9. colon cancer – Flashcards
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colorectal cancer is the _____ most common cancer
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3rd
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what are the 7 risk factors for colon cancer?
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-age > 50 -polyps -genetic predisposititon -family history of colon cancer -type 2 DM -personal hx of other cancers, ulcerative colitis, crohn's dz -lifestyle factors: high fat, low fiber, obesity, sedentary, alcohol, tobacco
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what are the two main types of genetic predispositions to colon cancer?
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-familial adenomatous polyposis (FAP) -hereditary nonpolyposis colorectal cancer (HNPCC) or lynch syndrome
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what is familial adenomatous polyposis (FAP)?
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-genetic predisposition to colon cancer -mutation in the adenomatous polyposis coli gene (APC) -large # of polyps in colon and rectum -between ages 5-40 -in untreated, 100% risk for developing cancer
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what is hereditary nonpolyposis colorectal cancer (HNPCC) or lynch syndrome?
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-genetic predisposition to colon cancer -mutation in DNA mismatch-repair genes (MMR) -most common mutations in MLH1, MSH2, MSH6 responsible -other cancers are associated with HNPCC: endometrial, ovarian
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what are potential protective factors for colon cancer?
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-diet: high fiber, fruits, vegetables -calcium and vit D -NSAIDs and ASA -surgical resection in extremely high risk patients
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what agent can be used to potentially prevent recurrence of colon cancer?
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ASA may be beneficial
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what is considered an "average risk" patient?
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-age > 50 -no hx of adenoma, colorectal cancer, Inflamm Bowel Dz -negative fam hx
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what is considered a "high risk" patient?
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-personal history -family history -known genetic predisposition -begin screening earlier in life
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what are the 3 methods of screening for colon cancer?
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-fecal occult blood or immunochemical test -endoscopy -radiology
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describe patient counseling points for hemoccult testing for cancer screening
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...
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what are the screening recommendation choices for an "average risk" patient?
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-colonoscopy Q10 years -FOBT/FIT Qyear -flex sig Q5 year -double contrast barium enema Q 5 year -CT colonography Q5 years
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if a patient has a postive result from any of the colon screening choices, what is the next step?
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colonoscopy
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what are the clinical presentation of colon cancer
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-changes in bowel habits -GI: n/v, discomfort, gas, bloating, fullness, cramps, abdominal pain -Rectal bleeding or blood in stool -fatigue, weight loss -leg edema, pain, back pain with lymph node involvement -hepatomegaly, jaundice, incr LFTs with metastatic dz
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what are the components of a colon cancer diagnostic work-up?
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-hx and physical exam -baseline labs -radiography: determine extent of disease and possible metastasis -PET (2nd line): confirm metastisis -biopsy: tissue sample for evaluation by pathology for staging
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what test is used for monitoring therapy of colon cancer?
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carcinoembryonic antigen (CEA)
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what is Carcinoembryonic antigen?
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-an oncofetal protein -expressed in embryos and in many carcinomas (GI cancers) -insensitive and non-specific -if positive, correlates with amount of tumor, differentiation, residual disease, recurrence, poor survival
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what are the 5 factors that influence prognosis of colon cancer?
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-stage at diagnosis -degree of lymph invasion -clinical factors (performance status, bowel obstruction at presentation, location of tumors) -high proliferation indices -molecular markers - differentiation of cells
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what are the 3 treatment principles of colon cancer?
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-surgery -radiation (palliative) -adjuvant chemotherapy
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surgery for colon cancer should be offered as an option for which patients?
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all patients for a potential cure; usually stages 1-3
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what does colon cancer surgery entail?
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resection of primary tumor mass with regional lymphadenectomy
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what role does radiation play in the treatment of colon cancer?
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palliative role, not routinely used; well established in rectal cancers
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when is adjuvant chemotherapy typically recommended for colon cancer patients?
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stage 3 or 4 (stage 2 for patients with "high risk features")
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when might adjuvant chemotherapy be appropriate to use in a patient with stage 2 colon cancer?
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patients with "high risk features" - bowel perforation
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what are the 4 regimen options for stage 3 adjuvant chemotherapy for treatment of colon cancer?
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1. Fluorouracil + leucovorin + oxaliplatin (FOLFOX) 2. Capecitabine + Oxaliplatin (CapeOx) 3. Capecitabine monotherapy PO 4. Fluorouracil + leucovorin
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what agent is considered equivalent to fluorouracil in adjuvant and metastatic setting for treatment of colon cancer?
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capecitabine monotherapy
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where is the most common site for metastasis for colon cancer?
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liver
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T/F: surgery is the standard of care for stage 4 advanced colon cancer?
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false
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T/F: Adjuvant chemotherapy is the standard of care for stage 3 colon cancer?
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true
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when might surgery be appropriate for stage 4 advanced colon cancer?
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-neoadjuvant + colectomy + synchronous or staged liver or lung resection -may extend disease free survival in some patients
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what are the chemotherapy options for stage 4 advanced colon cancer?
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1. Fluorouracil + leucovorin + oxaliplatin (FOLFOX) 2. Capecitabine + Oxaliplatin (CapeOX) 3. Fluorouracil + leucovorin + irinotecan (FOLFIRI) 4. Fluorouracil + leucovorin OR capecitabine 5. Fluorouracil + leucovorin + oxaliplatin + irinotecan (FOLFOXIRI)
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what 3 agents can be added to the stage 4 colon cancer main chemo regimens?
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-bevacizumab -cetuximab -panitunumab
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bevacizumab cannot be used concurrantly with which other 2 additional chemo agents used for colon cancer?
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-cetuximab -panitunumab
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what are therapies for stage 4 colon cancer after progression?
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-ziv-aflibercept + FOLFIRI (in naive patients) -ziv-aflibercept + irinotecan -regorafenib if patient progressed on all standard therapies
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what are the pharmacogenomics related to tumor KRAS mutation and colorectal cancer?
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-EGFR drugs might not work -guidelines recommend mutation analysis screening prior to starting EGFR agents
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what are the pharmacogenomics related to thymidylate synthase (TS or TYMS) and colorectal cancer?
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-TS is involved in DNA synthesis -TS is inhibited by fluorouracil -TS overexpression associated with drug resistance
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what are the pharmacogenomics related to glutathione s-transferase (GSTPI) and colorectal cancer?
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-GSPs attach glutathione to electrophiles - eliminating toxic compounds -GSP polymorphisms may predict resistance or toxicity to OXALIPLATIN
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what are the pharmacogenomics related to dihydropyrimidine dehydrogenase (DPD or DPYD) and colorectal cancer?
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-DPD responsible for degrading pyrimidines -DPD deficiency results in FLUOROURACIL OR CAPECITABINE TOXICITY
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what are the pharmacogenomics related to UDP-glucuronosyltransferase (UGT1A1) and colorectal cancer?
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-part of a series of drug metabolism enzymes -involved in metabolism of: bili, estrogens, thyroid hormone, chemo agents (ETOPOSIDE, IRINOTECAN) -*28 and *6 variants result in DRUG TOXICITY
