Young-onset Colorectal Cancer Patients Research Articles

Atypical Exon 2/3 Mutants G48C, Q43K, and E37K Present Oncogenic Phenotypes Distinct from Characterized NRAS Variants.

NRAS belongs to the RAS family of GTPases. In colorectal cancer (CRC), NRAS mutations are rare compared to KRAS, but may lead to worse outcomes. We report the functional characterization of the novel NRAS mutants-G48C, Q43K, and E37K-identified in Filipino young-onset CRC patients. Unlike previously characterized NRAS mutants with no apparent effects on cell proliferation, these mutants enhanced proliferation of both HCT116 and NIH3T3 cells. This was confirmed in 3D spheroid assays to mimic the spatial organization of cells. G48C and E37K showed apoptosis resistance in both cell lines, and Q43K showed resistance in HCT116 cells. All three showed no effect on cellular migration in NIH3T3, but G48C enhanced the migration rate of HCT116 cells. Actin staining of NIH3T3 cells expressing the mutants showed a shrunken cytoplasm and transient structures associated with motility and invasiveness. Docking simulations show that GDP is only able to bind fully within the binding pocket of wild-type NRAS, but not in the mutants. Further, G48C, Q43K, and E37K all have less negative ΔG values, indicating a weaker GDP-binding affinity compared to wild-type NRAS. Taken together, the results suggest that oncogenic readouts of NRAS mutants are codon- and mutation-specific, with potential repercussions on the aggressiveness, resistance, and therapeutic response.

Evolving survival gains in patients with young-onset colorectal cancer and synchronous resectable liver metastases

We aimed to evaluate the practice and the associated outcomes of surgical treatment for young-onset colorectal cancer (YOCRC) patients presenting with synchronous liver metastases. The study cohort was divided into two groups according to surgery date: 131 patients in the early era (EE, 1998–2011) and 179 in the contemporary era (CE, 2012–2020). The CE had a higher rate of node-positive primary tumors, higher carcinoembryonic antigen level, and lower rate of RAS/BRAF mutations. The CE had higher rates of reverse or combined resection, multi-drug prehepatectomy chemotherapy, and two-stage hepatectomy. The median survival was 8.4 years in the CE and 4.3 years in the EE (p = 0.011). On multivariate analysis, hepatectomy in the CE was independently associated with improved overall survival (HR 0.48, p = 0.001). With a combination of perioperative systemic therapy, careful selection of treatment approach, and coordinated resections, durable cure can be achieved in YOCRC patients.

Dietary Factors Differ Between Young-Onset and Older-Onset Colorectal Cancer Patients

We aimed to evaluate differences in dietary factors between young-onset (diagnosed at ages <50) and older-onset colorectal cancer (CRC). CRC patients diagnosed from 1998 to 2018 reported to the Puget Sound Surveillance, Epidemiology, and End Results registry were recruited using mail and telephone. Consented patients completed questionnaires assessing demographics, medical history, and CRC risk factors, including dietary factors. We used multi-variable logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing dietary intake in young-onset vs. older-onset CRC. Analyses included 1,087 young- and 2,554 older-onset CRC patients. Compared to older-onset CRC, young-onset CRC patients had lower intake of vegetables (OR for highest intake vs. lowest = 0.59 CI: 0.55, 0.64) and fruit (OR for highest intake vs. lowest = 0.94 CI: 0.88, 0.99) and higher intake of processed meat (OR for highest intake vs. lowest = 1.82 CI: 1.11, 2.99) and spicy food (OR for highest intake vs. lowest = 1.69 CI: 1.09, 2.61). There was no statistically significant difference between young- and older-onset CRC patients for red meat consumption. Dietary patterns differed between young- and older-onset CRC; young-onset CRC patients had lower intake of vegetables and fruit and higher intakes of processed meat and spicy food.

Development and validation of a clinical survival model for young-onset colorectal cancer with synchronous liver-only metastases: a SEER population-based study and external validation.

The morbidity and mortality of young-onset colorectal cancer (YO-CRC) patients have been increasing in recent years. Moreover, YO-CRC patients with synchronous liver-only metastases (YO-CRCSLM) have various survival outcomes. Therefore, the purpose of this study was to construct and validate a prognostic nomogram for patients with YO-CRCSLM. The YO-CRCSLM patients were rigorously screened from the Surveillance, Epidemiology, and End Results (SEER) database in January 2010 and December 2018 and then assigned to a training and validation cohort randomly (1488 and 639 patients, respectively). Moreover, the 122 YO-CRCSLM patients who were enrolled in The First Affiliated Hospital of Nanchang University were served as a testing cohort. The variables were selected using the multivariable Cox model based on the training cohort and then developed a nomogram. The validation and testing cohort were used to validate the model's predictive accuracy. The calibration plots were used to determine the Nomogram's discriminative capabilities and precision, and the decision analysis (DCA) was performed to evaluate the Nomogram's net benefit. Finally, the Kaplan-Meier survival analyses were performed for the stratified patients based on total nomogram scores classified by the X-tile software. The Nomogram was constructed including ten variables: marital status, primary site, grade, metastatic lymph nodes ratio (LNR), T stage, N stage, carcinoembryonic antigen (CEA), Surgery, and chemotherapy. The Nomogram performed admirably in the validation and testing group according to the calibration curves. The DCA analyses showed good clinical utility values. Low-risk patients (score<234) had significantly better survival outcomes than middle-risk (234-318) and high-risk (>318) patients (P < 0.001). A nomogram predicting the survival outcomes for patients with YO-CRCSLM was developed. In addition to facilitating personalized survival prediction, this nomogram may assist in developing clinical treatment strategies for patients with YO-CRCSLM who are undergoing treatment.

Exploring demographic differences and outcomes in young-onset colorectal cancer.

35 Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States (1). The incidence of young-onset CRC is on the rise based on recent data (2). Previous research on other cancers has shown that patients living in rural areas have worse outcomes (3). This study aimed to investigate the geographic and socio-demographic disparities in young-onset CRC patients. Methods: We conducted a retrospective study on colorectal cancer patients between 1975 and 2016 using the Surveillance, Epidemiology, and End Results (SEER) database. Both univariate and multivariable analyses were performed to evaluate overall survival (OS) and disease-specific survival (DSS). Socio-demographic factors, including the location of residence [metro area (MA) or rural area (RA)], gender, race, insurance status, and marital status, were analyzed. Young-onset colorectal cancer (CRC) was defined as the age of diagnosis less than 50 years. The program used for analysis was SAS software 9.4 (SAS Institute Inc., Cary, NC, USA.) Univariate and multivariable models were analyzed using Cox proportional models. Demographic differences between urban and rural population were assessed using Wilcoxon Rank Sum test (continuous variable) and Chi-square test (categorical variables). Results: A total of 73,378 [RA, N = 7,636(10.6%); MA, N = 64,605(89.4%)] young-onset CRC patients were included. RA had more Caucasian patients compared to MA (80.5% vs 60%, p &lt; 0.001). Patients living in RA were more likely to be uninsured (4.8% vs 3%, p &lt; 0.001) than MA. During the study period, the incidence and mortality rates were consistently higher in RA vs. MA. Univariate and multivariable analysis showed that RA had worse OS (multivariate HR = 1.14; p &lt; 0.01) and DSS (multivariate HR = 1.15; p &lt; 0.001) compared to MA. Similarly, males, single and uninsured patients had worse OS and DSS compared to females, married, and insured patients, respectively. Conclusions: Our study identified social and demographic disparities in young-onset CRC incidence and outcomes. Potential causes may include access to healthcare, diet, health behavior, and environmental factors. Future research is needed to understand and attenuate such disparities.

Clinical features of young onset colorectal cancer patients from a large cohort at a single cancer center.

The aim of this study is to describe the demographics and clinical features of patients with young onset (YO) CRC. A retrospective review of patients with CRC diagnosed between ages 20 and 49years was evaluated at the Memorial Sloan Kettering Cancer Center from 1/2004 to 6/2019. We excluded those with a hereditary CRC syndrome, inflammatory bowel disease, or prior CRC diagnosis. Patient demographics; presenting symptoms; medical, surgical, and smoking history; family history of cancer; tumor characteristics; and pathology were obtained from the electronic medical record. We identified 3856 YO CRC patients (median age CRC diagnosis 43; 52.5% male). A total of 59.1% were overweight or obese (32.2% and 26.9%, respectively). Most (90.1%) had no family history of CRC in a first-degree relative; 56.3% of patients reported being never smokers; 5.2% had diabetes. The most common presenting symptoms were rectal bleeding (47.7%), abdominal pain/bloating (33.1%), and change in bowel habits (24.7%). The majority presented with left-sided cancers (77.3%), at late-stage disease (68.4% at stages 3 or 4). Most YO CRC patients presented with rectal bleeding or abdominal pain, left-sided cancers, and later-stage disease and had no family history of CRC in a first-degree relative. Over half were overweight and obese and were more likely to have never smoked. More data are needed to better understand YO CRC risk factors and to help identify high-risk populations who may benefit from earlier screening.

S244 An Appraisal of the Referral, Uptake and Outcomes of Genetic Counseling and Testing in Patients With Young Onset Colorectal Cancer

Introduction: The incidence of young-onset colorectal cancer (YOCRC) defined as CRC in individuals < 50 years of age is rapidly rising. Germline genetic testing is currently recommended for all patients with CRC< 50 years. Germline pathogenic variants (PV) are detected in 16-20% of patients with YOCRC and many are diagnosed with an actionable PV not typically associated with CRC, highlighting a need for genetic counseling and multi-panel gene testing (MGPT) in these patients. We aimed to determine the rate of referral to genetic counseling, and uptake and outcomes of germline testing in YOCRC patients seen at a tertiary referral center. Methods: Patients diagnosed with YOCRC from 2010-2019 were included. Patients with appendiceal cancer, known family history of a hereditary cancer syndrome and inflammatory bowel disease were excluded. Demographic data including age, sex, race and family history of CRC were extracted from the electronic medical record (EMR).Genetic counseling referral was confirmed through an order in the EMR, clinical documentation in office visits with colorectal surgery, oncology or gastroenterology, or a completed visit with the genetic counselor. Data was analyzed using STATA, Chi-square and t-test and descriptive analyses were included. Results: 793 YOCRC patients (457 male and 336 female) were included. 56% (445) were referred for genetic counseling and 88% of referred patients completed genetic testing. 20.5% had a PV detected; 83% were in CRC associated genes and 18% were in other actionable genes (Table). Referral to genetic counseling was higher in younger patients (mean age= 40 years in those referred vs. mean age= 43 years in those not referred, p < 0.05) and those with a family history of CRC (70% of patients with family history of CRC vs. 53% of patients without family history were referred, p< 0.05) There was no significant association between referral rate and sex or race. Conclusion: Even in a large academic center, the rates of referrals for genetic counseling in patients with YOCRC were documented in only about half the patients. 1 in 5 YOCRC patients had a PV detected. If the 348 patients not referred to genetic counseling underwent testing, an additional 71 patients may be detected with a germline PV. Our findings highlight the need to raise awareness of the importance of genetic counseling and testing in YOCRC patients, and suggest that health systems should consider implementing care pathways to mitigate the potential impact of under-referral. Table 1. - Demographics, Referral to and Uptake of Genetic Counseling and Testing and Outcome of Genetic Testing Number of patients with YOCRC 793 Demographics N (%) Mean (SD) Age 41.9 (6.8) Sex Male 457 (57.6) Female 336 (42.4) Race White 684 (86.3) Black 72 (9.1) Other 37 (4.7) Family History of CRC Yes 280 (40.2) No 417 (59.8) Referral for Genetic Counseling 445 (56.1) Attended Genetic Counseling 390 (87.6) Underwent Genetic Testing 376 (96.4) • Pathogenic Variant Detected 77 (20.5) • Variant of Uncertain Significance Detected 88 (23.4) • No Variant Detected 211 (56.1) Genetic Testing Outcomes Genetic Syndrome Pathogenic Variant Number of Patients Total (%) CRC and polyposis genes N=64 (83%) Lynch syndrome N=37 (48%) MLH1 11 37 (48) MSH2 13 MSH6 8 PMS2 5 FAP N= 15 (19.4%) APC 15 15 (19.4) MYH- Associated polyposis N =10 (12.9%) MUTYH (Biallelic) 6 10 (12.9) MUTYH (Monoallelic) 4 Juvenile polyposis syndrome N = 1 (1.2%) SMAD4 1 1 (1.2) MSH3 (monoallelic) 1 1 (1.2) Other genes N=13 (17%) ATM 4 13 (17) BRCA1/2 4 BLM (monoallelic) 1 CHEK2 2 FLCN 1 CDKN2A 1

Metagenomic analysis of the fecal microbiome in patients with colorectal cancer compared to healthy controls as a function of age.

3532 Background: Colorectal cancer (CRC) incidence is increasing in young patients ( &lt; 50 years old) without a clear etiology. Emerging data has implicated the fecal microbiome in CRC carcinogenesis. However, its impact on young onset CRC (YO-CRC) is poorly defined. Colibactin producing E. Coli and fadA producing Fusobacterium nucleatum can drive CRC carcinogenesis, however their effects across the age spectrum are unknown. Methods: We performed a meta-analysis of fecal metagenomics sequencing from n = 692 patients with CRC and n = 602 healthy controls from eleven studies to evaluate species and known microbial derived factors (colibactin and FadA) associated with CRC as a function of age. Generalized linear mixed effects regression was used to model the predicted prevalence of gene families and taxa as a non-linear function of age. Two-stage individual patient data meta-analysis (IPDMA) with adjustment for gender, CRC status, and body mass index was also used to estimate summary odds ratios for colibactin, F. nucleatum, and E. Coli. Interaction ORs were obtained to assess the difference in the effect of each gene or taxa on CRC case status in YO-CRC. Shannon Diversity index and metabolic pathway differences in the fecal metagenome for YO-CRC patients were assessed using phyloseq and MetaCyc respectively using an IPDMA approach. Results: Summary odds ratios (OR) for CRC were increased relative to controls with the presence of colibactin (OR 1.92 95%CI 1.08-3.38), fadA (OR 4.57 95%CI 1.63-12.85), and F. nucleatum (OR 6.93 95%CI 3.01-15.96) in models of all patients adjusted for age, gender, and body mass index. The OR for CRC for the presence of E.coli was 2.02 (0.92-4.45). An increase in the prevalence of F. nucleatum (OR = 1.40 [1.18; 1.65] and Escherichia coli (OR = 1.14 [1.02; 1.28]) per 10-year increase in age was observed in models including samples from both CRC and healthy controls. No difference was observed for Shannon Diversity (OR 1.36 95%CI 0.68-2.72) or MetaCyc pathways in YO-CRC patients. Species relative abundance was differentially enriched in YO-CRC relative to old CRC patients and controls for five species- Intestinimonas butyriciproducens, Holdemania filiformis, Firimicutues bacterium CAG 83, Bilophilia wadsworthia, and Alistipes putredinis. Conclusions: Strong associations with CRC status were observed for colibactin, fadA, and F. nucleatum with increased F. nucleatum in older patients. Several species were enriched in YO-CRC patients including B. wadsworthia which can produce carcinogenic sulfur metabolites and is increased with adherence to a sulfur microbial diet-low in vegetables and legumes. A sulfur microbial diet has also been associated with higher incidence of YO-CRC in population studies (Nguyen Gastroenterology 2021). Additional study is warranted to understand causal mechanisms of enriched species observed in YO-CRC patients.

Association between environmental quality index and young onset colorectal cancer.

3548 Background: The factors associated with the rise of young-onset colorectal cancer (YOCRC) remain unclear. However, environmental exposures are believed to be associated with YOCRC in addition to hereditary factors. Therefore, we evaluated the association between the national level Environmental Quality Index (EQI) and YOCRC in the US. Methods: We queried the SEER database to identify adult colorectal cancer patients diagnosed between 2010-2016. YOCRC was defined as age at diagnosis &lt; 50 years. EQI (2005-2010) is a measure of county-level cumulative environmental exposures that includes 5 domains: sociodemographic, built, air, land, and water. A higher value represents a lower environmental quality. We distributed the total EQI and each EQI domain into five quintiles. Multivariable logistic regression analysis was used to assess the relationship between YOCRC and quintiles (upper-most vs. lowest) of EQI after adjusting by race (White, Black, and Others), gender, and stage at diagnosis. The age-adjusted incidence rate was also calculated using the SEER*Stat, and correlation efficiency was estimated between EQI domains and incidence rate. Results: A total of 261,417 CRC patients were included; 11% were YOCRC. In the adjusted multivariable analysis, poor built EQI (OR 1.15 [1.11-1.20]) and water EQI (OR 1.08 [1.03-1.12]) were more likely to be associated with YOCRC. Poor built EQI was more strongly associated with Black YOCRC (OR 1.21 [1.09-1.35]) as compared to White YOCRC (OR 1.14 [1.09-1.19]). Poor sociodemographic EQI was more strongly associated with Others (OR 1.47 [1.25-1.72]) compared to Black YOCRC (OR 1.14 [1.03-1.25]). In addition, poor built EQI (OR 1.19 [1.12-1.27]) and water EQI (OR 1.12 [1.05-1.19]) were more strongly associated with the metastatic disease among YOCRC patients. However, the total poor EQI was not associated with YOCRC (OR 0.99 [0.95-1.03]). On incidence analysis, there was a positive correlation between the incidence rate of YOCRC and sociodemographic EQI (rho = 0.49, p &lt; 0.001), air EQI (rho = 0.30, p &lt; 0.001), and land EQI (rho = 0.18, p &lt; 0.001). Conclusions: This study evaluated a population-based ecological approach and showed that YOCRC was associated with lower environmental quality, including built and water domains. EQI domains were also associated with different racial groups among YOCRC. Instead of studying single environmental exposures, the impact of the cumulative environmental index should be recognized and studied further to understand the mechanism of cancer development.

Predicting Distant Metastasis in Young-Onset Colorectal Cancer After Surgery: A Retrospective Study.

BackgroundAlthough overall colorectal cancer (CRC) cases have been declining worldwide, there has been an increase in the incidence of the CRC among individuals younger than 50 years old, which is associated with distant metastasis (DM) and poor prognosis.MethodsYoung-onset CRC patients’ postoperative data were collected from the Surveillance, Epidemiology, and End Results (SEER) database between January 2010 and December 2015. Data from the SEER database were divided into early stage and advanced stage according to whether chemoradiotherapy was recommended in the guidelines. Independent risk factors for DM were explored by using univariate and multivariate logistic regression separately. A predictive model was established and presented as nomogram in the training set of advanced stage. The model was internally verified in testing set and externally validated in a cohort of 145 patients from Zhongnan Hospital of Wuhan University. The accuracy, reliability, and clinical application value were assessed using the receiver operating characteristic curve (ROC), the area under the curve (AUC), calibration curve, and decision curve analysis (DCA), respectively. Different risk subgroups of DM were classified according to the scores of the nomogram in the training set of advanced stage.ResultsA total of 5,584 patients were eligible and enrolled in our study in which 1,277 were in early stage and 4,307 in advanced stage. Preoperative CEA positive was found to be an independent predictor of DM in early stage. Multivariate logistic regression analysis showed that tumor size, degree of differentiation, T stage, N stage, preoperative CEA, and whether radiation or chemotherapy performed were independent risk factors for DM (all, p < 0.05) in advanced stage. Great accuracies were achieved in our nomogram with AUC of 0.801 in training set, 0.811 in testing set, and 0.791 in the validation cohort, respectively. Calibration curves and DCA in internal validation and external validation both showed good stability and clinical utility values.ConclusionsPreoperative CEA positive was a significant predictor of DM for young-onset CRC patients. A novel nomogram containing clinical and pathological features was established for predicting DM of advanced CRC in patients younger than 50 years old. This tool may serve as an early alert for clinicians to DM and make better clinical treatment regimens.

Association between environmental quality index and young onset colorectal cancer.

75 Background: The factors associated with the rise of young-onset colorectal cancer (YOCRC) remain unclear. In addition to hereditary factors, environmental exposures are believed to be associated with YOCRC. Therefore, we aimed to study the association between the national level Environmental Quality Index (EQI) and YOCRC in the US. Methods: We used the SEER database to select the CRC patients diagnosed between 2010-2016. YOCRC was defined based on age at diagnosis &lt; 50 years. EQI (2005-2010) is a measure of county-level cumulative environmental exposures that includes 5 domains: sociodemographic, built, air, land, and water. A higher value represents a lower environmental quality. We distributed the total EQI and each EQI domain into five quintiles. Multivariable logistic regression analysis was used to assess the relationship between YOCRC and quintiles (upper-most vs. lowest) of EQI after adjusting by race (White, Black, and Others), gender, and stage at diagnosis. The age-adjusted incidence rate was also calculated using the SEER*Stat, and correlation efficiency was estimated between EQI domains and incidence rate. Results: A total of 261,417 CRC patients were included; 11% were YOCRC. In the adjusted multivariable analysis, poor built EQI (OR 1.15 [1.11-1.20]) and water EQI (OR 1.08 [1.03-1.12]) were more likely to be associated with YOCRC. Poor built EQI was more strongly associated with Black YOCRC (OR 1.21 [1.09-1.35]) as compared to White YOCRC (OR 1.14 [1.09-1.19]). Poor sociodemographic EQI was more strongly associated with Others (OR 1.47 [1.25-1.72]) compared to Black YOCRC (OR 1.14 [1.03-1.25]). In addition, poor built EQI (OR 1.19 [1.12-1.27]) and water EQI (OR 1.12 [1.05-1.19]) were more strongly associated with the metastatic disease among YOCRC patients. However, the total poor EQI was not associated with YOCRC (OR 0.99 [0.95-1.03]). On incidence analysis, there was a positive correlation between the incidence rate of YOCRC and sociodemographic EQI (rho=0.49, p&lt;0.001), air EQI (rho=0.30, p&lt;0.001), and land EQI (rho=0.18, p&lt;0.001). Conclusions: This study evaluated a population-based ecological approach and showed that YOCRC was associated with lower environmental quality, including built and water domains. EQI domains were also associated with different racial groups among YOCRC. [Table: see text]

Molecular characteristics of young-onset colorectal cancer in Vietnamese patients.

Colorectal cancer (CRC) is one of the most common cancer globally. Understanding the genetic characteristics of CRC is essential for appropriate treatment and genetic counseling. The genetic profile of CRC tumor tissues was identified using next-generation sequencing of 17 target genes (MLH1, MSH2, MSH6, PMS2, EPCAM, APC, SMAD4, BMPR1A, MUTYH, STK11, PTEN, TP53, ATM, CDH1, CHEK2, POLE, and POLD1) in a cohort of 101 Vietnamese patients diagnosed with young-onset CRC. Corresponding germline genetic alterations of determined somatic mutations were subsequently confirmed from patients' blood samples. Somatic mutations were determined in 96 out of 101 CRC patients. Two-thirds of the tumors harbored more than two mutations, and the most prevalent mutated genes were TP53 and APC. Among confirmed germline mutations, 10 pathogenic mutations and 11 variants of unknown significance were identified. Given the burden of CRC and the gradually reducing cost of genetic testing, multigene panel screening can benefit young-onset CRC patients as well as their relatives.

Clinicogenomic Characteristics and Treatment of Young-Onset Colorectal Cancer Patients Treated With Palliative Therapy in Real-World Practice.

IntroductionYoung-onset colorectal cancer (YOCR) is increasing. This study aimed to determine the difference between advanced YOCR and non-YOCR patient outcomes.MethodsWe retrospectively included patients with recurrent/metastatic colorectal cancer treated with palliative systemic therapy between 2016 and 2018. Diagnosis at < 50 years was defined as YOCR. Targeted sequencing was used to assess the mutational status.ResultsAmong the 969 patients included, 210 (21.7%) were YOCR. The median progression-free survival with first-line chemotherapy (PFS1) was 9.7 vs 9.4 months (P = .755), and the median overall survival (OS) was 25.9 vs 22.3 months (P = .581) in the YOCR and the non-YOCR group, respectively. However, the youngest patients diagnosed at < 30 years showed poorer survival outcomes (median PFS1, 3.9 months; median OS, 8.6 months) compared with other age groups. PFS1 did not differ between YOCR and non-YOCR by choice of treatment regimen. Among the 340 patients with targeted sequencing results, YOCR had fewer APC mutations (61% vs 80%), but had similar KRAS (53% vs 48%), NRAS (7% vs 3%), and BRAF class I mutations (4% vs 6%). The median tumor mutational burden (TMB) was 10.9 vs 12.5 mut/Mb in YOCR and non-YOCR patients, respectively (P = .064). TMB increased with age in tumors with high microsatellite instability (Pearson’s R = .69, P = .028), but not in microsatellite-stable tumors (R = .02, P = .658).ConclusionsSurvival outcomes with palliative systemic therapy were similar between recurrent/metastatic YOCR and non-YOCR with an age cut-off of 50 years. However, patients diagnosed at < 30 years of age showed poorer outcomes compared with other age groups.

Colorectal cancer patients in a tertiary hospital in Indonesia: Prevalence of the younger population and associated factors

BACKGROUNDAn increasing trend in colorectal cancer (CRC) occurring at younger ages has been observed worldwide, even though incidence is declining in the general population. Most currently available guidelines still recommend CRC screening for older populations, despite an alarming rise in early-onset CRC incidence. Risk stratification is necessary to further determine the population most at risk for early-onset CRC. However, epidemiological data on related clinical characteristics and potential risk factors, especially in developing countries, have not been widely reported.AIMTo investigate the prevalence, demographics, clinicopathologic features, and associated factors of young-onset CRC patients in a tertiary hospital in Indonesia.METHODSPatients undergoing colonoscopy examination between 2008 and 2019, yielding a diagnosis of CRC were identified from medical records. The subjects were classified into two groups according to their age at diagnosis, namely early-onset (18-49 years old) and late-onset (≥ 50-years-old). Demographic data, characteristics, and risk factors of both onset age groups were evaluated using the chi-square and Fisher’s exact test.RESULTSAmong 495 CRC patients confirmed by histopathology, 205 (41.4%) were classified as early-onset and 290 (58.6%) as late-onset. Most subjects in the early-onset CRC group were male (53.7%), with 89.8% displaying adenocarcinoma histopathology. A majority (78%) of the early-onset CRC patients had left-sided tumors, with the rectum (41%) and rectosigmoid (17.6%) being the most common sites. Abdominal pain was the most frequent symptom in the early-onset CRC patients (55.6%), which was significantly higher than that in the late-onset CRC patients (43.8%, P < 0.05). Early-onset CRC cases were more likely to be underweight (34.6% vs 20.0%, P < 0.001) compared to late-onset CRC cases. The proportion of subjects with suspected hereditary nonpolyposis colorectal cancer (HNPCC) was also higher in the early-onset CRC group than in the late-onset age group (9.3% vs 4.1%, P < 0.05). However, no difference was observed in the parental or family histories of CRC cases.CONCLUSIONEarly-onset CRC patients were more likely to have abdominal pain, underweight status, and HNPCC suspicion than late-onset CRC patients.

Young-onset colorectal cancer: A review.

Despite the general decrease in overall incidence of colorectal cancer since the early 1990s, the incidence of colorectal cancer in patients less than 50 years old has nearly doubled. A systematic review was performed using the PubMed database (2011-2020) and Cochrane Database of Systematic Reviews (2011-2021) to identify studies (published in English) evaluating epidemiologic, clinical, hereditary, and molecular features; as well as evaluation, management, and prognosis of young-onset colorectal cancer patients. Our search yielded a total of 3401 articles, after applying our inclusion criteria. We fully reviewed 94 full-length studies. This systematic review demonstrates the increasing incidence of young-onset colorectal cancer and highlights the importance of being hypervigilant for the differential diagnosis colorectal cancer when evaluating a young adult who presents with gastrointestinal symptoms.

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.

Racial disparities and treatment trends among young-onset colorectal cancer patients: An analysis of a hospital cancer registry

BackgroundThere is an increasing trend of colorectal cancer (CRC) incidence and mortality in individuals under the age of 50. The impact of age on the outcomes of CRC remains controversial. This study examined the characteristics and treatment trends of young-onset CRC by comparing patients < 50 years of age to those ≥50. MethodsData were retrospectively obtained from one of the largest hospital systems in Virginia. The sample included patients diagnosed with CRC from 2008 to 2016. Bivariate analyses were used to describe patients’ characteristics. Stratified and multivariate analyses were used to evaluate the association between treatments and age groups in different stages at diagnosis. ResultsApproximately 11.6 % (n = 522) of the cohort were younger than 50 years old at diagnosis with a mean age of 42.7 (SD = 5.9) years. Compared to their older counterpart (50 and older), young-onset patients were more likely to be African American (28.7 % (n = 150) vs. 23.7 % (n = 944)), to own private insurance (68.5 % (n = 313) vs. 27.6 % (n = 1032)), to have never used tobacco products (50.4 % (n = 237) vs. 43.8 % (n = 1616)), and to be late stage at diagnosis (68.6 % (n = 358) vs. 52.5 % (n = 2090)) (all p < 0.05). For early stage diagnosis, over 98 % of the young-onset treatments were surgery. For late stage diagnosis, the cancer treatment for young onset patients were a combination of surgery (89.4 %), radiation (82.5 %), and chemotherapy (86.3 %). The results of the analyses also demonstrated that patients with young-onset CRC have higher odds for surgery [OR = 1.76, 95 %CI (1.26, 2.47)], radiation [OR = 1.31, 95 %CI (1.17, 1.47)], and chemotherapy [OR = 3.34, 95 %CI (2.62, 4.25)]. ConclusionsFindings confirmed late-stage prevalence among young-onset as well as significant demographic differences with patients’ age ≥50. This study is one of few to explore the characteristics and assess treatment of young patients with CRC using U.S hospital data. Moreover, further studies need to clarify the effects of biological properties like genetic influences and environmental factors between races on cancer patient outcomes.

Clinicopathologic Factors Associated with Mismatch Repair Status Among Filipino Patients with Young-Onset Colorectal Cancer.

IntroductionYoung-onset colorectal cancer is recognized as a distinct disease that may be sporadic or hereditary in nature. Microsatellite instability testing is recommended as a routine procedure in evaluating colorectal cancer specimens, especially in young-onset disease, because of implications in management. Immunohistochemistry of mismatch repair proteins serves as an inexpensive alternative to microsatellite instability testing with the added advantage of monitoring protein expression levels that may suggest underlying genetic or epigenetic alterations. This descriptive study aimed to determine the frequencies of proficient and deficient mismatch repair status among Filipino young-onset colorectal cancer patients, and to investigate their clinicopathologic profile.MethodsTumor tissues were prospectively collected from patients from two tertiary hospitals in the Philippines. Patients of age ≤45 years with resected adenocarcinoma of the colon or rectum were recruited.ResultsSeventy-seven out of 124 patients had tumor samples sent for immunohistochemistry. Of these, 61 samples (79%) were found to have proficient status while 16 samples (21%) had deficient status. Mismatch repair protein deficiencies, when present, more commonly involved MSH2 and MSH6 (9%) rather than MLH1 and PMS2 (5%). The deficient group had a mean age of 37.1 years and a female preponderance (56.25%), presenting as locally advanced ascending or descending colon tumors with mucinous histology in half of the population. The mismatch repair proficient group presented as locally advanced rectal and sigmoid tumors but with fewer mucinous adenocarcinomas (26.2%) compared to the deficient group. In both the mismatch repair proficient and deficient patients with family history reports, most did not have any known relative with cancer (75.4% and 68.75%, respectively).ConclusionThis is the first attempt to perform mismatch repair testing among young-onset colorectal cancer patients in the Philippines and to gather data on their clinicopathologic characteristics. However, the limited sample size precludes conclusive results for the associations of mismatch repair with clinicopathologic features.

A delayed path to diagnosis: Findings from young-onset colorectal cancer patients and survivors.

5 Background:Colorectal cancer (CRC) is the second-leading cause of cancer-related death among males and females in the US. Despite a decrease in overall incidence and mortality, there has been an alarming increase of CRC diagnosis among young adults (20-49 years old). In an article from 2014, authors predicted an increase in colon cancer diagnosis in people under the age of 50 with the largest increase in the 20-34-year age group of 37.8% and 90.0% by 2020 and 2030, respectively. The increase for rectal cancer is higher in the 20-34-year age group by 2020 and 2030 it is estimated to increase by 49.7% and 124.2% respectively. The Colorectal Cancer Alliance launched a comprehensive survey for Young-Onset Colorectal Cancer (YO-CRC) patients and survivors to capture self-reported experiences of this often overlooked population. Methods:The survey was completed by 1089 patients, survivors and caregivers. Questions were designed based on several established and validated instruments, including AYA-HOPE, EORTC-QOL-30, EORTC-CR-29, EORTC-SHC-22, PROMIS-29, FACT-C, and COH-47. The final survey instrument and study plan were reviewed and approved by the Aspire, Inc. Institutional Review Board. Results:Most respondents (62%) waited 3-12 months before visiting a doctor after they noticed symptoms. Furthermore, when patients visited their doctors, most indicated that they were initially misdiagnosed. Many patients reported they had to see multiple doctors and had multiple appointments before they were correctly diagnosed with YO-CRC. The majority of the respondents (75%) saw at least 2 physicians, and about 20% saw 4 physicians or more, prior to their diagnosis. Patients who saw 3 or more physicians prior to diagnosis were more likely to be diagnosed with advanced disease. Conclusions:The findings expose a critical issue of YO-CRC patients being diagnosed at late stages. This is often due to multiple challenges around misinformation and medical providers dismissing symptoms and not trusting the patients' self-knowledge. Medical professionals need to be aware of the possibility of colorectal cancer more readily and screen patients regardless of age. The Colorectal Cancer Alliance is dedicated to working with all stakeholders and is committed to supporting researchers who are leaders in the field to better understand YO-CRC, as well as research that looks at improved therapies for those in treatment to improve outcomes.

Trends and Clinical Outcomes in Young-onset Colorectal Cancer Patients

Young individuals with colorectal cancer (CRC) tend to be diagnosed at advanced stages and are not routinely included in screening programmes. This study describes the incidence, disease pattern and factors affecting overall survival in young-onset CRC. A retrospective study of young-onset CRC patients diagnosed between 2010 and 2017 in a tertiary hospital was conducted. There were 99 patients, 69.7% had left-sided while 30.3% had right-sided CRC. The mean age was 43.3 years (43.3±5.0) and 62 patients (62.6%) were male. The incidence of young-onset CRC has been on the rise since 2014. Out of 99 patients, 65 (65.7%) underwent elective surgery, 30 (30.3%) underwent emergency surgery and the remainder 5 (4.0%) were palliated. The most common presenting complaints for patients who underwent elective surgery were abdominal pain, per-rectal bleeding and altered bowel habits. For patients who required emergency surgery, 20 (66.6%) presented with intestinal obstruction and 10 (33.3%) had intestinal perforation. There were 42 (42.4%) stage III CRC and 20 (20.2%) stage IV CRC. The most frequent metastatic site was the liver (20/20, 100%). Five patients had signet ring cells (5.1%) in their histology while 15 (15.2%) had mucinous features. The overall 5-year survival of young-onset CRC was 82.0%. Advanced overall stage (hazard ratio (HR) 6.1, CI 1.03-3.62) and signet ring histology (HR 34.2, CI 2.24-5.23) were associated with poor prognosis. Young-onset CRC tend to be left-sided with advanced presentations. However, their 5-year survival remains favourable as compared to the general population.