Transcript COLON CANCER - Oncology Hematology Associates

COLON CANCER
Thomas M. Waits, M.D.
2017
1

135,000 new cases each year in U.S.

50,000 will end up dying of their disease

One of 17 people develop colon cancer

Associated with a low fiber, high fat diet

Can be detected with proper screening
2
Inherited Disorders
TYPE
Familial adenomatous
polyposis
Hereditary nonpolyposis syndrome
RISK OF COLON
CANCER
Very High
Very High
OTHER CANCERS
Stomach, thyroid and
adrenal
Uterine, stomach and
bladder
3
Inherited Disorders (cont’d)

70% of cases are sporadic or random

20% have a first degree relative with a history of
colon cancer but not a defined inheritable
syndrome

10% are part of an inherited disorder either due
to the familial adenomatous polyposis (FAP) or
the hereditary non-polyposis (HNPCPC)
syndromes.
4
Familial Adenomatous Polyposis

Usually associated with hundreds if not thousands
of polyps throughout the colon.

Autosomal dominant.

Screening colonoscopy begins at age 10-12.

Prophylactic colectomy is almost always advocated.
5
Hereditary Non-Polyposis Syndrome

Lynch I Syndrome

Most patients are young, average in their early 40’s.

Right sided colon cancer much more common than
left sided colon cancer.

Frequently have synchronous colon cancers.
6
Hereditary Non-Polyposis Syndrome

Lynch II Syndrome
Also young patients with right sided colon cancers.
 Other cancers such as uterine and ovary cancer are
common.
 Also sometimes seen but less common include
tumors of the stomach, small bowel, and urinary
tract.
 Screening of these patients usually begins at age 25.

7
8
Suppressor Genes in Colon
Cancer

Suppressor genes responsible for fixing
mutations, DNA mismatches that can lead to
tumor development

Loss of chromosome 18 found in many
HNPCC patients and 15-20% of sporadic
colon cancer cases
9
Risk Factors

Diet
Low fiber, high fat
 High fiber intake can reduce the risk by 1/3


Family History
First degree relative increases the risk by 2-3x
 75% of colon cancer occur in those without a family
history

10
Risk Factors (cont’d)

Ulcerative Colitis
Form of inflammatory bowel disease
 Degree of risk is dependent upon

a) duration of disease
 b) amount of colon involvement


Aspirin
One aspirin per day decreases the risk
 Actually can cause regression of tumors
 Can lead to earlier detection

11
Screening of Colon Cancer

Age 50-beyond- annual fecal occult blood
testing of the stool is recommended.

Age 50-beyond-colonoscopy is recommended at
age 50 and then every 10 years depending on
history and findings.
*Mortality from colon cancer is reduced by 30-40% by
fecal occult blood testing.
12
Common Presenting Symptoms

Constipation

Diarrhea

Blood loss



Acute - dark or maroon-colored stools with a normocytic
normochromic anemia
Chronic - hemoccult positive stools with a microcytic
hypochromic anemia due to iron deficiency
Abdominal pain – chronic or acute
13
Common Presenting Symptoms
(cont’d)

Acute - may mimic appendicitis


Usually due to obstruction
Chronic - may be present for months prior to
the diagnosis
14
Diagnostic Tests

Colonoscopy with biopsy - 95-99% sensitive

Barium enema – only done if patient could not
tolerate or complete colonoscopy
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Pre-cancerous Lesions

Polyps


Three types

Tubular (low malignant potential)

Tubulovillous (intermediate)

Villous (high malignant potential)
Worrisome features

>2 cm

Severe epithelial dysplasia

Villous type
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Polyps

Treatment

Usually removal via the “snare technique” during
colonoscopy is adequate

Deeper invasion may require surgical resection

Following resection, yearly colonoscopy is
important
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Diagnostic Preoperative Evaluation

Complete colonoscopy - 3-5% of patients will
have a synchronous lesion (biopsy obtained)

CXR

CT abdomen

CEA
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Surgical Treatment

Methods
End to end anastomosis
 Abdominoperineal resection


Important components of surgery
Removal of the malignancy and adjacent bowel
(5 cm margin if possible)
 Removal of adjacent lymph nodes
 Inspection of the liver

19
Laparoscopic Colon Resection

Cure rates and benefits are equivalent to open
resection

Cannot be used in rectal and transverse colon
cancers

20 – 25% of cases are converted to an open
resection
20
Laparoscopic Colon Resection
Benefits

Less postoperative pain

More rapid return of bowel function

Shorter duration of hospitalization and recovery
period
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Spread of Colon Cancer

Laterally in the colon

Lymphatic spread to adjacent intra-abdominal
lymph nodes

Hematogenous spread with the liver being the
most common metastatic site and lungs second
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Staging System

TNM System

T1 - invades the submucosa

T2 - invades the muscularis propria

T3 - invades the serosa

T4 - extends through the serosa into free
peritoneal air or invades adjacent organs (vagina,
prostate, ureters, kidney)
23
Staging System (cont’d)

N0 - no lymph nodes involved

N1 - 1-3 lymph nodes involved

N2 - 4 or more lymph nodes involved

M0 - no distant metastasis

M1 - distant metastasis present
24
Prognostic Factors

Extent of bowel wall involvement (T)

Extent of lymph node involvement (N)

Presence of metastatic disease (M)
25
Staging Systems and Survival
AJCC
Dukes
5 year survival

T1, N0, M0
T2, N0, M0
I
A
>90%

T3, N0, M0
II
B
75-80%

Any T, N1-3
T4, N0, M0
III
C
40-55%

Any T, Any N, M1
IV
D
10-20%

Number of nodes involved is inversely proportional to
the 5 year survival rate
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Treatment for Colon Cancer

Stage I - surgery only

Stage II – surgery only vs adjuvant chemotherapy

Stage III and IV - surgery followed by
chemotherapy
May delay or forgo surgery in stage IV patients if
there is no obstruction or significant bleeding
30
Stage II Colon Cancer- Negative
Prognostic Factors

T4 tumor

Poorly Differentiated histology

Lymphovascular invasion

pMMR tumors ( dMMR = better prognosis )

Perforation

Less than 12 lymph nodes sampled
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Chemotherapy
Stage II

Preferred treatment is 5FU + Leucovorin ( oral
xeloda can be substituted for IV 5FU )

Treatment duration is 6 months

Benefit is a 5% reduction in recurrence

Toxicity: Diarrhea, mucositis, weakness, fatigue
32
Chemotherapy





Stage III
Standard is Oxaliplatin, 5FU and leucovrin
Treatment duration is 6 months
Each treatment is 48 hours continuous every
other week ( 12 treatments )
Benefit: improvement in 5 year survival of 15%
Toxicity: neuropathy, myelosuppression,
diarrhea, mucositis, fatigue
33
Chemotherapy Stage IV

FOLFOX plus Avastin

Same FOLFOX regimen plus Avastin (a vascular
endothelial GF inhibitor)

Toxicity: Hypertension, bleeding , proteinuria
34
Other forms of Chemotherapy

Camptosar – inhibits topoisomerase I

Typically used with 5-FU and Leucovorin because
the response rate is higher in combination with
these agents.

The regimen is similar to that for FOLFOX. This
regimen is called FOLFIRI and the only difference
is the Camptosar is given instead of the
Oxaliplatin.
35
Other forms of Chemotherapy
(cont.)

FOLFIRI

Side effects – usually more diarrhea, hair loss, and
myelosuppression than FOLFOX but no
neuropathy or cold intolerance.
36
Targeted Therapies in Colorectal
Cancer

Vascular Endothelial Growth Factor Inhibitors
Bevacizumab (Avastin)
 Regorafenib (Stivarga)


EGFR Targeting Agents
Cetuximab (Erbitux)
 Panitumumab (Vectibix)

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Bevacizumab (Avastin)

Angiogenesis or development of new blood
vessels is necessary to facilitate tumor growth.

Avastin is a monoclonal antibody that binds to
and inhibits the activity of a substance known as
vascular endothelial growth factor (VEGF).

Specifically prevents the interaction of VEGF
interacting on the surface of endothelial cells
and exerting its effect.
38
Bevacizumab (Avastin)

Several studies using various forms of
chemotherapy plus Avastin show a benefit.

Presence of Avastin improves the response rate
by 10% to approximately 50% and overall
survival rate by 16 to 21 months in patients with
metastatic disease.
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Bevacizumab (Avastin)

Dose – 5 mg/kg given over 2 hours on an every
two-week basis.

Given the same day as chemotherapy.

Given over 30-60 minutes
40
Bevacizumab (Avastin)
Toxicity

Should not be given within 4-6 weeks of surgery
as it may initiate bleeding episodes.

Can cause acceleration of hypertension.

Can cause proteinuria but rarely causes a
nephrotic syndrome.
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Regorafenib (Stivarga)

Only oral VEGF inhibitor

Response rate only 1% but improved survival
from 5 months to 6.4 months

Dose: 160 mg orally 3 out of 4 weeks

Side effects: liver toxicity, rash, proteinuria,
hypertension and fatigue
42
Trifluridine/Tipiracil ( Lonsurf )





Oral oncolytic agent
Combined therapy: nucleoside metabolic
inhibitor ( trifluridine ) and a thymidine
phosphorylase inhibitor ( tipiracil )
Basically the tipracil decreases metabolism of the
trifluridine increasing its bioavailability.
Given orally days 1-5 & 8-12 every 4 weeks
Toxicity: myelosuppression , diarrhea
43
Erbitux

Binds to the human epidermal growth factor
receptor (EGFR).

Access to the EGFR by tumor produced
substances is necessary for tumor growth.

Approved for use in patients who are
Camptosar refractory or intolerant.
44
Erbitux

In conjunction with Camptosar, response rate is
increased to 25%.

Monotherapy with Erbitux produces response
rates of 10-15%.
45
Erbitux

Dose: First week it is 400mg per metered sq
over 2 hours.

Given weekly thereafter at 250mg per metered
sq over 1 hour.
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Erbitux

Toxicity
Main toxicity is a nonseparative acneform rash
present in about 35% of patients.
 Allergic reaction: anaphylaxis in approximately 1%


Other Toxicities

Diarrhea 20% nausea, 15% weakness 20%
47
Vectibix
•
•
•
Similar to erbitux- binds to EGFR
Used alone or in combination with
chemotherapy
Main toxicities: acneform rash and occasional
diarrhea but no allergic/anaphylaxis reactions
48
Rectal Cancer

Risk factors, staging and prognosis identical to
colon cancer

40,000 cases per year in the U.S.

Treatment identical as well except:

1) Surgery often results in a colostomy
(abdominoperineal resection)

2) Radiation therapy is required in the treatment of
stage II and III patients
49
Anal Cancer

<2000 cases per year

More common in women than men

Associated with the human papilloma virus

Most common symptom: pain in the anal region
50
Treatment


Chemotherapy

Mitomycin C, Day 1

5FU via 24 hour infusion, Days 1-4 and 29-32
Radiation Therapy

Daily M-F for 5 weeks
51
Side Effects

Radiation dermatitis

Myelosuppression

Diarrhea

Anal strictures
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Cure Rate

Tumors <3 cm = 85-90%

Tumors >3 cm = 70%

Much better than surgery alone
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CANCER STAGING
AND
DIAGNOSTICS
Thomas M. Waits, M.D.
2017
54
Cancer Staging and Diagnostics

Staging of cancer

Enhances ability to compare different treatments

Enables the physician to accurately choose the
optimal therapy

Furnishes prognostic information
55
Staging System and
Nomenclature
AJCC (American Joint Committee on
Cancer)
 System is the most widely utilized
 The AJCC uses the TNM System

T = size and extent of the tumor
N = presence and extent of lymph node
involvement
M = presence of metastatic spread
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Components of Staging

Radiology
Plain radiographs including chest x-ray
 Computed tomography (CT)
 Magnetic resonance imaging (MRI)
 Positron emission tomography (PET)

57
Components of Staging
(continued)

Procedural testing
Endoscopy
 Bone marrow exam
 Surgical biopsies
 Fine needle aspiration
 Endoscopic ultrasound

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Mammography

Screening mammography




No history of breast cancer
Begins at age 40
Recommended annually ( or every 2 years; or begin at 45)
Diagnostic mammography


Utilized when a suspicious lump is noted on screening
mammography
Uses spot compression, increased magnification and breast
ultrasound technique
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Suspicious Findings on
Mammography

Clustering of calcium deposits

Heterogeneous in shape and size
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Breast Ultrasound

Not utilized in screening ( discerns solid from
cystic )

Used primarily to evaluate palpable masses and
equivocal mammogram abnormalities

Guide for cyst aspiration/needle biopsies
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Computed Tomography
(CT)

No more radiation than with regular x-rays of
the chest, skull or bone

Revolutionized staging due to its exceptional
sensitivity and specificity in evaluating different
parts of the body
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Computed Tomography
•
Oral contrast taken 1 to 4 hours prior to exam
to illuminate bowel
•
Intravenous contrast ( iodine based ) given a few
minutes prior to exam to illuminate vascular
structures
•
Images taken typically at 3 to 5 mm intervals
64
CT Scanning in Lung Cancer

CT of the chest and upper abdomen
- Evaluates the possibility of metastatic disease
(i.e. liver and adrenals)
- Evaluates the mediastinal lymph nodes which is very
important in determining resectability
- Mediastinal node accuracy
sensitivity 79%
specificity 65%
65
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CT Abdomen and Pelvis

Evaluates primarily liver, spleen, abdominal
lymph nodes, kidneys, bladder and uterus

Not particularly sensitive in evaluating bowel
abnormalities i.e. stomach, colon, etc.
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Magnetic Resonance Imaging

Principle – Creation of a magnetic field designed
to pull hydrogen atoms from their axis

More sensitive than CT scanning for evaluation of:
- brain
- spine
- joints and bones
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Ultrasound

Cystic versus solid
- Liver, ovary and kidneys

Extent of disease
- transrectal evaluation in prostate cancer
and rectal cancer
- endoscopic ultrasound in esophageal cancer
73
Endoscopic Ultrasound

Important for assessing tumor extent in
gastrointestinal tumors

Assesses both depth of involvement (T) and
lymph node status (N)

Valuable in localizing disease in prostate cancer
for biopsy purposes and in staging of esophageal
and rectal cancer
74
Bone Scan





Uses technetium-99m pyrophosphate
Sensitivity 88%, specificity 92%
Widely used to evaluate patients with prostate
cancer as well as breast cancer
Ordered frequently in a patient with malignancy
if bone pain is present or elevation of the
calcium or alkaline phosphatase is noted
Is not indicated in multiple myeloma
75
Positron Emission Tomography
(PET)

Designed to identify metabolic differences
between normal and malignant cells

Example: Malignant cells show an increased rate
of DNA synthesis and glycolysis; thus, FDG is
preferentially taken up by malignant cells
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PET Superiority over CT

Pulmonary nodule – Positive predictive value of
PET is 94%, negative predictive value is 100%

Superior to CT scanning in evaluating
mediastinal lymph nodes in determining lung
cancer resectability
Sensitivity
CT
79%
PET
85%
Specificity
65%
81%
77
PET Scanning

Superior to bone scan in identifying lytic
bone mets

Useful in assessing response to treatment in
some cancers

Use is and will continue to increase in
medicine
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Pathologic or Procedural Staging

Thoracentesis

Frequently important to determine the cause of a
pleural effusion

May alter treatment strategy (i.e., in lung cancer,
difference between operable and inoperable)

Technique: needle is placed posteriorly just above
the rib and inserted into the pleural space and the
fluid is extracted
79
Thoracentesis
Needle
Insertion
Area
Left Lung
Pleural Membrane
Pleural Effusion
Diaphragm
Needle
80
Paracentesis

Can be used as a diagnostic and/or therapeutic
procedure

Diagnostic: determining if the ascites is
secondary to liver dysfunction, malignancy or
infection

Therapeutic tool: Relief of pressure and pain
when massive amounts of malignant ascitic fluid
accumulates
81
Bone Marrow Aspirate and Biopsy

Aspiration – Obtaining a cell count such as the
number of plasma cells in patients with multiple
myeloma

Biopsy – Evaluate cellularity – normally be
about 50% (drops some with age)
82
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Mediastinoscopy

Used to assess the mediastinal lymph nodes

Important in evaluating the operability of a
patient with non-small cell lung cancer

Technique involves an incision in the area of the
suprasternal notch; however, a left anterior chest
wall incision may be needed as well

Indication has decreased with the advent of CT
and PET scanning
84
ONCOLOGIC
EMERGENCIES
Thomas M. Waits, M.D.
2017
85
Oncologic Emergencies

Superior vena cava syndrome – surrounded by
lymph node chains that drain the right thoracic
cavity and lower left thoracic cavity

Azygos, internal mammary, lateral thoracic,
paraspinous and esophageal venous systems
serve as collaterals
86
Malignancies Associated With
SVC Obstruction

Lung cancer (both small cell and non-small cell)

Non-Hodgkin’s lymphoma

Germ cell tumors

Thymomas

Hodgkin’s disease
87
Non-Malignant Causes of SVC
Syndrome

Central venous catheter clot

Pacemaker clot

Mediastinal fibrosis
88
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Treatment of SVC Obstruction

General support
Evaluation of head and upper body
 Oxygen
 Diuretics


Specific treatment directed by biopsy

Use of chemotherapy, radiation therapy or surgery to
treat the malignancy
95
Treatment of SVC Obstruction
(continued)

Central venous catheter clot

Thrombolytic therapy

Angioplasty

Heparin
96
Spinal Cord Compression

Overall outcome is influenced by neurologic status at the
time treatment is started

Spinal cord compression is either extradural or intradural

Extradural – more common



Vertebral body compressing anteriorly on the dural sac
Symptoms: Pain followed by weakness and sensory deficit
Intradural


Seen occasionally with breast cancer
More difficult to treat
97
98
Spinal Cord Compression

Signs and Symptoms:

Back pain 80-90% - localizes the lesion

Numbness or sensory loss

Lower extremity weakness

Hyper-reflexiveness

Incontinent of bowel / bladder
99
Spinal Cord Compression
Treatment and Evaluation

Begin on Decadron - steroid that reduces edema
or swelling

MRI of the spine

Treatment – radiation therapy alone or surgery
followed by radiation therapy
100
Hypercalcemia of Malignancy

Mechanism: Bone destruction caused by OAF
(osteoclast activating factor )or similar proteins
produced by malignant cells (i.e., multiple
myeloma or squamous carcinoma of the lung )

Release of calcium into the bloodstream from
the disease altered bone
101
Hypercalcemia
Signs and Symptoms

Lethargy/stupor

Polyuria/nocturia

Obstipation/constipation

Renal insufficiency or failure
102
Treatment of Hypercalcemia

Hydration: usually with normal saline at
150-200 cc/hour

Osteoclast inhibitors: zoledronate ( zometa ) &
denosumab ( xgeva )

Loop diuretics (furosemide) which eliminate
Ca++, only used when the patient has been well
hydrated
103
Zolendric Acid

Given over 15 minutes

85% of patients have a normal calcium by day 10

Can worsen renal insufficiency (should not be used
with creatinine >3.0)
104
Denosumab ( Xgeva )

Binds to RANKL which prevents preosteoclasts from maturing to osteoclasts

Given sub Q

Main side effect: hypocalcemia- maybe
prolonged
105
Hyperuricemia

Associated cancers include non-Hodgkin’s
lymphoma, chronic myelogenous leukemia and
acute leukemia

Clinic manifestations – gout, renal insufficiency,
renal failure
106
Hyperuricemia Treatment

Prophylactic administration of allopurinol

Discontinuation of drugs that increase uric acid
such as thiazides and salicylates

Keep the urine pH greater than 7.0 (sodium
bicarb or acetazolamide)

Hydration
107
Tumor Lysis Syndrome

Consists of:
Hyperuricemia
 Hyperkalemia
 Hyperphosphatemia
 Hypocalcemia


Cause: Rapid death of malignant cells and
release of their cellular content
108
Treatment

Identify patients at risk

Rigorous hydration

Allopurinol

Urine alkalinization

Frequent electrolyte checks and correction of
abnormalities
109
Hypoglycemia
Associated Tumors

Certain pancreatic islet cell tumors (i.e. insulinoma)

Certain sarcomas (fibro, leiomyo, rhabdo or
liposarcomas)

Mechanism:
increased insulin
 Production of insulin-like proteins
 Increased glucose utilization

110
Hypoglycemia Symptoms

Weakness

Confusion

Dizziness

Headache

Hunger

Instability

Agitation

Combativeness
111
Hypoglycemia Physical Signs

Tachycardia

Diaphoresis

Pallor

Lethargy

Seizures

Coma
112
Hypoglycemia
Whipple’s Triad

Symptoms compatible with hypoglycemia

Low serum glucose level

Relief of symptoms when glucose is normal
113
Hypoglycemia Treatment

Dextrose or glucagon

Treatment of the underlying tumor
114
Adrenal Failure

Involvement of the adrenal glands with metastatic
cancers, especially lung cancer

Cause of adrenal insufficiency by these tumors is
rare

Symptoms include fatigue, hypotension,
hyperkalemia, hyponatremia
115
Urinary Obstruction

Causes:
Extrinsic compression by various tumors
(lymphomas, sarcoma, etc.)
 Intrinsic blockage by metastatic disease (breast
cancer; rare)
 Retroperitoneal fibrosis caused by prior surgery,
radiation therapy or chemotherapy

116
Urinary Obstruction
Signs and Symptoms

Acute obstruction – colicky pain

Chronic obstruction
Unilateral – no symptoms
 Bilateral – dull flank pain, hypertension, weakness,
edema and renal failure

117
Urinary Obstruction
Treatment

Percutaneous technique

Endourologic technique
Retrograde
 Antegrade

118