Colorectal Flashcards
Intake of fiber-rich foods is associated with a higher or lower risk of colorectal cancer.
Lower
30% of colorectal cancers develop via a serrated neoplasia pathway which is associated with the following features:
BRAF mutations, methylation of CpG islands phenotype, and right-sided colon cancers.
What are the risk factors for colon cancer?
Polyposis syndromes (familial polyposis, Peutz-Jeghers syndrome, juvenile polyposis), hereditary nonpolyposis colorectal cancer, IBS, prior colon cancer, prior polyps, first degree relative diagnosed at age < 50, Western diet, alcohol, sedentary lifestyle, obesity, diabetes
What causes familial adenomatous polyposis (FAP)?
An inherited mutation in the FAP coli (APC) gene.
What causes HNPCC (Lynch I and Lynch II syndromes)?
Mutations in genes coding for DNA mismatch repair enzymes
What is a good way to test MSI in colorectal cancer?
IHC
How does HNPCC usually present?
Early onset age, proximal location, mucinous histology, higher grade. Usually better prognosis than MSS rumors.
What is Gardner’s syndrome?
> 100 colon polyps, diffuse; epidermoid cysts, desmoid tumors, osteomas, fibromas.
What is Turcot syndrome?
> 100 colon polyps, diffuse; brain tumors
What are the common DNA mismatch repair genes?
MSH-2, MLH1-1, PMS-1, PMS-2, MSH-6
Patients with type II HNPCC, which makes up about 5% of all colorectal cancers, also develop what other cancers?
Ovarian, pancreas, breast, biliary, endometrial, gastric, genitourinary, small bowel.
What other cancers do patients with Peutz-Jeghers syndrome have besides colorectal cancer?
Ovarian and testicular.
T or F: HNPCC has a lower response rate to 5-FU-based chemo than MSS tumors but a better prognosis.
True
Screening for HNPCC patients? For FAP?
Colonoscopy every 1-3 years beginning at age 20-25 for HNPCC. Starting at age 10 for FAP.
What’s the general treatment approach to colon cancer?
Stage I: surgery. Stage II: surgery with or without chemo. Stage III: surgery with chemo. Stage IV: chemo with or without surgery.
What is the standard adjuvant chemo for stage III colon cancer?
Oxaliplatin-containing regimen for 6 mos, not irinotecan-based regimen. However, for patients > 70 yo, 5-FU/LV might be as good as FOLFOX. Bev and cetuximab have no role in the adjuvant setting.
Is there a role for adjuvant chemo in stage II colon cancer?
Unclear. MSI-high tumors do not need adjuvant chemo.
In which selected group of patients with resected colon cancer is aspirin an effective secondary prophylaxis?
Those with PIK3CA mutations (exon 9 and 20)
What is the response rare to 5-FU/LV in advanced colon cancer?
15-25%
Is single-agent oxaliplatin effective in advanced colon cancer?
No. But it is effective in combination with a fluoropyrimidine.
How do the different chemo regimens compare in advanced colon cancer?
FOLFOX > IROX > IFL (bolus 5-FU). FOLFOX ~ FOLFIRI. Bev + chemo > chemo. Bev + cetuximab is harmful. Continuing bev with a new chemo regimen after progression is helpful. Cetuximab or panitumumab is helpful in tumors without KRAS exon 2, exon 3, exon 4 or NRAS mutations. BRAF-mutated tumors are bad and might require FOLFOXIRI. FOLFIRI + cetux has better OS than FOLFIRI + bev but same RR and PFS. Aflibercept and regorafenib also have activities
Is local excision of T1 rectal cancer without high-risk factors reasonable?
Yes. For other stages, total mesorectal excision is preferred.
What is the most common radiosensitizing chemo agent as neoadjuvant therapy in rectal cancer?
Capecitabine 825 mg/m2 bid or prolonged infusion of 5-FU.
What is the data on neoadjuvant vs adjuvant chemorad for stage II or III rectal cancers?
German trial: neoadjuvant with rad + 5-FU has lower rate of local recurrence, lower toxicities, and higher sphincter preservation rate than adjuvant chemorad. The addition of oxaliplatin had not been proven to be definitively helpful.
What are the risk factors for anal cancer?
HPV, venereal infection, condylomata, HSV-1, Chlamydia, gonorrhea, AIDS
What is the treatment for anal cancers?
Chemorad (with 5-FU plus mitomycin-C). Local excision only for small tumors that are well differentiated.
What is MEN1 syndrome?
Mutations in MEN1 -> Tumors of pituitary gland, parathyroid gland, pancreatic neuroendocrine tumors.
What is MEN2 syndrome?
Mutations is RET -> tumors of parathyroid, pheochromocytoma, medullary thyroid.
Main treatment for pancreatic neuroendocrine tumors and carcinoid tumors?
Surgery. Radiation for symptomatic relief. Octreotide analogues. Chemo has poor response. For pancreatic NET, sunitinib, everolimus
