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

E. MORAN - 2018 9

E. MORAN - 2018 10

E. MORAN - 2018 11

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

E. MORAN - 2018 19

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

E. MORAN - 2017 21

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23

Antibody

Antigen

Antigen binding site

Immunoglobulin Molecule, Antigen, and

Antibody

E. MORAN - 2018 24

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)

E. MORAN - 2018 26

%

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

29

Anti-angiogenesis

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

E. MORAN - 2018 35

Blood film (smear) to show: Red blood cells, white blood cells

(neutrophils), and a platelet

E. MORAN - 2018 36

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

E. MORAN - 2018 40

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

E. MORAN - 2018 41

• Genetic factors

• Viral infection

• Radiation exposure

• Chemicals exposure

ACUTE LEUKEMIAEtiology

E. MORAN - 2018 42

• Weakness, fatigue

• Recurrent infections

• Bleeding, gum bleeding

• Bone pain

• Anorexia

LEUKEMIA Symptoms

E. MORAN - 2018 43

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)

E. MORAN - 2018 52

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

E. MORAN - 2018 58

E. MORAN - 2017 59

Classified by their rate of proliferation:

• Low-grade

• Intermediate grade

• Hi-grade

Lymphomas other than Hodgkin’s

Disease

E. MORAN - 2018 60

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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E. MORAN - 2018 83

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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E. MORAN - 2018 86

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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

E. MORAN - 2018 92

Neo-adjuvant chemotherapy – 3 months

Surgery

Adjuvant chemotherapy +/- radiation

therapy

Cancer of the Esophagus

Treatment

STOMACH

93

E. MORAN - 2018 94

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

114

Normal Uterine Cervix

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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