scholarly journals Metastasis Initiation Precedes Detection of Primary Cancer—Analysis of Metastasis Growth in vivo in a Colorectal Cancer Test Case

2020 ◽  
Vol 11 ◽  
Author(s):  
Gili Hochman ◽  
Einat Shacham-Shmueli ◽  
Stephen P. Raskin ◽  
Sara Rosenbaum ◽  
Svetlana Bunimovich-Mendrazitsky
Keyword(s):  
Colorectal Cancer ◽  
Exponential Growth ◽  
Primary Tumor ◽  
Lung Metastases ◽  
Growth Models ◽  
Tumor Resection ◽  
Test Case ◽  
Tumor Doubling Time ◽  
Metastasis Growth

Most cases of deaths from colorectal cancer (CRC) result from metastases, which are often still undetectable at disease detection time. Even so, in many cases, shedding is assumed to have taken place before that time. The dynamics of metastasis formation and growth are not well-established. This work aims to explore CRC lung metastasis growth rate and dynamics. We analyzed a test case of a metastatic CRC patient with four lung metastases, with data of four serial computed tomography (CT) scans measuring metastasis sizes while untreated. We fitted three mathematical growth models—exponential, logistic, and Gompertzian—to the CT measurements. For each metastasis, a best-fitted model was determined, tumor doubling time (TDT) was assessed, and metastasis inception time was extrapolated. Three of the metastases showed exponential growth, while the fourth showed logistic restraint of the growth. TDT was around 93 days. Predicted metastasis inception time was at least 4–5 years before the primary tumor diagnosis date, though they did not reach detectable sizes until at least 1 year after primary tumor resection. Our results support the exponential growth approximation for most of the metastases, at least for the clinically observed time period. Our analysis shows that metastases can be initiated before the primary tumor is detectable and implies that surgeries accelerate metastasis growth.

Tumor bulk as a prognostic biomarker and predictor of benefit from anti-EGFR therapy in patients with metastatic colorectal cancer: Analysis of 476 patients from the ARCAD Clinical Trials Program.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 108-108
Author(s):  
Benjamin Adam Weinberg ◽  
Manel Rakez ◽  
Benoist Chibaudel ◽  
Tim Maughan ◽  
Richard Adams ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Primary Tumor ◽  
Lung Metastases ◽  
Performance Status ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Wild Type ◽  
Cox Models ◽  
Study Results

108 Background: Primary tumor sidedness has emerged as a prognostic and predictive biomarker for patients (pts) with metastatic colorectal cancer (mCRC). Tumor bulk has also been postulated to predict response to anti-EGFR therapy. We sought to evaluate the role of tumor bulk as a predictive biomarker to anti-EGFR therapy in pts with left- (LS) and right-sided (RS) mCRC. Methods: Data from 476 pts with mCRC enrolled across 2 first-line trials of anti-EGFR plus chemotherapy versus chemotherapy were pooled. Pts were included if there was available information on tumor sidedness and tumor bulk. All were KRAS wild-type and BRAF wild-type or unknown BRAF status. The right colon was defined as the cecum through the transverse colon, and the left colon as the splenic flexure through the rectum. Tumor bulk was the mean tumor size of target lesions at baseline, bulky defined as > 3.5 cm. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for performance status (PS), platelet count, primary tumor (PT) resection, number of metastatic sites, and stratified by study. Results: Pts with bulky tumors (211, 44%) had higher PS, white blood cell and platelet counts, higher CEA, fewer sites of metastatic disease, more liver than lung metastases, and fewer had PT resection. OS and PFS medians in months (mos) are presented in the table with 95% confidence intervals (95%CIs). Bulky tumors had inferior median OS compared with non-bulky (mOS, 17.9 vs. 21.3 mos, HRadj 1.33, 95% CI 1.05-1.69, P = 0.016) although median PFS was similar (mPFS, 8.6 vs. 8.7 mos, HRadj 1.15, 95% CI 0.92-1.42, P = 0.21). Conclusions: Tumor bulk is an independent prognostic factor for OS in KRAS wild-type and BRAF wild-type or unknown BRAF status pts. Pts with non-bulky RS tumors have survival outcomes similar to pts with bulky LS tumors. Although the mPFS for pts with RS tumors treated with anti-EGFR therapy was the lowest across subgroups, this finding was not statistically significant. Further research is warranted into whether pts with bulky RS tumors benefit from anti-EGFR therapy. Clinical trial information: NCT00182715, NCT00640081. [Table: see text]

A Novel Derivation Predicting Survival After Primary Tumor Resection in Stage IV Colorectal Cancer

2017 ◽  
Vol 60 (9) ◽  
pp. 895-904 ◽  
Author(s):  
Winson Jianhong Tan ◽  
Sreemanee Raaj Dorajoo ◽  
Madeline Yen Min Chee ◽  
Wah Siew Tan ◽  
Fung Joon Foo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Primary Tumor ◽  
Tumor Resection ◽  
Stage Iv ◽  
Primary Tumor Resection ◽  
Stage Iv Colorectal Cancer

scholarly journals Subdivision of metastatic colorectal cancer for identifying patients who benefit more from primary tumor resection

2021 ◽  
Author(s):  
Dakui Luo ◽  
Zezhi Shan ◽  
Zhiqiang Li ◽  
Simin Chen ◽  
Sanjun Cai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factors ◽  
Primary Tumor ◽  
Cox Regression ◽  
Tumor Resection ◽  
Signet Ring Cell ◽  
Normal Serum ◽  
Primary Tumor Resection ◽  
Cox Regression Analysis ◽  
Serum Cea

Abstract Background Stage IV colorectal cancer (CRC) patients are heterogeneous with distinctive clinicopathologic features and prognosis. Radical resection of primary tumor and distant metastases is associated with improved survival outcomes in metastatic CRC. The value of palliative primary tumor resection is controversial. The present study explored which subgroups benefited more from primary tumor resection in metastatic CRC. Methods Between 2004 and 2015, patients with metastatic CRC were identified using the surveillance, epidemiology, and end results (SEER) database. Uni- and multivariable Cox regression analysis were performed to identify factors associated with decreased cancer-specific mortality. The subgroups were divided based on the independent prognostic factors. Results Age, marital status, race, serum CEA, histologic type, differentiation, tumor location, surgery of primary or metastatic lesion, site of metastases, number of metastatic sites, chemotherapy and radiotherapy were identified as independent prognostic factors. Patients with non-white race, normal serum CEA, non-signet ring cell carcinoma, well or moderate differentiation, surgery of metastases, isolated liver metastasis, single metastasis, receiving chemotherapy or radiotherapy presented more survival benefit from primary tumor resection. Conclusion Subgroup of metastatic CRC optimizes decision-making and selected patients will benefit more from primary tumor resection.

scholarly journals Role of Primary Tumor Resection Among Chemotherapy-Treated Patients with Synchronous Stage IV Colorectal Cancer: A Survival Analysis

2013 ◽  
Vol 18 (3) ◽  
pp. 592-598 ◽  
Author(s):  
Walter Y Tsang ◽  
Argyrios Ziogas ◽  
Bruce S. Lin ◽  
Tara E. Seery ◽  
William Karnes ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Analysis ◽  
Primary Tumor ◽  
Tumor Resection ◽  
Stage Iv ◽  
Primary Tumor Resection ◽  
Stage Iv Colorectal Cancer

Primary Tumor Resection in Patients With Metastatic Colorectal Cancer Is Associated With Reversal of Systemic Inflammation and Improved Survival

2015 ◽  
Vol 14 (3) ◽  
pp. 185-191 ◽  
Author(s):  
Natalie Turner ◽  
Ben Tran ◽  
Phillip V. Tran ◽  
Mathuranthakan Sinnathamby ◽  
Hui-Li Wong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Systemic Inflammation ◽  
Primary Tumor ◽  
Tumor Resection ◽  
Primary Tumor Resection
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