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Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer.

ABSTRACT: Histological 'phenotypic subtypes' that classify patients into four groups (immune, canonical, latent and stromal) have previously been demonstrated to stratify survival in a stage I-III colorectal cancer (CRC) pilot cohort. However, clinical utility has not yet been validated. Therefore, this study assessed prognostic value of these subtypes in additional patient cohorts along with associations with risk of recurrence and response to chemotherapy. Two independent stage I-III CRC patient cohorts (internal and external cohort) were utilised to investigate phenotypic subtypes. The primary endpoint was disease-free survival (DFS) and the secondary endpoint was recurrence risk (RR). Stage II-III patients, from the SCOT adjuvant chemotherapy trial, were utilised to further validate prognostic value and for exploratory analysis assessing associations with adjuvant chemotherapy. In an 893-patient internal cohort, phenotypic subtype independently associated with DFS (p = 0.025) and this was attenuated in stage III patients (p = 0.020). Phenotypic subtype also independently associated with RR (p?

SUBMITTER: Roseweir AK

PROVIDER: S-EPMC7578335 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer.

Roseweir Antonia K AK Park James H JH Hoorn Sanne Ten ST Powell Arfon Gmt AG Aherne Susan S Roxburgh Campbell Sd CS McMillan Donald C DC Horgan Paul G PG Ryan Elizabeth E Sheahan Kieran K Vermeulen Louis L Paul James J Harkin Andrea A Graham Janet J Sansom Owen O Sansom Owen O Church David N DN Tomlinson Ian I Saunders Mark M Iveson Tim J TJ Edwards Joanne J

The journal of pathology. Clinical research 20200513 4

Histological 'phenotypic subtypes' that classify patients into four groups (immune, canonical, latent and stromal) have previously been demonstrated to stratify survival in a stage I-III colorectal cancer (CRC) pilot cohort. However, clinical utility has not yet been validated. Therefore, this study assessed prognostic value of these subtypes in additional patient cohorts along with associations with risk of recurrence and response to chemotherapy. Two independent stage I-III CRC patient cohorts ...[more]

PMID: 32401426

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Project description:BackgroundThere are robust data supporting the contribution of oxaliplatin (L-OHP) regarding clinical outcomes for colorectal cancer (CRC) in an adjuvant setting in European and US trials; however, there is no Japanese clinical evidence although L-OHP has been approved since 2009. We examined the transition of adjuvant chemotherapy for stage III colorectal cancer in our institute.MethodsA total of 642 patients with histopathologically confirmed stage III CRC underwent curative surgery from 2005 to 2010. We examined disease free survival (DFS), overall survival (OS) and prognostic factors for stage III CRC patients who underwent adjuvant chemotherapy.ResultsA total of 509 patients received adjuvant chemotherapy. 3-year DFS and 5-year OS rates were 74.5% and 87.5%, respectively. The frequency of inclusion of L-OHP as adjuvant chemotherapy was increased after 2008. A total of 189 patients received adjuvant chemotherapy from 2005 to 2007 increasing to 320 patients from 2008 to 2010; the 5-year OS rates were 82.4% and 91.5%, respectively, and the 3-year DFS rates were 69.2% and 76.6%, respectively (OS, P = 0.007; DFS, P = 0.023). In univariate analysis, adjuvant chemotherapy including L-OHP was no significant deference compared to FU monotherapy. (OS: HR 0.88, 95%CI 0.4-1.91, p = 0.75, DFS: HR 0.78, 95%CI 0.21-2.3, p = 0.29). In multivariate analysis, the OS was predicted by means of N stage (HR = 2; 95%CI, 1.1-3.8; P = 0.02) and pathology (HR = 0.28; 95%CI, 0.13-0.59; P = 0.0008). The DFS was predicted by means of N stage (HR = 2.67; 95%CI, 1.82-3.9; P < 0.05), T stage (HR = 1.61; 95%CI, 1.1-2.3; P = 0.01) pathology (HR = 0.47; 95%CI, 0.29-0.75; P < 0.05) and venous invasion (HR = 2.06; 95%CI, 1.12-3.77; P = 0.01).ConclusionsClinical outcomes of stage III CRC patients receiving adjuvant chemotherapy improved. The frequency of L-OHP usage was increasing annually, however it was no influence for clinical outcomes in this study. It will be necessary to reevaluate additional effect of L-OHP with more patients.

Project description:BackgroundSince 2004, a regimen of 6 months of treatment with oxaliplatin plus a fluoropyrimidine has been standard adjuvant therapy in patients with stage III colon cancer. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy could spare toxic effects and health expenditures.MethodsWe performed a prospective, preplanned, pooled analysis of six randomized, phase 3 trials that were conducted concurrently to evaluate the noninferiority of adjuvant therapy with either FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) administered for 3 months, as compared with 6 months. The primary end point was the rate of disease-free survival at 3 years. Noninferiority of 3 months versus 6 months of therapy could be claimed if the upper limit of the two-sided 95% confidence interval of the hazard ratio did not exceed 1.12.ResultsAfter 3263 events of disease recurrence or death had been reported in 12,834 patients, the noninferiority of 3 months of treatment versus 6 months was not confirmed in the overall study population (hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15). Noninferiority of the shorter regimen was seen for CAPOX (hazard ratio, 0.95; 95% CI, 0.85 to 1.06) but not for FOLFOX (hazard ratio, 1.16; 95% CI, 1.06 to 1.26). In an exploratory analysis of the combined regimens, among the patients with T1, T2, or T3 and N1 cancers, 3 months of therapy was noninferior to 6 months, with a 3-year rate of disease-free survival of 83.1% and 83.3%, respectively (hazard ratio, 1.01; 95% CI, 0.90 to 1.12). Among patients with cancers that were classified as T4, N2, or both, the disease-free survival rate for a 6-month duration of therapy was superior to that for a 3-month duration (64.4% vs. 62.7%) for the combined treatments (hazard ratio, 1.12; 95% CI, 1.03 to 1.23; P=0.01 for superiority).ConclusionsAmong patients with stage III colon cancer receiving adjuvant therapy with FOLFOX or CAPOX, noninferiority of 3 months of therapy, as compared with 6 months, was not confirmed in the overall population. However, in patients treated with CAPOX, 3 months of therapy was as effective as 6 months, particularly in the lower-risk subgroup. (Funded by the National Cancer Institute and others.).

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Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer.

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Histological phenotypic subtypes predict recurrence risk and response to adjuvant chemotherapy in patients with stage III colorectal cancer.

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