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  1. ONCOLOGY BOARD REVIEW Calvin Thigpen, M.D. July 18, 2014

  2. If you could only… Study 5 things in oncology, they should be: • Breast Cancer • Lung Cancer • Colon Cancer • Prostate Cancer • Complications (of these diseases and their therapy)

  3. As you study… Pay close attention to: • Interventions that lead to a cure • Emergent situations • Inherited conditions • Atypical approaches to cancer care These are the kinds of things practicing general internists need to know.

  4. Breast Cancer It will DEFINITELY be on the exam.

  5. What they will ask • Risk factors • Locoregional disease therapy • Hormone/endocrine therapy • Indications • Side effects • Recurrent disease

  6. What they won’t ask • Exactly when to start, or how often to get, mammograms • Specific combinations of chemotherapy

  7. Look for this in the stem • Age and family history • Menopausal status • Exposure to estrogen • Hormone receptor status • Previous cancer therapy • Site of metastasis • Drugs

  8. We Are Young A nulliparous 29-year-old Ashkenazi Jewish woman has a palpable left breast mass present for 6 months. Her mother was adopted; her father is 72 years old and has a history of prostate cancer. Her paternal aunt was diagnosed with ovarian cancer at age 48 years. Another paternal aunt was diagnosed with breast cancer at age 49 years. Her paternal grandmother died of complications from breast cancer at age 60 years. On exam, there is a 4-cm mass in the left breast affixed to the chest wall and a 1-cm, freely movable left axillary lymph node. Biopsy reveals moderately differentiated ER+, PR+, H2N- invasive ductal carcinoma. CT and bone scan show no metastatic disease. She will receive preoperative chemotherapy followed by surgery. Which of the following will be most helpful in determining the best surgical approach? A. Counseling and genetic testing B. Genomic profile assay C. PET scan D. Tumor marker testing

  9. Key Point For women who have breast cancer and are at high risk for BRCA1 or BRCA2 mutations, genetic testing and counseling may inform surgical options.

  10. BRCA1 and BRCA2 risk • 2 1st degree relatives with breast cancer (one at <50 years of age) • 3 or more 1st or 2nd degree relatives with breast cancer regardless of age; • Both breast and ovarian cancer among 1st and 2nd degree relatives; • 1st degree relative with bilateral breast cancer; • 2 or more 1st or 2nd degree relatives with ovarian cancer regardless of age; • 1st or 2nd degree relative with both breast and ovarian cancer at any age; or • Breast cancer in a male relative.

  11. Why genetic testing? • The history suggests genetic cancer • Test results either: • Establish the diagnosis • Influence the management of family members at risk • Test those already with cancer if at all possible

  12. I Can’t Go For That A 65-year-old woman is evaluated for a 2-cm right breast mass discovered on routine mammography. Vital signs and physical exam are unremarkable, and there is no palpable breast mass or lymphadenopathy. Ultrasound-guided needle biopsy reveals a well-differentiated, ER+, PR+, H2N- invasive ductal carcinoma. Which of the following is the most appropriate next step in management? A. Right breast lumpectomy B. Right breast lumpectomy, sentinel lymph node biopsy, and radiation C. Right breast mastectomy D. Right breast mastectomy, sentinel lymph node biopsy, and radiation

  13. Key Point Breast conservation therapy, which consists of excision of the primary tumor and radiation therapy, is equivalent to mastectomy in long-term survival.

  14. Primary therapy • All breast cancer patients need surgery at some point. • Breast-conserving therapy is equivalent to mastectomy. • Sentinel lymph node biopsy: • For clinically lymph node negative disease • Fewer side effects (far less lymphedema) • Adjuvant radiation reduces local recurrence.

  15. Endocrine therapy • ER+/PR+ • Premenopausal • Tamoxifen for 5 years • If tumor large, chemotherapy + Tamoxifen • Postmenopausal • Aromatase inhibitor (anastrazole, letrozole, exemestane) for 5 years • +/- Tamoxifen for 5 years prior to AI • If tumor large, chemotherapy + AI • H2N+ • One year of Trastuzumab

  16. Hormone Therapy

  17. Systemic therapy For those with the two most important prognostic factors: • Positive lymph nodes • Larger tumors (>1 cm)

  18. Metastatic therapy • Endocrine therapy + chemotherapy • Endocrine therapy • Premenopausal – Tamoxifen • Postmenopausal – Aromatase inhibitor • Chemotherapy • Sequential single agents equivalent to combination • Anthracyclines, Taxanes, Methotrexate, Cytoxan, 5-FU • H2N • Trastuzumab • In combination with chemotherapy or not • Zoledronic acid or denosumab for bony disease

  19. She’s Always a Woman A 45-year-old woman undergoes evaluation after a recent diagnosis of stage II ER+, PR+, H2N- breast cancer. She is premenopausal. She was treated with modified radical mastectomy and just completed adjuvant chemotherapy. She had a DVT associated with oral contraceptive pill use 20 years ago. She is a nonsmoker and is very physically active. Physical exam and labs are unremarkable. Which of the following is the most appropriate next step in management? A. Adjuvant aromatase inhibitor therapy B. Adjuvant trastuzumab therapy C. Baseline imaging with whole-body CT scan or PET scan D. Ovarian ablation

  20. Key Point Tamoxifen can increase the risk for thromboembolic complications.

  21. Hello Again A 60-year-old woman is evaluated for 6 weeks of worsening left hip and right arm pain. She had stage III ER+, PR+, HER2- breast cancer diagnosed 5 years agoand treated withmodified radical mastectomy, chemotherapy, and radiation. She declined adjuvant hormonal therapy. Physical exam reveals tenderness over the left sacroiliac joint and the right humerus. Bone scan shows uptake in the bilateral femurs, lumbar spine, and right humerus consistent with metastases. CT shows no abnormalities in the lungs or liver, but bony lesions are evident and are consistent with the bone scan findings. No pathologic fractures are present. Which of the following is the most appropriate intervention? A. Aromatase inhibitor B. Bone biopsy C. Chemotherapy D. Radiation therapy E. Trastuzumab therapy

  22. Key Point A lesion due to a first recurrence of breast cancer should be biopsied to confirm malignancy and hormone receptor and HER2 status, which then guides treatment.

  23. Tamoxifen • Originally, the only FDA approved drug for primary breast cancer prevention (5 years) • Used in adjuvant treatment for ER+ tumors to reduce the risk of recurrence (5 years) • Used in treatment of ER+ metastatic breast cancer • Side effects: • Thromboembolism • Endometrial cancer • Serotonin syndrome (when given with SSRIs)

  24. Aromatase inhibitors • Anastrazole, letrozole, exemestane • Adjuvant therapy for postmenopausal women with ER+ tumors to prevent recurrence • Therapy for postmenopausal women with metastatic ER+ tumors • Side effects: • Hot flashes • Arthralgias • Osteoporosis

  25. Anthracyclines • Doxorubicin, epirubicin, daunorubicin • Reduce dose for hepatic dysfunction • Cardiac toxicity • Determined by cumulative dose of drug • Cardiomyopathy largely irreversible, difficult to treat

  26. Trastuzumab (Herceptin) • For women with Her-2-neu + tumors • To be given for 52 weeks as adjuvant therapy • Reduces recurrence by 50% • Reduces mortality by up to 30% • Given in metastatic disease • MAJOR side effect – can induce heart failure • Especially when given with an anthracycline (so don’t do it) • Monitor LV EF before, during, and after treatment

  27. I Gotta Feeling A 45-year-old woman is evaluated for severe hot flushes that significantly limit her quality of life as well as vaginal dryness that is controlled with local lubricants. She had stage II ER+, PR+, HER2- invasive breast cancer diagnosed 1 year ago and treated with lumpectomy, chemotherapy, and radiation therapy. She has not had a menstrual cycle since her 4th cycle of chemotherapy. She began taking tamoxifen 3 months ago after completing radiation therapy. Nonpharmacologic interventions for hot flushes have brought no improvement. Physical exam is normal other than evidence of surgery on the left breast and radiation changes on her skin. Which of the following is the most appropriate therapy for this patient? A. Fluoxetine B. Low-dose estrogen-progesterone C. Red clover D. Venlafaxine

  28. Key Point Selective serotonin reuptake inhibitors that are potent CYP2D6 inhibitors (such as fluoxetine and paroxetine) should be avoided in patients with menopausal symptoms caused by tamoxifen.

  29. 50 Ways to Say Goodbye A 65-year-old woman is evaluated during a routine examination. She is asymptomatic. She had stage I ER-, PR-, HER2- breast cancer diagnosed 3 years ago treated with modified radical mastectomy followed by chemotherapy with docetaxel and cyclophosphamide. On physical exam, the left chest wall is well healed with no nodularity. No right breast masses, axillary lymphadenopathy, or supraclavicular lymphadenopathy arepresent. The patient will undergo periodic mammography and routine health maintenance. Which of the following would be the most appropriate additional evaluation in this patient? A. Bone scan yearly B. CT scan yearly C. PET scan yearly D. Tumor marker measurement, complete blood count, and comprehensive metabolic panel yearly E. No additional studies

  30. Key Point The use of screening blood tests (including tumor markers) and imaging is not recommended for routine breast cancer follow-up in an otherwise asymptomatic patient with no specific findings on clinical examination.

  31. Lung Cancer The most common and the biggest killer

  32. What they may ask • Knowing when to search for it – smoker with symptoms • Non-small cell • Early stage therapy – surgery or radiation • Metastatic therapy – platinum-based chemotherapy • Isolated recurrent therapy – resection, then chemotherapy

  33. What they may ask • Small cell • Limited stage therapy – concurrent chemoradiation, then prophylactic brain irradiation • Extended stage therapy – platinum-based chemotherapy

  34. What they won’t ask • Specifics of staging in non small cell • Use of gamma knife radiation in brain metastases • Specific combinations of chemotherapy

  35. A few definitions… • Non small cell • Early stage – I or II • Tumor confined to one lobe • No mediastinal nodes • Advanced stage – III • Another nodule in the same lung • Mediastinal nodes • Metastatic disease • Nodule in opposite lung • Pleural effusion • Disease in other organs

  36. A few definitions… • Small cell • Limited stage • Disease confined to one hemithorax or radiation port • Includes mediastinal and ipsilateral supraclavicular nodes • Extensive stage • Any spread outside of the above • 1/3 of the time, this is in the brain

  37. …and generalities… • Non-small cell • Slower growing • Not very chemo- or radiosensitive • Resect disease confined to one lobe and nodes on one side • Small cell • Faster growing • Very chemo- and radiosensitive • Surgery only accidentally

  38. …and paraneoplasias • Hypercalcemia – PTHrP – squamous cell • Hyponatremia – ectopic ADH – small cell • Cushing’s syndrome – from ectopic ACTH – small cell • Hypertrophic pulmonary osteoarthropathy • Lambert-Eaton Syndrome • Cerebellar degeneration

  39. Non-small cell lung cancer More serious than the common cold

  40. Keep the Faith A 56-year-old woman is evaluated for a persistent cough of 2.5 months' duration. She also notes a 10-lb weight loss. The patient has no history of pulmonary disease and has never smoked cigarettes. Physical exam is unremarkable. Right hilar and subcarinal lymphadenopathy, as well as several hepatic hypodensities consistent with metastatic disease, are identified on CT of the chest and abdomen. MRI brain is normal. Bone scan notes uptake in several ribs. Lung biopsy demonstrates adenocarcinoma. Which of the following is the most appropriate next step in the evaluation of this patient? A. CT-guided biopsy of the liver B. Epidermal growth factor receptor mutation tumor analysis C. Mediastinoscopy with biopsy D. Serum chromogranin measurement

  41. Key Point Patients with epidermal growth factor receptor (EGFR) gene tumor mutations—most commonly women with adenocarcinoma who are never smokers or have a very limited smoking history and women of East Asian descent—often benefit dramatically from therapy targeting this receptor.

  42. Who gets the knife? • Patients with no evidence of nodal disease, or with nodal disease only in the ipsilateral lung (and hilum) on PET, PET/CT, or medastinoscopy • Patients with a single lesion recurrence in the liver or brain • Patients with cord compression • Patients with a good performance status Remember this is in non-small cell only!

  43. Who gets chemo? Anyone with positive lymph nodes or metastatic disease

  44. Who gets radiation? • Any patient who was a candidate for surgery, but for their functional status • Patients with localized pain from their tumor • Patients with brain metastases • Patients with cord compression where surgery was not performed

  45. I’m Coming Out A 52-year-old man is evaluated for a 5-week history of hemoptysis, a 6-month history of cough, and a 10-lb weight loss. He has a 60-pack-year smoking history. On physical exam, he hasexpiratory wheezing localized to the left upper pulmonary lobe. CT of the thorax and abdomen reveals a 7-cm pulmonary mass in the left upper lobe and small mediastinal lymph node enlargement. Biopsy of the lung lesion shows squamous cell carcinoma. A PET/CT shows extensive uptake in the mass but a low level of uptake in the mediastinal nodes. An MRI brain is normal. Mediastinoscopy and lymph node sampling reveal no evidence of cancer. Stage II disease is confirmed. Which of the following is the most appropriate treatment of this patient? A. Combination radiation and chemotherapy B. Surgical resection C. Surgical resection followed by chemotherapy D. Systemic chemotherapy

  46. Key Point Stage II non-small cell lung cancer is potentially curable with surgical resection and adjuvant postoperative chemotherapy to reduce the recurrence risk.

  47. Troublemaker A 54-year-old woman is evaluated for shortness of breath of 3 months' duration and a 10-lb weight loss. She has a 35-pack-year smoking history. On physical exam, O2 sat is 92% on room air. The patient has clubbing of the fingertips. The lung fields are clear on the left, with diminished breath sounds and dullness to percussion over the lower half of the right lung. CXR reveals a large right pleural effusion. A thoracentesis demonstrates an exudate, with cytologic analysis indicating adenocarcinoma. A chest tube is placed, and talc pleurodesis is performed. A CT scan reveals a 4-cm right peripheral lung mass with no obvious lymphadenopathy. A bone scan and brain MRI are normal. Which of the following is the most appropriate treatment? A. Combination chemotherapy and radiation B. Radiation C. Surgical resection of the lung mass D. Systemic chemotherapy

  48. Key Point Patients with non-small cell lung cancer and a malignant pleural effusion have, by definition, metastatic disease, and the most appropriate therapy is palliative systemic chemotherapy.

  49. Small Cell Lung Cancer Not a small deal

  50. Always on My Mind A 65-year-old man is evaluated for a 3-week history of hemoptysis and a recent 10-lb weight loss. He has a 90-pack-year smoking history. On physical exam, vital signs are normal. The pulmonary exam reveals occasional crackles at the posterior right midlung field. CT of the chest shows a 5-cm right hilar mass with bulky mediastinal lymphadenopathy. Bronchoscopy reveals small cell lung cancer. MRI brain and bone scan are negative. The patient receives 6cycles of cisplatin and etoposide chemotherapy with radiation to the lung mass and regional disease concurrent with the first cycle of chemotherapy. A follow-up CT chest shows a residual 1.5-cm right hilar abnormality. Which of the following is the most appropriate next step in this patient's management? A. Biopsy of the residual mass B. Three additional cycles of chemotherapy C. Whole-brain radiation D. Observation