scholarly journals Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy

2016 ◽  
Vol 5 (8) ◽  
pp. 1840-1849 ◽  
Author(s):  
Kjetil Boye ◽  
Havjin Jacob ◽  
Kari‐Anne M. Frikstad ◽  
Jahn M. Nesland ◽  
Gunhild M. Mælandsmo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Prognostic Significance ◽  
Population Based ◽  
Stage Ii ◽  
Phase Iii ◽  
S100a4 Expression ◽  
Phase Iii Study

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

BMC Cancer ◽  
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.

Use of Adjuvant Chemotherapy and Radiation Therapy for Colorectal Cancer in a Population-Based Cohort

2003 ◽  
Vol 21 (7) ◽  
pp. 1293-1300 ◽  
Author(s):  
John Z. Ayanian ◽  
Alan M. Zaslavsky ◽  
Charles S. Fuchs ◽  
Edward Guadagnoli ◽  
Cynthia M. Creech ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Radiation Therapy ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Population Based ◽  
Stage Ii ◽  
Stage Iii Colon Cancer ◽  
Adjuvant Therapies

Purpose: Randomized trials have demonstrated that adjuvant chemotherapy improves survival for patients with stage III colon cancer and that chemotherapy combined with radiation therapy improves survival for patients with stage II or III rectal cancer. This population-based study was designed to assess use of these treatments in clinical practice. Patients and Methods: From the California Cancer Registry, we identified all patients diagnosed during 1996 to 1997 with stage III colon cancer (n = 1,422) and stage II or III rectal cancer (n = 534) in 22 northern California counties. To supplement registry data on adjuvant therapies and ascertain reasons they were not used, we surveyed physicians or reviewed office records for 1,449 patients (74%). Results: Chemotherapy rates varied widely by age from 88% (age < 55 years) to 11% (age ≥ 85 years), and radiation therapy varied similarly. Adjusting for demographic, clinical, and hospital characteristics, chemotherapy was used less often among older and unmarried patients, and radiation therapy was used less often among older patients, black patients, and those initially treated in low-volume hospitals. Adjusted rates of chemotherapy varied significantly (P < .01) among individual hospitals: 79% and 51%, respectively, at one SD above and below average (67%). Physicians’ reasons for not providing adjuvant therapy included patient refusal (30% for chemotherapy, 22% for radiation therapy), comorbid illness (22% and 14%, respectively), or lack of clinical indication (22% and 45%, respectively). Conclusion: Use of adjuvant therapy for colorectal cancer varies substantially by age, race, marital status, hospital volume, and individual hospital, indicating opportunities to improve care. With enhanced data on adjuvant therapies, population-based registries could become a valuable resource for monitoring the quality of cancer care.

Immunohistochemical Test for MLH1 and MSH2 Expression Predicts Clinical Outcome in Stage II and III Colorectal Cancer Patients

2006 ◽  
Vol 24 (15) ◽  
pp. 2359-2367 ◽  
Author(s):  
Giovanni Lanza ◽  
Roberta Gafà ◽  
Alessandra Santini ◽  
Iva Maestri ◽  
Laura Guerzoni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Stage Ii ◽  
Stage Iii ◽  
Prognostic Information ◽  
Colorectal Cancer Patients ◽  
Risk Of Cancer

Purpose To evaluate the prognostic significance of DNA mismatch repair (MMR) status in a large series of stage II and III colorectal cancer patients. The relationship among MMR status, adjuvant chemotherapy, and clinical outcome was also investigated. Patients and Methods The study included 718 patients with colorectal adenocarcinoma (393 stage II and 325 stage III) who underwent curative surgical resection. MMR status was determined by immunohistochemical analysis of MLH1 and MSH2 expression. Microsatellite instability (MSI) was assessed in 363 patients using mononucleotide and dinucleotide markers. Results One hundred fourteen (15.9%) carcinomas showed abnormal MMR protein (MMRP) expression (96 MLH1 negative and 18 MSH2 negative) and were classified as MMRP negative, whereas 604 tumors demonstrated normal MLH1/MSH2 immunoreactivity (MMRP positive). MLH1/MSH2 expression was closely related to MSI status (P < .001) and several clinicopathologic features. Patients with MMRP-negative carcinomas demonstrated a marked reduction in the risk of cancer-related death with respect to patients with MMRP-positive tumors (hazard ratio, 0.2579; 95% CI, 0.1289 to 0.5159). A better clinical outcome for patients with MMRP-negative tumors was observed in both stage II (P = .0006) and stage III (P = .0052) disease. In stage III disease, the survival advantage conferred by MMRP-negative tumors was more evident among patients treated with surgery alone than among patients who received adjuvant chemotherapy. A nonsignificant trend for survival benefit from adjuvant chemotherapy was observed among patients with MMRP-positive carcinomas but not among those with MMRP-negative carcinomas. Conclusion Immunohistochemical testing for MLH1/MSH2 expression provides useful prognostic information for the management of stage II and III colorectal cancer patients.

ALINA: A phase III study of alectinib versus chemotherapy as adjuvant therapy in patients with stage IB–IIIA anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS8569-TPS8569 ◽  
Author(s):  
Benjamin J. Solomon ◽  
Jin Seok Ahn ◽  
Fabrice Barlesi ◽  
Rafal Dziadziuszko ◽  
Makoto Nishio ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Survival Rates ◽  
Stage Ii ◽  
Phase Iii ◽  
Disease Stage ◽  
Efficacy And Safety ◽  
Anaplastic Lymphoma ◽  
Stage Ib ◽  
Phase Iii Study ◽  
Stage Ia

TPS8569 Background: Patients with early-stage NSCLC (stage IA–IIIA) account for ~40% of cases at diagnosis; despite surgery, 5-year survival rates are low. Platinum-based adjuvant chemotherapy is the standard of care (SoC) for stage II–IIIA disease. Although patients with stage IA NSCLC do not benefit from adjuvant chemotherapy, patients with stage IB disease and large tumors (≥4cm) do. Adjuvant chemotherapy produces a 4–5% increase in 5-year survival rates, leaving significant unmet need for improved treatments. Approximately 5% of patients with NSCLC harbor an oncogenic fusion of the ALK gene. Treatment of advanced ALK+ NSCLC with ALK inhibitors improves efficacy and safety compared with chemotherapy. Alectinib, a potent ALK inhibitor, is the SoC first-line treatment for advanced ALK+ NSCLC. The ongoing ALINA trial will compare alectinib versus chemotherapy as adjuvant treatment for patients with stage IB–IIIA ALK+ NSCLC. Methods: ALINA is a randomized, multicenter, open-label phase III study investigating the efficacy and safety of adjuvant alectinib versus chemotherapy in ALK+ NSCLC (confirmed by an FDA-approved and CE-marked test). Adult patients (≥18 years) with completely resected stage IB (tumors ≥4cm) to IIIA disease and ECOG PS 0–1 are eligible for inclusion. Patients (N=255) from ~170 centers across ~30 countries will be randomized 1:1 to receive twice-daily alectinib 600mg for 24 months or four 21-day cycles of platinum-based chemotherapy (cisplatin 75mg/m2 [day 1] plus vinorelbine 25mg/m2 [days 1 and 8] or gemcitabine 1250mg/m2 [days 1 and 8] or pemetrexed 500mg/m2 [day 1]) according to local prescribing information. Stratification factors are disease stage (stage IB [≥4cm] vs stage II vs stage IIIA) and race (Asian vs non-Asian). Treatment will continue until planned completion, disease recurrence, unacceptable toxicity, withdrawal of consent, or death, whichever occurs first. The primary endpoint is disease-free survival per investigator; secondary endpoints are overall survival, safety, and pharmacokinetics. Clinical trial information: NCT03456076.

Prognostic significance of pathological biomarkers in patients with stage II-III colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14518-14518
Author(s):  
C. Funaioli ◽  
C. Pinto ◽  
C. Ceccarelli ◽  
F. Di Fabio ◽  
D. Cuicchi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Primary Tumor ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Stage Ii ◽  
Stage Iii ◽  
Disease Stage ◽  
Primary Tumor Site ◽  
The Impact

14518 Background: Biopathological colorectal cancer (CRC) studies have provided information on pathogenesis, but it is unclear how important biomarkers actually are in predicting prognosis. The aim of our study was to define the prognostic significance of biomarkers and a biopathological profile that could predict an increase in the disease relapse risk in stage II-III CRC patients (pts). Methods: The primary tumor of the CRC pts treated with surgery was immunohistochemically evaluated on the Ki67, p53, bcl-2, TS, EGFR, MLH1 and MSH2 expressions. All 7 markers were measured using standard immunohistochemical techniques. The biomarker evaluations were scored by just one pathologist. Results: Between March 2001 and October 2006 the primary tumor of 242 consecutive pts was investigated. Pt characteristics were: males 141(58.3%), females 101(41.7%); median age 68.5 (24–88); primary tumor site: right colon 94(38.8%), left colon 148(61.2%); stage II 102(42.1%), stage III 81(33.5%), stage IV 59(24.4%). 5-fluorouracil based adjuvant chemotherapy was performed in 121 (66.1%) pts. After a median follow up of 30 months (1–80), 34 pts (10 pts stage II, 24 pts stage III) of 183 stage II-III pts (18.6%) had a disease recurrence. In a univariate analysis of stage II-III pts, a higher expression of Ki67 (= 50% positive cells) was significantly associated with an improved DFS (p= 0.014) and overall survival (OS) (p=0.010). Expression of p53, bcl-2, TS, EGFR, MLH1 and MSH2 were not significantly associated with DFS and OS. In a multivariate analysis adjusted for the impact of the disease stage and adjuvant chemotherapy, a higher expression of Ki67 was significantly associated with diminished risk of recurrence (HR: 0.395; 95% CI: 0.183–0.855, p=0.018) and death (HR: 0.179; 95% CI: 0.046–0.696, p=0.013). The evaluation of DNA mismatch repair status (MLH1, MSH2) demonstrated that the lack of MLH1 is more frequent in non-relapsed II-III stage pts than in IV stage pts (p= 0.024). Conclusions: This analysis showed a significant correlation between higher Ki67 expression and better DFS and OS in pts with stage II-III CRC. An higher frequency of MLH1 deficiency was observed in non-relapsed pts with stage II-III than in advanced disease. No significant financial relationships to disclose.

Final DFS results of the SCOT study: An international phase III randomised (1:1) non-inferiority trial comparing 3 versus 6 months of oxaliplatin based adjuvant chemotherapy for colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3502-3502 ◽  
Author(s):  
Timothy Iveson ◽  
Rachel Kerr ◽  
Mark P. Saunders ◽  
Niels Henrik Hollander ◽  
Josep Tabernero ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Cox Model ◽  
Disease Free Survival ◽  
Patient Choice ◽  
Stage Ii ◽  
Phase Iii ◽  
Stage Iii ◽  
Duration Of Treatment

3502 Background: Six months of oxaliplatin-based treatment has been the mainstay of adjuvant chemotherapy for colorectal cancer for the last 13 years. Neurotoxicity from oxaliplatin is cumulative, dose limiting, and potentially irreversible. A shorter duration of treatment would save patients significant toxicity/time and substantially reduce the costs of the drug, its administration, and treatment of adverse effects. Methods: SCOT is a non-inferiority randomised study designed to determine whether 3 months of adjuvant chemotherapy with OxMdG or Xelox (physician/patient choice) in Stage III/high risk Stage II colorectal cancer is as effective as 6 months treatment. Non-inferiority was determined to be a maximum 2.5% fall in 3-year disease-free survival (DFS) on the 3 month arm (from 78% on the 6 month arm) corresponding to a hazard ratio upper limit of 1.13. The study was designed with 90% power at the 2.5% 1-sided level of statistical significance and aimed to recruit 9500 patients to observe 2,750 DFS events (relapses/deaths/new colorectal cancers). Analysis used a Cox model adjusted for study minimisation factors. Results: 6088 patients (60% male, median age 65) with Stage III/high risk Stage II cancers of the colon or rectum were randomised between 27th March 2008 and 29th November 2013. The arms were balanced for clinical and pathological factors. Intended treatment was OxMdG for 1981 and Xelox for 4107 patients. There were 1469 DFS events (734 in 3 month arm and 735 in 6 month arm) giving the study 66% power. 3 year DFS was 76.8% (se = .8%) for the 3 month arm and 77.4% (se = .8%) for the 6 month arm (HR 1.008, 95% CI 0.910-1.117, test for non-inferiority p = 0.014). Non-inferiority appeared stronger for Xelox than OxMdG (test for heterogeneity, p = .059). Results will be shown broken down by stage, site, age, gender and achieved duration of treatment. Conclusions: The SCOT study has shown that 3 months adjuvant treatment is not inferior to 6 months treatment. However the SCOT study is part of the IDEA consortium and the results from the 6 studies in the IDEA consortium addressing the same duration question will also be presented at ASCO 2017. Clinical trial information: ISRCTN59757862.

Sign in / Sign up

Export Citation Format

Share Document