Update: Top Ten Cancers. David C. Dale, MD Professor of Medicine University of Washington

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1 Update: Top Ten Cancers David C. Dale, MD Professor of Medicine University of Washington

2 Common Cancers-USA Type New Cases Deaths 1. Breast 232,000 40, Lung 221, , Prostate 220,000 28, Colo-Rectal 133,000 50, Bladder 74,000 16, Melanoma 74,000 10, NH Lymphoma 72,000 20, Thyroid 62,000 2, Renal 62,000 14, Endometrial 55,000 10, Leukemia (all types) 54,000 24, Pancreatic 49,000 41,000 Statistics:

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4 Outline Common Cancers Diagnosis and guidelines Recent reports Advances-genetics, biological and targeted therapies Keeping up-finding information

5 Case 72 F ask do I need another mammogram? The best answer is: 1. No you are too old 2. No, not if you have had 5 negative exams 3. Yes, but just one more 4. Yes, annually until age Yes, annually until age 75

6 Mammography Recommendations Beyond Age 70 USPHSTF yes, to age 75 Canadian Task Force yes, to age 74 Natl Health Service (UK) yes, to age 73 Natl Cancer Institute yes AMA yes ACP Am College Ob Gyn yes yes and discuss with you doctor after 75

7 Early Detection-Breast Cancer Breast self-examination-begin early 20 s; Women should know benefits/limitations Breast physical examination-every 3 years, age 20-39, annually after age 40 US Preventive Services Task Force recommends mammography for women age 50 to 74 years of age. Screening before age 50 should be based on the individual woman s preferences, situation and family history The American Cancer Society recommends starting at age 40 Key: Know family history, modify above by history of cancer, breast cancer, ovarian cancer Mackenzie S, et al, Breast Cancer Screening, Medical Clinics of North America, 2015; 99:

8 Genetic risk factors BRCA1 and BRCA2: Most common cause of hereditary breast cancer; BRCA1 life time risk 55-65%, BRCA2 45%. Cancer at younger age, also associated with ovarian CA. Accounts for Other mutations associated with breast cancer ATM (causes DNA repair defect), TP53 (growth regulator-also leukemia, brain CA), CHEK2 (Li-Fraumini syndrome), PTEN (Cowen syndrome ad others), CDH1 (also gastric CA), STK11 (Peutz-Jeghers syndrome), PALB2 (product interacts with BRCA2 protein)

9 BRCA1 and BRCA2 Testing Prevalence: 0.2 to 0.3 percent in general populations. Positive test result: Women with breast CA 3%, breast CA before age 40 years-6%,ovarian cancer-10%, high-risk families -20%. Among Ashkenazi Jewish women is 2 percent positive in unselected populations Penetrance: Breast cancer penetrance to age 70 years if the test is positive is 46 to 71 percent for BRCA1 or BRCA2; ovarian cancer penetrance is 41 to 46 percent for BRCA1 and 17 to 23 percent for BRCA2. Worry and anxiety increased after testing in women with positive results and decreased with negative result Nelson HD et al, Agency for Healthcare Research and Quality (US); 2013 Dec. Report No.: EF-1.U.S. Preventive Services Task Force Evidence Syntheses

10 How is breast cancer diagnosed? Medical history and physical exam Mammogram +/- ultrasound Magnetic resonance imaging (MRI) Nipple discharge exam Ductal lavage and nipple aspiration Fine needle aspiration biopsy Core needle biopsy Surgical (open) biopsy Lymph node biopsy American Cancer Society

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12 Staging Early Breast Cancer

13 Treatment Options Surgery-breast conservation vs mastectomy Surgery then radiation therapy Surgery then adjuvant chemotherapy HER2 positive-chemo plus trastuzumab ER positive-tamoxifen, xemestane ER neg, HER2 neg-chemotherapy

14 HER2 and Breast Cancer

15 What s New-Breast Cancer Treatment 2015 in UptoDate Anastrozole better than tamoxifen for DCIS Palbociclib-(a cyclin-dependent kinase 4/6 inhibitor) favorable results with fulvestrant (estrogen antagonist) for ER+ disease Surgical cavity shaving may reduce residual cancer Accuracy of breast biopsy interpretationconcordance 75% Pertuzumab (binds to HER2) slows tumor growth

16 Lung Cancer

17 Lung Cancer

18 Case 75 M smoking 30 pack years, stopped smoking 20 years ago. Active, running, sports Routine x-rays show mild emphysema and small nodule, 3 mm, stable for > 5 years. What surveillance is indicated? 1. X-ray annually 2. Bronchoscopy and cytology annually 3. Low-dose spiral CT annually 4. Sputum cytology annually 5. None of the above

19 Answer-5. None of the above USPHSTF Recommends: Low-dose CT (LDCT) in person with history of smoking> 30 pack years who are currently smoking or quit less than 15 years ago Discontinue screening: If not smoking > 15 years, If changes in health status limiting life expectance, If unwilling to have surgery

20 US Lung Cancer Deaths 2014 NCI/ACS data: 221,000 new cases, 158,000 deaths, > 70% Low-dose spiral CT predicted to save 20,000 patients from lung cancer deaths per year Discontinuation of all smoking after 15 years could probably prevent 80% of lung cancer deaths. Source: USPSTF: December 31, 2013, American Lung Association, update April 2015

21 Presentations for Lung Cancer Pulmonary: Cough, dyspnea, chest pain, hemoptysis, pneumonia Chest and airway: Hoarse, dysphagia General: Wt loss, weak, bone pain, headache Paraneoplastic: hypercalcemia, leukocytosis

22 Staging-What s New Tumor-Size <2 cm, >3 cm Nodes-mediastinal ipsilateral/contralateral Metastases: local, regional, distal Newer modalities Imaging: PET and CT

23 Non-Small Cell Lung Cancer Treatment Recommendations Stage I: Surgery, radiation for high risk patients, consider chemotherapy-cisplatin plus second drug Stage II: Surgery, chemotherapy recommended, palliative radiation Stage III: consider surgery, chemotherapy recommended, radiation palliative Stage IV: Consider chemotherapy, radiation palliative

24 Small Cell Lung Cancer Treatment Recommendations Stage 1-Sugery and post operative chemotherapy, consider prophylactic cranial irradiation-5 year survival % Stage II-same, survival 18-38% Stage III-no surgery, recommend chemotherapy and radiation concomitantly Stage IV-no surgery, chemotherapy, palliative radiation Rx.

25 What s New Fluorescence bronchoscopy Virtual bronchoscopy Video-assisted and robotic-assisted surgery Real-time tumor imaging Biomarkers as prognostic indicators Targeted therapies-e.g.,bevacizumab, erlotinib, sorafenib, sunitinib Drugs blocking PD-1 and PD-L1, e.g.,nivolumab

26 What s New: Prognostic Biomarkers and NSCLC EGFR=unknown EML4ALK=unknown ERCCI-increased expression=good K-ras-presence of mutation=bad RRMI-increased expression=less responsive to gemcitabine TS=unknown

27 What s New for NSCLC EGFR inhibitors-gefitinib FDA approved NSCLC with EGFR exon 19 deletion or exon 21 substitution Bevacizumab, pemetrexed, cisplatin may improve mesothelioma outcomes Nivolumab (anti PD-1 antibody) favorable results in NSCLC September 2015

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29 Prostate Cancer

30 Case 80 retired male internist in good health, mild high BP, well controlled, plays tennis and golf, active family life. At my annual visit, I want a PSA test. Which is the best response: Fine! Really! Haven t you had enough? Your insurance may not pay! I don t recommend testing in men over 80!

31 All of these answers are acceptable!

32 Early Detection Rectal exam PSA testing Guidelines ACS USPHSTF Urology

33 What s New-Prostate Cancer Genetics-HOXB13 linked to early cancer Prevention-studies of tomatoes, soybeans, etc Early detection-some new ideas in testing Diagnosis-nothing new Staging-studies of PET and enhanced MRI Radiation therapy-intensity modulated RT New hormone therapies: abiraterone, others Chemotherapy: docetaxel and combinations Immune checkpoint modulators: ipilimumab

34 Colon Cancer

35 Screening for Colon Cancer

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37 Principles of Colon Cancer Dx and Rx Diagnosis:Colonoscopy with biopsy Pretreatment: Family history cancer/colon cancer, physical examination, CT -abdomen, pelvis and chest. CEA should be obtained preoperatively. Surgical resection is the only curative modality. Postoperative (adjuvant) chemotherapy eradicates micrometastases, educes the likelihood of disease recurrence, and increases cure rates. For metastatic disease palliative chemotherapy is generally recommended. However, surgery may provide a potentially curative option for selected patients with limited metastatic disease The most important indicator of outcome following resection of colon cancer is pathologic stage

38 What s New Melanoma Surgery remains the primary treatment Interferon alpha is effective to prolong survival-has challenging adverse effects Check point inhibitors-anti-pd1 antibodiesnivolumab, ipilimumab, pembrolizumabshowed good results to prolong survival with relative low toxicity in advanced disease

39 Ovarian Cancer Fifth most common cancer cause of cancer deaths in women, in US about 22,000 new cases per year. Screening tests:ca-125, transvaginal ultrasound Average risk no screening of established benefit Family history breast or ovarian CA, especially Ashkenazi Jewish heritage-under study BRCA1 or BRCA2 mutation-may benefit begin age 30 Memorial Sloan-Kettering screening guidelines 2015

40 Cervical Cancer Screening Guidelines Screen years with cytology every 3 years or screen with cytology and HPV testing every 5 years. (A) Do not screen < 21 years (D) Do not screen > 65 years, if adequate prior tests (D) Do not screen if hysterectomy and removal of cervix and no history of high grade pre-cancer or cervical cancer (D) Do not screen with HPV alone (D) USPHSTF Cervical Cancer Screening Guidelines-2012

41 Pancreas I wish I had something good to say!

42 What s New? What Do I Do? Consult, Use Up-to-Date, Medical Texts American Cancer Society NIH-National Cancer Institute National Comprehensive Cancer Network Journals: JCO, NEJM, Blood