bone cancer - nccn 2012

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Version 2.2012, 01/18/12 National Comprehensive Cancer Network, Inc. 2012,All rights reserved. The NCCN Guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN .

NCCN Guidelines IndexBone Cancer Table of Contents

Discussion

NCCN.org

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NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines )

Bone Cancer

Version 2.2012


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Discussion

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NCCN Guidelines Panel Disclosures

NCCN Guidelines Version 2.2012 Panel MembersBone Cancer

Surgery/Surgical oncology Medical oncology Hematology/Hematology oncology

Orthopedics Pediatric oncology

Radiotherapy/Radiation oncology

*Writing committee member

J. Sybil Biermann, MD/Chair

University of MichiganComprehensive Cancer Center

Douglas R. Adkins, MDSiteman Cancer Center atBarnes-Jewish Hospital and WashingtonUniversity School of Medicine

Mark Agulnik, MD

Robert H. Lurie Comprehensive CancerCenter of Northwestern University

Robert S. Benjamin, MDThe University of TexasMD Anderson Cancer Center

Brian Brigman, MD, PhDDuke Cancer Institute

James E. Butrynski, MDDana-Farber/Brigham and WomensCancer Center

David Cheong, MDH. Lee Moffitt Cancer Center& Research Institute

Warren Chow, MD, FACPCity of Hope ComprehensiveCancer Center

Brian McGrath, MD

Roswell Park Cancer Institute

Carol D. Morris, MD Memorial Sloan-Kettering Cancer Center

Richard J. ODonnell, MD UCSF Helen Diller FamilyComprehensive Cancer Center

R. Lor Randall, MD, FACS Huntsman Cancer Instituteat the University of Utah

Victor M. Santana, MDSt. Jude Childrens Research Hospital/University of Tennessee Cancer Institute

Robert L. Satcher, MD, PhD The University of TexasMD Anderson Cancer Center

Herrick J. Siegel, MD University of Alabama at BirminghamComprehensive Cancer Center

Margaret von Mehren, MD

Fox Chase Cancer Center

* William T. Curry, MD

Massachusetts General HospitalCancer Center

Deborah A. Frassica, MDThe Sidney Kimmel ComprehensiveCancer Center at Johns Hopkins

Frank J. Frassica, MDThe Sidney Kimmel Comprehensive

Cancer Center at Johns Hopkins

Kenneth R. Hande, MDVanderbilt-Ingram Cancer Center

Francis J. Hornicek, MD, PhD

Robin L. Jones, MD, BS, MRCP

Joel Mayerson, MDThe Ohio State UniversityComprehensive Cancer Center -James Cancer Hospital and Solove

Research Institute

Sean V. McGarry, MDUNMC Eppley Cancer Center atThe Nebraska Medical Center

Massachusetts General HospitalCancer Center

University of Washington/Seattle

Cancer Care Alliance

NCCNMary Anne BergmanHema Sundar, PhD

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Discussion

NCCN Bone Cancer Panel Members

Summary of the Guidelines Updates

Bone Cancer Workup (BONE-1)

Multidisciplinary Team (BONE-A)

Principles of Bone Cancer Management (BONE-B)

Bone Cancer Systemic Therapy Agents (BONE-C)

Staging (ST-1)

Chondrosarcoma:

Ewings Sarcoma:

Osteosarcoma:

Presentation and Primary Treatment (CHON-1)

Workup and Primary Treatment (EW-1)

Adjuvant Treatment, Surveillance and Relapse (EW-2)

Workup and Primary Treatment (OSTEO-1)

Surveillance and Relapse (OSTEO-3)

Clinical Trials:

Categories of Evidence andConsensus:NCCN

All recommendationsare Category 2A unless otherwisespecified.

Thebelieves that the best managementfor any cancer patient is in a clinicaltrial. Participation in clinical trials isespecially encouraged.

NCCN

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

See NCCN Categories of Evidenceand Consensus

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 patients 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.

NCCN Guidelines Version 2.2012 Table of ContentsBone Cancer

Printed by salman paris on 8/30/2012 10:53:09 PM. For personal use only. Not approvedfor distribution. Copyright 2012 National Comprehensive Cancer Network, Inc., All Rights Reserved.
http://contents.pdf/http://www.nccn.org/clinical_trials/physician.htmlhttp://www.nccn.org/clinical_trials/physician.htmlhttp://www.nccn.org/clinical_trials/physician.htmlhttp://www.nccn.org/clinical_trials/physician.htmlhttp://contents.pdf/http://www.nccn.org/clinical_trials/physician.html


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Discussion

UPDATES

NCCN Guidelines Version 2.2012 UpdatesBone Cancer

Updates in Version 1.2012 of the NCCN Bone Cancer Guidelines from Version 2.2011 include:

Chondrosarcoma:

Ewings Sarcoma

:

Under surveillance changed local imaging to imaging of chest and primary site.

Adjuvant chemotherapy for patients with low-grade or periosteal osteosarcomas with pathologic findings of high-grade disease changed

from a category 2A to a category 2B.

Restage: changed local imaging to imaging of primary site.

Under surveillance changed local imaging to imaging of primary site.

The combination of ifosfamide and etoposide was removed from first-line therapy options for osteosarcoma.

Systemic therapy for malignant fibrous histiocytoma (MFH) of the bone is now category 2B.

Osteosarcoma:

deleted

CHON-1

Radiation therapy for low-grade and high-grade chondrosarcoma is now designated as a category 2B.Under surveillance changed lesion x-ray to imaging of chest and primary site.

Restage: changed local imaging to imaging of primary site.

On the Periosteal branch, footnote: Chemotherapy may be intravenous or intra-arterial.

Deleted footnote: Chemotherapy may be intravenous or intra-arterial.

EW-1

EW-2

OSTEO-1

OSTEO-2

OSTEO-3

BONE-C

The 2.2012 version of the Bone Cancer Guidelines represents the addition of the updated discussion section - .MS-1

http://contents.pdf/http://contents.pdf/


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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.

BONE-1

NCCN Guidelines Version 2.2012Bone Cancer

< 40

40

Painful bone

lesiona

Workup for

potential bone

metastasis

a

bPainless bone lesions require evaluation by a musculoskeletal radiologist and referral to multidisciplinary teams. .

.

See Multidisciplinary Team (BONE-A)

See Principles of Bone Cancer Management (BONE-B)

Abnormal

radiograph

H&PAs clinically indicated:

Bone scanChest radiograph

SPEP/labs

Chest/abdominal/

pelvic CT

PSA

Mammogram

No other lesions

(Possible bone

primary)

Other lesions

(Non-bone primary

suspected)

Refer to

appropriate NCCN

Guideline.

Go to NCCN Table

of Contents

Refer to orthopaedic

oncologist

Biopsy should be

performed at

treating institution

WORKUPb

Refer to

orthopaedic

oncologist

Biopsy should

be performed

at treating

institution

See Bone Cancer

Table of Contents

for specific bone

sarcomas


P i t d b l i 8/30/2012 10 53 09 PM F l l N t d f di t ib ti C i ht 2012 N ti l C h i C N t k I All Ri ht R d
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Discussion



CHON-1

NCCN Guidelines Version 2.2012Chondrosarcoma

Positive

margins

Negative

marginsObserve

Consider RT

PRESENTATIONa,b,c PRIMARY TREATMENT SURVEILLANCE RELAPSE

Low gradeandIntracompartmental

Dedifferentiated

Mesenchymal

Treat as osteosarcoma (category 2B)

See NCCN Osteosarcoma Guidelines (OSTEO-1)

Treat as Ewings Sarcoma (category 2B)See NCCN Ewings Sarcoma Guidelines (EW-1)

Intralesional excision surgical adjuvantorWide excision,if resectableorConsider RT, ifunresectable

(category 2B)

d

Physical exam,

chest and primary site

every 6-12 mo for 2 y then

yearly as appropriate

imaging of

Localrecurrence

Wideexcision,if resectable

or

RT, ifunresectable

(category 2B)

d

a .

.

There is considerable controversy regarding the grading of Chondrosarcoma. In addition to histology, radiologic features, size, and location of tumors should also beconsidered in deciding local treatment.

Wide excision should provide negative surgical margins for tumor. This may be achieved by either limb-sparing resection or limb amputation.

b

c

d



Positive

margins

Negative

marginsObserve

Consider RT

High grade(grade ll, grade lll)or

Clear cellorExtracompartmental

Wideexcision,if resectableor

Consider RT, ifunresectable(category 2B)

d

Localrelapse

Systemicrelapse

Wideexcision,if resectableorRT, ifunresectable(category 2B)

d

Clinical trialorSurgical excision

Physical exam

Primary site

radiographs and/or

cross-sectional

imaging as indicated

Chest imaging

every 3-6 mo for 5 y,then yearly for

a minimum of 10 y

Reassess function at

every follow-up visit


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Discussion



NCCN Guidelines Version 2.2012Ewings Sarcoma

EW-1

Ewings sarcoma

MRI CT of primary site

Chest CT

PET scan and/or bone

scan

Consider bone marrowbiopsy or screening

MRI of spine and

pelvis

Consider cytogenetics

and/or molecular

studies

(may require re-biopsy)

LDHFertility consultation as

appropriate

d

e

Multiagentchemotherapyf

(category 1)for at least

12-24 weeks

prior to local

therapyFor patients withmetastatic diseaseRestage with:

Repeat otherabnormal studies

Chest imagingImaging of

primary site

Consider PET

scan or bone

scang

Response

Progressive

disease

a

b

c

e

.

.

Any member of the Ewings family of tumors can be treated using this algorithm including primitive neuroectodermal tumor, Askins tumor, PNET of boneand extraosseous Ewings sarcoma.

Kumar J, Seith A, Kumar A, et al. Whole-body MR imaging with the use of parallel imaging for detection of skeletal metastases in pediatric patients withsmall cell neoplasms: comparison with skeletal scintigraphy and FDG PET/CT. Pediatr Radiol 2008;38:953-962. Epub 2008 Jul 18.

90% of Ewings family tumors will have one of four specific cytogenetic translocations.

d

f

g

Use the same imaging technique that was performed in the initial workup.



See Bone Cancer Systemic Therapy Agents (BONE-C).

For patients with

localized diseaseRestage with:

Chest imaging

Consider PET

scan or bonescan

Imaging of

primary site

g

PRESENTATIONa,b,c WORKUP PRIMARY

TREATMENT

RESTAGE

See Stabledisease following

response toPrimary Treatment(EW-2)

See Progressivedisease followingPrimary Treatment(EW-2)


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Discussion



NCCN Guidelines Version 2.2012Ewings Sarcoma

EW-2

Preoperative RT

ADJUVANT TREATMENT/

ADDITIONAL THERAPY

Stable diseasefollowingresponse to

primary treatment

Progressive diseasefollowing primarytreatment

SURVEILLANCE PROGRESSIVE

DISEASE/RELAPSE

Wide excision

Definitive RT and chemotherapyf,i

Amputation in selected cases(such as tumors of the foot)

Positivemargins

Negativemarginsh

Chemotherapy

additional RT

f,i

Post-operativechemotherapy,consider RTdepending onmargin status

f

RT and/or surgery toprimary site for localcontrol or palliation

Chemotherapy(category 1)

f,i

Continue chemotherapy(category 1) followed by RTorRT and chemotherapy(category 1, forchemotherapy)

f,i

f,i

Physical exam,

imaging of chest

and primary site

every 2-3 mo

CBC and otherlaboratory studies

as indicated

Increase intervals

for physical exam,

imaging of chest

and primary site

after 24 mo

Annually after 5 y(category 2B)

(indefinitely)

Consider PET

scan or bone

scan g

Earlyrelapse

Laterelapsej

Clinical trialorChemotherapy

RT

f,j

or

or

Wide

excision

ChemotherapyorBest supportive

care

f

or

LOCAL CONTROL

THERAPY

f

g

hUse the same imaging technique that was performed in the initial workup.

RT may be considered for close margins.

or late relapse, c

i

j

There is category 1 evidence for between 28 and 49 weeks of chemotherapy depending on the chemotherapy and dosing schedule used.

F onsider re-treatment with previously effective regimen.





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Discussion



NCCN Guidelines Version 2.2012Osteosarcoma

OSTEO-1

WORKUPa,b PRIMARY TREATMENT

Plain films

MRI CT of

primary siteChest imaging

including

chest CT

PET scan

and/or bone

scan

LDH

Alkalinephosphatase

Fertility

consultation

as appropriate

High gradeosteosarcoma:

Intramedullary+ surface

See

Surveillance(OSTEO-3)

a

b

c

.

.

Dedifferentiated parosteal osteosarcomas are not considered to be low grade tumors.d




Low grade osteosarcoma :Intramedullary + surface

c Wideexcision

High

grade

Chemotherap

(category 2B)

yd

Periostealosteosarcoma

Considerchemotherapyd

Wideexcision

Low

grade

See Primary Treatment

(OSTEO-2)

ADJUVANT TREATMENT

y p p y pp py g p , , g



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Discussion




OSTEO-2

Positive

margins

Negative

margins

Chemotherapy

Consider

additional localtherapy

d

Reassess

tumor as

appropriateRestage with

pretreatment

imaging

modalities:

Chest

imaging

Imaging of

primary site

Consider

PET scan

Consider

bone scan

Preoperativechemotherapy(category 1)

d,e

Wide excision,if resectable

Goodresponsef

Poorresponsef

Chemotherapyd

Unresectable

Good

responsef

Poor

responsefConsider changing

chemotherapyd

RT sensitizers

Chemotherapyd

Consider

additional local

therapy

Consider

changing

chemotherapyd

High gradeosteosarcoma:Intramedullary +surface

SeeSurveillance(OSTEO-3)

d

e

fSelected elderly patients may benefit from immediate surgery.

Response defined by pathologic mapping.


RESTAGENEOADJUVANT

TREATMENT

ADJUVANT

TREATMENT



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Discussion




OSTEO-3

Surveillance

SURVEILLANCE RELAPSE

Physical exam

Chest imaging

CBC and other laboratorystudies as indicated

Reassess function every visit

Every 3 mo for y 1 and 2

Every 4 mo for y 3Every 6 mo for y 4 and 5

and yearly thereafter

Follow-up schedule:

Imaging of primary site :

Consider PET scan and/or

bone scan (category 2B)

g

RelapseChemotherapyand/or resectionif possible

d

Response

Relapse

Resector

Best supportive careorClinical trialorSamariumorPalliative RT

d

g

Use the same imaging technique that was performed in the initial workup.




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Discussion



BONE-A


MULTIDISCIPLINARY TEAM

Primary bone tumors and selected metastatic tumors should be evaluated and treated by a multidisciplinary team withexpertise in the management of these tumors. The team should meet on a regular basis and should include:

Core group

Specialists critical in certain cases

Orthopaedic oncologist

Bone pathologist

Medical/pediatric oncologist

Radiation oncologist

Musculoskeletal radiologist

Thoracic surgeon

Plastic surgeon

Interventional radiologist

Physiatrist

Vascular surgeon

Additional surgical subspecialties



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Discussion



BONE-B


PRINCIPLES OF BONE CANCER MANAGEMENT

Biopsy

Surgery

Lab Studies

Treatment

Long Term Follow-up and Surveillance/Survivorship

Biopsy diagnosis is necessary prior to any surgical procedure or fixation of primary site.

Optimally performed at center which will do definitive management.

Placement of biopsy is critical.

Technique: Apply same principles for core needle or open biopsy.

Appropriate communication between surgeon, musculoskeletal radiologist, and bone pathologist is critical.

Fresh tissue may be needed for molecular studies.In general, failure to follow appropriate biopsy procedures may lead to adverse patient outcomes.

Wide excision should achieve histologically negative surgical margins.

Negative surgical margins optimize local tumor control.

Local tumor control may be achieved by either limb-sparing resection or limb amputation (individualized for a given patient).

Limb-sparing resection is preferred to optimize function if reasonable functional expectations can be achieved.

Lab studies such as CBC, LDH, ALP, may have relevance in the diagnosis, prognosis, and management of bone sarcoma

patients and should be done prior to definitive treatment and periodically during treatment and surveillance.

Fertility issues should be addressed with patients prior to commencing chemotherapy.

Care for bone cancer patients should be delivered directly by physicians on the multidisciplinary team

Patients should have a survivorship prescription to schedule follow-up with a multidisciplinary team.

Biopsy should be core needle or surgical biopsy.

(category 1).

Extended therapy and surveillance may be necessary to address potential late effects of surgery, radiation and chemotherapy

for long-term survivors.

See (BONE-A)


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Discussion

ST-1

NCCN Guidelines Version 2.2012 StagingBone Cancer

Table 1

Table 2

American Joint Committee on Cancer (AJCC)TNM Staging System for Bone

TX

T0

T1T2

T3

NX

N0

N1

NX

N0

M0

M1

M1aM1b

Histopathologic Grade (G)

GX

G1

G2

G3

G4

Surgical Staging System (SSS)

Stage Grade Site

(Primary malignant lymphoma and

multiple myeloma are not included)

Note

Note

Primary tumor cannot be assessed

No evidence of primary tumor

Tumor 8 cm or less in greatest dimensionTumor more than 8 cm in greatest dimension

Discontinuous tumors in the primary bone site

Regional lymph nodes cannot be assessed

No regional lymph node metastasis

Regional lymph node metastasis

: Because of the rarity of lymph node involvement in bonesarcomas, the designation may not be appropriate and

cases should be considered unless clinical node

involvement is clearly evident.

No distant metastasis

Distant metastasis

LungOther distant sites

Grade cannot be assessed

Well differentiated Low Grade

Moderately differentiated Low Grade

Poorly differentiated

Undifferentiated

: Ewing's sarcoma is classified as G4.

IA Low (G1) Intracompartmental (T1)

IB Low (G1) Extracompartmental (T2)

IIA High (G2) Intracompartmental (T1)

IIB High (G2) Extracompartmental (T2)

III Any (G) + Any (T)Regional ordistant metastasis

From Enneking WF, Spanier SS, Goodman MA: A system for the surgical

staging of musculoskeletal sarcoma. Clin Orthop 1980:153:106-120.

(7th ed., 2010)

Primary Tumor (T)

Regional Lymph Nodes (N)

Distant Metastasis (M)

Stage Grouping

Stage IA T1 N0 M0 G1, 2 Low grade, GXStage IB T2 N0 M0 G1, 2 Low grade, GX

T3 N0 M0 G1, 2 Low grade, GX

Stage IIA T1 N0 M0 G3, 4 High gradeStage IIB T2 N0 M0 G3, 4 High gradeStage III T3 N0 M0 G3,Stage IVA Any T N0 M1a Any GStage IVB Any T N1 Any M Any G

Any T Any N M1b Any G

Used with the permission of the American Joint Committee on Cancer (AJCC),

Chicago, Illinois. The original and primary source for this information is the

AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer

Science and Business Media LLC (SBM). (For complete information and data

supporting the staging tables, visit .) Any citation or quotation

of this material must be credited to the AJCC as its primary source. The

inclusion of this information herein does not authorize any reuse or further

distribution without the expressed, written permission of Springer SBM, on

behalf of the AJCC.

www.springer.com


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Version 2.2012, 01/18./2012 National Comprehensive Cancer Network, Inc. 2012, All rights reserved.The NCCN Guidelines and this illustration may not be reproduced in any form without t he express written permission of NCCN.REF-13

DiscussionBone Cancer

extremity. Tumori 1990;76:537-542. Available at:

http://www.ncbi.nlm.nih.gov/pubmed/2178284.

178. Bacci G, Picci P, Mercuri M, et al. Neoadjuvant chemotherapy forhigh grade malignant fibrous histiocytoma of bone. Clin Orthop RelatRes 1998:178-189. Available at:http://www.ncbi.nlm.nih.gov/pubmed/9577426.

179. Bramwell VH, Steward WP, Nooij M, et al. Neoadjuvantchemotherapy with doxorubicin and cisplatin in malignant fibrous

histiocytoma of bone: A European Osteosarcoma Intergroup study. JClin Oncol 1999;17:3260-3269. Available at:http://www.ncbi.nlm.nih.gov/pubmed/10506628.

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