Tumor size predicts long term survival in colon cancer: an analysis of the National Cancer Data Base

Saha, Sukamal; Shaik, Mohammed; Berbiglia, Lindsay; Saha, Supriya K.; Johnston, Gregory; Dhar, Vikrom K.; Singh, T.; Arora, Madan L.; Wiese, David

doi:10.1016/j.jamcollsurg.2014.07.589

Cited by 16 publications

(27 citation statements)

References 13 publications

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“…The positive detection rates were 55.6%, 80.5%, and 96.0%, respectively for tumors of <3 cm, 3‐6 cm and >6 cm in sizes by methylated SEPT9 alone, 33.3%, 71.4%, and 72.0% by methylated SDC2 alone, and 66.7%, 88.3%, and 96.0% by ColoDefense test. As the positive correlation between larger tumor sizes and higher TNM stages was previously reported, the apparent positive correlation between positive detection rates and tumor sizes we observed further suggested a positive correlation between positive detection rates and TNM stages.…”

Section: Resultssupporting

confidence: 89%

Multiplex methylated DNA testing in plasma with high sensitivity and specificity for colorectal cancer screening

Zhao

Yang

et al. 2019

Cancer Medicine

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Methylated SEPT9 showed relatively low sensitivity in detecting early stage colorectal cancer (CRC) and advanced adenomas (AA) in plasma. Combination of multiple biomarkers was an effective strategy to improve sensitivity in early stage cancer diagnosis and screening. A new qPCR‐based assay combining the detection of methylated SEPT9 and SDC2 (ColoDefense test) was used. Methylation statuses of SEPT9 and SDC2 were examined in 40 sets of cancer tissues and paired adjacent tissues, 10 adenomatous polyps and 3 hyperplastic polyps (HP). Then evaluated with 384 plasma samples, including 117 CRC patients, 23 AA patients, 78 small polyps patients, and 166 normal individuals. The limit of detection of ColoDefense was about 25 pg per reaction. Both SEPT9 and SDC2 were shown by ColoDefense to be heavily methylated in CRC tissues when compared to paired paracancerous tissues and HP (P < .01). The sensitivities for detecting AA and stage I CRC by plasma SEPT9 methylation alone were 12.1% and 65.0%, and those by plasma SDC2 methylation alone were 43.5% and 55.0%. In comparison, the sensitivities to detect AA and stage I CRC by ColoDefense improved to 47.8% and 80.0%. The overall sensitivity of ColoDefense in detecting CRC was 88.9% (95% CI: 81.4%‐93.7%) with a specificity of 92.8% (95% CI: 87.4%‐96.0%). Detection of the combinatorial biomarker of methylated SEPT9 and/or SDC2 is a powerful, convenient and highly effective strategy for early CRC screening with high sensitivity and specificity.

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Section: Resultssupporting

confidence: 89%

Multiplex methylated DNA testing in plasma with high sensitivity and specificity for colorectal cancer screening

Zhao

Yang

et al. 2019

Cancer Medicine

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“…Therefore, although both are a growth index, vertical infiltration seems to be much more important than horizontal proliferation, which might explain why the prognostic prediction value of tumor size dwindled as the T stage became more advanced. Like many previous studies , we confirmed the independent predictive effect of tumor size in prognosis among all patients with stage I–III colon cancer. However, the HR of tumor size decreased gradually with the increase of T stage.…”

Section: Discussionsupporting

confidence: 90%

“…Previous studies suggested that solid tumors including gastrointestinal tumors can obtain the potential of dissemination during the process of growing both horizontally and vertically . Currently, although many investigators have confirmed the negative prognostic role of tumor size, the value of tumor size in survival prediction is still underappreciated . However, the vertical growth index reflected by T stage has been established as one of the dominating prognostic factors and has been incorporated into the widely accepted TNM staging system in colon cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Tumor size, defined as the maximal horizontal tumor diameter, has been studied for decades, and large horizontal tumor extent has generally been considered to be negatively associated with prognosis in many solid tumors, including colonic malignancies . However, because of the vertical index of infiltration depth reflected by T stage, tumor size has not been recognized as a valuable factor in predicting prognosis in colon cancer.…”

Section: Introductionmentioning

confidence: 99%

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The Critical Role of Tumor Size in Predicting Prognosis for T1 Colon Cancer

Dai

Xiang

et al. 2019

The Oncologist

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Background The role of horizontal growth index of tumor size in survival prediction is still underappreciated in colon cancer because of the identification of vertical infiltration index reflected by T stage. We sought to reveal the impact of T stage on the prognostic and predictive value of tumor size in colon cancer. Materials and Methods Data of patients with stage I–III colon cancer were extracted from Surveillance, Epidemiology, and End Results Program (SEER) and Fudan University Shanghai Cancer Center (FUSCC) databases. Harrell's concordance index (c‐index) and time‐dependent receiver operating characteristic curve (ROC) were used to analyze the discriminative ability of prognostic factors. Results Stratified analyses based on T stage found that the increase of T stage significantly and negatively repressed the effect of tumor size on death and recurrence risk. In addition, tumor size showed the greatest hazard ratio of cancer‐specific death and relapse in T1 colon cancer. Even more importantly, the discriminatory ability of tumor size outperformed any other widely accepted prognostic clinical features in predicting cancer‐specific survival (SEER: c‐index 0.637, area under the ROC [AUC] 0.649; FUSCC: c‐index 0.673, AUC 0.686) and disease‐free survival (FUSCC: c‐index 0.645, AUC 0.656) in T1 stage colon cancer. Conclusion Tumor size is a critical clinical factor with considerable prognostic and predictive value for T1 colon cancer, and it should be selectively incorporated into the current staging system to facilitate prediction of death and recurrence risk. Implications for Practice To date, no consensus has been reached about the prognostic and predictive value of tumor size in colon cancer. Although tumor size is an independent prognostic factor for patients with colon cancer, the impact of tumor size on death or recurrence risk decreased notably with the increase of T stage. More importantly, the discriminative ability of tumor size outperformed any other clinical factors including N stage in patients with T1 colon cancer. Therefore, tumor size should be recommended to be incorporated into current staging systems to facilitate prognosis prediction for patients with T1 colon cancer.

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“…7 Extensive local spread and/or large size of the tumor, the presence of metastases in lymph nodes, mucinous differentiation, invasion into lymphatic vessels, perineural growth and peritoneal involvement all indicate an unfavorable prognosis of colorectal carcinoma. [8][9][10] Recently, the prognostic importance of the extent of cancer necrosis has been discussed. 11 These factors could show bidirectional associations with chronic inflammation, which is an important component of tumor pathogenesis, beginning from the initiation and accompanying the progression and spread.…”

Section: Introductionmentioning

confidence: 99%

<p>The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma</p>

Briede¹,

Štrumfa²,

Vanags³

et al. 2020

JIR

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Background: Inflammation plays an important albeit dual role in carcinogenesis. Survival studies have highlighted the prognostic significance of peritumorous inflammation. Currently, the theoretical background allows inflammation, epithelial mesenchymal transition (EMT) and the closely associated stem cell differentiation in colorectal carcinoma (CRC) to be linked. However, there is scarce direct morphological evidence. Purpose and methods: The aim of our study was to investigate the role of inflammation in cancer growth and invasion by analyzing the association between inflammation and known morphological prognostic features of colorectal cancer, EMT, stemness and mismatch repair (MMR) protein expression. The study was designed as a retrospective morphological and immunohistochemical assessment of 553 consecutive cases of surgically treated primary CRC. Results: There were statistically significant associations between high-grade inflammation and lower pT (p = 0.002), absence of lymph node metastases (p < 0.001) and less frequent lymphatic (p = 0.003), venous (p = 0.017), arterial (p = 0.012), perineural (p = 0.001) and intraneural (p = 0.01) invasion. In contrast, Crohn's like reaction (CLR) by density of lymphoid follicles in the invasive front lacked significant differences in regard to pT, pN, tumor invasion into surrounding structures (blood or lymphatic vessels, nerves), grade or necrosis (all p > 0.05). The expression of E-cadherin, CD44 and MMR proteins yielded no statistically significant associations with peritumorous inflammation by Klintrup-Mäkinen score or the density of lymphoid follicles. Nevertheless, E-cadherin levels were significantly associated with the density of eosinophils (p = 0.007). Conclusion: High-grade peritumorous inflammation is associated with beneficial morphologic CRC features, including less frequent manifestations of invasion, and is not secondary to tissue damage and necrosis. CLR is not associated with cancer spread by pTN; this finding indirectly suggests an independent role of CLR in carcinogenesis. Further, inflammation by Klintrup-Mäkinen grade and CLR is not dependent on epithelial-mesenchymal transition and stem cell differentiation. Our study highlights the complex associations between inflammation, tumor morphology, EMT, stemness and MMR protein expression in human CRC tissues.

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Tumor size predicts long term survival in colon cancer: an analysis of the National Cancer Data Base

Cited by 16 publications

References 13 publications

Multiplex methylated DNA testing in plasma with high sensitivity and specificity for colorectal cancer screening

Multiplex methylated DNA testing in plasma with high sensitivity and specificity for colorectal cancer screening

The Critical Role of Tumor Size in Predicting Prognosis for T1 Colon Cancer

<p>The Association Between Inflammation, Epithelial Mesenchymal Transition and Stemness in Colorectal Carcinoma</p>

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