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An Introduction to
GASTROINTESTINAL STROMAL TUMORS

By The Life Raft Group
•
•

•

Cancer consists of over 100 diseases.
Cancer begins when there is an abnormal growth of cells
that cannot be controlled.
Because different types of cancers behave differently, it
is important to get treated according to the specific
diagnosis.

Diagnosis: a medical decision that determines the nature of a disease.
2
Intro to GIST
•

The GI tract or the digestive
system consists of all organs
located between the
esophagus and the rectum.

•

This organ system’s role is to
absorb the needed water and
nutrients from ingested food.

•

GIST’s can occur all along the
GI tract, most commonly
found in the stomach and
small intestine.

esophagus

liver
stomach
gallbladder
colon
small intestine
rectum

4
•

Gastrointestinal stromal tumors
(GISTs) belong to a group of
cancers called sarcomas.

•

Sarcomas are a rare type of cancer
that can occur in
bones, muscles, fat, nerves, blood
vessels, connective tissues, and
cartilage.

•

GIST cancers arise from unique
cells called Interstitial Cells of
Cajal due to mutations in these
cells. These special cells move
digested food throughout the GI
tract.
5
• ICCs are found in the
muscles that line the
digestive system.
• Their role is to gently
contract to propel ingested
food along the GI tract.
• Similar to the cells that
make your heart beat, the
ICCs are also called
―pacemaker‖ cells, as they
rhythmically coordinate
digestion.

Santiago Ramón y Cajal
(1852-1934)
A
pathologist, histologist, neuroscientist
and Nobel laureate.
6
•

40-70% of GISTs arise from
the stomach.

•

20-40% arise from the small
intestine.

•

5-15% arise from the colon
and rectum.

•

Less than 5% can also be
found in the esophagus or
elsewhere in the GI tract.

•

The original GIST site is
called the Primary.
7
•

When GIST spreads to additional locations beyond the
primary tumor site it is called a metastasis (mets).

•

Some common sites for GIST mets are the liver and
elsewhere in the abdomen.

8
•

GIST is assessed by its risk of recurrence, sometimes
referred to as staging in other cancers.

•

Staging is commonly used in other cancers but it typically is
not used with GIST.

•

Four important criteria in risk of recurrence:
•

Tumor size (measured in centimeters)

•

Mitotic index (or mitotic count, mitotic rate)

•

Tumor location

•

Whether or not the tumor has ruptured

Risk of recurrence: the chances of GIST returning after surgery.
Staging: the process of determining how far a cancer has spread in the body, often helping to select
9
treatment options and predicting the patient’s outcome.
These numbers are
based on a group of
patients from Western
Sweden* but give a
good representation of
GIST patients as a
whole. Some other
series have shown
slightly
different
numbers.

* Nilsson, Bengt, Per Bümming, Jeanne M Meis-Kindblom, Anders Odén, Aydin Dortok, Bengt
Gustavsson, Katarzyna Sablinska, and Lars-Gunnar Kindblom. "Gastrointestinal Stromal Tumors: The
Incidence, Prevalence, Clinical Course, and Prognostication in the Preimatinib Mesylate Era--a Populationbased Study in Western Sweden." Cancer 103, no. 4 (February 15, 2005): 821-829. doi:10.1002/cncr.20862.

10
•

Mitotic index is the measurement of how
quickly the cancer cells are growing and
dividing (a low mitotic index predicts a better
outcome).

•

Based on tumor size and location, mitotic
index and whether or not the tumor has
ruptured, the doctor determines the risk of
recurrence of the cancer.

Risk of recurrence: the chances of GIST returning after surgery.
11
With the advent of a drug called Gleevec
and other treatments the survival rate has
increased dramatically.

The five-year survival rate is about 80%.

12
Most GISTs are not
inherited and have
no clear cause, but
rare cases have
found members of
the same family to
have GIST – this is
called familial or
hereditary GIST.

13
•

The exact number of people diagnosed with GIST
every year is unknown.
• In the United States, it is

estimated that there are
about 4,000 to 5,000
new cases of GIST each
year.
• Most people diagnosed

with GIST are older than
50, but it can occur at
any age.
14
*A diagnosis is a medical decision that determines the nature of a disease.
•

At this time, no effective
screening, such as blood tests, is
available for GIST

•

Some GISTs are found incidentally
during an exam or surgery for another
problem

•

Most are found because of symptoms
or signs

•

Not all tumors may cause symptoms
16
•
•
•
•
•
•

•

Black and tarry stool
Abdominal/belly discomfort
Mass/swelling in the abdomen
Loss of appetite
Weight loss/gain
Feeling full after eating a small
amount of food
However, many cases are asymptomatic and these
symptoms can also describe other diseases.

17
•

•

Chris Corless, M.D.
LRG Research Team
Pathologist
Oregon Health & Science
University

Accurate diagnosis of GIST is
determined by a pathologist who
views a tissue sample obtained
from surgery or a biopsy under a
microscope.
The pathologist examines the
unique features of the cells using
stains that detect the presence of a
specific protein called KIT.

18
•

GISTs can also be caused by the mutation of
PDGFRA gene. KIT and PDGFRA have a
similar structure, and belong to the same subfamily of proteins (tyrosine kinases).

•

GIST tumors that do not have a mutation in
KIT or PDGFRA are called "wild-type"
GIST, whose mutation is in one of the
succinate dehydrogenase genes.
19
•

When masses are
found, small pieces
removed by
surgery, endoscopy, or
needle biopsy are prepared
for identification under a
microscope. This process is
called a biopsy.

•

A biopsy is read by a
pathologist.

•

This is how a GIST is
diagnosed.
20
•

•

•

Mutational testing is done using a tissue sample
from surgery or the biopsy to identify the specific
GIST mutation.
This is essential because targeted treatments are
available that can maximize outcomes based on
specific mutations.
One way to get mutational testing is to join the Life
Raft Group’s GIST Collaborative Tissue
Bank, which also makes the tissue available to
researchers working to find a cure for GIST.
21
•

•

Performed by a gastroenterologist, this procedure uses a
slim, flexible tube to view inside the body.
An endoscope is equipped with micro tools that can
view, film, remove or take biopsies of any masses inside
the body

22
Imaging tests create pictures of the inside of the
body and are used to monitor GIST. They include:
o

X-rays

o

Computed tomography or CT scans
Magnetic resonance imaging or MRI scans
Positron emissions topography or PET scans

o
o

23
Intro to GIST
•

Doctors appointments, lab results, insurance forms
and invoices can accumulate quickly. Organize
each in a simple file or binder.

•

Write down any questions and bring them with you
when you visit the doctor or call the office.

•

Read and learn about GIST in reputable
information sources. The Life Raft Group can help
identify these.
25
•

Ideally, a patient should seek
treatment from a GIST specialist.
If there is not one locally, it is
advised that one be consulted
and seen at least once.

•

Frequently a GIST patient will
have a local oncologist who
works in concert with the
specialist at another institution.
This method maximizes
treatment outcome for the
patient.
26
It is common to have different types of doctors who work
together to diagnose and manage your care. They may
include:
o An oncologist: choose someone with
experience in GIST
o A gastroenterologist: treats diseases in
the digestive tract.
o A gastrointestinal surgeon: removal of
your GIST tumor is imperative to your
wellness goals.
27
•

Physician assistants, nurse
practitioners, nutrition specialists
and social workers may also
play a role in your treatment.

•

Support groups and connecting
with others living with GIST can
help navigate the emotional
issues that arise from a cancer
diagnosis.

28
Intro to GIST
Initial treatment will depend
on several factors including:
•

Whether GIST has spread or
metastasized

•

The expected difficulty of the
surgery

•

The size of the original tumor

•

The general health of the patient

Metastasize: The spread of a tumor to a distant location from the original tumor.
30
•

•

The goal is to remove the tumor
entirely and achieve clear
margins.

•

Resectable: Removable

Surgery is typically the first
treatment for GIST to remove
resectable tumors.

If the tumor cannot be
removed, the doctor may treat
the patient with medication first
to shrink the tumor enough to
remove it.
31
Intro to GIST
The following data are obtained from your surgeon and
pathologist to evaluate your GIST risk of recurrence:

•
•
•
•
•
•

Tumor size (measured in centimeters)
Mitotic Index
Location of the tumor
Tumor rupture before or during surgery
Failure to obtain clear margins during surgery
Your KIT mutation (preliminary data)
33
• Recurrences that occur while a patient is taking
Gleevec can mean that the tumors might have become
resistant to this drug.
• Sutent is considered a second line drug and can be
used to treat GIST patients who have become resistant
to Gleevec.
• If a patient has stopped taking Gleevec before the
recurrence, chances are good that they could be
responsive to Gleevec again.
• Stivarga is a third line drug that is given when the tumor
is not responding to Gleevec or Sutent.
34
 Also known as ―imatinib‖
or Glivec, Gleevec is a pill
that is taken daily.
 Gleevec targets the
specific protein that is
causing the tumor to grow.

35
•

Gleevec is sometimes given before surgery with the
goal of shrinking the size of the tumor(s). This makes
surgical removal of the GIST more successful. This is
called neoadjuvant treatment.

•

Gleevec can be given as adjuvant treatment to help to
prevent GIST recurrence and increase overall survival.

•

Gleevec is given to patients whose tumors are
unresectable or metastatic.

Neoadjuvant: treatment given before surgery.
Adjuvant: additional treatment usually given after surgery.

36
•
•
•
•
•
•

Nausea
Edema
Fatigue
Diarrhea
Eye puffiness
Cramping

• Cramping
• Reflux
• Muscle or Joint
Aches/Pain
• Weight change
• Skin problems
(such as rashes)

NOTE: In the beginning of treatment, patients may feel side effects but over time they
subside. For more information, visit the Side Effects section at www.liferaftgroup.org

Edema: abnormal accumulation of fluid beneath the skin that produces swelling.
Fatigue: a feeling of tiredness, exhaustion, or lack of energy.
Reflux: regurgitated gastric content.

37
• Sutent is also called sunitinib. It is
given after failure or intolerance to
Gleevec.

• Like Gleevec, Sutent works against
GIST by inhibiting the KIT protein.
Sutent is taken as a pill and its most common side effects are:
• Diarrhea
• Mouth irritation
• Fatigue

•
•
•
•

High blood pressure
Hand and foot syndrome
Increased risk of bleeding
Hypothyroidism
38
•

Stivarga is also known as
regorafenib.

•

Newly approved in the United
States for GIST patients who
do not respond to Gleevec
and Sutent.

•

Side effects may include
hand and foot
syndrome, hypertension
and diarrhea.
39
Intro to GIST
•

Clinical trials are available for all
stages of GIST.

•

Clinical trials are carefully
conducted research studies that
determine reactions and effects of
promising drugs and therapy
methods.

•

Volunteer patients are chosen
based on the criteria set by the
trial. If a patient is interested in
learning more about
volunteering, he/she should look
into the facilities doing trials for
GIST.
41
The LRG website offers information about all trials
ongoing or completed that are relevant to GIST

www.liferaftgroup.org
42
Intro to GIST
•

Make regular follow-up appointments with
doctors to keep a close watch on any new
growth or side effects.

•

It is usually recommended that patients get CT
scans every 3 to 6 months for at least several
years after treatment.

•

Patients should never hesitate to contact their
doctors about any questions or concerns.
44
Consider making simple
lifestyle changes to feel your
best and promote wellness:
•

•
•
•

Make healthy diet
choices
Exercise
Cut down on alcohol
Give up tobacco
45
•

Several U.S. cities and many regions throughout the world have
GIST support groups.

•

Attending a support group has shown to increase the ability to
cope, both for the person with cancer and their caregiver.

•

For more information, visit the Find a Support Group section under
the Get Support section of the LRG website: www.liferaftgroup.org

•

If there is no support group listed for your area, please consider
starting one. We can help—email us for details:
liferaft@liferaftgroup.org

46
FOR MORE INFORMATION, VISIT:
WWW.LIFERAFTGROUP.ORG
EMAIL US AT:
LIFERAFT@LIFERAFTGROUP.ORG

OR CALL US AT:
973.837.9092
The Life Raft Group (LRG) recognizes that coping with GIST can be
very stressful and no one should be without the right support and
educational resources.
The Life Raft Group has a simple focus: to cure a form of cancer –
GIST- and to help those living with it until then.
Our mission is to ensure the survival of GIST patients through a
comprehensive approach connecting individual patients’ needs, the
worldwide community of GIST advocates and the global health and
research environment.
At Life Fest 2010, a few of our Life Raft Group
members who are 10-year survivors were honored.
49

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Intro to GIST

  • 1. An Introduction to GASTROINTESTINAL STROMAL TUMORS By The Life Raft Group
  • 2. • • • Cancer consists of over 100 diseases. Cancer begins when there is an abnormal growth of cells that cannot be controlled. Because different types of cancers behave differently, it is important to get treated according to the specific diagnosis. Diagnosis: a medical decision that determines the nature of a disease. 2
  • 4. • The GI tract or the digestive system consists of all organs located between the esophagus and the rectum. • This organ system’s role is to absorb the needed water and nutrients from ingested food. • GIST’s can occur all along the GI tract, most commonly found in the stomach and small intestine. esophagus liver stomach gallbladder colon small intestine rectum 4
  • 5. • Gastrointestinal stromal tumors (GISTs) belong to a group of cancers called sarcomas. • Sarcomas are a rare type of cancer that can occur in bones, muscles, fat, nerves, blood vessels, connective tissues, and cartilage. • GIST cancers arise from unique cells called Interstitial Cells of Cajal due to mutations in these cells. These special cells move digested food throughout the GI tract. 5
  • 6. • ICCs are found in the muscles that line the digestive system. • Their role is to gently contract to propel ingested food along the GI tract. • Similar to the cells that make your heart beat, the ICCs are also called ―pacemaker‖ cells, as they rhythmically coordinate digestion. Santiago Ramón y Cajal (1852-1934) A pathologist, histologist, neuroscientist and Nobel laureate. 6
  • 7. • 40-70% of GISTs arise from the stomach. • 20-40% arise from the small intestine. • 5-15% arise from the colon and rectum. • Less than 5% can also be found in the esophagus or elsewhere in the GI tract. • The original GIST site is called the Primary. 7
  • 8. • When GIST spreads to additional locations beyond the primary tumor site it is called a metastasis (mets). • Some common sites for GIST mets are the liver and elsewhere in the abdomen. 8
  • 9. • GIST is assessed by its risk of recurrence, sometimes referred to as staging in other cancers. • Staging is commonly used in other cancers but it typically is not used with GIST. • Four important criteria in risk of recurrence: • Tumor size (measured in centimeters) • Mitotic index (or mitotic count, mitotic rate) • Tumor location • Whether or not the tumor has ruptured Risk of recurrence: the chances of GIST returning after surgery. Staging: the process of determining how far a cancer has spread in the body, often helping to select 9 treatment options and predicting the patient’s outcome.
  • 10. These numbers are based on a group of patients from Western Sweden* but give a good representation of GIST patients as a whole. Some other series have shown slightly different numbers. * Nilsson, Bengt, Per Bümming, Jeanne M Meis-Kindblom, Anders Odén, Aydin Dortok, Bengt Gustavsson, Katarzyna Sablinska, and Lars-Gunnar Kindblom. "Gastrointestinal Stromal Tumors: The Incidence, Prevalence, Clinical Course, and Prognostication in the Preimatinib Mesylate Era--a Populationbased Study in Western Sweden." Cancer 103, no. 4 (February 15, 2005): 821-829. doi:10.1002/cncr.20862. 10
  • 11. • Mitotic index is the measurement of how quickly the cancer cells are growing and dividing (a low mitotic index predicts a better outcome). • Based on tumor size and location, mitotic index and whether or not the tumor has ruptured, the doctor determines the risk of recurrence of the cancer. Risk of recurrence: the chances of GIST returning after surgery. 11
  • 12. With the advent of a drug called Gleevec and other treatments the survival rate has increased dramatically. The five-year survival rate is about 80%. 12
  • 13. Most GISTs are not inherited and have no clear cause, but rare cases have found members of the same family to have GIST – this is called familial or hereditary GIST. 13
  • 14. • The exact number of people diagnosed with GIST every year is unknown. • In the United States, it is estimated that there are about 4,000 to 5,000 new cases of GIST each year. • Most people diagnosed with GIST are older than 50, but it can occur at any age. 14
  • 15. *A diagnosis is a medical decision that determines the nature of a disease.
  • 16. • At this time, no effective screening, such as blood tests, is available for GIST • Some GISTs are found incidentally during an exam or surgery for another problem • Most are found because of symptoms or signs • Not all tumors may cause symptoms 16
  • 17. • • • • • • • Black and tarry stool Abdominal/belly discomfort Mass/swelling in the abdomen Loss of appetite Weight loss/gain Feeling full after eating a small amount of food However, many cases are asymptomatic and these symptoms can also describe other diseases. 17
  • 18. • • Chris Corless, M.D. LRG Research Team Pathologist Oregon Health & Science University Accurate diagnosis of GIST is determined by a pathologist who views a tissue sample obtained from surgery or a biopsy under a microscope. The pathologist examines the unique features of the cells using stains that detect the presence of a specific protein called KIT. 18
  • 19. • GISTs can also be caused by the mutation of PDGFRA gene. KIT and PDGFRA have a similar structure, and belong to the same subfamily of proteins (tyrosine kinases). • GIST tumors that do not have a mutation in KIT or PDGFRA are called "wild-type" GIST, whose mutation is in one of the succinate dehydrogenase genes. 19
  • 20. • When masses are found, small pieces removed by surgery, endoscopy, or needle biopsy are prepared for identification under a microscope. This process is called a biopsy. • A biopsy is read by a pathologist. • This is how a GIST is diagnosed. 20
  • 21. • • • Mutational testing is done using a tissue sample from surgery or the biopsy to identify the specific GIST mutation. This is essential because targeted treatments are available that can maximize outcomes based on specific mutations. One way to get mutational testing is to join the Life Raft Group’s GIST Collaborative Tissue Bank, which also makes the tissue available to researchers working to find a cure for GIST. 21
  • 22. • • Performed by a gastroenterologist, this procedure uses a slim, flexible tube to view inside the body. An endoscope is equipped with micro tools that can view, film, remove or take biopsies of any masses inside the body 22
  • 23. Imaging tests create pictures of the inside of the body and are used to monitor GIST. They include: o X-rays o Computed tomography or CT scans Magnetic resonance imaging or MRI scans Positron emissions topography or PET scans o o 23
  • 25. • Doctors appointments, lab results, insurance forms and invoices can accumulate quickly. Organize each in a simple file or binder. • Write down any questions and bring them with you when you visit the doctor or call the office. • Read and learn about GIST in reputable information sources. The Life Raft Group can help identify these. 25
  • 26. • Ideally, a patient should seek treatment from a GIST specialist. If there is not one locally, it is advised that one be consulted and seen at least once. • Frequently a GIST patient will have a local oncologist who works in concert with the specialist at another institution. This method maximizes treatment outcome for the patient. 26
  • 27. It is common to have different types of doctors who work together to diagnose and manage your care. They may include: o An oncologist: choose someone with experience in GIST o A gastroenterologist: treats diseases in the digestive tract. o A gastrointestinal surgeon: removal of your GIST tumor is imperative to your wellness goals. 27
  • 28. • Physician assistants, nurse practitioners, nutrition specialists and social workers may also play a role in your treatment. • Support groups and connecting with others living with GIST can help navigate the emotional issues that arise from a cancer diagnosis. 28
  • 30. Initial treatment will depend on several factors including: • Whether GIST has spread or metastasized • The expected difficulty of the surgery • The size of the original tumor • The general health of the patient Metastasize: The spread of a tumor to a distant location from the original tumor. 30
  • 31. • • The goal is to remove the tumor entirely and achieve clear margins. • Resectable: Removable Surgery is typically the first treatment for GIST to remove resectable tumors. If the tumor cannot be removed, the doctor may treat the patient with medication first to shrink the tumor enough to remove it. 31
  • 33. The following data are obtained from your surgeon and pathologist to evaluate your GIST risk of recurrence: • • • • • • Tumor size (measured in centimeters) Mitotic Index Location of the tumor Tumor rupture before or during surgery Failure to obtain clear margins during surgery Your KIT mutation (preliminary data) 33
  • 34. • Recurrences that occur while a patient is taking Gleevec can mean that the tumors might have become resistant to this drug. • Sutent is considered a second line drug and can be used to treat GIST patients who have become resistant to Gleevec. • If a patient has stopped taking Gleevec before the recurrence, chances are good that they could be responsive to Gleevec again. • Stivarga is a third line drug that is given when the tumor is not responding to Gleevec or Sutent. 34
  • 35.  Also known as ―imatinib‖ or Glivec, Gleevec is a pill that is taken daily.  Gleevec targets the specific protein that is causing the tumor to grow. 35
  • 36. • Gleevec is sometimes given before surgery with the goal of shrinking the size of the tumor(s). This makes surgical removal of the GIST more successful. This is called neoadjuvant treatment. • Gleevec can be given as adjuvant treatment to help to prevent GIST recurrence and increase overall survival. • Gleevec is given to patients whose tumors are unresectable or metastatic. Neoadjuvant: treatment given before surgery. Adjuvant: additional treatment usually given after surgery. 36
  • 37. • • • • • • Nausea Edema Fatigue Diarrhea Eye puffiness Cramping • Cramping • Reflux • Muscle or Joint Aches/Pain • Weight change • Skin problems (such as rashes) NOTE: In the beginning of treatment, patients may feel side effects but over time they subside. For more information, visit the Side Effects section at www.liferaftgroup.org Edema: abnormal accumulation of fluid beneath the skin that produces swelling. Fatigue: a feeling of tiredness, exhaustion, or lack of energy. Reflux: regurgitated gastric content. 37
  • 38. • Sutent is also called sunitinib. It is given after failure or intolerance to Gleevec. • Like Gleevec, Sutent works against GIST by inhibiting the KIT protein. Sutent is taken as a pill and its most common side effects are: • Diarrhea • Mouth irritation • Fatigue • • • • High blood pressure Hand and foot syndrome Increased risk of bleeding Hypothyroidism 38
  • 39. • Stivarga is also known as regorafenib. • Newly approved in the United States for GIST patients who do not respond to Gleevec and Sutent. • Side effects may include hand and foot syndrome, hypertension and diarrhea. 39
  • 41. • Clinical trials are available for all stages of GIST. • Clinical trials are carefully conducted research studies that determine reactions and effects of promising drugs and therapy methods. • Volunteer patients are chosen based on the criteria set by the trial. If a patient is interested in learning more about volunteering, he/she should look into the facilities doing trials for GIST. 41
  • 42. The LRG website offers information about all trials ongoing or completed that are relevant to GIST www.liferaftgroup.org 42
  • 44. • Make regular follow-up appointments with doctors to keep a close watch on any new growth or side effects. • It is usually recommended that patients get CT scans every 3 to 6 months for at least several years after treatment. • Patients should never hesitate to contact their doctors about any questions or concerns. 44
  • 45. Consider making simple lifestyle changes to feel your best and promote wellness: • • • • Make healthy diet choices Exercise Cut down on alcohol Give up tobacco 45
  • 46. • Several U.S. cities and many regions throughout the world have GIST support groups. • Attending a support group has shown to increase the ability to cope, both for the person with cancer and their caregiver. • For more information, visit the Find a Support Group section under the Get Support section of the LRG website: www.liferaftgroup.org • If there is no support group listed for your area, please consider starting one. We can help—email us for details: liferaft@liferaftgroup.org 46
  • 47. FOR MORE INFORMATION, VISIT: WWW.LIFERAFTGROUP.ORG EMAIL US AT: LIFERAFT@LIFERAFTGROUP.ORG OR CALL US AT: 973.837.9092
  • 48. The Life Raft Group (LRG) recognizes that coping with GIST can be very stressful and no one should be without the right support and educational resources. The Life Raft Group has a simple focus: to cure a form of cancer – GIST- and to help those living with it until then. Our mission is to ensure the survival of GIST patients through a comprehensive approach connecting individual patients’ needs, the worldwide community of GIST advocates and the global health and research environment.
  • 49. At Life Fest 2010, a few of our Life Raft Group members who are 10-year survivors were honored. 49