Dataset Information

Unraveling the role of tumor sidedness in prognosis of stage II colon cancer.

ABSTRACT:

Background

Stage II colon cancer has varying risks for metastasis, and treatment strategies depend on molecular and clinicopathological features. While tumor-sidedness is a well-accepted prognostic factor for stage III/IV colon cancer, its role in stage II is controversial. Understanding its effect in stage II is crucial for improving treatment strategies.

Methods

We analyzed clinical and follow-up data of colon cancer from the Surveillance, Epidemiology, and End Results database (2004-2017). Patients were divided into a primary study cohort (2010-2017) and a validation cohort (2004-2009). The baseline characteristics between right-sided colon cancer (RCC) and left-sided colon cancer (LCC) groups were compared. Moreover, the effect of tumor size on cancer-specific survival (CSS) was evaluated using Kaplan-Meier analysis.

Results

The study involved 87,355 patients in the study cohort and 65,858 in the validation cohort. Of the study cohort, 52.3% were diagnosed with RCC. The median age was 64 years old, with 48.5% females and 76.8% of white people. In addition, stage II RCC showed better CSS compared with LCC (5-year CSS 88.0% vs 85.5%, P < 0.001), while stage III/IV RCC demonstrated poorer outcomes. Multivariate Cox regression analysis identified that the right-sidedness was a positive prognostic factor in stages I/II but negative in stages III (HR 1.10, P < 0.001) and IV (HR 1.26, P < 0.001). Chemotherapy rates decreased in RCC, particularly in stage II (RCC vs LCC: 16.2% vs 28.5%, P < 0.001). Subgroup analysis, stratified by T3/T4 stages and chemotherapy status, further highlighted better survival outcomes in RCC.

Conclusions

RCC is associated with a significantly better prognosis in stage II. The importance of considering tumor-sidedness in clinical decision-making and the design of future clinical trials should be emphasized.

SUBMITTER: Yang Y

PROVIDER: S-EPMC11014780 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Unraveling the role of tumor sidedness in prognosis of stage II colon cancer.

Yang Yun Y Yang Xiaobao X Bai Zhigang Z Gu Xiaozhe X Shah Saloni Rameshchandra SR Salewala Kenish Sirajbhai KS Kevadiya Mansi Pankajbhai MP Zhang Zhongtao Z

Gastroenterology report 20240412

<h4>Background</h4>Stage II colon cancer has varying risks for metastasis, and treatment strategies depend on molecular and clinicopathological features. While tumor-sidedness is a well-accepted prognostic factor for stage III/IV colon cancer, its role in stage II is controversial. Understanding its effect in stage II is crucial for improving treatment strategies.<h4>Methods</h4>We analyzed clinical and follow-up data of colon cancer from the Surveillance, Epidemiology, and End Results database ...[more]

PMID: 38617706

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Project description:ImportanceRecent data have suggested that disease biology and outcome of colon cancer may differ between right-sided and left-sided tumors. However, the literature on the prognostic value of tumor laterality is conflicting.ObjectiveTo explore differences in laterality based on disease characteristics and outcomes in a population-based cohort of early-stage colon cancer.Design, setting, and participantsThis investigation was a population-based retrospective cohort study of patients with early-stage colon cancer from the province of Ontario, Canada. Electronic records of treatment were linked to the Ontario Cancer Registry to identify all patients with colon cancer who underwent resection between January 1, 2002, and December 31, 2008. The date of the final analysis was October 20, 2016. The study population included a 25% random sample of all patients with resected stage I to III disease. Right-sided colon cancer was defined as any tumor arising in the cecum, ascending colon, hepatic flexure, or transverse colon. Left-sided colon cancer was defined as any tumor arising in the splenic flexure, descending colon, sigmoid colon, or rectosigmoid colon.Main outcomes and measuresOverall survival (OS) and cancer-specific survival (CSS) measured from the time of resection.ResultsThis study identified 6365 patients with early-stage colon cancer (48.7% [3098 of 6365] female). Their median age was 72 years, and 51.7% (3291 of 6365) had right-sided disease. Stage distribution was 18.3% (1163 of 6365) stage I, 38.4% (2446 of 6365) stage II, and 43.3% (2756 of 6365) stage III. Patients with right-sided colon cancer were more likely to be older (median age, 73 vs 70 years; P < .001) and female (54.4% [1790 of 3291] vs 42.6% [1308 of 3074], P < .001) and have greater comorbidity. Right-sided cancers were more likely to be T4 (19.2% [631 of 3291] vs 15.9% [490 of 3074], P < .001) and poorly differentiated (21.1% [695 of 3291] vs 9.6% [295 of 3074], P < .001) but less likely to be node positive (42.0% [1383 of 3291] vs 44.7% [1373 of 3074], P = .03) compared with left-sided disease. In adjusted analyses, there was no difference in long-term survival for right-sided compared with left-sided colon cancer: the hazard ratios were 1.00 (95% CI, 0.92-1.08) for OS and 1.00 (95% CI, 0.91-1.10) for CSS. These results were consistent when the survival analyses were restricted to stage III disease: the hazard ratios were 1.03 (95% CI, 0.93-1.14) for OS and 1.10 (95% CI, 0.97-1.24) for CSS.Conclusions and relevanceIn this population-based cohort of early-stage resected colon cancer, disease laterality was not associated with long-term OS or CSS.

Project description:BackgroundTumor-infiltrating lymphocytes (TILs) are a robust and independent prognostic variable in localized colon cancer. Given reported differences in molecular features and prognosis of right- versus left-sided tumors, we examined the association of TIL densities with patient survival by primary tumor sidedness in stage III cancers, including clinical low- (T1-3, N1) and high-risk (T4 and/or N2) groups.Patients and methodsIn a phase III trial of FOLFOX-based adjuvant chemotherapy, TIL densities were analyzed and dichotomized in colon carcinomas (N = 1532) based on a previously determined cut point optimized for disease-free survival (DFS). Right-sided tumors were defined as proximal to the splenic flexure. Associations of TILs and sidedness with 5-year DFS were examined using Kaplan-Meier methodology along with multivariable modeling and relative contribution analysis by Cox regression.ResultsLower TIL densities were found in left- versus right-sided tumors (P < 0.0001). The association of TIL densities with DFS differed significantly by tumor sidedness (Pinteraction = 0.045). Overall, patient tumors with low (versus high) TILs had significantly poorer DFS in right-sided (hazard ratio 2.02, 95% confidence interval 1.45-2.82; Padj < 0.0001), but not left-sided tumors (Padj = 0.1731). Among clinical low-risk patients, low (versus high) TILs were adversely prognostic only in right-sided tumors (Padj = 0.0058). Among high-risk patients, low TILs were prognostic independent of sidedness (Padj < 0.025). The relative contribution of TILs to DFS was substantially greater in right- versus left-sided tumors (24% versus 1.5%). In high-risk tumors, TILs had the highest relative contribution to DFS (42%) of all variables. In low-risk tumors, the contribution of TILs (16%) to DFS was second to KRAS.ConclusionsThe association of TIL densities with patient survival differed by primary tumor sidedness and clinical risk group, suggesting that TILs should be interpreted in this context among stage III colon cancers.ClinicaltrialsGov identifierNCT00079274; https://clinicaltrials.gov/ct2/show/NCT00079274.

Project description:BackgroundThe role of adjuvant chemotherapy in stage II colon cancer continues to be debated. The presence of circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood.MethodsWe conducted a trial to assess whether a ctDNA-guided approach could reduce the use of adjuvant chemotherapy without compromising recurrence risk. Patients with stage II colon cancer were randomly assigned in a 2:1 ratio to have treatment decisions guided by either ctDNA results or standard clinicopathological features. For ctDNA-guided management, a ctDNA-positive result at 4 or 7 weeks after surgery prompted oxaliplatin-based or fluoropyrimidine chemotherapy. Patients who were ctDNA-negative were not treated. The primary efficacy end point was recurrence-free survival at 2 years. A key secondary end point was adjuvant chemotherapy use.ResultsOf the 455 patients who underwent randomization, 302 were assigned to ctDNA-guided management and 153 to standard management. The median follow-up was 37 months. A lower percentage of patients in the ctDNA-guided group than in the standard-management group received adjuvant chemotherapy (15% vs. 28%; relative risk, 1.82; 95% confidence interval [CI], 1.25 to 2.65). In the evaluation of 2-year recurrence-free survival, ctDNA-guided management was noninferior to standard management (93.5% and 92.4%, respectively; absolute difference, 1.1 percentage points; 95% CI, -4.1 to 6.2 [noninferiority margin, -8.5 percentage points]). Three-year recurrence-free survival was 86.4% among ctDNA-positive patients who received adjuvant chemotherapy and 92.5% among ctDNA-negative patients who did not.ConclusionsA ctDNA-guided approach to the treatment of stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free survival. (Supported by the Australian National Health and Medical Research Council and others; DYNAMIC Australian New Zealand Clinical Trials Registry number, ACTRN12615000381583.).

Project description:Colorectal cancer (CRC) is influenced by perturbations in the colonic microbiota, characterized by an imbalance favoring pathogenic bacteria over beneficial ones. This dysbiosis contributes to CRC initiation and progression through mechanisms such as carcinogenic metabolite production, inflammation induction, DNA damage, and oncogenic signaling activation. Understanding the role of external factors in shaping the colonic microbiota is crucial for mitigating CRC progression. This study aims to elucidate the gut microbiome's role in CRC progression by analyzing paired tumor and mucosal tissue samples obtained from the colon walls of 17 patients. Through sequencing of the V3-V4 region of the 16S rRNA gene, we characterized the tumor microbiome and assessed its association with clinical variables. Our findings revealed a significant reduction in alpha diversity within tumor samples compared to paired colon biopsy samples, indicating a less diverse microbial environment within the tumor microenvironment. While both tissues exhibited dominance of similar bacterial phyla, their relative abundances varied, suggesting potential colon-specific effects. Fusobacteriota enrichment, notably in the right colon, may be linked to MLH1 deficiency. Taxonomy analysis identified diverse bacterial genera, with some primarily associated with the colon wall and others unique to this region. Conversely, several genera were exclusively expressed in tumor tissue. Functional biomarker analysis identified three key genes with differential abundance between tumor microenvironment and colon tissue, indicating distinct metabolic activities. Functional biomarker analysis revealed three key genes with differential abundance: K11076 (putrescine transport system) and K10535 (nitrification) were enriched in the tumor microenvironment, while K11329 (SasA-RpaAB circadian timing mediator) dominated colon tissue. Metabolic pathway analysis linked seven metabolic pathways to the microbiome. Collectively, these findings highlight significant gut microbiome alterations in CRC and strongly suggest that long-term dysbiosis profoundly impacts CRC progression.

Dataset Information

Unraveling the role of tumor sidedness in prognosis of stage II colon cancer.

Background

Methods

Results

Conclusions

Publications

Unraveling the role of tumor sidedness in prognosis of stage II colon cancer.

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