Young Colorectal Cancer Patients Research Articles

Colorectal cancer in young patients: a retrospective cohort study in a single institution.

Young onset colorectal cancer is on the rise, with a disproportionate increase in incidence among young people, both in Australia and internationally. Current national guidelines for bowel cancer screening in average risk individuals include only patients greater than 50 years of age. It is well recognized that colorectal cancer is a highly treatable malignancy when detected at an early stage, and timely diagnosis yields a greater than 90% chance of cure and survival. The aims of this study were to define the clinical presentations leading to colonoscopy in young patients and assess the incidence of malignancy in this group. This is a retrospective cohort study including all patients ≤35 years of age without any baseline indication for early bowel cancer surveillance that underwent colonoscopy at Caboolture Hospital from January 2017 to April 2018. A total of 224 patients underwent colonoscopy in the study period. A total of 210 (93.8%) had symptoms including rectal bleeding (51.7%), altered bowel habit (25.9%), abdominal pain (10.3%) and symptomatic anaemia (6.7%) prior to colonoscopy. Two cases of invasive adenocarcinoma were identified (0.89%, P < 0.01), both of which were symptomatic and were defined as stage IIIB disease on histopathology. In a theoretically low-risk population, the incidence of malignancy was nearly 1%. More advanced disease at diagnosis may be due to a delay in investigating these patients due to an overall low suspicion of cancer in young individuals. As such, investigation should be offered early to young patients presenting with any warning symptoms.

Young-age onset colorectal cancer in Brazil: Analysis of incidence, clinical features, and outcomes in a tertiary cancer center

BackgroundRecent studies report increasing incidence of colorectal cancer (CRC) in the young-age population, but data concerning clinical behavior, pathologic findings, and prognosis are controversial for this group. Early recognition of CRC in young patients is a challenge and diagnosis at advanced stage is clearly associated with worse outcomes. Materials and methodsWe retrospectively reviewed medical records of 5806 patients diagnosed with CRC between January/2011 and November/2016 and identified 781 patients aged less than 50-years-old. ResultsWe found an absolute increasing in the incidence of CRC in patients <50 years old of 1.88%–2.23% annually, with a relative increasing of 35.3% between 2011 and 2016. Median age was 42 years, 57.4% were female and 20.9% reported family history of CRC. Left-sided tumors were more frequent and the majority of patients were symptomatic. The most common stages at diagnosis were III (34.1%) and IV (37.3%). The median overall survival (OS) for stage IV was 25 months (95% CI 20.7-29.3) and was not reached for Stages I-III (P < 0.001). Family history of CRC was independently associated with better OS in stage IV(P = 0.02). For stages I-III, wild-type KRAS, family history of CRC, and absence of angiolymphatic invasion were associated with better OS (P = 0.02, P = 0.01 and P < 0.001, respectively). ConclusionsIn our cohort, the incidence of early-onset CRC is increasing over the past years. Young patients were more likely to be diagnosed with metastatic disease, left-sided and/or rectum site and symptoms at presentation. These findings highlight the emerging importance of young-age onset CRC and the need to discuss strategies to early diagnosis.

Patient and disease characteristics of colorectal cancer in a cohort of young patients.

513 Background: Despite effective screening for colorectal cancer (CRC), the incidence has been steadily rising in younger patients; the etiology for this phenomenon remains elusive. Methods: CRC patients diagnosed at &lt; 50 years of age (UF institutional registry 2000-2017) constituted the IRB approved study cohort. Results: Young CRC patients (n = 286) comprised 16% of total CRC patients (n = 1806) treated at our institution. (See table for demographics and tumor characteristics.) The median age at diagnosis was 45 years (range 17-50) with two-thirds diagnosed at age 40-50 (n-212, 74%) and 182 patients (63.6%) had a history of tobacco and/or alcohol use. The majority of patients (73.1%) had a left-sided tumor and 35% (n = 99) had stage 4 disease at presentation. The median time to diagnosis from onset of first symptoms was 90 days. DNA mismatch repair gene deficiencies (dMMR) and/or microsatellite instability (MSI) was tested in 172 patients (60.1%); 18 (10.5%) had MSI-H or dMMR tumors and 11 of those had confirmed Lynch syndrome through. Next generation sequencing (NGS, n = 71) or mutational analysis (n =79) was performed on 52.4%; most common mutation was KRAS (40.7%, n = 61) followed by TP53 (7.33%; n = 11) and PIK3CA (5.33%; n = 8). BRAF V600E was seen in five patients and another two had BRAF variant. Conclusions: Our results reveal that the majority of younger CRC were 40-50 years age group with a female preponderance. Advanced disease at diagnosis and longer median time to diagnosis should prompt educational efforts regarding appropriate screening and timely diagnostic investigation in this patient cohort. [Table: see text]

Disease characteristics and treatment outcomes of young colorectal cancer patients.

691 Background: The incidence of colorectal cancer (CRC) in young patients (&lt; 50 years) is increasing but little is known about disease characteristics and treatment outcomes in this patient population. Methods: CRC patients diagnosed at &lt; 50 years of age (UF institutional registry 2000-2017) constituted the IRB approved study cohort. Statistical methods included descriptive statistics, uni-variable cox proportional hazard regression model, Pearson chi-square exact and Wilcoxon rank-sum test. Results: The median age at diagnosis was 45 years (range 17-50, n = 286) with 212 (74%) diagnosed between age 40-50. One third (35.7%) of patients had rectal primary and most common histology was adenocarcinoma (ACa, 84.6%) and 20% of those had poorly differentiated tumor. More than half of patients had an advanced primary (T3/T4, 65%) and 44% had lymph node positive disease. A trend towards increased delivery of perioperative therapy was seen in early staged disease. (See table) Patients who underwent curative resections had better hemoglobin (p = 0.005) and albumin levels (Alb, p &lt; 0.001) and lower CEA level (p &lt; 0.001). Factors associated poor survival were low alb levels ≤ 34 g/l, advanced primary tumor (T3/T4), nodal disease (N1/N2) and presence of diffuse metastasis. For stage 4 disease, the cancer-specific survival (CSS) at 1 year was 77.2%, 3-year CSS was 46.1% and 5-year CSS was 29%; survival was better (HR = 0.4; 95% CI 0.2-0.6, p &lt; 0.001) among patients who underwent metastatectomy. Conclusions: Our data suggests that younger CRC patients were more likely to be managed in an aggressive manner with a higher proportion of early stage patients receiving perioperative therapy. A suggestion of an improved CSS was seen in advanced stage disease even with similar prognostic factors. Review of larger datasets are warranted. [Table: see text]

Differences in non-metastatic colorectal cancer in young patients – an analysis of the SEER registry

Differences in non-metastatic colorectal cancer in young patients – an analysis of the SEER registry

Microsatellite instability in young patients with mucinous colorectal cancers – characterization using molecular testing, immunohistochemistry, and histological features

The incidence of colorectal cancers (CRCs) in young Indian patients is higher than the international average. CRCs in young patients are commonly of mucinous type and show microsatellite instability (MSI). To ascertain the MSI status of mucinous CRCs in patients ≤40 years of age by molecular testing and to correlate this with immunohistochemical (IHC) analysis and tumor histology. Archived formalin-fixed paraffin embedded tissue blocks of 30 young mucinous CRC patients were retrieved. MSI testing was done using two mononucleotide markers - BAT26 and NR24. IHC analysis was done using MLH1, MSH2, and MSH6. Histological features of all cases were studied. Data were analyzed using the SPSS software and the Pearson's chi-square test and Fisher's exact test. Eight out of 30 cases (26.7%) showed MSI by molecular testing. IHC identified seven of these cases. Histological features showing a statistically significant association with MSI were the presence of a well-differentiated adenocarcinoma component (P = 0.003), peritumoral lymphocytes (P = 0.002) and tumor budding (P = 0.021). The detection of defective mismatch repair (MMR) proteins using IHC for MLH1, MSH2, and MSH6 and molecular testing using BAT26 and NR24 appears to be a good protocol to detect CRCs with MSI. Histology could be useful in identifying cases that require screening for presence of MMR protein defects.

145P - Pregnancy had no significant impact on young colorectal cancer patients

145P - Pregnancy had no significant impact on young colorectal cancer patients

Colorectal Cancer in Young Patients: Is 50 Still the Magic Number?

Colorectal Cancer in Young Patients: Is 50 Still the Magic Number?

Young versus Older-Onset Colorectal Cancer in a Safety Net Hospital

Introduction: To better understand recent increases in colorectal cancer (CRC) among younger adults (age <50 years), we compared demographic, clinicopathologic, and molecular characteristics of youngvs. older-onset CRC. Methods: We identified patients newly diagnosed with CRC at a large, integrated safety-net system between January 2009 and December 2017. We manually reviewed electronic medical records for patient demographics, tumor characteristics (e.g., stage, grade, histology), mutation testing, and treatment (e.g., surgery, chemotherapy, radiation). Results: Of 1,224 patients, 319 (26.1%) were diagnosed before age 50 years (median age 44.0), and 905 were diagnosed after age 50 years (median age 60.3). A higher proportion of younger patients were Hispanic (50.6% vs. 32.9%), had a family history of CRC (25.1% vs. 15.2%), were diagnosed with poorly differentiated tumors (24.3% vs. 14.2%), and had mucinous histology (11.3% vs. 7.2%). Of those with a family history of CRC (n=218), more young-onset patients reported CRC in a second- (50.0% vs. 23.9%) or third-degree (12.5% vs. 4.4%) relative. Distribution of CRC by anatomic subsite and stage at diagnosis was similar between the two groups, with 24.6% and 32.1% having stage I/II CRC, respectively. Receipt of surgery (77.7% vs 71.2%) and radiation therapy (24.8% vs 22.9%) was similar, compared to receipt of chemotherapy (75.6% vs 60.0%). More young patients underwent testing for BRAF (17.9% vs 13.7%), KRAS (49.2% vs 39.0%) and MMR deficiency (79.0% vs 61.6%). Of those who received MMR deficiency testing (n=809), 45 younger and 56 older patients were MMR deficient; 2 younger and 12 older patients had hypermethylation of the MLH1 promoter. About half (52.0%, n=166) of younger patients were referred to genetic counseling, and of those who received genetic testing (n=102), 43 had a germline mutation. Survival was similar between younger (mean 52.5 months) and older (mean 61.4 months) patients, after adjusting for stage at diagnosis (HR 0.82, 95% CI 0.64 - 1.02). Conclusion: We found few differences in anatomic subsite, stage at diagnosis, treatment, and survival between young- and older-onset CRC. Younger CRC patients more frequently reported second- or thirddegree relatives with CRC, which may provide clues for understanding mechanisms, beyond inherited syndromes (e.g., Lynch), that contribute to increasing incidence in this population.206 Figure 1 No Caption available.

Germline Pathogenic Variants in Homologous Recombination and DNA Repair Genes in an Asian Cohort of Young-Onset Colorectal Cancer.

BackgroundGrowing evidence suggests a role for cancer susceptibility genes such as BRCA2 and PALB2 in young-onset colorectal cancers. Using a cohort of young colorectal cancer patients, we sought to identify and provide functional evidence for germline pathogenic variants of DNA repair genes not typically associated with colorectal cancer.MethodsWe recruited 88 patients with young-onset colorectal cancers seen at a general oncology center. Whole-exome sequencing was performed to identify variants in DNA repair and colorectal cancer predisposition genes. Pathogenic BRCA2 and PALB2 variants were analyzed using immunoblot and immunofluorescence on patient-derived lymphoblastoid cells.ResultsIn general, our cohort displayed characteristic features of young-onset colorectal cancers. Most patients had left-sided tumors and were diagnosed at late stages. Four patients had familial adenomatous polyposis, as well as pathogenic APC variants. We identified 12 pathogenic variants evenly distributed between DNA repair and colorectal cancer predisposition genes. Six patients had pathogenic variants in colorectal cancer genes: APC (n = 4) and MUTYH monoallelic (n = 2). Another six had pathogenic variants in DNA repair genes: ATM (n = 1), BRCA2 (n = 1), PALB2 (n = 1), NTHL1 (n = 1), and WRN (n = 2). Pathogenic variants BRCA2 c.9154C>T and PALB2 c.1059delA showed deficient homologous recombination repair, evident from the impaired RAD51 nuclear localization and foci formation.ConclusionA substantial portion of pathogenic variants in young-onset colorectal cancer was found in DNA repair genes not previously associated with colorectal cancer. This may have implications for the management of patients. Further studies are needed to ascertain the enrichment of pathogenic DNA repair gene variants in colorectal cancers.

Clinical Characteristic of Young Indonesian Colorectal Cancer Patients: A Preliminary Study

&lt;p&gt;Introduction: Colorectal cancer (CRC) is generally a disease of persons aged above 40 year-old. Controversies still exist regarding clinical characteristics of CRC in young persons. The aim of this study is to know the clinical characteristics of young CRC patients in Siloam General Hospital, Karawaci, Banten.&lt;/p&gt;&lt;p&gt;Material And Methods: A total of 14 patients with diagnosis of CRC from December 2013 to January 2014 in Siloam General Hospital, Karawaci, Banten were studied cross – sectionally. The symptoms and signs, family history of cancer, diabetes, location of mass were collected and evaluated.&lt;/p&gt;&lt;p&gt;Results: There were 5 (35.7%) cases of CRC patients aged below 40 year-old (young patients) and 9 (64.3%) above 40 years-old (old patients). The most common symptom was constipation followed by bloody diarrhea i.e. 57.1% and 42.9% consecutively. Constipation occurred in 2 and 6 young and old patients consecutively and in 3 and 3 young and old patients consecutively. In young patients, 2 (14.2%) had a history of cancer in the family compared to none in the old patients. According to the location of tumor in the colon 4 (28.5%) were in ascending colon with 2 and 2 in young and old patients consecutively, 3 (21.7%) were in descending colon with 2 and 1 in young and old patients consecutively, 8 (57.1%) were in rectum with 2 and 6 in young and old patients consecutively. One young patient had diabetes, and one other young patient had positive &lt;em&gt;Clostridium difficile&lt;/em&gt; antigen and toxin.&lt;/p&gt;&lt;p&gt;Conclusion: Approximately 35.7% cases CRC patient in our hospital was of young patients. Two patients were having family history of cancer. The location of mass was not specific for young CRC patients.&lt;/p&gt;&lt;strong&gt;&lt;em&gt;Key words: colorectal cancer, young patients&lt;/em&gt;&lt;/strong&gt;

Impact of Patient Age on Molecular Alterations of Left-Sided Colorectal Tumors.

The incidence of colorectal cancer (CRC) in younger patients is rising, mostly due to tumors in the descending colon and rectum. Therefore, we aimed to explore the molecular differences of left-sided CRC between younger (≤45 years) and older patients (≥65). In total, 1,126 CRC tumor samples from the splenic flexure to (and including) the rectum were examined by next-generation sequencing (NGS), immunohistochemistry, and in situ hybridization. Microsatellite instability (MSI) and tumor mutational burden (TMB) were assessed by NGS. Younger patients (n = 350), when compared with older patients (n = 776), showed higher mutation rates in genes associated with cancer-predisposing syndromes (e.g., Lynch syndrome), such as MSH6 (4.8% vs. 1.2%, p = .005), MSH2 (2.7% vs. 0.0%, p = .004), POLE (1.6% vs. 0.0%, p = .008), NF1 (5.9% vs. 0.5%, p < .001), SMAD4 (14.3% vs. 8.3%, p = .024), and BRCA2 (3.7% vs. 0.5%, p = .002). Genes involved in histone modification were also significantly more mutated: KDM5C (1.9% vs. 0%, p = .036), KMT2A (1.1% vs. 0%, p = .033), KMT2C (1.6% vs. 0%, p = .031), KMT2D (3.8% vs. 0.7%, p = .005), and SETD2 (3.2% vs. 0.9%, p = .039). Finally, TMB-high (9.7% vs. 2.8%, p < .001) and MSI-high (MSI-H; 8.1% vs. 1.9%, p = .009) were more frequent in younger patients. Our findings highlight the importance of genetic counseling and screening in younger CRC patients. MSI-H and TMB-high tumors could benefit from immune-checkpoint inhibitors, now approved for the treatment of MSI-H/deficient mismatch repair metastatic CRC patients. Finally, histone modifiers could serve as a new promising therapeutic target. With confirmatory studies, these results may influence our approach to younger adults with CRC. The increasing rate of colorectal cancers (CRC), primarily distal tumors, among young adults poses a global health issue. This study investigates the molecular differences between younger (≤45 years old) and older (≥65) adults with left-sided CRCs. Younger patients more frequently harbor mutations in genes associated with cancer-predisposing syndromes. Higher rates of microsatellite instability-high and tumor mutational burden-high tumors occur in younger patients, who could benefit from immune-checkpoint inhibitors. Finally, histone modifiers are more frequently mutated in younger patients and could serve as a new promising therapeutic target. This study provides new insights into mutations that may guide development of novel tailored therapy in younger CRC patients.

Disease Characteristics, Clinical Management, and Outcomes of Young Patients With Colon Cancer: A Population-based Study

IntroductionThe incidence of colorectal cancer in young patients has been increasing. We evaluated whether the disease characteristics, management, and outcomes of patients with colon cancer differ among patients aged ≤ 40 years compared with those of older patients. Materials and MethodsUsing the Ontario Cancer Registry, all cases of colon cancer (stage I, II, III) treated with surgery in Ontario from 2002 to 2008 were identified. The electronic medical records of treatment were used to identify the use of surgery and adjuvant chemotherapy (ACT). The pathology reports were obtained for a random 25% sample of all cases. A Cox model was used to identify the factors associated with overall (OS) and cancer-specific survival (CSS). ResultsThe study population included 6775 patients. The age distribution was 2%, 5%, 14%, and 79% for patients aged ≤ 40, 41 to 50, 51 to 60, and > 60 years, respectively. Compared with patients aged > 60 years, younger patients (age ≤ 40 years) were more likely to have lymphovascular invasion (35% vs. 27%; P = .005), T3/T4 tumors (88% vs. 79%; P = .005) and lymph node–positive disease (58% vs. 41%; P < .001). The stage distribution varied by age: stage I, 8% versus 19%; stage II, 34% versus 40%; and stage III, 58% versus 41% for those aged ≤ 40 years versus those aged > 60 years, respectively (P < .001). ACT was delivered more often to patients aged ≤ 40 years than to those aged > 60 years for stage II (50% vs. 13%; P < .001) and stage III (≥ 92% vs. 57%; P < .001) disease. The adjusted OS (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.21-0.49) and CSS (HR, 0.41; 95% CI, 0.26-0.64) were superior for patients aged ≤ 40 years compared with the OS and CSS for those aged > 60 years. ConclusionYoung patients with colon cancer have more aggressive and advanced disease but improved outcomes compared with older patients.

Later Stage Disease and Earlier Onset of Rectal Cancer: Epidemiology and Outcomes Comparison of Rectal Cancer in a Rural Appalachian Area to State and National Rates

Although the overall rate of colorectal cancer (CRC) has remained stable, studies have shown an increase in the rate of CRC in young patients (<50) nationwide. We hypothesize that the rectal cancer (RC) rate in young people has increased in rural Appalachia. The goal is to provide insight into the future of RC epidemiology in underserved populations. This Institutional Review Board-approved retrospective study evaluated RC patients diagnosed in 2003 to 2016, and compared the ratio of early-onset RC to the state and national ratios using West Virginia State Cancer Registry, North American Association of Central Cancer Registries (NAACCR) and Surveillance, Epidemiology, and End Results Program Database. Demographics include age, gender, ethnicity, and county. We also evaluated cancer stage, family history, and comorbidities, including body mass index, smoking, and alcohol history. The rate of early-onset RC in our area is 1.5 times higher than the national rates. In our population, 100 per cent of patients were white with an equal gender distribution. Young patients with RC were noted to be more overweight than national rates. Young RC patients are more likely to have a first- or second-degree relative with cancer diagnosis. Smoking was strongly associated with young RC. Compared with national statistics, a higher proportion of young patients had Stage 1 or 2 disease which correlated with better survival. The rate of early-onset RC in the Tristate Appalachian area in West Virginia is higher than the national rate with risk factors including white ethnicity, obesity, diabetes mellitus, smoking, family history, and history of pelvic surgeries. It warrants further investigation and discussion of current CRC screening guidelines that begin at age 50.

PO-108 Nonstandard hypofraction radiotherapy in neoadjuvant chemo-radiation therapy in treatment of locally advanced rectal cancer

IntroductionNeoadjuvant chemoradiotherapy has become the standard treatment for locally advanced rectal cancer. Neoadjuvant chemoradiotherapy not only can reduce tumour size and recurrence, but also increase the tumour resection rate and anus retention rate with very slight side effect. Comparing with preoperative chemotherapy, preoperative chemoradiotherapy can further reduce the local recurrence rate and downstage.Material and methodsThe study of the efficacy of the developed neoadjuvant method of treatment of colorectal cancer with the use of remote nonstandard hypofraction radiotherapy SD 4 Gy every other day 3 fraction in week to achieve cumulative dose 36–40 Gy conducted in patients receiving capecitabine at a dose of 1700 mg/m2 during the entire course of radiation therapy (21 days), 3 infusion of oxaliplatin at a dose of 50 mg/m2 in 3, 10 and 17 days of treatment and 4–5 sessions of local microwave hyperthermia with course of metronidazole intrarectal administration radiosensitizing mixture consisting in 2 and 3 days of the course microwave hyperthermia. The treatment included 73 patients age of patients is from 45 to 68 with III stage (T3CD-4N0-2M0) of rectal cancer. (RT +CT + OXA+microwave hyperthermia+metronidazole). After a neoadjuvant treatment, all patients were operated in a radical amount within 7–8 weeks.Results and discussionsThe results of our study were as follows: complete clinical response in 33 patients, a partial response in 28 patients and the stabilisation of process in 12. In 33 patients due to clinical response was restaging disease. Postoperative complications were seen in 5 (6.8%) cases. In study group the use of preoperative nonstandard hypofraction radiotherapy in patients receiving capecitabine, oxaliplatin, microwave hyperthermia and metronidazole has increased the 5 year survival rate of up to 64.5%. The incidence of local recurrence was 37.6%, and the frequency of distant metastases of 21.8%ConclusionMethod of neoadjuvant treatment (RT +CT + OXA+microwave hyperthermia+metronidazole) in combination therapy of colorectal cancer in young patients does not affect intra-and postoperative complications and slightly increases the frequency of the 5 year survival. The hypofractive course of radiotherapy reduces the duration of radiotherapy and the duration of radiotherapy from 38 to 22 days compared with classical fractionation, which will favourably affect the financial situation and the quality of life of patients.

Long-term oncological outcomes of local excision versus radical resection for early colorectal cancer in young patients without preoperative chemoradiotherapy: a population-based propensity matching study.

The incidence and mortality of colorectal carcinoma are rising in young adults. This population‐based propensity matching study aimed to compare long‐term oncological outcomes of local excision with radical resection for early localized colorectal cancer (CRC) in young patients without preoperative chemoradiotherapy. Patients under 45 years old with T1 colon or rectal adenocarcinoma who underwent local excision or radical resection were included from the Surveillance, Epidemiology, and End Results (SEER) database between 1998 and 2014. Survival curves were plotted using the Kaplan–Meier method. Cancer‐specific survival (CSS) was compared using adjusted hazard ratios (HRs) between local excision and radical resection. After propensity score matching procedure, total of 1719 patients were included in the analysis, among which 573 treated with local excision and 1146 treated with radical resection. The median follow‐up was 80 months (interquartile range(IQR): 37–132), with 1074 patients followed for ≥5 years and 508 patients followed for ≥10 years. Five‐year CSS of local excision versus radical resection was 93.4% versus 96.7% for colon cancer and 96.6% versus 98.4% for rectal cancer. Ten‐year CSS of local excision versus radical resection was 91.4% versus 94.0% for colon cancer and 92.8% versus 96.7% for rectal cancer. On multivariable analysis, compared with radical resection, local excision was not associated with inferior CSS for colon (HR 1.74, 95% CI: 0.92–3.29, P = 0.090) and rectal cancer (HR 2.16, 95% CI: 0.99–4.71, P = 0.052). There is no evidence of differential long‐term oncological outcomes between local excision and radical resection. These findings supported clinical application of local excision for early colon and rectal cancer in young adults.

Poorer prognosis in young female patients with non-metastatic colorectal cancer: a hospital-based analysis of 5,047 patients in China.

PurposeTo investigate the association of age and sex on survival in non-metastatic colorectal cancer (CRC) patients and to identify groups at high risk for poor outcomes.Materials and methodsWe performed a retrospective analysis of 5,047 non-metastatic CRC patients from 2008 to 2013. Data regarding age at diagnosis; gender; tumor site; tumor stage; differentiation; lymphatic, neural or vascular invasion; and survival outcomes were collected. Patients were stratified into 10-year age groups (≤35, 36–45, 46–55, 56–65, 66–75, >75) and then further analyzed in three age groups (≤35, 36–75, >75). Disease-free survival (DFS) and overall survival (OS) were evaluated using univariate and multivariate Cox regression models.ResultsOf the 5,047 eligible patients, 41.3% were female. The tumor stages were balanced between the genders. In the female patients, the tumor stages were similarly distributed among the different age groups, while younger male patients were diagnosed with more advanced disease (P<0.001 for trend). When stratified into three age groups, young females experienced significantly poorer survival than young males (DFS: hazard ratio [HR]=1.85 [1.04–3.30], OS: HR=2.65 [1.11–6.34]). After adjusting for tumor stage, site, differentiated grade and lymphatic or vascular invasion status, females ≤35 and >75 had shorter DFS than patients between 36 and 75 years old (HR=1.57 [1.03–2.38] and HR=1.51 [1.11–2.05, respectively]), while there was no difference in DFS between females ≤35 and those >75. For male patients, older age was associated with poorer OS after the same adjustment.ConclusionYoung female CRC patients (≤35 years old) had the poorest DFS and quite poor OS compared to the other age groups. This emphasizes the need for health care providers to have a heightened awareness and to conduct further research when caring for young female CRC patients.

The caregiver voice: Insights into caring for the young adult colorectal cancer patient.

148 Background: According to data from the National Cancer Institute’s Surveillance, Epidemiology &amp; End Results (SEER) Program, since 1994 statistics show a 50% increase in young onset colorectal cancer incidence in the 20-49 age group. Researchers estimate that by 2030, more than 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in young adults under 50 years of age. Based on these alarming statistics and understanding the vital role caregivers play throughout the cancer continuum, our study explores the emotional and psychosocial implications for caregivers of young adult colorectal cancer survivors. Methods: From September 2015 – September 2017, our professional facilitator with over 25 years of cancer advocacy work hosted nationwide caregiver focus groups. Primary goals included reaching caregivers in rural, urban and community oncology settings to gain perspective from diverse populations. During the study period, we spoke with caregivers in 32 states via traditional focus group settings and online via Skype format. Results: 576 caregivers (37% male, 63% female) participated in our national focus groups. When asked to describe in one word their current feelings, the top ten responses were: Stressed, Anxious, Alone, Exhausted, Angry, Needed, Guilty, Burned-Out, Overwhelmed, Frustrated. 55% of the young caregivers reported they were experiencing self-health decline ( Can’t sleep, can’t focus – feel sad all the time). 73% reported they felt lost and totally helpless ( No control over situation or outcome). 89% reported depression ( We hurt because we can’t take their pain away). 76% reported they felt ill-equipped to help their loved one leading to stress and anxiety ( Desperate for whatever might help). Conclusions: New and expanded caregiver support services are needed. Emotional and psychosocial support are essential to the well-being of our caregivers as they provide vital support to patients in need throughout the cancer care continuum. We will continue the conversation with caregivers as we create programs and expand support services.

Age-related differences in gene expression in colorectal cancer (CRC).

654 Background: Colorectal cancer (CRC) in young patients is increasing in incidence and is associated with worse outcomes than CRC in older patients. While distinct molecular subtypes of CRC have been recently characterized, it is unclear whether there are molecular differences between the tumors of young and old patients. We sought to identify differences in gene expression of CRC between these two groups. Our discovery analysis identified a gene signature of several differentially expressed RNAs, from which we validated PEG10. The PEG10 gene on chromosome 7q21.3 has been implicated in liver, gallbladder, thyroid, and blood cancers, and is thought to play a role in cancer cell survival and regulation of apoptosis. In hepatocellular carcinoma, increased PEG10 expression has been associated with younger patient age. Methods: RNA sequencing data was obtained from The Cancer Genome Atlas (TCGA) and analyzed for differences in gene expression between patients ≤ 45 years old and those ≥ 65 years old. The identified differentially expressed genes were then validated with qPCR using human CRC tissue from patients ≤ 45 years old and those ≥ 65 years old. Results: RNA sequencing data from patients ≤ 45 years old (n = 29) and patients ≥ 65 years old (n = 299) identified seven genes with increased expression in younger patients: ZNF334 (log2 [fold change] = 2.30), DSC3 (1.78), PEG10 (1.67), CACNA1I (1.54), PKIA (1.33), MAP9 (1.27), and EPHX3 (1.17) (p &lt; 0.07). Validation with qPCR for PEG10 was most promising, and was performed on both young (n = 10, mean age = 39) and old patient samples ( n= 8, mean age = 72). Two cancers (20%) in the young group received radiation treatment and five (50%) received chemotherapy. One cancer (12.5%) in the old group received radiation and two (25%) received chemotherapy. PEG10 had increased expression in the young group with log2 [fold change] = 3.16 (p &lt; 0.02). Conclusions: We have identified a potentially unique gene expression signature for CRC in young patients, which includes PEG10. Functional analysis of PEG10 and other genes is underway using in vitro cell culture, archived human tumor tissue, and mouse tumor models.

Curative treatment for metastatic colorectal cancer in the young population: is it worth it?

A significant proportion of patients with colorectal cancer (CRC) presents with metastatic disease. In younger patients, a more aggressive approach is often adopted in an attempt to achieve cure and improve survival. The aim of this paper is to review the management and outcomes of young patients with metastatic CRC. All patients under 50 years diagnosed with CRC in a single institution from January 2007 to December 2015 were reviewed. Patient demographics, details of their treatments, progress and outcomes of treatment were collected for our review. There were 154 newly diagnosed CRC patients who were <50 years old during the study period. Thirty-three patients (21.4%) had stage IV disease on presentation. Seventeen (51.5%) of these 33 patients were treated with curative intent; 9 (52.9%) of whom underwent upfront surgical resection alone while the remaining 8 (47.1%) patients had neoadjuvant therapy followed by surgical resection. Among the 16 patients who were treated with palliative intent, 9 (56.3%) had surgery while 7 (43.7%) had definitive chemo- or radio-therapy. There was no significant difference in the median survival of patients treated with curative and palliative intent (29 vs. 24 months, P=0.140). Young CRC patients with stage IV disease typically survive for 2 years upon diagnosis. Those who were treated and underwent surgery with curative intent have a slightly longer but not statistically significant median survival than those treated with palliative intent. The role of aggressive treatment in these young patients with metastatic patients merits further evaluation.