Validation of the Glasgow Microenvironment Score in patients with colon cancer: A pathology-based prognostic tool.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 206-206
Author(s):  
Peter G Alexander ◽  
Antonia K. Roseweir ◽  
Kathryn AF Pennel ◽  
Hester Catharina Van Wyk ◽  
Arfon GMT Powell ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Subgroup Analysis ◽  
Small Sample Size ◽  
Prognostic Score ◽  
Venous Invasion ◽  
Small Sample ◽  
Inflammatory Cell Infiltrate ◽  
Emergency Presentation ◽  
Node Positive Disease

206 Background: The Glasgow Microenvironment Score (GMS), comprised of assessment of the tumour inflammatory cell infiltrate (using Klintrup-Mäkinen (KM) grade) and tumour-associated stroma (TSP), has been reported as a stage-independent prognostic score in patients with colorectal cancer. The present study aims to validate the GMS and examines its prognostic utility in the context of stage and MMR status. Methods: Patients who had undergone resection of stage I-III colon cancer were included ( n= 495). GMS was scored by combining KM and TSP as follows: high KM scores 0; low KM with low TSP scores 1; low KM and high TSP scores 2. Cancer specific (CSS) and overall survival (OS) were primary endpoints. Subgroup analysis was performed to assess the utility of GMS according to TNM, venous invasion and MMR status. Results: There were 30% of patients with GMS 0, 56% with GMS 1 and 14% with GMS 2. Five-year survival for GMS 0, 1 and 2 across the whole cohort were 89%, 74% and 66%, respectively. GMS was associated with age, mode of presentation, TNM, venous invasion and MMR status. On multivariate analysis, GMS was independently associated with CSS (HR 1.35, 95% CI: 1.02-1.79, p= 0.04) and OS (HR 1.23, 95% CI: 1.02-1.48, p= 0.03); this was independent of emergency presentation ( p< 0.01), T-stage ( p= 0.03) and N-stage ( p< 0.001) for CSS. Subgroup analysis found that GMS was able to stratify CSS regardless of node-negative or node-positive disease (both p< 0.01), venous invasion ( p< 0.05), elective presentation ( p< 0.01) and MMR-proficient tumours ( p< 0.001), although it was not able to stratify emergency presentation ( n= 154) or MMR-deficient disease ( n= 102) due to small sample size. Universally, the prognosis for GMS 0 was good, but was poor for GMS 2. The prognosis for GMS 1 varied depending on MMR and nodal status. Conclusions: This study validates the use of the GMS as an independent prognostic pathology-based tool for stratification of colon cancer. It could be readily applied to routine clinical practice and may be used to aid decision making regarding adjuvant treatments in colorectal cancer. It should be further validated in prospective randomised trials.

Prognostic implications of tumor sidedness in colorectal cancer patients in South Dakota, 2006-2015.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 46-46
Author(s):  
Jonathan Scott Bleeker ◽  
Muslim Atiq ◽  
Morgan Nelson ◽  
Kay Dosch
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
South Dakota ◽  
Metastatic Disease ◽  
Small Sample Size ◽  
Hepatic Flexure ◽  
Small Sample ◽  
Colon And Rectum ◽  
Prognostic Implications ◽  
Colorectal Cancer Patients

46 Background: Tumor “sidedness” is emerging as an important prognostic and predictive factor in patients with metastatic colorectal cancer (CRC), with right sided colon cancer (RC) associated with poorer overall survival (OS) than left sided colon cancer (LC). This distinction has been noted in clinical trials and large databases, where American Indian (AI) populations are generally underrepresented. This project aims to investigate the prognostic implications of CRC sidedness in the state of South Dakota, focusing on the AI population. Methods: Data from patients diagnosed with CRC in the South Dakota cancer registry from January 1, 2006 to December 31, 2015 were analyzed for demographic and presenting features as well as survival outcomes. A total of 3,637 cases were included in the analysis, of which 191 (5%) were AI. Tumors arising from the cecum, ascending colon, hepatic flexure and transverse colon were considered RC while those arising from the splenic flexure, descending colon, sigmoid colon and rectum were considered LC. Results: In all patients, 47.1% of cases were RC; Caucasians (C) were significantly more likely to have RC, as 47.7% of cases in Caucasians were RC, whereas in the AI population, 35.6% cases were RC (p=0.005). Patients with RC were more likely to be female and older and less likely to present with metastatic disease than LC. Tumor sidedness was not associated with OS when analyzing all patients regardless of stage or in patients with non-metastatic disease. In patients with metastatic disease, RC was associated with inferior OS compared to LC [Median OS (mo): 9.9 v. 23.6, p<0.001]. When analyzed by race, RC was associated with inferior OS in C [Median OS (mo): 9.6 v. 23.6, p=0.002] but not in AI [Median OS (mo): 10.2 v. 10.4, p=0.082]. Conclusions: Although limited by small sample size, this analysis is hypothesis generating, as AI patients with CRC were more likely to have LC than Caucasians and the well described prognostic implications of RC were not noted in the AI population. Larger population studies and further investigation as to potential explanations for this finding are recommended.

scholarly journals The Relationship Between Tumor Budding, Tumor Microenvironment, and Survival in Patients with Primary Operable Colorectal Cancer

2019 ◽  
Vol 26 (13) ◽  
pp. 4397-4404 ◽  
Author(s):  
Hester C. van Wyk ◽  
Antonia Roseweir ◽  
Peter Alexander ◽  
James H. Park ◽  
Paul G. Horgan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Evaluation Method ◽  
Venous Invasion ◽  
Staging System ◽  
Consensus Conference ◽  
Tumor Budding ◽  
Inflammatory Cell Infiltrate ◽  
Cancer Specific Survival ◽  
The Relationship

Abstract Background Tumor budding is an independent prognostic factor in colorectal cancer (CRC) and has recently been well-defined by the International Tumour Budding Consensus Conference (ITBCC). Objective The aim of the present study was to use the ITBCC budding evaluation method to examine the relationship between tumor budding, tumor factors, tumor microenvironment, and survival in patients with primary operable CRC. Methods Hematoxylin and eosin-stained slides of 952 CRC patients diagnosed between 1997 and 2007 were evaluated for tumor budding according to the ITBCC criteria. The tumor microenvironment was evaluated using tumor stroma percentage (TSP) and Klintrup–Makinen (KM) grade to assess the tumor inflammatory cell infiltrate. Results High budding (n = 268, 28%) was significantly associated with TNM stage (p < 0.001), competent mismatch repair (MMR; p < 0.05), venous invasion (p < 0.001), weak KM grade (p < 0.001), high TSP (p < 0.001), and reduced cancer-specific survival (CSS) (hazard ratio 8.68, 95% confidence interval 6.30–11.97; p < 0.001). Tumor budding effectively stratifies CSS stage T1 through to T4 (all p < 0.05) independent of associated factors. Conclusions Tumor budding effectively stratifies patients’ survival in primary operable CRC independent of other phenotypic features. In particular, the combination of T stage and budding should form the basis of a new staging system for primary operable CRC.

Methylated DNA markers for monitoring palliative chemotherapy response in advanced colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15511-e15511
Author(s):  
Mojun Zhu ◽  
Douglas W. Mahoney ◽  
Kelli Burger ◽  
Patrick H. Foote ◽  
Karen A. Doering ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Treatment Response ◽  
Systemic Therapy ◽  
Small Sample Size ◽  
High Sensitivity ◽  
Response Assessment ◽  
Small Sample ◽  
Chemotherapy Response ◽  
Continuous Variables ◽  
Methylated Dna

e15511 Background: Aberrantly methylated DNA marker (MDM) candidates are strongly associated with primary colorectal cancer (CRC) before treatment and detect CRC recurrence with high sensitivity when assayed from plasma. The relationship of these MDMs in association to chemotherapy treatment response is unknown. Methods: In a prospective cohort of patients receiving systemic therapy for advanced CRC, peripheral blood was collected serially during restaging visits. 15 patients were retrospectively identified to have partial response (PR), stable disease (SD) and progressive disease (PD) to treatment (n=5 for each group) based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Using paired samples from each patient before and after response assessment, we analyzed 11 MDMs ( GRIN2D, ZNF671, ANKRD13B, QKI, VAV3, JAM3, SFMBT2, CHST2, ZNF568, FER1L4 and CNNM1) to assess correlation with treatment response. Cell-free DNA was extracted and bisulfite treated before MDMs were quantified by target enrichment long-probe quantitative-amplified signal assay and normalized to a methylated sequence of B3GALT6. Continuous variables are summarized as a median with corresponding interquartile ranges (IQR) and comparisons between subgroups were based on the Wilcox Rank Sums test. Results: The median interval between pre- and post-response assessment visits was 69 days (IQR: 63-83 days) and the level of tumor burden at pre-assessment was similar across all response types (Table 1). Patients with PD had higher levels of methylated GRIN2D, ZNF671 and ANKRD13B than those with PR or SD at baseline and may offer additional prognostic value over CEA which was similar in the PR and PD groups before treatment (Table 1). Elevation of pre-assessment MDMs preceded radiographic evidence of disease progression by 82 days (IQR 69-83 days). Conclusions: Three MDMs, GRIN2D, ZNF671 and ANKRD13B, were found to reflect treatment response (PD vs. PR + SD) as shown in the table. Although this pilot study was limited by a small sample size, it demonstrated the feasibility of using plasma-based MDMs in monitoring treatment response to systemic therapy for advanced CRC and should be compared to CEA in a larger study.[Table: see text]

scholarly journals Extramural Venous Invasion as Prognostic Factor of Recurrence in Stage 1 and 2 Colon Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-6
Author(s):  
E. E. van Eeghen ◽  
M. J. Flens ◽  
M. M. R. Mulder ◽  
R. J. L. F. Loffeld
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cox Regression ◽  
Venous Invasion ◽  
Prognostic Indicator ◽  
Hazard Ratio ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
Additional Value ◽  
Stage 1

Aim. Extramural venous invasion (EMVI) is a prognostic indicator in patients with colorectal cancer. However, its additional value in patients with stage 1 and 2 colorectal cancer is uncertain. In the present study, the incidence of EMVI and the hazard ratio for recurrence in patients with stage 1 and 2 colon cancer were studied. Methods. 184 patients treated for stage 1 and 2 colon cancer were included with a follow-up of at least 5 years. Chart review was performed and EMVI was assessed by two separate pathologists. EMVI was scored with additional caldesmon staining on the resection specimen. Primary outcomes were recurrence-free survival (RFS) measured through the Cox regression analysis and prevalence of EMVI. Results. There were 10 cases of EMVI and 3 cases of intramural venous invasion (IMVI) all occurring in patients with stage 2 disease corresponding to a prevalence of 9%. Thirty-one percent of the patients with venous invasion experienced recurrence versus 14% in patients without, corresponding with a hazard ratio of 2.39 (p=0.11). Conclusion. The present study demonstrates a trend towards an increased risk of recurrence in patients with stage 2 colon cancer with venous invasion. This warrants consideration of adjuvant chemotherapy despite the lack of lymph node metastases.

Subgroup analysis of patients enrolled in the United States in the CORRECT phase 3 trial of the multikinase inhibitor regorafenib (REG) in metastatic colorectal cancer (mCRC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 767-767
Author(s):  
Heinz-Josef Lenz ◽  
Eric Van Cutsem ◽  
Udit N. Verma ◽  
Marc Saltzman ◽  
Jyotsna Fuloria ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Small Sample Size ◽  
The United States ◽  
Small Sample ◽  
Wild Type ◽  
Correct Trial ◽  
Multikinase Inhibitor ◽  
Kras Status ◽  
The Us ◽  
Dose Modifications

767 Background: The CORRECT trial (NCT01103323) showed that REG improves overall survival (OS) vs placebo (PBO) in patients with mCRC who failed approved therapies (OS HR 0.77; 1-sided p=0.0052; Grothey 2013). A total of 760 patients were randomized to REG (n=505) or PBO (n=255) in more than 100 centers across North America, Europe, Asia, and Australia. We conducted a post-hoc exploratory subgroup analysis of the 83 (11%) patients from 18 US centers. Methods: Eligible patients had an ECOG PS ≤1 and had received approved therapies, including a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab, and if KRAS wild-type cetuximab and/or panitumumab. Data from the overall cohort, including US patients, are provided for perspective. Descriptive statistics are shown. Results: Of the 83 US patients, 36 (43%) were randomized to PBO and 47 (57%) to REG. Baseline characteristics of the US group were consistent with the overall cohort: median age in the US was 58 yr (range, 34 – 85) vs 61 (22 – 85) overall, 49% of US patients were ECOG PS1 (vs 46%), and 46% received ≤ 3 treatments for mCRC (vs 52%). KRAS status mutant/wild-type was 57%/34% in the US vs 57%/39% overall. All patients in the trial had prior bevacizumab and 57% of US patients also had prior cetuximab and/or panitumumab (vs 51% overall). However, higher proportion of patients in the US were Black (11% vs 2%), KRAS status unknown (10% vs 4%), and had colon as the primary disease site (82% vs 65%). Mean percentages of planned REG dose were similar (76% US vs 79% overall) and mean REG treatment duration was 3.1 mos in US vs 2.8 mos overall. Rates of dose modifications REG/PBO were 87%/47% in the US vs 76%/38% overall and grade ≥3 adverse events REG/PBO were 74%/64% vs 78%/49%, respectively. Based on 44 total death events, the HR for OS in the US subgroup was 0.46 (95%CI 0.25 – 0.84) favoring REG; median OS was 4.7 mos for PBO, but could not be estimated for REG due to censored data. However, this analysis was based on a relatively small sample size and event count. Conclusions: Patients treated in the CORRECT study in the US appear similar to the overall cohort and results are generally consistent with the overall findings of the trial. Clinical trial information: NCT01103323.

An observational study of a team management approach for first-line XELOX therapy in patients with advanced/recurrent colorectal cancer: The SMILE study (the study of metastatic colorectal cancer to investigate impact of learning effect).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 554-554
Author(s):  
Michio Nakamura ◽  
HIroshi Matsuoka ◽  
Yoshihisa Shibata ◽  
Yoshinori Munemoto ◽  
Hiroyuki Okuda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Observational Study ◽  
Small Sample Size ◽  
Depression Scale ◽  
Dose Intensity ◽  
Small Sample ◽  
Management Approach ◽  
First Line ◽  
Fighting Spirit ◽  
Supportive Interventions

554 Background: Although oral chemotherapies such as XELOX are widely favored for convenience and flexibility, these have several disadvantages such as drug non-compliance and delayed discovery of adverse events. So we designed a multicenter, prospective, observational study to evaluate the efficacy of supportive interventions in first-line XELOX for colorectal cancer (CRC) patients (pts). Methods: CRC pts undergoing first-line XELOX (+Bevacizumab) therapy practicing one or more of supportive interventions as follows: 1) a telephone follow-up (TF), 2) instruction on dosage and administration by a pharmacist, 3) skin care instruction by a nurse, and 4) pts education by a doctor were eligible. The objective was to evaluate the incident rate of grade 2 or worse hand-foot syndrome (HFS), QoL, safety, and efficacy. QoL was assessed at baseline, 2, 4, 5 and 8 cycles after the treatment started, using the Hospital Anxiety and Depression Scale (HADS) and the Mental adjustment to cancer scale (MAC). Results: From April 2011 to September 2012, 80 pts were enrolled from 14 institutes. The characteristics were as follows: male/female: 46/34, age median: 63 (36-75), and supportive intervention 1)/2)/3)/4): 36/68/73/78. The incidence of grade 2 or worse HFS during 6 months were 11.1% (n=4) for those received TF (n=36), and 20.5% (n=9) for those received other intervention except TF (n=44). Relative dose intensity (RDI) was 75.7% (TF+/-: 77.7/74.3%) in oxaliplatin and 77.5% (TF+/-: 80.2/75.3%) in capecitabine, respectively. Although a tendency of the QoL score improvement about anxiety, fighting spirit and helplessness in a TF group was observed during the periods from start of therapy to 4 courses, there were no significant differences compared to other interventions except TF. Conclusions: We confirmed that HFS incidence was mitigated in a TF group. In regard to QoL, although we could not show the statistical differences due to some limitations of this study such as small sample size and non-randomized, it was indicated that TS had the potential to improve several QoL about anxiety, fighting spirit, and helplessness. Clinical trial information: UMIN000007185.

Molecular profiling of TOPO1: A way to evaluate irinotecan treatment in colorectal cancer?

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 546-546
Author(s):  
Julia Marie Cunningham ◽  
Petra Prins ◽  
Brian Conkright ◽  
Simina Boca ◽  
Shruti Rao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Small Sample Size ◽  
Predictive Marker ◽  
Molecular Profiling ◽  
Small Sample ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Control Group ◽  
Similar Response ◽  
Second Line

546 Background: Front-line chemotherapy for metastatic colorectal cancer (mCRC) consists of a fluoropyrimidine backbone plus either oxaliplatin (FOLFOX or XELOX) or irinotecan (FOLFIRI or XELIRI). Large, prospective trials enrolling chemotherapy-naïve patients (pts) show FOLFOX and FOLFIRI treatment to be equivalent with similar response rates. Methods: Irinotecan inhibits TOPO1, which is now a candidate marker for irinotecan treatment benefit. Thus, we retrospectively analyzed TOPO1 expression level in 49 pts with mCRC who were treated with irinotecan-containing regimens at the Lombardi Comprehensive Cancer Center between 2009 and 2014. Patient characteristics and outcomes were compiled through chart review and the effect of TOPO1 expression on clinical outcomes was assessed. TOPO1 expression in tumor tissue from each pt was analyzed using a commercially available molecular profiling (MP) service (Caris Life Sciences). Results: The median overall survival (OS) for all pts was 33.9 months (mo), defined as the time from metastasis to death or censorship. When grouped by “high” or “low” TOPO1 expression, as defined by Caris at the time of the testing, 29 pts were high-expressers and 20 were low-expressers. High TOPO1 expressers receiving irinotecan (n = 22) had a median OS of 27.2 mo, compared with median 41.5 mo for low-expressers (n = 14) (p = 0.27). Irinotecan is conventionally given as second-line therapy. The median OS of pts receiving second-line irinotecan was 38.2 mo for high-expressers [n = 11] vs. 68.5 mo for low-expressers [n = 5]) (p = 0.32). Conclusions: Our limited data do not support the use of TOPO1 expression levels as a predictive marker for irinotecan therapy in mCRC. However, our conclusions are limited by small sample size, lack of a control group to distinguish prognostic from predictive markers, and timing of TOPO1 measurement, which in many cases was after irinotecan therapy. Physicians currently lack an evidence-based way to choose between potentially efficacious regimens for mCRC. More rigorous studies are needed to assess the benefit of MP in mCRC care. We are currently planning a prospective study with the hope of validating the use of TOPO1 expression as a predictive marker for treatment of this disease.

scholarly journals Prognostic value of preoperative high-sensitivity modified Glasgow prognostic score in advanced colon cancer: a retrospective observational study

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Kenta Kasahara ◽  
Masanobu Enomoto ◽  
Ryutaro Udo ◽  
Tomoya Tago ◽  
Junichi Mazaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Multivariate Analysis ◽  
Prognostic Value ◽  
Prognostic Score ◽  
Glasgow Prognostic Score ◽  
High Sensitivity ◽  
Prognostic Predictors ◽  
Advanced Colon Cancer ◽  
Significant Difference

Abstract Background Several studies have demonstrated that the preoperative Glasgow prognostic score (GPS) and modified GPS (mGPS) reflected the prognosis in patients undergoing curative surgery for colorectal cancer. However, there are no reports on long-term prognosis prediction using high-sensitivity mGPS (HS-GPS) in colorectal cancer. Therefore, this study aimed to calculate the prognostic value of preoperative HS-GPS in patients with colon cancer. Methods A cohort of 595 patients with advanced resectable colon cancer managed at our institution was analysed retrospectively. HS-GPS, GPS, and mGPS were evaluated for their ability to predict prognosis based on overall survival (OS) and recurrence-free survival (RFS). Results In the univariate analysis, HS-GPS was able to predict the prognosis with significant differences in OS but was not superior in assessing RFS. In the multivariate analysis of the HS-GPS model, age, pT, pN, and HS-GPS of 2 compared to HS-GPS of 0 (2 vs 0; hazard ratio [HR], 2.638; 95% confidence interval [CI], 1.046–6.650; P = 0.04) were identified as independent prognostic predictors of OS. In the multivariate analysis of the GPS model, GPS 2 vs 0 (HR, 1.444; 95% CI, 1.018–2.048; P = 0.04) and GPS 2 vs 1 (HR, 2.933; 95% CI, 1.209–7.144; P = 0.017), and in that of the mGPS model, mGPS 2 vs 0 (HR, 1.51; 95% CI, 1.066–2.140; P = 0.02) were independent prognostic predictors of OS. In each classification, GPS outperformed HS-GPS in predicting OS with a significant difference in the area under the receiver operating characteristic curve. In the multivariate analysis of the GPS model, GPS 2 vs 0 (HR, 1.537; 95% CI, 1.190–1.987; P = 0.002), and in that of the mGPS model, pN, CEA were independent prognostic predictors of RFS. Conclusion HS-GPS is useful for predicting the prognosis of resectable advanced colon cancer. However, GPS may be more useful than HS-GPS as a prognostic model for advanced colon cancer.

Incidence of chemotherapy-induced amenorrhea in premenopausal women treated with adjuvant FOLFOX for colorectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14112-e14112
Author(s):  
Andrea Cercek ◽  
Cara Siegel ◽  
Diane Lauren Reidy ◽  
Leonard Saltz
Keyword(s):  
Colorectal Cancer ◽  
Small Sample Size ◽  
Premenopausal Women ◽  
Small Sample ◽  
Stage Ii ◽  
Bilateral Oophorectomy ◽  
Folfox Chemotherapy ◽  
Stage Ii Colon Cancer ◽  
One Year ◽  
The Impact

e14112 Background: The gonadotoxicity of oxaliplatin-based chemotherapy is largely unknown. Studies indicate that the incidence of young women diagnosed with colorectal cancer is rising, thus there is an increasing number of female colorectal cancer (crc) survivors of premenopausal and child-bearing age. Adjuvant FOLFOX chemotherapy is the most widely used standard treatment for stage III and high-risk stage II colon cancer. The objective of this analysis was to evaluate the incidence of FOLFOX induced amenorrhea in women age 50 or younger treated with adjuvant therapy for colorectal cancer. Methods: A search of computerized pharmacy records identified 119 women age 50 or younger who received adjuvant FOLFOX chemotherapy at Memorial Sloan-Kettering for stage II or III colorectal cancer from January 2002 and January 2011 . Eligible patients were mailed an anonymous questionnaire. The returned surveys were reviewed and the results tallied. Results: Seventy three patients returned the questionnaire. Twenty four patients were excluded from analysis; 19 were treated with radiotherapy, 1 patient had undergone bilateral oophorectomy, 1 had a hysterectomy and 3 stopped menstruating prior to diagnosis. Forty nine patients were analyzed. In total, 41% experienced amenorrhea during chemotherapy. Sixteen percent had persistent amenorrhea approximately one year after completion of chemotherapy. The incidence of amenorrhea during chemotherapy and persistent amenorrhea was higher in patients age 40 or older than in patients under 40 (59% vs 31% (p=.17) and 24% vs 13% (p=.33), respectively). Conclusions: In this retrospective study, it appears that the incidence of FOLFOX chemotherapy induced amenorrhea is increased with age. Due to the small sample size the study may be underpowered to detect a statistical difference. Prospective studies are planned to more accurately characterize the impact of FOLFOX on early menopause and fertility.

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.

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