Differences in the immune microenvironment between early and late-onset colon and rectal cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 214-214
Author(s):  
Ivy Hernandez Gardner ◽  
Ragavan Siddharthan ◽  
Kate Watson ◽  
Rebecca Ruhl ◽  
Sudarshan Anand ◽  
...  

214 Background: Over the past 35 years, there has been a significant increase in the number of patients below the recommended initial screening age (50 years old) diagnosed with colorectal cancer (CRC). Early onset colorectal cancer is more likely to occur in non-white patients, be located in the rectum, be diagnosed at a more advanced stage, and have concerning pathological features. The immune microenvironment in CRC is a key player in disease progression, therapy response, and overall survival. However, the role of the immune microenvironment in early onset CRC, particularly in rectal cancer has not been investigated. This study aims to characterize the immune microenvironment of early onset ( 50 years old) and late onset ( 65 years old) colon and rectal cancer patients. Methods: We used Nanostring immune profiling to analyze FFPE surgical specimens and identified genes that were differentially expressed between early and late onset colon and rectal cancer groups. We validate our results with qPCR. The differentially expressed genes in the rectal cancer cohort were compared to our analysis of a publically available database (GSE8721) of gene expression profiles for 203 rectal cancer and 160 matched normal mucosa samples. Immunohistochemistry (IHC) was performed on FFPE colorectal specimens for CXCL3. Results: Using Nanostring, we identified two genes that were differentially expressed between early and late onset colon cancer (IFITM1, CXCL3) and two genes in the rectal cancer cohort (FLT3, SAA1). CXCL3 has increased expression in late onset colon cancer utilizing qPCR and IHC. High expression of CXCL3 in both IHC and qPCR is associated with improved disease free survival. Analysis of the GSE8721 database also showed that FLT3 and SAA1 were differentially expressed in early versus late onset rectal cancer. Using qPCR, FLT3 is increased in early onset rectal cancer specimens compare to late onset rectal cancer, early and late onset colon cancer, and normal colon. Conclusions: There are distinct differences in the immune microenvironment between early and late onset colon and rectal cancer that may hold the potential for targeted therapeutics.

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e035556
Author(s):  
Heigo Reima ◽  
Jaan Soplepmann ◽  
Anneli Elme ◽  
Mari Lõhmus ◽  
Rena Tiigi ◽  
...  

ObjectivesLarge disparities in colorectal cancer (CRC) management and survival have been observed across Europe. Despite recent increases, the survival deficit of Estonian patients with CRC persists, particularly for rectal cancer. The aim of this study was to examine diagnostic, staging and treatment patterns of CRC in Estonia, comparing clinical data from 1997 and 2011.DesignNationwide population-based retrospective study.SettingEstonia.ParticipantsAll incident cases of colon and rectal cancer diagnosed in 1997 and 2011 identified from the Estonian Cancer Registry. Clinical data gathered from medical records.Outcome measuresDifferences in diagnostic, staging and treatment patterns; 5-year relative survival ratios.ResultsThe number of colon cancer cases was 337 in 1997 and 498 in 2011; for rectal cancer, the respective numbers were 209 and 349. From 1997 to 2011, large increases were seen in the use of colonoscopy and lung and liver imaging. Radical resection rate increased from 48% to 59%, but emergency surgeries showed a rise from 18% to 26% in colon and from 7% to 14% in rectal cancer. The proportion of radically operated patients with ≥12 lymph nodes examined pathologically increased from 2% to 58% in colon cancer and from 2% to 50% in rectal cancer. The use of neoadjuvant radiotherapy increased from 6% to 39% among stage II and from 20% to 50% among patients with stage III rectal cancer. The use of adjuvant chemotherapy in stage III colon cancer increased from 42% to 63%. The 5-year RSR increased from 50% to 58% in colon cancer and from 37% to 64% in patients with rectal cancer.ConclusionsMajor improvements were seen in the diagnostics, staging and treatment of CRC in Estonia contributing to better outcomes. Increase in emergency surgeries highlights possible shortcomings in timely diagnosis and treatment.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4072-4072
Author(s):  
Abdul Moiz Khan ◽  
Zainub Ajmal ◽  
Usman Naseer ◽  
Darren Gemoets ◽  
Syed Arzoo Mehdi

4072 Background: While the overall incidence of colorectal cancer (CRC) is decreasing, the rate has increased in population under 50, with higher stages at diagnosis and a greater proportion of African Americans (AA). Hence, there is an ongoing debate about the age of CRC screening. These trends have not been studied in the VA population. Methods: ICD-10 codes C18-C20 were used to identify the cases of colon and rectal cancer in National VA Cancer Cube Registry. 43,544 cases of colon cancer, 1,278 below and 42,254 above age 50, and 19,815 cases of rectal cancer, 862 below and 18,948 above age 50 were identified between 2003-17. Younger age group was defined as patients less than 50 years old. IRB approval was obtained. Results: Our data comprised > 97% of male patients. In younger group, in the 5 year periods, 2003-07, 2008-12 and 2013-17, colon cancer rate increased from 2.59% to 2.79% to 3.59%, while for rectal cancer it increased from 3.5% to 4.3% to 5.3% (p < .0001). Blacks comprise 31.6% cases of colon cancer and 27.15% cases of rectal cancer in under 50 group, compared to 18.5% and 15.9% of cases in above 50 group respectively (p < .0001). For under 50 group, 48.6% cases of colon and 42.2% cases of rectal cancer were diagnosed in stage III or IV compared to 35.7% and 34.05% cases in above 50 group respectively (p < .0001). For colon cancer, 51.87% of patients in the younger group have a < 5 year survival, worse compared to 45.05% in 50-60 group (p < .0001) and similar to 49.3% in 60-70 group (p = .08). For rectal cancer, 5 year survival showed no difference between these groups. Stage specific survival shows no difference for either colon or rectal cancer across < 50, 50-60 and 60-70 age groups. Conclusions: Rate of CRC is rising in < 50 age group with more advanced stage at diagnosis and higher proportion of African Americans. For colon cancer, < 50 group has a worse 5 year survival as compared to 50-60 age group likely due to increased proportion of patients in stage III or IV, as there is no difference in stage specific survival. For rectal cancer, the 5 year survival or stage specific survival shows no difference in < 50, 50-60 and 60-70 groups. These results add to our understanding of the trends of CRC and should be accounted for in the screening guidelines.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9596-9596
Author(s):  
Haider Samawi ◽  
Abdel Aziz Shaheen ◽  
Patricia Tang ◽  
Daniel Yick Chin Heng ◽  
Winson Y. Cheung ◽  
...  

9596 Background: Colorectal cancer (CRC) patients have a higher risk of suicide as compared with the general population. Due to differences in the sites/morbidity of recurrences as well as ostomy rates, we sought to evaluate the distribution and predictors of suicide among patients with colon and rectal cancer. Methods: A retrospective analysis was undertaken using the Surveillance, Epidemiology, and End Results (SEER) database from 1973-2009. Patients included were >18yrs and had confirmed adenocarcinoma of the colon or rectum. Results: Included in this analysis were 187,996 rectal cancer and 443,368 colon cancer patients. Colon cancer patients were older (median age 71 vs. 67 yrs, p <0.001) and included more females (51 vs. 43%, p <0.001) as compared to rectal cancer patients. Suicide rates were similar (611 [0.14%] vs. 337 [0.18%], p <0.001), as was the median time to suicide for colon vs. rectal cancer patients respectively (37 vs.32 months, p = 0.13). On univariate analysis, having rectal cancer was a predictor of suicide (HR 1.26; 95% CI: 1.10-1.43). However after adjustment for age, sex, race, marital, primary site surgery, stage and one primary, rectal cancer was not a predictor of suicide (HR 1.05; CI: 0.83- 1.33). In the combined CRC cohort, independent predictors of suicide included age >70 (HR 1.55; CI: 1.23-1.94), male gender (HR 7.56; CI: 5.34-10.70), being single (HR 1.56; CI: 1.14- 2.13), distant metastases at diagnosis (HR 1.58; CI: 1.13- 2.21), and white race (HR 3.21; CI: 1.75- 5.88). Also, lack of resection of primary tumor was associated with increased risk of suicide (HR 2.83; CI: 1.97- 4.05). Among colon cancer cohort, older age, male gender, and white race as well as lack of primary resection were independent predictors of suicide. Similarly, the aforementioned predictors as well as metastatic disease on presentation were the independent predictors of suicide in the rectal cohort. Conclusions: The suicide risk in CRC patients is low (< 0.2%) and no difference was found based on location of primary tumor. Gender, age, distant spread of disease, intact primary tumour and race are the main predictors of suicide among colorectal patients. Future studies and interventions are needed to target these high risk groups.


2017 ◽  
Vol 24 (6) ◽  
pp. 513 ◽  
Author(s):  
H.H. Samawi ◽  
A.A. Shaheen ◽  
P.A. Tang ◽  
D.Y.C. Heng ◽  
W.Y. Cheung ◽  
...  

Background The risk of suicide is higher for patients with colorectal cancer (crc) than for the general population. Given known differences in morbidity and sites of recurrence, we sought to compare the predictors of suicide for patients with colon cancer and with rectal cancer.Methods Using the U.S. Surveillance, Epidemiology, and End Results database, adult patients with confirmed adenocarcinoma of the colon or rectum during 1973–2009 were identified. Parametric and nonparametric tests were used to assess selected variables, and Cox proportional hazards regression models were used to determine predictors of suicide.Results The database identified 187,996 patients with rectal cancer and 443,368 with colon cancer. Compared with the rectal cancer group, the colon cancer group was older (median age: 70 years vs. 67 years; p < 0.001) and included more women (51% vs. 43%, p < 0.001). Suicide rates were similar in the colon and rectal cancer groups [611 (0.14%) vs. 337 (0.18%), p < 0.001]. On univariate analysis, rectal cancer was a predictor of suicide [hazard ratio (hr): 1.26; 95% confidence interval (ci): 1.10 to 1.43]. However, after adjusting for clinical and pathology factors, rectal cancer was not a predictor of suicide (hr: 1.05; 95% ci: 0.83 to 1.33). In the colon cancer cohort, independent predictors of suicide included older age, male sex, white race, and lack of primary resection. The aforementioned predictors, plus metastatic disease, similarly predicted suicide in the rectal cancer cohort.Conclusions The suicide risk in crc patients is low (<0.2%), and no difference was found based on location of the primary tumour. Sex, age, race, distant spread of disease, and intact primary tumour were the main predictors of suicide among crc patients. Further studies and interventions are needed to target these high-risk groups.


2020 ◽  
Vol 52 (3) ◽  
pp. 938-944
Author(s):  
Sun Jin Park ◽  
Kil Yeon Lee ◽  
Suk-Hwan Lee

PurposeWe report nationwide data on the current status of laparoscopic surgery for colorectal cancer (CRC) in Korea.Materials and MethodsNationwide data of patients who underwent surgery for CRC from 2013 to 2018 were obtained from the Health Insurance Review & Assessment Service database. Data and trends of laparoscopy use for colorectal resection over six years were examined. ResultsIn Korea, a total of 117,320 patients underwent surgical resection for CRC from 2013 to 2018. The proportion of laparoscopic resection increased from 64.9% in 2013 to 78.5% in 2018. The rate of laparoscopic resection for colon cancer increased from 64.7% in 2013 to 77.4% in 2018. For rectal cancer, the rate of laparoscopic resection increased from 65.4% to 81.6%. Males accounted for 59.8% of all patients, but females surpassed males at over 80 years of age. The age of peak incidence was in the 60s for males and in the 70s for females. A steady increase in the number of patients undergoing surgery for CRC was observed over 80 years of age.ConclusionThe laparoscopic penetration rate for CRC in Korea continued to increase annually and reached 78.5% in 2018.


2020 ◽  
Author(s):  
Ivy H. Gardner ◽  
Ragavan Siddharthan ◽  
Katherine Watson ◽  
Elizabeth Dewey ◽  
Rebecca Ruhl ◽  
...  

AbstractDespite a decrease in the incidence of colorectal cancer (CRC) over the last 40 years, the incidence of CRC in people under 50 years old is increasing around the globe. Early onset (≤50 years old) and late onset (≥65 years old) CRC appear to have differences in their clinicopathological and genetic features, but it is unclear if there are differences in the tumor microenvironment. We hypothesized that the immune microenvironment of early onset CRC is distinct from late onset CRC and promotes tumor progression. We used Nanostring immune profiling to analyze mRNA expression of immune genes in FFPE surgical specimens from patients with early (N=40) and late onset (N=39) CRC. We found three genes, SAA1, C7, and CFD, have increased expression in early onset colorectal cancer and distinct immune signatures based on the tumor location. After adjusting for clinicopathological features, increased expression of CFD and SAA1 were associated with worse progression free survival and increased expression of C7 was associated with worse overall survival. Our data demonstrate that the immune microenvironment in early onset CRC is unique, location dependent, and associated with worse outcomes.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15089-e15089
Author(s):  
M. B. Jameson ◽  
M. Head ◽  
S. Deva

e15089 Background: Adjuvant chemotherapy for colorectal cancer (CRC) using fluorouracil (5FU) and folinic acid (FA) has been proven effective and the QUASAR trial showed that a weekly administration schedule was as effective as, and less toxic than, the same daily doses delivered over 5 days every 4 weeks (the “Mayo regimen”). However the 5FU dose used (370 mg/m2) was lower than in some trials and a higher 5FU dose was considered desirable if tolerated. We therefore implemented a weekly regimen using 5FU 425 mg/m2 and DL-folinic acid 50mg in 2001 and retrospectively evaluated its efficacy and tolerability. Methods: Patients with non-metastatic CRC at assessment by medical oncologists in this institution between 2001 and 2004 were included in the analysis. Data was gathered on patient characteristics, duration of adjuvant chemotherapy and survival. Actuarial survival was calculated using the Kaplan-Meier method. Results: 417 patients (pts) were seen: 181 females, 236 males; median age 67 yrs (24–89); 291 with colon cancer, 126 with rectal cancer; 1 stage 1; 100 stage 2, 316 stage 3. Median follow-up was 6.2 years. 210 pts with colon cancer received adjuvant weekly 5FU/FA (32 stage 2, 178 stage 3) as did 58 pts with rectal cancer (50 of whom also received concurrent chemoradiation). 75% of pts with colon cancer received all 30 planned doses and 59% of rectal cancer pts received all 20 planned doses. 3 year survival for all pts treated with this regimen was 83.0% and for the subgroups with colon and rectal cancer it was 82.4% and 84.5% respectively. For stage 2 and 3 colon cancer pts treated with this regimen 3 year survival was 87.9% and 76.0% respectively; for stage III rectal cancer pts it was 84.1%. Conclusions: These outcomes compare favorably on indirect comparison with results from the QUASAR trial (which reported 3 year survival of 70.6%) and suggest that using a higher 5FU dose in this regimen is tolerable and may be advantageous. No significant financial relationships to disclose.


2006 ◽  
Vol 4 (4) ◽  
pp. 384 ◽  
Author(s):  
_ _

Colorectal cancer is the third most frequently diagnosed cancer in men and women in the United States. An estimated 104,950 new cases of colon cancer and 40,340 new cases of rectal cancer will occur in the United States in 2005. During the same year, an estimated 56,290 people will die from colon and rectal cancer. Because patients with localized colon cancer have a 90% 5-year survival rate, screening is a critical and particularly effective procedure for colorectal cancer prevention. Screening options include colonoscopy; combined fecal occult blood test (FOBT) and sigmoidoscopy; sigmoidoscopy alone; or double-contrast barium enema. For the most recent version of the guidelines, please visit NCCN.org


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15539-e15539
Author(s):  
Dylan E. O'Sullivan ◽  
Yibing Ruan ◽  
Robert Liam Sutherland ◽  
Winson Y. Cheung ◽  
Steven J. Heitman ◽  
...  

e15539 Background: There has been a consistent increase in the incidence of early-onset colorectal cancer (eoCRC), under the age of 50, in Canada since the late 1990s. Questions remain surrounding how these trends vary by topography, histology, and stage, and related trends with CRC-specific mortality. Methods: CRC incidence data were obtained from the Canadian Cancer Registry and CRC-specific mortality data from the Canadian Vital Statistics – Death Database for the years 2000 to 2017. Age-specific average annual percent changes (AAPC) in the incidence (by topography and histology) and mortality rates of CRC were estimated using the National Cancer Institute’s Joinpoint Regression Program. To determine age-specific differences (5-year age groups) in CRC diagnosis at late stage (III and IV) for years 2011 to 2017 combined, a logistic regression model adjusting for sex with the 50-54 age group as the referent was conducted. Results: AAPCs and 95% confidence intervals in the rates of incidence (topography and histology) and mortality of eoCRC from 2000 to 2017 in Canada are presented in Table. Different trends in topography were observed across sexes with the largest increases in the distal colon (splenic flexure, descending, and sigmoid) and rectum among males and rectum only among females. Significant increases were observed for non-mucinous adenocarcinomas, while significant decreases were observed for mucinous adenocarcinomas among the 40-49 age group. Compared to the 50-54 age group, only the 45-49 group had a significantly higher odds of developing late-stage colon cancer, while men and adults 25-49 had a higher odds of developing late stage rectal cancer. Despite increases in the incidence of eoCRC there has only been a significant increase in mortality for men aged 20-39. Trends in mortality vary by site, with significant decreases observed for colon cancer-specific mortality among the 40-49 age group and increases in rectal cancer-specific mortality for adults aged 20-49. Conclusions: These results indicate that the largest increases in incidence and mortality for eoCRC have occurred in the rectum and trends have varied by sex. Further research on the etiology and treatment outcomes of eoCRC patients are warranted for this patient population.[Table: see text]


Author(s):  
C. Montuclard ◽  
V. Jooste ◽  
V. Quipourt ◽  
S. Marilier ◽  
J. Faivre ◽  
...  

Background/Objectives: Data on the time between colorectal cancer diagnosis and treatment in real-life practice for elderly patients are scarce. We measured times from diagnosis to first-course therapy in elderly patients with colon and rectal cancers. Design: The study was carried out on the population-based Burgundy Digestive Cancer Registry (France). Setting: Therapeutic delays were described by medians and interquartile ranges and compared by the Kruskal-Wallis rank test. Factors associated with changes in therapeutic delay were identified using a multivariate Cox model. Participants: The analysis was carried out on 2,884 patients aged 60 years and over with colorectal adenocarcinoma diagnosed between 2005 and 2011. Measurements and Results: The median therapeutic delay for colon cancer was 25 days in patients aged 60 to 69 years and 24 days for those aged 70-79 years. The delay fell significantly to 19 days in patients aged 80 and over (p<0.001). The median therapeutic delay for rectal cancer did not vary according to age group (respectively 39, 38 and 33 days). For colon cancer, a Charlson comorbidity score=0, in all age groups, and private care for patients under 80 years, significantly shortened the therapeutic delay. It was significantly longer during the period [2008-2011] only in patients under 80 (HR: 0.89 [0.81 - 0.99] p=0.037). For rectal cancer, only advanced stage (HR advanced vs II: 1.39 [1.04-1.86], p=0.025) shortened the therapeutic delay in patients under 80, while private care shortened therapeutic delay only in patients over 80 (HR private vs public: 1.66 [1.00-2.74], p=0.049). Conclusion: This study highlights that differences in therapeutic delay for the elderly increased over time for colon and rectal cancer. The therapeutic delay did not differ much between the 60-69 and the 70-79 years age groups, whereas it was shorter for patients aged 80 and over.


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