Optimal Criteria for G3 (Poorly Differentiated) Stage II Colon Cancer: Prospective Validation in a Randomised Controlled Study (SACURA Trial)

Ueno, Hideki; Ishiguro, Megumi; Nakatani, Eiji; Ishikawa, Toshiaki; Uetake, Hiroyuki; Matsui, Shigeyuki; Teramukai, Satoshi; Murotani, Kenta; Maeda, Atsuyuki; Takuma, Kunio; Yoshida, Takefumi; Kambara, Takeshi; Matsuda, Keiji; Takagane, Akinori; Tomita, Naohiro; Sugihara, Kenichi

doi:10.2139/ssrn.3588571

Cited by 3 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, a randomized controlled trial led by Ueno also confirmed our view. The study found that the 5-year RFS rate of patients with poorly differentiated tumors in the chemotherapy group achieved greater improvement (9.1%) than the surgery-alone group ( 14 ). Positive CEA, PNI, LN examined less than 12, unmarried status, mucin-producing tumors and left tumors were associated with significant increased risk of mortality compared with patients with no HRFs, and there was a cumulative effect of HRF on OS.…”

Section: Discussionmentioning

confidence: 91%

A retrospective study based on SEER database: not all high-risk factors are equal for stage II colon cancer

Liu¹,

Jiang²,

Xiang³

et al. 2022

Transl Cancer Res TCR

View full text Add to dashboard Cite

Background: For stage II colon cancer, understanding of high-risk factors (HRFs) that affect the overall survival (OS) and the benefit of chemotherapy is limited. Meanwhile, no stable predictor can effectively predict OS of stage II colon cancer to date. Our study is aimed to identify HRFs associated with OS of stage II colon cancer, to quantify the risk conferred by each HRF, and to evaluate OS benefit gained by chemotherapy. Meanwhile, we attempt to establish a nomogram model for stage II colon cancer. Methods:The clinical variables of patients with stage II colon cancer between 2000 and 2018 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate analysis were performed to filtered out all the HRFs. We calculated the hazard ratios (HR) and evaluated the survival benefit of adjuvant chemotherapy for each HRF and combinations of HRFs. Then, a nomogram model based on all HRFs was established and verified.Results: A total of 39,103 patients with stage II colon cancer were included. T4b tumors were the highest risk for reduced OS [HR =2.821; 95% confidence interval (CI): 1.949-4.082], mucin-producing tumors (HR =2.412; 95% CI: 1.326-4.388) the second, and lymph node (LN) examined less than 12 (HR =2.200; 95% CI: 1.786-2.710) the third. T4 tumors (HR =0.790; 95% CI: 0.542-1.151), poorly/undifferentiated tumors (HR =0.468; 95% CI: 0.237-0.924), and some combinations of HRFs containing either could benefit from adjuvant chemotherapy. Meanwhile, we established an effective nomogram model based on the identified HRFs. Conclusions:The study has identified several novel HRFs for stage II colon cancer. Adjuvant chemotherapy has considerable OS benefit for stage II colon cancers with some specific HRFs, and treatment plans need to be individualized. Type and number of HRFs should be taken into consideration when recommending adjuvant chemotherapy. Our new nomogram model has better predictive ability and stability than the tumor-node-metastasis (TNM) stage system of American Joint Committee on Cancer (AJCC) staging system.

show abstract

Section: Discussionmentioning

confidence: 91%

A retrospective study based on SEER database: not all high-risk factors are equal for stage II colon cancer

Liu¹,

Jiang²,

Xiang³

et al. 2022

Transl Cancer Res TCR

View full text Add to dashboard Cite

show abstract

“…It should be noted that many classical morphological features with prognostic value, such as tumor grade, still lack biological explanation. It is of interest that previous structural analyses in CRC have indicated that growth patterns quite similar to putative AR structures, including micropapillary, solid and cribriform growth, and some of the so called poorly differentiated clusters [ 36 , 37 ] associate with poor prognosis [ 38 ]. However, quantification of such components has often been poorly specified and prognostic value is not always straightforward [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Putative anoikis resistant subpopulations are enriched in lymph node metastases and indicate adverse prognosis in colorectal carcinoma

Mattila

Patankar

Väyrynen

et al. 2022

Clin Exp Metastasis

View full text Add to dashboard Cite

Anoikis refers to apoptosis induced by the loss of contact with the extracellular matrix. Anoikis resistance is essential for metastasis. We have recently shown that it is possible to quantitatively evaluate putative anoikis resistant (AR) subpopulations in colorectal carcinoma (CRC). Abundance of these multi-cell structures is an independent marker of adverse prognosis. Here, we have quantified putative AR subpopulations in lymph node (LN) metastases of CRC and evaluated their prognostic value and relationship with the characteristics of primary tumors. A case series included 137 unselected CRC patients, 54 with LN metastases. Areal densities (structures/mm2) of putative AR structures in primary tumors had been analyzed previously and now were determined from all nodal metastases (n = 183). Areal density of putative AR structures was higher in LN metastases than in primary tumors. Variation of the areal density within different LN metastases of a single patient was lower than between metastases of different patients. Abundance of putative AR structures in LN metastases was associated with shorter cancer specific survival (p = 0.013), and this association was independent of T and N stages. Abundance of putative AR structures in primary tumors and LN metastases had a cumulative adverse effect on prognosis. Enrichment of putative AR subpopulations in LN metastases suggest that in metastasis formation, there is a selection favoring cells capable of forming these structures. Higher intra-case constancy relative to inter-case variation suggests that such selection is stable in metastasis development. Our findings indirectly support the biological validity of our concept of putative AR structures.

show abstract

“…Areas of poorly differentiated components (PORs) were defined as regions where the cancer had no glandular formation 13 . The lowest magnification of the objective lens for which the poorly differentiated component filled the field of vision was regarded as the extent of the poorly differentiated component of CRC.…”

Section: Methodsmentioning

confidence: 99%

Simultaneous analysis of tumor-infiltrating immune cells density, tumor budding status, and presence of lymphoid follicles in CRC tissue

Markowski¹,

Markowska

Ustymowicz

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Colorectal cancer (CRC) affects more than 1,000,000 people worldwide each year. Recently, the number of young patients with early-onset colorectal cancer has increased, and right-sided colorectal cancer is still often diagnosed only in advanced stages. The TNM classification is not perfect for CRC staging. This study aimed to perform, for the first time, simultaneous analysis of tumor-infiltrating immune cell density, presence of lymphoid follicles, and budding status in CRC tissue. Intraoperative samples of neoplastic tissue were collected from 195 consecutive patients who were admitted to the surgical ward for elective colorectal surgery. Histological parameters were assessed in the tissue samples: tumor budding foci, poorly differentiated clusters and areas of poorly differentiated components. Tumor-infiltrating immune cells (tumor-associated neutrophils and tumor-infiltrating lymphocytes) were detected in five randomly chosen, areas at the tumor center and at the invasive front. Additionally, the presence of lymphoid follicles in CRC tissue was assessed. Tumor budding parameters were positively correlated with colorectal cancer advancement or histologic (mucinous) type of CRC. The number of poorly differentiated clusters was higher in younger patients. Lower densities of CD3 and CD4 lymphocytes were seen in CRC with a greater depth of tumor invasion. Lower densities of CD3 and CD8 lymphocytes were found in CRC with metastases to the surrounding lymph nodes. The lower density of CD8 lymphocytes was observed in CRC with distant metastases. Lower densities of tumor-associated neutrophils and tumor-infiltrating lymphocytes (CD3 and CD8) were revealed in CRC without lymphoid follicles. The number of lymphoid follicles was higher in patients with less advanced CRCs. Three histopathology markers, such as high tumor budding, scanty lymphocyte infiltration, and the poverty of lymphoid follicles, complement each other, appear to be reliable indicators of colorectal cancer progression, and could be useful in everyday medical practice, but their widespread use requires further research. We propose to take into account these markers, in the assessment of colorectal cancer advancement, in addition to the TNM classification.

show abstract

Optimal Criteria for G3 (Poorly Differentiated) Stage II Colon Cancer: Prospective Validation in a Randomised Controlled Study (SACURA Trial)

Cited by 3 publications

References 0 publications

A retrospective study based on SEER database: not all high-risk factors are equal for stage II colon cancer

A retrospective study based on SEER database: not all high-risk factors are equal for stage II colon cancer

Putative anoikis resistant subpopulations are enriched in lymph node metastases and indicate adverse prognosis in colorectal carcinoma

Simultaneous analysis of tumor-infiltrating immune cells density, tumor budding status, and presence of lymphoid follicles in CRC tissue

Contact Info

Product

Resources

About