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

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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 It will DEFINITELY be on the exam.
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) 2 or more 1st or 2nd degree relatives with ovarian cancer regardless of age; 3 or more 1st or 2nd degree relatives with breast cancer regardless of age; 1st or 2nd degree relative with both breast and ovarian cancer at any age; or Both breast and ovarian cancer among 1st and 2nd degree relatives; Breast cancer in a male relative. 1st degree relative with bilateral breast cancer;

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+ H2N+ Premenopausal Postmenopausal
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 Premenopausal Postmenopausal Primary prevention
Tamoxifen Tamoxifen, OR Raloxifene, OR Aromatase Inhibitor Adjuvant therapy Small tumor (≤ 1 cm) Tamoxifen x 5 yrs Tamoxifen x 5 yrs followed by AI x 5 yrs, OR AI x 5 yrs Big tumor and/or +LN Tamoxifen x 5 yrs, PLUS chemotherapy Tamoxifen x 5 yrs followed by AI x 5 yrs, OR AI x 5 yrs (both + chemotherapy) Metastatic therapy Non-visceral disease Tamoxifen +/- chemotherapy AI +/- chemotherapy Visceral disease Tamoxifen + chemotherapy AI + chemotherapy

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
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 Tamoxifen can increase the risk for thromboembolic complications.
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 ago and treated with modified 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 are present. 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 The most common and the biggest killer
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 Extensive 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 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 Remember this is in non-small cell only!
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 Anyone with positive lymph nodes or metastatic disease
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 has expiratory 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 6 cycles 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

51 Key Point Patients with limited-stage small cell lung cancer who respond to chemotherapy and radiation should receive prophylactic brain irradiation to decrease central nervous system relapses and prolong median survival.

52 In small cell, they all do!
Who gets chemo? In small cell, they all do!

53 In small cell, no one does! (at least for the board exam)
Who gets the knife? In small cell, no one does! (at least for the board exam)

54 Remember that we’re talking about small cell here!
Who gets radiation? Patients with limited stage disease – to the chest Patients with limited stage disease and good response to chest therapy – to the brain prophylactically Patients with extensive stage disease (and no brain mets) who respond to therapy Patients with brain mets Remember that we’re talking about small cell here!

55 Whip It A 63-year-old man is evaluated for fatigue and a persistent cough of 7 weeks' duration. He has a 60-pack-year smoking history. Physical exam is unremarkable. CT of the thorax shows a right perihilar mass and enlarged hilar and mediastinal lymph nodes. An endobronchial mass is identified by bronchoscopy; brushings and biopsy reveal small cell lung cancer. CT of the abdomen and pelvis is negative. A bone scan and MRI brain are negative. Which of the following is the most appropriate next step in the management of this patient? A. Chemotherapy with adjunctive radiation therapy B. Mediastinoscopy C. Radiation therapy D. Resection for cure

56 Key Point Patients with limited-stage small cell lung cancer are treated with combination chemotherapy and radiation therapy.

57 The 4th most common malignancy, the 2nd leading cause of death
Colorectal Cancer The 4th most common malignancy, the 2nd leading cause of death

58 What they may ask Screening measures Colon cancer
Treatment for node negative disease – surgery Treatment for node positive disease – surgery, then adjuvant chemotherapy Treatment for metastatic disease – surgery, then chemotherapy (with bevacizumab) Treatment for isolated recurrence in the liver – resection Treatment for localized rectal cancer – surgery, then adjuvant chemoradiation

59 All patients with colorectal cancer need surgery! All of them!
Common ground All patients with colorectal cancer need surgery! All of them!

60 What they won’t ask Hair-splitting questions about high-risk Stage II disease The use of monoclonal antibodies other than bevacizumab Chemotherapy combinations for metastatic rectal cancer 2nd line chemotherapy

61 At risk groups FAP – Familial Adenomatous Polyposis
Mutation in the APC gene HNPCC – Hereditary Non-Polyposis Colorectal Cancer Mutation in the MSH2, PMS1, or PMS2 genes At risk for ovarian and endometrial cancer Or any of the following Personal history of adenomatous, villous, or tubulovillous polyps Family history of the same Inflammatory bowel disease Diabetes, obesity, tobacco, alcohol

62 Screening – When? Average risk – age 50
1st degree relative affected (by cancer or with adenomatous polyp) Age 40, OR 10 years younger than the family member was diagnosed

63 Screening – What? Guaiac FOBT – annual
Fecal Immunochemical Testing (FIT) – annual Sigmoidoscopy – every 5 years (with FOBT every 3 years) Colonoscopy – every 10 years (or every 3-5 for those with relatives diagnosed at <60)

64 Surveillance Colon cancer Rectal cancer Perioperative colonoscopy
Colonoscopy at 1 year, repeat in 3 years, then repeat in 5 years (assuming all were normal) CEA every 3 months for 2 years, every 6 months for 3 more years CT Chest/Abdomen/Pelvis annually for 3 years Rectal cancer Same as above, PLUS Proctosigmoidoscopy every 3 to 6 months for 3 years

65 Colon vs. Rectal Colon Rectal Above the peritoneal reflection
Tends to metastasize to the liver first NO ROLE WHATSOEVER FOR RADIATION Rectal Below the peritoneal reflection Can spread to the lungs before the liver Radiation used to reduce local recurrence

66 What chemotherapy? Colon Rectal Oxaliplatin based (often with 5-FU)
With bevacizumab for metastatic disease Rectal 5-FU based for localized disease Metastatic depends on squamous vs. adenocarcinoma (highly unlikely to be tested)

67 Alive and Kicking A 51-year-old man is evaluated for 6 months of increased fatigue and decreased exercise tolerance. He is otherwise well with no significant medical history. Physical exam is unremarkable. FOBT discloses brown, guaiac-positive stool. Labs: Hgb 8.4; MCV 80. Colonoscopy reveals a 5-cm mass in the cecum. Biopsy shows moderately differentiated adenocarcinoma. CT of the chest, abdomen, and pelvis demonstrates the cecal mass and no evidence of metastatic disease. Final pathology from right hemicolectomy reveals a tumor penetrating into the pericolonic fat with clear margins, and 3 of 28 lymph nodes have cancer (T3N1M0; stage III). Which of the following is the most appropriate management? A. 5-Fluorouracil and leucovorin B. 5-Fluorouracil, leucovorin, and oxaliplatin (FOLFOX) C. Radiation therapy D. Radiation therapy plus 5-fluorouracil followed by FOLFOX

68 Key Point An adjuvant chemotherapy regimen of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) has been shown to improve disease-free survival in patients with stage III colon cancer.

69 C’est La Vie A 68-year-old woman underwent right hemicolectomy 2 years ago for stage III colon cancer. She received 6 months of chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) after surgery. On a recent follow-up visit, CEA was 43 ng/mL (upper limit of normal, 5 ng/mL). She has no comorbidities and takes no medications. She works full time and is fully functional. Physical exam reveals a palpable liver edge just below the right costal margin. Labs: Hgb 13.5, WBC 9000, platelets 288,000. CT of the chest, abdomen, and pelvis shows 3 hypodense lesions on the right lobe of the liver ranging from 1.5 to 4.0 cm. Which of the following is the most appropriate management? A. CT-guided fine-needle aspiration of liver lesion B. Hepatic arterial embolization C. Palliative systemic chemotherapy D. Radiation therapy to the liver E. Right hepatectomy

70 Key Point Surgical resection of a few isolated metastatic lesions may be curative for patients with colorectal cancer.

71 The most common cancer in men
Prostate Cancer The most common cancer in men

72 What they may ask Making a decision on whether or not to treat – risk categories Treatment for disease confined to prostate Side effects of therapy Cord compression

73 What they won’t ask Screening recommendations
Differentiating between types of radiation Chemotherapy other than docetaxel

74 Risk categories Risk Tumor Gleason PSA Low Not palpable or visible 2-6
<10 Intermediate Confined to prostate 7 10-20 High Extends outside prostate 8-10 >20

75 Treatment Risk Life Expectancy Treatment Options Low <10 years
Observe Observe, or XRT, or prostatectomy XRT, or prostatectomy Intermediate ≥10 years High <5 years ≥5 years Observe with hormone therapy XRT with hormone therapy, or XRT alone, or prostatectomy

76 I Will Wait An 80-year-old man undergoes an annual physical exam. He has had mild stable nocturia for many years. He reports no bone pain, weight loss, fever, chest pain, or shortness of breath. Medical history is notable for HTN and type 2 DM for which he takes antihypertensive and diabetic medications. Rectal exam reveals an enlarged prostate gland with a nodule on the right side. PSA 6.4 ng/mL. Prostate biopsy reveals several small foci of adenocarcinoma in 2 of 12 cores on the right side, with a Gleason score of 6. Which of the following is the most appropriate management? A. Androgen deprivation therapy B. Radiation with androgen deprivation therapy C. Radical prostatectomy D. Observation

77 Key Point Patients with low-risk prostate cancer and a short life expectancy are optimally managed with observation.

78 Up All Night A 73-year-old man is evaluated for a 6-month history of progressive nocturia. Rectal exam reveals a hard, irregular, and markedly enlarged prostate gland. PSA is 22.5 ng/mL. Bone scan is negative. CT scan reveals a markedly enlarged prostate gland and extension into the seminal vesicles. No lymphadenopathy or evidence of metastatic disease is present. Prostate biopsy reveals adenocarcinoma in all 12 cores with a Gleason score of 8. He has high-risk T3 stage III prostate cancer. Which of the following is the most appropriate treatment? A. Androgen deprivation therapy (ADT) B. ADT and radiation therapy C. Brachytherapy D. Radiation therapy E. Radical prostatectomy

79 Key Point Patients with high-risk prostate cancer are optimally managed with a combination of androgen deprivation therapy and radiation.

80 Order of therapy Surgery and radiation equally effective for early stages Check PSA q6-12 months x 5 years after primary treatment Goal with recurrence: achieve castrate levels of testosterone Orchiectomy or androgen deprivation therapy (ADT) Surgical and hormonal (ADT) castration equivalent Docetaxel based chemotherapy for those who are hormone refractory

81 Hormone therapy? Potential side effects:
Impotence Hot flashes Weight gain Fatigue Gynecomastia Osteopenia Diarrhea Hepatotoxicity Diabetes Cardiovascular disease Observation doesn’t sound so bad

82 Or other therapy? Radiation side effects: Prostatectomy side effects:
Proctitis Cystitis Erectile dysfunction Prostatectomy side effects: Urinary incontinence

83 Back in Time A 55-year-old man is evaluated in the ER for gradually increasing midback pain for 3 weeks. Metastatic prostate cancer was diagnosed 18 months ago and progressed on antiandrogen therapy. He is now taking bicalutamide, zoledronic acid, docetaxel, and prednisone. On physical exam, the lower extremities are diffusely weak. He has diminished pinprick sensation from the nipples downward. Reflexes are 2+ in the biceps and triceps and 3+ in the knees and ankles. An extensor plantar response is present bilaterally. Anal sphincter tone is diminished. IV dexamethasone is administered. MRI confirms spinal cord compression at the 4th thoracic vertebra. Which of the following is the most appropriate next step in treatment? A. Addition of leuprolide B. Anterior surgical decompression C. Radiation therapy D. Substitution of paclitaxel for docetaxel

84 Key Point Clinical outcomes in solid tumors are better with surgical decompression of spinal cord compression than they are with radiation or chemotherapy.

85 Cord Compression Breast, Lung, Prostate (blastic only), Renal, Lymphoma, and Myeloma (lytic only) MRI of the entire spine IV Decadron to reduce vasogenic edema, relieve pain Neurosurgical consultation for surgical decompression and spine stabilization

86 Don’t Know What You Got A 63-year-old woman presents with abrupt onset left upper-extremity weakness and no other symptoms. Until today, she has been active and fully functional. She had stage IIB non-small cell lung cancer diagnosed 1 year ago and underwent right upper lobectomy followed by adjuvant cisplatin and vinorelbine chemotherapy. Mediastinoscopy at the time was negative, and PET showed no metastatic disease. Neurologic exam shows weakness of the left arm with hyperreflexia of the brachioradialis reflex. MRI brain demonstrates a right parietal lesion measuring 1.5 cm, with evidence of significant edema. She has no evidence of extracranial disease. Dexamethasone is initiated. Which of the following is the most appropriate next step in management? A. Best supportive care B. Initiation of erlotinib C. Initiation of temozolomide followed by radiation therapy D. Surgical resection of metastasis

87 Key Point Resect isolated brain (or liver) metastases when there is no other evidence of cancer.

88 Remember Brain mets are life-limiting; they must always be addressed immediately when found. Decadron immediately Surgery Radiation Chemotherapy

89 Head Games A 46-year-old woman is evaluated for the recent onset of headaches that are most intense on waking in the morning and are not relieved by analgesics. She has no nausea or vomiting but notes some difficulty with fine motor skills when using her right hand. The patient has a 2-year history of stage II breast cancer last treated with chemotherapy 2 years ago. Funduscopic exam reveals papilledema. She has reduced strength (4/5+) in her right hand. A CT of the head reveals 2 separate masses in the left temporal lobe with associated edema, as well as blastic lesions involving the skull. Which of the following is the most appropriate management? A. Chemotherapy B. Intravenous dexamethasone and radiation therapy C. Lumbar puncture D. Resection of the masses

90 Key Point Immediate corticosteroid administration and early initiation of radiation therapy are indicated to treat brain metastasis and increased intracranial pressure.

91 Ovarian Cancer

92 Risk and Screening The most significant risk factor for ovarian cancer, especially in premenopausal women, is the presence of BRCA1/BRCA2 gene mutations; hereditary nonpolyposis colorectal cancer syndrome also confers a significantly increased risk. Use of oral contraceptive agents decreases the risk of ovarian cancer by as much as 50% with the protective effect lasting up to 20 years after oral contraception cessation. Screening for ovarian cancer is not recommended for average-risk women. In women at high risk for developing ovarian cancer, prophylactic bilateral salpingo-oophorectomy before age 40 years reduces the risk of developing cancer by 95%.

93 Diagnosis and Staging Most patients with ovarian cancer have advanced disease at initial evaluation. Findings on ultrasonography suggestive of ovarian cancer include a solid mass, a cyst with thick septations, and ascites. The diagnosis of advanced ovarian cancer is usually made by CT or ultrasound-guided biopsy of a suspicious mass or cytologic examination of ascitic fluid.

94 Surgical Role Optimal tumor debulking (no residual tumor mass >1 cm) is associated with increased survival in patients with ovarian cancer. Surgical resection is appropriate for patients with a recurrent solitary ovarian tumor or with limited relapse of cancer at sites favorable for surgical removal.

95 Chemotherapy Adjuvant chemotherapy is indicated for patients with high-risk, early-stage ovarian cancer and those with advanced disease. Use of hematopoietic growth factors to maintain adequate blood counts has helped improve the quality of life and decrease complication rates in patients with ovarian cancer who are receiving chemotherapy.

96 Follow-up Patients who have completed initial treatment for ovarian cancer require routine follow-up clinical evaluations, including history, physical examination, and serum CA-125 measurement.

97 Gastrointestinal Cancer

98 Pancreatic Cancer Patients with metastatic pancreatic cancer have a median survival ranging from 4 to 6 months; those with locally unresectable disease have a median survival of about 1 year. Surgery is the only potentially curative intervention for patients with pancreatic cancer who have an apparent technically resectable tumor without evidence of metastases.

99 Gastric Cancer Helicobacter pylori infection is a major risk factor for development of gastric cancer. In patients who undergo surgery as initial therapy for gastric cancer, postoperative 5-fluorouracil and leucovorin plus radiation therapy have been shown to confer a survival benefit compared with postoperative observation alone. Patients with gastric and gastroesophageal junction adenocarcinoma whose tumors expressed HER2 experienced statistically significantly improved median survival when trastuzumab was added to cisplatin plus 5-fluorouracil or capecitabine.

100 Esophageal Cancer Gastroesophageal reflux disease, Barrett esophagus, and obesity are risk factors for esophageal cancer. The diagnosis of esophageal cancer is established by upper endoscopy and biopsy. Local and locoregional esophageal cancers are usually treated surgically; perioperative treatment with chemotherapy or chemotherapy plus radiation therapy may improve survival.

101 Anal Cancer Anal cancer is treated initially with combined radiation therapy and chemotherapy. Mitomycin plus 5-fluorouracil is the standard chemotherapy regimen used in conjunction with radiation therapy in the treatment of anal cancer.

102 Urgencies & Emergencies

103 Structural Superior vena cava syndrome is most often caused by lung cancer; other causes are lymphoblastic and diffuse large B-cell lymphoma, Hodgkin lymphoma, and germ cell tumors. Primary therapy for the underlying malignancy is usually associated with rapid and complete resolution of symptoms and physical findings of superior vena cava syndrome. Lumbar puncture is contraindicated when increased intracranial pressure is due to mass effect because the procedure may precipitate catastrophic brainstem herniation.

104 Structural Corticosteroids such as dexamethasone are initially used to treat patients with increased intracranial pressure. Patients with breast, lung, and prostate cancer are most likely to develop spinal cord compression. Patients with suspected spinal cord compression require prompt diagnosis (MRI of the spine), usually before any motor deficit is detected, and immediate administration of corticosteroids.

105 Structural A malignant pleural effusion is most often caused by lung cancer, breast cancer, and lymphoma, and less frequently by cancer of unknown primary site. Thoracentesis is required for immediate palliation of a symptomatic malignant pleural effusion. Excessive drainage in patients with malignant pleural effusion should be avoided to prevent pulmonary edema following lung re-expansion. Echocardiography is essential to establish the diagnosis of malignant pericardial effusion.

106 Metabolic Prevention and treatment of tumor lysis syndrome require hydration with normal saline as well as allopurinol or rasburicase in high-risk patients to limit the degree of hyperuricemia. Symptoms of hypercalcemia include nausea and vomiting, constipation, polyuria and polydipsia, weakness, and confusion. The mainstays of treatment of hypercalcemia are aggressive hydration with normal saline for short-term control and parenteral bisphosphonates for longer-term control.

107 Effects of Cancer Therapy

108 Chemotherapy The risk of life-threatening infection in patients receiving cancer treatment significantly increases with absolute neutrophil counts lower than 500/µL (0.5 × 109/L) and as the duration of neutropenia increases. Recombinant granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor are effective in preventing neutropenia and neutropenic fever and maintaining the dose intensity of chemotherapy. Myelodysplasia and leukemia can be caused by chemotherapy and, to a lesser extent, radiation therapy.

109 Other Involved-field radiation therapy may cause acute and chronic cardiac disorders. Patients with breast cancer who are treated with combined chemotherapy or radiation have an increased lifetime risk for developing myelodysplasia, leukemia, endometrial cancer, and rarely, soft tissue sarcoma. Long-term administration of aromatase inhibitors in women with breast cancer has significantly increased the incidence of osteopenia and risk for late pathologic fractures.

110 Head & Neck Cancer

111 Risk and Presentation The major risk factors for development of head and neck cancer are alcohol and tobacco use. Epstein-Barr virus and human papillomavirus infection may be responsible for development of head and neck cancer in a subset of patients without a history of tobacco use.

112 Diagnosis and Staging Presenting signs and symptoms of head and neck cancer depend on the location of the primary tumor. Patients with cervical lymphadenopathy require expert evaluation of the upper aerodigestive tract to identify a primary lesion; fine-needle aspiration of a palpable lymph node is performed, followed by a lymph node biopsy if the aspirate is nondiagnostic.

113 Treatment Goals of treatment of head and neck cancer focus on improving survival while preserving organ function and minimizing complications. Early-stage (stage I and II) head and neck cancer is highly curable with surgical resection or radiation therapy. Locally advanced stage III and IV head and neck cancer is treated with a combination of surgical resection, radiation therapy, and chemotherapy. Complications following treatment of head and neck cancer include damage to cranial and sensory nerves, xerostomia, swallowing dysfunction, voice changes, altered taste sensation, fibrosis, dental problems, and esophageal strictures.

114 Genitourinary Cancer

115 Germ Cell Tumor Testicular cancer is the most common solid tumor in young men and is one of the most highly curable of all malignancies. The primary risk factors for development of testicular cancer are the presence of Klinefelter syndrome, cryptorchidism, and a family history of testicular cancer. Patients with testicular cancer usually present with a unilateral mass or testicular swelling.

116 Germ Cell Tumor Initial urologic evaluation of a patient with suspected testicular cancer includes a chest radiograph, CT scan of the abdomen and pelvis, and determination of serum tumor marker levels. All patients with testicular cancer (either seminoma or nonseminoma) require radical orchiectomy as initial treatment. Patients with nonseminoma have a poorer prognosis than those with seminoma and require more aggressive treatment, but even with widespread metastases, may be cured with additional surgery and combination chemotherapy.

117 Bladder Cancer Most bladder cancers occur in men, who are typically over 60 years of age. Cigarette smoking is the major risk factor for development of bladder cancer. Patients with bladder cancer most often present with painless hematuria. All components of the urinary tract must be evaluated in patients with hematuria to identify a potential malignant source (or sources) of bleeding.

118 Bladder Cancer Approximately 60% of patients with bladder cancer are found to have noninvasive disease at the time of initial TNM staging. Patients with noninvasive bladder cancer are usually treated with transurethral resection of the bladder tumor and have an excellent prognosis. Patients with bladder cancer that invades muscle usually require radical cystectomy, including removal of the bladder, adjacent pelvic organs, and regional lymph nodes. Metastatic bladder cancer is incurable, and palliative platinum-based chemotherapy is often used in this setting.

119 Renal Cell Cancer Most patients with renal cell cancer present with a mass found incidentally on a radiographic study performed for other reasons. Large solid tumors seen on ultrasound imaging are so likely to be renal cell carcinoma that needle biopsy is not needed before definitive surgical resection is planned. Partial nephrectomy is appropriate for patients with renal cell tumors measuring less than 4 cm that are not adjacent to the renal pelvis. Molecularly targeted agents such as sunitinib, sorafenib, bevacizumab, temsirolimus, and everolimus have been shown to be effective in treating patients with resected renal cell cancer who develop metastatic disease.

120 Cancer of Unknown Primary

121 Diagnosis Before more specialized studies are done in patients with cancer of unknown primary site, biopsy samples of tumor from the most accessible location should be obtained for immunohistochemical marker determinations. An exhaustive search for a primary tumor should not be done in patients with cancer of unknown primary site because finding an asymptomatic and occult primary tumor has not been shown to improve outcome. Evaluation of patients with cancer of unknown primary (CUP) site should focus on whether findings are consistent with a treatable primary tumor or a treatable subtype of CUP.

122 Treatment & Prognosis Women with cancer of unknown primary site associated with isolated malignant axillary lymphadenopathy should be assumed to have locoregional breast cancer until proved otherwise. Women with cancer of unknown primary site presenting as abdominal carcinomatosis and ascites should be assumed to have ovarian cancer until proved otherwise. Patients with cancer of unknown primary site that is not included in a favorable subgroup generally have a poor prognosis and typically receive empiric therapy.

123 Melanoma

124 Risk & Treatment Risk factors for melanoma include sun exposure, a history of multiple sunburns, fair complexion, the presence of multiple cutaneous nevi, and a personal or family history of melanoma or dysplastic nevi. The primary treatment of local and locoregional melanoma is surgical resection. Resection is indicated for patients with limited metastatic melanoma that is surgically resectable.

125 Final Advice If you get stuck, remember these generalities:
The only way to “cure” cancer includes surgery. Cancer that has spread to lymph nodes or beyond requires systemic treatment (i.e., chemotherapy). If you’re going to act, make it definitive (e.g., obtain a diagnosis, prefer curative treatments). You stand a good chance of guessing correctly.

126 If you prepare well, you won’t need it.
Good Luck! If you prepare well, you won’t need it.

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