nccn melanoma
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NCCN Guidelines IndexMelanoma Table of Contents
Discussion
NCCN.org
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NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ) ®
Melanoma
Version 2.2014
NCCN Guidelines for Patients available at ®
www.nccn.org
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NCCN Guidelines IndexMelanoma Table of Contents
Discussion
NCCNLauren Gallagher, RPh, PhD
Maria Ho, PhDNicole McMillian, MS
Continue
NCCN Guidelines Version el MembersMelanoma
® 2.2014 Pan
Daniel G. Coit, MD/Chair
Memorial Sloan-Kettering Cancer Center
John A. Thompson, MD /Vice-Chair
Fred Hutchinson Cancer Research
Center/Seattle Cancer Care Alliance
Huntsman Cancer Institute
at the University of Utah
Huntsman Cancer Institute
at the University of Utah
William E. Carson, III, MDThe Ohio State University
Comprehensive Cancer Center -
James Cancer Hospital and
Solove Research Institute
Gregory A. Daniels, MD
UC San Diego Moores Cancer Center
¶
‡
¶
§
¶
Þ‡
Robert Andtbacka, MD
Christopher J. Anker, MD
Christopher K. Bichakjian, MDUniversity of Michigan
Comprehensive Cancer Center
Julie R. Lange, MD ScM
The Sidney Kimmel ComprehensiveCancer Center at Johns Hopkins
Mary C. Martini, MDRobert H. Lurie Comprehensive Cancer Center of Northwestern University
Anthony J. Olszanski, MDFox Chase Cancer Center
Merrick I. Ross, MDThe University of TexasMD Anderson Cancer Center
April Salama, MDDuke Cancer Institute
Susan M. Swetter, MDStanford Cancer Institute
Kenneth K. Tanabe, MDMassachusetts General HospitalCancer Center
Vijay Trisal, MDCity of Hope Comprehensive
Cancer Center
Marshall M. Urist, MDUniversity of Alabama at BirminghamComprehensive Cancer Center
, ¶
†
¶
¶
¶
¶
†Þ
¶
¥
Þ
†
¶
†
Adil Daud, MD
UCSF Helen Diller FamilyComprehensive Cancer Center
Dominick DiMaio, MDUNMC Eppley Cancer Center atThe Nebraska Medical Center
The University of Tennessee
Health Science Center
Rene Gonzalez, MDUniversity of Colorado Cancer Center
Valerie GuildAim at Melanoma
Allan C. Halpern, MDMemorial Sloan-Kettering Cancer Center
F. Stephen Hodi, Jr. MDDana-Farber/Brigham and Women’sCancer Center
Mark C. Kelley, MD Vanderbilt-Ingram Cancer Center
Ragini R. Kudchadkar, MDMoffitt Cancer Center
Martin D. Fleming, MD
Nikhil I. Khushalani, MDRoswell Park Cancer Institute
†
† Medical oncology
Þ Internal medicine
¶ Surgery/Surgical oncology
‡ Hematology/Hematology oncology
* Writing committee member
Dermatology
Pathology
¥ Patient advocacy
§ Radiotherapy/Radiation oncology
*
NCCN Guidelines Panel Disclosures
*
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NCCN Guidelines IndexMelanoma Table of Contents
Discussion
Continue
NCCN Guidelines VersionMelanoma
® 2.2014 Sub-Committee
Workup/Follow-up Recommendations Review
Susan M. Swetter, MD LeadStanford Cancer Institute
Merrick I. Ross, MD /Co-LeadThe University of TexasMD Anderson Cancer Center
Robert Andtbacka, MDHuntsman Cancer Institute
at the University of Utah
Christopher K. Bichakjian, MDUniversity of Michigan
Comprehensive Cancer Center
Daniel G. Coit, MD
Memorial Sloan-Kettering Cancer Center
¶
¶
¶
† Medical oncology
Þ Internal medicine
¶ Surgery/Surgical oncology
Dermatology
NCCN Guidelines Panel Disclosures
Adil Daud, MDUCSF Helen Diller FamilyComprehensive Cancer Center
Martin D. Fleming, MD
The University of TennesseeHealth Science Center
Mark C. Kelley, MD Vanderbilt-Ingram Cancer Center
Kenneth K. Tanabe, MDMassachusetts General Hospital Cancer Center
John A. Thompson, MD
Fred Hutchinson Cancer Research
Center/Seattle Cancer Care Alliance
†Þ
¶
¶
¶
‡
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®
NCCN Guidelines IndexMelanoma Table of Contents
Discussion
NCCN Melanoma Panel Members
Summary of the Guidelines UpdatesClinical Presentation and Preliminary Workup (ME-1)Stage 0 (in situ), Stage IA (ME-2)Stage IB, Stage II (ME-3)Stage III (ME-4)Stage III In-Transit (ME-5)
Stage IV Metastatic (ME-6)Follow-up (ME-7)Persistent Disease or True Local Scar Recurrence, In-Transit Recurrence (ME-8)Nodal Recurrence (ME-9)Distant Metastatic Disease (ME-10)Principles of Biopsy and Pathology (ME-A)Principles of Surgical Margins for Wide Excision of Primary Melanoma (ME-B)
Principles of Complete Lymph Node Dissection (ME-C)Principles of Radiation Therapy for Melanoma (ME-D)Systemic Therapy Options for Advanced or Metastatic Melanoma (ME-E)Staging (ST-1)
Clinical Trials:
Categories of Evidence andConsensus:NCCN
All recommendationsare category 2A unless otherwisespecified.
NCCN believes thatthe best management for any cancer patient is in a clinical trial.Participation in clinical trials isespecially encouraged.
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 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. ©2013.
®
NCCN Guidelines Version Table of ContentsMelanoma
® 2.2014
NCCN Guidelines for Patients
available at
®
www.nccn.org
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NCCN Guidelines IndexMelanoma 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.
ME-1
NCCN Guidelines VersionMelanoma
2.2014
Breslow thickness
+
Ulceration status
(present or absent)
+Assess deep and
peripheral margin
status+Microsatellitosis
(present or absent)
+Dermal mitotic rate
+
Clark level (for nonulcerated lesions
where mitotic rate is
not determined, for
lesions 1 mm)+Pure desmoplasia if
present
c
d
Suspicious
pigmented
lesion
Biopsya
Inadequateb
Melanoma
confirmedb
Rebiopsy
H&P with
attention tolocoregional
area, draining
lymph nodes
Complete skin
exam
Assessment of
melanoma-
related riskfactorse
a
d
b
e
If diagnostic biopsy is inadequate for treatment decisions, rebiopsy may be appropriate.
When a pure desmoplastic lesion is suspected, it is important that an experienced dermatopathologist examine the entire lesion before making the decision to performa sentinel lymph node biopsy (SLNB). (Busam KJ. Desmoplastic Melanoma. Clin Lab Med 2011. 31:321-330.)
Risk factors for melanoma include family history of melanoma, prior primary melanoma, and other factors such as atypical moles/dysplastic nevi.
cMicrosatellitosis is defined in the CAP 2011 melanoma protocol (version 3.1.0.0) as “the presence of tumor nests greater than 0.05 mm in diameter, in the reticular dermis, panniculus, or vessels beneath the principal invasive tumor but separated from it by at least 0.3 mm of normal tissue on the section in which the Breslowmeasurement was taken.” (Harrist TJ, Rigel DS, Day CL Jr, et al. “Microscopic satellites” are more highly associated with regional lymph node metastases than isprimary melanoma thickness. Cancer 1984;53:2183-2187.)
See Principles of Biopsy and Pathology (ME-A).
Stage IB, Stage II (ME-3)
Stage IV Metastatic (ME-6)
CLINICAL
PRESENTATION
PATHOLOGY
REPORTa
PRELIMINARY
WORKUP
Stage III (ME-4) and (ME-5)
CLINICAL STAGE
Stage 0 in situ (ME-2)
Stage IA (ME-2)
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Version 2.2014, 09/12/13 © National Comprehensive Cancer Network, Inc. 2013, 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 IndexMelanoma 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.
ME-2
NCCN Guidelines VersionMelanoma
2.2014
g
Decision not to perform SLNB may be based on significant patient comorbidities,patient preference, or other factors.
.
Sentinel lymph nodes should be evaluated with multiple sectioning andimmunohistochemistry.
hSLNB is an important staging tool, but the impact of SLNB on overall survival isunclear.
i
jSee Principles of Surgical Margins for Wide Excision of Primary Melanoma (ME-B)
Wide excision(category 1)
with sentinel
node biopsy(category 2B)
i
j
Sentinel
node
negative
Sentinel
node
positive
See Stage III Workup andPrimary Treatment (ME-4)
Wide excision i
WORKUP PRIMARY TREATMENT ADJUVANT TREATMENTCLINICAL STAGE
Discuss and
consider
sentinel node
biopsyg,h
SeeFollow-Up(ME-7)
Wide excision
(category 1)
i
Stage 0 in situ
Stage IA
(0.76-1.0 mm thick,
no ulceration, mitotic
rate <1 per mm )2 f
f In general, SLNB is not recommended for primary melanomas 0.75 mmthick, unless there is significant uncertainty about the adequacy of microstaging. For melanomas 0.76-1.0 mm thick, SLNB may be consideredin the appropriate clinical context. In patients with thin melanomas
( 1.0 mm), apart from primary tumor thickness, there is little consensus asto what should be considered “high-risk features” for a positive SLN.Conventional risk factors for a positive SLN, such as ulceration, highmitotic rate, and lympovascular invasion (LVI), are very uncommon in
melanomas 0.75 mm thick; when present, SLNB may be considered on an
individual basis.
Stage IA( 0.75 mm thick,no ulceration, mitotic rate<1 per mm )Stage IB( 0.75 mm withulceration, and/or mitoticrate 1 per mm
2 f
2 f )
H&P
Routine imaging/lab
tests not
recommended
Imaging (CT scan,
PET/CT, MRI) only to
evaluate specific
signs or symptoms
H&P
Routine imaging/lab tests not
recommended
Imaging (CT scan, PET/CT,
MRI) only to evaluate specific
signs or symptoms
y p y pp py g p , , g
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Version 2.2014, 09/12/13 © National Comprehensive Cancer Network, Inc. 2013, 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 IndexMelanoma 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.
ME-4
NCCN Guidelines VersionMelanoma
2.2014
Stage III
(clinically positive
node[s])
Clinical trial
or
and/or
Consider RT to nodal basin in
selected patients based onlocation, size and number of
involved nodes, and/or
macroscopic extranodal
extension (category 2B)
or Observation
( )Interferon alfa category 2Bm
p
(SeeFollow-upME-7)
i
m
n
Interferon can be given as high-dose alfa interferon for one year or as peginterferon alfa-2b for up to 5 years. Adjuvant interferon has been shown to improve DFS(category 1); its impact on overall survival remains unclear (category 2B).
Clinical trials assessing alternatives to complete lymph node dissection, such as careful observation with nodal basin ultrasound.
Adjuvant nodal basin RT is associated with reduced lymph node field recurrence but has no impact on relapse-free or overall survival, and its benefits must be weighed
against the increased probability of long-term skin and regional toxicities and potential reduced quality of life.
o
p
See Principles of Surgical Margins for Wide Excision of Primary Melanoma (ME-B)
See Principles of Radiation Therapy (ME-D)
.
.
See Principles of Complete Lymph Node Dissection (ME-C).
for Melanoma
FNA preferred, if feasible, or
lymph node biopsy
Recommend baseline
imaging for staging and toevaluate specific signs or
symptoms (CT, PET/CT, MRI)
CLINICAL/
PATHOLOGIC STAGE
WORKUP PRIMARY TREATMENT ADJUVANT TREATMENT
Stage III
(sentinel node
positive)
Consider baseline imaging
for staging (category 2B) and
to evaluate specific signs or
symptoms (CT, PET/CT, MRI)
Clinical trialor
n
oComplete lymph node dissection
Clinical trialor Observationor Interferon alfa ( )m category 2B
Wide excision of primary tumor
(category 1)
+ complete lymph node dissection
i
o
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NCCN Guidelines IndexMelanoma 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.
ME-5
NCCN Guidelines VersionMelanoma
2.2014
Clinical trial
or
or
Observation
( )
Interferon alfa
category 2B
m
Stage III
in-transitqIf free of
disease
(SeeFollow-upME-7)
m
q
r
s
t
Interferon can be given as high-dose alfa interferon for one year or as peginterferon alfa-2b for up to 5 years. Adjuvant interferon has been shown to improve DFS(category 1); its impact on overall survival remains unclear (category 2B).
In-transit metastasis is defined as intralymphatic tumor in skin or subcutaneous tissue more than 2 cm from the primary tumor but not beyond the nearest regional lymphnode basin. (Definition from CAP 2012 Melanoma Protocol [version 3.2.0.0])
Consider sentinel node biopsy for resectable in-transit disease (category 2B). Sentinel lymph nodes should be evaluated with multiple sectioning andimmunohistochemistry.
See Principles of Radiation Ther E-D)
See Systemic Therapy Options for Advanced or Metastatic Melanoma (ME-E)
.
.
apy for Melanoma (M
FNA preferred, if feasible, or biopsy
Recommend baseline
imaging for staging and to
evaluate specific signs or
symptoms (CT, PET/CT, MRI)
CLINICAL/
PATHOLOGICSTAGE
WORKUP PRIMARY TREATMENT ADJUVANT TREATMENT
Clinical trial (preferred)
Complete surgical excision to clear
margins, if feasible
Regional therapy options:Isolated limb infusion/perfusion
(ILI/ILP)
Local therapy options:
Intralesional injection (BCG, IFN, IL-2)
(category 2B)Local ablation therapy (category 2B)Topical imiquimod for superficial
dermal lesions (category 2B)Consider palliative RT for
unresectable disease
(category 2B)
with melphalan
Systemic therapy
r
s
t
( )See ME-D
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Version 2.2014, 09/12/13 © National Comprehensive Cancer Network, Inc. 2013, 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 IndexMelanoma 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.
ME-6
NCCN Guidelines VersionMelanoma
2.2014
Stage IV
Metastatic
See Treatment for Limited (Resectable)or Disseminated Disease (Unresectable)
ME-10)
Biopsy preferred over FNA if archival tissue
not available for genetic analysis
LDH
Recommend chest/abdominal/pelvic CT, brain
MRI, and/or PET/CT for baseline imaging andto evaluate specific signs and symptoms
u
CLINICAL/
PATHOLOGICSTAGE
WORKUP
uInitial clinical recurrence should be confirmed pathologically if clinically indicated. Obtain tissue for genetic analysis from either archival material or biopsy of themetastasis if the patient is being considered for targeted therapy or if the tissue is relevant to eligibility for participation in a clinical trial.
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Version 2.2014, 09/12/13 © National Comprehensive Cancer Network, Inc. 2013, 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 IndexMelanoma 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.
ME-9
NCCN Guidelines VersionMelanoma
2.2014
Nodalrecurrence
No previousdissection
Previous
dissection
Complete lymphnode dissectiono
FNA (preferred) or
lymph node biopsy
Recommend
baseline imaging for
staging and to
evaluate specific
signs or symptoms
(category 2B)
(CT, PET/CT, MRI)
Pelvic CT if
inguinofemoral
nodes clinically
positive
z
TREATMENT OF RECURRENCEWORKUP
Resectable
Unresectableor Systemic
disease
Complete
resection
Incomplete
resection
Clinical trial
Interferon alfa
or
Observation
or
( )
Consider RT to nodal
basin in selected
patients based on
location, size and
number of involved
nodes, and/or
macroscopic
extranodal extension
(category 2B)
m
category 2B
p
Clinical trialor
Systemic therapy
RT
or
or Best supportive care
s
t
(
)
See NCCN
Guidelines for Palliative Care
m
o
p
Interferon can be given as high-dose alfa interferon for one year or aspeginterferon alfa-2b for up to 5 years. Adjuvant interferon has been shown toimprove DFS (category 1); its impact on overall survival remains unclear (category 2B).
Adjuvant nodal basin RT is associated with reduced lymph node field recurrencebut has no impact on relapse-free or overall survival, and its benefits must beweighed against the increased probability of long-term skin and regional toxicitiesand potential reduced quality of life.
See Principles of Complete Lymph Node Dissection (ME-C)
See Princip
.
.
les of Radiation Therapy for
Melanoma (ME-D)
Excise recurrence; if
previously incomplete
lymph node
dissection, complete
lymph node dissection
ADJUVANT TREATMENT
st
zInitial clinical recurrence should be confirmed pathologically whenever possible.Obtain tissue for genetic analysis from either archival material or biopsy of themetastasis if the patient is being considered for targeted therapy or if it is relevant toeligibility for participation in a clinical trial.
See Principles of Radiation Thera -D)See Systemic Therapy Options for Advanced or Metastatic Melanoma (ME-E)
..
py for Melanoma (ME
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NCCN Guidelines IndexMelanoma 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.
ME-10
NCCN Guidelines VersionMelanoma
2.2014
Distant
metastatic
disease
Limited(Resectable)
Negative for other disease
Positive for
other disease
Resect
Treat as
disseminated
pathway
(below)
Clinical trial
or
Observation
(See Follow-up
on )ME-7
With brainmetastases
Systemic therapyor Clinical trialand/or Consider palliativeresection and/or RTfor symptomatic patientsor Best supportive care
t
s
()
See NCCN Guidelinesfor Palliative Care
Consider resection and/or RT for patients with brain metastases
s
( )See NCCN Guidelines for CNS Cancers
FNA (preferred)
or biopsy
LDH
Recommend CT
chest/abdomen/
pelvis ± MRI
brain, and/or
PET/CT for baseline imaging
and to evaluate
specific signs
and symptoms
u
TREATMENT OF METASTATIC DISEASEWORKUP
No evidence
of disease
Residual disease
Disseminated(Unresectable)
Resect
Observe or systemic
therapy
then repeat
scans
, t
or
Without brain
metastases
s
u
t
Initial clinical recurrence should be confirmed pathologically if clinically indicated. Obtain tissue for genetic analysis from either archival material or biopsy of the metastasisif the patient is being considered for targeted therapy or if it is relevant to eligibility for participation in a clinical trial.
See Principles of Radiation E-D)
See Systemic Therapy Options for Advanced or Metastatic Melanoma (ME-E)
.
.
Therapy for Melanoma (M
Residual disease Treat as disseminated
pathway (below)
No evidenceof disease
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Version 2.2014, 09/12/13 © National Comprehensive Cancer Network, Inc. 2013, 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 IndexMelanoma 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.
NCCN Guidelines VersionMelanoma
2.2014
ME-B
PRINCIPLES OF SURGICAL MARGINS FOR
WIDE EXCISION OF PRIMARY MELANOMA
1.0 mm
1.01-2 mm
2.01-4 mm
>4 mm
Recommended Clinical Margins2
0.5 cm
1.0 cm (category 1)
1-2 cm (category 1)
2.0 cm (category 1)
2.0 cm (category 1)
-1.0
Margins may be modified to accommodate individual anatomic or functional considerations.
Tumor Thickness
In situ1
1
2
For large melanoma in situ (MIS), lentigo maligna type, surgical margins >0.5 cm may be necessary to achieve histologically negative margins; techniques for more
exhaustive histologic assessment of margins should be considered. For selected patients with positive margins after optimal surgery, consider topical imiquimod (for
patients with MIS) or RT (category 2B).Excision recommendations are based on clinical margins taken at the time of surgery and not gross or histologic margins, as measured by the pathologist (category 1).
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NCCN Guidelines IndexMelanoma 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.
NCCN Guidelines VersionMelanoma
2.2014
ME-C
PRINCIPLES OF COMPLETE LYMPH NODE DISSECTION
Adequacy of regional lymph node dissection:
An anatomically complete dissection of involved nodal basin is required.
In the groin, consider elective iliac and obturator lymph node dissection if clinically positive superficial
nodes or 3 superficial nodes are positive. (category 2B)
Iliac and obturator lymph node dissection indicated if pelvic CT is positive (category 2A) or if Cloquet’s
node is positive (category 2B).
For primary melanomas of the head and neck with clinically or microscopically positive lymph nodes in
the parotid gland, a parotidectomy and appropriate neck dissection of the draining nodal basins is
recommended.
1
1 Anatomic boundaries of lymph node dissection should be described in operative report.
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NCCN Guidelines IndexMelanoma 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.
NCCN Guidelines VersionMelanoma
2.2014
PRINCIPLES OF RADIATION THERAPY FOR MELANOMA
ME-D(1 of 2)
Consider RT in the following situations:
Adjuvant treatment in selected patients with desmoplastic melanoma with extensive
neurotropism.
Adjuvant treatment in selected patients f
LDH <1.5 x upper limit of normal ANDGross nodal extracapsular extension AND/OR
Parotid: 1 involved node, any size of involvement
Cervical: 2 involved nodes and/or 3 cm tumor within a node
Axillary: 2 involved nodes and/or 4 cm tumor within a node
Inguinal: 3 involved nodes and/or 4 cm tumor within a node
Brain metastasesStereotactic radiosurgery and/or whole brain radiation therapy either as adjuvant or the primary treatment
Other symptomatic or potentially symptomatic soft tissue and/or bone metastases
1
PRIMARY DISEASE
REGIONAL DISEASE
METASTATIC DISEASE
narrow margins, locally recurrent disease, or
ollowing resection of clinically appreciable nodes (category 2B) if
2
3
2
PalliativeUnresectable nodal, satellite, or in-transit disease
(see NCCN Guidelines for Central Nervous System Cancers)
1
2
3
Interactions between radiation therapy and systemic therapies need to be very carefully considered. A wide range of radiation dose/fractionation schedules is effective. Hypofractionated regimens may increase the risk for long-term complications. Adjuvant nodal basin RT is associated with reduced lymph node field recurrence but has no impact on relapse-free or overall survival, and its benefits must be weighed
against the increased probability of long-term skin and regional toxicities and potential reduced quality of life.
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NCCN Guidelines IndexMelanoma 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.
NCCN Guidelines VersionMelanoma
2.2014
Preferred RegimensIpilimumab
Vemurafenib
High-dose IL-2
Margolin K, Ernstoff MS, Hamid O, et al. Ipilimumab in patients with melanoma and brain metastases: an open-label, phase 2 trial. Lancet
Oncol 2012;13:459-465.
Weber JS, Kahler KC, Hauschild A. Management of Immune-Related Adverse Events and Kinetics of Response With Ipilimumab. J Clin
Oncol 2012.
Sosman JA, Kim KB, Schuchter L, et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med
2012;366:707-714.
Hauschild A, Grob JJ, Demidov LV, et al. Dabrafenib in -mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised
controlled trial. Lancet 2012;380:358-365.
Rosenberg SA, Yang JC, Topalian SL, et al. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using
high-dose bolus interleukin 2. JAMA 1994;271:907-913. Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270
patients treated between 1985 and 1993. J Clin Oncol 1999;17:2105-2116.
Atkins MB, Kunkel L, Sznol M, Rosenberg SA. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term
survival update. Cancer J Sci Am 2000;6 Suppl 1:S11-14.
Hodi FS, O’Day SJ, McDermott DF, Weber RW, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Eng J Med
2010;363:711-723.
Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med
2011;364:2517-2526.
Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med
2011;2507-2516.
Smith FO, Downey SG, Klapper JA, et al. Treatment of metastatic melanoma using interleukin-2 alone or in conjunction with vaccines. Clin
Cancer Res 2008;14(17):5610-5618.
Dabrafenib
BRAF
PRINCIPLES OF SYSTEMIC THERAPY FOR ADVANCED OR METASTATIC MELANOMA (REFERENCES)
ME-E(2 of 4)
Continued
NCCN G id li V i 2 2014
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NCCN Guidelines IndexMelanoma 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.
NCCN Guidelines VersionMelanoma
2.2014
Other Active RegimensTrametinib
Temozolomide
Flaherty KT, Robert C, Hersey P, et al. Improved Survial with MEK Inhibition in BRAF-mutated melanoma. N Eng J Med 2012;367:107-114.
Imatinib
Albumin-bound paclitaxel
Carvajal RD, Antonescu CR, Wolchok, JD, et al. KIT as a therapeutic target in metastatic melanoma. JAMA 2011;395:2327-2334.
M, et al. Dacarbazine-based chemotherapy for metastatic melanoma: thirty-year experience overview.J Exp Clin Cancer Res 2000;19:21-34.
Middleton MR, Grob JJ, Aaronson N, et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with
advanced metastatic malignant melanoma. J Clin Oncol 2000;18:158-166.
Hersh EM, O'Day SJ, Ribas A, et al. A phase 2 Clinical trial of nab-Paclitaxel in previously treated and chemotherapy-naïve patients with
metastatic melanoma. Cancer 2010;116:155-163.Kottschade LA, Suman VJ, Amatruda T, et al. A phase II trial of nab-paclitaxel (ABI-007) and carboplatin in patients with unresectable stage iv
melanoma: a north central cancer treatment group study, N057E(1). Cancer 2011;117:1704-1710.
Dacarbazine
Serrone L, Zeuli M, Sega F
PRINCIPLES OF SYSTEMIC THERAPY FOR ADVANCED OR METASTATIC MELANOMA (REFERENCES)
ME-E(3 of 4)
Continued
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NCCN Guidelines IndexNCCN Guidelines Version Staging2 2014
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NCCN Guidelines IndexMelanoma Table of Contents
Discussion
ST-2
NCCN Guidelines Version StagingMelanoma
2.2014
Distant Metastasis (M)
M0
M1a
M1b
Clinical Staging*
Stage 0Stage IAStage IB
Stage IIA
Stage IIB
Stage IIC
Stage IIIStage IV
Pathologic Staging**Stage 0Stage IAStage IB
Stage IIA
Stage IIB
Stage IICStage IIIA
Stage IIIB
Stage IIIC
Stage IV
No detectable evidence of distant metastases
Metastases to skin, subcutaneous, or distant lymph nodes
Metastases to lung
Tis N0 M0T1a N0 M0T1b N0 M0T2a N0 M0
T2b N0 M0T3a N0 M0T3b N0 M0T4a N0 M0T4b N0 M0
AnyT N1 M0 Any T Any N M1
Tis N0 M0T1a N0 M0T1b N0 M0T2a N0 M0T2b N0 M0T3a N0 M0T3b N0 M0T4a N0 M0
T4b N0 M0T(1–4)a N1a M0T(1–4)a N2a M0T(1–4)b N1a M0T(1–4)b N2a M0T(1–4)a N1b M0T(1–4)a N2b M0T(1–4)a N2c M0T(1–4)b N1b M0T(1–4)b N2b M0
T(1–4)b N2c M0 Any T N3 M0 Any T Any N M1
M1c Metastases to all other visceral sites or distant metastases to
any site combined with an elevated serum LDH
: Serum LDH is incorporated into the M category as shown below:
M1a Distant skin, subcutaneous, Normal
or nodal mets
M1b Lung metastases Normal
M1c All other visceral Normal
metastases
Any distant metastasis Elevated
NoteM Classification Site Serum LDH
Anatomic Stage/Prognostic Groups
*Clinical staging includes microstaging of the primary melanoma and
clinical/radiologic evaluation for metastases. By convention, it should beused after complete excision of the primary melanoma with clinical
assessment for regional and distant metastases
**Pathologic staging includes microstaging of the primary melanoma and
pathologic information about the regional lymph nodes after partial or
complete lymphadenectomy. Pathologic Stage 0 or Stage IA patients are
the exception; they do not require pathologic evaluation of their lymphnodes.
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+Business Media, LLC (SBM). (For complete information and datasupporting the staging tables, visit .) Any citation or quotationof this material must be credited to the AJCC as its primary source. Theinclusion of this information herein does not authorize any reuse or further distribution without the expressed, written permission of Springer SBM, onbehalf of the AJCC.
.
www.springer.com
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NCCN Guidelines IndexMelanoma Table of Contents
Discussion
NCCN Guidelines Version 2.2014Melanoma
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expectations. Furthermore, the NCCN Melanoma Guidelines undergo
annual revision and are continually updated as new data becomeavailable.
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NCCN Guidelines IndexMelanoma Table of Contents
Discussion
NCCN Guidelines Version 2.2014Melanoma
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163. Green AC, Williams GM, Logan V, Strutton GM. Reducedmelanoma after regular sunscreen use: randomized trial follow-up. JClin Oncol 2011;29:257-263. Available at:http://www.ncbi.nlm.nih.gov/pubmed/21135266 .