2013NCN guidlines

120
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NCCN Guidelines IndexColon Cancer Table of Contents

Discussion

NCCN.org

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ) ® 

Colon Cancer 

Version 3.2013

Continue

IMPORTANT NOTE REGARDING

LEUCOVORIN SHORTAGE,

PLEASE SEE MS-13

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NCCN Guidelines IndexColon Cancer Table of Contents

Discussion

NCCN Colon Cancer Panel Members

Summary of the Guidelines Updates

Pedunculated polyp (adenoma [tubular, tubulovillous, or villous])

with invasive cancer (COL-1)

Sessile polyp with

invasive cancer (COL-1)

Colon cancer appropriate for resection (COL-2)

Pathologic Stage, Adjuvant Therapy, and Surveillance (COL-3)

Recurrence and Workup (COL-9)

Principles of Pathologic Review (COL-A)

Chemotherapy for Advanced or Metastatic Disease (COL-C)

Principles of Risk Assessment for Stage II Disease (COL-D)

Principles of Adjuvant Therapy (COL-E)

Principles of Radiation Therapy (COL-F)

Principles of Survivorship (COL-G)

Staging (ST-1)

·

·

··

(adenoma [tubular, tubulovillous, or villous])

Suspected or proven metastatic adenocarcinoma (COL-5)

Principles of Surgery (COL-B)

Clinical Presentations and Primary Treatment:

Clinical Trials:

Categories of Evidence andConsensus:NCCN

 All recommendationsare category 2A unless otherwisespecified.

See

believes thatthe best management for any cancer patient is in a clinical trial.Participation in clinical trials isespecially encouraged.

NCCN

To find clinical trials online at NCCNMember Institutions, click here:nccn.org/clinical_trials/physician.html .

NCCN Categories of Evidenceand Consensus

NCCN Guidelines Version 3.2013 Table of ContentsColon Cancer 

The NCCN Guidelines are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment.

 Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual clinical

circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network (NCCN ) makes no representations or 

warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN

Guidelines are copyrighted by National Comprehensive Cancer Network . All rights reserved. The NCCN Guidelines and the illustrations herein may not

be reproduced in any form without the express written permission of NCCN. ©2012.

®

® ®

®

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®

NCCN Guidelines IndexColon Cancer Table of Contents

Discussion

UPDATES

Summary of changes in the 2.2013 version of the Colon Guidelines from the 1.2013 version include:

NCCN Guidelines Version 3.2013 UpdatesColon Cancer 

COL-11

COL-C 1 of 9, COL-C 2 of 9, COL-C 3 of 9

COL-C 8 of 9

COL-C 9 of 9

COL-D

MS-1

· Unresectable metachronous metastases, previous adjuvant FOLFOX within the past 12 months: Primary treatment regimens made consistentwith therapy after first progression regimens on page COL-C 1 of 9. The following regimens added: FOLFIRI ± ziv-aflibercept, Irinotecan ±bevacizumab, Irinotecan ± ziv-aflibercept, (Cetuximab or panitumumab) (KRAS WT gene only) + irinotecan.

Regorafenib added as a treatment option in therapy after first, second, or third progression, depending on previous lines of therapy. Bestsupportive care and clinical trial also listed as alternate options to regorafenib.

Regorafenib regimen added: regorafenib 160 mg PO daily days 1-21, repeat every 28 days.

Reference for regorafenib added: Grothey A, Sobrero AF, Siena S, et al. Results of a phase III randomized, double-blind, placebo-controlled,multicenter trial (CORRECT) of regorafenib plus best supportive care (BSC) versus placebo plus BSC in patients (pts) with metastaticcolorectal cancer (mCRC) who have progressed after standard therapies [abstract]. J Clin Oncol 2012;30 (suppl 4):LBA385.

Bullet 4 modified:

stageII MSI-H patients may have a good prognosis and do not benefit from 5-FU adjuvant therapy.

The Discussion section updated to reflect the changes in the algorithm.

·

·

·

· Testing for MMR proteins should be considered for all patients <50 years of age or with stage II disease. 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 II disease, because

·

Summary of changes in the 3.2013 version of the Colon Guidelines from the 1.2013 version include:

COL-C 3 of 9· FOLFOX and CapeOx added as treatment options in therapy after second progression for patients treated previously with irinotecan-based

chemotherapy.

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NCCN Guidelines IndexColon Cancer Table of Contents

Discussion

UPDATES

COL-C 7 of 9

COL-C 9 of 9

http://meeting.ascopubs.org/cgi/content/abstract/30/15_suppl/3505COL-D

COL-E

COL-F

·

·

·

·

·

·

·

·

The following regimen was added:FOLFIRI + ziv-aflibercept12

Irinotecan 180 mg/m IV over 30-90 minutes, day 1Leucovorin 400 mg/m IV infusion to match duration of irinotecan infusion, day 15-FU 400 mg/m IV bolus day 1, then 1200 mg/m /day x 2 days (total 2400 mg/m over 46-48 hours)† continuous infusionZiv-aflibercept 4 mg/kg IVRepeat every 2 weeks

Reference 12 is new to the page: Allegra CJ, Lakomy R, Tabernero J, et al. Effects of prior bevacizumab (B) use on outcomes from the VELOUR study: A phase III study of aflibercept (Afl) and FOLFIRI in patients (pts) with metastatic colorectal cancer (mCRC) after failureof an oxaliplatin regimen [abstract]. J Clin Oncol 2012;30 (suppl.):3505. Available at:

Bullet 2, sub-bullet 2 modified to be consistent with COL-3: “Poor prognostic features (eg, poorly differentiated histology [exclusive of those that are MSI-H], lymphatic/vascular invasion, bowel obstruction, perineural invasion, localized perforation or close,indeterminate or positive margins)”

Bullet 4 modified to be consistent with COL-3: “Testing for MMR proteins should be considered for all patients <50 years of age.”

Bullet 3 added: A survival benefit has not been demonstrated for the addition of oxaliplatin to 5-FU/leucovorin in stage II colon cancer.Bullet 4 added: A benefit for the addition of oxaliplatin to 5-FU/leucovorin in patients age 70 and older has not been proven.Reference “5” is new to the page.

Bullet 3 modified: , conformal external beam radiation should be routinely usedand intensity-modulated radiation therapy (IMRT) should be reserved only for unique clinical situations including

re-irradiation of previously treated patients with recurrent disease.

2

2

2 2 2

or withstage II disease

If radiation therapy is to be used  for T4 non-metastaticdisease radiotherapy

Summary of changes in the 1.2013 version of the Colon Guidelines from the 3.2012 version include:

NCCN Guidelines Version 3.2013 UpdatesColon Cancer 

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NCCN Guidelines IndexColon Cancer Table of Contents

Discussion

Note: All recommendations are category 2Aunless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

Suspected or proven

metastatic adenocarcinoma

SeePathologicStage,AdjuvantTherapy, and

Surveillance(COL-3)

·

·

·

·

Pathology review

Colonoscopy

CBC, platelets,

chemistry profile,CEA

bdominal/

pelvic

PET-CT scan is not

routinely indicated

e

· Chest/a

i

CTh

Resectable,

nonobstructing

See management of suspected or proven metastatic synchronousadenocarcinoma (COL-5)

CLINICAL

PRESENTATIONa,b

WORKUP FINDINGS SURGERY

Colon cancer 

appropriate for resection (non-

metastatic)

Resectable,obstructing

Locally

unresectable

or medicallyinoperable

Colectomy with en

bloc removal of 

regional lymph nodes

g

One-stage colectomy

with en bloc removal of 

regional lymph nodes

or Resection with diversion

or Stentor Diversion

g

Colectomy with en

bloc removal of 

regional lymph nodes

g

See Chemotherapyfor Advanced or 

Metastatic Disease(COL-C)

a

b

Small bowel and appendiceal adenocarcinoma may be treated with systemic chemotherapy according to the NCCN Guidelines for Colon Ca

.

 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 FAP, see the

- Colon cancer appropriate for resection, pathological stage, and lymph node evaluation.e

g

i

PET-CT does not supplant a contrast-enhanced diagnostic CT scan.

ncer. Peritonealmesothelioma and other extrapleural mesotheliomas may be treated with systemic therapy along NCCN Guidelines for Pleural Mesothelioma, as outlined on pageMPM-A

NCCN Guidelines for Colorectal Cancer Screening

See Principles of Pathologic Review (COL-A)

.

See Principles of Surgery (COL-B 1 of 3).hCT should be with IV and oral contrast. Consider abd/pelvic MRI with MRI 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.

COL-2

NCCN Guidelines Version 3.2013Colon Cancer 

y g p y pp py g p , , g

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NCCN Guidelines IndexColon Cancer Table of Contents

Discussion

Note: All recommendations are category 2Aunless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

Suspected or 

proven metastatic

synchronous

adenocarcinoma

(Any T, any N, M1)

CLINICAL

PRESENTATION

WORKUP FINDINGS

·

·

·

·

·

·

·

Colonoscopy

Chest/abdominal/pelvic CT

CBC, platelets, chemistry profileCEA

Needle biopsy, if clinically indicated

z

e

· Determination of tumor KRAS gene

status (if KRAS non-mutated,

consider BRAF testing)

PET-CT scan only if potentially

surgically curable M1 disease

Multidisciplinary team evaluation,including a surgeon experienced in

the resection of hepatobiliary and

lung metastases

See Treatmentand AdjuvantTherapy (COL-6)

See PrimaryTreatment (COL-8)

Synchronous

liver only and/or 

lung only

metastases

Synchronous

abdominal/peritoneal

metastases

Resectableg

e

g

z

- KRAS and BRAF Mutation Testing.

CT should be with IV contrast. Consider MRI with IV contrast if CT is inadequate.

See Principles of Pathologic Review (COL-A 4 of 5)

See Principles of Surgery (COL-B 2 of 3).

See Treatmentand AdjuvantTherapy (COL-7)

Unresectable

(potentially

convertible or 

unconvertible)

g

COL-5

NCCN Guidelines Version 3.2013Colon Cancer 

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NCCN Guidelines IndexColon Cancer Table of Contents

Discussion

Colon resection

or 

Diverting colostomy

or 

Bypass of impendingobstruction

or 

Stenting

g

FINDINGS PRIMARY TREATMENT

Nonobstructing

Obstructed

or imminentobstruction

Note: All recommendations are category 2Aunless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

Synchronousabdominal/

peritoneal

metastasesee

See Chemotherapy for Advanced or Metastatic

Disease (COL-C)

See Chemotherapy for 

Advanced or MetastaticDisease (COL-C)

g .

 Aggressive cytoreductive debulking and/or intraperitoneal chemotherapy are not recommended outside the setting of a clinical trial.eeSee Principles of Surgery (COL-B 2 of 3)

COL-8

NCCN Guidelines Version 3.2013Colon Cancer 

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NCCN Guidelines IndexColon Cancer Table of Contents

Discussion

Note: All recommendations are category 2Aunless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

WORKUPRECURRENCE

Serial

CEA

elevation

Negative

findings

Positivefindings

·

·

·

·

Physical exam

Colonoscopy

Chest/abdominal/

pelvic CT

Consider PET-CT

scan

·

·

Consider PET-CT scan

Re-evaluate chest/

abdominal/pelvic CT

in 3 mo

Negativefindings

Positive

findings

Documented

metachronous

metastases

by CT, MRI,

and/or biopsy

ff,gg

See treatment for 

Documentedmetachronous

metastases, below

See treatment for 

Documented

metachronous

metastases, below

g

gg

ff Determination of tumor KRAS .(if KRAS non-mutated, consider BRAF testing) - KRAS and BRAF Mutation Testing.

Patients should be evaluated by a multidisciplinary team including surgical consultation for potentially resectable patients.

See Principles of Surgery (COL-B 2 of 3).

See Principles of Pathologic Review (COL-A 4 of 5)

COL-9

Resectable

g

See Primary

Treatment (COL-10)

See Primary

Treatment (COL-11)

Resectableg

Unresectable

Consider 

PET-CTscan

Unresectable

(potentially

convertible or unconvertible)

g

NCCN Guidelines Version 3.2013Colon Cancer 

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NCCN Guidelines IndexColon Cancer Table of Contents

Discussion

Note: All recommendations are category 2Aunless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

Neoadjuvant

chemotherapy

( )

(2-3 mo)

See COL-4

PRIMARY TREATMENT

Previous

chemotherapy

Resectionaa

No previous

chemotherapy

or 

Resectionaa

Neoadjuvant

chemotherapy

( )

(2-3 mo)

See COL-C

Resectionaa

or 

Resectionaa

Observation (preferred for 

previous oxaliplatin-based therapy)

or Active chemotherapy regimen

( )

hh

See COL-C

No growth on

neoadjuvant

chemotherapy

Growth on

neoadjuvant

chemotherapy

Active chemotherapy

regimen ( )hh See COL-Cor Observation

Repeat neoadjuvant

therapyor FOLFOX

hh

aaHepatic 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.

Perioperative therapy should be considered for up to a total of 6 months.hh

COL-10

RESECTABLE

METACHRONOUS METASTASES

Active chemotherapy

regimen ( )hh See COL-Cor Observation

Repeat neoadjuvant

therapyor FOLFOXor Observation

hh

FOLFOX/CapeOx preferred

ADJUVANT TREATMENT

No growth on

neoadjuvant

chemotherapy

Growth on

neoadjuvant

chemotherapy

NCCN Guidelines Version 3.2013Colon Cancer 

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NCCN Guidelines IndexColon Cancer Table of Contents

Discussion

Note: All recommendations are category 2Aunless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

e

hh

- KRAS and BRAF Mutation Testing.

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.

Perioperative therapy should be considered for up to a

s progressed on first-line therapy.

aa

See Principles of Pathologic Review (COL-A 4 of 5)

See Principles of Surgery (COL-B 2 of 3).g

iitotal of 6 months.

Patients with a V600E BRAF mutation appear to have a poorer prognosis. Limited available data suggest a lack of antitumor activity from anti-EGFR monoclonalantibodies in the presence of a V600E mutation when used after a patient ha

PRIMARY TREATMENT

·

·

·

Previous adjuvant FOLFOX

>12 months

Previous 5-FU/LV or 

capecitabine

No previous chemotherapy

Active chemotherapy

regimen ( )See COL-C

Converted to

resectable

Remainsunresectable

Active

chemotherapyregimen

( )or Observation

hh

See COL-CResectionaa

Active chemotherapyregimen ( )See COL-C

Re-evaluate for 

conversion to

resectable every

2 mo if conversion

to resectability is

a reasonable goal

g

COL-11

UNRESECTABLE

METACHRONOUS METASTASES

· Previous adjuvant FOLFOX

within past 12 months

FOLFIRI ± bevacizumab

or 

or FOLFIRI ± ziv-afliberceptor Irinotecan ± bevacizumabor Irinotecan ± ziv-aflibercept

FOLFIRI + (cetuximab or panitumumab)

(KRAS WT gene only)or 

(Cetuximab or 

panitumumab) (KRAS WT

gene only) + irinotecan

e,ii

e,ii

NCCN Guidelines Version 3.2013Colon Cancer 

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NCCN Guidelines IndexColon Cancer Table of Contents

Discussion

Note: All recommendations are category 2Aunless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

PRINCIPLES OF SURGERY (1 of 3)

See Criteria for Resectability of Metastases andLocoregional Therapies Within Surgery on COL-B 2 of 3

ColectomyLymphadenectomy

Management of patients with carrier status of kConsider more extensive colectomy for patients with a strong family history of colon cancer or young age (<50 y).

·

·

·

>

>

>

>

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.1

· 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.

nown or clinically suspected HNPCC

2

3,4

5

>

>

>

>

>

> Consider preoperative marking of small lesions.

See NCCN Guidelines for Colorectal Cancer Screening

Resection needs to be complete to be considered curative.

See footnotes on COL-B 3 of 3

COL-B1 of 3

NCCN Guidelines Version 3.2013Colon Cancer 

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NCCN G id li I dNCCN G id li V i 3 2013

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NCCN Guidelines IndexColon Cancer Table of Contents

Discussion

Note: All recommendations are category 2Aunless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

CONTINUUM OF CARE - CHEMOTHERAPY FOR ADVANCED OR METASTATIC DISEASE: (PAGE 1 of 9)1

Patient

appropriate

for 

intensive

therapy2

FOLFOX ±bevacizumabor CapeOX ±

bevacizumab

3

4

5,6

FOLFOX

± panitumumab(KRAS wild-type

[WT] gene only)

3

6,7

8,9

or 

FOLFIRI ± bevacizumab

or 

5,10

or 

FOLFIRI ± ziv-afliberceptor Irinotecan ± bevacizumabor Irinotecan ± ziv-aflibercept

FOLFIRI + (cetuximab or 

panitumumab)

(KRAS WT gene only)

or (Cetuximab or 

panitumumab) (KRAS

WT gene only) + irinotecan

11

11

6,

8

6,

8

10

10

12-15

12-15

10

Regorafenibor Clinical trialor Best supportive care16

(Cetuximab or panitumumab)

(KRAS WT gene only) +

irinotecan;

for patients not able to toleratecombination, consider single agent

(cetuximab or panitumumab)

(KRAS WT gene only)

6,

8

6,12-15

8

12-15

10

or Regorafenib (KRAS mutant only)

COL-C1 of 9

See footnotes on COL-C 5 of 9

Initial Therapy Therapy After  First Progression

Therapy After Second Progression

Additional options on

throughCOL-C 2 of 9 COL-C 3 of 9

For patients not appropriate for intensive therapy, see COL-C 4 of 9

Therapy After Third Progression

Regorafenib (if not

given previously)

or Clinical trialor Best supportive care16

NCCN Guidelines Version 3.2013Colon Cancer 

NCCN Guidelines IndexNCCN Guidelines Version 3 2013

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NCCN Guidelines IndexColon Cancer Table of Contents

Discussion

Note: All recommendations are category 2Aunless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

COL-C2 of 9

See footnotes on COL-C 5 of 9

CONTINUUM OF CARE - CHEMOTHERAPY FOR ADVANCED OR METASTATIC DISEASE: (PAGE 2 of 9)1

Patient

appropriate

for 

intensive

therapy2

FOLFIRI +bevacizumab

105,6

FOLFOX

or 

3,5

4,5

12-15

10

± bevacizumabor 

CapeOX ± bevacizumab

(Cetuximab or 

panitumumab)

(KRAS WT gene only) +

irinotecan; for patients

not able to tolerate

combination, consider 

single agent (cetuximab or panitumumab)

(KRAS WT gene only)

6,

8

6,12-15

8

FOLFOX3

4or 

CapeOX

FOLFIRI ±

cetuximab or 

panitumumab

(KRAS WT gene

only)

10

6,7

8,9

or 

Initial Therapy

Additional options onthroughCOL-C 1 of 9 COL-C 3 of 9

For patients not appropriate for intensive therapy, see COL-C 4 of 9

Therapy After First Progression

Therapy After Second Progression

Therapy After Third Progression

(Cetuximab or panitumumab)

(KRAS WT gene only) +

irinotecan;

for patients not able to tolerate

combination, consider single agent

(cetuximab or panitumumab)

(KRAS WT gene only)

6,

8

6,12-15

8

12-15

10

or Regorafenib (KRAS mutant only)

Regorafenib (if not

given previously)or Clinical trialor Best supportive care16

NCCN Guidelines Version 3.2013Colon Cancer 

NCCN Guidelines IndexNCCN Guidelines Version 3 2013

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NCCN Guidelines IndexColon Cancer Table of Contents

Discussion

Note: All recommendations are category 2Aunless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

COL-C3 of 9

See footnotes on COL-C 5 of 9

CONTINUUM OF CARE - CHEMOTHERAPY FOR ADVANCED OR METASTATIC DISEASE: (PAGE 3 of 9)1

Additional options onthroughCOL-C 1 of 9 COL-C 2 of 9

For patients not appropriate for intensive therapy, see COL-C 4 of 9

NCCN Guidelines Version 3.2013Colon Cancer 

Patient

appropriate

for 

intensive

therapy2

Irinotecan + oxaliplatin ±

bevacizumab

or 

± bevacizumab

or 

Irinotecan ± ziv-afliberceptor FOLFIRI ± bevacizumabor FOLFIRI ± ziv-aflibercept

10

10

10

10

Irinotecan

11

11

5-FU/leucovorinor Capecitabine± bevacizumab

17

5,6,19

18

FOLFOXIRI(category 2B)

20

Irinotecan10

or 

FOLFOX ±

bevacizumab

or 

CapeOX ±

bevacizumab

3,5

4,5

or 

Initial Therapy Therapy After First Progression Therapy After Second Progression Therapy After ThirdProgression

(Cetuximab or panitumumab)

(KRAS WT gene only) +

irinotecan;

for patients not able to tolerate

combination, consider single agent

(cetuximab or panitumumab)

(KRAS WT gene only)

6,

8

6,12-15

8

12-15

10

or Regorafenib (KRAS mutant only)

Regorafenib (if not

given previously)or Clinical trialor 

Best supportive care16

(Cetuximab or panitumumab)

(KRAS WT gene only) +

irinotecan;

for patients not able to tolerate

combination, consider single agent

(cetuximab or panitumumab)(KRAS WT gene only)

6,

8

6,12-15

8

12-15

10

or Regorafenib (KRAS mutant only)

Regorafenib (if not

given previously)or Clinical trialor Best supportive care16

FOLFOX or CapeOX3 4

NCCN Guidelines IndexNCCN Guidelines Version 3 2013

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NCCN Guidelines IndexColon Cancer Table of Contents

Discussion

Note: All recommendations are category 2Aunless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

CONTINUUM OF CARE - CHEMOTHERAPY FOR ADVANCED OR METASTATIC DISEASE: (PAGE 4 of 9)1

Initial Therapy Therapy After First Progression

See footnotes on COL-C 5 of 9

COL-C4 of 9

Patient not

appropriatefor 

intensive

therapy2

Infusional 5-FU + leucovorin or 

Capecitabine ± bevacizumab Improvement in

functional status

No improvement in

functional status

Consider initial therapy as21COL-C 1 of 9 COL-C 3 of 9through

Best supportive careSee NCCN Guidelines for Palliative Care

Cetuximab (KRAS WT geneonly) (category 2B)8,9

or 

Panitumumab (KRAS WT gene

only) (category 2B)8,9

or 

NCCN Guidelines Version 3.2013Colon Cancer 

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NCCN Guidelines IndexColon Cancer Table of Contents

NCCN Guidelines Version 3.2013C l C

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Colon Cancer Table of ContentsDiscussion

Note: All recommendations are category 2Aunless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

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.

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 isnot available, additional 10-20 Gy external beam radiation and/or brachytherapy could be considered to a limited volume.

:>

>

>

·

·

·

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.

Some institutions use arterially directed embolization 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).

using Yttrium-90 microspheres

COL-F

Colon Cancer 

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NCCN Guidelines IndexColon Cancer Table of Contents

Discussion

NCCN Guidelines Version 3.2013Colon Cancer  

rather than discrete. Principles to consider at initiation of therapy include

pre-planned strategies for altering therapy for patients in both the

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presence and absence of disease progression, including plans for 

adjusting therapy for patients who experience certain toxicities.

Recommended initial therapy options for advanced or metastatic

disease depend on whether the patient is appropriate for intensive

therapy. The more intensive initial therapy options include FOLFOX,

FOLFIRI, CapeOx, and FOLFOXIRI (category 2B). Addition of a biologic

agent (eg, bevacizumab, cetuximab, panitumumab) is either 

recommended or listed as an option in combination with some of these

regimens, depending on available data. Chemotherapy options for 

patients with progressive disease depend on the choice of initial

therapy. The panel endorses the concept that treating patients in a

clinical trial has priority over standard treatment regimens.

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Discussion

NCCN Guidelines Version 3.2013Colon Cancer  

475. Meyerhardt JA, Heseltine D, Niedzwiecki D, et al. Impact of physical activity on cancer recurrence and survival in patients with stageIII colon cancer: findings from CALGB 89803. J Clin Oncol

2006;24:3535-3541. Available at:http://www.ncbi.nlm.nih.gov/pubmed/16822843 .

476. Meyerhardt JA, Niedzwiecki D, Hollis D, et al. Association of 

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y , , ,dietary patterns with cancer recurrence and survival in patients withstage III colon cancer. JAMA 2007;298:754-764. Available at:http://www.ncbi.nlm.nih.gov/pubmed/17699009 .

477. Meyerhardt JA, Giovannucci EL, Ogino S, et al. Physical activityand male colorectal cancer survival. Arch Intern Med 2009;169:2102-2108. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20008694 .

478. Kushi LH, Byers T, Doyle C, et al. American Cancer SocietyGuidelines on Nutrition and Physical Activity for cancer prevention:reducing the risk of cancer with healthy food choices and physicalactivity. CA Cancer J Clin 2006;56:254-281; quiz 313-254. Available at:http://www.ncbi.nlm.nih.gov/pubmed/17005596 .

479. Hewitt M, Greenfield S, Stovall E, eds. From Cancer Patient toCancer Survivor: Lost in Transition. Committee on Cancer Survivorship:Improving Care and Quality of Life, Institute of Medicine and NationalResearch Council: National Academy of Sciences; 2006. Available at:http://www.nap.edu/catalog/11468.html .