Principles of Oncology

Jeffrey T. Reisert, DO

University of New England

Physician Assistant Program

25 FEB-4 MAR 2010

Case

• A 55 y/o male “new patient” comes in for a routine physical.

• They ask you to order “all the cancer blood tests so they will know if they are going to get cancer”

• They tell you that many of their aunts, uncles, and cousins have had assorted different cancers.

Case questions

• What are they talking about? Cancer blood test? PSA? Something else?

• What family history is significant?

• What do you advise them?

Objectives

• Understand general approach to cancer evaluation and treatment

• Given a case in common cancers, such as lung, breast, colon, prostate, and skin, select a treatment plan for diagnosis, work up and treatment

Overview

• Diagnosis

• Staging

• Further testing and work up

• Treatment planning

• Screening for cancers

• Approach to lung, breast, prostate, colon, and skin cancers

Cancer

• Single clone of cells

• Autonomous growth-Unregulated– Apoptosis (pre-programmed cell death) lost

• Anaplastic-Abnormal differentiation

• Metastatic-Spread

Growth

• Growth is unregulated

• Cancer growth usually slows when tumors become large

• Not a constant doubling time

• At least in part due to blood supply

Etiology of Cancer

• Not completely understood

• Involves a predisposition (Genetics)

• Environmental role

Genetic role

• Oncogenes– Tumor growth stimulated by presence of gene

• Tumor suppresser genes – These genes if present prevent malignant growth. Involved in

preprogrammed cell death (apoptosis)

– If absent, increased risk of malignancy as cells don’t die

– Example is mutant p53 gene

• P53 is a tumor suppressor protein controlling cancer and aging

• Mutant gene if present puts cells at risk for uncontrolled growth

Genetics II

• Many family members may be at risk– Familial polyposis syndromes in colon cancer– Multiple endocrine neoplasia (MEN

syndromes)

• Can be transmitted via viruses– HTLV-I causes T cell lymphoma transported

by retrovirus

Family history?

• You can pick your friends but you can’t pick your relatives

• Primary relatives?– P– S– O/C

Environmental

• Radiation

• Carcinogens such as tobacco

• Viruses

• Diet

• Obesity (next slide)

• Previous chemotherapy

Obesity in cancer

• Associated in men with 14% of cancer deaths including:– Liver

– Pancreas

– Stomach

– Esophagus

– Colon/Rectal

– Gallbladder

• Associated in women with 20% of cancer deaths including– Uterus

– Kidney

– Cervix

– Pancreas

– Esophagus

Tobacco

• Oral

• Pharynx/Larynx

• Lung

• Esophagus

• Renal Cell

• Breast

• Ovary

Problems with cancer

• Direct effect-Invasion

• Indirect– Cytokines, TNF, Hormonal, Metabolic

• Psychological

• Stigma

• Death

Spread patterns

• Direct

• Lymph/ nodes

• Hematogenous after spreading through a vessel

• Through serous cavities after exiting an organ

Diagnosis of cancer

• Kills 25% of Americans (#2 to cardiovascular diseases when totaled)

• Common patterns of disease

Common patterns of disease

• History– Age– Sex– Family History– Social History

• Physical

Examples

• Klinefelter’s syndrome-Male breast cancer

• Mother with breast cancer

• Daughters of DES mothers-Vaginal cancer

• Asbestos-Mesothelioma

• Reflux with Barrett’s esophagus

Work up and testing

• Begin with H&P

• Labs

• X-rays, other diagnostics

• Tissue diagnosis

• Staging

Lab work up

• Complete blood count

• Other specific tests– Chemistries– Tumor markers– Genetics

Genetics

• Philadelphia chromosome– (9,22) translocation- CML

• BRCA-Breast and ovarian cancer

Tumor markers

• Use

• Misuse

• ***Not for screening***

Tumor markers-Examples

• hCG– Pregnancy– Testicular and ovarian cancer

• CEA– Bowel, other– Also seen in smokers, COPD

• AFP– Non seminomatous testicular cancer

Staging

• TNM

• Pathologic

• Others

Why stage?

• Treatment planning– Initial– Subsequent

• Prognostication

• Research studies

TNM

• Tumor-Size, location, invasion

• Node-Regional spread

• Metastasis-Distant spread

Pathologic staging

• Tissue diagnosis

• Origin of tissue

• Grade or differentiation– For example, prostate cancer Gleason’s stage

Stage groupings

• See overhead for lung example

• Don’t memorize

Introduction to treatment planning

• Surgery

• Chemotherapy

• Hormonal therapy

• Radiation therapy

Treatment planning-Goal

• Cure

• Prevent local recurrence

• Palliation

• Organize treatment plan– i.e.: neoadjuvant

Surgery

• Diagnosis-Must have tissue to diagnosis

• Staging• Prevent complications

– Local invasion– Prevent obstruction– Reduce tumor burden

• We will discuss this more soon

Chemotherapy

• Vesicants-Need central access

• Recognize side effects

• Cancer killing drugs

• Other disease modifiers– Hormones– Cytokines (i.e.: IFN)

Common chemo problems

• Bone marrow toxicity

• GI

• Skin– Alopecia

Specific chemotherapy examples

• Doxorubicin (Adriamycin)-Cardiac

• Bleomycin-Pulmonary fibrosis

• Cisplatin-Renal dysfunction

• We will discuss this more soon

Radiation therapy

• Short term problems– Skin– GI toxicity

• Long term problems– Scarring/Fibrosis– Malignancy potential

• We will discuss this more soon

Screening for cancers

• American Cancer Society recommendations

• Others also publish guidelines for screening

• Are often changing

• See handout

Lung cancer approach

• #1 MC cancer killer, men and women

• Tobacco association (95%+)

• No benefit of “screening chest x-ray” even in smokers

• Other associations– Asbestos (pleural tumor…..mesothelioma)

Lung Cancer cont.

• Small cell or non-small cell• Local vs.. spread• Surgery vs.. no surgery• Central or peripheral

– Large cell and adenocarcinoma-peripheral– Small cell (oat cell) and squamous cell-central

• Smoker vs. non-smoker– MC cell type in non-smoker is adenocarcinoma

Breast cancer approach

• Screening/prevention

• Lump and greater than 30--->Mammogram

• Radical mastectomy vs.. lumpectomy/RT..

• CMF, FAC

• Tamoxifen (Prevents reoccurrence)

Risk factors-Breast cancer

• Age >40• Early menarche (before 11), Late menopause• Nulliparity or first child late (after 25)• Primary relative• Previous biopsy• Radiation exposure• ETOH, tobacco• (Fat in diet is not clearly a RF)• (Breast feeding may reduce risk)• Estrogen ???

– May increase risk– Seems to come up in the literature commonly

Prognosis/Staging-Breast cancer

• Large tumor

• Positive lymph nodes

• Negative receptors

Spread- Breast Cancer

• 2 L’s, 3 B’s– Lung– Liver– Bone– Brain– Breast

Prostate cancer approach

• Risk factors

• Lump

• Testing

• Bone metastasis

Risk factors-Prostate cancer

• Age

• Race-African American

• Family history

Prostate specific antigen (PSA)

• NOT A PERFECT TEST• Never been shown to decrease

mortality/morbidity• Only effective as screening with

digital rectal exam• Routine screening of men over 75

not recommended by some (2009 change)

Colon cancer approach

• Risk factors (Family history, colitis, polyps)

• Colon vs.. rectal

• Surgery usually indicated (obstruction)

• Chemo or adjuvant chemotherapy

Colon Cancer cont.

• One of screenable cancers• Colonoscopy

– 50 and up– Every 5-10 years

• Fecal Occult Blood testing– Not great– Can be useful, and with low risk– Annual, over 50

Skin cancer approach

• 700,000 new cases per year• Sun exposed areas

– SPF 30 or greater recommended

• Basal cell-Raised, umbilicated, non-pigmented pearly lesions

• Squamous cell-Often excoriated• Melanoma (32,000 of the new cases)• Others

Skin cancer-ABCD’s

• Asymmetry– Mirror image if divided in half

• Border– Scalloped?

• Color– Variation, unusual

• Diameter– 6mm (pencil eraser size)

Case wrap up

• There are no real cancer blood tests recommended for healthy folks.

• Cousins and aunts/uncles don’t really increase your risk

• Let there exam and symptoms guide you.

• More to come……

Summary

• Look for common cancers and prevent them if you can!

• Recognize spread patterns

• Multidisciplinary approach

• Realistic goals for patient

References

• Cecil’s or Harrison’s• DeVida’s textbook of oncology• American Cancer Society

– Cancer Manual and website (www.cancer.org)– Textbook of Clinical Oncology (Murphy et al)– CA-A Cancer Journal for Clinicians (For free

subscription Email journals@cancer.org)

• Clinical Oncology (Rubin)