Evaluation of 5-Fluorouracil Metabolic Enzymes as Predictors of Response to Adjuvant Chemotherapy Outcomes in Patients with Stage II/III Colorectal Cancer: A Decision-Curve Analysis

Background Previous literature demonstrates correlations between comorbidities and failure to complete adjuvant chemotherapy. Frailty and socioeconomic disparities have also been implicated in affecting cancer treatment outcomes. This study examines the effect of demographics, comorbidities, frailty, and socioeconomic status on chemotherapy completion rates in colorectal cancer patients. Methods This was an observational case-control study using retrospective data from Stage II and III colorectal cancer patients offered chemotherapy between January 01, 2013 and January 01, 2018. Data was obtained using the cancer registry, supplemented with chart review. Patients were divided based on treatment completion and compared with respect to comorbidities, age, Eastern Cooperative Oncology Group (ECOG) score, and insurance status using univariate and multivariate analyses. Results 228 patients were identified: 53 Stage II and 175 Stage III. Of these, 24.5% of Stage II and 30.3% of Stage III patients did not complete chemotherapy. Neither ECOG status nor any comorbidity predicted failure to complete treatment. Those failing to complete chemotherapy were older (64.4 vs 60.8 years, P = .043). Additionally, those with public assistance or self-pay were less likely to complete chemotherapy than those with private insurance ( P = .049). Both factors (older age/insurance status) remained significant on multivariate analysis (increasing age at diagnosis: OR 1.03, P =.034; public insurance: OR 1.84, P = .07; and self-pay status: OR 4.49, P = .03). Conclusions No comorbidity was associated with failure to complete therapy, nor was frailty, as assessed by ECOG score. Though frailty was not significant, increasing age was, possibly reflecting negative attitudes toward chemotherapy in older populations. Insurance status also predicted failure to complete treatment, suggesting disparities in access to treatment, affected by socioeconomic factors.

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Clinical implementation of the universal tumor screening with the mismatch repair (MMR) proteins on decision impact of adjuvant chemotherapy in patients with resected stage II/III colorectal cancer (CRC)

Annals of Oncology ◽

10.1093/annonc/mdx659.039 ◽

2017 ◽

Vol 28 ◽

pp. x53

Author(s):

Y. Yamamoto ◽

Y. Tsukada ◽

H. Bando ◽

T. Sasaki ◽

Y. Nishizawa ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Mismatch Repair ◽

Stage Ii ◽

Clinical Implementation ◽

Resected Stage ◽

Mmr Proteins

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Prognostic significance of MUC2, CDX2 and SOX2 in stage II colorectal cancer patients

BMC Cancer ◽

10.1186/s12885-021-08070-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sara Ribeirinho-Soares ◽

Diana Pádua ◽

Ana Luísa Amaral ◽

Elvia Valentini ◽

Daniela Azevedo ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Prognostic Significance ◽

Tumor Resection ◽

Disease Free Survival ◽

Predictive Biomarkers ◽

Stage Ii ◽

Health Concern ◽

Rank Test ◽

Low Expression

Abstract Background Colorectal cancer (CRC) remains a serious health concern worldwide. Despite advances in diagnosis and treatment, about 15 to 30% of stage II CRC patients subjected to tumor resection with curative intent, develop disease relapse. Moreover, the therapeutic strategy adopted after surgery is not consensual for these patients. This supports the imperative need to find new prognostic and predictive biomarkers for stage II CRC. Methods For this purpose, we used a one-hospital series of 227 stage II CRC patient samples to assess the biomarker potential of the immunohistochemical expression of MUC2 mucin and CDX2 and SOX2 transcription factors. The Kaplan-Meier method was used to generate disease-free survival curves that were compared using the log-rank test, in order to determine prognosis of cases with different expression of these proteins, different mismatch repair (MMR) status and administration or not of adjuvant chemotherapy. Results In this stage II CRC series, none of the studied biomarkers showed prognostic value for patient outcome. However low expression of MUC2, in cases with high expression of CDX2, absence of SOX2 or MMR-proficiency, conferred a significantly worst prognosis. Moreover, cases with low expression of MUC2 showed a significantly clear benefit from treatment with adjuvant chemotherapy. Conclusion In conclusion, we observe that patients with stage II CRC with low expression of MUC2 in the tumor respond better when treated with adjuvant chemotherapy. This observation supports that MUC2 is involved in resistance to fluorouracil-based adjuvant chemotherapy and might be a promising future predictive biomarker in stage II CRC patients.

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Development and validation of a robust prognostic and predictive signature for colorectal cancer (CRC) patients

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4036 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 4036-4036

Author(s):

A. M. Glas ◽

P. Roepman ◽

R. Salazar ◽

G. Capella ◽

V. Moreno ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Gene Signature ◽

Low Risk ◽

Stage Ii ◽

Significant Difference ◽

Independent Cohort

4036 Background: Between 25 and 35% of stage II CRC patients will experience a recurrence of their disease and may benefit from adjuvant chemotherapy. Official guidelines give suggestions but no clear recommendation for best risk stratification. Here we describe the development a robust signature that predicts disease relapse and can assist in treatment decisions. Methods: Fresh frozen tumor tissues from 180 patients with stage I, II and III colorectal cancer undergoing surgery were analyzed using high density Agilent 44K oligonucleotide arrays. Median FU was 70.2 months; 85% of patients did not receive adjuvant chemotherapy. Unsupervised hierarchical clustering based on full-genome gene expression measurement indicated the existence of 3 main colon molecular subclasses. Survival analysis of the 3 classes showed that subtype C (n= 27) had a poor outcome and subtype A (n= 48) good outcome. Only the intermediate group B (n=104) was used to develop a signature by using a cross validation procedure to score all genes for their association with 5-yr distant metastasis free survival (DMFS) and subsequently applied to all samples (n=180). The obtained gene signature was further validated on an independent cohort of 178 stage II + III colon samples. Results: A set of 38 prognosis related gene probes showed robust DMFS association in over 50% of all iterations in the Training Set of 180 samples. The gene signature was validated on an independent cohort of 178 samples from stage II + III colon cancer patients. The profile classified 61% of the validation samples as low-risk and 39% as high-risk. The low- and high-risk samples showed a significant difference in DMFS with a HR of 3.19 (P= 8.5e-4). Five-year DMFS rates were 89% (95%CI 83–95) for low-risk and 62% (95%CI 50–77) for high-risk samples. Moreover, the profile showed a significant performance within stage II (P=0.0058) and III (P=0.036) only samples. The performance of the profile was significant for both untreated (P=0.0082) and treated patients (P=0.016) suggesting that its power is independent of treatment benefits. Conclusions: ColoPrint is able to predict the prognosis of stage II and III colon cancer patients and facilitates the identification of patients who would benefit from adjuvant chemotherapy. [Table: see text]

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Clinical predictive value of in vitro anticancer drug sensitivity test for the therapeutic effect of 5-FU based adjuvant chemotherapy in patients with stage II-III colorectal cancer: 10-year follow up results.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.e15605 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. e15605-e15605

Author(s):

Hiromichi Sonoda ◽

Eiji Mekata ◽

Tomoharu Shimizu ◽

Toru Miyake ◽

Tomoyuki Ueki ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Therapeutic Effect ◽

Anticancer Drug ◽

Predictive Value ◽

Drug Sensitivity ◽

Stage Ii ◽

Drug Sensitivity Test

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Clinical impact of diverting ileostomy on the dose intensity of adjuvant chemotherapy for colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.867 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 867-867

Author(s):

Shusuke Yagi ◽

Eiji Shinozaki ◽

Keisho Chin ◽

Mitsukuni Suenaga ◽

Daisuke Takahari ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Dose Intensity ◽

Clinical Impact ◽

Stage Ii ◽

Stage Iii ◽

Diverting Ileostomy ◽

Grade 3

867 Background: CAPOX as adjuvant chemotherapy is a standard care option for stage III and high risk stage II colorectal cancer(CRC). And then chemotherapy induced diarrhea (CID) is known as one of the dose-limiting toxicities for CAPOX. Although diverting ileostomy is useful for preventing serious complications of high risk anastomosis, it is well recognized that high ileostomy output is hard to manage. Furthermore, the effect of diverting ileostomy on CID of adjuvant chemotherapy is unclear. In this study, we addressed the clinical impact of diverting ileostomy on the dose intensity of adjuvant chemotherapy for CRC. Methods: Patients who diagnosed with stage III colon cancer and stage II or III rectal cancer after curative surgery and received CAPOX as adjuvant chemotherapy during 2011- 2014 were reviewed retrospectively. We investigated the relationship between diverting ileostomy and dose intensity, toxicities and disease-free survival (DFS). Results: 112 patients (median age 60 years, 52% male, 69% colon cancer, 63% stage III, median follow-up 47 months) were enrolled in this study. Of 112 patients, 100 patients were received chemotherapy without ileostomy (non-ileostomy group: NIG) and 12 patients were received chemotherapy with ileostomy (ileostomy group: IG). 112 Patients received 870 chemotherapy cycles. All treatment related grade 3/4 adverse events were documented in 39% of patients in NIG and 33% of patients in IG (P = 0.77). Grade 3/4 of CID occurred in 8% of patients in NIG and 8% of patients in IG (P = 1). Grade 3/4 of neutropenia were recognized in 21% of patients in NIG and 17% of patients in IG (P = 1). Average relative dose intensity (RDI) in NIG were 75.7% and 85.8% for capecitabine and oxaliplatin, respectively. Average RDI of capecitabine and oxaliplatin in IG were 76.1% and 82.7%, respectively. Significant difference of RDI of capecitabine and oxaliplatin were not shown in comparison between NIG and IG (P = 0.93, P = 0.63). The 3-year DFS rate was 85.0% in NIG and 75.0% in IG. The HR for DFS for NIG compared to IG was 1.709 (95% CI, 0.49 to 5.95; P = 0.40). Conclusions: The presence of diverting ileostomy does not affect RDI of CAPOX as adjuvant chemotherapy.

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