CANCER

A N OV E RV I E W Mini medical school

Oct 18,2018

Dr. Bruce Colwell

DISCLOSURES

• I have been involved in clinical trials, advisory boards and worked as a speaker for a number of

companies including Amgen, Celgene, Lilly, Merck, Novartis, Shire, and Taiho, and the following

organizations - Colorectal association of Canada and Canadian Society of Internal Medicine

• I will not discuss or promote any pharmaceutical agents in this talk

• I have furthermore vetted this talk to ensure non bias with an independent party

OBJECTIVES

• To define the diseases called Cancer.

• Outline naming and staging of cancers

• To discuss current and future epidemiology of cancer

• To outline the natural history

• To broadly outline treatment options

• To discuss future directions

WHAT IS CANCER

• Cancer is a large group of diseases characterized by uncontrolled growth of cells in a part of

the body. They have also lost the ability to stay within the normal boundaries of that tissue and

the controls that make that tissue stop growing.

• Cancer is diagnosed by pathologists who look at cells at the microscopic level. Surgeons and

oncologists and radiologists often suspect cancer and are usually right but gold standard is the

examination of the tissue under the microscope. This often aided by special stains and tests

including genetic and molecular tests

NAMING

• The cancers are usually named after the organ of origin however even by organ they can come

in many varieties for example breast cancer is most commonly called infiltrating ductal

carcinoma (about 80%) but could also be lobular, tubular, medullary, mucinous, metaplastic,

adenocystic, papillary and cystosarcoma phyllodes .

• If the cancer spreads to another place that is called a metastasis and the cancer is still named

after the cell of origin. i.e. Infiltrating ductal breast cancer with metastasis to the bone and lung

STAGING

• Staging tells the oncologist how advanced the cancer is and often helps in deciding prognosis

and treatment.

• Most staging systems use the TNM staging system that then is converted into stage I through

IV. Stage IV always involves M1 disease meaning the cancer has spread from its origin to

another organ. T refers to the primary Tumor and N refers to the local area usually nodes.

Other factors can be incorporated into this system including grade, tumor markers, the timing

of the staging and the way the staging takes place

WHAT IS CANCER

• Cancer is a genetic disease in that there is always something wrong in the cell regulation either

directly at the DNA level or through signaling molecules for the DNA. This could be

hereditary, for those who are born with DNA mutations that predispose one to cancer, or

more commonly acquired over time. Sometimes this error is brought on by an outside

influence like radiation or chemicals and sometimes it just happens.

• The biggest risk of getting cancer is unavoidable. It is getting older. Think of it like a car the

older it is the more likely to break down. Your body is a machine that eventually will start to

break and make errors in DNA.

WHAT IS CANCER

• Cancer starts as one cell but is not clonal. In other words it continues to change and evolve as

it grows and the cells are not all the same. This is why it is often hard to get rid of completely.

• Cancer spreads directly by invading outside of where the tissue it came from started. It also

can send individual cancer cells out from the main growth through the blood and/or lymphatic

systems. These circulating tumor cells can then set up home in a different organ and start to

grow (metastasis).

WHY DO WE NOT ALL HAVE CANCER?

• Cancer is kept in check by our bodies various safety systems

• If a big mistake is made when a cell replicates then the cell may not be viable and it will not

survive. It undergoes what is called apoptosis or programmed cell death.

• If minor mistakes are made then they can be fixed by DNA repair enzymes. People who lack

these enzymes have a much higher incidence of cancer

• Most people are killed when the cancer spreads or metastasizes. To do this it must be able to

successfully travel through the blood or lymphatics, find a way out to get back of the highway

and then survive in the new environment. Most of the “tools” needed to do this the cancer

cell must have.

WHY DO WE NOT ALL HAVE CANCER?

• Besides all the properties that tumor cells need to spread they also are attacked by our

immune system. Our immune system recognizes our own cells but not foreign cells which it

attacks. Sometimes cancer can trick the immune system and shut down its attack. Recently

the 2018 Nobel Prize in Medicine was awarded related to finding some of the so called

“brakes” of the immune system which has lead to a dramatic new group of drugs that have

revolutionized therapies for a number of cancers.

CANCER –THE NUMBERS

• Cancer is the number one cause of death in Canada with cardiovascular disease second. It

represents a little more then 1 in every three deaths,

• One in 2 people will get cancer sometime in their lives.

• Some cancers are becoming a chronic disease with people living with the disease for many

years in addition to the many “survivors “ of cancer but there are still too many that do not

survive and pass away quickly.

CANCER- THE BURDEN

• In Canada in 2010 all causes of death resulted in 3.367 million potential years of life lost

(PYLL). 1.108 million was related to cancer

Type of cancer % of PYL from cancer

Lung 27.1

Colorectal 10.8

Breast 8.5

Pancreas 5.3

Brain/CNS 3.9

Non-Hodgkins lymphoma 3.4

Leukemia 3.4

Prostate 3.2

CANCER – FUTURE BURDEN

• We live in an aging population with the baby boom population between 72 and 54 and

therefore we will be seeing a substantial increase in cancer incidence over the next decade or

two

Canadian Cancer Statistics 2015

Canadian Cancer Statistics 2015

CURRENT INCIDENCE AND MORTALITY

• In 2017 - 206,000 cases and 80,000 deaths

• 5 yr net survival for all cancers 60% which ranges from 98 and 96 % for thyroid and testes

cancer to 8 and 14 % for pancreas and esophageal cancers.

Canadian Cancer Statistics 2017

Canadian Cancer Statistics 2017

Canadian Cancer Statistics 2017

Canadian Cancer Statistics 2017

Canadian Cancer Statistics 2018

NATURAL HISTORY

• Cancer usually starts as a single cell and is not usually detectable until it is more than 107 cells.

It is usually around 1 cm3 in size. Sometimes it is detectable because of its location can be felt,

or it blocks or disrupts some body function. Sometimes it is only found when the cancer has

spread. Some cancers this occurs early and some very late or never.

SCREENING

• Some cancers can be detected early by screening programs. These are proven effective for

– Colon cancer detecting blood in the stool

– Breast cancer through mammography

– Lung cancer in certain populations through special imaging

– Cervical cancer with pap smear

SCREENING

• The most effective is an intervention that leads to a cancer being found earlier and that lead to

an overall survival benefit. Some screening tests find a cancer but treatment intervention does

not lead to a change in survival.

• The best evidence of a screening test showing change in survival is for colon cancer. It has

shown to pick up precancerous lesions and those cancers found are at a lower stage and thus

better over all survival

Canadian Cancer Statistics 2015

30% -21,000 less deaths

80% -40,000 less deaths

PREVENTION

• Prevention involves intervening to prevent a cancer from ever occurring. For cervical cancer,

many head and neck cancers, cancer of the anal canal and penile cancer there is a virus, Human

papilloma virus, that has been strongly implemented in being the major cause

• We have a vaccine that has shown to protect us against this virus. If we vaccinate girls at age

12 and 70% get vaccinated we will then be able to change screening so vaccinated girls will not

need cytology resulting in significant cost savings. ( as well as lives saved)

Canadian Cancer Statistics 2015

TREATMENT

• Surgery

• Radiation or other local therapies

• Systemic therapies

SURGERY

• General principle

– Plan ahead as much as possible with imaging techniques to plan best approach and discuss with

colleagues

– Remove all visible tumor with margins of normal tissues ideally at least 1 cm

– Maintain and preserve organ function

– Maintain normal tissue planes to prevent spillage of tumor cells.

– Refer to other specialties for post op therapies if beneficial

RADIATION AND OTHER LOCAL THERAPIES

• Radiation (external beam ) is the most common local therapy

• Often used to sterilize the surgical field

• Can be given for some cancer alone or together with systemic therapy with curative intent

• Other local therapies include

– Local radiation – beads and rods

– Radiofrequency ablation

– Cryotherapy

– Microwave

SYSTEMIC THERAPY

• Drug treatment that is given to a patient either by mouth or intravenously that travels

throughout the body to attack cancer cells anywhere in the body (which unfortunately could

lead to side effects throughout the body)

• Most commonly used are cytotoxic therapies that attack cancer cells usually by damaging the

DNA of rapidly growing cells.

• Could also target hormone that are signals inside the body that turn on certain functions, most

commonly used with breast and prostate cancers

SYSTEMIC THERAPY

• Could target intracellular signals ( cytokines) that are overexpressed and part of what is

turning the cell cancerous.

• Could target extracellular proteins that are also important for turning the cell cancerous

• Target the immune system and allowing it to keep the cancer in check or destroy it.

MULTIDISCIPLINARY TEAMS

• Oncologists realize that no one treatment is best for every patient and every patients is

different. They often discuss cases with members of a team to ensure the best treatment. This

involves not all but a significant number of cases where radiologists, pathologists, radiation

oncologists, medical oncologists surgeons, nutritionists, social workers, nurses and medicine

resource specialists all discuss a case.

• We believe that to try something you need evidence that it works and part of what we do is

look for better treatments through what we call clinical trials

CLINICAL TRIALS

• Phase I trial- where a new therapy is being tried in a human to see if it is safe

• Phase II trial when a new therapy is being tried in a human to see if it works

• Phase III trial when a new therapy has been shown to work and is compared to the standard

treatment to see if it is better.

FUTURE TESTING

• Blood tests are not good at detecting cancer with exception of leukemia's but this may not be

true in the future with liquid biopsies and circulating tumor cells.

• Future treatments may significantly prolong survival or cure more cancers

• Tailoring expensive treatments to those who would most benefit could save money as well as

government policies to control drug costs

• All these things will need to balance costs with the potential benefits in terms of saved lives

and prolonged lives.

CASE 1

• 49 yo lady presented with a year history of vague abdominal pain which eventually got bad

enough that she went to the emergency department. She had a CT scan that showed an

abscess ( collection of puss) related to diverticular disease. She had it drained and was put on

antibiotics . Her pain got better and she was sent home with a plan to scope her in about 4-6

weeks but after about 4 weeks she had worsening pain again and had a scope that showed a

bowel cancer. She was admitted and operated on. The cancer was removed and sent to the

pathologist and staged as a pT3N0M0. She was sent to me to discuss any further treatment

needs.

• Issues screening

• Family history

• Diverticular disease

• Path review and MSI testing

• Operative report

• Potential harms and benefits of adjuvant therapy

• Patients wishes

SUMMARY

• Cancer is many different disease that are treated differently.

• Best treatment for cancer involves collaboration between various specialties.

• Outcomes are improving but overall incidence will increase as babyboom population ages.

• Screening ,prevention and new treatments will help but costs will be an issue.

QUESTIONS