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CANCER METASTASIS

A Mathematical Modelling

CHN-302 ENGINEERING ANALYSIS AND PROCESS MODELLING


Krishna Hemanth, Kashyap Madarayil, Durga Prasad Murmu
Definition
As Defined by World Health Organization (WHO),

Cancer is a generic term for a large group of diseases characterized by the growth of
abnormal cells beyond their usual boundaries that can then invade adjoining parts of the body
and/or spread to other organs

The cells that exhibit these aberrant behaviours are collectively named Neoplasms,
synonymous with its more generic term, Tumour. WHO classification further divides them into four
subgroups, benign neoplasms, in situ neoplasms, malignant neoplasms (Cancer), and neoplasms of
uncertain or unknown behaviour. The movement of one type of cancerous cells from one part of the
body to another followed by its growth and proliferation is known as metastasis.

Metastatic cancer cells can move either by direct contact with new organ sites or through the
blood or lymphatic systems of the body, but there is a generally accepted path process for this
spread. First, the cells invade healthy tissue close to the original cancerous site, most likely by lymph
or blood vesselsthis is called intravasation. Once they are in one of these circulatory systems, the
cancer cells travel to distant parts of the body. They stop in small blood vessels called capillaries
where they traverse through the vessel walls and into surrounding tissues through a process called
extravasation. The cells reproduce to develop small micro metastatic tumours. If the small tumour is
able to stimulate growth of new blood vessels to attain a blood supply, the tumour can grow larger
into a full-fledged metastatic tumour. Thriving metastases are also contingent on the properties of
the noncancerous cells, such as immune system cells at the original and new sites as well as ones
they encounter on their journey through the body. While it is believed that all types of cancer are
able to spread, not every singular cancer cell has the ability to metastasize on its own. The most
common sites of metastasis for all cancers (excluding lymph nodes since they are a method of transit
for the cells) are the bone, liver, and lungs. The diagram below shows how cancer will spread from
any original tumour site to various metastatic growth sites in the body. [1]

Fig (1). Cancer Growth and Progression [3]


Statistics
The website owned by WHO provides the following data:

Cancer is a leading cause of death worldwide, accounting for 8.8 million deaths in 2015. The
most common causes of cancer deaths are cancers of:

Lung 1.69 million deaths


Liver 788 000 deaths
Colorectal 774 000 deaths
Stomach 754 000 deaths
Breast 571 000 deaths

The number is expected to increase further by 70% in the coming two decades. Currently,
one in six deaths are due to Cancer and 70% of these occur in the low to middle income population.
The causalities of Cancer ranges from tobacco, alcohol use to dietary risks like obesity and lack of
physical exercise. According to the National Cancer Institute, USA, Cancer mortality is higher among
men than women (207.9 per 100,000 men and 145.4 per 100,000 women). It is highest in African
American men (261.5 per 100,000) and lowest in Asian/Pacific Islander women (91.2 per 100,000).
(Based on 2008-2012 deaths).

Complications
The difficulty to reliably forecast the risk of cancer metastasis for individual patients stems
from the fact that cancer is the result of a complex interplay between numerous factors, namely:
cellular parametersaltered rates of cell proliferation, apoptosis, migration, adhesion, metabolism
and mutationand micro environmental parametersextracellular matrix (ECM) composition,
angiogenesis, inflammation and proteases [1]. The multitude of variables and the labyrinthine nature
of its inter-relationships, makes it almost impossible to predict using human intuition.

Medical practitioners across the globe assess the treatment by the average reduction in size
of cancer cells after treatment. This however, is not an effective tool to evaluate the affectivity of a
particular drug or treatment. A median patient from the data would be the best control for this
comparison. If the tumour has grown by (say) 1% by the end of a month of treatment, and a growth
of 5% had been observed on the median patient without treatment, the treatment is successful to an
extent. Clinical trials without comparison to quondam data will brand the treatment as ineffective,
although it was able to control the growth of the tumour. Hence, it could be asserted that novel
methods that consider existing data in an objective manner are necessary to prevent such mistakes.

Strategy
Since the intuitive approaches based on clinical trials alone have proved to be ineffective, the
next big step will be to implement mathematical modelling approaches to analyse the enormous
amount of data being produced and extract useful answers. There is no single accepted model for
the process of cancer invasion. While some prefer a purely genetic explanation, others find a
regulatory one to be more convincing. However, it would be obtuse not to utilize any one of these
notions since existing evidence rules out neither of them. Such a broad range of positionsall
founded in experimental observations to some extentsuggest strongly that, in reality, a large
number of biological variables affect invasion. In this case, a mathematical modelling approach is
ideal to illustrate this process since it considers such variables and their relative importance to a
particular type of cancer. A quantitative approach to cancer invasion requires that relevant biological
parameters and variables are:

Standardized across laboratories, for comparison


Weighted for their relative impact in invasion.

Thus, mathematical modelling coalesced with experimental validation has the potential to
satisfy all of these requirements, particularly in the case of cell-based mathematical models.

Relation to Chemical Engineering


Chemical engineering being a branch of engineering that applies physical sciences (physics
and chemistry), life sciences (microbiology and biochemistry), together with applied mathematics
and economics to produce, transform, transport, and properly use chemicals, materials and energy
[2]
, can be used to analyse the component balance, mass transfer and other complex flow
phenomena that occur both within and without the tumour cell. This may prove to be a very
complex procedure that can be confirmed only by laboratory experiments. Nonetheless, we aim at
creating an abstract mathematical model that involves these processes.

Objective
The objective of the project is to come up with a paradigm model for tumour cells that can
replicate the growth patterns by considering the publically available data. The fundamental aim of
the project is to come up with a regression equation (linear or non-linear) solely from the data. The
process will involve Variable Categorisation accrediting its availability, Dynamic Dimension Reduction
using available software such as Matlab, R or numpys in Python.

As explained before a model will be formulated utilizing as many chemical engineering


phenomena as feasible. Though there is a probability that this will have to be a separate model
altogether due to the uncertainty of the number and types of variables that are already present in
the available data.

Visual implementation will be limited to graphs and Pi charts. Analysis of available software
that implements visual interpretation of the growth and proliferation process deemed infeasible due
to the sheer number of biological terms that have to be familiarised with, and the lack of flexibility of
the model. Software such as CellSys implements a single model and executes commands based on a
fixed number of variables. Since the software was not an open sourced one, any analysis of the
implemented is also negated.

Fig (2). Growth rate models already in use [4]