]> This is an ontology for represeting clinical practice guidelines that establishes different types of information primitives. Confirm the presence of invasive cancer. Evaluation of tumor size and extent of disease. Medical decision of the best surgical procedure. Medical decision of the best surgical procedure. Diagnosis of gastrointestinal bleeding, suspected tumours and inflammatory bowel disease. Tumor size evaluation and extent of disease. Comprehensive metabolic evaluation. Evaluation of colon cancer. PET-CT scan only if potentially curable M1 disease Check for the presence of cancer cells. Multidisciplinary team evaluation. Genetic mutation testing. Diagnosis of gastrointestinal bleeding, suspected tumours and inflammatory bowel disease. Detection of BRAF V600E mutation Procedure to assess the Treatment 1 action. Procedure to assess the Treatment 2 action. Medical decision of the best surgical procedure. Removal of regional lymph nodes. Procedure to assess the adjuvant therapy 1 action. Procedure to assess the Adjuvant therapy 2 action. Procedure to assess the Adjuvant therapy 3 action. Marking of cancerous polyp site. No adjuvant therapy, proceed to surveillance procedure. Procedure to assess the Surveillance action. Conduct a research study of an innovative therapy for colon cancer. Patient surveillance. Medication Recommendation for adjuvant therapy. Medication recommendation for adjuvant therapy. Medication recommendation for adjuvant therapy Medication recommendation for adjuvant therapy. Conduct a research study of an innovative therapy for colon cancer. Medication recommendation for adjuvant therapy. Removal of regional lymph nodes. Medication Recommendation for adjuvant therapy (preferred). Medication recommendation for adjuvant therapy (preferred). Medication recommendation for adjuvant therapy. Grade 3-4 diarrhea is considerably higher with FLO than FOLFOX in cross study comparison. Obtaining the patient's history and physical. Comprehensive metabolic evaluation. Tumor size evaluation and extent of disease Diagnosis of gastrointestinal bleeding, suspected tumours and inflammatory bowel disease. Diagnosis of gastrointestinal bleeding, suspected tumours and inflammatory bowel disease. Evaluation of colon cancer. PET-CT scan is not routinely recommended. Analysis of the principles of survival. The patient should be put under surveillance. Obtain the patient's history and physical. Procedure to assess the recurrence action. Comprehensive metabolic evaluation. Diagnosis of gastrointestinal bleeding, suspected tumours and inflammatory bowel disease. Procedure to assess the neoadjuvant theraphy action. Surgical resection of any extent of the colon. Medication recommendation for neoadjuvant therapy. Medication recommendation for neoadjuvant therapy. Medication recommendation for neoadjuvant therapy. Medication recommendation for neoadjuvant therapy. Confirm the presence of non-metastatic colon cancer. Medication recommendation for neoadjuvant therapy. Medication recommendation for neoadjuvant therapy. Surgical resection of any extent of the large intestine (colon). Procedure for treatment Surgical resection of any extent of the large intestine (colon). Procedure to acess the treatment action Procedure to assess the chemotherapy action Medication recommendation for treatment. Medication recommendation for treatment. Medication recommendation for treatment. Diagnosis of intestinal bleeding, suspected tumours and inflammatory bowel disease. Medication recommendation for treatment Medication recommendation for treatment. Medication recommendation for treatment. Procedure for treatment. Medication Recommendation for adjuvant therapy. Medication Recommendation for adjuvant therapy Adjuvant therapy. Procedure to assess the surveillance action. Tumor size evaluation and extent of disease. Comprehensive metabolic evaluation. Tumor size evaluation and extent of disease. Procedure to assess the systemic theraphy action. Surgical resection of any extent of the large intestine (colon) Medication recommendation for systemic therapy. Medication recommendation for systemic therapy. Medication recommendation for systemic therapy. Medication recommendation for systemic therapy. Medication recommendation for systemic therapy. Medication recommendation for systemic therapy. Medication recommendation for systemic therapy. Evaluation of tumor size and extent of disease. Re-evaluation procedure Procedures for adjuvant therapy. Procedure for metastases converted to resectable. Consider PET-CT scan. Tumor size evaluation and extent of disease. Diagnosis of gastrointestinal bleeding, suspected tumours and inflammatory bowel disease. Procedures for a positive evolution after neoadjuvant therapy. Procedures for a negative evolution after neoadjuvant therapy. Preparation for the active therapy regimen. Perform a full physical exam. Primary treatment for metachronous metastases. Preferred adjuvant treatment. Resection. Hepatic artery infusion +/- 5-1FU/leucovori is also an option at institutions with experience in both the surgical and medical oncologic aspects of this procedure Procedures for a positive evolution after neoadjuvant therapy. Procedures for a negative evolution after neoadjuvant therapy. Assessment of primary treatment procedures. Preparation for chemotherapy. Preparation for chemotherapy. Preparation for chemotherapy. Preparation for chemotherapy. Therapy after first progression. Combination therapy involving cytotoxics, anti-EGFRs, and anti-VEGFs is not recommended. Cetuximab is indicated in combination with innotecan-based therapy or as single-agent therapy for patients who cannot tolerate irinotecan. There are no data, nor is there a compelling rationale, to support the use of panitumumab after clinical failure on cetuximab, or the use of cetuximab after clinical failure on panitumumab. As such, the use of one of these agents after therapeutic failure on the other is not recommended. EGFR testing has no demonstrated predictive value; therefore, routine EGFR testing is not recommended. No patient should be included or excluded from cetuximab or panitumumab therapy on the basis of EGFR test results. Patients with a V600E BRAF mutation appear to have a poorer prognosis. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. lrinotecan should be used with caution and with decreased doses in patients with Gilbert’s disease or elevated serum bilirubin. There is a commercially available test for UGT1 Al. Guidelines for use in clinical practice have not been established. Principles of pathologic review: -KRAS Mutation Testing: --Mutations in codons 12 and 13 in exon 2 of the coding region of the KRAS gene predict lack of response to therapy with antibodies targeted to the EGFRA. --Testing for mutations in codons 12 and 13 should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) as qualified to perform high complexity clinical laboratory (molecular pathology) testing. No specific methodology is recommended (eg, sequencing, hybridization). --The testing can be performed on formalin-fixed paraffin-embedded tissue. The testing can be performed on the primary colorectal cancers and/or the metastasis, as literature has shown that the KRAS mutations are similar in both specimen types. -BRAF Mutation Testing: --Patients with a V600E BRAF mutation appear to have a poorer prognosis. There are insufficient data to guide the use of anti-EGFR therapy in the first-line setting with active chemotherapy based on BRAF V600E mutation status. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. --Testing for the BRAF V600E mutation can be performed on formalin-fixed paraffin-embedded tissues. This is usually performed by amplification and direct DNA sequence analysis. Allele-specific PCR is another acceptable method for detecting BRAF V600E mutation. This testing should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) and qualified to perform high complexity clinical laboratory (molecular pathology) testing. -MSI Testing - See NCCN Guidelines for Colorectal Cancer Screening: --The panel recommends that MMR protein testing be performed for all patients younger than 50 years with coloncancer, based on na increased likelihood of Lynch syndrome in this population. MMR testing should also be considered for all patients with stage II disease, because stage II MSI-H patients may have a good prognosis and do not benefit from 5-FU adjuvant therapy. Preparation for chemotherapy. Therapy after second progression For patients not able to tolerate the combination, consider single agent cetuximab or panitumumab. Combination therapy involving cytotoxics, anti-EGFRs, and anti-VEGFs is not recommended. Cetuximab is indicated in combination with innotecan-based therapy or as single-agent therapy for patients who cannot tolerate irinotecan. There are no data, nor is there a compelling rationale, to support the use of panitumumab after clinical failure on cetuximab, or the use of cetuximab after clinical failure on panitumumab. As such, the use of one of these agents after therapeutic failure on the other is not recommended. EGFR testing has no demonstrated predictive value; therefore, routine EGFR testing is not recommended. No patient should be included or excluded from cetuximab or panitumumab therapy on the basis of EGFR test results. Patients with a V600E BRAF mutation appear to have a poorer prognosis. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. lrinotecan should be used with caution and with decreased doses in patients with Gilbert’s disease or elevated serum bilirubin. There is a commercially available test for UGT1 Al. Guidelines for use in clinical practice have not been established. Principles of pathologic review: -KRAS Mutation Testing: --Mutations in codons 12 and 13 in exon 2 of the coding region of the KRAS gene predict lack of response to therapy with antibodies targeted to the EGFRA. --Testing for mutations in codons 12 and 13 should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) as qualified to perform high complexity clinical laboratory (molecular pathology) testing. No specific methodology is recommended (eg, sequencing, hybridization). --The testing can be performed on formalin-fixed paraffin-embedded tissue. The testing can be performed on the primary colorectal cancers and/or the metastasis, as literature has shown that the KRAS mutations are similar in both specimen types. -BRAF Mutation Testing: --Patients with a V600E BRAF mutation appear to have a poorer prognosis. There are insufficient data to guide the use of anti-EGFR therapy in the first-line setting with active chemotherapy based on BRAF V600E mutation status. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. --Testing for the BRAF V600E mutation can be performed on formalin-fixed paraffin-embedded tissues. This is usually performed by amplification and direct DNA sequence analysis. Allele-specific PCR is another acceptable method for detecting BRAF V600E mutation. This testing should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) and qualified to perform high complexity clinical laboratory (molecular pathology) testing. -MSI Testing - See NCCN Guidelines for Colorectal Cancer Screening: --The panel recommends that MMR protein testing be performed for all patients younger than 50 years with coloncancer, based on na increased likelihood of Lynch syndrome in this population. MMR testing should also be considered for all patients with stage II disease, because stage II MSI-H patients may have a good prognosis and do not benefit from 5-FU adjuvant therapy. Preparation for chemotherapy. Preparation for therapy. Preparation for chemotherapy. Therapy after first progression. for patients not able to tolerate combination, consider single agent (cetuximab or panitumumab). Combination therapy involving cytotoxics, anti-EGFRs, and anti-VEGFs is not recommended. Cetuximab is indicated in combination with innotecan-based therapy or as single-agent therapy for patients who cannot tolerate irinotecan. EGFR testing has no demonstrated predictive value; therefore, routine EGFR testing is not recommended. No patient should be included or excluded from cetuximab or panitumumab therapy on the basis of EGFR test results. There are no data, nor is there a compelling rationale, to support theuse of panitumumab after clinical failure on cetuximab, or the use of cetuximab after clinical failure on panitumumab. As such, the use of one of these agents after therapeutic failure on the other is not recommended. Patients with a V600E BRAF mutation appear to have a poorer prognosis. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. lrinotecan should be used with caution and with decreased doses in patients with Gilbert’s disease or elevated serum bilirubin. There is a commercially available test for UGT1A1. Guidelines for use in clinical practice have not been established. Preparation for chemotherapy. Preparation for chemotherapy. Preparation for chemotherapy. Preparation for chemotherapy. Preparation for chemotherapy. Primary treatment for metachronous metastases. Set of exams to assess cancer recurrence given serial CEA elevation Resection. Artery infusion +/- systemic 5-FU/leucovorin is also an option at institutions with experience in both the surgical and medical oncologic aspects of this procedure. Adjuvant treatment. Resection. Hepatic artery infusion +/- 5-1FU/leucovori is also an option at institutions with experience in both the surgical and medical oncologic aspects of this procedure Repeat neoadjuvant therapy. Adjuvant treatment. Surveillance of tumor growth. Observation (preferred for previous oxaliplatin-based therapy) Medication recommendation for primary treatment. Consider PET-CT scan. Re-evaluate chest/abdominal/pelvic CT in 3 months. Re-evaluation of resectability. Resection. Hepatic artery infusion +/- 5-1FU/leucovori is also an option at institutions with experience in both the surgical and medical oncologic aspects of this procedure. Initial therapy. Discontinuation of oxaliplatin should be strongly considered from FOLFOX or CapeOX after 3-4 months of therapy (or sooner if significant neurotoxicity develops higher than grade 2) with other drugs maintained (fluoropyrimidine + bevacizumab) until time of tumor progression. Oxaliplatin may be reintroduced if it was discontinued previously for neurotoxicity rather than disease progression. Initial therapy.The majority of safety and efficacy data for this regimen have been developed in Europe, where a capecitabine starting dose of 1000 mg/m2 twice daily for 14 days, repeated every 21 days, is standard. Evidence suggests that North American patients may experience greater toxicity with capecitabine (as well as with other fluoropyrimidines) than European patients, and may require a lower dose of capecitabine. The relative efficacy of CapeOx with lower starting doses of capecitabine has not been addressed in large-scale randomized trials. There is an increased risk of stroke and other arterial events, especially in those aged higher than 65 years. The use of bevacizumab may interfere with wound healing. Combination therapy involving cytotoxics, anti-EGFRs, and anti-VEGFs is not recommended. Initial therapy. Discontinuation of oxaliplatin should be strongly considered from FOLFOX or CapeOX after 3-4 months of therapy (or sooner if significant neurotoxicity develops higher than grade 2) with other drugs maintained (fluoropyrimidine + bevacizumab) until time of tumor progression. Oxaliplatin may be reintroduced if it was discontinued previously for neurotoxicity rather than disease progression. Combination therapy involving cytotoxics, anti-EGFRs, and anti-VEGFs is not recommended. lf cetuximab or panitumumab is used as initial therapy, then neither cetuximab nor panitumumab should be used in second or subsequent lines of therapy. There are insufficient data to guide the use of anti-EGFR therapy in the first-line setting with active chemotherapy based on BRAF V600E mutation status. Principles of pathologic review: -KRAS Mutation Testing: --Mutations in codons 12 and 13 in exon 2 of the coding region of the KRAS gene predict lack of response to therapy with antibodies targeted to the EGFRA. --Testing for mutations in codons 12 and 13 should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) as qualified to perform high complexity clinical laboratory (molecular pathology) testing. No specific methodology is recommended (eg, sequencing, hybridization). --The testing can be performed on formalin-fixed paraffin-embedded tissue. The testing can be performed on the primary colorectal cancers and/or the metastasis, as literature has shown that the KRAS mutations are similar in both specimen types. -BRAF Mutation Testing: --Patients with a V600E BRAF mutation appear to have a poorer prognosis. There are insufficient data to guide the use of anti-EGFR therapy in the first-line setting with active chemotherapy based on BRAF V600E mutation status. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. --Testing for the BRAF V600E mutation can be performed on formalin-fixed paraffin-embedded tissues. This is usually performed by amplification and direct DNA sequence analysis. Allele-specific PCR is another acceptable method for detecting BRAF V600E mutation. This testing should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) and qualified to perform high complexity clinical laboratory (molecular pathology) testing. -MSI Testing - See NCCN Guidelines for Colorectal Cancer Screening: --The panel recommends that MMR protein testing be performed for all patients younger than 50 years with coloncancer, based on na increased likelihood of Lynch syndrome in this population. MMR testing should also be considered for all patients with stage II disease, because stage II MSI-H patients may have a good prognosis and do not benefit from 5-FU adjuvant therapy. Initial therapy. lrinotecan should be used with caution and with decreased doses in patients with Gilbert’s disease or elevated serum bilirubin. There is a commercially available test for UGT1 Al. Guidelines for use in clinical practice have not been established. There is an increased risk of stroke and other arterial events, especially in those aged over 65 years. The use of bevacizumab may interfere with wound healing. Combination therapy involving cytotoxics, anti-EGFRs, and anti-VEGFs is not recommended. Initial therapy. Combination therapy involving cytotoxics, anti-EGFRs, and anti-VEGFs is not recommended. lf cetuximab or panitumumab is used as initial therapy, then neither cetuximab nor panitumumab should be used in second or subsequent lines of therapy. There are insufficient data to guide the use of anti-EGFR therapy in the first-line setting with active chemotherapy based on BRAF V600E mutation status. lrinotecan should be used with caution and with decreased doses in patients with Gilbert’s disease or elevated serum bilirubin. There is a commercially available test for UGT1A1. Guidelines for use in clinical practice have not been established. Principles of pathologic review: -KRAS Mutation Testing: --Mutations in codons 12 and 13 in exon 2 of the coding region of the KRAS gene predict lack of response to therapy with antibodies targeted to the EGFRA. --Testing for mutations in codons 12 and 13 should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) as qualified to perform high complexity clinical laboratory (molecular pathology) testing. No specific methodology is recommended (eg, sequencing, hybridization). --The testing can be performed on formalin-fixed paraffin-embedded tissue. The testing can be performed on the primary colorectal cancers and/or the metastasis, as literature has shown that the KRAS mutations are similar in both specimen types. -BRAF Mutation Testing: --Patients with a V600E BRAF mutation appear to have a poorer prognosis. There are insufficient data to guide the use of anti-EGFR therapy in the first-line setting with active chemotherapy based on BRAF V600E mutation status. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. --Testing for the BRAF V600E mutation can be performed on formalin-fixed paraffin-embedded tissues. This is usually performed by amplification and direct DNA sequence analysis. Allele-specific PCR is another acceptable method for detecting BRAF V600E mutation. This testing should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) and qualified to perform high complexity clinical laboratory (molecular pathology) testing. -MSI Testing - See NCCN Guidelines for Colorectal Cancer Screening: --The panel recommends that MMR protein testing be performed for all patients younger than 50 years with coloncancer, based on na increased likelihood of Lynch syndrome in this population. MMR testing should also be considered for all patients with stage II disease, because stage II MSI-H patients may have a good prognosis and do not benefit from 5-FU adjuvant therapy. Initial therapy. Combination therapy involving cytotoxics, anti-EGFRs, and anti-VEGFs is not recommended. lf cetuximab or panitumumab is used as initial therapy, then neither cetuximab nor panitumumab should be used in second or subsequent lines of therapy. There are insufficient data to guide the use of anti-EGFR therapy in the first-line setting with active chemotherapy based on BRAF V600E mutation status. lrinotecan should be used with caution and with decreased doses in patients with Gilbert’s disease or elevated serum bilirubin. There is a commercially available test for UGT1A1. Guidelines for use in clinical practice have not been established. Principles of pathologic review: -KRAS Mutation Testing: --Mutations in codons 12 and 13 in exon 2 of the coding region of the KRAS gene predict lack of response to therapy with antibodies targeted to the EGFRA. --Testing for mutations in codons 12 and 13 should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) as qualified to perform high complexity clinical laboratory (molecular pathology) testing. No specific methodology is recommended (eg, sequencing, hybridization). --The testing can be performed on formalin-fixed paraffin-embedded tissue. The testing can be performed on the primary colorectal cancers and/or the metastasis, as literature has shown that the KRAS mutations are similar in both specimen types. -BRAF Mutation Testing: --Patients with a V600E BRAF mutation appear to have a poorer prognosis. There are insufficient data to guide the use of anti-EGFR therapy in the first-line setting with active chemotherapy based on BRAF V600E mutation status. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. --Testing for the BRAF V600E mutation can be performed on formalin-fixed paraffin-embedded tissues. This is usually performed by amplification and direct DNA sequence analysis. Allele-specific PCR is another acceptable method for detecting BRAF V600E mutation. This testing should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) and qualified to perform high complexity clinical laboratory (molecular pathology) testing. -MSI Testing - See NCCN Guidelines for Colorectal Cancer Screening: --The panel recommends that MMR protein testing be performed for all patients younger than 50 years with coloncancer, based on na increased likelihood of Lynch syndrome in this population. MMR testing should also be considered for all patients with stage II disease, because stage II MSI-H patients may have a good prognosis and do not benefit from 5-FU adjuvant therapy. Initial therapy lnfusional 5-FU is preferred. There is an increased risk of stroke and other arterial events, especially in those aged over 65 years. The use of bevacizumab may interfere with wound healing. Combination therapy involving cytotoxics, anti-EGFRs, and anti-VEGFs is not recommended. A treatment option for patients not able to tolerate oxaliplatin or irinotecan. Initial therapy Patients with diminished creatinine clearance may require dose modification of capecitabine. There is an increased risk of stroke and other arterial events, especially in those aged over 65 years. The use of bevacizumab may interfere with wound healing. Combination therapy involving cytotoxics, anti-EGFRs, and anti-VEGFs is not recommended. A treatment option for patients not able to tolerate oxaliplatin or irinotecan. Initial therapy. Data are not mature for the addition of biologic agents to FOLFOXIRI. Therapy after first progression. There is an increased risk of stroke and other arterial events, especially in those aged more than 65 years. The use of bevacizumab may interfere with wound healing. Therapy after first progression.lrinotecan should be used with caution and with decreased doses in patients with Gilbert’s disease or elevated serum bilirubin. There is a commercially available test for UGT1A1. Guidelines for use in clinical practice have not been established. Therapy after first progression. lrinotecan should be used with caution and with decreased doses in patients with Gilbert’s disease or elevated serum bilirubin. There is a commercially available test for UGT1A1. Guidelines for use in clinical practice have not been established. Therapy after first progression. lrinotecan should be used with caution and with decreased doses in patients with Gilbert’s disease or elevated serum bilirubin. There is a commercially available test for UGT1A1. Guidelines for use in clinical practice have not been established. There are no data to suggest activity of FOLFIRI-ziv-aflibercept in a patient who has progressed on FOLFIRI-bevacizumab, or vice versa. Ziv-aflibercept has only shown activity when given in conjunction with FOLFIRI in FOLFIRI-naive patients. Therapy after first progression. Combination therapy involving cytotoxics, anti-EGFRs, and anti-VEGFs is not recommended. Cetuximab is indicated in combination with innotecan-based therapy or as single-agent therapy for patients who cannot tolerate irinotecan. There are no data, nor is there a compelling rationale, to support the use of panitumumab after clinical failure on cetuximab, or the use of cetuximab after clinical failure on panitumumab. As such, the use of one of these agents after therapeutic failure on the other is not recommended. EGFR testing has no demonstrated predictive value; therefore, routine EGFR testing is not recommended. No patient should be included or excluded from cetuximab or panitumumab therapy on the basis of EGFR test results. Patients with a V600E BRAF mutation appear to have a poorer prognosis. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. Principles of pathologic review: -KRAS Mutation Testing: --Mutations in codons 12 and 13 in exon 2 of the coding region of the KRAS gene predict lack of response to therapy with antibodies targeted to the EGFRA. --Testing for mutations in codons 12 and 13 should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) as qualified to perform high complexity clinical laboratory (molecular pathology) testing. No specific methodology is recommended (eg, sequencing, hybridization). --The testing can be performed on formalin-fixed paraffin-embedded tissue. The testing can be performed on the primary colorectal cancers and/or the metastasis, as literature has shown that the KRAS mutations are similar in both specimen types. -BRAF Mutation Testing: --Patients with a V600E BRAF mutation appear to have a poorer prognosis. There are insufficient data to guide the use of anti-EGFR therapy in the first-line setting with active chemotherapy based on BRAF V600E mutation status. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. --Testing for the BRAF V600E mutation can be performed on formalin-fixed paraffin-embedded tissues. This is usually performed by amplification and direct DNA sequence analysis. Allele-specific PCR is another acceptable method for detecting BRAF V600E mutation. This testing should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) and qualified to perform high complexity clinical laboratory (molecular pathology) testing. -MSI Testing - See NCCN Guidelines for Colorectal Cancer Screening: --The panel recommends that MMR protein testing be performed for all patients younger than 50 years with coloncancer, based on na increased likelihood of Lynch syndrome in this population. MMR testing should also be considered for all patients with stage II disease, because stage II MSI-H patients may have a good prognosis and do not benefit from 5-FU adjuvant therapy. Therapy after first progression. Combination therapy involving cytotoxics, anti-EGFRs, and anti-VEGFs is not recommended. Cetuximab is indicated in combination with innotecan-based therapy or as single-agent therapy for patients who cannot tolerate irinotecan. There are no data, nor is there a compelling rationale, to support the use of panitumumab after clinical failure on cetuximab, or the use of cetuximab after clinical failure on panitumumab. As such, the use of one of these agents after therapeutic failure on the other is not recommended. EGFR testing has no demonstrated predictive value; therefore, routine EGFR testing is not recommended. No patient should be included or excluded from cetuximab or panitumumab therapy on the basis of EGFR test results. Patients with a V600E BRAF mutation appear to have a poorer prognosis. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. Therapy after first progression. Combination therapy involving cytotoxics, anti-EGFRs, and anti-VEGFs is not recommended. Cetuximab is indicated in combination with innotecan-based therapy or as single-agent therapy for patients who cannot tolerate irinotecan. There are no data, nor is there a compelling rationale, to support the use of panitumumab after clinical failure on cetuximab, or the use of cetuximab after clinical failure on panitumumab. As such, the use of one of these agents after therapeutic failure on the other is not recommended. EGFR testing has no demonstrated predictive value; therefore, routine EGFR testing is not recommended. No patient should be included or excluded from cetuximab or panitumumab therapy on the basis of EGFR test results. Patients with a V600E BRAF mutation appear to have a poorer prognosis. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. lrinotecan should be used with caution and with decreased doses in patients with Gilbert’s disease or elevated serum bilirubin. There is a commercially available test for UGT1 Al. Guidelines for use in clinical practice have not been established. Principles of pathologic review: -KRAS Mutation Testing: --Mutations in codons 12 and 13 in exon 2 of the coding region of the KRAS gene predict lack of response to therapy with antibodies targeted to the EGFRA. --Testing for mutations in codons 12 and 13 should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) as qualified to perform high complexity clinical laboratory (molecular pathology) testing. No specific methodology is recommended (eg, sequencing, hybridization). --The testing can be performed on formalin-fixed paraffin-embedded tissue. The testing can be performed on the primary colorectal cancers and/or the metastasis, as literature has shown that the KRAS mutations are similar in both specimen types. -BRAF Mutation Testing: --Patients with a V600E BRAF mutation appear to have a poorer prognosis. There are insufficient data to guide the use of anti-EGFR therapy in the first-line setting with active chemotherapy based on BRAF V600E mutation status. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. --Testing for the BRAF V600E mutation can be performed on formalin-fixed paraffin-embedded tissues. This is usually performed by amplification and direct DNA sequence analysis. Allele-specific PCR is another acceptable method for detecting BRAF V600E mutation. This testing should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) and qualified to perform high complexity clinical laboratory (molecular pathology) testing. -MSI Testing - See NCCN Guidelines for Colorectal Cancer Screening: --The panel recommends that MMR protein testing be performed for all patients younger than 50 years with coloncancer, based on na increased likelihood of Lynch syndrome in this population. MMR testing should also be considered for all patients with stage II disease, because stage II MSI-H patients may have a good prognosis and do not benefit from 5-FU adjuvant therapy. Procedure for positive findings of metachronous metastases. Therapy after second progression For patients not able to tolerate the combination, consider single agent cetuximab or panitumumab. Combination therapy involving cytotoxics, anti-EGFRs, and anti-VEGFs is not recommended. Cetuximab is indicated in combination with innotecan-based therapy or as single-agent therapy for patients who cannot tolerate irinotecan. There are no data, nor is there a compelling rationale, to support the use of panitumumab after clinical failure on cetuximab, or the use of cetuximab after clinical failure on panitumumab. As such, the use of one of these agents after therapeutic failure on the other is not recommended. EGFR testing has no demonstrated predictive value; therefore, routine EGFR testing is not recommended. No patient should be included or excluded from cetuximab or panitumumab therapy on the basis of EGFR test results. Patients with a V600E BRAF mutation appear to have a poorer prognosis. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. lrinotecan should be used with caution and with decreased doses in patients with Gilbert’s disease or elevated serum bilirubin. There is a commercially available test for UGT1 Al. Guidelines for use in clinical practice have not been established. Principles of pathologic review: -KRAS Mutation Testing: --Mutations in codons 12 and 13 in exon 2 of the coding region of the KRAS gene predict lack of response to therapy with antibodies targeted to the EGFRA. --Testing for mutations in codons 12 and 13 should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) as qualified to perform high complexity clinical laboratory (molecular pathology) testing. No specific methodology is recommended (eg, sequencing, hybridization). --The testing can be performed on formalin-fixed paraffin-embedded tissue. The testing can be performed on the primary colorectal cancers and/or the metastasis, as literature has shown that the KRAS mutations are similar in both specimen types. -BRAF Mutation Testing: --Patients with a V600E BRAF mutation appear to have a poorer prognosis. There are insufficient data to guide the use of anti-EGFR therapy in the first-line setting with active chemotherapy based on BRAF V600E mutation status. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. --Testing for the BRAF V600E mutation can be performed on formalin-fixed paraffin-embedded tissues. This is usually performed by amplification and direct DNA sequence analysis. Allele-specific PCR is another acceptable method for detecting BRAF V600E mutation. This testing should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) and qualified to perform high complexity clinical laboratory (molecular pathology) testing. -MSI Testing - See NCCN Guidelines for Colorectal Cancer Screening: --The panel recommends that MMR protein testing be performed for all patients younger than 50 years with coloncancer, based on na increased likelihood of Lynch syndrome in this population. MMR testing should also be considered for all patients with stage II disease, because stage II MSI-H patients may have a good prognosis and do not benefit from 5-FU adjuvant therapy. Therapy after second progression. Therapy after second progression. Therapy after second progression Conduct a research study of an innovative therapy for colon cancer. Therapy after second progression. Single-agent or combination therapy with capecitabine, mitomycin, or gemcitabine has not been shown to be effective in this setting. Therapy after third progression. Administer regorafenib if not given previously. Therapy after first progression. Discontinuation of oxaliplatin should be strongly considered from FOLFOX or CapeOX after 3-4 months of therapy (or sooner if significant neurotoxicity develops higher than grade 2) with other drugs maintained (fluoropyrimidine + bevacizumab) until time of tumor progression. Oxaliplatin may be reintroduced if it was discontinued previously for neurotoxicity rather than disease progression. There are insufficient data to support the routine use of Ca/Mg infusion to prevent oxaliplatin-related neurotoxicity. There is an increased risk of stroke and other arterial events, especially in those aged over 65 years. The use of bevacizumab may interfere with wound healing. Therapy after first progression. The majority of safety and efficacy data for this regimen have been developed in Europe, where a capecitabine starting dose of 1000 mg/m2 twice daily for 14 days, repeated every 21 days, is standard. Evidence suggests that North American patients may experience greater toxicity with capecitabine (as well as with other fluoropyrimidines) than European patients, and may require a lower dose of capecitabine. The relative efficacy of CapeOx with lower starting doses of capecitabine has not been addressed in large-scale randomized trials. There is an increased risk of stroke and other arterial events, especially in those aged over 65 years. The use of bevacizumab may interfere with wound healing. Therapy after first progression. for patients not able to tolerate combination, consider single agent (cetuximab or panitumumab). Combination therapy involving cytotoxics, anti-EGFRs, and anti-VEGFs is not recommended. Cetuximab is indicated in combination with innotecan-based therapy or as single-agent therapy for patients who cannot tolerate irinotecan. EGFR testing has no demonstrated predictive value; therefore, routine EGFR testing is not recommended. No patient should be included or excluded from cetuximab or panitumumab therapy on the basis of EGFR test results. There are no data, nor is there a compelling rationale, to support theuse of panitumumab after clinical failure on cetuximab, or the use of cetuximab after clinical failure on panitumumab. As such, the use of one of these agents after therapeutic failure on the other is not recommended. Patients with a V600E BRAF mutation appear to have a poorer prognosis. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. lrinotecan should be used with caution and with decreased doses in patients with Gilbert’s disease or elevated serum bilirubin. There is a commercially available test for UGT1A1. Guidelines for use in clinical practice have not been established. Therapy after second progression. Discontinuation of oxaliplatin should be strongly considered from FOLFOX or CapeOX after 3-4 months of therapy (or sooner if significant neurotoxicity develops higher than grade 2) with other drugs maintained (fluoropyrimidine + bevacizumab) until time of tumor progression. Oxaliplatin may be reintroduced if it was discontinued previously for neurotoxicity rather than disease progression. There are insufficient data to support the routine use of Ca/Mg infusion to prevent oxaliplatin-related neurotoxicity. Consider PET-CT scan. Therapy after second progression. The majority of safety and efficacy data for this regimen have been developed in Europe, where a capecitabine starting dose of 1000 mg/m2 twice daily for 14 days, repeated every 21 days, is standard. Evidence suggests that North American patients may experience greater toxicity with capecitabine (as well as with other fluoropyrimidines) than European patients, and may require a lower dose of capecitabine. The relative efficacy of CapeOx with lower starting doses of capecitabine has not been addressed in large-scale randomized trials. Therapy after first progression. Discontinuation of oxaliplatin should be strongly considered from FOLFOX or CapeOX after 3-4 months of therapy (or sooner if significant neurotoxicity develops higher than grade 2) with other drugs maintained (fluoropyrimidine + bevacizumab) until time of tumor progression. Oxaliplatin may be reintroduced if it was discontinued previously for neurotoxicity rather than disease progression. There are insufficient data to support the routine use of Ca/Mg infusion to prevent oxaliplatin-related neurotoxicity. There is an increased risk of stroke and other arterial events, especially in those aged over 65 years. The use of bevacizumab may interfere with wound healing. Therapy after first progression. The majority of safety and efficacy data for this regimen have been developed in Europe, where a capecitabine starting dose of 1000 mg/m2 twice daily for 14 days, repeated every 21 days, is standard. Evidence suggests that North American patients may experience greater toxicity with capecitabine (as well as with other fluoropyrimidines) than European patients, and may require a lower dose of capecitabine. The relative efficacy of CapeOx with lower starting doses of capecitabine has not been addressed in large-scale randomized trials. There is an increased risk of stroke and other arterial events, especially in those aged over 65 years. The use of bevacizumab may interfere with wound healing. Therapy after first progression. lrinotecan should be used with caution and with decreased doses in patients with Gilbert’s disease or elevated serum bilirubin. There is a commercially available test for UGT1A1. Guidelines for use in clinical practice have not been established. Therapy after first progression. lrinotecan should be used with caution and with decreased doses in patients with Gilbert’s disease or elevated serum bilirubin. There is a commercially available test for UGT1A1. Guidelines for use in clinical practice have not been established. Therapy after first progression. lrinotecan should be used with caution and with decreased doses in patients with Gilbert’s disease or elevated serum bilirubin. There is a commercially available test for UGT1A1. Guidelines for use in clinical practice have not been established. Therapy after first progression. lrinotecan should be used with caution and with decreased doses in patients with Gilbert’s disease or elevated serum bilirubin. There is a commercially available test for UGT1A1. Guidelines for use in clinical practice have not been established. Therapy after first progression. lrinotecan should be used with caution and with decreased doses in patients with Gilbert’s disease or elevated serum bilirubin. There is a commercially available test for UGT1A1. Guidelines for use in clinical practice have not been established. Therapy after first progression. There are no data to suggest activity of FOLFIRI-ziv-aflibercept in apatient who has progressed on FOLFIRI-bevacizumab, or vice versa. Ziv-aflibercept has only shown activity when given in conjunction with FOLFIRI in FOLFIRI-naive patients. Therapy after second progression. Discontinuation of oxaliplatin should be strongly considered from FOLFOX or CapeOX after 3-4 months of therapy (or sooner if significant neurotoxicity develops higher than grade 2) with other drugs maintained (fluoropyrimidine + bevacizumab) until time of tumor progression. Oxaliplatin may be reintroduced if it was discontinued previously for neurotoxicity rather than disease progression. There are insufficient data to support the routine use of Ca/Mg infusion to prevent oxaliplatin-related neurotoxicity. Treatment for resectable metastases. Therapy after second progression. The majority of safety and efficacy data for this regimen have been developed in Europe, where a capecitabine starting dose of 1000 mg/m2 twice daily for 14 days, repeated every 21 days, is standard. Evidence suggests that North American patients may experience greater toxicity with capecitabine (as well as with other fluoropyrimidines) than European patients, and may require a lower dose of capecitabine. The relative efficacy of CapeOx with lower starting doses of capecitabine has not been addressed in large-scale randomized trials. Initial therapy Initial therapy. There are insufficient data to guide the use of anti-EGFR therapy in the first-line setting with active chemotherapy based on BRAF V600E mutation status. Principles of pathologic review: -KRAS Mutation Testing: --Mutations in codons 12 and 13 in exon 2 of the coding region of the KRAS gene predict lack of response to therapy with antibodies targeted to the EGFRA. --Testing for mutations in codons 12 and 13 should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) as qualified to perform high complexity clinical laboratory (molecular pathology) testing. No specific methodology is recommended (eg, sequencing, hybridization). --The testing can be performed on formalin-fixed paraffin-embedded tissue. The testing can be performed on the primary colorectal cancers and/or the metastasis, as literature has shown that the KRAS mutations are similar in both specimen types. -BRAF Mutation Testing: --Patients with a V600E BRAF mutation appear to have a poorer prognosis. There are insufficient data to guide the use of anti-EGFR therapy in the first-line setting with active chemotherapy based on BRAF V600E mutation status. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. --Testing for the BRAF V600E mutation can be performed on formalin-fixed paraffin-embedded tissues. This is usually performed by amplification and direct DNA sequence analysis. Allele-specific PCR is another acceptable method for detecting BRAF V600E mutation. This testing should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) and qualified to perform high complexity clinical laboratory (molecular pathology) testing. -MSI Testing - See NCCN Guidelines for Colorectal Cancer Screening: --The panel recommends that MMR protein testing be performed for all patients younger than 50 years with coloncancer, based on na increased likelihood of Lynch syndrome in this population. MMR testing should also be considered for all patients with stage II disease, because stage II MSI-H patients may have a good prognosis and do not benefit from 5-FU adjuvant therapy. Initial therapy. Initial therapy. There are insufficient data to guide the use of anti-EGFR therapy in the first-line setting with active chemotherapy based on BRAF V600E mutation status. Principles of pathologic review: -KRAS Mutation Testing: --Mutations in codons 12 and 13 in exon 2 of the coding region of the KRAS gene predict lack of response to therapy with antibodies targeted to the EGFRA. --Testing for mutations in codons 12 and 13 should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) as qualified to perform high complexity clinical laboratory (molecular pathology) testing. No specific methodology is recommended (eg, sequencing, hybridization). --The testing can be performed on formalin-fixed paraffin-embedded tissue. The testing can be performed on the primary colorectal cancers and/or the metastasis, as literature has shown that the KRAS mutations are similar in both specimen types. -BRAF Mutation Testing: --Patients with a V600E BRAF mutation appear to have a poorer prognosis. There are insufficient data to guide the use of anti-EGFR therapy in the first-line setting with active chemotherapy based on BRAF V600E mutation status. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. --Testing for the BRAF V600E mutation can be performed on formalin-fixed paraffin-embedded tissues. This is usually performed by amplification and direct DNA sequence analysis. Allele-specific PCR is another acceptable method for detecting BRAF V600E mutation. This testing should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) and qualified to perform high complexity clinical laboratory (molecular pathology) testing. -MSI Testing - See NCCN Guidelines for Colorectal Cancer Screening: --The panel recommends that MMR protein testing be performed for all patients younger than 50 years with coloncancer, based on na increased likelihood of Lynch syndrome in this population. MMR testing should also be considered for all patients with stage II disease, because stage II MSI-H patients may have a good prognosis and do not benefit from 5-FU adjuvant therapy. See NCCN Guidelines for Palliative Care. Procedure for improvement in functional status. Medication recommendation for primary treatment. Medication recommendation for primary treatment. Medication recommendation for primary treatment. Procedures for unresectable metachronous metastases. Medication recommendation for primary treatment. Medication recommendation for primary treatment. Medication recommendation for primary treatment. Medication recommendation for primary treatment. Assessment of procedures for active chemotherapy regimen. Resection for primary treatment. Hepatic artery infusion +/- 5-1FU/leucovori is also an option at institutions with experience in both the surgical and medical oncologic aspects of this procedure invasive cancer yes null suspected or proven metastatic synchronous adenocarinoma no null synchronous metastases abdominal/peritoneal null metastases resectability unresectable unconvertible null colon cancer yes null histologic features of polyp favorable null polyp margins clear null shape of polyps pedunculated null shape of polyps sessile null colon cancer appropriate for resection yes null tumor resectability resectable null bowel obstruction nonobstructing string suspected or proven metastatic synchronous adenocarcinoma yes null potentially surgically curable M1 disease yes null clinically indicated yes null colon cancer no null KRAS mutated no null tumor resectability locally unresectable null medically inoperable yes null obstructing or imminently obstructing metastases no null tumor resectability resectable null bowel obstruction obstructing null obstructing or imminenttly obstructing metastases yes null Primary Tumor (T) T1 null Regional Lymph Nodes (N) N0 null colon cancer yes null Distant Metastasis (M) M0 null Primary Tumor (T) T2 null Primary Tumor (T) Tis null Primary Tumor (T) T3 null cancer high-risk features no null cancer high-risk features yes null Primary Tumor (T) T4a null Regional Lymph Nodes (N) N1 null shape of polyps sessile null Regional Lymph Nodes (N) N2 null advanced adenoma yes null advanced adenoma no null synchronous metastases liver and/or lung only null metastases resectability resectable null metastases resectability unresectable convertible null stage IV yes null imminent risk of obstruction yes null shape of polyps pedunculated null significant bleeding yes null metastases converted to resectable no null cancer recurrence yes null mutated KRAS gene yes null evidence of disease no null regorafenib given previously no null metastases converted to resectable yes null level of triglycerides 150.0 mg/dL type of polyp specimen fragmented null level of fasting glucose 110.0 mg/dL waist circumference 102.0 cm level of triglycerides 150.0 mg/dL waist circumference 102.0 cm level of fasting glucose 110.0 mg/dL high cholesterol CUI035 yes null Primary Tumor (T) T4 null Regional Lymph Nodes (N) N1a null Regional Lymph Nodes (N) N1 null Regional Lymph Nodes (N) N1 null polyp margins cannot be assessed null Regional Lymph Nodes (N) N2 null Regional Lymph Nodes (N) N2b null histologic features of polyp unfavorable null type of polyp specimen single null metachronous metastases no null improvement in functional status yes null improvement in functional status no null serial carcinoembryonic antigen (CEA) elevation yes null serial carcinoembryonic antigen (CEA) elevation no null resectability of metachronous metastases unresectable unconvertible null previous chemotherapy no null previous chemotherapy yes null metachronous metastases yes null previous chemotherapy adjuvant FOLFOX within past 12 months null previous chemotherapy adjuvant FOLFOX >12 months ago null previous chemotherapy previous 5-FU/LV or capecitabine null previous chemotherapy no null metastases converted to resectable yes null patient appropriate for intensive therapy yes null patient appropriate for intensive therapy no null Conversion to resectability is a reasonable goal yes null resectability of metachronous metastases resectable null resectability of metachronous metastases unresectable convertible null tumor growth on neoadjuvant chemotherapy no null tumor growth on neoadjuvant chemotherapy yes null Colonoscopy at 1 year: -If advanced adenoma, repeat in 1 year. -If no advanced adenoma (villous polyp, polyp bigger than 1 cm, or high-grade dysplasia), repeat in 3 years, then every 5 years. Colonoscopy -5-fluorouracil -leucovorin -leucovorin 500 mg/m2 -5-fluorouracil 500 mg/m2 Principles of adjuvant therapy: -Capecitabine appears to be equivalent to bolus 5-FU/leucovorin in patients with stage Ill colon cancer. -FOLFOX is superior to fluoropyrimidine therapy alone for patients with stage Ill colon cancer. FOLFOX is reasonable for high-risk or intermediate-risk stage Il patients and is not indicated for good- or average-risk patients with stage Il colon cancer. FLOX is an alternative to FOLFOX. - Asurvival benefit has not been demonstrated for the addition of oxaliplatin to 5-FU/leucovonn in stage Il colon cancer. -A benefit for the addition of oxaliplatin to 5-FU/leucovorin in patients age 70 and older has not been proven. - Bolus 5-FU/leucovorin/innotecan should not be used in adjuvant therapy, and infusional 5-FU/leucovorin/innotecan (FOLFIRI) has not been shown to be superior to 5-FUlLy. Capecitabineloxaliplatin is superior to bolus 5-FUlleucovorin. -Bevacizumab, cetuximab, panitumumab, or innotecan should not be used in the adjuvant setting for patients with stage Il or Ill colon cancer outside the setting of a clinical trial. 5-FU/leucovorin lV -leucovorin 500 mg/m2 given as a 2-hour infusion and repeated weekly x6 -5-fluorouracil 500 mg/m2 given bolus 1 hour after the start of leucovorin and repeated 6 x weekly Computerized tomography (CT) to the chest, abdomen and pelvis. CT should be with IV and oral contrast. Consider abd/pelvic MRI with MRl contrast plus a non-contrast chest CT if either CT of abd/pelvis is inadequate or if patient has a contraindication to CT with IV contrast. Computerized Tomography (CT) Distinction between benign and malignant tumors. PET-CT does not supplant a contrast-enhanced diagnostic CT scan. Positron Emission Tomography-Computer Tomography (PET-CT) scan Colectomy: -Lymphadenectomy: --Lymph nodes at the origin of feeding vessel should be identified for pathologic exam. --Clinically positive lymph nodes outside the field of resection that are considered suspicious should be biopsied or removed, if possible. --Positive nodes left behind indicate an incomplete (R2) resection. --A minimum of 12 lymph nodes need to be examined to establish N stage. -Laparoscopic-assisted colectomy may be considered based upon the following criteria: -The surgeon has experience performing laparoscopically assisted colorectal operations. --There is no disease in the rectum or prohibitive abdominal adhesions. --There is no locally advanced disease. --It is not indicated for acute bowel obstruction or perforation from cancer. --Thorough abdominal exploration is required. --Consider preoperative marking of small lesions. -Management of patients with can-icr status of known or clinically suspected HNPCC. --Consider more extensive colectomy for patients with a strong family history of colon cancer or young age (<50 y). See NCCN Guidelines for Colorectal Cancer Screening -Resection needs to be complete to be considered curative. One-Stage colectomy with en bloc removal of regional lymph nodes or resection with diversion. Stent or Diversion. Surgical procedures -oxaliplatin -leucovorin -5-fluorouracil -oxaliplatin 85 mg/m2 - leucovorin 400 mg/m2 IV over 2 hours, day I -5-fluorouracil 400 mg/m2 and afterwards 1200 mg/m2 day x 2 days (total 2400 mglm2 ) Principles of adjuvant therapy: -Capecitabine appears to be equivalent to bolus 5-FU/leucovorin in patients with stage Ill colon cancer. -FOLFOX is superior to fluoropyrimidine therapy alone for patients with stage Ill colon cancer. FOLFOX is reasonable for high-risk or intermediate-risk stage Il patients and is not indicated for good- or average-risk patients with stage Il colon cancer. FLOX is an alternative to FOLFOX. - Asurvival benefit has not been demonstrated for the addition of oxaliplatin to 5-FU/leucovonn in stage Il colon cancer. -A benefit for the addition of oxaliplatin to 5-FU/leucovorin in patients age 70 and older has not been proven. - Bolus 5-FU/leucovorin/innotecan should not be used in adjuvant therapy, and infusional 5-FU/leucovorin/innotecan (FOLFIRI) has not been shown to be superior to 5-FUlLy. Capecitabineloxaliplatin is superior to bolus 5-FUlleucovorin. -Bevacizumab, cetuximab, panitumumab, or innotecan should not be used in the adjuvant setting for patients with stage Il or Ill colon cancer outside the setting of a clinical trial. Consider Radiation Therapy orT4 with penetration to a fixed structure. See Principles of Radiation Therapy. Principles of Radiation Therapy: -Radiation therapy fields should include the tumor bed, which should be defined by preoperative radiological imaging and/or surgical clips. -Radiation doses should be 45-50 Gy in 25-28 fractions. --Consider boost for close or positive margins. --Small bowel dose should be limited to 45 Gy. --5-FU-based chemotherapy should be delivered concurrently with radiation. -If radiation therapy is to be used, conformal external beam radiation should be routinely used and intensity-modulated radiation therapy (IMRT) should be reserved only for unique clinical situations including re-irradiation of previously treated patients with recurrent disease. -Intraoperative radiation therapy (IORT), if available, should be considered for patients with T4 or recurrent cancers as an additional boost.Preoperative radiation therapy with concurrent 5-FU-based chemotherapy is a consideration for these patients to aid resectability. If IORT is not available, additional 10-20 Gy external beam radiation and/or brachytherapy could be considered to a limited volume. -Some institutions use arterially directed embolization using Yttrium-90 microspheres in select patients with chemotherapy resistant/refractory disease, without obvious systemic disease, and with predominant hepatic metastases (category 3). -In patients with a limited number of liver or lung metastases, radiotherapy can be considered in highly selected cases or in the setting of a clinical trial. Radiotherapy should not be used in the place of surgical resection. Radiotherapy should be delivered in a highly conformal manner. The techniques can include 3-D conformal radiation therapy, IMRT, or stereotactic body radiation therapy (SBRT) (category 3). A survival benefit has not been demonstrated for the addition of oxaliplatin to 5-FU/leucovorin in stage Il colon cancer. A benefit for the addition of oxaliplatin to 5-FU/leucovorin in patients age 70 and older has not been proven. FOLFOX IV -oxaliplatin 85 mg/m2 IV over 2 hours on day 1 -leucovorin 400 mg/m2 IV over 2 hours on day 1 -5-fluorouracil 400 mg/m2 IV bolus on day 1, then 1200 mg/m2 day x 2 days (total 2400 mglm2 over 46-48 hours) IV continuous infusion Use of a special needle to extract cells from the suspicious area for further testing, if clinically applicable. Needle biopsy Multidisciplinary team evaluation, including a surgeon experienced in the resection of hepatobiliary and lung metastases. Multidisciplinary team evaluation KRAS Mutation Testing: -Mutations in codons 12 and 13 in exon 2 of the coding region of the KRAS gene predict lack of response to therapy with antibodies targeted to the EG FR. -Testing for mutations in codons 12 and 13 should be performed only in laboratores that are certified under the dinical laboratory improvement amendments of 1988 (CLIA-88) as qualified to perform high complexity dinical laboratory (molecular pathology) testing. No specific methodology is recommended (eg, sequencing, hybridization). -The testing can be performed on formalin-fixed paraffin-embedded tissue. The testing can be performed on the primary colorectal cancers and/or the metastasis, as literature has shown that the KRAS mutations are similar in both specimen types. BRAF Mutation Testing: -Patients with a V600E BRAF mutation appear to have a poorer prognosis. There are insufficient data to guide the use of anti-EGFR therapy in the first-line setting with active chemotherapy based on BRAF V600E mutation status. Limited available data suggest lack of antitumor activity from anti-EGFR monoclonal antibodies in the presence of a V600E mutation when used after a patient has progressed on first-line therapy. -Testing for the BRAF V600E mutation can be performed on formalin-flxed paraffin-embedded tissues. This Is usually performed by amplification and direct DNA sequence analysis. Allele-specific PCR is another acceptable method for detecting BRAF V600E mutation. This testing should be performed only in laboratories that are certified under the clinical laboratory improvement amendments of 1988 (CLIA-88) and qualified to perform high complexity clinical laboratory (molecular pathology) testing. MSI Testing - See NCCN Guidelines for Colorectal Cancer Screening: -The panel recommends that MMR protein testing be performed for all patients younger than 50 years with colon cancer, based on an increased likelihood of Lynch syndrome In this population. MMR testing should also be considered for all patients with stage Il disease, because stage Il MSI-H patients may have a good prognosis and do not benefit from 5-FU adjuvant therapy. KRAS mutation test testing for the BRAF V600E mutation performed on formalin-fixed paraffin-embedded tissues BRAF mutation test Confirm the presence of invasive cancer (pT1). pTis has no biological potential to metastasize. It has not been established if molecular markers are useful in treatment determination (predictive markers) and prognosis. Pathology review Criteria for Resectability of metastases and Locregional therapies within Surgery Liver Hepatic resection Is the treatment of choice for resectable liver metastases from colorectal cancer. Complete resection must be feasible based on anatomic grounds and the extent of disease; maintenance of adequate hepatic function is required. The primary tumor must have been resected for cure (RO). There should be no unresectable extrahepatic sites of disease. Having a plan for a debulking resection (less than an RO resection) is not recommended. Patients with resectable metastatic disease and a primary tumor In place should have both sites resected with curative intent. These can be resected in one operation or as a staged approach, depending on the complexity of the hepatectomy or colectomy, comorbid diseases, surgical exposure, and surgeon expertise. When hepatic metastatic disease is not optimally resectable based on insufficient remnant liver volume, approaches utilizing preoperative portal vein embolization or staged liver resection can be considered. Ablative techniques may be considered alone or in conjunction with resection. All original sites of disease need to be amenable to ablation or resection. Some institutions use arterially directed embolic therapy (category 3) in highly select patients with chemotherapy-resistant/-refractory disease, without obvious systemic disease, with predominant hepatic metastases. Conformal external beam radiation therapy (category 3) may be considered in highly selected cases or in the setting of a dinical trial and should not be used indiscriminately in patients who are potentially surgically resectable. Re-resection can be considered in selected patients. Lung Complete resection based on the anatomic location and extent of disease with maintenance of adequate function is required. The primary tumor must have been resected for cure (RO). Resectable extrapulmonary metastases do not preclude resection. Re-resection can be considered in selected patients. Ablative techniques can be considered when unresectable and amenable to complete ablation. Patients with resectable synchronous metastases can be resected synchronously or using a staged approach. Conformal external beam radiation therapy may be considered in highly selected cases or in the setting of a clinical trial and should not be used indiscririnately in patients who are potentially surgically resectable (category 3). Evaluation for Conversion to Resectable Disease Re-evaluation for resection should be considered in otherwise unresectable patients after 2 months of preoperative chemotherapy and every 2 months thereafter. Disease with a higher likelihood of being converted to resectable are those with initially convertible disease distributed within limited sites. When considering whether disease has been converted to resectable, all original sites need to be amenable to resection. Preoperative chemotherapy regimens with high response rates should be considered for patients with potentially convertible disease. Colon resection or Diverting Colostomy or Bypass of impending obstruction or Stenting -capecitabine -capecitabine 125 mg/m2 Capecitabine is a prodrug that is enzymatically converted to 5-fluorouracil in the tumor, where it inhibits DNA synthesis and slows growth of tumor. Principles of adjuvant therapy: -Capecitabine appears to be equivalent to bolus 5-FU/leucovorin in patients with stage Ill colon cancer. -FOLFOX is superior to fluoropyrimidine therapy alone for patients with stage Ill colon cancer. FOLFOX is reasonable for high-risk or intermediate-risk stage Il patients and is not indicated for good- or average-risk patients with stage Il colon cancer. FLOX is an alternative to FOLFOX. - Asurvival benefit has not been demonstrated for the addition of oxaliplatin to 5-FU/leucovonn in stage Il colon cancer. -A benefit for the addition of oxaliplatin to 5-FU/leucovorin in patients age 70 and older has not been proven. - Bolus 5-FU/leucovorin/innotecan should not be used in adjuvant therapy, and infusional 5-FU/leucovorin/innotecan (FOLFIRI) has not been shown to be superior to 5-FUlLy. Capecitabineloxaliplatin is superior to bolus 5-FUlleucovorin. -Bevacizumab, cetuximab, panitumumab, or innotecan should not be used in the adjuvant setting for patients with stage Il or Ill colon cancer outside the setting of a clinical trial. Capecitabine -capecitabine 125 mg/m2 twice daily days 1-14 Redirect patient to clinical trial. Clinical trial Put the patient under surveillance. Observation -5-fluorouracil -leucovorin -oxaliplatin -5-fluorouracil 500 mg/m2 -leucovorin 500 mg/m2 -oxaliplatin 85 mg/m2 Principles of adjuvant therapy: -Capecitabine appears to be equivalent to bolus 5-FU/leucovorin in patients with stage Ill colon cancer. -FOLFOX is superior to fluoropyrimidine therapy alone for patients with stage Ill colon cancer. FOLFOX is reasonable for high-risk or intermediate-risk stage Il patients and is not indicated for good- or average-risk patients with stage Il colon cancer. FLOX is an alternative to FOLFOX. - Asurvival benefit has not been demonstrated for the addition of oxaliplatin to 5-FU/leucovonn in stage Il colon cancer. -A benefit for the addition of oxaliplatin to 5-FU/leucovorin in patients age 70 and older has not been proven. - Bolus 5-FU/leucovorin/innotecan should not be used in adjuvant therapy, and infusional 5-FU/leucovorin/innotecan (FOLFIRI) has not been shown to be superior to 5-FUlLy. Capecitabineloxaliplatin is superior to bolus 5-FUlleucovorin. -Bevacizumab, cetuximab, panitumumab, or innotecan should not be used in the adjuvant setting for patients with stage Il or Ill colon cancer outside the setting of a clinical trial. Consider Radiation Therapy orT4 with penetration to a fixed structure. See Principles of Radiation Therapy. Principles of Radiation Therapy: -Radiation therapy fields should include the tumor bed, which should be defined by preoperative radiological imaging and/or surgical clips. -Radiation doses should be 45-50 Gy in 25-28 fractions. --Consider boost for close or positive margins. --Small bowel dose should be limited to 45 Gy. --5-FU-based chemotherapy should be delivered concurrently with radiation. -If radiation therapy is to be used, conformal external beam radiation should be routinely used and intensity-modulated radiation therapy (IMRT) should be reserved only for unique clinical situations including re-irradiation of previously treated patients with recurrent disease. -Intraoperative radiation therapy (IORT), if available, should be considered for patients with T4 or recurrent cancers as an additional boost.Preoperative radiation therapy with concurrent 5-FU-based chemotherapy is a consideration for these patients to aid resectability. If IORT is not available, additional 10-20 Gy external beam radiation and/or brachytherapy could be considered to a limited volume. -Some institutions use arterially directed embolization using Yttrium-90 microspheres in select patients with chemotherapy resistant/refractory disease, without obvious systemic disease, and with predominant hepatic metastases (category 3). -In patients with a limited number of liver or lung metastases, radiotherapy can be considered in highly selected cases or in the setting of a clinical trial. Radiotherapy should not be used in the place of surgical resection. Radiotherapy should be delivered in a highly conformal manner. The techniques can include 3-D conformal radiation therapy, IMRT, or stereotactic body radiation therapy (SBRT) (category 3). A survival benefit has not been demonstrated for the addition of oxaliplatin to 5-FU/leucovorin in stage Il colon cancer. A benefit for the addition of oxaliplatin to 5-FU/leucovorin in patients age 70 and older has not been proven. FLOX IV -5-fluorouracil IV weekly x 6 -leucovorin IV 500 mglm2 weekly x 6, each 8-week cycle x 3 -oxaliplatin IV 85 mg/m2 on weeks 1, 3, and 5 of each 8-week cycle x 3 Preparation for the Surveillance procedures. Surveillance Obtain the patient's history and physical state. History and physical Inspection of the inside of the colon and rectum, using a colonoscope. Colonoscopy Procedure for Recurrence cancer Recurrence Carcinoembryonic antigen (CEA) test if patient is a candidate for further intervention. CEA Exam that views the inside of the colon (large intestine) and rectum, using a tool called a colonoscope. This examination should be performed in 1 year except if no preoperative colonoscopy due to obstructing lesion, otherwise the colonoscopy should be performed in 3-6 months. Colonoscopy Exam that views the inside of the colon (large intestine) and rectum, using a tool called a colonoscope. Colonoscopy Revision of the principles of survivorship. Colorectal Cancer Surveillance: -Long-term surveillance should be carefully managed with routine good medical care and monitoring, including cancer screening, routine health care, and preventive care. -Routine CEA monitoring and routine CT scanning are not recommended beyond 5 years. Management of Late Sequelae of Disease or Treatment: -For chronic diarrhea or incontinence: --Consider anti-diarrheal agents, bulk-forming agents, diet manipulation, and protective undergarments. Prescription for Survivorship and Transfer of Care to Primary Care -Physician (If primary physician will be assuming cancer surveillance responsibilities): --Include overall summary of treatment, including all surgeries, radiation treatments, and chemotherapy received. --Describe possible clinical course, including expected time to resolution of acute toxicities, long-term effects of treatment, and possible late sequelae of treatment. --Include surveillance recommendations. --Delineate appropriate timing of transfer of care with specific responsibilities identified for primary care physician and oncologist. Cancer Screening Recommendations: -These recommendations are for average-risk patients: --Recommendations for high-risk individuals should be made on an individual basis. --Breast Cancer: See the NCCN Guidelines for Breast CancerScreening. --Cervical Cancer: See the NCCN Guidelines for Cervical Cancer Screening. --Prostate Cancer: See the NCCN Guidelines for Prostate Early Detection. Counseling Regarding Healthy Lifestyle and Wellness: -Maintain a healthy body weight throughout life. -Adopt a physically active lifestyle (At least 30 minutes of moderate intensity activity on most days of the week). Activity recommendations may require modification based on treatment sequelae (ie, ostomy, neuropathy). -Consume a healthy diet with emphasis on plant sources. -Limit alcohol consumption. -Receive smoking cessation counseling as appropriate. Additional health monitoring and immunizations should be performed as indicated under the care of a primary care physician. Survivors are encouraged to maintain a therapeutic relationship with a primary care physician throughout their lifetime. Choice of the following procedures in Treatment 1. Treatment 1 Procedure to acess the neoadjuvant theraphy action Neoadjuvant therapy for 2-3 months. -irinotecan -leucovorin -5-fluorouracil -bevacizumab -irinotecan 180 mg/m2 -leucovorin 400 mg/m2 -5-fluorouracil 400 mg/m2, then 1299 mg/m2/day x 2 days (total of 2400 mg/m2) -bevacizumab 5 mg/kg FOLFIRI +/- bevacizumab IV -irinotecan 180 mg/m2 IV over 30-90 minutes on day 1 -leucovorin 400 mg/m2 IV infusion to match duration of irinotecan infusion on day 1 -5-fluorouracil 400 mg/m2 IV bolus day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) IV continuous infusion -bevacizumab 5 mg/kg IV on day 1 -oxaliplatin -leucovorin -5-fluorouracil -bevacizumab -oxaliplatin 85 mg/m2 - leucovorin 400 mg/m2 -5-fluorouracil 400 mg/m2, then 1200 mg/m2/day x 2 days (total 2400 mg/m2) -bevacizumab 5 mg/kg FOLFOX +/- bevacizumab IV -oxaliplatin mg/m2 IV over 2 hours on day 1 -leucovorin 400 mg/m2 IV over 2 hours on day 1 -5-fluorouracil 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) IV continuous infusion -bevacizumab 5 mg/kg IV on day 1 Injection of small amounts of sterile India ink or carbon black into the bowel wall during colonoscopy or within 2 weeks. Marking of cancerous polyp site -oxaliplatin -capecitabine -bevacizumab -oxaliplatin 130 mg/m2 -capecitabine 850-1000 mg/m2 -bevacizumab 7.5 mg/kg The majority of safety and efficacy data for this regimen have been developed in Europe, where a capecitabine starting dose of 1000 mg/m2 twice daily for 14 days, repeated every 21 days, is standard. Evidence suggests that North American patients may experience greater toxicity with capecitabine (as well as with other fluoropyrimidines) than European patients, and may require a lower dose of capecitabine. The relative efficacy of CapeOx with lower starting doses of capecitabine has not been addressed in large-scale randomized trials. The safety of administering bevacizumab pre- or postoperatively, in combination with 5-FU-based regimens, has not been adequately evaluated. There should be at least a 6-week interval between the last dose of bevacizumab and elective surgery and re-initiation of bevacizumab at least 6-8 weeks postoperatively. There is an increased risk of stroke and other arterial events, especially in those aged years. The use of bevacizumab may interfere with wound healing. CapeOX +/- bevacizumab IV and PO -oxaliplatin 130 mg/m2 lV over2 hours on day 1 -capecitabine 850-1000 mg/m2 PO twice daily for 14 days -bevacizumab 7.5 mg/kg IV on day 1 -irinotecan -leucovorin -5-fluorouracil -cetuximab -irinotecan 180 mg/m2 -leucovorin 400 mg/m2 -5-fluorouracil 400 mg/m2 , then 1200 mg/m2/day x 2 days (total 2400 mg/m2) -cetuximab 400 mg/m2 IV , then 250 mg/m2 IV or cetuximab 500 mg/m2 There are insufficient data to guide the use of anti-EGFR therapy in the first-line setting with active chemotherapy based on BRAF V600E mutation status. FOLFIRI +/- cetuximab IV -irinotecan 180 mg/m2 IV over 30-90 minutes on day 1 -leucovorin 400 mg/m2 IV infusion to match duration of irinotecan infusion on day 1 -5-fluorouracil 400 mg/m2 IV bolus day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) IV continuous infusion -cetuximab 400 mg/m2 IV over 2 hours first infusion, then 250 mg/m2 IV over 60 minutes weekly or cetuximab 500 mg/m2 IV over 2 hours, day 1, every 2 weeks -oxaliplatin -leucovorin -5-fluorouracil -panitumumab -oxaliplatin 85 mg/m2 -leucovorin 400 mg/m2 -5-fluorouracil 400 mg/m2, then 1200 mg/m2/day x 2 days(total 2400 mg/rn2) -panitumumab 6 mg/kg FOLFOX +/- panitumumab IV -oxaliplatin 85 mg/m2 IV over 2 hours on day 1 -leucovorin 400 mg/m2 IV over 2 hours on day 1 -5-fluorouracil 400 mg/m2 IV bolus on day I, then 1200 mg/m2/day x 2 days (total 2400 mg/rn2 over 46-48 hours) IV continuous infusion -panitumumab 6 mg/kg IV over 60 minutes on day 1 -irinotecan -leucovorin -5-fluorouracil -irinotecan 180 mg/m2 -leucovorin 400 mg/m2 -5-fluorouracil 400 mg/m2, then 1200 mg/m2/day x 2 days (total 2400 mg/m2) FOLFORI IV -irinotecan 180 mg/m2 IV over 30-90 minutes on day 1 -leucovorin 400 mg/m2 IV infusion to match duration of irinotecan infusion on day 1 -5-fluorouracil 400 mg/m2 IV bolus day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) continuous infusion Incision (laparotomy) by means of laparoscopy, with resection of any part of the colon. Entails mobilization and ligation of the corresponding blood vessels. Hepatic artery infusion ± systemic 5-FU/Ieucovonn (category 2B) is also an option at institutions with experience in both the surgical and medical oncologic aspects of this procedure. Synchronous or staged Colectomy Resection of metastatic disease. Resection Incision (laparotomy) by means of laparoscopy, with resection of any part of the colon. Entails mobilization and ligation of the corresponding blood vessels. Hepatic artery infusion ± systemic 5-FU/Ieucovorin (category 2B) is also an option at institutions with experience in both the surgical and medical oncologic aspects of this procedure. Colectomy Procedure to acess the treatment action Treatment 2 Choice of the best chemotherapy regimen. Chemotherapy Staged resection of metastatic disease. Staged resection Colectomy: -Lymphadenectomy: --Lymph nodes at the origin of feeding vessel should be identified for pathologic exam. --Clinically positive lymph nodes outside the field of resection that are considered suspicious should be biopsied or removed, if possible. --Positive nodes left behind indicate an incomplete (R2) resection. --A minimum of 12 lymph nodes need to be examined to establish N stage. -Laparoscopic-assisted colectomy may be considered based upon the following criteria: --The surgeon has experience performing laparoscopically assisted colorectal operations. --There is no disease in the rectum or prohibitive abdominal adhesions. --There is no locally advanced disease. --It is not indicated for acute bowel obstruction or perforation from cancer. --Thorough abdominal exploration is required. --Consider preoperative marking of small lesions. -Management of patients with can-icr status of known or clinically suspected HNPCC: --Consider more extensive colectomy for patients with a strong family history of colon cancer or young age (<50 y). See NCCN Guidelines for Colorectal Cancer Screening -Resection needs to be complete to be considered curative. Colectomy with en bloc removal of regional lymph nodes Incision (laparotomy) by means of laparoscopy, with synchronous or staged liver or lung resection. Entails mobilization and ligation of the corresponding blood vessels. Hepatic artery infusion ± systemic 5-FU/leucovorin (category 2B) is also an option at institutions with experience in both the surgical and medical oncologic aspects of this procedure. Colectomy with synchronous or staged liver or lung resection. Recommendations for adjuvant therapy Consider observation or shortened course of chemotherapy. Procedure to acess the Treatment 2 action Treatment 2 Recommendations for systemic terapy. Systemic theraphy Recommendations for surveillance procedures. Surveillance -irinotecan -leucovorin -5-fluorouracil -panitumumab -irinotecan 180 mg/m2 -leucovorin 400 mg/m2 -5-fluorouracil 400 mg/m2, then 1200 mg/m2/day x 2 days (total 2400 mg/m2) -panitumumab 6 mg/kg IV FOLFIRI +/- panitumumab IV -irinotecan 180 mg/m2 IV over 30-90 minutes on day 1 -leucovorin 400 mg/m2 IV infusion to match duration of irinotecan infusion on day 1 -5-fluorouracil 400 mg/m2 IV bolus day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) IV continuous infusion -panitumumab 6 mg/kg IV over 60 minutes on day 1 -irinotecan -oxaliplatin -leucovorin -fluorouracil -irinotecan 165 mg/m2 -oxaliplatin 85 mg/m2 -leucovorin 400 mg/m2 -fluorouracil 1600 mg/m2/day x 2 days FOLFOXIRI (category 2B) IV -irinotecan 165 mg/m2 IV on day 1 -oxaliplatin 85 mg/m2 on day 1 -leucovorin 400 mg/m2 on day 1 -fluorouracil 1600 mg/m2/day x 2 days (total 3200 mg/m2 over 48 hours) continuous infusion starting on day 1 Resection of any part of the colon entails mobilization and ligation of the corresponding blood vessels Colon resection Re-evaluate for conversion to resectable Re-evaluate for conversion to resectable every two months if conversion to resectability is a reasonabe goal. Observation may be considered, with the understanding that there is significantly greater incidence of adverse outcomes (residual disease, recurrent disease, mortality,hematogenous metastasis, but not lymph node metastasis) than polypoid malignant polyps. Endoscopically Removed Malignant Polyps: -A malignant polyp is defined as one with cancer invading through the musculans mucosae and into the submucosa (pT1). pTis is not considered a maIignant polyp. -Favorable histologic features: grade 1 or 2, no angiolymphatic invasion, and negative margin of resection. There is no consensus as to the definition of what constitutes a positive margin of resection. A positive margin has been defined as 1) tumor <1 mm from the transected margin, 2) tumor <2 mm from the transected margin, and 3) tumor cells present within the diathermy of the transected margin. -Unfavorable histologic features: grade 3 or4, angiolymphatic invasion, or a positive margin. See the positive margin definition above. -There is controversy as to whether malignant colorectal polyps with a sessile configuration can be successfully treated by endoscopic removal. The literature seems to indicate that endoscopically removed sessile malignant polyps have a significantly greater incidence of adverse outcomes (residual disease, recurrent disease, mortality, and heinatogenous metastasis, but not lymph node metastasis) than do polypoid malignant polyps. However, when one closely looks at the data, configuration by itself is not a significant variable for adverse outcome, and endoscopically removed malignant sessile polyps with grade I or lI histology, negative margins, and no lymphovascularinvasion can be successfully treated with endoscopic polypectomy. Observation Active chemotherapy regimen for advanced disease (category 2B) or if patient received neoadjuvant therapy, consider observation or shortened course of chemotherapy. Adjuvant therapy Synchronized or staged resection of colon and metastatic cancer. Resection Assessment of the Adjuvant therapy 1 procedures. Adjuvant therapy 1 Assessment of the Adjuvant therapy 2 procedures. Adjuvant therapy 2 Assessment of the Adjuvant therapy 3 procedures. Adjuvant therapy 3 Preparation for workup procedures. Workup1 Preparation for workup procedures. Workup2 Preparation for workup procedures. Workup3 -irinotecan -leucovorin -5-fluorouracil -ziv-aflibercept -irinotecan 180 mg/m2 -leucovorin 400 mg/m2 -5-fluorouracil 400 mg/m2, then 1200 mg/m2/day x 2 days (total 2400 mg/m2) -ziv-aflibercept 4 mg/kg FOLFIRI + ziv-aflibercept IV -Irinotecan 180 mg/m2 IV over 30-90 minutes on day 1 -leucovorin 400 mg/m2 IV infusion to match duration of irinotecan infusion on day 1 -5-FU 400 mg/m2 IV bolus day on day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) continuous infusion -ziv-aflibercept 4 mg/kg IV -irinotecan -bevacizumab -irinotecan 125 mg/m2 or irinotecan 300-350 mg/m2 Irinotecan +/- bevacizumab IV -irinotecan 125 mg/m2 IV over 30-90 minutes on days 1 and 8 or irinotecan 300-350 mg/m2 IV over 30-90 minutes on day 1 -oxaliplatin -capecitabine -oxaliplatin 130 mg/m2 -capecitabine 1000 mg/m2 Principles of adjuvant therapy: -Capecitabine appears to be equivalent to bolus 5-FU/leucovorin in patients with stage Ill colon cancer. -FOLFOX is superior to fluoropyrimidine therapy alone for patients with stage Ill colon cancer. FOLFOX is reasonable for high-risk or intermediate-risk stage Il patients and is not indicated for good- or average-risk patients with stage Il colon cancer. FLOX is an alternative to FOLFOX. - Asurvival benefit has not been demonstrated for the addition of oxaliplatin to 5-FU/leucovonn in stage Il colon cancer. -A benefit for the addition of oxaliplatin to 5-FU/leucovorin in patients age 70 and older has not been proven. - Bolus 5-FU/leucovorin/innotecan should not be used in adjuvant therapy, and infusional 5-FU/leucovorin/innotecan (FOLFIRI) has not been shown to be superior to 5-FUlLy. Capecitabineloxaliplatin is superior to bolus 5-FUlleucovorin. -Bevacizumab, cetuximab, panitumumab, or innotecan should not be used in the adjuvant setting for patients with stage Il or Ill colon cancer outside the setting of a clinical trial. Consider Radiation Therapy orT4 with penetration to a fixed structure. See Principles of Radiation Therapy. Principles of Radiation Therapy: -Radiation therapy fields should include the tumor bed, which should be defined by preoperative radiological imaging and/or surgical clips. -Radiation doses should be 45-50 Gy in 25-28 fractions. --Consider boost for close or positive margins. --Small bowel dose should be limited to 45 Gy. --5-FU-based chemotherapy should be delivered concurrently with radiation. -If radiation therapy is to be used, conformal external beam radiation should be routinely used and intensity-modulated radiation therapy (IMRT) should be reserved only for unique clinical situations including re-irradiation of previously treated patients with recurrent disease. -Intraoperative radiation therapy (IORT), if available, should be considered for patients with T4 or recurrent cancers as an additional boost.Preoperative radiation therapy with concurrent 5-FU-based chemotherapy is a consideration for these patients to aid resectability. If IORT is not available, additional 10-20 Gy external beam radiation and/or brachytherapy could be considered to a limited volume. -Some institutions use arterially directed embolization using Yttrium-90 microspheres in select patients with chemotherapy resistant/refractory disease, without obvious systemic disease, and with predominant hepatic metastases (category 3). -In patients with a limited number of liver or lung metastases, radiotherapy can be considered in highly selected cases or in the setting of a clinical trial. Radiotherapy should not be used in the place of surgical resection. Radiotherapy should be delivered in a highly conformal manner. The techniques can include 3-D conformal radiation therapy, IMRT, or stereotactic body radiation therapy (SBRT) (category 3). A survival benefit has not been demonstrated for the addition of oxaliplatin to 5-FU/leucovorin in stage Il colon cancer. A benefit for the addition of oxaliplatin to 5-FU/leucovorin in patients age 70 and older has not been proven. CapeOX IV -oxaliplatin 130 mg/m2 over 2 hours in day 1 -capecitabine 1000 mg/m2 twice daily days 1-14 -irinotecan -ziv-aflibercept -irinotecan 125 mg/m2 or irinotecan 300-350 mg/m2 Irinotecan +/- ziv-aflibercept IV -irinotecan 125 mg/m2 IV over 30-90 minutes on days 1 and 8 or irinotecan 300-350 mg/m2 IV over 30-90 minutes on day 1 -cetuximab -irinotecan -cetuximab 400 mg/m2 or cetuximab 500 mg/m2 -irinotecan 300-350 mg/m2, or irinotecan 180 mg/m2 or irinotecan 125 mg/m2 Cetuximab + irinotecan IV -cetuximab 400 mg/m2 first infusion then 250 mg/m2 IV weekly or cetuximab 500 mg/m2 IV every 2 weeks -irinotecan 300-350 mg/m2 IV every 3 weeks or irinotecan 180 mg/m2 IV every 2 weeks or irinotecan 125 mg/m2 on days 1 and 8 and repeat every 3 weeks -panitumumab 6 mg/kg IV -irinotecan 125 mg/m2 IV -panitumumab 6 mg/kg IV over 60 minutes -irinotecan 125 mg/m2 or irinotecan 300-350 mg/m2 Panitumumab +/- irinotecan IV -panitumumab 6 mg/kg IV over 60 minutes every 2 weeks -irinotecan 125 mg/m2 IV over 30-90 minutes on days 1 and 8 every 3 weeks or irinotecan 300-350 mg/m2 IV over 30-90 minutes on day 1 every 3 weeks -cetuximab -irinotecan -cetuximab 400 mg/m2, then 250 mg/m2 or cetuximab 500 mg/m2 -irinotecan 125 mg/m2, or irinotecan 300-350 mg/m2 or irinotecan 125 mg/m2 Cetuximab +/- irinotecan IV -cetuximab 400 mg/m2 first infusion, then 250 mg/m2 IV weekly or cetuximab 500 mg/m2 every 2 weeks -irinotecan 125 mg/m2 on days 1 and 8 and repeat every 3 weeks, or irinotecan 300-350 mg/m2 IV every 3 weeks or irinotecan 180 mg/m2 IV every 2 weeks -regorafenib -regorafenib 160 mg Regorafenib PO -regorafenib 160 mg PO daily days 1-21 not defined Provide palliative care. Best supportive care -5-fluorouracil -leucovorin -bevacizumab 5-FU/leucovorin +/- bevacizumab -capecitabine -bevacizumab -capecitabine 850-1250 mg/m2 P -bevacizumab 7.5 mg/kg Capecitabine +/- bevacizumab PO -capecitabine 850-1250 mg/m2 PO twice daily, days 1-14 -bevacizumab 7.5 mg/kg IV on day 1 -irinotecan -oxaliplatin -bevacizumab Irinotecan + oxaliplatin +/- bevacizumab -leucovorin -5-fluorouracil -leucovorin 500 mg/m2 -5-fluorouracil 500 mg/m2 Infusional 5-FU + leucovorin IV -leucovorin 500 mg/m2 IV over 2 hours, days 1, 8, 15, 22, 29, and 36 -5-fluorouracil 500 mg/m2 IV bolus 1 hour after start of leucovorin, days 1,8, 15, 22,29, and 36 Confirm the presence of non-metastatic cancer, review pathological stage and evaluate lymph nodes. Endoscopically Removed Malignant Polyps: -A malignant polyp is defined as one with cancer invading through the muscularis mucosae and into the submucosa (pT1). pTis is not considered a malignant polyp. -Favorable histologic features: grade 1 or 2, no angiolymphatic invasion, and negative margin of resection. There is no consensus as to the definition of what constitutes a positive margin of resection. A positive margin has been defined as 1) tumor <1mm from the transected margin, 2) tumor <2 mm from the transected margin, and 3) tumor cells present within the diathermy of the transected margin. -Unfavorable histologic features: grade 3 or4, angiolymphatic invasion, or a positive margin. See the positive margin definition above. -There is controversy as to whether malignant colorectal polyps with a sessile configuration can be successfully treated by endoscopicremoval. The literature seems to indicate that endoscopically removed sessile malignant polyps have a significantly greater incidence of adverse outcomes (residual disease, recurrent disease, mortality, and hematogenous metastasis, but not lymph node metastasis) than do polypoid malignant polyps. However, when one closely looks at the data, configuration by itself is not a significant variable for adverse outcome, and endoscopically removed malignant sessile polyps with grade I or Il histology, negative margins, and no lymphovascular invasion can be successfully treated with endoscopic polypectomy. Colon Cancer Appropriate for Resection: -Histologic confirmation of primary col onic malignant neoplasm. Pathological Stage: -The following parameters should be reported: --Grade of the cancer --Depth of penetration, (T) --Number of lymph nodes evaluated and number positive (N) --Status of proximal, distal, and radial margins --Lymphovascular invasion --Perineural invasion --Extranodal tumor deposits - Radial (circumferential) margin evaluation - The serosal surface (peritoneal) does not constitute a surgical margin. In colon cancer the circumferential (radial) margin represents the adventitial soft tissue closest to the deepest penetration of tumor, and is created surgically by blunt or sharp dissection of the retroperitoneal aspect. The radial margins should be assessed in all colonic segments with non peritonealized surfaces. The circumferential resection margin corresponds to any aspect of the colon that is not covered by a serosal layer of mesothelial cells, and must be dissected from the retroperioteum to remove the viscus. On pathological examination It is difficult to appreciate the demarcation between a peritonealized surface and non-peritonealized surface. Therefore, the surgeon is encouraged to mark the area of non-peritonealized surface with a clip or suture. The mesenteric resection margin is the only relevant circumferential margin in segments completely encased by the peritoneum. -Perineural invasion (PNI)- The presence of PNI is associated with a significantly worse prognosis. In multivariate analysis, PNI has been shown to be an independent prognostic factor for cancer-specific and overall disease-free survival. For stage Il carcinoma, those with PNI have a significantly worse 5-year disease-free survival compared to those without PNI (29% vs. 82% [p=.OOO5]). -Extra nodal tumor deposits - Irregular discrete tumor deposits in pencolic or perirectal fat away from the leading edge of the tumor and showing no evidence of residual lymph node tissue, but within the lymphatic drainage of the primary carinoma, are considered peritumoral deposits or satellite nodules and are not counted as lymph nodes replaced by tumor. Most examples are due to lymphovascular or, more rarely, PNI. Because these tumor deposits are associated with reduced disease-free and overall suivival, their number should be recorded in the surgical pathology report. This poorer outcome has also been noted in patients with stage Ill card noma. Lymph Node Evaluation: -The AJCC and College of American Pathologists recommend examination of a minimum of 12 lymph nodes to accurately identify stage II colorectal cancers. The literature lacks consensus as to what is the minimal number of lymph nodes to accurately identify stage II cancer. The minimal number of nodes has been reported as >7, >9, >13, >20, >30. The number of lymph nodes retrieved can vary with age of the patient, gender, tumor grade, and tumor site.21 For stage Il (pNO) colon cancer, if fewer than 12 lymph nodes are initially identified, it is recommended that the pathologist go back to the specimen and resubmit more tissue of potential lymph nodes. If 12 lymph nodes are still not identified, a comment in the report should indicate that an extensive search for lymph nodes was undertaken. The pathologist should attempt to retrieve as many lymph nodes as possible. It has been shown that the number of negative lymph nodes is an independent prognostic factor for patients with stage IlIB and IIIC colon cancer. Pathology review -cetuximab -cetuximab 400 mg/m2 , then 250 mg/m2 or cetuximab 500 mg/m2 Cetuximab IV -cetuximab 400 mg/m2 first infusion, then 250 mg/m2 IV weekly or cetuximab 500 mg/m2 IV over 2 hours, day 1 -capecitabine -bevacizumab -capecitabine 850-1250 mg/m2 -bevacizumab 7.5 mg/kg Capecitabine +/- bevacizumab IV and PO -capecitabine 850-1250 mg/m2 PO twice daily, days 1-14 -bevacizumab 7.5 mg/kg IV, day 1 -panitumumab panitumumab 6 mg/kg Panitumumab IV -panitumumab 6 mg/kg IV over 60 minutes -irinotecan -irinotecan 125 mg/m2 -irinotecan 300-350 mg/m2 Irinotecan IV -irinotecan 125 mg/m2 IV over 30-90 minutes, days 1 and 8 -irinotecan 300-350 mg/m2 IV over 30-90 minutes, day 1 Complete Blood Count (CBC), platelets, chemistry profile and Carcinoembryonic Antigen (CEA) Blood tests National Comprehensive Cancer Network 2012-09-20T00:00:00 2012-11-26T00:00:00 The NCCN Guidelines are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to colon cancer treatment. NCC Clinical Practice Guidelines in Oncology: Colon Cancer 3.2013 National Heart,Lung and Blood Institute 2002-09-01T00:00:00 2002-09-01T00:00:00 Recommendations for cholesterol testing and management. It focuses on the role of the clinical approach to prevention of coronary heart disease (CHD). Detection of High Blood Cholesterol in Children and Adults 1.0 Decision task to determine if a patient ha metabolic syndrome based on the values for triglycerides, waist circumference and fasting glucose. 2.0 6.0 5.0 2.0 5.0 5.0 3.0 2.0 24.0 3.0 2.0 The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The clinical pathway has ended. The guideline is complete. The plan summarizes the NCCN clinical practice recommendations for managing colon cancer. It begins with the clinical presentation of the patient to the primary care physician or gastroenterologist. The plan adresses diagnosis, pathologic staging, surgical management, perioperative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. metabolic syndrome CUI034 yes null metabolic syndrome CUI034 no null false Description paramter 004 CUI003 no yes invasive cancer null false CUI001 pedunculated sessile shape of polyps null false Criteria for Resectability of metastases and Locoregional therapies within Surgery: -Liver: --Hepatic resection Is the treatment of choice for resectable liver metastases from colorectal cancer. --Complete resection must be feasible based on anatomic grounds and the extent of disease; maintenance of adequate hepatic function is required. --The primary tumor must have been resected for cure (RO). There should be no unresectable extrahepatic sites of disease. Having a plan for a debulking resection (less than an RO resection) is not recommended. --Patients with resectable metastatic disease and a primary tumor In place should have both sites resected with curative intent. These can be resected in one operation or as a staged approach, depending on the complexity of the hepatectomy or colectomy, comorbid diseases, surgical exposure, and surgeon expertise. --When hepatic metastatic disease is not optimally resectable based on insufficient remnant liver volume, approaches utilizing preoperative portal vein embolization or staged liver resection can be considered. --Ablative techniques may be considered alone or in conjunction with resection. All original sites of disease need to be amenable to ablation or resection. --Some institutions use arterially directed embolic therapy (category 3)in highly select patients with chemotherapy-resistant/-refractory disease, without obvious systemic disease, with predominant hepatic metastases. --Conformal external beam radiation therapy (category 3) may be considered in highly selected cases or in the setting of a dinical trial and should not be used indiscriminately in patients who are potentially surgically resectable. --Re-resection can be considered in selected patients. -Lung: --Complete resection based on the anatomic location and extent of disease with maintenance of adequate function is required. --The primary tumor must have been resected for cure (RO). --Resectable extrapulmonary metastases do not preclude resection. --Re-resection can be considered in selected patients. --Ablative techniques can be considered when unresectable and amenable to complete ablation. --Patients with resectable synchronous metastases can be resected synchronously or using a staged approach. --Conformal external beam radiation therapy may be considered in highly selected cases or in the setting of a clinical trial and should not be used indiscririnately in patients who are potentially surgically resectable (category 3). -Evaluation for Conversion to Resectable Disease: --Re-evaluation for resection should be considered in otherwise unresectable patients after 2 months of preoperative chemotherapy and every 2 months thereafter. --Disease with a higher likelihood of being converted to resectable are those with initially convertible disease distributed within limited sites. --When considering whether disease has been converted to resectable, all original sites need to be amenable to resection. --Preoperative chemotherapy regimens with high response rates should be considered for patients with potentially convertible disease. CUI011 unresectable unconvertible unresectable convertible resectable metastases resectability null false CUI012 liver and/or lung only abdominal/peritoneal synchronous metastases null false CUI013 yes no obstructing or imminently obstructing metastases null false Regional Lymph Nodes (N): -NX Regional lymph nodes cannot be assessed -N0 No regional lymph node metastasis -N1 Metastasis in 1-3 regional lymph nodes -N1a Metastasis in one regional lymph node -N1b Metastasis in 2-3 regional lymph nodes -N1c Tumor deposit(s) in the subserosa. mesentery, or nonpentonealized pericolic or perirectal tissues without regional nodal metastasis -N2 Metastasis in four or more regional lymph nodes -N2a Metastasis in 4-6 regional lymph nodes -N2b Metastasis in seven or more regional lymph nodes CUI014 N0 N1 N2 Regional Lymph Nodes (N) null false Primary Tumor (T): -TX Primary tumor cannot be assessed -T0 No evidence of primary tumor -Tis Carcinoma in situ: intraepithelial or invasion of lamina propria -T1 Tumor invades submucosa -T2 Tumor invades muscularis propria -T3 Tumor invades through the muscularis propria into the pencolorectal tissues -T4a Tumor penetrates to the surface of the visceral peritoneum b -T4b Tumor directly invades or is adherent to other organs or structures Tis indudes cancer cells confined within the glandular basement membrane (intraepithebal) a mucosal lanmina propria (intramucosal) with no extension through the muscularis mucosae into the submucosa. Direct invasion in T4 includes invasion of other organs or other segments of the colorectum as a result of direct extension through the serosa, as confirmed on microscopic examination (for example, invasion of the sigmoid colon by a carcinoma of the cecum) or, for cancers in a retropentoneal or subperitoneal location, direct invasion of other organs or structures by virtue of extension beyond the muscularis propria (i.e., respectively, a tumor on the posterior wall of the descending colon invading the left kidney or lateral abdominal wall; or a mid or distal rectal cancer with invasion of prostate, seminal vesicles, cervix. or vagina). A tumor that is adherent to other organs or structures, gossly, is dassified cT4b. However, if no tumor is present in the adhesion, microscopically, the classification should be pT1-4a depending on the anatomical depth of wall invasion. The V and L classifications should be used to identify the presence or absence of vascular or lymphatic invasion whereas the PN site-specific factor should be used for perineural invasion. CUI015 T1 T4 T3 T2 Tis Primary Tumor (T) null false Distant Metastasis (M): -M0 No distant metastasis -M1 Distant metastasis -M1a Metastasis confined to one organ or site (eg. liver, lung, ovary, nonregional node) -M1b Metastases in more than one organ/site or the peritoneum CUI016 M0 M1 Distant Metastasis (M) null false High-risk factors for recurrence: poorly differentiated histology (exclusive of those cancers that are MSI-H), Iymphatic/vascular invasion, boweI obstruction, <12 lymph nodes examined, perineural invasion, localized perforation, or close, indeterminate, or positive margins. In high-risk stage II patients, there are no data that correlate risk features and selection of chemotherapy. Testing for mismatch repair (MMR) proteins should be considered d for all patients <50 years of age or with stage Il disease. Stage II M SI-H patients may have a good prognosis and do not benefit from 5-FU adjuvant therapy. Principles of risk assessment for stage II disease: -Patient/physidan discussion regarding the potential risks of therapy compared to potential benefits, including prognosis. This should indude discussion of evidence supporting treatment, assumptions of benefit from indirect evidence, morbidity associated with treatment, high-risk characteristics, and patient preferences. -When determining if adjuvant therapy should be administered, the following should be taken into consideration: --Number of lymph nodes analyzed after surgery (<12) --Poor prognostic features (eg, poorly differentiated histology [exclusive of those that are MSI-H]; lymphatic/vascular invasion; bowel obstruction; perineural invasion; localized perforation; close, indeterminate, or positive margins). --Assessment of other comorbidities and anticipated life expectancy. -The benefit of adjuvant chemotherapy does not improve survival by more than 5%. -The panel recommends that MMR protein testing be performed for all patients younger than 50 years with colon cancer, based on an increased likelihood of Lynch syndrome in this population. MMR testing should also be considered for all patients with stage Il disease, because stage Il MSI-H patients may have a good prognosis and do not benefit from 5-FU adjuvant therapy. yes no cancer high-risk features null false CUI019 no yes metastases converted to resectable null false CUI002 no yes colon cancer appropriate for resection null false CUI019 yes no advanced adenocarcinoma null true CUI030 waist circumference cm true CUI031 level of triglycerides mg/dL true CUI033 level of fasting glucose mg/dL false CUI004 yes no suspected or proven metastatic synchronous adenocarcinoma null false Endoscopically Removed Malignant Polyps: -A malignant polyp is defined as one with cancer invading through the musculans mucosae and into the submucosa (pT1). pTis is not considered a maIignant polyp. -Favorable histologic features: grade 1 or 2, no angiolymphatic invasion, and negative margin of resection. There is no consensus as to the definition of what constitutes a positive margin of resection. A positive margin has been defined as 1) tumor <1 mm from the transected margin, 2) tumor <2 mm from the transected margin, and 3) tumor cells present within the diathermy of the transected margin. -Unfavorable histologic features: grade 3 or4, angiolymphatic invasion, or a positive margin. See the positive margin definition above. -There is controversy as to whether malignant colorectal polyps with a sessile configuration can be successfully treated by endoscopicremoval. The literature seems to indicate that endoscopically removed sessile malignant polyps have a significantly greater incidence of adverse outcomes (residual disease, recurrent disease, mortality, and heinatogenous metastasis, but not lymph node metastasis) than do polypoid malignant polyps. However, when one closely looks at the data, configuration by itself is not a significant variable for adverse outcome, and endoscopically removed malignant sessile polyps with grade I or lI histology, negative margins, and no lymphovascularinvasion can be successfully treated with endoscopic polypectomy. CUI005 favorable unfavorable histologic features of polyp null false CUI006 single fragmented type of polyp specimen null false CUI006 clear impossible to assess polyp margins null false CUI008 obstructing nonobstructing bowel obstruction null false CUI009 resectable unresectable locally unresectable tumor resectability null false CUI010 yes no medically inoperable null false CUI020 yes no serial carcinoembryonic antigen (CEA) elevation null false CUI025 yes no patient appropriate for intensive therapy null false CUI026 no yes improvement on functional status null false CUI023 no yes previous chemotherapy null false CUI024 previous 5-FU/LV or capecitabine adjuvant FOLFOX >12 months adjuvant FOLFOx within past 12 months no previous chemotherapy null false Documented metachronous metastases by CT, MRI, and or biopsy CUI021 yes no metachronous metastases null false CUI022 unresectable unconvertible unresectable convertible resectable resectability of metachronous metastases null false CUI023 no yes tumor growth on neoadjuvant chemotherapy null 6.0 3.0 1.0 1 3.0 1 6.0 3.0 6.0 3.0 6.0 3.0 1.0 12.0 6.0 2.0 3.0 8.0 24 3.0 1 3 2.0 28.0 8.0 Chemotherapy for Advanced or Metastatic Disease. Active chemotherapy regimen. Perioperative therapy should be considered for up to a total of 6 months. Active chemotherapy regimen. Set of procedures for perioperative chemotherapy. Set of procedures for perioperative chemotherapy. Perioperative therapy should be considered for up to a total of 6 months. Neoadjuvant chemotherapy between 2-3 months. Primary treatment for patients who haven't previously undergone chemotherapy. Neoadjuvant chemotherapy between 2 to 3 months. Primary treatment for patients who haven't previously undergone chemotherapy. Active chemotherapy regimen. Perioperative therapy should be considered for up to a total of 6 months. Chemotherapy for advanced or metastatic disease. Chemotherapy for Advanced or Metastatic Disease Procedures for the diagnostic and treatment of metabolic syndrome. Set of exams to determine extent of recurrence. Recurrence assessment. Set of procedures for perioperative chemotherapy. Chemotherapy regimen Procedures for patients having metachronous metastases who did not previously undergo chemotherapy. Primary treatment Set of chemotherapy procedures for primary treatment. Primary Treatment Preparation for the most suitable chemotherapy regimen Active chemotherapy regimen Set of procedures for chemotherapy regimen 1. PET-CT should not be used to monitor progress of therapy. CT with contrast or MRI is recommended . Chemotherapy regimen 1 Set of procedures for chemotherapy regimen 2. PET-CT should not be used to monitor progress of therapy. CT with contrast or MRI is recommended . Chemotherapy regimend 1 Set of procedures for chemotherapy regimen 3. PET-CT should not be used to monitor progress of therapy. CT with contrast or MRI is recommended . Chemotherapy regimen 3 Set of procedures for chemotherapy regimen 4. PET-CT should not be used to monitor progress of therapy. CT with contrast or MRI is recommended . Chemotherapy regimen 4 Set of procedures for chemotherapy after first progression. Therapy after first progression See treatment for documented metachronous metastases. Treatment for metachronous metastases Set of procedures for chemotherapy after first or second second progression. Therapy after first or second progression Set of procedures for therapy after second or third progression. Therapy after second or third progression Set of procedures for chemotherapy after first progression. Therapy after first progression. Set of procedures for chemotherapy after second pprogression. Therapy after second progression Set of procedures for chemotherapy after second progression. Therapy after second progression Set of procedures for chemotherapy after first progression. Therapy after first progression. Set of procedures for chemotherapy after second progression. Therapy after second progression. Consider initial therapy. Initial therapy. Observation of growth on neoadjuvant chemotherapy. Observation Re-evaluate for conversion to resectable every 2 months if conversion to resectability is a reasonable goal. Re-evaluation See primary treatment for resectable metachronous metastases. Primary treatment for resectable metachronous metastases. Procedures for patients having metachronous metastases who did not previously undergo chemotherapy. Primary treatment Either continue with an active chemotherapy regimen or with FOLFOX. Treatment for ungrown tumor. Repeat neoadjuvant therapy. Adjuvant therapy. Either continue with an active chemotherapy regimen or with observation. Treatment for grown tumor after neoadjuvant treatment. The purpose of this question task is to determine the clinical presentation of the cancer. Small bowel and appendiceal adenocarcinoma may be treated with systemic chemotherapy according to the NCCN Guidelines for Colon Cancer. Peritoneal nesothelioma and other extrapleural mesotheliomas may be treated with systemic therapy along NCCN Guidelines for Pleural Mesothelioma. All patients with colon cancer should be counseled for family history and considered for risk assessment. Patients with suspected hereditary non-polyposis colon cancer (HNPCC), familial adenomatous polyposis (FAP), and attenuated FAR see the NCCN Guidelines for Colorectal Cancer Screening. Characterization of cancerous polyps. Unresectable metachronous metastases. colon cancer oncologists patients with colon cancer hypercholesterolemia coronary heart disease cardiologist patients with high cholesterol Procedure to direct the patient to a workup, given the clinical presentation of pedunculated or sessile polyps and invasive cancer. Procedure to direct the patient to a workup, given the clinical presentation of non-metastatic colon cancer appropriate for ressection. Procedure to direct the patient to a workup, given the clinical presentation of suspected or proven metastatic synchronous adenocarcinoma. #End End #OWLDataProperty_9fd061d3_771a_4d69_8146_2f6a2a275945 ClinicalPracticeGuidelineProperty #medicationRecommendationDescription medicationRecommendationDescription