Cancer – the Essentials

1. Cancer – the Essentials Michele Ritter, M.D. Argy Resident – February, 2007

2. Breast Early menarche, nulliparity, or late first full-term pregnancy Exogenous estrogens Ionizing radiation Family History Colon Family History Inflammatory Bowel Disease Lung Tobacco Ionizing Radiation Asbestos (with tobacco) Pleura/Mesothelioma Asbestos Esophagus Tobacco Alcohol Barrett’s esophagus Ovary Nulliparity Pancreas Tobacco Prostate Family history Hepatocellular (liver) Hep. C, Hep. B Aflatoxin Vinyl chloride Alcohol (cirrhosis) Urinary Bladder Tobacco Schistosoma haematobium Aromatic amine exposure Cervical Human Papillomavirus Endometrial Obesity Exogenous, unopposed estrogen Diabetes mellitus Low parity Risk Factors fo Cancer

3. Cancer Prevention • Lung Cancer • Smoking cessation!!! • Tobacco is related to lung, head and neck, esophagus, pancreas, bladder, kidney, stomach and possibly ccolon and uterine cancers • Second hand smoke has been shown to be risk factor for lung cancer

4. Smoking Cessation • The 5 “A’s” for smoking cessation • Ask: Systematically identify all tobacco users at every visit • Advise: Strongly urge all tobacco users to quit • Assess: Determine a patient’s willingness to attempt to quit • Assist: Aid the patient in quitting. • Includes counseling, pharmacotherapy, social support • Arrange: Schedule follow-up contact.

5. Smoking Cessation (cont.) • Pharmacotherapy • Nicotine Replacement • Design to ameliorate symptoms of nicotine withdrawal: anxiety, dysphoria or depressive symptoms, insomnia, increased appetite/weight gain, • Includes gum, patches, nasal spray, inhaler • Bupropion (Zyban) • Enhance noradrenergic, dopaminergic function • Also used as an anti-depressant (Wellbutrin) • Has been shown to significantly increase rate of smoking cessation (especially when used in combination with nicotine replacement). • Caution in anorexic/bulemics (increased rate of seizures) • Varenicline • Is a partial agonist of nicotine acetylcholine receptor • Has been shown to increase rate of quitting (may even be better than bupropion)

6. Cancer Prevention (cont.) • Breast Cancer • Tamoxifen therapy • Shown to be beneficial in women who have at least a 1.7% absolute risk of developing the disease over the subsequent 5-year period (http://bcra.nci.nih.gov/brc) • At 20 mg/day for 5 years , a decreased risk for invasive and noninvasive cancer of 50% was seen. • Caution: • Increased risk for endometrial cancer • Increased risk for life-threatening thromboembolic events • No evidence yet showing that prophylactic mastectomy, oophorectomy is beneficial woman with average risk. • Limit exposure to postmenopausal hormone replacement therapy

7. Cancer Prevention (cont.) • Colon Cancer • Possible benefit with NSAID use (specifically in patients with familial adenomatous polyposis) – but not yet recommended routinely. • Gastric Cancer • Antibiotic eradiation of Helicobacter pylori • -carotene, vitamin E, selenium supplementation (in Chinese)

8. Cancer Prevention • Prostate Cancer • Finasteride • A 5- reductase inhibitor, blocks conversion of testosterone to dihydrotestosterone. • Show to decrease the risk for prostate cancer in men aged 55 years and older (but mortality was equal) • Decreased urinary symptoms with finasteride

9. Cancer Prevention • Diet • While increased fruits and vegetables have been found to decrease cardiovascular disease, there has been no significant benefit seen in cancer prevention with fruits/vegetables.

10. Cancer Screening • Cervical Cancer • Pap Smear • Beginning when patient becomes sexually active until age 65 (or until total hysterectomy) • At least every 3 years. • Insufficient evidence to screen routinely for human papillomavirus (HPV) • HPV-DNA testing as follow-up if low-grade atypia or other abnormalities found..

11. Cancer Screening (cont.) • Breast Cancer • Mammogram • Once every 1 to 2 years age 40-49 years • Annual mammogram for age ≥ 50 • Breast exam • Either performed by patient or provider, has not been found to have any effect on outcome.

12. Cancer Screening (cont.) • Colon Cancer • Beginning at age ≥ 50 • Colonoscopy, flexible sigmoidoscopy, feocal occult blood testing, barium enema used alone or in combination are equally effective. • If family history of colon cancer in first degree relative, first colonoscopy 10 years prior to his/her age at diagnosis.

13. Cancer Screening (cont.) • Prostate Cancer • USPSTF has not found evidence supporting the routine use of PSA. • Also has not found that routine DRE is helpful. • Skin Cancer • Routine screening for skin cancer using a total body skin exam not recommended. • Ovarian Cancer • Does not recommend vaginal ultrasound or CA-125 measurement • Lung Cancer • No established guidelines yet for the use of screening CT of the chest

14. Hypercalcemia The most common metabolic paraneoplastic syndrome Seen in: Squamous cell carcinoma (lung, head, neck) Frequently produce PTHrP Multiple myeloma Breast carcinoma T-cell lymphoma Renal Cell carcinoma Symptoms: Confusion Fatigue Constipation Nausea Polyuria Management Vigorous hydration Lasix Bisphosphonates Pamidronate Zoledronic acid Oncologic Complications

15. Superior Vena Cava Syndrome Symptoms Swelling face, neck, arms (especially when patient is supine) Cough Dyspnea Hoarseness due to laryngeal edema Headaches (increased intracranial pressure) Most commonly occurs in Lung Cancer (small cell) Lymphoma (Hodgkin and non-Hodgkin) Mediastinal germ cell tumors Exam: Periorbital and arm edema Elevated JVP Increased number of collateral veins covering anterior chest wall Diagnosed via: CT scan Should show right hilar mass with SVC occlusion An oncologic urgency Tissue diagnosis recommended Radiation therapy (or chemo. if small cell or lymphoma) Oncologic Complications

16. Spinal Cord Compression Symptoms: New or significantly worsening back pain/tenderness with neurologic deficits. Urinary incontinence, fecal incontinence Lower extremity weakness Exam: Point tenderness of spine Lower extremity weakness Decreased rectal tone Evaluation: STAT MRI Of Spine (all levels) Treatment: Start Dexamethasone 4-8 mg IV q 6h (as soon as suspect) Neurosurgery Consult Radiation Oncology consult Radiation is most frequent treatment. Oncologic Complications

17. Malignant Pleural Effusions Can be: Exudative Caused by metastases to major lymphatic structures or pleural surface Chylous Lymphatic/thoracic duct obstruction Commonly caused by: Lung Cancer Any other cancer with mets to lung (Breast, Colon) Non-Hodgkins lymphoma (chylous) Evaluation: Thoracentesis Send for cytology Pleural biopsy Treatment: Therapeutic thoracentesis Chest-tube w/ talc pleurodesis Pleurex catheter Oncologic Complications

18. Pericardial Effusion Caused by local disease into the pericardium or hematogenous spread into pericardium Most frequent cancers: Lung Breast Non-Hodgkins Lyphoma Treatment: If signs of tamponade on echocardiogram, may perform pericardial window. Peritoneal metastases Ascites Peritoneal carcinomatosis Frequent cause of bowel obstruction Frequently seen in: Ovarian cancer Colon cancer Stomach cancer Breast Cancer Non-Hodgkins Lymphoma Diagnosis: Paracentesis – cytology Treatment Symptomatic control Oncologic Complications

19. Breast Cancer • Most common cause of cancer in females • 215,000 women diagnosed with and 40,000 died from breast cancer in 2004. • Genetic Risk Factors: • BRCA 1, BRCA 2 • Risk of breast cancer > 50% by age 60 • Very high risk of ovarian cancer as well • Only present in ~ 5% of breast cancers • Only women who have very strong, premenopausal family history of breast cancer should be tested for BRCA • 90% reduction in breast cancer after prophylactic mastectomy • Oophorectomy may be ebeneficial • Number 1 risk factor for breast cancer is AGE!

20. Breast Cancer - Treatment • Surgery • Lumpectomy • Frequently Breast Conserving therapy, with radiation • Mastectomy • Sentinel Node Mapping • Injecting blue dye or radioactive material into tumor site/breast – if sentinel node has no tumor, no further surgery needed. • If sentinel node positive, further axillary node biopsy needed • Estrogen Receptor (ER) positive? Progesterone Receptor (PR) Positive? • If yes – overall prognosis better, endocrine therapy useful (tamoxifen, aromatase inhibitors) • Chemotherapy • May include Herceptin (traztuzumab) if Her2-positive.

21. Colon cancer • Age is greatest risk factor (90% of cases in patients > 50 years) • 75% occur in patients without risk factors. • Remaining cases have family history, familial hereditary cancer syndromes, inflammatory bowel disease. • Sign/Symptoms: • Abdominal pain, bloating, constipation, diarrhea, hematochezia, melena • Iron deficiency anemia: Need to rule out colon cancer in anyone over age 50 presenting with iron-deficiency anemia! • Clinical features • Liver is most frequent site of metastases • Elevated CEA ( > 5 ng/mL) – higher value = worse prognosis • Treatment • Surgery • Radiation • Chemotherapy – 5-Fluoruracil based regimens

22. Lung Cancer • Number one cause of cancer death • 1 million new cases a year, and 900,000 deaths per year • Symptoms • Asymptomatic “solitary pulmonary nodule” • A lesion < 3cm seen on chest X-ray/chest CT • Malignant features include older age, tobacco use, irregular border, low density on CT, doubling time < 1 year • If suspicion high, should biopsy • If suspicion low, should be monitored with subsequent studies • 3-4 months for first CT scan, 6 to 8 months for second, third scan at a year • New or worsening Cough – most common symptom • Hoarse voice – left recurrent laryngeal nerve involvement • Hemoptysis

23. Lung Cancer – Small-Cell • Small-Cell • Central Location • Almost 100% smokers • Almost 100% metastases • Chemotherapy only, no surgery • Paraneoplastic syndromes: • Eaton-Lambert Syndrome • SIADH • Ectopic ACTH

24. Squamous Cell Central Location 95% smokers 60% metastases Paraneoplastic Syndrome: Hypercalcemia Large Cell Peripheral location 90% smokers 80% metastases Adenocarcinoma Peripheral location 50% smokers 80% metastases Hypercoagulability Hypertrophic pulmonary osteoarthropathy Lung Cancer – Non-Small Cell

25. Lung Cancer • Treatment: • Surgery • Only way to cure lung cancer is to perform surgical excision of Stage I • Chemotherapy • Works best in Small Cell Carcinoma (also the only option!) • Special Cases: • Pancoast tumor • Apical tumor • lower brachial plexopathy, shoulder pain, Horner’s syndrome (unilateral constricted pupil, facial dryness, ptosis)

26. Prostate Cancer • Incidence has doubled sinced PSA testing began. • The lifetime risk of developing prostate cancer is 17.8% • The lifetime risk of dying from prostate cancer is 3%. • Risk factors: • Age (vast majority > 50 years of age) • African-American race • Diagnosis • Gold standard – prostate biopsy • Performed in patients with abnormal digital rectal exam or elevated serum PSA • Gleason score helps determine prognosis • PSA • Some labs say abnormal if > 4 ng/mL; NOT diagnostic of cancer • Rate of change in PSA is most helpful. • Age specific • Most patients with metastatic prostate cancer have PSA well above 10 • There are some patients with colon cancer with PSA < 4.

27. Prostate Cancer • Treatment: • Nothing • Prostatectomy • Radiation • Endocrine therapy • Bilateral orchiectomy • GNRH-agonists • Can cause impotence, hot flushes, gynecomastia, and loss of libido • Androgen-deprivation therapy • Need to watch for osteopenia

28. Question # 1 • A 59-year old man presents with cough, dyspnea and facial edema of 2 weeks’ duration. He has a 40-pack year smoking history. Except for an anteroseptal myocardial infarction 4 years ago, he has been healthy.

29. Question # 1 (cont.) • Physical examination reveals a blood pressure of 130/85 mmHg and normal heart sounds with a pulse rate of 72/min., but there is reduced air entry in the right middle chest, dilated veins in the upper chest, and a slightly tender liver palpable 3 cm below the costal margin. The results of hematology and chemistry screens (including liver function tests) are normal, but a chest CT scan shows a central right upper lobe mass, with collapse and extensive mediastinal adenopathy. Blodd gases are within normal limits, but spirometry shows an obstructive pattern.

30. Question #1 (cont.) • The next step in management of this patient would be: • Immediate radiotherapy • Immediate chemotherapy • Bronchoscopy • Mediastinoscopy • Intravenous furosemide

31. Question # 2 • A 36-year old woman with no previous medical history presents with an eczematoid scaly eruption on her left nipple. She says that she has recently taken up jogging and this has irritated her breast.

32. Question # 2 (cont.) • On physical examination, she has a 1-cm reddened and slighlty crusty lesion on the left nipple. There is no discharge or masses or other abnormalities on either breast. Topical skin treatment with emollients and corticosteroids is prescribed, and she is told to return for re-examination in 2 weeks. At return 2 weeks later, the crust is somewhat decreased, but the scaly eruption on the nipple is still present, although somewhat diminished. She has continued to jog.

33. Question # 2 (cont.) • Which of the following is the best course of management? • Continue topical therapy • Continue topical therapy, and recommend she wear a running bra or consider stopping her jogging program • Continue topical therapy, but add an antifungal agent • Order a mammogram, and refer her to a surgeon for biopsy • Order a mammogram, and if negative, continue topical therapy.

34. Question # 3 • A 70-year old male with advanced hormone-refractory prostate cancer presents with multifocal pain, especially in hiss back. He has been treated by bilateral orchiectomy and radiotherapy to the hemipelvis. His PSA is 100 ng/mL, and a recent bone scan showed multiple “hot spots”. He states that he also has noticed increasing weakness of the lower limbs and severe constipation despite the use of stool softeners.

35. Question # 3 (cont.) • The next step in management should be: • Cytotoxic chemotherapy • Referral for physical therapy • MRI of the spine • Increased laxatives • Referral for radioactive strontium