tumor-node-metastasis (TNM) staging system enhanced prognostic prediction accuracy compared with using the TNM staging system alone. Noteworthy features of the risk score were identified, such as immature tumor mesenchyme, disorganized gland structures, small clusters of cancer cells associated with unfavorable prognosis, and infiltrating inflammatory cells associated with favorable prognosis. The TCGA multiomics data revealed potential correlations between the CRCRS and the activation of energy production and metabolic pathways, the tumor immune microenvironment, and genetic mutations in APC, SMAD2, EEF1AKMT4, EPG5, and TANC1. In summary, our deep learning algorithm identified the CRCRS as a prognostic indicator in CRC, providing a significant approach for prognostic risk stratification and tailoring precise treatment strategies for individual patients.

Colorectal Cancer Outcomes: A Comparative Review of Resource-Limited Settings in Low- and Middle-Income Countries and Rural America.

Background/Objectives: Colorectal cancer remains a significant global health challenge, particularly in resource-limited settings where patient-centered outcomes following surgery are often suboptimal. Although more prevalent in low- and middle-income countries (LMICs), segments of the United States have similarly limited healthcare resources, resulting in stark inequities even within close geographic proximity. Methods: This review compares and contrasts colorectal cancer outcomes in LMICs with those in resource-constrained communities in rural America, utilizing an established implementation science framework to identify key determinants of practice for delivering high-quality colorectal cancer care. Results: Barriers and innovative, community-based strategies aimed at improving patient-centered outcomes for colorectal cancer patients in low resource settings are identified. We explore innovative approaches and community-based strategies aimed at improving patient-centered outcomes, highlighting the newly developed colorectal surgery fellowship in Sub-Saharan Africa as a model of innovation in this field. Conclusions: By exploring these diverse contexts, this paper proposes actionable solutions and strategies to enhance surgical care of colorectal cancer and patient outcomes, ultimately aiming to inform global health practices, inspire collaboration between LMIC and rural communities, and improve care delivery across various resource settings.

Clinicopathological Characteristics and Outcomes of Colorectal Cancer With Heterogenous Staining of Mismatch Repair Protein.

Scant data are available on heterogenous staining of mismatch repair protein in colorectal cancer. This study aimed to improve insights into clinicopathologic features and prognosis of colorectal cancer harboring heterogenous mismatch repair protein staining. A single-center retrospective observational study. This study was conducted in a tertiary referral center in China between 2014 and 2018. Colorectal cancers with heterogenous staining of mismatch repair protein were included. Clinicopathologic and molecular features, and survival outcomes were analyzed. A total of 151 out of 6721 colorectal cancers (2.2%) exhibited heterogenous staining for at least one mismatch repair protein, with intraglandular heterogeneity being the most common pattern (89.4%). Heterogenous MLH1 staining was significantly associated with distant metastasis (p = 0.03), while heterogenous MSH2 staining was associated with left-sided (p = 0.03) and earlier pT stage tumors (p = 0.02). The rates of microsatellite instability-high, KRAS and BRAF mutation were 12.6%, 47.3% and 3.4%, respectively. Microsatellite instability-high was significantly associated with higher intraglandular MSH6 heterogeneity frequency (p < 0.001) and decreased MSH6 expression level (< 27.5%, p = 0.01). BRAF mutation was associated with the coexistence of intraglandular and clonal heterogeneity (p = 0.003) and decreased PMS2 expression level (p = 0.01). Multivariable analysis revealed that progression-free survival was significantly associated with tumor stage (p = 0.003), stroma fraction (p = 0.004), and heterogenous PMS2 staining (p = 0.02). Overall survival was linked to tumor stage (p = 0.006) and BRAF mutation (p = 0.01). The limitations of this study include the absence of testing for MLH1 promoter methylation and mismatch repair gene mutations, its retrospective design, and insufficient data related to direct comparison with deficient mismatch repair and proficient mismatch repair colorectal cancer. Heterogenous mismatch repair protein staining in colorectal cancer exhibits distinct associations with tumor location, stage, microsatellite instability, BRAF mutation and prognosis. It is recommended to report MSH6 heterogeneity as it may indicate microsatellite instability-high. See Video Abstract.

Predictive nomogram of the clinical outcomes of colorectal cancer based on methylated SEPT9 and intratumoral IL-10+ Tregs infiltration

BackgroundGene methylation and the immune-related tumor microenvironment (TME) are highly correlated in tumor progression and therapeutic efficacy. Although both of them can be used to predict the clinical outcomes of colorectal cancer (CRC) patients, their predictive value is still unsatisfactory. Whether a combination risk model comprising these two prediction parameters performs better predictive effectiveness than independent factor is still unclear. Methylated Septin9 (mSEPT9) is an early diagnosis biomarker of CRC, in this study, we aimed to investigate mSEPT9-related biomarkers of immunosuppressive TME and identify the value of the combination risk model in predicting the clinical outcomes of CRC.MethodsImmunofluorescence staining was performed to clarify the correlation between intratumoral IL-10+ Treg infiltration and mSEPT9 in peripheral blood. Survival time, response to 5-fluorouracil (5-FU)-based chemotherapy and PD-1 blockade, and the probability of recurrence or metastasis were analyzed in study (197 CRC samples) and validation (195 CRC samples) sets to evaluate the efficacy of combination risk model. Potential mechanisms were explored by mRNA sequencing.ResultsHypermethylated SEPT9 in the peripheral blood of patients with CRC (stage I-III, and stage IV with resectable M1) before radical resection was positively correlated with high intratumoral IL-10+ Treg infiltration. The high-risk model revealed poor overall survival and progression-free survival, inferior therapeutic response to 5-FU-based chemotherapy and PD-1 blockade, and high probability of recurrence or metastasis. The underlying mechanisms may be associated with the increase in mSEPT9 and mediation of IL-10 via methionine metabolic reprogramming-induced infiltration of IL-10+ Tregs in the TME, which promotes tumor progression and resistance to 5-FU-based chemotherapy and PD-1 blockade.ConclusionsThe combination risk model of peripheral mSETP9 and intratumoral IL-10+ Treg infiltration in CRC can effectively predict prognosis, responsiveness to 5-FU-based chemotherapy and PD-1 blockade, and the probability of recurrence or metastasis. Therefore, this model can be used for precision treatment of CRC.

Sex differences in survival outcomes of early-onset colorectal cancer

Colorectal cancer (CRC) is one of the most fatal cancers in the United States. Although the overall incidence and mortality rates are declining, an alarming rise in early-onset colorectal cancer (EOCRC), defined as CRC diagnosis in patients aged < 50 years, was previously reported. Our study focuses on analyzing sex-specific differences in survival among EOCRC patients and comparing sex-specific predictors of survival in both males and females in the United States. We retrieved and utilized data from the Surveillance, Epidemiology, and End Results (SEER) program. EOCRC patients, between the ages of 20 and 49, were exclusively included. We conducted thorough survival analyses using Kaplan–Meier curves, log-rank tests, Cox regression models, and propensity score matching to control for potential biases. Our study included 58,667 EOCRC patients (27,662 females, 31,005 males) diagnosed between 2000 and 2017. The baseline characteristics at the time of diagnosis were significantly heterogeneous between males and females. Males exhibited significantly worse overall survival (OS), cancer-specific survival (CSS), and noncancer-specific survival (NCSS) in comparison to females in both the general cohort, and the matched cohort. Predictors of survival outcomes generally followed a similar pattern in both sexes except for minor differences. In conclusion, we identified sex as an independent prognostic factor of EOCRC, suggesting disparities in survival between sexes. Further understanding of the epidemiological and genetic bases of these differences could facilitate targeted, personalized therapeutic approaches for EOCRC.

Genetic Variation and Regulation of MICA Alters Natural Killer Cell-Mediated Immunosurveillance in Early-Onset Colorectal Cancer.

The incidence of colorectal cancer (CRC) among individuals under age 50, or early-onset CRC (EOCRC), has been rising over the past few decades for unclear reasons, and the etiology of the disease remains largely unknown. Known genetic risk factors do not explain this increase, pointing to possible environmental and as-yet unidentified genetic contributors and their interactions. Previous research linked genetic variation on chromosome 6 to increased CRC risk. This region harbors multiple immune genes, including the gene encoding Major Histocompatibility Complex (MHC) class I polypeptide-related sequence A (MICA). MICA is a polygenic ligand for the Natural Killer Group 2D receptor (NKG2D), a receptor expressed on Natural Killer (NK) cells and other lymphocytes. Given that intra-tumoral NK cell infiltration correlates with favorable CRC outcomes, we hypothesized that germline genetic variation in MICA could influence CRC risk. In a discovery set of 40,125 cases and controls, we show that the minor G allele at Chr6:31373718C>G (hg19) is associated with increased risk for CRC (odds ratio (OR) = 1.09, 95% confidence interval (CI) 1.04 - 1.15, p = 0.0009). The effect is stronger in EOCRC (OR = 1.26, 95% CI 1.08 - 1.44, p = 0.0023) than in those 50 and over (OR = 1.07, 95% CI 1.02 - 1.13; p = 0.012) (Ratio of ORs = 1.32, 95% CI 1.14 - 1.52, p = 0.0002). In an independent validation set of 77,983 cases and controls, the adjusted interaction by age-of-onset was significant at OR = 1.15 (95% CI 1.03 - 1.34, p = 0.0150) with a higher risk in EOCRC. Expression quantitative trait locus analysis in normal colonic epithelia showed that MICA RNA expression decreases linearly with each additional copy of the minor G allele (p = 3.345 × 10e-18). Bulk RNA analysis of the tumor immune microenvironment revealed that tumors from patients with CG or GG genotypes have lower resting and activated NK cell infiltration as compared to tumors from patients with CC genotype. Multiplex immunofluorescence analysis demonstrated that patients with a G allele (i.e. CG or GG genotype, but not CC genotype) have a statistically significant decrease in the number of NK cells in tumor compared to adjacent normal colonic mucosa. Taken together, population-based epidemiologic, molecular, genetic, cellular and immunologic evidence demonstrate that MICA genotype is associated with increased risk of EOCRC and reduced number of NK cells in colorectal tumors, suggesting that patients with a G allele have altered NK cell-mediated immunosurveillance. These novel findings suggest that EOCRC may have a previously unrecognized innate immune-mediated etiology which merits further investigation.

Abstract B166: Impact of rurality on early-onset colorectal cancer outcomes: Age, geographic disparities, and the need for improved access and awareness in the United States

Abstract BACKGROUND: While overall colorectal cancer (CRC) rates have stabilized or declined in the United States (U.S.), early-onset CRC (EO-CRC), diagnoses before age 50, has increased. Rural U.S. residents face a higher CRC incidence (43.9 vs. 40.1 per 100,000) than urban residents. CRC mortality, once highest in the Northeast, is now most prevalent in the South and Midwest, particularly among Non-Hispanic Black populations. This geographic shift is also evident in EO-CRC. Existing literature lacks comprehensive analysis on the influence of rurality and age at CRC diagnosis. In this study, we sought to elucidate the relationships between age at diagnosis with CRC outcomes, while examining the moderating role of rurality. Methods: We used data from the 2006-2020 Surveillance, Epidemiology, and End Results (SEER) Program. Rurality was defined using census tract level U.S. Department of Agriculture (USDA)’s 2010 Rural Urban Commuting Area (RUCA) codes: rural (codes 8, 9, 10) and urban (all other listed codes). We conducted multilevel regression modeling (logistic and Cox proportional hazards) to examine the associations between age at diagnosis, rurality, and CRC outcomes (late-stage diagnosis and survival), adjusting for race, marital status, sex, and year of diagnosis. Results: We identified 835,907 patients aged 20-79 from the 2006-2020 SEER program. Most patients lived in urban areas (86%), were non-Hispanic white (66%), and married (41%). After adjusting for marital status, race, sex, and diagnosis year, we found that patients aged 30-39 (aOR: 1.49, 95% CI: 1.44–1.55) and 40-49 (aOR: 1.43, 95% CI: 1.39–1.46) had over a 40% increased likelihood of late-stage CRC compared to patients aged 50-59. Urban patients aged 30-39 had a 52% higher likelihood of late-stage CRC (aOR: 1.52, 95% CI: 1.46–1.58). Patients aged 20-29 (aOR: 0.81, 95% CI: 0.77–0.86) had a reduced risk of CRC death compared to those aged 50-59. Conversely, patients aged 40-49 (aOR: 1.09, 95% CI: 1.07–1.11), 60-69 (aOR: 1.16, 95% CI: 1.14–1.17), and 70-79 (aOR: 1.39, 95% CI: 1.28–1.36) had increased risks of CRC death compared to patients aged 50-59. Rural patients aged 20-29 (aOR: 0.79, 95% CI: 0.68–0.94) and 30-39 (aOR: 0.95, 95% CI: 0.87–1.03) had a reduced risk of CRC death compared to rural patients aged 50-59. Conclusion: We observed that patients aged 30-49 were more likely to be diagnosed with late- stage CRC compared to those aged 50-59, particularly in urban areas. To reduce the burden of EO-CRC and prevent advanced-stage diagnoses in young adults, it is essential to enhance access to care and raise awareness of CRC symptoms among younger Americans. Future research should explore urban -rural barriers to healthcare access, including the role of healthcare infrastructure, transportation, and provider availability, to develop strategies for improving EO-CRC early detection and treatment outcomes. Citation Format: Meng-Han Tsai, Justin X. Moore, Caitlyn Grunert. Impact of rurality on early-onset colorectal cancer outcomes: Age, geographic disparities, and the need for improved access and awareness in the United States [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B166.

Abstract C106: Enhanced characterization of molecular attributes through multi-omics analysis and comprehensive evaluation of global and local genomic ancestry in colorectal cancer among Hispanic-Latinos

Abstract Introduction: Colorectal cancer (CRC) remains a significant public health challenge, representing the second leading cause of cancer-related mortality in the United States. Although mortality rates have generally decreased, the Hispanic/Latino (H/L) population in the Los Angeles area still experiences mortality rates up to 20% higher than those of their Caucasian American counterparts. Additionally, they are often diagnosed at a younger age and with more advanced disease stages, highlighting significant disparities in CRC outcomes. Currently, there are limited studies integrating clinical and multi-omics data from H/L populations, which are crucial for understanding the implications of colorectal tumorigenesis and addressing these disparities effectively. Methods: Clinical and genomic sequencing data were obtained from 60 primary CRC Tumor/Normal (T/N) samples within the Hispanic/Latino (H/L) population in the Los Angeles area through the PE-CGS network. For comparison, we analyzed 3,578 samples from non-Hispanic Whites (NHW) obtained from public databases. Additionally, we retrieved three CRC samples with spatial transcriptomic (ST) data from the 10xGenomics database. Using Whole Exome and RNA sequencing data, we performed somatic mutations, somatic copy number alterations (SCNAs), differential gene expression, cellular pathways, gene fusions, and global &amp; local genomic ancestry analyses. The ST data underwent analysis utilizing newly released bioinformatics tools. Clinical and genomic data were integrated. Results: In these studies, distinct Amerindian (AMR) genomic ancestry proportion, age at diagnosis, and tumor localization patterns were observed, alongside significant mutations in key genes such as APC, TP53, and KRAS. The studies revealed evident cancer heterogeneity, influenced by factors such as mutation type, microsatellite instability, tumor subsite, and ethnicity. Additionally, several previously well-defined SCNAs were detected in the majority of tumors. Comparative analysis of gene expression and cellular pathways between H/L and NHW samples revealed distinct patterns. Furthermore, we identified gene fusions that potentially contribute to oncogenic activity in CRC. Ancestry analysis pointed to a predominant AMR ancestry. Notably, distinct associations of genetic ancestry with CRC tumor clinicopathological characteristics were identified. ST analysis delineated separate cancer, immune, and stroma components within the tumors. Conclusion: Our research has explored the molecular profiling of CRC tumors in H/L patients, providing crucial insights into the characterization of CRC tumors at the DNA and RNA levels, as well as the complex clinical and genomic diversity within our target population. Additionally, it offers valuable insights into the heterogeneity of CRC tumors and the tumor microenvironment. These findings establish the groundwork for subsequent projects, potentially leading to precision medicine approaches. Citation Format: Enrique I. Velazquez-Villarreal, Brigette Waldrup, Yonatan Amzaleg, Yuxin Jin, Mackenzie Postel, Donna Loza, Serina Ovalle, Elizabeth Quino, Carmen Chavez, Julie Culver, Mariana C. Stern, Heinz-Josef Lenz, David W. Craig, John D. Carpten. Enhanced characterization of molecular attributes through multi-omics analysis and comprehensive evaluation of global and local genomic ancestry in colorectal cancer among Hispanic-Latinos [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C106.

Abstract A009: Determinants of increased generalized self-efficacy among Hispanic/Latino colorectal cancer patients participating in a Cancer Moonshot Study

Abstract Background: Colorectal cancer (CRC) accounts for a greater proportion of all cancer deaths among Hispanic/Latino/a/x (H/L) individuals compared to Non-Hispanic White (NHW) subjects. However, the tumor landscape and key determinants of outcomes for CRC among H/L patients remain understudied. Methods: As a Cancer Moonshot initiative, we launched the “Enfrentando el Cancer en Comunidad” (ENLACE) study, which engages H/L CRC patients to characterize their germline genetics and tumor genomic landscape, and to collect data to identify determinants of participation in genetics/genomics research and cancer outcomes. H/L CRC patients &amp;gt;=18 years of age are being recruited from two healthcare facilities: a safety-net hospital, Los Angeles General Medical Center (LA Gen), and a university medical center, USC Norris Comprehensive Cancer Center (Norris). An H/L bilingual team administered surveys to assess patient demographics, acculturation level, Latino values, health literacy, numeracy, CRC risk factors, genetics knowledge (Knowgene scale), and generalized self-efficacy (GSE) upon recruitment for the study, and after return-of-results (ROR) of somatic and germline testing. Results: 165 H/L CRC patients have joined the ENLACE study, with 105 completing baseline surveys (56 male, median age 53 (IQR = 45-60)), and 39 with finalized ROR. Most of the participants self-identified as White (58.1%), were Mexico-born (52.4%), and married (50%). Patients from Norris (n = 33) were more likely to be US-born (55%), college graduates (21%), and annually earn at least $100,000 (69%) while employed full-time (45%) than LA Gen patients (all p-values &amp;lt;0.01). Additionally, Norris patients had higher numeracy and health literacy scores at baseline than LA Gen (p = 0.006 &amp; p = 0.042, respectively). LA Gen patients (n = 72) showed higher scores for familism, respect, traditional gender roles, material success, and mainstream values in the Latino-American cultural values scale (all p-values &amp;lt; 0.05). Higher levels of GSE across all patients were associated with increased numeracy (p = 0.014). LA Gen participants with a higher score for GSE, had on average, higher subscores for material success (p = 0.011), competition and personal achievements (p = 0.07), and mainstream values (p = 0.051), and decreased uncertainties about genetic testing (p = 0.05). A multivariable logistic regression model adjusted for treatment facility, acculturation, age, gender, and income reported that a 1 unit increase in numeracy was statistically significantly associated with 1.62 times the odds of having a greater than the median GSE score (95% CI: 1.09-2.39, p = 0.016). After ROR, a decrease in the number of times participant selected “Don’t know” in the KnowGene scale was reported (p &amp;lt;0.001). Conclusion: We report differences in baseline characteristics for ENLACE participants across healthcare facilities and determinants of generalized self-efficacy. These findings can help inform future interventions to improve self-efficacy and optimize engagement of H/L patients navigating CRC treatment. Citation Format: Joel Sanchez Mendez, Carmen Chavez, Lucia Enriquez, Julie O Culver, Charité N Ricker, Natalia Gutierrez, Sandra Algaze, Lourdes Baezconde-Garbanati, John D. Carpten, Heinz-Josef Lenz, Mariana C. Stern. Determinants of increased generalized self-efficacy among Hispanic/Latino colorectal cancer patients participating in a Cancer Moonshot Study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A009.

Abstract C157: Unraveling Early Onset Disparities and Determinants: A Two-decade Analysis of Colorectal Cancer Trends in Texas

Abstract Background: Colorectal cancer (CRC) remains a significant public health concern in the United States, with substantial disparities observed in survival rates and age at diagnosis among different racial and ethnic groups. In Texas counties bordering Mexico, which have predominantly Hispanic populations, show higher CRC diagnoses. Hispanic patients generally exhibit lower screening rates, higher mortality, and late-stage diagnosis compared to non- Hispanic counterparts. Understanding the factors behind these disparities is crucial for developing targeted interventions to improve outcomes and reduce the burden of CRC. Methods: Using data from the Texas Cancer Registry, a retrospective study examined CRC survival rates and age at diagnosis among 235,076 patients of various racial and ethnic groups in Texas from 1995 to 2016. The association between Race and ethnicity and survival time over two periods (1995-2005 and 2006-2016) was analyzed using Kaplan-Meier survival analysis and pairwise comparisons. Additionally, the effects of Race and ethnicity on age at diagnosis were examined for the same periods using Welch ANOVA and posthoc comparisons. Results: Persistent survival disparities were observed, with Black patients facing the lowest median survival times across both periods (1995-2005 and 2006-2016). Hispanic patients showed significantly lower median survival rates compared to their non-Hispanic counterparts. Comparisons between races showed significant differences in median survival time between the two periods (1995-2005 and 2006-2016). Black: Hispanic patients showed no significant improvement in survival time between the periods. Significant improvements in survival time were observed in Black: non-Hispanic, White: Hispanic, and White: non-Hispanic patients. Lastly, the mean age at diagnosis depended on the ethnicity of the patient, with Hispanic patients displaying an earlier onset of CRC compared to non-Hispanic equivalents. Hispanic ethnicity was associated with an earlier onset of CRC compared to non-Hispanic counterparts. Conclusion: Geographic and ethnic disparities significantly influence CRC outcomes in Texas. Hispanic populations in border counties face increased risks due to lower screening and socioeconomic challenges. The rising incidence of early-onset CRC, particularly among younger, socioeconomically disadvantaged, and minority populations, necessitates targeted public health interventions to improve screening, early detection, and treatment access. Addressing these disparities is crucial to enhancing CRC survival rates and reducing mortality across diverse demographic groups. Citation Format: Tyler J Torres, Elias Arellano Villanueva, Yossef Alsabawi, Manish Tripathi. Unraveling Early Onset Disparities and Determinants: A Two-decade Analysis of Colorectal Cancer Trends in Texas [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C157.

Colorectal cancer care continuum: Navigating screening, treatment, and outcomes disparities.

This review investigates the disparities in colorectal cancer screening, treatment, and outcomes among different racial, ethnic, socioeconomic, and geographic groups. Although there has been progress, notable disparities continue to exist as a result of socioeconomic status, access to healthcare, and systemic prejudices. Approaches to tackle these challenges involve expanding screening access, enhancing healthcare utilization, addressing socioeconomic obstacles, ensuring fair treatment, and boosting representation in research.

The Value of Systemic Inflammatory Indices for Predicting Early Postoperative Complications in Colorectal Cancer.

Background and Objectives: Systemic inflammatory indices have been largely investigated for their potential predictive value in multiple inflammatory, infectious, and oncological diseases; however, their value in colorectal cancer is still a subject of research. This study investigates the dynamics of pre- and postoperative values of NLR, PLR, SII, and MLR in patients with colorectal cancer and their predictive value for early postoperative outcomes. Materials and Methods: A 2-year retrospective cohort study was performed on 200 patients operated for colorectal adenocarcinoma. Systemic inflammatory indices were calculated based on complete blood count preoperatively and on the first and sixth postoperative days. The patients were divided into two groups based on their emergency or elective presentation. The pre- and postoperative values of serum inflammatory biomarkers and their correlations with postoperative outcomes were separately analyzed for the two study subgroups. Results: There were no significant differences in sex distribution, addressability, associated comorbidities, or types of surgery between the two groups. Patients in the emergency group presented higher preoperative and postoperative values of WBC, neutrophils, NLR, and SII compared to elective patients. The postsurgery hospital stays correlated well with pre- and postoperative day one and day six values of NLR (p = 0.001; 0.02; and <0.001), PLR (p < 0.001), SII (p = 0.037; <0.001; <0.001), and MLR (p = 0.002; p = 0.002; <0.001). In a multivariate analysis, reintervention risk was higher for emergency presentation and anemia, and lower in right colon cancer. In the emergency group, a multivariate model including age, MLR PO1, and pTNM stage was predictive for severe postoperative complications (AUC ROC 0.818). First-day postoperative inflammatory indices correlated well with sepsis, with the best predictive value being observed for the first postoperative day NLR (AUC 0.836; sensibility 88.8%; specificity 66.7%) and SII (AUC 0.796; sensitivity 66.6%; specificity 90%). For elective patients, the first postoperative day PLR and anemia were included in a multivariate model to predict Clavien-Dindo complications graded 3 or more (AUC ROC 0.818) and reintervention (AUC ROC 0.796). Conclusions: Easy-to-calculate and inexpensive systemic inflammatory biomarkers could be useful in predicting early postoperative outcomes in colorectal cancer for both elective and emergency surgery.

Evaluating the Outcomes in Patients with Colorectal Cancer Using the Malnutrition Universal Screening Tool: A Systematic Review.

The current systematic review aimed to evaluate the Malnutrition Universal Screening Tool (MUST) for its effectiveness in determining patient outcomes (length of hospital stay, postoperative complications, infection rates, and survival) for colorectal cancer. Utilizing a comprehensive search strategy, this review mined literature up to December 2023 from the PubMed, Scopus, and Embase databases. The focus was on identifying studies that scrutinize the prognostic value of MUST in relation to hospital outcomes in colorectal cancer contexts. Adherence to PRISMA guidelines ensured a systematic approach, encompassing various study designs and outcome measures. Among the seven studies incorporating 1950 patients, a significant correlation emerged between MUST scores and key hospital outcomes. Specifically, patients categorized as high MUST risk faced longer hospital stays, with a mean length of stay for high-risk patients extending up to 26.6 days compared to 14 days for those at lower risk. The prevalence of postoperative complications was substantially higher in the high-risk group, with up to 41.4% of high MUST risk patients experiencing severe complications (Clavien-Dindo 3-5) compared to 8.5% in the low-risk category. Notably, the review found that high MUST scores were strongly predictive of increased postoperative complications and a prolonged hospital stay, underscoring the tool's critical predictive utility for quality of life and use in clinical settings. Therefore, MUST's capability to predict longer hospital stays and a higher incidence of postoperative complications among high-risk patients highlights its essential function in preoperative evaluations and supports the integration of MUST into routine clinical assessments.

1584P Association of travel burden (TB) with colorectal cancer (CRC) outcomes in resource-limited settings (RLS)

1584P Association of travel burden (TB) with colorectal cancer (CRC) outcomes in resource-limited settings (RLS)

Impact ofCOVID-19 Pandemic on the Clinical and Pathologic Characteristics ofColorectal Cancer: A Retrospective Multicenter Study in South Korea.

The COVID-19 pandemic has influenced various aspects of colorectal cancer (CRC) patient care, including diagnosis, treatment, and outcomes. This study assesses the pandemic's impact on CRC patients. We performed a retrospective analysis of medical records for CRC patients who underwent surgery at five hospitals affiliated with Hallym University from January 2017 to December 2022. Patients were divided into two groups: the pre-COVID group (2017-2019) and the COVID group (2020-2022). Among 2038 patients, 987 (48.4%) were in the pre-COVID group, and 1051 (51.6%) were in the COVID group. The COVID group had more patients with two or more comorbidities (P < 0.001) and a higher incidence of rectal cancer (P = 0.010). While the rates of laparoscopic surgeries were similar, the COVID group had increased emergency surgeries (P = 0.005) and diversion procedures (P = 0.002). Additionally, the COVID group faced more overall complications (P < 0.001) and severe complications (Grade III-V, P = 0.004). There was a rise in lymphovascular invasion (P < 0.001) and T4 stage tumors (P < 0.001) within the COVID group. Despite these differences, both groups had similar 2-year overall survival rates (P = 0.409). Although patients treated during the COVID period experienced more frequent stoma formation, complications, and adverse prognostic factors, there were no differences in short-term oncologic outcomes, which was likely due to the follow-up period being insufficient to detect differences in OS.

Integrated single-cell and bulk RNA-seq analysis identifies a prognostic T-cell signature in colorectal cancer

Colorectal cancer (CRC) is a major contributor to global morbidity and mortality, necessitating more effective therapeutic approaches. T cells, prominent in the tumor microenvironment, exert a crucial role in modulating immunotherapeutic responses and clinical outcomes in CRC. This study introduces a pioneering method for characterizing the CRC immune microenvironment using single-cell sequencing data. Unlike previous approaches, which focused on individual T-cell signature genes, we utilized overall infiltration levels of colorectal cancer signature T-cells. Through weighted gene co-expression network analysis, Lasso regression, and StepCox analysis, we developed a prognostic risk model, TRGS (T-cell related genes signatures), based on six T cell-related genes. Multivariate Cox analysis identified TRGS as an independent prognostic factor for CRC, showcasing its superior predictive efficacy compared to existing immune-related prognostic models. Immunoreactivity analysis revealed higher Immunophenoscore and lower Tumor Immune Dysfunction and Exclusion scores in the low-risk group, indicating potential responsiveness to immune checkpoint inhibitor therapy. Additionally, patients in the low-risk group demonstrated heightened sensitivity to 5-fluorouracil-based chemotherapy regimens. In summary, TRGS emerges as a standalone prognostic biomarker for CRC, offering insights to optimize patient responses to immunotherapy and chemotherapy, thereby laying the groundwork for personalized tumor management strategies.

Preoperative nutritional factors as predictors of postoperative early outcomes in colorectal cancer - A prospective cohort study.

in colorectal cancer (CRC) surgery, preoperative nutritional factors are often overlooked or underestimated. This situation represents a significant deficiency that may negatively affect patients' postoperative recovery processes. the objective of this study was to evaluate the impact of preoperative malnutrition, sarcopenia, obesity, and dietary inflammatory potential on early postoperative outcomes in CRC. preoperative sarcopenia was identified using European Working Group on Sarcopenia in Older People (EWGSOP2) criteria based on skeletal muscle obtained from computed tomography (CT) scans, and malnutrition was identified using Global Leadership Initiative on Malnutrition (GLIM) criteria. Visceral and subcutaneous obesity were assessed using CT scans. The energy-adjusted dietary inflammatory index (E-DII) was calculated from dietary records. a total of 121 patients were included in the study, and 45.5 % of them were malnourished according to GLIM, 15.7 % were sarcopenic according to EWGSOP2. Multivariate logistic regression analysis showed that sarcopenia [OR = 3.973 (1.028-15.353), p = 0.043], malnutrition [OR = 3.954 (1.479-10.575), p = 0.006], and E-DII [OR = 4.955 (1.397-17.571), p = 0.013] were independent risk factors for complications. Sarcopenia [OR = 6.894 (1.080-43.998), p = 0.041] was also risk factor for long-term hospitalization. a comprehensive evaluation of preoperative nutrition and related factors in CRC surgery, along with timely interventions, has the potential to significantly reduce postoperative complications and length of hospital stays.

Real-world treatment costs of first-line treatment for metastatic colorectal cancer: a survey of the JCOG colorectal cancer study group.

Although treatment outcomes for metastatic colorectal cancer (mCRC) have dramatically improved over the past few decades, drug costs have also significantly increased. This study aimed to investigate which first-line treatment regimens for mCRC are actually used (frequency) in Japanese practice and at what cost. We collected data on patients with mCRC who received first-line treatment at 37 institutions of the Japan Clinical Oncology Group Colorectal Cancer Study Group from July 2021 to June 2022, and calculated the cost of regimens. The cost per month of each regimen was estimated based on standard usage, assuming a patient with a weight of 70kg and a body surface area of 1.8m2. We categorized the regimens into very high-cost (≥1 000 000 Japanese yen [JPY]/month), high-cost (≥500 000 JPY/month), and others (<500 000 JPY/month). The study included 1880 participants, 24% of whom were≥75years. Molecular targeted containing regimens were received by 78% of the patients. The most frequently used regimen was the doublet regimen (fluoropyrimidine with either oxaliplatin or irinotecan) plus bevacizumab (43%), followed by doublet plus cetuximab or panitumumab (21%). The cost of molecular targeted drugs-containing regimens (ranging from 85 406 to 843 602 JPY/month) is much higher than that of only cytotoxic drug regimens (ranging from 17 672 to 51 004 JPY/month). About 16% received high-cost treatments that included panitumumab-containing regimens and pembrolizumab (17% of patients aged ≤74years and 11% of patients aged ≥75years). About 16% of mCRC patients received first-line treatment with regimens costing >500 000JPY/month, and molecular targeted drugs being the main drivers of cost.

UCN-Centric Prognostic Model for Predicting Overall Survival and Immune Response in Colorectal Cancer.

Colorectal cancer (CRC), a prevalent malignancy, ranks third in global incidence and second in mortality rates. Despite advances in screening methods such as colonoscopy, the accurate diagnosis of CRC remains challenging due to the absence of reliable biomarkers. This study aimed to develop a robust prognostic model for precise CRC outcome prediction. Employing weighted co-expression network analysis (WGCNA) and Cox regression analysis on data from The Cancer Genome Atlas (TCGA), we identified a panel of 12 genes strongly associated with patient survival. This gene panel facilitated accurate CRC outcome predictions, which is also validated via the external validation cohort GSE17536. We conducted further investigations into the key gene, urocortin (UCN), using single-cell transcriptomic data and immune infiltration analysis in CRC patients. Our results revealed a significant correlation between high UCN expression and the reduced prevalence of key immune cells, including B cells, CD4+ cytotoxic T cells, CD8+ T cells, and NKT cells. Functional experiments showed that UCN gene interference in the CRC cell lines significantly decreased cancer cell proliferation, underscoring UCN's role in intestinal immunity modulation. The UCN-centric prognostic model developed enhances prognosis prediction accuracy and offers critical insights for CRC diagnosis and therapeutic interventions.