E. MORAN - 2018 1
Primary tumor (T)
TX: Main tumor cannot be measured.
T0: Main tumor cannot be found.
T1, T2, T3, T4: The size and/or extent of the main tumor.
Regional lymph nodes (N)
NX: Cancer in nearby lymph nodes cannot be measured.
N0: There is no cancer in nearby lymph nodes.
N1, N2, N3: Refers to the number and location of lymph nodes that contain cancer.
Distant metastasis (M)
MX: Metastasis cannot be measured.
M0: Cancer has not spread to other parts of the body.
M1: Cancer has spread to other parts of the body.
The Tumor (T), the Lymph Nodes (N),
and the Cancer Spread (M)
1. In all sites, there is good correlation between the
size of the tumor and its local penetration (T),
the involvement of lymph nodes (N), and the
spread of the cancer to remote sites
(metastases) (M)
2. Staging dictates the best treatment
3. Staging weighs heavily on prognosis
CORRELATION BETWEEN TUMOR, LYMPH NODES, AND METASTASES
E. MORAN - 2018 2
E. MORAN - 2018 3
Patient’s general condition, co-morbidities
Performance status
Psychological index
Tumor histology, grade of aggressiveness
Tumor stage (T, N, and M)
Treatment modality available
Responsiveness to treatment
Cancer is no longer the most lethal of chronic diseases.
Cancer is now the most chronic of lethal diseases.
Cancer Prognosis and Survival
E. MORAN - 2018 4
II III IV NR TOTAL
PSA n % n % n % n % n %
0 - 4 29 14% 2 1% 2 1% 11 5% 44 21%
5 - 10 44 22% 3 1% 5 2% 36 18% 88 43%
11 - 20 19 9% 0 0% 2 1% 16 8% 37 18%
21 - 30 5 2% 1 0% 1 0% 1 0% 8 4%
31 - 40 4 2% 0 0% 1 0% 0 0% 5 2%
> 40 15 7% 2 1% 1 0% 1 0% 19 9%
116 58% 8 4% 12 6% 65 32% 201 100%
STAGE
PSA and the TNM Stage
E. MORAN 2018
LECTURE #4
6
7
CANCER TREATMENT
8
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CANCER TREATMENTPRINCIPLES
Localized – Adjuvant ChemoRx + Surgery +/- RT
Regional (N+) – Surgery + Adjuvant RT + CT +/-
ImmunoRx.
Metastatic (spread +) – ChemoRx, Biologicals,
Immunotherapy +/- Surgery for “debulking” +
ChemoRx +/- ImmunoRx +/- Radiation
E. MORAN - 2018 12
E. MORAN - 2018 13
Debulking the tumor mass
Removal of the primary tumor in presence of
metastases
Removal of metastases in liver, lungs, brain
NEW SURGICAL TREATMENTS
CANCER CHEMOTHERAPYFIRST FINDINGS
14
15
Principles of Combination Chemotherapy
16
ADJUVANT CHEMOTHERAPY
E. MORAN - 2018 17
E. MORAN - 2018 18
Immunotherapy
Monoclonal agents
Anti-angiogenesis factors
Anti-target therapy
IMMUNOTHERAPY OF CANCER
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CELL MEMBRANE RECEPTOR
T-lymphocytes (activated in the thymus) identify
aggressors and try to destroy them through the
production of lymphokines (synthesized proteins)
• Killer T-cells
• Helper T-cells
• Suppressor cells
CELL-MEDIATED IMMUNITY
E. MORAN - 2017 20
B-lymphocytes (from the bone marrow) synthesize
immunoglobulins which function as antibodies
combining with foreign antigens (bacteria and
viruses):
IgG – major immunoglobulin (80%)
IgM – mostly intravascular
IgA – in body secretions, GI and respiratory tract
IgE – active in hypersensitivity (allergy)
IgD
HUMORAL IMMUNITY
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23
Antibody
Antigen
Antigen binding site
Immunoglobulin Molecule, Antigen, and
Antibody
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Active immunotherapy:
Non-specific: BCG
Levamisole
Interferon
Interleukin 2
Specific: Tumor antigen vaccines
IMMUNOTHERAPY OF CANCER (1)
E. MORAN - 2018 25
Passive immunotherapy
Antibodies: Monoclonal or Polyclonal Antibodies
Conjugated with toxins
Radiolabeled
Cells: Tumor-infiltrating lymphocytes
Immunotherapy of Cancer (2)
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%
Urinary bladder 60-70
Kidney cancer 15-20
Malignant melanoma 10-15
Cutaneous T-cell lymphoma 80
Lymphoma 40-50
Multiple myeloma 50
Response to Cancer Immunotherapy
27
Monoclonal Antibodies to Cancer
Cell
Development of a Malignant Tumor
E. MORAN 2018
Tumor cells and T cells
30
DIAGNOSIS of BLOOD FORMING
ORGANS
LEUKEMIA
31
Active (Normal) Bone Marrow
32
Active (Normal) Bone Marrow
33
Stem Cell and Blood Cells
34
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Blood film (smear) to show: Red blood cells, white blood cells
(neutrophils), and a platelet
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RBC 120 days
WBC 8.5 -14 days
Platelets ~ one week
LIFETIME OF BLOOD CELLS
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38
Homeostasis of the White Blood Cells
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Leukemia – Microscopic view of the bone marrow
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Clinically:
Acute leukemia: Acute course, with bleeding, infections
Chronic leukemia: Course is chronic - years
Microscopically:
Acute: Primitive bone marrow cells in the bone marrow and in the blood
Chronic: Relatively differentiated bone marrow cells in the blood
ACUTE VS. CHRONIC LEUKEMIA
US 2017 est. new cases 62,000
Acute lymphocytic leukemia 6,000
Chronic lymphocytic leukemia 20,000
Acute myeloid leukemia 21,000
Chronic myeloid leukemia 9,000
Other leukemias 5,800
LEUKEMIA Burden of Suffering
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• Genetic factors
• Viral infection
• Radiation exposure
• Chemicals exposure
ACUTE LEUKEMIAEtiology
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• Weakness, fatigue
• Recurrent infections
• Bleeding, gum bleeding
• Bone pain
• Anorexia
LEUKEMIA Symptoms
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A child with bleeding in the mouth mucosa had low platelets in the blood
44
E. MORAN - 2018 45
Petechiae in Leukemia
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47
View of the eye fundus showing multiple spot bleeding caused by low platelets in a patient with acute leukemia
BLEEDING INTO THE BRAIN IN LEUKEMIA B/O LOW PLATELETS
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E. MORAN - 2018 49
Acute leukemia (lymphatic and myeloid): Chemotherapy
Bone marrow transplantation
Chronic lymphatic leukemia: Chemotherapy
Chronic myeloid leukemia: Chemotherapy
BMT (?)
Polycythemia rubra vera: Phlebotomies
Chemotherapy
LEUKEMIATreatment
E. MORAN - 2018 50
LYMPHOMAS
51
Subjective: tender or painless
Objective: Acute or chronic
Local or general
Isolated or matted glands
Differential diagnosis: Chronic infections
Cancer
Diagnosis: Biopsy and pathologic examination
No needle biopsy
ENLARGED GLANDS(LYMPHADENOPATHY)
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E. MORAN - 2018 53
Left cervical lymphadenopathy
(Enlarged lymph nodes) –
Chonic lymphatic leukemia
(CLL)
54
Right Cervical (Neck) Enlarged Lymph
Nodes - Lymphoma
55
Burkitt’s lymphoma
E. MORAN - 2018
Relapse of “Testicular Cancer”On pathology review: Large cell lymphoma
56
Liver scan with focal areas of involvement
57
Abdominal CT Scan of a Patient with Lymphoma
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E. MORAN - 2017 59
Classified by their rate of proliferation:
• Low-grade
• Intermediate grade
• Hi-grade
Lymphomas other than Hodgkin’s
Disease
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Low-grade (Indolent) lymphomas:
Observation
Chemotherapy at time of progression +/- Radiation
High-grade (aggressive) lymphomas:
Chemotherapy
Bone marrow transplantation
Treatment of Lymphomas
E. MORAN - 2018 61
TREATMENT of LUNG CANCER
62
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E. MORAN - 2018 64
Surgery for curative intent
Surgery for palliative intent
Radiation therapy
Systemic chemotherapy
Intra-cavitary (intra-pleural) chemotherapy
LUNG CANCERTreatment
E. MORAN - 2018
LUNG CANCER: Localized or not?
65
E. MORAN - 2018 66
Provided that Pulmonary Function Tests (PFT’s)
are minimally OK one can do:
• Wedge resection
• Segmental resection of small peripheral
lesions
• Lobectomy
• Pneumonectomy
LUNG CANCER
Surgery
67
E. MORAN - 2018 68
Effective as used alone or in combination with systemic chemotherapy
Dose depends on the histologic type of the cancer
New modalities showed increased effectiveness
LUNG CANCERRadiation Therapy
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Atelectasis (collapse of lung tissue)
Infection → Bronchopneumonia
Pleural effusion (fluid)
Metastases to brain, adrenals, bones, liver
Paraneoplastic syndromes with metabolic alterations
LUNG CANCERComplications
INTERMISSION
72
TREATMENT of PROSTATE CANCER
73
74
Prostate Needle Biopsy/ies
E. MORAN - 2018 75
PROSTATE CANCER
OCCULT LYMPHNODE METASTASESVS. TUMOR STAGE AND GRADE
Clinical Stage Tumor Grade (Gleason)
(Localized Dis.) Well Intermediate Poor
(2-4) (5-7) (8-10)
% % %
T1, N0, M0 5 23 50
T2, N0, M0 5-28 20-27 27-38
T3, N0, M0 18 42 68
E. MORAN - 2018 76
PROSTATE CANCER METASTASES
77
78
Metastatic Prostate Cancer to the Skeleton
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What should we know?
• Disease control - rates?
• Side effects?
• Indicated for the particular patient?
• Quality of life?
Radical prostatectomy with removal of seminal vesicles
• Retropubic prostatectomy
• Perineal prostatectomy
• Laparoscopic/robotic prostatectomy
(Nerve-sparing technique and Pelvic lymph node sampling are necessary)
SURGERY
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Prostate cancer Intervention Versus Observation Trial (PIVOT) Study
Prostatectomy vs. Observation
1994 – 2002 - 731 men, mean 67 y.o.
Localized prostate cancer
PSA median 7.8 ng/ml
Any Gleason score
Follow-up 8 yrs.
Conclusion: Prostatectomy did not reduce mortality rate
Clinically Localized Prostate Cancer
84
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LHRH agonists – Turn off the testicle production of male hormone. Shots given q. 3 – 12 months (Lupron, Zoladex)
Combined Androgen Blockade – LHRH agonist + antiandrogen (Flutamide)
Side effects:
• Decreased libido
• Hot flashes
• Breasts enlargement
• Loss of muscle and increase in body fat
• Osteoporosis
• Risk of Coronary heart disease and of Type 2 diabetes
Androgen Deprivation Therapy
UPPER GI CANCER
88
Limit Alcohol and Tobacco
40x
30x
20x
10x
Alcoholic Drinks Consumed per Day
Packs of Cigarettes Consumed per Day
Combination of Alcohol and Cigarettes Increases Risk for Cancer of the Esophagus
Risk Increase
AND
N. C. I. 89
E. MORAN - 2018 90
Difficulty swallowing solid foods
Later difficulty and pain swallowing fluids
Weight loss
Change in taste
ESOPHAGEAL CANCER
Symptoms
Endoscopy – Esophageal cancer
91
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Neo-adjuvant chemotherapy – 3 months
Surgery
Adjuvant chemotherapy +/- radiation
therapy
Cancer of the Esophagus
Treatment
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Lack of appetite and Unexplained weight loss is a common
sign of cancer.
Nausea & vomiting: Sometimes the vomit may have blood
in it.
Stomach pain in the upper abdomen.
Early satiety (Feeling full after a small meal).
Heartburn.
STOMACH CANCER
E. MORAN - 2018 95
Surgery with dissection and removal of the
satellite lymph nodes.
Adjuvant chemotherapy.
5-year survival rates: 18% - 94%, depending
on the stage
STOMACH CANCERTreatment
TREATMENT of COLORECTAL
CANCER
96
E. MORAN - 2018 97
Surgery:
• Surgical removal of the area involved
• Careful dissection of satellite lymph nodes (N1-N3
• sites)
• Examination of the liver
Chemotherapy
• If N+ (Stage 2) adjuvant
• If distant mets. (Stage 4)
Treatment of Colon Cancer
E. MORAN - 2018 98
E. MORAN - 2018 99
TREATMENT of TESTICULAR CANCER
100
TESTICULAR CANCERPresentation
• Symptoms:
• Painless swelling in one testicle
• Scrotal pain (rare)
• Occasional: symptoms related to mets.
• Signs:
• Firm testicular nodule or mass
• Epididymis involvement
• Hydrocele
E. MORAN - 2018 101
TESTICULAR CANCERTumor Markers
• After orchiectomy, markers should become normal
• Persistent elevation = residual disease
• Useful in dx. of relapse (clinical f/u)
E. MORAN - 2018 102
Staging: Is the disease limited to the testicle?
Chest X-ray and abdominal CT scan
Biomarkers: - Alpha-Fetoprotein (AFP)
- β subunit of human chorionic gonadotropin
(beta-hCG)
- Lactic dehydrogenase (LDH)
All biomarkers must became normal after orchiectomy
TESTICULAR CANCERManagement
E. MORAN - 2018 103
Normal left testicle
Seminoma in right testicle
104
Ultrasound of the Scrotum: Right Testicle Cancer
RADICAL ORCHIECTOMY (Removal of the testicle and of the spermatic cord = “the only acceptable diagnostic and therapeutic procedure”
Retroperitoneal lymph node dissection
Radiation therapy for pure seminoma
Chemotherapy for extra-testicular disease
TESTICULAR CANCERTreatment
E. MORAN - 2018 105
CANCER of the UTERUS
106
CANCER OF THE UTERUS
Risk Factors
E. MORAN - 2018 107
• Menstruating at an early age.
• Starting menopause at a later age.
• Never giving birth.
• Taking estrogen only (HRT) after menopause.
• Taking tamoxifen to prevent or treat breast cancer.
• Obesity and Metabolic syndrome.
E. MORAN - 2018 108
• Having type 2 diabetes.
• Having polycystic ovarian syndrome.
• Having a family history of endometrial cancer in a
first-degree relative (mother, sister).
• Having certain genetic conditions, such as Lynch
• syndrome.
• Having endometrial hyperplasia.
CANCER OF THE UTERUSRisk Factors (cont’d)
Metabolic Syndrome. Weight 182 Kg/400 lbs.,
Height 6 ft. 1 in. The BMI is 53.
DEFINITION: 1. ABDOMINAL OBESITY, 2. HIGH BLOOD PRESSURE,
3. HIGH BLOOD SUGAR, 4. HIGH SERUM TRIGLYCERIDE,
5. LOW HIGH-DENSITY SERUM LIPOPROTEIN (LDL) LEVEL 109
E. MORAN - 2018 110
Irregular periods
Menorrhagia
Abundant blood discharge – Metrorrhagia
Pelvic pain
Cancer of the Uterus - Symptoms
111
Endometrial Cancer - Ultrasound
Cancer of the Uterus - Treatment
112
CANCER OF THE UTERINE
CERVIX
113
Cervical Cancer (invasive carcinoma)
©University of Alabama at Birmingham
Cervical Cancer (Invasive Carcinoma)
115
CERVICAL CANCER SCREENING
RECOMMENDATIONS
• All women who are or have been sexually active
• Papanicolaou (Pap.) test 3 yrs. after first vaginal intercourse
and no later than 21 y.o.
• Pap. q. yr. in hi-risk cases
• After 30 y.o., if Pap. negative (x 3), screening with Pap. and
HPV DNA testing q. 3 yrs.
• Pap. may be discontinued at 70 y.o. if previously normal
E. MORAN - 2018 116
Avoid Cancer Viruses
Noninfected women
HPV Infection Increases Risk for Cervical Cancer
CervicalCancerRisk
Low
High
Women infected
with HPVN. C. I. 117
CANCER of the URINARY
BLADDER
118
E. MORAN - 2018 119
Blood in the urine
Having to urinate more often than usual
Pain or burning during urination
Urgency = feeling that one needs to go right away, although the bladder
is not full
Having trouble urinating or having a weak urine stream
Late symptoms:
Being unable to urinate
Loss of appetite and weight loss
Feeling tired or weak
Bone pain
Cancer of the Urinary Bladder.
Symptoms are not specific
BLADDER CANCER STAGES
LIVER, PANCREAS, and
ABDOMEN
121
LIVER SCAN SHOWING DEFECTS
E. MORAN - 2017 122
123
CT Scan - Metastatic cancer to the liver
Upper AbdomenDuodenum, Pancreas, and Spleen
124
125
Endoscopic retrograde cholangiopancreatography (ERCP)
PERITONEUM - SCHEMA
126
LAPARASCOPY (Looking into the Abdominal Space)
127
SKIN CANCER
SKIN CANCER SCREENING Risk Factors
• Atypical moles (dysplastic nevi)
• Congenital moles
• Large number of common moles
• Immunosuppression
• Family/personal history of skin cancer
• Fair skin, poor tanning ability
• Intense sun exposure
• Severe sun burns in childhood
E. MORAN 2018
E. MORAN 2018
2017 - >5 million new cases in U.S.
1:5 Americans will have skin cancer
>95% are basal cell or squamous cell carcinoma
Organ transplant patients x 100 times more at risk
90% of non-melanoma are associated with exposure to
UV radiation
Actinic keratosis = most common precancer
2017 – 87,000 new malignant melanoma cases
2017 – 9,700 deaths
SKIN CANCER SCREENING Burden of Suffering
Malignant melanoma vs. Benign nevi (moles)
Asymmetry
Borders
Color
Diameter changing
E. MORAN 2018
Malignant Melanoma of the Skin
132
Sites of Melanoma Development
133
STAGES OF MELANOMA
Malignant melanoma – Stage and SurvivalFive-Year Survival Rates for
Patients with Melanoma (by stage)
Stage at Time of Initial Diagnosis
100%
50%
I II III
N. C. I.
END OF LECTURE #4
END OF THIS CLASS
THANK YOU
☺
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