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Oncology Exam 4
Frei Colon Cancer D
| Question | Answer |
|---|---|
| Colon cancer is ranked ___ in cancer incidence and mortality in men and women | 3rd ⭐️ |
| Epidemiology of Colorectal cancer? | -Lifetime risk for developing colorectal cancer is about 5% -Slightly higher in men than in women -AA have ↑ incidence and mortality rates -Asian/Hispanic ethnicities have ↓ incidence |
| Etiology and Risk Factors for Development of Colorectal Cancer? | -Age, Gender, Race/Ethnicity, Family History, Genetic predisposition, Familial adenomatosis polyposis (FAP) - mutation in adenomatous polyposis coli gene, Hereditary nonpolyposis colon cancer (HNPCC) or Lynch syndrome (most common); with these mutations can be seen in younger ages Inflammatory bowel disease, Ulcerative colitis, Diabetes, Polyps (could develop into cancer, "colon polyps" |
| Other Etiology and risk factors for development of Colorectal cancer | -Sedentary lifestyle -Overweight -Diet (High fat, low fiber diet, Excessive caloric intake) -Moderate to heavy use of alcohol ⭐️ |
| Most Likely Cause of CRC? | -Sporadic (avg risk 65-85%); -Family history (10-30%); -Rare syndromes (<0.1%) -Familial adenomatous polyposis (FAP 1%) -Hereditary nonpolypsis colorectal cancer (HNPCC 5%) |
| CRC Histology | Adenocarcinomas – 90% Other histologic types: (Mucinous adenocarcinoma, Signet-ring adenocarcinoma, Carcinoid simplex, Carcinoid tumors) *staging on how far it goes through the organ (through the colon and what layers it goes through (mucosa, serosa sub mucosa, mucosa) |
| Prevention for Colon Cancer? | -Diet (High in fruits and vegetables, Long term consumption of red and processed meat and mod to heavy alcohol consumption associated with increased risk of CRC) -Smoking cessation recommended -Regular physical activity recommended |
| Other preventions for Colon Cancer includes? | -Colectomy (Familial adenomatous polyposis + polyps, Hereditary nonpolyposis colorectal cancer)—> remove if you have these gen. Mutations); -ASA, NSAIDs, COX 2 inhibitors—> only in certain groups such as for—> Prevention of polyps in patients with FAP -ASA (Not recommended for primary prevention due to toxicity (gastric and kidney) but is effective) |
| How do we screen for colon cancer? | -Digital Rectal Examination (DRE) -In conjunction with other screening tools -Detects ~10% of all colorectal cancers within 7 – 10 cm of anus |
| Summary of guidelines (Avg risk & Age >/= 45: Direct visualization: 1. Colonoscopy 2. CT Colonograpy 3. Flex Sig | NCCN: 1. Q 10 years (Gold Standard ⭐️) 2. Q 5 years 3. Q 5-10 years |
| Besides a DRE (Digital Rectal Exam), other screening tools that we can use includes? | Total Colonic Examination -Colonoscopy (More inconvenient and risky for patient compared to enema, Sedation usually. Allows for biopsy if polyps/masses found) -Flexible Sigmoidoscopy (35 – 60% of the bowel) |
| Explain Total Colonic Examination? | CT Colonography: -A number of studies have demonstrated a high level of sensitivity for cancer and large polyps, -Minimally invasive (rectal tube for air insufflation) -No sedation required *negatives: cannot detect really small polyps (if you find something, can’t remove it) |
| Stool Testing includes which tests? and NCCN states how often? | FIT (yearly); FOBT (Yearly); Multi-targeted Stool DNA (Q 3 yr) *stool sample but only finds blood |
| FOBT (Fecal Occult Blood Testing) Getting an annual of FOBTs ___ colorectal mortality 15-33% | decreases |
| To avoid false + for the FOBT test (Fecal Occult Blood testing)? | -No Red Meat ⭐️ and Vegetables with peroxidase activity for 3 days -Avoid iron products⭐️ for 3 days prior to testing -Avoid NSAIDS⭐️ for up to 7 days prior to testing |
| To avoid false - for the FOBT test (Fecal Occult Blood testing)? | -Avoid Vit C ⭐️ for 3 days prior to testing -Avoid testing dehydrated⭐️ samples (rehydrating not recommended) |
| When screening for colon cancer in High Risk individuals what is the recommendation for the following? -Family Hx? -HNPCC (Lynch Syndrome)? -FAP (genetic syndrome)? -IBD? | -Screening at age 40 or 10 years before family member diagnosed -Screening at age 30 -Screening at age 10 – 12 -Screening as early as 8 years after onset of Ulcerative collitis |
| Early stage clinical presentation can be Asymptomatic. What about late stage clinical presentation? | Changes in bowel habits, Blood in stool, Anorexia, Abdominal pain, Weakness, Unexplained Weight loss *20% of pts present with metastatic disease (late stage) |
| Conducting a workup for colon cancer? | -Biopsy, pathologic tissue review, total colonoscopy, CBC, chemistry profile, CEA determination (prognosis), and baseline CT scans of the chest, abdomen, and pelvis, -Testing for Mismatch repair (MMR)/microsatellite instability – high (MSI-H) to help with detection of Lynch syndrome and to inform treatment decision-making -If metastatic disease (Stage IV), further testing is warranted (BRAF V600E mutation, KRAS, NRAS) |
| Staging of colorectal cancer: Stage I and II & (node - ) 5-yr survival rates? Tx options? | 91%, (surgery) *Staging of Colorectal Cancer: Stage I (90 to > 95%), II (70-85%), III (1-3 nodes) (50-70%), >4 nodes ( 25-60%), IV (<5%). Stage III has node + disease means its spreading and could get metastatic down the road. *node (-) colon cancer, will only have surgery as treatment. Surgery is the primary mainstay in stage I and II colon cancer. |
| Staging of colorectal cancer: Stage III & (node +) 5-yr survival rates? Tx options? | 72%, (surgery, XRT, chemo) *Overall relative survival rate for CRC is 65% at 5 years following diagnosis (all stages) *XRT--> used for rectal cancer only (bottom portion of colon) *stages I-III are curable |
| Staging of colorectal cancer: Stage IV 5-yr survival rates? Surgery? Tx options? | 14%, (Chemo, surgery not done much *Overall relative survival rate for CRC is 65% at 5 years following diagnosis (all stages) |
| Tx for Curable Colorectal Cancer: Stage I; 5-yr survival? Medication Therapy? | 91%; Observation |
| Tx for Curable Colorectal Cancer: Stage II; 5-yr survival? Medication Therapy? | 72%; Observation OR Consider 5FU/Leucovorin or capecitabine OR FOLFOX** or CapeOx** ** - only in high risk groups – Poorly differentiated histology, lymphatic/vascular invasion, bowel obstruction, < 12 lymph nodes dissected, perineural invasion, localized perforation, positive or indeterminate margins. |
| Tx for Curable Colorectal Cancer: Stage III; 5-yr survival? Medication Therapy? Stage III gets chemo *remember that stage III is node +, left the colon and going to other places | 14%; FOLFOX** or CapeOx** 3-6 months (6 months preferred) OR If d (deficiency)MMR/MSI-H can treat with neoadjuvant (after biopsy but b4 surgery) h nivolumab +/- ipilimumab or pembrolizumab **** - only in high risk groups – Poorly differentiated histology, lymphatic/vascular invasion, bowel obstruction, < 12 lymph nodes dissected, perineural invasion, localized perforation, positive or indeterminate margins. *stage III must get chemo |
| FOLFOX stands for? | folinic acid (leucovorin), fluorouracil (5-FU), oxaliplatin |
| CapeOx stands for? | capecitabine oxaliplatin |
| What toxicities do you expect from FOLFOX? (5-FU) | 5-FU: (D/Mouth sores, N/V (mild), Possible hair loss, Hand foot syndrome (mild). -If severe, early onet toxicities occur, pt may have DPD deficiency *management includes stopping cancer med and supportive care |
| What toxicities do you expect from CapeOx? (Capecitabine) | Capecitabine: Hand foot syndrome (Palmar-plantar Erythrodysesthesia); SE of 5-FU; -Counseling points: take with food, do not take with PPIs (may reduce efficacy of capecitabine), if immediate and severe symptoms occur, stop med and call MD (may have dpd deficiency) ⭐️ |
| Toxicities from Oxaliplatin (part of FOLFOX and CapeOx) include? | N/V (moderate), Neuropathy (cold induced - temporary), Sensory (cumulative and can be permanent), Metallic taste in mouth, Possible hair loss, Myelosuppression; pharyngeal parasethesia (cold) and peripheral neuropathy |
| Landmark Colon Cancer Trial: MOSAIC trial Grade 3 peripheral Sensory Neuropathy Comparision of FOLFOX4 and 5-FULV | Combination worked better than Leucovorin. Standard of care for last 20 years. Oxaliplatin improved outocomes; Oxaliplatin causes a lot of problems with NEUROPATHY (dose-limiting toxicity); found that 12% had grade 3 neuropathy (not just bothersome, but limited to hold a fork, tripping, affects daily lives); 5-FU and Lucovroin compared. Follow up trial--> followed 2 months that neuropathy went away and only 1% were left with the debilitating neruopathy |
| Leucovorin Question??why do we give it with 5-FU. does it make it more effective? SE more or less? Combo with MTX? | -More effective in combining; more SE (making 5-FU active and keeping it from metabolizing, otherweise effect would be less) *more effective but more toxic ⭐️ (rescues and alleviates the toxicities with MTX; but Leucovorin with 5-FU (more toxic) with MTX: alleviates the toxicitites |
| Metastatic Colorectal Cancer setting: | -25% of CRC presents with mets -50 - 60% dx CRC will develop mets -Most common site of mets is LIVER ⭐️ (proximity) -Determine KRAS/NRAS/BRAF genotyping and HER2 testing |
| Metastatic Colorectal Cancer Stage IV: Medication therapy? | LOTS OF CHOICES (length of tx is indefinite) |
| CRC: Liver Only or Lung Only Mets? | -Of those, 80 – 90% have unresectable mets -If resectable (isolated), localized resection is treatment of choice -Other options: chemoembolization (conc. amount of chemo and catheter upstream of where cancer is and inject where Mets are) and radiation therapy *main tx is surgery |
| Preoperative Chemo (neoadjuvant) for CRC w/ possible resectable mets? | -If p(proficient)MMR/MSI-S(stable), FOLFOX or CapeOx -If d(deficient)MMR/MSI-H(High), then give neoadjuvant nivolumab ± ipilimumab, pembrolizumab, or dostarlimab-gxly -Reassess every 2 months for resection -6 months of preoperative chemo *only difference from Stage III is the addition of dostarlimab |
| Metastatic Colorectal Cancer with Unresectable mets or not candidate for surgery--> Tx options? (General) | MET-CRC--> dMMR/MSI H (Immunotherapy) (deficient) (meds—> checkpoint) OR pMMR/MSS (FOLFOX or FOLFIRI or FOLIRINOX) PLUS mab depending with markers) (proficient) |
| Metastatic Colon Cancer: dMMR/MSI-H Treatment: 1st line --> | Any line of therapy--> Candidate for immunotherapy and no prior immunotherapy received--> Checkpoint inhibitor immunotherapy -Checkpoint inhibitor options (Pick one)--> -nivolumab + ipilimumab -pembrolizumab -dostarlimab-gxly *deficient Mismatch repair (dMMR)/microsatellite instability - high (MSI-H) |
| Metastatic Colon Cancer: dMMR/MSI-H Treatment 2nd line--> | After progression on a checkpoint inhibitor, follow to pMMR/MSS treatment algorithm *deficient Mismatch repair (dMMR)/microsatellite instability - high (MSI-H) |
| Metastatic Colon Cancer: pMMR/MSS: Intensive 1st line Treatment: Continuum of Care - systemic Therapy for AD: pMMR/MSS (or ineligible for or progression on checkpoint inhibitor immunotherapy)--> intensive therapy recommended: *chemo options: FOX/Cap/Fol (all equivalent) and combine with mAB (3 choices-> combine with (Bev (everyone), Cetux (EGFR but specific criteria), Pani (EGFR but specific criteria) | Initial therapy: FOLFOX +/- Bevacizumab or CapeOx +/- bevacizumab or FOLFOX +/- (Cetuximab or panitumumab) (KRAS/NRAS/BRAF WT and left-sided tumors only) or CapeOx + (cetuximab or panitumumab) (KRAS/NRAS/BRAF WT and left-sided tumors only) or FOLFIRI +/- bevacizumab or FOLFIRI + (cetuximab or pani) (KRAS/NRAS/BRAF WT and left-sided tumors only) or FOLFIRINOX +/- bevaciziumab *Proficient Mismatch repair (pMMR)/microsatellite stability (MSS); WT – wildtype (no mutations) |
| Metastatic Colon Cancer: pMMR/MSS: NOT Intensive 1st line Treatment: Intensive therapy NOT recommended--> | 5-FU +/- leucovorin +/- bevacizumab or Capecitabine +/- bevacizumab or (Cetuximab or panitumumab) (Category 2B) (KRAS/NRAS/BRAF WT and left-sided tumors only) or Trastuzumab + (pertuzumab or lapatinib or tucatinib) (Her2-amplified and RAS and BRAF WT) *HER2 amplification and RAS/BRAF WT--> give Her2 drug |
| Reasons to NOT use mAb? *how to pick your mAB | -mAbs only used in metastatic setting for CRC -Bevacizumab (Should NOT use within 4 week window pre and post major surgery due to impaired healing (wound dehiscence - delayed wound healing) -Recent history of hemoptysis (throwing up ) - won't use Bevacizumab at all |
| KRAS Gene: CO.17 trial: | pts that had WT KRAS that responded to cetuximab benefited and had imporvied Survival numbers. mutation in KRAS-> no benefit to Cetuximab *looking for WT, also seen with BRAF and NRAS. any have a mutation? dont use drug |
| KRAS Gene: CO.17 trial where tumor arised (left or right side) | Left side--> benefit Right side--> survival curve fall on top of each other so no benefit *theory that left and right arose from differnt embroyonic tissue and so may have genetics that are slightly different fromm left or right side of colon |
| CRC: Which mAb? | -mAbs only used in metastatic setting for CRC -Cetuximab or Panitumumab (KRAS wildtype NRAS wildtype and BRAF wildtype AND LEFT sided tumors (all have to present) -Bevacizumab (everyone) *caveat is if you have a hx of hemoptysis, can’t use, or recent major surgery, make sure its been 4 weeks (give them that window of time otherwise, infection will open up) -Trastuzumab + (Pertuzumab or lapatinib or tucatinib) (overamplification and Her2 expression |
| CRC Incidence by location: | Rectum (29%) Sigmoid Colon (26%) Ascending Colon (26%) Transverse Colon (13%) Descending Colon (6%) |
| ADRs of Fluorouracil: | -Mouth Sores -Diarrhea -Myelosuppression -Hand/Foot Syndrome (palmar plantar erythrodysesthesia or Hand and foot syndrome) |
| ADRs of Oxaliplatin: | -Neuropathy -Cold Induced Neuropathy -Myelosuppression -N/V -Fatigue |
| ADRs of Irinotecan: | -Early Onset Diarrhea -Late Onset Diarrhea -Myelosuppression -N/V -Alopecia *i run to the can (diarrhea biggest SE) ⭐️ |
| ADRs of Pembrolizumab: | -Fatigue (most common) (70%) -Rash (71%) -Hyperglycemia (45%) -Hypertriglyceridemia (43%) -Immune mediated pneumonitis/ colitis/ hepatitis/ endocrinopathies/ nephritis/ skin disorders |
| ADRs of Bevacizumab: | -HTN -VTE -Proteinuria -Bleeding (nose bleeds) -Wound dehiscence (impaired wound healing) *Target is *Vascular Endothelial Growth Factor ⭐️ (vascular things are BP, bleeding) |
| ADRs of Cetuximab/ Panitumumab: | -Electrolyte Abnormalities -Low mag, pot, calc -Infusion Reactions -Acneiform Rash *Target is EGFR (epidermal growth factor, so pts will get acne) |
| ADRs of Trastuzumab: | -Allergic rxn -LVEF decrease |
| ADRs of Pertuzumab: | -Allergic rxn -Diarrhea -Acnelike rash -LVEF decrease |
| ADRs of Lapatinib/Tucatinib | -HFS -Acnelike rash -Dyspepsia -D |
| EGFRI Rash? | -Epidermal growth factor is involved with growth and keratinization of skin -Acneiform eruption on face, scalp, upper chest, back appears 1 – 6 weeks after start EGFRI |
| Prevention of EGFRI rash? | -Moisturize twice daily and minimize sun exposure Sunscreen (sun protection factor or SPF ≥ 15) -Lukewarm showers |
| Tx of EGFRI Rash? | -Minocycline 100 mg po daily/Doxycycline 100 mg po bid -Clindamycin 1% wipes -Systemic steroids |
| Minimizing ADRs – EGFRI Induced Diarrhea: | -Treat early and aggressively -Clinical Consequences (Dehydration, Electrolyte imbalances, Acute renal insufficiency or failure) -Important to obtain detailed health history and description of diarrhea -If grade 3 or higher diarrhea, then consider dose reduction or discontinuation *Loperamide, Hydration, Octreotide (IV or SQ but Oct is last choice if they dont respond to hydration or loperamide) |
| CRC Conclusion: | -3rd leading cause of cancer in both women and men and has the third highest cancer mortality rate -CRC has established risk factors -Screening guidelines are in place for early detection of CRC -CRC therapy is based on staging and involves both surgery, XRT, and chemotherapy -Treatment choices are limited in early stage CRC |
| Which of the following pts needs colonoscopy? -20 yo with FAP -34 yo with ulcerative colitis diagnosed 2 years ago -45 yo with no family history | 20 yo with FAP |
| Pt has Stage I colon cancer. Which of the following is a recommended treatment? | Surgery *Surgery and FOLFOX would be correct for stage III, and if Frei said stage II high risk—> surgery and folfox would be correct |
| Common SE of Oxaliplatin (select all) -Cold induced neuropathy -diarrhea 0sensoy neuropathy -mouth sores -cardiomyopathy | -cold-induced neuropathy and sensory induced neuropathy |
| What is the dose limiting toxicity of oxaliplatin? | Sensory neuropathy |
| What is a common ADR of Cetuximab and Panitumumab? | Acne-like rash |
| Metastatic colon cancer arose in the descending colon. Molecular analysis of tumor show KRAS wildtype, NRAS wildtype, BRAF mutation, dMMR/MSI-high. What is first line tx? | Pembrolizumab (checkpoint inhibitor and look for dMMR/MSI-high |
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Xander635
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