Young Colorectal Cancer Patients Research Articles

Prediction of Postoperative Survival in Young Colorectal Cancer Patients: A Cohort Study Based on the SEER Database.

Objective Our aim is to make accurate and robust predictions of the risk of postoperative death in young colorectal cancer patients (18-44 years old) by combining tumor characteristics with medical and demographic information about the patient. Materials and Methods We used the SEER database to retrieve young patients diagnosed with colorectal cancer who had undergone surgery between 2010 and 2015 as the study cohort. After excluding cases with missing information, the study cohort was divided in a 7 : 3 ratio into a training dataset and a validation dataset. To assess the predictive ability of each predictor on the prognosis of colorectal cancer patients, we used two steps of Cox univariate analysis and Cox stepwise regression to screen variables, and the screened variables were included in a multifactorial Cox proportional risk regression model for modeling. The performance of the model was tested using calibration curves, decision curves, and area under the curve (AUC) for receiver operating characteristic (ROC). Results After excluding cases with missing information (n = 23,606), a total of 11,803 patients were included in the study with a median follow-up time of 45 months (1-119). In the training set, we determined that ethnicity, marital status, insurance status, median annual household income, degree of tumor differentiation, type of pathology, degree of infiltration, and tumor location had independent effects on prognosis. In the training dataset, taking 1 year, 3 years, and 5 years as the time nodes, the areas under the working characteristic curve of subjects are 0.825, 0.851, and 0.839, respectively, and in the validation dataset, they are 0.834, 0.837, and 0.829, respectively. Conclusion We trained and validated a model using a large multicenter cohort of young colorectal cancer patients with stable and excellent performance in both training and validation datasets.

Young-onset colorectal cancer: Insights from an English population-based study.

Young colorectal cancer (CRC) patients are reported to have more aggressive disease, an advanced stage at diagnosis and conflicting survival outcomes. The aim of this study was to analyse the demographics, clinicopathological features and prognosis of young CRC at a population-based level in England. This is a retrospective review of all CRC patients using data from Public Health England collated from regional cancer registries in England between 2010 and 2014. Those aged 40 years and below were classified as young and those over 40 were classified as older. Overall, 167,501 patients had CRC. Of these, 3757 patients (2.2%) were young. Right-sided cancers were more common in younger patients (48.2% vs. 32.9%, p< 0.001). Favourable histological grade (well or moderately differentiated) was present in 83.1% and 73.5% of young and older patients, respectively. The percentage of young and older patients being diagnosed at an early stage (Stages 1 and 2) was similar at 40.6% vs. 42.9%. The 5-year age- and gender-adjusted relative survival (cancer specific) was significantly better for young patients when compared with older patients diagnosed with CRC. Additionally, overall 5-year survival was better for younger patients (71.6% and 47.2%, p< 0.001 in young and older CRC patients respectively). The increased right-sided colon cancer in young CRC patients in England warrants attention. Contrary to previous reports, they do not present at later stage. Young CRC patients have better overall and relative survival than older patients with CRC.

Incorporation of functional status, frailty, comorbidities and comedication in prediction models for colorectal cancer survival.

Limitations in functional status, frailty, multiple comorbidities and comedications are common among older colorectal cancer (CRC) patients. We investigated whether adding these factors could improve the predictive value of a reference model containing age, sex, tumor stage and location for prediction of 5-year overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), recurrence-free survival (RFS) and nondisease-specific survival (nDSS) for all CRC patients as well as for younger (<65 years) and older patients (≥65 years). Overall, 3410 CRC patients from the DACHS study were analyzed and area under receiver operating characteristic curves (AUC) and net reclassification improvements (NRI) were assessed. In prediction of OS, the reference model plus functional status was identified as the best model among all CRC patients (AUC: 0.762) and younger CRC patients (AUC: 0.820). In older CRC patients, comorbidity should additionally be added (AUC: 0.747). For nDSS, the reference model plus comorbidity and frailty had the best predictive performance in all CRC patients (AUC: 0.776). For the outcomes DFS (AUC: 0.727), DSS (AUC: 0.838) and RFS (AUC: 0.784), the reference model was already the best model in all CRC patients because no significant NRIs were observed. The pattern "The less CRC-specific the survival outcome and the older the CRC patients, the more relevant the inclusion of functional status, comorbidity, and frailty in CRC prognostic scores is" was observed. Thus, different nomograms for younger and older CRC patients for 1-, 3- and 5-year OS prognosis estimation are being suggested.

Hereditary evaluation and genetic counselling in young individuals with colorectal cancer in a population-based cohort

AimEarly-onset colorectal cancer should raise suspicions of a hereditary colorectal cancer (CRC) syndrome, including Lynch syndrome (LS) and Familial Adenomatous Polyposis (FAP). Collection of family history and genetic counselling (GC) is mandatory but previous studies have revealed low awareness of hereditary CRC among clinicians why there has been an incentive to implement universal LS screening. In this population-based cohort study, we aimed to observe the uptake of GC in the Swedish South-Eastern medical care region for young CRC patients and to investigate the frequency of patients diagnosed with LS. MethodsPatients below 50 years of age diagnosed with CRC between 2008 and 2017 were identified from the national Swedish Colorectal Cancer Registry. Medical records were reviewed regarding family history, co-morbidity and referral for GC, with a follow-up time of at least three years. ResultsThe analysis included 278 patients with 287 tumours, 108 (38%) located in rectum and 179 (62%) in colon. One hundred sixteen (42%) individuals were referred to the Regional Clinical Genetics service, whereof 74 (27%) underwent complete investigation. Thirteen (18%) patients were identified with a mutation, eleven (15%) had LS and two (3%) FAP. The remaining 61 (82%), without proven mutation, were considered as familial CRC. Younger age correlated with a higher chance of referral for GC. ConclusionThe study found that only a minority of young CRC patients underwent genetic counselling, contrary to clinical guidelines. Hereditary CRC is therefore probably underdiagnosed even among young individuals.

Understanding the psychosocial impact of colorectal cancer on young-onset patients: A scoping review.

ObjectiveThe incidence of young‐onset (<50 years) colorectal cancer (CRC) has been increasing internationally. The psychosocial experience of younger cancer patients is vastly different from older patients, especially in domains such as financial toxicity, body image, and sexual dysfunction. What is unknown is the cancer type‐specific experience. The aim of the current scoping review was to examine (1) the psychosocial factors and/or outcomes associated with young‐onset CRC and (2) other determinants that influences these outcomes.MethodsA systematic search was conducted on four databases (PubMed, CINAHL, Scopus and PsycINFO) from inception to December 2020 using key terms and combinations. Primary literature that examined the psychosocial (e.g., quality‐of‐life, emotional, social, sexual) impact of young‐onset CRC were included.ResultsA total of 1389 records were assessed by four reviewers, with a total of seven studies meeting inclusion criteria (n = 5 quantitative, n = 1 qualitative and n = 1 case series). All studies indicated there was significant psychosocial impact in younger CRC patients, including emotional impact, social impact, physical burden, sexual impact, work impact, unmet needs, financial impact and global quality of life. Three studies explored other determinants that influenced the psychosocial experience and found that socioeconomic background (e.g., being female, lower education), CRC treatment (e.g., chemotherapy) and health status were associated with worse psychosocial impact.ConclusionsYoung‐onset CRC patients face severe psychosocial impact unique to this age group, such as self‐image and sexual impact. Social support services and resources needs to be uniquely tailored. More empirical investigations are required to understand its long‐term impact and influence of other psychosocial domains.

Iron Deficiency Anemia and Hematochezia Are Red Flags for Colorectal Cancer in Young Patients

Incidence of colorectal cancer (CRC) diagnosed in individuals under age 50, or young-onset colorectal cancer (YCRC), is rising. Iron deficiency anemia (IDA) and hematochezia are potential red-flag symptoms of YCRC, however there is minimal data on the magnitude of risk associated with these symptoms, and therefore mixed guidance on appropriate evaluation of these symptoms in patients under age 50.

Trends of Colonic Neoplasia in US Outpatient Endoscopy Centers.

A variety of studies have shown rising trends in the occurrence of colorectal cancer in younger patients as opposed to falling trends among older patients aged 55years or more. We hypothesized that the time trends of benign colonic precursor lesions would reveal similar patterns. The present study was designed to test this hypothesis in a large nationwide sample of the US population undergoing colonoscopy in community-based endoscopy centers. The Inform Diagnostics database is an electronic repository of histopathologic records of patients distributed throughout the USA. A cross-sectional study analyzed the detection rates of sessile serrated adenomas (SSA), hyperplastic polyps (HP), tubular adenomas (TA), traditional serrated adenomas (TSA), or adenocarcinomas (colorectal cancer, CRC) in 2,910,174 colonoscopies done 2008-2020. During the 13-year time period, the rate of SSA showed a significant rise, both in patients younger and older than 55years. HP and TA both showed a significant decline during the same time period. The trends of CRC in the older age group decreased significantly between 2008 (or its peak in 2012) and 2020. The trends of CRC in the younger age group increased significantly between 2008 and its peak in 2017. The age-specific time trends of benign and malignant colonic neoplasia are characterized by dissimilar temporal patterns. Such dissimilarity could suggest that besides a set of shared risk factors that affect all types of colonic neoplasia alike, there is yet another set of environmental risk factors that specifically influence malignant transformation.

Predictors of Lymph Node Metastasis in T1 Colorectal Cancer in Young Patients: Results from a National Cancer Registry.

The objective of this study is to fill the knowledge gap by examining predictors of lymph node metastasis (LNM) in young patients, less than 45 years, using a national cancer registry. Methods: Patients diagnosed with T1 colorectal cancer were identified in the Surveillance, Epidemiology, and End Results registry. In total, 692 patients with T1 colorectal cancer were identified. Most tumors occurred in white race (77.7%), between 40 and 44 years of age (49.4%), with grade III tumor differentiation (59.8%) and 1 to 1.9 cm size (32.2%), and were left-sided tumors (61.1%). The overall rate of LNM was 22.5% (n = 149). LNM was associated with tumor grade IV (undifferentiated) (odds ratio (OR) 2.94, CI: 1.06–8.12; p = 0.038), and increasing tumor size (1 cm–1.9 cm: OR 2.92, CI: 1.71–4.97, p < 0.001; 2.0 cm–2.9 cm: OR 2.00, CI: 1.05–3.77, p = 0.034; and ≥3.0 cm: OR 2.68, CI: 1.43–5.01, p = 0.002). Five-year cancer-specific survival for patients with LNM was 91% and for patients without LNM this was 98%. Adjusted cox proportion models showed that LNM was associated with a four times higher rate of mortality (hazard ratio (HR) 4.43, CI: 1.27–15.52, p = 0.020). In this population-based analysis of patients with T1 colorectal cancer, tumor size and grade were significant predictors of LNM.

Survey of germline variants in cancer-associated genes in young adults with colorectal cancer.

Colorectal cancer (CRC) incidence in young adults is rising. Identifying genetic risk factors is fundamental for the clinical management of patients and their families. This study aimed to identify clinically significant germline variants among young adults with CRC. Whole-exome sequencing data of blood-derived DNA from 133 unrelated young CRC patients (<55 years of age) underwent a comprehensive analysis of 133 cancer-predisposition/implicated genes. All patient tumors were evaluated for mismatch repair deficiency (dMMR). Among 133 patients (aged 16-54 years), 15% (20/133) had clinically actionable pathogenic or likely pathogenic (P/LP) variants in at least 1 well established cancer-predisposing gene: dMMR genes (6), MUTYH [bi-allelic (2), mono-allelic (3)], RNF43 (1), BMPR1A (1), BRCA2 (4), ATM (1), RAD51C (1), and BRIP1 (1). Five patients (4%) had variants in genes implicated in cancer but where the significance of germline variants in CRC risk is uncertain: GATA2 (1), ERCC2 (mono-allelic) (1), ERCC4 (mono-allelic) (1), CFTR (2). Fourteen (11%) had dMMR tumors. Eighteen (14%) reported a first-degree relative with CRC, but only three of these carried P/LP variants. Three patients with variants in polyposis-associated genes showed no polyposis (one each in MUTYH [bi-allelic], RNF43, and BMPR1A). Approximately one in five young adults in our series carried at least one P/LP variant in a cancer-predisposing/implicated gene; 80% of these variants are currently considered clinically actionable in a familial cancer setting. Family history and phenotype have limitations for genetic risk prediction; therefore multigene panel testing and genetic counseling are warranted for all young adults with CRC regardless of those two factors.

Pattern of colorectal cancers at tertiary rural hospital in Central India

Background: In India the incidence of colorectal cancers is moderate to low but the five year survival of colorectal cancers in India is one of the lowest in the world. The poor survival rate warrants the assessment of reasons. Population based data is available only from few regions in India. Hospital based data may give a crude idea regarding the cancer distribution in the respective areas.Methods: The present study was carried out at a tertiary rural hospital in central India. A total of 216 cases of primary malignant tumors of colon and rectum presenting over a period of 10 year interval from 1994 to 2004 were analyzed for demographic and clinical presentation.ResultsThe peak incidence of cancer of colon and rectum was in 7th and 6th decade respectively. The M: F ratio was found to be 1.6: 1 for colorectal cancers combined. The mean age of presentation was 50.6 years. 25% patients with colorectal cancers were below age of 40 years. 48.3% patients with cancer of colon and 79.5% with cancer of rectum had locoregional disease, while 38.2% and 15.7% had distant spread respectively.Conclusions: Rectal cancer was found to be much commoner than colonic cancer supporting the case of independent etiologies. The incidence of colorectal cancer in young patients was high. Disease confined to the primary organ when the patient is first treated was very low.

The role of PDGFRA as a therapeutic target in young colorectal cancer patients

BackgroundYoung patients with colorectal cancer (CRC) exhibit poor prognoses compared to older patients due to the difficulty in early diagnosis and treatment. However, the underlying molecular characteristics are still unclear.MethodsWe conducted a comprehensive analysis of 49 CRC patients without hereditary CRC using the whole-exome and RNA sequencing with tumor and matched normal samples. A total of 594 TCGA samples and 4 patient-derived cells were utilized for validation.ResultsConsensus molecular subtype 4 (CMS4) (53.85%) and CMS2 (38.46%) were enriched in the young (≤ 40 years) and old (> 60 years) age groups, respectively. A CMS4-associated gene, platelet-derived growth factor receptor α (PDGFRA), was significantly upregulated in young patients with CRC (FC = 3.21, p = 0.0001) and was negatively correlated with age (p = 0.0001, R = − 0.526). Moreover, PDGFRA showed a positive co-expression with metastasis-related genes in young CRC patients. In vitro validation confirmed that young patient-derived cells (PDCs) showed an enriched expression of PDGFRA compared to old PDCs and a reduced proliferation rate by knockdown of PDGFRA. Furthermore, young CRC patients were more sensitive to regorafenib, a PDGFRA-targeting drug, than old CRC patients.ConclusionsOur study suggests that CRC in young patients is associated with CMS4 and PDGFRA. In addition, PDGFRA may serve potential of novel therapeutic strategies and represent a predictive biomarker of response to regorafenib for young CRC patients.

The Prevalence of Pathogenic or Likely Pathogenic Germline Variants in a Nationwide Cohort of Young Colorectal Cancer Patients Using a Panel of 18 Genes Associated with Colorectal Cancer.

Simple SummaryThis study reveals that pathogenic or likely pathogenic germline variants are detected in one fourth of all young patients with colorectal cancer in a nationwide cohort. Immunohistochemistry staining for mismatch repair deficiency is an easy way to detect Lynch syndrome in the young colorectal cancer patient.Introduction: The prevalence of pathogenic or likely pathogenic germline variants (PGV) in colorectal cancer (CRC) in young patients is seen in approximately one in five patients, with the majority of cases having gene variants associated with Lynch syndrome (LS). The primary aim was to describe the prevalence of 18 genes, all associated with hereditary polyposis and CRC, in a nationwide population of young CRC (yCRC) patients, and outline disease characteristics in patients with or without germline variants. Methods: We screened 98 patients aged 18–40 with CRC diagnosed in 2010–2013 for variants in MSH2, MSH6, MLH1, PMS2, EPCAM, APC, MUTYH, SMAD4, BMPR1A, STK11, PTEN, POLE, POLD1, NTHL1, AXIN2, MSH3, GREM1 and RNF43 using Next Generation Sequencing. Comparisons between patients’ characteristics in patients with PGV, and patients without germline variants (NPGV) were analyzed. Results: PGV were detected in twenty-four patients (24.5%), and twenty-one patients (21.1%) had variants in the mismatch repair (MMR) genes associated with LS. Variants in the APC and MUTYH genes were detected in 1% and 4%, respectively. Patients with NPGV had more advanced disease with adverse histopathological features. Conclusion: PGV was detected in one in four yCRC patients, and one in five yCRC patients had disease causing variants in the mismatch repair genes associated with LS.

Early-Onset Colorectal Cancer in Younger Patients with a More Advanced Stage and Worse Postoperative Results: A Retrospective Review

Early-Onset Colorectal Cancer in Younger Patients with a More Advanced Stage and Worse Postoperative Results: A Retrospective Review

Genetic Analysis of Archived Tumor Specimens for Hereditary Colorectal Cancer Syndromes in the Cajuns of Louisiana, a US Founder Population.

INTRODUCTION:The Louisiana Acadian region (population 1.2 million), home of the Cajuns, has among the highest US colorectal cancer (CRC) rates. Although Cajuns are a known genetic founder population, studies assessing for hereditary CRC have not been performed.METHODS:A retrospective review of 2 hospital cancer registries was performed to identify young (<55) Cajun CRC patients in Lafayette, Louisiana (the Acadian region population center), diagnosed from 2003 to 2016. Men were studied because of the higher likelihoods of retaining Cajun surnames for ancestry identification compared with women. Immunohistochemistry for mismatch repair proteins associated with the Lynch syndrome (LS) was performed on tumors. Germline sequencing was performed on adjacent normal tissue of these archived formalin-fixed paraffin-embedded surgical resection specimens for pathogenic variants underlying CRC-associated syndromes, including LS, familial adenomatous polyposis, and others.RESULTS:Of 9 young Cajuns, a germline analysis revealed LS in 2 (MLH1 frameshift, MLH1 missense pathogenic variants). Both had immunohistochemistry-deficient MLH1. Two others had the same adenomatous polyposis coli variant of unknown significance (2 algorithms predicting deleterious and probably damaging change), making this a potential familial adenomatous polyposis founder effect candidate.DISCUSSION:This is the first study assessing for hereditary CRC in a large US regional founder population. This small study did not identify clear Cajun founder pathogenic variants. However, larger studies are warranted, which could also help clarify the clinical significance of the adenomatous polyposis coli variant of unknown significance. This study is important because it demonstrates that a retrospective tumor analysis can be used to ascertain the prevalence of genetic susceptibility in specific populations.

Clinical and phenotypic variants of hereditary and sporadic colorectal cancer in young patients

Relevance: In the Republic of Kazakhstan, colorectal cancer (CRC) ranks third in the structure of oncological pathology. In 2008-2019, the CRC incidence in the Republic was growing each year. There is an upward trend in CRC incidence among young people. Cohort studies show that, in young patients, CRC is characterized by distal localization of the tumor process, advanced stages of the disease, an aggressive course, and low tumor differentiation. The known association of phenotypic signs with clinical characteristics of the disease, such as the response to therapy and survival rates, urges addressing this problem. The phenotypic and molecular genetic aspects of CRC in young people have not been systematically studied in Kazakhstan.&#x0D; The purpose of the study was to compare the phenotypic features of hereditary and sporadic colorectal cancer in young patients and patients over 65 years.&#x0D; Results: The study involved 185 patients aged 17 to 50 years (Group 1) and 112 patients aged 65 to 85 (Group 2). In Group 1, a locally advanced process (stage III) was 14.8% more often than in Group 2; stage IV was 1.23 times more common in men; and multiple primary tumors were 3.1% more often, with a prevailing metachronous course. In Groups 1 &amp; 2, most tumors were localized in the rectum; 84.8% and 78.6% of tumors, respectively, occurred in the left half of the colon. The frequency of right-sided tumors increased with age modified by gender (in Group 2). Hereditary burdened anamnesis was detected in 14.6% patients before 50 (6.57% more than in Group 2); family history of CRC – in 4.8% patients. The latter is consistent with published data. The studied syndromic variants met the diagnostic criteria for familial adenomatous polyposis, Lynch syndrome, Peutz-Jeghers syndrome, and familial type X colorectal cancer.&#x0D; Conclusion: The increase in CRC incidence at the age of 50-70 years is explained by the effectiveness of screening. However, the upward trend for the age below 50 needs a detailed study of etiological (dietary, environmental, behavioral, hereditary) factors. Effective early diagnostics requires considering the phenotypic characteristics and hereditary history associated with a high risk of CRC onset.

Abstract 2629: Young onset colorectal cancer patients, survivors and caregivers: self-report clinical, psychosocial, financial and quality of life outcomes

Abstract Background: Colorectal cancer is the third-most commonly diagnosed cancer and the second-leading cause of cancer death in men and women combined in the United States. Young-onset colorectal cancer refers to individuals diagnosed under the age of 50. In recent years, the incidence has increased by 2.2% annually in individuals younger than 50 years, and 1% in individuals 50-64, in contrast to a 3.3% decrease in adults 65 years and older. Young-onset (YO) CRC patients and caregivers face unique clinical challenges including fear and stress around the disruption of family and career developmental tasks and goals suggesting a need for additional psychosocial and financial support. Methods: A cross-sectional study, conducted in the form of an online survey, was launched to better understand the experiences of YO-CRC patients and caregivers. YO-CRC patients and survivors (N=885) and caregivers (N=204) completed an online questionnaire that was based on established instruments including PROMIS, EORTC-QOL-30, and EORTC-CR-29. The final survey instrument and study plan were reviewed and approved by the Aspire Inc. Institutional Review Board. Results: Nearly 75% of patients/survivors shared that they have been concerned about their mental health and 64% responded that they have needed help for their depression. Further, 67% of caregivers surveyed responded that they were also concerned about their own mental health and 68% responded that they needed help with their depression. Emotional exhaustion was reported by 77% of caregivers, whether they were providing round-the-clock care or caregiving from a distance. Emotional exhaustion was more pronounced in the patient/survivor cohort, with 95% indicating that emotional exhaustion impacted their lives. As a result of psychosocial distress, 71% of caregivers and 29% of patients/survivors indicated that they had withdrawn from other people. YO-CRC diagnosis changes what the patient/survivor can contribute to the family, both physically and emotionally, resulting in the caregiver having a change in their previous responsibilities. Of our respondents, 48% of caregivers indicated that their role in childcare changed; in addition, changes occurred in household responsibilities (77%), sexual/intimacy (51%), work (59%), and financial responsibility (42%). Conclusions: These survey results indicate a need for the YO-CRC community to have access to resources to address unique issues. The physical and emotional stress on patients, survivors and caregivers is frequently not discussed which indicates a knowledge gap, not only in the lay population but also within the medical community. The Alliance is dedicated to working with all stakeholders, including policymakers, to address the unmet needs among caregivers, aiming to improve quality of life outcomes for caregivers in conjunction with their patients. Citation Format: Kimberly Lynn Newcomer, Ronit Yarden, Laura Porter. Young onset colorectal cancer patients, survivors and caregivers: self-report clinical, psychosocial, financial and quality of life outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2629.

Predictors of lymph node metastasis in T1 colorectal cancer in young patients: Results from a national cancer registry.

e15590 Background: The incidence of colorectal cancer in young adults ( &lt; 44 years) is on the rise. Identifying young patients at risk of regional lymph node metastasis (LNM) is crucial for long-term survival. Prior studies have examined rates of LMN in average risk patients. The objective of this study is to fill the knowledge gap by examining predictors of LMN in young patients using a national cancer registry. Methods: Patients diagnosed with T1 colorectal cancer were identified in the Surveillance, Epidemiology, and End Results register 2000-2017. Potential predictors of LNM and its impact on cancer-specific survival were assessed in logistic and Cox regression with and without multivariable adjustment. Results: In total, 692 patients with T1 colorectal cancer were identified. Most tumors occurred in White race (77.7%), between 40-44 years of age (49.4%), grade III tumor differentiation (59.8%), 1 to 1.9 cm in size (32.2%), and were left sided tumors (61.1%). The overall LNM rate was 22.5 % (n = 149). Using multivariate analysis, LMN was associated with tumor grade IV (undifferentiated) (odds ratio (OR) 2.94, CL: 1.06-8.12; p = 0.038), and increasing tumor size (1 cm – 1.9 cm: OR 2.92, CL: 1.71-4.97, p &lt; 0.001; 2.0 cm – 2.9 cm: OR 2.00, CI: 1.05-3.77, p = 0.034; and ≥ 3.0 cm: OR 2.68, CI: 1.43-5.01, p = 0.002). Five-year cancer-specific survival for patients with LNM was 91% and for patients without LNM 98%. Adjusted cox proportion models showed that LMN was associated with four times higher rate of mortality (hazard ratio (HR) 4.43, CI: 1.27-15.52, p = 0.020). Conclusions: In conclusion, the overall LNM rate is approximately 22% for T1 CRC in young patients (less than 45 years). Tumor size and tumor grade are significant predictors for LNM in patients with T1 CRC cancer. Moreover, positive lymph node involvement is a significant prognostic factor for cancer specific survival. Thus, careful preoperative assessment of lymph node status is essential in clinical decision making, to achieve better long-term outcomes

Somatic and germline mutation profiles of Chinese young colorectal cancer patients.

e15522 Background: In recently years, although CRC morbidity and mortality can be mitigated through appropriate screening and surveillance, the incidence rate of colorectal cancer (CRC) younger than 50 years old increased annually. Limited studies have investigated the underpinnings driving CRC development in Chinese younger population. In our study, we aim to explore the comprehensive mutational profile of Chinese CRC patients old (＞50) and young (≤50) diagnosed with CRC. Methods: Targeted sequencing with a 539 cancer-related genes panel was performed on 235 patients diagnosed with CRC. We investigate the landscape and difference of old and young CRC somatic and germline mutations in our Chinese cohort and compare with TCGA CRC cohort (N = 592). Results: Analysis revealed an overall 20.9% (49/235) mutation detection rate of young CRC in our Chinese cohort, which is higher than TCGA cohort (13.9%, 82/592). In our cohort, all Chinese young CRC patients can detect mutation and median mutation count is 10 mutations which is similar to old CRC patients (11 mutations). Comparing high frequency somatic mutations (young group with top 20), we found that BRCA2 mutation in young CRC group is significantly higher than old group (18.4% vs 7.0%, P = 0.025). In TCGA cohort, there is no difference between two groups with top 20 mutations and frequency of BRCA2 is 13.4% (11/82) in young CRC. For germline mutation, 12.29% (29/236) patients in our Chinese cohort harbored pathogenic and likely pathogenic (P/LP) germline mutations and 24.1% (7/29) CRC with P/LP germline mutations is young patients. In these seven P/LP mutation young patients, three patients have MMR gene mutation, two patients harbor ATM mutation, one patient has APC and another has SLX4 mutation. Moreover, young CRC have higher frequency MSI-H than old CRC patients (28.6% vs 18.2%). Conclusions: Our study has identified that young CRC patients account for a higher proportion in Chinese population and BRAC2 mutation may be an important factor in the early development of colorectal tumors in younger patients. In addition, our results also support the role of MSI statues in tumor oncogenesis in Chinese patients with early-onset CRC, indicating the need to include a more comprehensive germline mutation and genetic screening in our population.

Free Fatty Acid is a Promising Biomarker in Triage Screening for Patients with Colorectal Cancer: A Case-Control Study.

PurposeThe aim of our study was to identify the diagnostic ability of free fatty acids (FFAs) in younger colorectal cancer (CRC) patients by comparing carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9).MethodsPatients screened for CRC at Fujian Medical University Union Hospital from January 2011 to December 2014 were recruited. Patients pathologically diagnosed with CRC or colorectal adenoma (CA) and healthy control participants were included. The enzyme endpoint method was applied to measure FFA levels. Receiver operating characteristic (ROC) curve analysis was performed to further evaluate the diagnostic ability of FFAs.ResultsFFA levels in late-stage patients (tumour-node-metastasis (TNM) stages III–IV) were higher than those in early-stage patients (TNM stages I–II) (P=0.02). The FFA levels in CRC patients were higher than those in controls of all ages, those younger than 50 years, males and females (P<0.001), and this difference was larger for patients younger than 50 years and females than for the all ages group. There was no significant difference in the FFA level between CA patients and healthy participants (P=0.53). The area under the curve (AUC) values of FFA, CEA, CA19-9, FFA+CEA, FFA+CA19-9 and FFA+CEA+CA19-9 distinguished CRC patients from controls at all ages, with values of 0.604, 0.731, 0.640, 0.754, 0.678 and 0.758, respectively; however, in the younger CRC patients (age≤50), the AUC values were 0.701, 0.735, 0.669, 0.798, 0.749, and 0.801. The AUC in female patients younger than 50 years was larger than that in males (0.769 vs 0.660), and this value was greater than the value for CEA in males (0.739) and females (0.729).ConclusionThe FFA level not only can complement the predictive ability of the CEA and CA19-9 levels but also has a superior predictive ability in female and younger patients with CRC. FFA levels may have a potential role in triage screening of early CRC.

Colorectal cancer in 18- to 49-year-olds: rising rates, presentation, and outcome in a large integrated health system

Colorectal cancer (CRC) rates are increasing in young people, and new guidelines recommend screening should begin at age 45 years. We aimed to evaluate CRC detection rates in a large integrated healthcare system to assess treatment outcomes in younger CRC patients and to determine factors that could aid in identifying these individuals. We analyzed confirmed cases of CRC using a cancer database spanning from 1985 to 2017 from a large integrated healthcare system composed of 15 hospitals, 150 outpatient clinics, and 20 outpatient oncology clinics. Three cohorts were evaluated (18-44 years, 45-49 years, and≥50 years). Significant increases in CRC detection were seen in the cohort aged 18 to 44 (annual percentage change, 2.70%) and the cohort aged 45 to 49 (annual percentage change, 4.15%). A higher proportion of African American, Hispanic, and obese subjects were seen in the younger cohorts. A family history of CRC was found in 49% of patients aged 18 to 44 and 38% of patients aged 45 to 50. Patients younger than age 50 were more likely to have metastases at diagnosis (6.8%) versus the cohort over 50 (4.15%; P< .05). Survival was better in younger cohorts, and they were more likely to receive multimodality treatment (surgery with chemotherapy or radiation). Survival probability was similar in different ethnic groups. CRC is increasing at similar rates in young people aged 18 to 44 and 45 to 49, and they are more likely to present with advanced disease needing multimodality treatment. A family history identifies some patients<50 years. Young patients presenting with changes in bowel habit, rectal bleeding, anemia, and weight loss should undergo colonoscopy. Rectal and anal symptoms should prompt careful physical and endoscopic evaluation.