Perineural Invasion is a Major Prognostic and Predictive Factor of Response to Adjuvant Chemotherapy in Stage I–II Colon Cancer

Cienfuegos, Javier A.; Martínez, P.; Baixauli, Jorge; Beorlegui, Carmen; Rosenstone, S.; Sola, J. J.; Rodríguez, Javier Jacob; Hernández-Lizoain, José Luís

doi:10.1245/s10434-016-5561-0

Cited by 59 publications

(52 citation statements)

References 49 publications

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“…Molecular features of tumors are generally used to guide decision making for adjuvant chemotherapy in patients with stage II disease, although evidence supporting this practice is still weak [35][36][37][38][39][40][41][42][43][44][45]. In most countries (including Taiwan), the most common, reliable, and affordable methods of determining risk features are examinations of high-risk clinicopathologic features and the tumor, node, and metastasis (TNM) stage [46][47][48][49][50][51][52].…”

Section: Discussionmentioning

confidence: 99%

Adjuvant Therapy for High-Risk Stage II or III Colon Adenocarcinoma: A Propensity Score-Matched, Nationwide, Population-Based Cohort Study

Chang

Yuan

et al. 2019

Cancers

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Purpose: To determine the optimal adjuvant chemotherapy regimen for patients with high-risk stage II or III colon adenocarcinoma, we conducted this propensity score-matched, nationwide, population-based cohort study to estimate the effects of adjuvant treatments in high-risk stage II or III colon adenocarcinoma. Patients and Methods: Using propensity score matching, we minimized the confounding effects of sex, age, pathologic stage, tumor location, total chemotherapy cycles, and Charlson comorbidity index scores on adjuvant treatment outcomes in patients with high-risk stage II or III resectable colon adenocarcinoma. We selected the patients from the Taiwan Cancer Registry database and divided them into four groups: Group 1, comprising patients who received surgery alone; group 2, comprising those who received adjuvant fluoropyrimidine alone; group 3, comprising those who received adjuvant oxaliplatin-fluoropyrimidine-leucovorin (FOLFOX); and group 4, comprising those who received adjuvant folinic acid-fluorouracil-irinotecan (FOLFIRI). Results: In both univariate and multivariate Cox regression analyses, the adjusted hazard ratios (aHRs, as well as the 95% confidence intervals (Cis)) for mortality observed for groups 1, 2, and 4 relative to group 3 were 1.55 (1.32 to 1.82), 1.22 (1.05 to 1.43), and 2.97 (2.43 to 3.63), respectively. After a stratified subgroup analysis for high-risk stage II colon adenocarcinoma, we noted that the aHR (95% CI) for mortality for group 2 relative to group 3 was 0.52 (0.30 to 0.89). Conclusions: Adjuvant fluoropyrimidine alone is the most optimal regimen for patients with high-risk stage II colon adenocarcinoma compared with the other adjuvant chemotherapy regimens. Adjuvant FOLFOX can serve as an optimal regimen for patients with pathologic stage III colon adenocarcinoma, regardless of age, sex, or tumor location.

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Section: Discussionmentioning

confidence: 99%

Adjuvant Therapy for High-Risk Stage II or III Colon Adenocarcinoma: A Propensity Score-Matched, Nationwide, Population-Based Cohort Study

Chang

Yuan

et al. 2019

Cancers

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“…Recent studies have indicated the potential predictive role of perineural invasion and microsatellite instability in disease progression and for chemotherapy benefit for patients with stage II CRC, but no definite conclusive statements have been made due to limited supporting data [22,23]. Epithelial-mesenchymal transition (EMT) as an oncogenic molecular event has been extensively investigated in the CRC field during the past decade.…”

Section: Discussionmentioning

confidence: 99%

Stromal Expression of Vimentin Predicts the Clinical Outcome of Stage II Colorectal Cancer for High-Risk Patients

et al. 2017

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BackgroundIncreased expression of vimentin in tissue samples from patients with colorectal cancer (CRC) has been previously demonstrated, but its prognostic significance remains controversial, and the clinical significance for patients with stage II CRC is still unknown. The aim of this study was to evaluate the expression of vimentin in CRC and its potential prognostic significance.Material/MethodsWe analyzed vimentin expression in 203 CRC tissue samples from patients with stage II cancer using immunohistochemistry, and correlated the findings with clinicopathological patient features. CRC-specific survival (CSS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method. Univariate and multivariate analysis was performed using the Cox proportional hazards method for survival.ResultsVimentin expression was significantly correlated only with tumor (T) stage (p=0.024). Kaplan-Meier survival analysis indicated that vimentin expression could stratify the CSS and DFS of patients with stage II CRC at high risk (p=0.029, p=0.042, respectively), but not those of low-risk stage II patients (p=0.208, p=0.361, respectively). Univariate and multivariate analysis further revealed that stromal vimentin expression is an independent prognostic factor for CSS and DFS of high-risk stage II patients (p=0.043, p=0.022, respectively). Moreover, high-risk stage II patients with low stromal vimentin expression benefitted more from standard adjuvant chemotherapy than those with high stromal vimentin expression (CSS: p=0.012 vs. p=0.407; DFS: p=0.017 vs. p=0.420).ConclusionsOur study suggests that stromal vimentin expression is a promising indicator for survival prediction and adjuvant chemotherapy response in patients with stage II CRC with high-risk factors for recurrence.

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“…However, overemphasis on LNM in the colon cancer TNM staging system is controversial. Many studies have reported the prognostic impact of high-risk features beyond LNM [11][12][13][14][15][16][17][18][19][20][21][22][23]. One study showed the relationship between the number of high-risk features and prognosis, demonstrating that 5-year OS rate was less than 20% in patients with stage II colon cancer with four or more high-risk features [18].…”

Section: Discussionmentioning

confidence: 99%

Comparison of vascular invasion with lymph node metastasis as a prognostic factor in stage I-III colon cancer: an observational cohort study

Bae

Lee

Han

et al. 2020

Preprint

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Abstract Background: The oncological impact of vascular invasion (VI), when compared with that of lymph node metastasis (LNM), has been underestimated in clinicopathological staging of colon cancer. This study aimed to evaluate the prognostic impact of VI in comparison with that of LNM in non-metastatic colon cancer.Methods: Patients who underwent surgery for stage I-III colon cancer were divided into four groups depending on the status of VI and LNM (Group I: VI-/LNM-; Group II: VI+/LNM-; Group III: VI-/LNM+; Group IV: VI+/LNM+). Group III was subdivided according to the node (N) stage (Group IIIA: VI-/N1; Group IIIB: VI-/N2). Disease-free survival (DFS) and overall survival were compared.Results: In total, 793 non-metastatic colon cancer patients were included. Group II (hazard ratio [HR] 2.34, 1.01-5.41), Group III (HR 1.91, 1.26-2.89), and Group IV (HR 2.34, 1.33-4.14) were independently associated with poor DFS. All recurrences in Group II occurred within 2 years and were distant metastases. The 1- and 2-year DFS rates were 76.3% and 71.6% in Group II and 88.3% and 79.8% in Group III, respectively (P = 0.067 and 0.247). In subgroup analysis, the 5-year DFS rates tended to be lower in Group II (71.6%) than in Group IIIA (79.7%) and higher than those in Group IIIB (61.4%).Conclusion: VI is a prognostic factor as significant as LNM and may be regarded as a stronger prognostic factor than N1 stage in non-metastatic colon cancer. Furthermore, a potential association was observed between VI and recurrence patterns, such as early recurrence and distant metastasis.

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Perineural Invasion is a Major Prognostic and Predictive Factor of Response to Adjuvant Chemotherapy in Stage I–II Colon Cancer

Abstract: PNI a major prognostic and predictive factor in stage II colon cancer, and our results support the use of adjuvant chemotherapy in patients with PNI.

Cited by 59 publications

References 49 publications

Adjuvant Therapy for High-Risk Stage II or III Colon Adenocarcinoma: A Propensity Score-Matched, Nationwide, Population-Based Cohort Study

Adjuvant Therapy for High-Risk Stage II or III Colon Adenocarcinoma: A Propensity Score-Matched, Nationwide, Population-Based Cohort Study

Stromal Expression of Vimentin Predicts the Clinical Outcome of Stage II Colorectal Cancer for High-Risk Patients

Comparison of vascular invasion with lymph node metastasis as a prognostic factor in stage I-III colon cancer: an observational cohort study

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