Colorectal cancer in young patients: An institutional experience.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15140-e15140
Author(s):  
Wissam Hanayneh ◽  
Yu Wang ◽  
Thomas J. George ◽  
Miles Cameron ◽  
Sanda Tan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mutational Analysis ◽  
Early Stage ◽  
Young Patients ◽  
Braf V600e ◽  
Mismatch Repair Gene ◽  
Study Cohort ◽  
Common Mutation ◽  
Perioperative Therapy ◽  
Cancer Specific Survival

e15140 Background: The incidence of colorectal cancer (CRC) in young patients (<50 years) is increasing but little is known about disease characteristics and treatment outcomes in this patient population. Methods: CRC patients diagnosed at < 50 years of age (UF 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: 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 74% diagnosed between age 40-50. One third (35.7%) of patients had rectal primary. DNA mismatch repair gene deficiencies (dMMR) and/or microsatellite instability (MSI) was tested in 60.1%; 10.5% had MSI-H or dMMR tumors and 11 of those had confirmed Lynch syndrome. Next generation sequencing (n= 71) or mutational analysis (n= 79) was performed. Most common mutation was exon 12 of K- ras (40.7%, n = 61) followed by TP53 (7.33%; n = 11) and PIK3CA (5.33%; n = 8). BRAF V600E was seen in 5 patients. Patients who underwent curative resections had better hemoglobin (p=0.005), albumin levels (p <0.001) and lower CEA level (p<0.001). Factors associated with poor survival were low albumin ≤34 g/l, advanced primary tumor (T3/T4), nodal disease (N1/N2) and presence of diffuse metastases. 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<0.001) among patients who underwent metastatectomy. Conclusions: Our results reveal that the most young CRC were 40-50 years age group with a female preponderance. Young 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 data sets are warranted. [Table: see text]

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

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 513-513
Author(s):  
Wissam Hanayneh ◽  
Thomas J. George ◽  
Thomas Read ◽  
Sanda Tan ◽  
Atif Iqbal ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Median Time ◽  
Mutational Analysis ◽  
Young Patients ◽  
Braf V600e ◽  
Mismatch Repair Gene ◽  
Study Cohort ◽  
Common Mutation ◽  
Repair Gene ◽  
Time To Diagnosis

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 < 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.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 691-691 ◽  
Author(s):  
Hiral D. Parekh ◽  
Yu Wang ◽  
Wissam Hanayneh ◽  
Miles Cameron ◽  
Sanda Tan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Treatment Outcomes ◽  
Early Stage ◽  
Young Patients ◽  
Study Cohort ◽  
Chi Square ◽  
Perioperative Therapy ◽  
Cancer Specific Survival ◽  
Disease Characteristics ◽  
Cox Proportional Hazard Regression

691 Background: The incidence of colorectal cancer (CRC) in young patients (< 50 years) is increasing but little is known about disease characteristics and treatment outcomes in this patient population. Methods: CRC patients diagnosed at < 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 < 0.001) and lower CEA level (p < 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 < 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]

Results from an institutional universal reflex testing program for MSI/MMR in colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 796-796 ◽  
Author(s):  
Aaron J Franke ◽  
Maira Gaffar ◽  
Michael Feely ◽  
Jason Scott Starr ◽  
Hiral D. Parekh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Impact Analysis ◽  
Early Stage ◽  
Stage Iv ◽  
Stage I ◽  
Braf V600e ◽  
Mismatch Repair Gene ◽  
Protein Loss ◽  
System Solution ◽  
Reflex Testing

796 Background: In colorectal cancer (CRC), clinical guidelines and immunotherapy treatment selection requires knowledge of tumor DNA mismatch repair gene deficiencies (dMMR) or accumulation of microsatellite repeats through genomic errors (MSI-H). Tumors harboring dMMR/MSI-H are found in 15- 20% of early stage CRC while the prevalence is ~5% in metastatic disease. Reflex testing of CRC to identify these important subsets has been proposed as a system-solution to improve identification. We present a large, single-institutional database of CRC reflexively profiled for MSI/MMR status at the University of Florida (UF). Methods: Beginning in 2009, stage IV CRC underwent reflex testing for MSI/MMR status. Earlier stage CRC testing began in subsequent years. For all new CRC diagnosed at UF, concurrent testing for dMMR by IHC (MLH1, PMS2, MSH2, MSH6), MSI by PCR (Promega MSI kit) and NGS is performed with appropriate positive and negative controls. IHC protein loss is confirmed by second GI pathologist. MSI is not performed if inadequate adjacent normal tissue. We conducted a retrospective analysis of all CRC samples analyzed between 2009 and 2017. Clinical data was collected from the EMR. This study was approved by the UF IRB. Results: A total of 388 new CRC cases were reflex tested (16% Stage I, 23% Stage II, 35% Stage III, and 25% Stage IV). Median age at diagnosis was 63 yrs (range: 17-98 yrs), 51% male and 79% white. Both MMR and MSI were performed in 244 (63%) tumors with 100% concordance when concurrently tested. dMMR/MSI-H incidence (20% in overall population) decreased with stage: I/II (31%), III (18%) and IV (~9%) and was associated with BRAF V600E mut in 36/76 cases (47%). Importantly, in pts < 50 yrs, 13% of stage IV patients were dMMR/MSI-H. Conclusions: Reflex testing of MMR/MSI status in CRC is feasible with concordant results. Routine testing results in identification of dMMR/MSI-H at or higher than published rates. Notable findings include the high prevalence in those with sporadic CRC and/or younger than 50 yrs. Continued impact analysis of this approach is warranted to maximize IO therapy offering.

Treatment monitoring of metastatic colorectal cancer by quantification and genotyping of mutated KRAS in circulating cell-free DNA.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15037-e15037 ◽  
Author(s):  
Thomas Seufferlein ◽  
Daniel Schwerdel ◽  
Hanna Welz ◽  
Ralf Marienfeld ◽  
Stefan A. Schmidt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mutational Analysis ◽  
Early Stage ◽  
Therapy Monitoring ◽  
Stage Iv ◽  
Therapy Resistance ◽  
Disease Monitoring ◽  
Liquid Biopsies ◽  
Kras Mutations ◽  
Non Invasive

e15037 Background: Treatment of stage IV colorectal cancer (mCRC) has made substantial progress over the last years but therapy monitoring still is in its early stage. A facile, non-invasive, repeatable assessment of the mutational state of a given tumor even during treatment could constitute a desirable biomarker for therapy stratification and disease monitoring. "Liquid biopsies" analyzing circulating free and circulating tumor DNA (cfDNA/ctDNA) from patients’ blood have been proposed as a a simple, non-invasive method that could fulfil this requirement. Methods: 27 patients with histologically confirmed mCRC were enrolled into a treatment surveillance cohort. For the analysis of concordance between tumor tissue DNA and cfDNA we analyzed 40 tissue and blood pairs from therapy naïve patients regarding their KRAS mutation status. The course of cfDNA values combined with targeted genotyping of KRAS mutations were assessed during several palliative chemotherapeutic regimens. cfDNA data were correlated with clinical parameters to establish its prognostic and predictive value. Results: Baseline cfDNA levels allow to significantly differentiate mCRC from healthy controls (14.23 ± 6.33 ng/ml vs. 2.60 ± 1.59 ng/ml; p < 0.0001). cfDNA values at baseline in therapy naïve patients correlate well with tumor burden (p < 0.05) and CEA levels (p < 0.05). cfDNA values significantly increased upon disease progression during 1st (p < 0.01) and 2nd line (p < 0.05) treatment, enabling a non-invasive disease monitoring approach. Moreover, there was a significant correlation between the cfDNA levels upon treatment and progression-free survival (p < 0.05). In addition, our data show that KRAS genotyping of cfDNA under therapy is feasible (80% blood-tissue concordance) and might benefit the patient due to early detection of therapy resistance. Conclusions: Repetitive quantitative and mutational analysis of cfDNA is likely to complement current diagnostic standards in stage IV CRC over the whole continuum of treatment.

Prognostic value of RAS, BRAF, and PIK3CA mutations in early-stage colorectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 594-594
Author(s):  
Jennifer Elizabeth Byer ◽  
Nishi Kothari ◽  
TzuHua Juan ◽  
Jamie K. Teer ◽  
Michael J. Schell ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Data ◽  
Braf Mutation ◽  
Prognostic Value ◽  
Early Stage ◽  
Stage I ◽  
Braf V600e ◽  
Pik3ca Mutations ◽  
1000 Genomes ◽  
Braf Mutant

594 Background: Activating mutations in the KRAS, BRAF and PIK3CA oncogenes deregulate growth-factor pathways and promote metastasis in colorectal cancer (CRC). The prognostic value of these mutations has been reported with conflicting results in early CRC. We evaluated RAS, BRAF, and PIK3CA mutations as prognostic biomarkers in early stage (stage I-III) colorectal cancer (CRC) patients. Methods: Tumor samples collected from 302 early stage CRC patients diagnosed between 1998 and 2010 were analyzed as part of a multi-institutional observational study. Targeted exome sequencing was performed using the Illumina NGS platform with 50-100X coverage of mutations. The BWA/GATK pipeline was used to identify variants and indels. Matched normal samples were not available for comparison to identify somatic mutations, therefore 1000 Genomes was used to filter normal variants. Variants identified in 1000 Genomes with an MAF <0.01 were filtered. Overall survival data was collected via retrospective chart review. Extended RAS, BRAF V600E, and PIK3CA (exon 9 and 20) mutations were evaluated. The log-rank test was used to compare survival distributions. Results: 302 patients were eligible for analysis (53 stage I, 125 stage II, 124 stage III). 109 patients had RAS mutations (KRAS or NRAS), 41 patients had BRAF mutations, and 29 patients had PIK3CA mutations. Of the 247 patients with microsatellite stability (MSS) 98 were RAS mutant, 10 were BRAF mutant, and 19 were PIK3CA mutant. Of the 55 patients with microsatellite instability high (MSI-H) 11 were RAS mutant, 31 were BRAF mutant, and 10 were PIK3CA mutant. BRAF mutation was prognostic for decreased OS (p= 0.0245), particularly in patients with MSS tumors (p=0.0141). RAS and PIK3CA mutations did not have prognostic value for OS (p =0.72 and 0.23 respectively). Conclusions: In early stage colorectal cancer, we confirmed BRAF mutation is prognostic for OS particularly in MSS patients. RAS and PIK3CA mutations did not confer prognostic value.

The relationship between the non-canonical NF-κB pathway, tumour microenvironment, systemic inflammation and survival in patients undergoing surgery for colorectal caner.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 631-631
Author(s):  
Meera Patel ◽  
Lindsay Bennett ◽  
Jean A Quinn ◽  
Hester Catharina van Wyk ◽  
Paul G. Horgan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Responses ◽  
Venous Invasion ◽  
Tumour Microenvironment ◽  
Braf V600e ◽  
High Expression ◽  
Inflammatory Cell Infiltrate ◽  
Cancer Specific Survival ◽  
Local Inflammatory Response ◽  
The Relationship

631 Background: In patients with colorectal cancer (CRC) the local and systemic inflammatory responses (LIR and SIR) are important determinants of disease progression. The present study examines the association of transcription factor RelB, a key member of the non-canonical NF-κB pathway and its association with LIR and SIR in patients undergoing resection of CRC. Methods: Patients with stage I-III CRC who underwent curative resection in a single institution and were in a previously constructed tissue microarray were studied. IHC was utilised to examine cytoplasmic and nuclear RelB expression. The relationship between RelB, clinicopathological characteristics, LIR (Klintrup-Mäkinen (KM) grade, CD3+ and CD8+T-cell density), SIR and cancer-specific survival (CSS) was examined. Results: 208 patients were included in the analysis. Cytoplasmic RelB (cyto-RelB) was associated with nuclear RelB ( p=0.006). High expression of cyto-RelB was associated with MMR competence ( p=0.010) but not with TNM stage ( p=0.468), venous invasion ( p=0.973), tumour budding ( p=0.068), tumour necrosis ( p=0.786), tumour cell proliferation ( p=0.907), BRAF V600E mutation ( p=0.585) or administration of adjuvant chemotherapy ( p=0.853). High cyto-RelB was inversely associated with mGPS (mGPS >1: low cyto-RelB – 19% vs. high cyto-RelB – 8%, p=0.017). Also, cyto-RelB was inversely associated with tumour inflammatory cell infiltrate at the margin, Klintrup-Mäkinen grade ( p=0.059), (CD3+ p=0.010, CD8+ p=0.007) and in the tumour (CD3+ p=0.002) and a trend with tumour stroma percentage ( p=0.079). High expression of cyto-RelB was not significantly associated with CSS ( p=0.052). Conclusions: In patients undergoing CRC resection, high expression of cyto-RelB was associated with an adverse host local inflammatory response. Up-regulation of the non-canonical NF- κB pathway may be an important mechanism whereby the tumour deregulates local inflammatory responses and evades host immunosurveillance. Further investigation of inflammation based signal transduction pathways in patients with colorectal cancer is warranted.

Second primary cancers in patients with sporadic deficient mismatch repair (dMMR) colorectal cancer (CRC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 45-45
Author(s):  
Ayman Alidina ◽  
Lara Rachel Lipton ◽  
Lucy Gately ◽  
Iain Skinner ◽  
Shehara Ramyalini Mendis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Stage ◽  
Elevated Risk ◽  
Stage I ◽  
Braf V600e ◽  
Second Primary ◽  
Primary Cancer ◽  
Colonoscopic Surveillance ◽  
Second Primary Cancers ◽  
Deficient Mismatch Repair

45 Background: Patients with hereditary non polyposis colorectal cancer (HNPCC) diagnosed with CRC have an elevated risk of a second primary CRC (SPCRC) and of rapid primary cancer development. This informs both initial surgical approach and endoscopic surveillance intervals. A feature of HNPCC is dMMR, also found in 15% of sporadic CRC, where the risk of SPCRC has yet to be defined. Methods: We examined a multi-site comprehensive CRC database (Melbourne, Australia), where prospectively collected data includes family history (including HNPCC), histology, surgery performed and incidence of second primary cancer. Sporadic dMMR included any case with a BRAF V600E mutation, confirmed hypermethylation, negative germline testing, or age over 60 years. We explored the incidence and timing of SPCRC in patients with early stage sporadic dMMR (or MSI-H) versus pMMR cancers. Results: From February 2004 to December 2019, 7442 patients diagnosed with stage I-III CRC were recorded. MMR status was known in 4079 (54.8%), including 714 with dMMR colorectal cancer (17.4%) of which 575 (14.6%) were deemed sporadic dMMR. Sporadic dMMR patients were older (mean 76.2 years vs 65.9 years, p = < 0.001), more likely to be female (65.2% vs 42%, p = < 0.001) and have a right sided primary (80.9% vs 32.8%, p = < 0.001), compared to patients with pMMR CRC. A SPCRC was diagnosed in 11/575 patients (1.91%) with sporadic dMMR CRC versus 27/3365 (0.83%) patients with pMMR CRC (HR = 2.57, 95% CI 1.28 - 5.17, p = 0.008). Median time to SPCRC was 1.13 years vs 2.38 years (p = 0.49). The SPCRC diagnosed in sporadic dMMR CRC vs pMMR CRC were more likely to be dMMR ((72.7%) vs (25.9%), p = 0.03), but a similar number were stage I or II ((81.8%) vs (81.5%)) and a similar number were surveillance detected ((72.7%) vs (77.8%). Conclusions: Patients with sporadic dMMR appear to have a significantly elevated risk of SPCRC compared to the pMMR population and were diagnosed at a shorter interval. The SPCRC is also more likely to also be dMMR. Increased colonoscopic surveillance of patients presenting with an initial sporadic dMMR cancer should be considered where clinically appropriate.

scholarly journals Racial/Ethnic Disparities in Survival Among Patients With Young-Onset Colorectal Cancer

2016 ◽  
Vol 34 (18) ◽  
pp. 2148-2156 ◽  
Author(s):  
Andreana N. Holowatyj ◽  
Julie J. Ruterbusch ◽  
Laura S. Rozek ◽  
Michele L. Cote ◽  
Elena M. Stoffel
Keyword(s):  
Colorectal Cancer ◽  
Racial Disparities ◽  
Early Stage ◽  
Tumor Biology ◽  
Ethnic Disparities ◽  
Cox Proportional Hazards ◽  
Cancer Specific Survival ◽  
Early Stage Disease ◽  
Young Onset ◽  
Significant Difference

Purpose Racial disparities in colorectal cancer (CRC) persist, despite overall reductions in morbidity and mortality. In addition, incidence is rising among individuals younger than 50 years of age. We compared the survival of young-onset CRC among non-Hispanic black (NHB), non-Hispanic white (NHW), and Hispanic individuals. Patients and Methods Using the National Cancer Institute’s Surveillance, Epidemiology, and End Results program data, we identified individuals between the ages of 20 and 49 years, diagnosed with CRC between 2000 and 2009. Survival rates and Cox proportional hazards models were used to compare stage-specific 5-year survival among NHBs, NHWs, and Hispanics. Results We identified 28,145 patients with young-onset CRC (19,497 NHW; 4,384 NHB; 4,264 Hispanic) during the 10-year study period. Overall survival at 5 years after CRC diagnosis was 54.9% among NHB, 68.1% among NHW, and 62.9% among Hispanic individuals (P < .001). NHB individuals had a significantly higher hazard of cancer-specific death compared with NHWs after adjusting for age, sex, race, stage, county-level poverty, and treatment history in cases of colon (hazard ratio [HR], 1.35; 95% CI 1.26 to 1.45) and rectum/rectosigmoid junction (HR, 1.51; 95% CI, 1.37 to 1.68) cancers, whereas there was no significant difference in survival between NHWs and Hispanics. The greatest racial disparities in cancer-specific survival were observed among NHB and NHW patients diagnosed with stage II cancers of the colon (HR, 1.69; 95% CI, 1.33 to 2.14) and stage III cancers of the rectum (HR, 1.98; 95% CI, 1.63 to 2.40). Conclusion Survival after CRC diagnosis at a young age is significantly worse among NHBs compared with NHWs, even among patients with early-stage disease. Further study is needed to determine whether differences in tumor biology and/or treatment are associated with racial disparities in outcomes, which would have implications for CRC treatment and prevention.

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