Why cancer at the primary site and in the lymph nodes contributes to the risk of cancer death

Abstract

BACKGROUND:Cancer at both the primary site and in the lymph nodes is associated with lethality, although the mechanism by which lethality arises from each site has been poorly understood. For breast carcinoma, each positive lymph node contributes an approximately 6% risk of death, and each millimeter of primary tumor greatest dimension contributes approximately 1%; whereas, for melanoma, each positive lymph node contributes an approximately 23% risk, and each millimeter of tumor thickness contributes approximately 8%: This is described by a pair of linked equations, the Size+Nodes method.METHODS:A simple expression, the ProbabilityEstimation equation, which was derived from the authors' binary‐biologic model of cancer metastasis, was used to calculate the probabilities of spread of cancer cells from data on tumor size, lymph node status, and death rate.RESULTS:In this report, the authors demonstrated, that when similar masses of cancer are compared, the chance of lethal spread of a cancer cell to the periphery is approximately the same whether the spread emerges from a lymph node or from the primary site. The greater the number of cells at the primary site (tumor size) or the greater the number of cells in the lymph nodes (number of positive lymph nodes), the greater is the aggregate chance that 1 or more cells has undergone a lethal event of spread, a process captured by the Size+Nodes equations.CONCLUSIONS:The lethal contributions of cancer at the primary site and lymph nodes can be explained by a simple mechanical process of the spread of cancer cells occurring with definable probabilities per cell. The presence of cancer in the lymph nodes does not indicate an intrinsic change in a malignancy but, rather, an increased mass of cancer from which spread can emerge. Cancer 2009. © 2009 American Cancer Society.

Gene Expression Profiling of Fixed Tissues Identified Hypoxia-Inducible Factor-1α, VEGF, and Matrix Metalloproteinase-2 as Biomarkers of Lymph Node Metastasis in Hepatocellular Carcinoma

“…Lymph node metastases (LNM), which contribute to the risk of cancer death (3), are found in approximately 7.45% of HCC patients (4). We have reported that LNM in HCC is sensitive to external beam radiotherapy (5), but the quality of life and survival of patients who undergo this procedure remains unsatisfactory.…”

How cancer at the primary site and in the lymph nodes contributes to the risk of cancer death

“…Note that we have framed the definition of p x so that it does not consider events of spread that do not lead to a macroscopic manifestation, nor does this definition assume that p x is constant, 3,7,8 nor does it require that every cell in the mass of cancer have the potential for spread, although this may be the case. For further discussion, see the accompanying article this series and the report by Michaelson et al 7,8 Because p x is the probability of a single successful event of lethal spread, the probability per cell that there will not be an event of spread is (1 À p x ), and the overall probability that a tumor of N cells will not give rise to 1 or more lethal metastases will be (1 À p x ) N .…”

“…We also examine the relation between primary tumor size and the risk of cancer in the lymph nodes for breast carcinoma and melanoma. In the accompanying articles, we extend these finding to examine the reason for the lethal contributions of cancer at the primary site and in the lymph nodes, 8 the impact of prognostic factors other than primary tumor size and lymph node status on the risk of cancer death, 9 and the application of these finding to the development of web-based calculators that physicians can use to estimate the risk of cancer death (available at: http://www.CancerMath.net accessed on July 29, 2009). 9 …”

“…[6][7][8] We call this approach the binary-biological model of cancer metastasis. We have described various aspects of this mathematical framework; herein, we present this mathematical framework in full.…”

Creating and Providing Predictions of Melanoma Outcome

“…CancerMath.net). 5,6 Our analysis, outlined in a technical report available at the CancerMath.net website, indicates that the outcome predictions provided by both our melanoma calculator, and that of Soong et al, accurately predict the chance of survival, as tested against the Surveillance, Epidemiology, and End Results (SEER) melanoma national dataset provided by the National Cancer Institute. 7 However, as noted previously, the calculator developed by Soong et al sorts patients into rather large bins, which contain mixes of patients with widely disparate risks of death.…”