JENNY MORRISON AM REPORT6/10/2009

Oncology Board Review

Overview

Cancer statisticsMalignancies

Breast Cancer Ovarian Cancer Prostate Cancer Testicular Cancer GI Malignancies Lung Cancer Bladder Cancer Head and Neck Cancer Random topics we missed on in service exam…

Estimated New Cases

1. Prostate2. Lung3. Colorectal4. Bladder5. Melanoma6. NHL7. Kidney8. Leukemia9. Head and Neck10.Pancreatic

1. Breast2. Lung3. Colorectal4. Uterine5. NHL6. Melanoma7. Thyroid8. Kidney9. Ovary10.Pancreatic

MALE FEMALE

Cancer Facts and Figures 2009 from American Cancer Society

Estimated Deaths

1. Lung2. Prostate3. Colorectal4. Pancreas5. Leukemia6. Liver7. Esophageal8. Bladder9. NHL10.Kidney

1. Lung2. Breast3. Colorectal4. Pancreas5. Ovarian6. NHL7. Leukemia8. Uterine9. Liver10.Brain

MALE FEMALE

Cancer Facts and Figures 2009 from American Cancer Society

Breast Cancer

Most frequently diagnosed cancer in women.

Ranks 2nd of cancer deaths in women.RF: Age, sex, genetics (BRCA1 and 2),

personal or family hx of breast CA, hx of XRT to chest, long menstrual hx (early menarche, late menopause), nulliparity, hormone therapy, 1st child after age 30, exogenous estrogen use

Breast Cancer

USPSTF recommends screening w/ mammography +/- CBE every 1-2 years starting at age 40. Evidence is strongest for women aged 50-69.

Over age 70, continue screening if life expectancy is at least 10 years.

For women 20-39, screen with CBE Q3yrs.For those at increased risk (ex. family hx), consider

screening earlier (ex. 5-10 years younger than youngest affected family member), consider alternative modalities such as MRI or u/s.

Testing for BRCA1 and 2 should only be performed in those with strong family hx of premenopausal breast cancer.

Breast Cancer

Tamoxifen (a SERM) may be used to decrease risk in those considered at high risk. Tamoxifen may increase risk for thrombosis and

uterine cancer. Raloxifene may also decrease risk.

Aromatase inhibitors (anastrozole, letrozole, exemestane) may reduce risk even further (under investigation). AI’s are associated with increased risk of

osteoporosis (as well as menopausal sx).

Breast Cancer

Recent declines in breast cancer mortality attributed to earlier detection and improved treatments.

Mammography detects ~80-90% of breast cancers in women without symptoms.

If at high risk, MRI may be more sensitive in detecting tumors.

Sentinel LN bx may be used in early stage breast cancer to detect spread to regional LN may prevent unnecessary axillary LND.

Breast Cancer

Primary therapy is surgical. Survival rates similar b/t lumpectomy + XRT and mastectomy are similar.

Adjuvant chemo is appropriate for pts at high risk for distant recurrence but who do not have detectable metastases.

Endocrine therapy (ovarian ablation- surgical or w/ meds) may be beneficial in ER+, PR+ tumors. Tamoxifen is used as adjuvant therapy for 5 years after surgical treatment of ER+ tumors. AI’s are another choice to use in lieu of or after Tamoxifen therapy.

Trastuzumab may be used in HER2 overexpressing tumors. DCIS should be treated- lumpectomy + XRT or mastectomy

followed by Tamoxifen. 5 year survival (all stages combined) is 89%.

Ovarian Cancer

S/sx: Abdominal swelling/ascites, bloating, pelvic or abdominal pain, early satiety, urinary urgency or frequency, bowel obstruction.

RF: Age (peaks in late 70’s), nulliparity, HRT with estrogen alone, family hx of breast/ovarian cancer, genetics (BRCA1 or 2, possibly HNPCC).

Pregnancy, long-term OCP use and possibly BTL and TAH decrease risk.

Serum CA-125 and u/s can detect early stage disease, but given low prevalence, routine screening is not performed in the general population.

Ovarian Cancer

Ovarian cancer likes to spread within the abdominal cavity ( ascites, bowel obstruction). It rarely metastasizes to liver, bone, lung, or brain.

Ovarian cancer is staged surgically.Treat with surgery, chemo (platinum or

taxane-based), and occasionally with XRT.Only 19% are detected at localized stage (5

yr 92%).Overall, 5 year survival 45%.

Uterine/Endometrial Cancer

S/sx: abnormal uterine bleeding or spotting, dysuria, dyspareunia, pelvic pain.

RF: estrogen (especially when taken without progestin), obesity, tamoxifen use (slight increase in risk), early menarche, late menopause, nulliparity, hx of PCOS, infertility, Lynch syndrome (HNPCC).

HRT (estrogen + progesterone) does not appear to increase risk.

Pregnancy and OCP use are protective.Typically diagnosed early during evaluation for

postmenopausal bleeding ( endometrial bx).Treat w/ surgery, XRT, hormones, +/- chemo.5 year survival is 83%.

Prostate Cancer

Most common cancer diagnosis in men.2nd leading cause of cancer deaths in men.Incidence higher among African American men. Death

rates are twice as high in AAM than Caucasians.RF: age (>65), ethnicity, family hx.Finasteride decreases risk for prostate CA in men >55.S/sx: Weak or interrupted urinary flow, inability to

urinate or difficulty starting or stopping stream, urinary frequency, nocturia, hematuria, dysuria, bony pain in hips, spine, ribs.

Most pts w/ prostate CA are asx at presentation with only an elevated PSA.

Prostate Cancer

There is insufficient data to recommend for or against screening men of average risk with age <75. They recommend against screening if age ≥75. (USPSTF)

PSA and DRE should be offered annually to men of average risk starting at age 50. (ACS)

For high risk individuals (African American men or strong family hx), screening should begin at age 45. (ACS)

Clinical stage, Gleason score, and serum (pretreatment) PSA are used to guide treatment.

Given slow progression of most prostate CA, comorbidities and life expectancy should be considered in treatment plans.

Prostate Cancer

If decision is made to screen, screen with PSA +/- DRE every 2-4 years.

If prostate exam is abnormal (nodules, induration, asymmetry), you should refer them to Urology.

If PSA is elevated, you should either repeat PSA several weeks later (esp if borderline- PSA 3-7) or refer for transrectal ultrasound-guided prostate biopsy.

Transient elevations in PSA can occur due to ejaculation, perineal trauma, or prostatitis.

Therefore, before retesting, pt needs to avoid ejaculation and bike riding for 48 hrs prior, and prostatitis should be treated with antibiotics.

Though PSA up to 4.0 is “normal,” some recommend following or further w/u of level >3.0.

Stop screening if <10 yr life expectancy or age >75.

Prostate Cancer

Radical prostatectomy, external beam radiation, brachytherapy, cryotherapy, hormonal therapy are used in treatment. For less aggressive tumors, some employ “watchful waiting.” Radical prostatectomy improves survival over watchful

waiting. Pts who receive definitive local therapy have 30-40%

recurrence within 5 years (as detected by rising PSA).

Prostate Cancer

Advanced/metastatic disease is usually treated w/ bilateral orchiectomy or GnRH agonists +/- antiandrogen therapy. Antiandrogen therapy is typically used at onset of therapy with

LHRH analogs to avoid “flare”- as testosterone levels initially rise with onset of therapy before falling. With this testosterone increase, sx from tumor burden may worsen.

Side effects of therapy: osteoporosis, hot flashes, impotence, loss of libido, gynecomastia.

GnRH/LHRH agonists Gosrelin Zoladex Leuprolide Lupron

Antiandrogens Bicalutamide Casodex Flutamide Eulexin

Prostate Cancer

Hormone-refractory disease is defined as progression despite having a castrate level (<50 ng/dl) of testosterone. Most patients will progress on androgen deprivation

therapy after a median of 18-24 months. Thereafter, the median survival is about one year.

Chemotherapy may improve survival w/ metastatic androgen-independent prostate cancer, though traditionally, prostate CA has been view as relatively chemo-resistant.

5 year survival for prostate cancer overall is 99%.

Testicular Cancer

Most common solid malignancy affecting males 15-35.Germ cell tumors account for 95% of testicular

cancers broken down into pure seminomas and nonseminomatous germ cell tumors (NSGCTs). NSGCT’s include embryonal carcinoma, teratoma,

choriocarcinoma, yolk-sac carcinoma.S/sx: nodule or painless swelling of one testicle, dull

ache or heavy sensation in lower abdomen, perianal area, or scrotum. Acute pain in only 10%. Metastatic disease s/sx in 10% (neck mass, cough or

dyspnea, anorexia, N/V, back pain, bone pain, CNS sx, LE swelling).

Gynecomastia and hyperthyroidism are endocrine manifestations from hCG production.

Testicular Cancer

Evaluation starts with bimanual exam of scrotum.DDx of testicular mass: testicular torsion, epididymitis,

epididymoorchitis, hydrocele, varicocele, hernia, hematoma, spermatocele, syphilitic gumma, cancer.

Ultrasonography is indicated with suspected tumor or abnormality found on exam. Other radiographic studies may also be indicated (CT A/P, CXR). U/S good at distinguishing intrinsic from extrinsic lesions.

Measurement of serum tumor markers (AFP, β-hCG, LDH). Beta-hCG and/or AFP are elevated in 80-85% of men with

NSGCT’s. Serum beta-hCG is elevated in fever than 20% of seminomas. AFP is not elevated in pure seminomas. Useful for subsequent follow-up of disease status after primary

trx.

Testicular Cancer

Prior to the 1970’s, death from testicular cancer accounted for 11% of all cancer deaths in men 25-34. It has now become one of the most curable of solid neoplasms due to treatment advances. 5-year survival rate is 95.5%.

Management/treatment radical inguinal orchiectomy +/- retroperitoneal LN dissection

Initial therapy is based on histology (seminoma vs NSGCT) and disease stage (TNM +tumor markers).

Consider semen cryopreservation for future fertility.

Testicular Cancer

Compared to NSGCT’s, pure seminomas are more likely to be localized at presentation. 80% seminomas present with stage I disease, 15% stage II Seminomas rarely spread via bloodstream. Therefore, mets

to liver, lung, bone, brain are more likely to be NSGCT.Seminomas are exquisitely sensitive to RT, while

NSGCT’s are more radioresistant.AFP or beta-hCG are elevated in 85% of NSGCT’s.Treatment options include excision +/- watchful

waiting, radiation, chemo (platinum-based regimens).Follow tumor markers (if initially elevated), imaging.

Colorectal Cancer

Ranks 3rd in cancer diagnoses and deaths for both men and women.

Incidence rates are decreasing over past 2 decades- likely due to increased screening w/ polyp removal.

RF: age (>50), genetics (FAP, HNPCC), personal or family hx, chronic IBD, obesity, inactivity, smoking, EtOH, red-meat rich diet, poor fruit/veggie intake.

NSAIDs/ASA, hormones (estrogen, progestin) may decrease risk.

S/sx: none, rectal bleeding or blood in stool, change in bowel habits- constipation or diarrhea, change in stool caliber, lower abdominal cramping, weight loss, fatigue.

Colorectal Cancer

At age 50, those at average risk should begin screening.

If 1st deg relative w/ colon CA before age 60, start screening at age 40 or 10 years younger than age that relative had cancer.

If 2 relatives w/ cancer at any age, start screening at 40 or 10 years younger than the youngest family member with colon CA.

Colorectal Cancer

Treatment: Surgery (resection of tumor, adjacent mesentary, regional LN’s), chemo (5’FU-based) +/- XRT. For rectal CA, often use preoperative XRT (+/- chemo) to shrink tumor burden-

goal for sphincter preservation, followed by adjuvant chemo/XRT. New targeted therapies include Bevacizumab (blocks blood vessels growth

feeding tumor) and Cetuximab and Panitumumab (block hormone pathways promoting cancer cell growth).

Colon CA typically spreads to liver, though rectal CA may bypass liver and spread to lungs via paravertebral venous and lymphatic channels.

Surveillance: CEA Q3mos for 2 yrs, colonoscopy Q3-5yrs. CEA is elevated in 2/3 recurrences, though measurement has not been shown to improve survival.

5 year survival 64% (all stages).

Gastric Cancer

Incidence increases with increasing age, peaks in 60’s. Disease is typically advanced or metastatic at time of dx.

Antrum and lower ½ of stomach are most common sites. Increased incidence recently in proximal gastric adenoCA’s and distal GE junction adenoCA’s.

RF: smoking, H. pylori, chronic gastritis, pernicious anemia, family hx, genetics (FAP, Lynch syndr), Menetrier’s disease, intestinal metaplasia, diet low in fruits/veggies and high in smoked, salted, or preserved foods.

S/sx: weight loss, abdominal pain, nausea, anorexia, dysphagia, anemia, +hemoccult, abnl LFT’s.

Treatment is surgical, +/- adjuvant chemo/XRT.

Pancreatic Cancer

Ranks 4th in cancer deaths (both men and women).RF: increasing age, smoking, family hx, and

possibly obesity, chronic pancreatitis, diabetes, cirrhosis.

95% of tumors arise in the exocrine pancreas, 50% in the head of the pancreas.

CA 19-9 is frequently elevated.Typically develops without early sx, therefore,

only ~7% are diagnosed at an early stage.S/sx: weight loss, abdominal pain, lumbar back

pain, anorexia, nausea, occasionally glucose intolerance, jaundice, VTE.

Pancreatic Cancer

Surgery, XRT/chemo are treatment options- used to extend survival or palliate but rarely lead to cure (unless disease is localized).

Gemcitabine is often used for pts with metastatic disease and good performance status.

Overall 5 year survival 5%. Poor prognosis even for those with localized

disease- 5 year survival 20%.

Lung Cancer

Leads cancer deaths in men and women.14% lung cancers are small cell.S/sx: New/worsening cough, hemoptysis, chest pain,

voice change, recurrent PNA or bronchitis, pleuritic CP.

Apical tumors may lead to Pancoast syndrome- shoulder pain, lower brachial plexopathy, Horner’s syndrome.

RF: Smoking, occupational or environmental exposures (smoke, asbestos, radiation), hx of TB

Efforts at early detection have not been shown to reduce mortality.

There is an ongoing trial to assess whether screening high risk individuals with CXR or CT may prevent lung cancer deaths.

Lung Cancer

PET scans routinely used in staging.NSCLC metastatic disease often precludes resection.Treatments include surgery, XRT, chemo, and targeted

biologics (Bevacizumab, Erlotinib, Geftinib).Studies have shown that survival with early stage

NSCLC is improved w/ chemo after surgery.Small cell is presumed to be disseminated. Cure is rare.Chemo +/- XRT is treatment of choice for small cell.5 year survival rate is 15% for all stages combined (49%

for localized disease).

Lung Cancer

Regarding management of hemoptysis in lung cancer pt…

Bronchogenic carcinoma is an infrequent cause of massive bleeding but commonly causes nonmassive hemoptysis.

Hemoptysis is common in pts with bronchial carcinoid tumors.

Only 3% of lung cancer pt had massive, terminal hemoptysis and these pts typically had large, centrally-located tumors, esp squamous cell carcinoma.

Lung Cancer

Acute mgmt- airway protection, oxygenation, ventilation, cardiovascular function. Reverse coagulation disorders. C/s pulm, thoracic surgery, +/- VIR. Once stable, bronchoscopy.

Place bleeding lung in dependent position. May need to selectively intubate contralateral bronchus. Bronchoscopy balloon tamponade, topical epi,

vasopressin, or thrombin, laser therapy or electrocautery. VIR arterial embolization Surgical contraindications include severe underlying

pulmonary disease, active TB, diffuse underlying lung disease (CF, multiple AVM’s, multifocal bronchiectasis), diffuse alveolar hemorrhage

Bladder Cancer

Incidence is ~4 times higher in men than in women and almost 2 times higher in Caucasians than AA.

S/sx: hematuria, increased urinary frequency.RF: Smoking, exposure to dye, rubber, and

leather industries, arsenic exposure.Dx by cystoscopy, examination of bladder

washings.Treatment is primarily surgical (+/- neoadjuvant

chemo, XRT), though intravesicular immunotherapy or chemo may be used.

5 year survival is 80%.

Head and Neck Cancer

Incidence is twice as high in men than in women.

S/sx: Sore that bleeds easily and does not heal, lump or thickening, ear pain, neck mass, hemoptysis, red or white patch that persists. Later sx include trouble chewing or swallowing, difficult/decreased mobility of jaw or tongue.

RF: Tobacco (smoked or chewed), EtOH.XRT and surgery, +/- chemo. Targeted therapy

with Cetuximab may be combined with XRT in initial treatment or used alone in recurrences.

5 year survival 59%.

Screening for 2◦ Cancers after HL Treatment

After treatment of Hodgkin Lymphoma, there is an increased risk of developing leukemia, NHL, or solid tumors (lung, breast, bone, stomach, colon, thyroid, melanoma). Risk for leukemia (typically AML) is related to use of

alkylating chemo agents whereas XRT (+/- chemo) is more-associated with solid tumor development.

~1/2 to 2/3 of 2nd malignancies are solid tumors that arise after ≥15 years of follow up.

Screening for 2◦ Cancers after HL Treatment

Lung and breast cancers are most common solid 2nd malignancies. Recommend annual chest imaging for those at

increased risk of lung CA (had chest XRT, treated with alkylating agent, +smoker).

Annual mammogram or breast MRI- initiate 8-10 yrs post therapy or age 40, whichever comes first if pt had chest or axillary XRT. ACS recommends breast MRI + mammogram for women who received XRT to chest b/t ages 10-30.

Paraneoplastic Erythrocytosis

Which of the following tumors is associated erythrocytosis? Hepatocellular Carcinoma Renal Cell Carcinoma Hemangioblastoma Pheochromocytoma Uterine myomata All of the above

Paraneoplastic Erythrocytosis

Which of the following tumors is associated erythrocytosis? Hepatocellular Carcinoma Renal Cell Carcinoma Hemangioblastoma Pheochromocytoma Uterine myomata All of the above

Caused by overproduction of Epo.This is in contrast to polycythemia vera, which is

characterized by a low serum Epo level. (PV is due to an essential increase in erythrocyte production by the bone marrow.)

References

Collichio, F., et al. A Manual for Medical Residents and Trainees in Medical Oncology . 2003.

Fletcher, S. W. and J. G. Elmore. Mammographic Screening for Breast Cancer. 2003. NEJM. 348: 1672-80.

MKSAP 14: Hematology and Oncology. 2006. 56-85. www.uptodate.com www.cancer.org

Cancer Facts & Figures 2009. (American Cancer Society) www.cancer.gov www.nccn.org www.ahrq.gov (USPSTF)