Gastric and Colon Cancer. Dr. Andres Wiernik 2017
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1 Gastric and Colon Cancer Dr. Andres Wiernik 2017
2 GASTRIC CANCER
3 Gastric Cancer Classification Epidemiology General principles of Management
4 25% GE Junction Gastric Cancer 75% Gastric Cancer
5 Epidemiology Gastric Cancer Word Incidence: 950,000 / year (4 th ) World Mortality 720,000 / year (2 nd ) NOT a big problem in the USA A HUGE problem in the rest of the world
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10 Risk Factors Gastric Cancer Helicobacter pylori? EBV - Epstein Barr Virus Tobacco Low consumption of fruits High intake of salts, nitrates, and pickled foods Obesity 1-3% Hereditary: Hereditary diffuse gastric cancer Gastric adenocarcinoma proximal polyposis of the stomach Familial intestinal gastric cancer.
11 Helicobacter pylori 1983 Identified for the 1 st time 1994 WHO Definitive Carcinogen
12 NEJM, 2001
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14 Management Gastric Cancer Surgery is the only curative treatment. Locally advanced disease: neoadjuvant or adjuvant therapy (chemotherapy) + Surgery Metastatic Disease Palliative chemotherapy Molecular Therapy (HER-2 and VEGFR2) Median OS ~ 1 year
15 ~500 Patients with Resectable Gastric Cancer Magic Trial NEJM, % 23%
16 Management Gastric Cancer Surgery is the only curative treatment. Locally advanced disease: neoadjuvant or adjuvant therapy (chemotherapy) + Surgery Metastatic Disease Palliative chemotherapy Median OS ~ 1 year
17 Chemotherapy in Metastatic Gastric Cancer
18 Any Target Therapy in Metastatic Gastric Cancer? Anti HER-2 (POSITIVE in 20-25% of Gastric Cancer) Anti VEGFR-2
19 +300 Patients with metastatic HER2+ Gastric Cancer TOGA Trial Lancet, 2010
20 VEGFR Family of Receptors Ramucirumab
21 +600 Patients with metastatic Gastric Cancer Paclitaxel +/- Ramucirumab RAINBOW Trial Lancet Onc, 2014 OS 9.6 months OS 7.4 months
22 Colon Cancer
23 Colon Cancer Epidemiology General principles of Management
24 Epidemiology Colon Cancer Word Incidence: ~ 1,200,000 / year (3 rd ) World Mortality 600,000 / year (4 th ) Incidence strongly varies globally and is closely linked to elements of a so-called western lifestyle Men > Women Median age Dx: ~ 70 years old
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29 NEJM 2016
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32 Risk Factors Colon Cancer
33 Sporadic Colon Cancer BOARDS: 55 yo with Bacteremia *** Streptococcus bovis Clostridium septicum
34 Sporadic >80% Colorectacal Cancer Genetic ~5-10% FAP / Familial Adenomatous Polyposis Hereditary Non-Polyposis Colon Cancer or Lynch Syndrome (5% of all Colon Cancer) Others (???)
35 Combined data on 44,788 pairs of twins listed in the Swedish, Danish, and Finnish twin registries in order to assess the risks of cancer at 28 anatomical sites for the twins of persons with cancer
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38 Familial forms of Colon Cancer Hereditary Colon Cancer: FAP / Familial Adenomatous Polyposis 100s to 1000s of polyps 100% incidence of colon cancer without prophylaxis Hereditary Non-Polyposis Colon Cancer or Lynch Syndrome 5% of ALL Colon Cancers Younger age Right sided lesions Associated with other adenocarcinomas Breast Ovary Small Bowel or Stomach Kidney NO preceeding polyposis
39 FAP Familial Adenomatous Polyposis
40 FAP Familial Adenomatous Polyposis
41 FAP Familial Adenomatous Polyposis
42 Colon Cancer Screening based on FH: Scenario When to start? Comments 1 st degree relative younger than 60 yo * Two 1 st degree relatives at any age * 1 st degree relative older than 60 yo Age 40 or 10 years younger Age 40 or 10 years younger Age 50 Screen every 5 years (not 10) Screen every 5 years (not 10) Every 10 (average risk) 2 nd or 3 rd Degree Age 50 Every 10 (average risk) * CRC or Adenomatous Polyps
43 Staging of Colon Cancer IV III II I
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45 Treatment Summary of Colorectal Cancer Main treatment Surgical Resection Hemicolectomy + LN dissection Neoadjuvant radiotherapy for patients with rectal cancer), Adjuvant chemotherapy (for patients with stage III/IV and high-risk stage II colon cancer).
46 Staging of Colon Cancer IV III II I
47 Management of Stage I and II Colon Cancer Hemicolectomy + LN dissection II I
48 Management of Stage IIII Colon Cancer 1) Hemicolectomy + LN dissection 2) Adjuvant Chemotherapy III (FOLFOX)
49 Management of Stage IV Colon Cancer IV 1) Surgery? Only if oligometastatic disease 2) Palliative Chemotherapy +/- Biologics
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51 Treatment of stage IV Colon Cancer Chemotherapy: FOLFOX FOLFIRI Biologics: Anti-VEGF Bevacizumab (Avastin) Anti-EGFR monoclonal antibodies Cetuximab Panitumumab Regorafenib Ramucirumab trifluridine-tipiracil (LONSURF) Immunotherapy (Nivolumab or Pembrolizumab)
52 VEGFR Family of Receptors
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54 Chemotherapy + Avastin
55 EGFR Pathway
56 Chemotherapy + anti-egfr (Cetuximab) JCO, 2015
57 EGFR Pathway KRAS MUTATION (30-50%)
58 Chemotherapy + Cetuximab in KRAS MUTATED JCO, 2015
59 Thank you!
60 Case: 55 yo male diagnosed with colon cancer on screening. Undergoes surgical resection and he is found to have a 2 cm tumor (invading the muscularis) with negative LNs. Adjuvant chemo? What about radiation?
61 Case: 55 yo male presents with acute abdomen. Undergoes laparotomy and is found to have a perforated bowel in addition to a 2 cm invading the muscularis which pathology reports is consistent with adenocarcinoma of the colon measuring 2 cm. 15 lymph nodes were resected and these are all negative for tumor. Adjuvant chemo? What about radiation?
62 Who gets adjuvant chemo in Colon Cancer? Stage 3 or higher: FOLFOX High risk stage 2: 5-FU or Capecitabine Grade 3-4 (exclusive of those cancers that are MSI- H) Lymphatic/vascular invasion Bowel obstruction < 12 lymph nodes examined Perineural invasion Localized perforation or close Indeterminate or positive margins.
63 MKSAP #67 67 yo man s/p right hemicolectomy + adjuvant chemotherapy for stage III colon cancer 3 years ago Annual CT and surveillance: Normal CEA 1 year ago: 2.4 Today: CEA 10.1 (nl=less than 2.1) CT scan: Solitary liver lesion
64 Next step in management? 1) Chemoembolization 2) Biopsy 3) Ethanol ablation 4) Systemic chemotherapy 5) Surgical Resection
65 Metastatic Stage IV Colon Cancer Who gets Surgery in stage IV Colon Cancer? Single Liver lesion or Lung Only RESECTION! (with curative intent!!!) Do PET before (ONLY indication for PET in Colon Ca) Obstructive palliative Sx Colostomy
66 MKSAP #77 56 yo woman with screening colonoscopy Mass is found 10 cms from anal verge Bx: Moderately differentiated adenocarcinoma Rectal US: Tumor extends into perirectal fat but not LN involvement CT C/A/P: No metastatic disease
67 Next Step in Management 1. Chemotherapy followed by surgery 2. Surgery follow by chemotherapy 3. Chemo +radiation followed by surgery followed by adjuvant chemotherapy 4. Surgery followed by radiation
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