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NCCN Clinical Practice Guidelines in Oncology™

Hodgkin Disease/Lymphoma

V.1.2007

www.nccn.org


Version 1.2007, 04/23/07 © 2007 National Comprehensive Cancer Network, Inc. All rights reserved. These guidelines and this illustration may not be reproduced in any form without the express written permission of NCCN.

Guidelines Index

Hodgkin Disease TOC

Staging, MS, ReferencesNCCN® Practice Guidelines

in Oncology – v.1.2007

NCCN Hodgkin Disease/Lymphoma Panel Members

Richard T. Hoppe, MD/Chair §Stanford

Ranjana Hira Advani, MD †

Stanford Comprehensive Cancer Center

Richard F. Ambinder, PhD, MD

UNMC Eppley Cancer Center at The

Nebraska Medical Center

Clara D. Bloomfield, MDArthur G. James Cancer Hospital &

Richard J. Solove Research Institute at

The Ohio State University

St. Jude Children's Research

Hospital/University of Tennessee Cancer

Institute

Comprehensive Cancer Center

Philip J. Bierman, MD † ‡

†

Francis Buadi, MD † ‡

Benjamin Djulbegovic, MD, PhD † ‡H. Lee Moffitt Cancer Center & Research

Institute at the University of South Florida

†The Sidney Kimmel Comprehensive

Cancer Center at John Hopkins

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Peter M. Mauch, MD §

Russell J. Schilder, MDFox Chase Cancer Center

Lawrence Weiss, MDCity of Hope

Jane N. Winter, MDRobert H. Lurie Comprehensive Cancer

Center of Northwestern University

Joachim Yahalom, MDMemorial Sloan-Kettering Cancer Center

Andrew D. Zelenetz, MD, PhD † ÞMemorial Sloan-Kettering Cancer Center

Dana-Farber/Brigham and Women's

Cancer Center | Massachusetts General

Hospital Cancer Center

Joseph O. Moore, MD †Duke Comprehensive Cancer Center

† ‡

‡

§

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Andres Forero, MD † ‡University of Alabama at Birmingham

Comprehensive Cancer Center

Leo I. Gordon, MD ‡Robert H. Lurie Comprehensive Cancer

Center of Northwestern University

†Roswell Park Cancer Institute

Mark S. Kaminski, MD †University of Michigan Comprehensive

Cancer Center

† ‡

Francisco J. Hernandez-Ilizaliturri, MD

Gena Love ¥New Mexico Department of Health

Comprehensive Cancer Programs

David G. Maloney, MDFred Hutchinson Cancer Research

Center/Seattle Cancer Care Alliance

David Mansur, MDSiteman Cancer Center at Barnes-

Jewish Hospital and Washington

University School of Medicine

* Writing Committee Member

*

§ Radiation oncology

† Medical Oncology

‡ Hematology/Hematology oncology

Bone Marrow Transplantation

Pathology

Þ Internal medicine

¥ Patient Advocacy

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Guidelines Index

Hodgkin Disease TOC



This manuscript is being

updated to correspond

with the newly updated

algorithm.

These guidelines are a statement of consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinicianseeking to apply or consult these guidelines is expected to use independent medical judgment in the context of individual clinical circumstances todetermine any patient's care or treatment. The National Comprehensive Cancer Network makes no representations nor warranties of any kindwhatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. These guidelines arecopyrighted by National Comprehensive Cancer Network. All rights reserved. These guidelines and the illustrations herein may not be reproduced inany form without the express written permission of NCCN. ©2007.

Table of Contents

Primary Treatment

Classical Hodgkin disease:

Nodular Lymphocyte-predominant Hodgkin disease:

NCCN Hodgkin Disease/Lymphoma Panel Members

Principles of Radiation Therapy (HODG-C)

Revised Response Criteria (HODG-D)

Principles of Salvage Chemotherapy (HODG-E)

Guideline Index

Print the Hodgkin Disease/Lymphoma Guidelines

Diagnosis and Workup (HODG-1)

CS IA-IIA (HODG-2)

CS IB-IIB (HODG-3)

CS III-IV (HODG-3)

CS IA-IIA (HODG-4)

CS IB-IIB (HODG-4)

CS IIIA-IVA (HODG-4)

CS IIIB-IVB (HODG-4)

Follow-up After Completion of Treatment and Monitoring For Late Effects (HODG-5)

Relapse (HODG-6)

Unfavorable Factors (localized and advanced disease) (HODG-A)

Principles of Chemotherapy (HODG-B)

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For help using thesedocuments, please click here

Staging

Manuscript

References

Clinical Trials:

Categories of Consensus:NCCNAll recommendations are Category2A unless otherwise specified.

See

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

NCCN Categories of Consensus

Summary of Guidelines Updates

http://www.nccn.org/clinical_trials/physician.html



Guidelines Index

Hodgkin Disease TOC



Summary of the Guidelines updates

UPDATES

Summary of changes in the 1.2007 version of the Hodgkin Disease/Lymphoma guidelines from the 1.2006 version include:

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In the workup of a patient with Hodgkin disease, category 2B was added to PET scan. Fertility counseling was also added

( ).

New treatment algorithms were developed for the management of classical Hodgkin Disease based upon type of chemotherapy

to be administered. The previous "Interim Restaging" pages have been removed. Footnotes g, i, and j are new to these

algorithms ( and ).

Footnote l is new to the page describing chemotherapy for NLPHD ( ).

The following was added to the "Follow-up after Completion of Treatment" - Surveillance PET is not encouraged due to the risk

for false positives. Management decisions should not be based on PET scan alone, clinical or pathological correlation is

needed ( ).

Chest imaging for Monitoring for Late Effects after 5 Years was clarified to "Consider spiral chest CT for patients at increased

risk for lung cancer.” The mammography recommendation was modified to "5"-8 years after initial therapy. The American

Cancer Society recommendation for breast MRI was added ( ).

Consider RT was added as an option after salvage therapy for Initial stage IA-IIA ( ).

Extranodal sites was added as an unfavorable factor for localized presentations.

Footnotes 1 and 4 are new to the page ( ).

The recommended RT dose to bulky sites was changed from 20 to 30 Gy ( ).

Revised Response Criteria for Lymphoma ( ).

HODG-1

HODG-2 HODG-3

HODG-4

HODG-5

HODG-5

HODG-6

HODG-A

HODG-C

HODG-D



Guidelines Index

Hodgkin Disease TOC



Note: All recommendations are category 2A unless 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.

DIAGNOSISa WORKUP

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Excisional biopsy

(recommended)

Core needle biopsy may

be adequate if diagnostic

FNA alone is insufficient

Immunohistochemistry

recommended but not

necessary for classical

Hodgkin disease.

For nodular lymphocyte-

predominant Hodgkin

disease, recommend

CD3, CD15, CD20, CD21,

CD30, CD57

For typical classical

Hodgkin disease,

recommend CD3, CD15,

CD20, CD30, CD45

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H&P including:

B symptoms

ETOH intolerance

Pruritus

Fatigue

Performance status

Exam lymphoid regions

Spleen, liver

CBC, differential, platelets

Erythrocyte sedimentation

rate (ESR)

LDH, LFT, albumin

BUN, creatinine

Chest x-ray

Chest/abdominal/pelvic CT

PET scan, especially if

equivocal CT (category 2B)

Adequate bone marrow

biopsy in stage IB-IIB and

stage III-IV

Counseling: Fertility,

smoking cessation,

psychosocial

Pregnancy test: women of

childbearing age

Fertility Counseling

Oophoropexy, if

premenopausal and pelvic

RT contemplated

Semen cryopreservation, if

chemotherapy or pelvic RT

contemplated

Neck CT

Pneumococcal, H-flu,

meningococcal vaccines,

if splenic RT contemplated

HIV, if risk factors, unusual

disease presentations

Evaluation of ejection

fraction (eg, if ABVD or

BEACOPP planned)

Pulmonary functions tests

(PFTs), Diffusion capacity

of the lungs for carbon

monoxide (DLCO) (eg,

ABVD or BEACOPP

planned)

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(

)

Useful in selected cases:

see NCCN Distress

Management Guidelines

HODG-1

a

c

Treatment recommendations for postadolescent Hodgkin disease.

Classical Hodgkin disease (HD) includes nodular sclerosis (NSHD), mixed cellularity (MCHD), lymphocyte-depleted (LDHD) and lymphocyte-rich (LRHD).

bNodular lymphocyte-predominant has a different natural history and response to therapy than does classical Hodgkin disease, especially stages I-II. For thatreason, separate guidelines are presented for NLPHD.

CLINICAL STAGING

See PrimaryTreatment(HODG-2)


Classical

Hodgkin

diseasec

Nodular lymphocyte-

predominant

Hodgkin disease

(NLPHD)b

Stage IA-IIANonbulky

Stage I-II

Bulky

Stage IB-IIB

Nonbulky

and III-IV





Guidelines Index

Hodgkin Disease TOC





Chemotherapy + involved-

field RT (category 1)

e

f g

PRIMARY TREATMENThCLINICAL PRESENTATION:Classical Hodgkin diseasec

c

d

e

f

g

i

j

Classical Hodgkin disease (HD) includes nodular sclerosis (NSHD), mixed cellularity(MCHD), lymphocyte-depleted (LDHD) and lymphocyte-rich (LRHD).

Bulky mediastinal disease or mass > 10 cm.

.

ma alonemay be considered for patients not able tolerate chemotherapy chemotherapy alonemay be considered patients .

A corresponding CT scan is always recommended with PET scan.

.Depending upon co-morbidities, subtotal lymphoid irradiation (category 1) or ntleand

for who are not candidates for radiation (category 2B)

hIndividualized treatment may be necessary for older patients and patientswith concomitant disease.

( )see Unfavorable Factors, HODG-A

Principles of Radiation Therapy

See Principles of Chemotherapy (HODG-B)

See (HODG-C).

See Revised Response Criteria for Lymphoma (HODG-D)

CS IA-IIANonbulkyd

HODG-2

2 additional

cycles

Positive

or PR by

PET/CT

j

Negative

or CR by

PET/CT

j

2 additional

cycles

Stage I-II

Bulkyd

Stanford Ve 3 cycles or

12 weeks

If initial disease > 5

cm or spleen

positive, RT (36 Gy

begins optimally

within 3 weeks)

Restage with

PET/CT after

3 months

Progressive

disease or

no change in

PET/CT

j

Follow-up, if

progressive disease,

see belowRestage

with

PET/CTi

Biopsy

Autologous

hematopoietic stem cell

transplant (AHSCT)orIFRTf

Restage

with

PET/CTi

or

See Follow-up HODG-5

ABVD x

4 cycles

e

Restage

with

PET/CTi

Consolidative

RTNegative

PositiveAHSCTorIFRTf

Biopsy

Restage

with

PET/CTi

Negative

or CR by

PET/CT

j Observe

Progressive

diseasejSee Progressive Disease

or Relapse HODG-6


Involved-

field RTfSee Follow-upHODG-5

< CR (not

progressive)

j Observe 2-3

months then

repeat PET PET negative

PET positive See HODG-6

See HODG-5

Negative

or CR by

PET/CT

j



Guidelines Index

Hodgkin Disease TOC



ABVD x

4 cycles

e Restage

with

PET/CTiPET Positive

Progressive

diseasej

2 additional

cycles

2 more cycles

or

ObserveAdd IFRT for stage I-IIf

BiopsyorIFRTf

2 additional

cycles

ObserveorIFRT (especially for stage I-II

unless contraindicated)

f

Restage

with

PET/CTi

c

e

f

h

i

j

k

Classical Hodgkin disease (HD) includes nodular sclerosis (NSHD), mixedcellularity (MCHD), lymphocyte-depleted (LDHD) and lymphocyte-rich (LRHD).

.

Individualized treatment may be necessary for older patients and patients withconcomitant disease.


.

If there is bulky mediastinal disease on CT after 6 cycles of ABVD,consolidative RT to mediastinum recommended. It is not known in the contextof PET negative whether the outcomes will be altered.

See Principles of Chemotherapy (HODG-B)

See (HODG-C).


Principles of Radiation Therapy

Stage IB-IIB

Nonbulky

and Stage

IIIA, IIIB and

IV Nonbulky

and Bulky

Stanford Ve 3 cycles or

12 weeks

CR or PRj jRestage with

PET/CT after

3 months

Progressive

disease or

no change in

PET/CT scan

j

Follow-up, if

progressive

disease, see

below

Negativek

Positivek

IFRT to initial sites

> 5 cm or involved

spleen (36 Gy

begins optimally

within 3 weeks)

f

Biopsy



CR or

PET negative

j

Restage

with

PET/CTi

Restage

with

PET/CTi

Biopsy AHSCT

or

PRIMARY TREATMENThCLINICAL PRESENTATION:Classical Hodgkin diseasec

HODG-3

AHSCT

AHSCT




Guidelines Index

Hodgkin Disease TOC





Involved-field or regional RTorObservation (if patient cannot tolerate RT)

f

PRIMARY TREATMENTCLINICAL PRESENTATION:Nodular lymphocyte-predominant Hodgkin Diseaseb

CS IIA

CS IA

Involved-field or regional RT

Observation (if patient cannot tolerate RT)

f

orChemotherapy + involved-field RT (category 2B)or

l,m f

b

i

j

l

m

Nodular lymphocyte-predominant has a different natural history and responseto therapy than does classical Hodgkin disease, especially stages I-II. For thatreason, separate guidelines are presented for NLPHD.


.

Chemotherapy may be different for NLPHD than for Classical HD. Alkylatingagent based regimens may be preferred.

f .

There are only limited data for combined modality or chemotherapy alone inearly stage LPHD.

See Principles of Radiation Therapy (HODG-C)


HODG-4

CS I-IIB

CS III-IVA

CS III-IVB

Chemotherapy + involved-field RT (category 2B)m f

Chemotherapy ± RTorRituximab (in selected symptomatic patients who

are not candidates for chemotherapy) (category 2B)

m f

Chemotherapy ± RT

orRituximab (in selected symptomatic patients who are not

candidates for chemotherapy or observation) (category 2B)

m f

orObservation (category 2B)orLocal RT (palliation only)

CR or

PET/CT

negative

j

Observe

Restage

with

PET/CTi

Restage

with

PET/CTi

< CRj

Observe, if

asymptomaticorChemotherapyorRT( )See also HODG-6

CR or

PET/CT

negative

j

Observe

< CRj

Observe, if

asymptomaticorChemotherapyorRT( )See also HODG-6



Guidelines Index

Hodgkin Disease TOC





FOLLOW-UP AFTER COMPLETION OF TREATMENT AND MONITORING FOR LATE EFFECTSn

Follow-up with an oncologist is recommended especially during the first 5 y interval to detect recurrence,

then annually due to the risk of late complications including second cancers and cardiovascular disease.o,p

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Interim H&P:

Every 2-4 mo for 1-2 y, then every 3-6 mo for next 3-5 yConsider annual influenza vaccine especially in high risk

patients (eg, treated with chest RT, bleomycin)

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Laboratory studies:CBC, platelets, ESR, chemistry profile every 2-4 mo for 1-2 y,

then every 3-6 mo for next 3-5 yTSH at least annually if RT to neck

Chest imaging:

Chest x-ray or CT (category 2B for CT) every 3-6 mo during

first 2-3 y, then annually thereafter depending on clinical

circumstancesq

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Abdominal/pelvic CT (category 2B):

Every 3-12 mo for first 2-3 y, then annually up to 5 y

Annual mammographic screening:

Initiate 5-8 y post-therapy, or at age 40, whichever comes first, if

RT above diaphragm

Counseling:

Reproduction, health habits, psychosocial, cardiovascular,

breast self-exam, skin cancer risk, end-of-treatment discussion.

Surveillance PET is not encouraged due to risk for false

positives. Management decisions should not be based on PET

scan alone, clinical or pathological correlation is needed.

See Recurrence(HODG-6)

HODG-5

n

oThe frequency and types of tests may vary depending on clinical circumstances; age and stage at diagnosis, social habits, treatment modality, etc.

Mauch P, Ng A, Aleman B, et al. Report from the Rockefellar Foundation sponsored International Workshop on reducing mortality and improving quality of life in long-term survivors of Hodgkin's disease: July 9-16, 2003, Bellagio, Italy. Eur J Haematol 2005;75(s66).

p

qAppropriate medical management should be instituted for any abnormalities.

Chest imaging optional after 5 y if patient treated with a non-alkylating agent, no RT to the chest and no other risk factors are present.

Follow-up after completion of treatment

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Interim H&P: Annually

Pneumococcal revaccination every 5-7 y, if patient treated

with splenic RT or previous splenectomyMeningococcal + H-flu in selected casesConsider annual influenza vaccine especially in high risk

patients (eg, treated with chest RT, bleomycin)

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Annual blood pressure, serum glucose and lipid screeningBaseline stress test/echocardiogram at 10 y

Laboratory studies:CBC, platelets, ESR, chemistry profile annuallyTSH at least annually if RT to neck

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Chest imaging:

Consider spiral chest CT for patients at increased risk for lung

cancer

Annual mammographic/breast MRI screening:

Initiate 5-8 y post-therapy, or at age 40, whichever comes first, if

RT above diaphragm. The American Cancer Society recommends

breast MRI in addition to mammography.

Counseling:

Reproduction, health habits, psychosocial, cardiovascular, breast

self-exam, skin cancer risk, end-of-treatment discussion.

q

Monitoring for Late Effects after 5 Yearso,p



Guidelines Index

Hodgkin Disease TOC





SALVAGE THERAPY

If primary therapy

was RT alone

Chemotherapy: ABVD

Treat to complete

response + 2 cycles

(6-8 cycles) ±

involved-field RT

(category 2B for RT),

if relapse is outside

original field

If primary therapy

was chemotherapy

aloneor combination

chemotherapy/RTAHSCT (category 1) ±

locoregional RTorCombined modality therapyorChemotherapy

u,v,w

x

x

If initial stage was IA-

IIA:

No prior RT and

failure in initial sites

only

s,t

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�

Appropriate treatment in

this setting has not been

identified, individualized

treatment is recommendedu

Consider RT

Less than

complete

response

Complete

responseFollow-up

AHSCTu,v

r

s

t

u

Patients with NLPHD may be managed according to the same algorithm; however, some patients with NLPHD have a chronic indolent course that may not requireaggressive retreatment. These asymptomatic patients may be observed.

There are no data to support a superior outcome with any modalities.

This applies to patients with relapse, not those with progressive disease.

.

Response is not essential to proceed to AHSCT.

v

w

x

Biopsy especially if plan to treat with high-dose therapy.

Conventional-dose chemotherapy may precede high-dose therapy. Timing of RT may vary.

For select patients with long disease-free interval and other favorable features; selection of chemotherapy should be individualized.

See Principles of Salvage Chemotherapy (HODG-E)

CLASSICAL HODGKIN DISEASE

PROGRESSIVE DISEASE OR RELAPSE

r

Progressive

disease or

Relapse

�

�

�

Rebiopsy

Restaging (same as

initial work-up,

including bone

marrow biopsy)

Consider cytogenetics

prior to transplant

HODG-6

All others



Guidelines Index

Hodgkin Disease TOC





UNFAVORABLE FACTORS

(advanced disease)2,3,4

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�

Albumin < 4 g/dL

Hemoglobin < 10.5 g/dL

Male

Age 45 years

Stage IV disease

Leukocytosis (white blood cell

count at least 15,000/mm

Lymphocytopenia (lymphocyte

count less than 8% of white blood

cell count, and/or lymphocyte

count less than 600/mm )

� �

3)

3

1

2

2

4

Only bulky disease is incorporated into the guideline algorithm for localized presentations, however the other factors are considered for assignment into some clinicaltrials.

Derived from Hasenclever D, Diehl V. A prognostic score for advanced Hodgkin’s disease: International Prognostic Factors Project on Advanced Hodgkin’s Disease. NEngl J Med 1998;339:1506-1514.

Consider use of dose-escalated BEACOPP if patient has 4 or more risk factors.

The unfavorable factors for advanced disease are not incorporated into the guideline algorithm for stage III-IV, however these factors are considered for assignment intosome clinical trials.

UNFAVORABLE FACTORS

(localized presentations)

1

�

� �

�

�

�

Bulky disease:Mediastinal mass (chest x-ray):

Mediastinal mass greater than 35% of

the thoracic diameter at T5-6

Erythrocyte sedimentation rate 50, if

asymptomatic

> 3 sites

B symptoms

Extranodal sites

�

�

� Any other mass > 10 cm (CT)

Maximum mass width

Maximum intrathoracic

diameter

1

3

HODG-A



Guidelines Index

Hodgkin Disease TOC





HODG-B

PRINCIPLES OF CHEMOTHERAPY1

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The most common variants of chemotherapy used at NCCN member institutions include ABVD and Stanford V. Some institutions

will use dose-escalated BEACOPP as an alternative regimen in selected cases for highly unfavorable, high-risk patients, usually

with an International Prognostic Score (IPS) 4.

Stage IA-IIA non-bulky diseaseABVD is generally administered for 4 cycles. Complete restaging takes place at completion of chemotherapy. Consolidative

irradiation follows. If no irradiation is given, but the patient has achieved a CR, two additional cycles of chemotherapy should be

administered.

Stage I-II bulky disease ( )ABVD is generally administered for 4-6 cycles. Complete restaging takes place either after 4 cycles or at the completion of

chemotherapy. Consolidative irradiation follows the completion of chemotherapy.

Stage IB-IIB non-bulky, Stage III-IVABVD is generally administered for 6-8 cycles. Complete restaging takes place after 4-6 cycles of chemotherapy following which

two additional cycles of chemotherapy are administered to patients who have achieved a CR. Patients with bulky disease may

have consolidative RT.

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Stanford V chemotherapy for Stage I-II non-bulky disease is administered for 8 weeks (2 cycles). Complete restaging takes place

at the completion of chemotherapy. Consolidative irradiation is optimally instituted within 3 wks (30 Gy to all involved fields).

Stanford V chemotherapy is administered for 12 weeks (3 cycles). Complete restaging takes place at the completion of

chemotherapy. Consolidative irradiation is optimally instituted within 3 wks (36 Gy to initial sites > 5 cm).

Stanford V chemotherapy is administered for 12 weeks (3 cycles). Complete restaging takes place at the completion of

chemotherapy. Consolidative irradiation is optimally instituted within 3 wks (36 Gy to initial sites > 5 cm and spleen if focal

nodules are present initially).BEACOPP (escalated dose) is administered every 3 weeks. Complete restaging takes place at the end of 4 cycles and at the end

of 8 cycles (completion of chemotherapy). This is followed by 30-40 Gy irradiation to initial sites > 5 cm.

See HODG-A

1Diehl V, Franklin J, Pfreundschuh M et al. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's Disease.N Engl J Med 2003;348(24):2386-95.

See Principles of Salvage Chemotherapy page HODG-E



Guidelines Index

Hodgkin Disease TOC





PRINCIPLES OF RADIATION THERAPY

COMBINED MODALITY-RT DOSES:

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Bulky disease sites (all stages)

If treated with ABVD: 30-36 Gy

If treated with Stanford V: 36 Gy

Nonbulky disease (stage I-II)

If treated with ABVD: 20-30 Gy

If treated with Stanford V: 30 Gy

RT-ALONE DOSES (uncommon scenario):

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Involved regions: 30-44 Gy

Uninvolved regions: 30-36 Gy

1

� When possible, the high cervical regions (all patients) and axillae

(women) should be excluded from the radiation fields.Involved-field:Regional-field:

involved lymphoid region(s) onlyinvolved and immediately adjacent lymphoid regions

RADIATION FIELDS

HODG-C

1The dose of 30 Gy is mainly used for excised NLPHD.



Guidelines Index

Hodgkin Disease TOC





HODG-D

REVISED RESPONSE CRITERIA FOR LYMPHOMA(including PET)

Response Definition

CR

PR

SD

Relapsed

disease or PD

Source: Table 2 from Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J of Clin Oncol 2007;25(5):579-586.Reprinted with permission from the American Society of Clinical Oncology.

Nodal Masses Spleen, Liver Bone Marrow

Disappearance

of all evidence

of disease

Regression of

measurable

disease and no

new sites

Failure to attain

CR/PR or PD

Any new lesion

or increase by

50% of

previously

involved sites

from nadir

�

(a) FDG-avid or PET positive prior

to therapy; mass of any size

permitted if PET negative(b) Variably FDG-avid or PET

negative; regression to normal

size on CT

� 50% decrease in SPD of up to 6

largest dominant masses; no

increase in size of other nodes(a) FDG-avid or PET positive prior

to therapy; one or more PET

positive at previously involved site(b) Variably FDG-avid or PET

negative; regression on CT

(a) FDG-avid or PET positive prior to

therapy; PET positive at prior sites of

disease and no new sites on CT or PET(b) Variably FDG-avid or PET negative; no

change in size of previous lesions on CT

Appearance of a new lesion(s) > 1.5 cm in

any axis, 50% increase in SPD of more

than one node, or 50% increase in

longest diameter of a previously identified

node > 1 cm in short axisLesions PET positive if FDG-avid

lymphoma or PET positive prior to therapy

�

�

Not palpable,

nodules

disappeared

� 50% decrease in

SPD of nodules(for

single nodule in

greatest transverse

diameter); no

increase in size of

liver or spleen

> 50% increase from

nadir in the SPD of

any previous lesions

Infiltrate cleared on repeat

biopsy; if indeterminate by

morphology,

immunohistochemistry

should be negative

Irrelevant if positive prior to

therapy; cell type should be

specified

New or recurrent

involvement



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Hodgkin Disease TOC



PRINCIPLES OF SALVAGE CHEMOTHERAPY

� The selection of salvage chemotherapy regimens depends on the pattern of relapse and the agents previously used.

Some studies suggest that late relapses (selected patients) can be successfully treated with the same regimen used for initial

remission induction with favorable results if a second CR is achieved.Induction failures and early relapses will require chemotherapy regimens composed of agents not previously used before

treatment with high-dose chemotherapy with stem-cell rescue. Some of the regimens previously evaluated are: Mini-BEAM,

MINE, VIM-D, and EVA .Some studies have suggested that patients with minimal disease burden at relapse (not refractory) may not need additional

treatment prior to high-dose chemotherapy with stem-cell rescue. However, patients tend to have an improved outcome when

transplanted in a minimal disease state. Thus, cytoreduction with chemotherapy (see above) before high-dose chemotherapy

with stem-cell rescue may be beneficial. In addition, salvage chemotherapy serves as a test for drug sensitivity and to facilitate

the harvest of stem cells.Some studies suggest that nitrogen mustard, procarbazine, carmustine, and melphalan may adversely affect both quality and

quantity of stem-cell collection.

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�

�

Examples of salvage chemotherapy prior to transplant include ICE (ifosfamide, carboplatin, etoposide), DHAP (dexamethasone,

cisplatin, high-dose cytarabine), ESHAP (etoposide, methylprednisolone, high-dose cytarabine and cisplatin).

1,2

3

4 5 6

7,8,9

10



1

2

3

4

5

6

7

8

9

10

Bonfante V, Santoro A, Viviani S, et al. Outcome of patients with Hodgkin's disease failing after primary MOPP-ABVD. J Clin Oncol 1997;15: 528-534.

Longo DL, Duffey PL, Young RC, et al. Conventional -dose salvage combination chemotherapy in patients relapsing with Hodgkin's disease after combinationchemotherapy: The low probability for cure. J Clin Oncol 1992;10:210-218).

Colwill R, Crump M, Couture F, et al. Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin's disease before intensive therapy and autologous bone marrowtransplantation. J Clin Oncol 1995;13:396-402.

Ferme C, Bastion Y, Lepage E, et al. The MINE regimen as intensive salvage chemotherapy for relapsed or refractory Hodgkin's disease. Ann Oncol 1995;6(6):543-9.

Phillips JK, Spearing RL, Davies JM, et al. VIM-D salvage chemotherapy in Hodgkin's disease. Cancer Chemother Pharmacol 1990;27(2):161-3

Canellos GP, Petroni GR, Barcos M, et al. Etoposide, vinblastine and doxorubicin: An active regimen for the treatment of Hodgkin's disease in relapse following MOPP.J Clin Oncol 1995;13:2005-2011.

Sweetenham JW, Taghipour G, Milligan D, et al. High-dose therapy and autologous stem cell rescue for patients with Hodgkin's disease in first relapse afterchemotherapy: results from the EBMT. Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. 1997;20(9):745-52.

Bierman PJ, Anderson JR, Freeman MB, et al. High-dose chemotherapy followed by autologous hematopoietic rescue for Hodgkin's disease patients following firstrelapse after chemotherapy. (2) .

Chopra R, McMillan AK, Linch DC, et al. The place of high-dose BEAM therapy and autologous bone marrow transplantation in poor-risk Hodgkin's disease. A single-center eight-year study of 155 patients. .

Stewart DA, Guo D, Gluck S, et al. Double high-dose therapy for Hodgkin's disease with dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP) prior tohigh-dose melphalan and autologous stem cell transplantation. Bone Marrow Transplant 2000;26(4):383-8.

Ann Oncol 1996;7 :151-6

Blood 1993;81:1137-45

HODG-E



Guidelines Index

Hodgkin Disease TOC



Table 1

Definitions of Stages in Hodgkin's Disease

Stage I

Stage II

Stage III

Stage IV

Involvement of a single lymph node region (I) or localized involvement of a single

extralymphatic organ or site (I ).

Involvement of two or more lymph node regions on the same side of the diaphragm (II)

or localized involvement of a single associated extralymphatic organ or site and its regional

lymph node(s), with or without involvement of other lymph node regions on the same side of

the diaphragm (II ).

Note: The number of lymph node regions involved may be indicated by a subscript (e.g. II ).

Involvement of lymph node regions on both sides of the diaphragm (III), which may

also be accompanied by localized involvement of an associated extralymphatic organ or site

(IIIE), by involvement of the spleen (III ), or by both (III ).

Disseminated (multifocal) involvement of one or more extralymphatic organs, with or

without associated lymph node involvement, or isolated extralymphatic organ involvement with

distant (nonregional) nodal involvement.

A No systemic symptoms present

B Unexplained fevers >38 C; drenching night sweats; or weight loss >10% of body weight

E

E

3

S E+S

Adapted from Carbone PP, Kaplan HS, Musshoff K et al. Report of the Committee on Hodgkin's Disease Staging

Classification. Cancer Res 1971;31(11):1860-1.

Staging

ST-1



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Manuscriptupdate inprogress

This manuscript is being updated to correspondwith the newly updated algorithm.

Manuscript

NCCN Categories of Consensus

Overview

Category 1

Category 2A

Category 2B

Category 3

All recommendations are category 2A unless otherwise noted.

: There is uniform NCCN consensus, based on high-level

evidence, that the recommendation is appropriate.

: There is uniform NCCN consensus, based on lower-

level evidence including clinical experience, that the

recommendation is appropriate.

: There is nonuniform NCCN consensus (but no major

disagreement), based on lower-level evidence including clinical

experience, that the recommendation is appropriate.

: There is major NCCN disagreement that the

recommendation is appropriate.

National statistics demonstrate improvement in the 5-year survival

rates of patients with Hodgkin disease (HD). Such an improvement is

unmatched in any other cancer over the past four decades. There will

be 7,350 new cases and 1,410 estimated deaths in 2005 in the United

States alone. Provided that the proper therapy is selected and appro-

priately administered, the newly diagnosed patient has an overwhelm-

ing likelihood of being cured. In fact, cure rates for Hodgkin disease

have increased to such an extent that the overriding treatment consid-

erations often relate to long-term toxicity, especially for patients with

early- or intermediate-stage disease . For advanced disease,

clinical trials still emphasize improvement in cure rates, but the poten-

tial long-term effects of treatments remain an important consideration.

The NCCN guidelines for HD focus exclusively on patients from

post-adolescence through the seventh decade of life who do not

have serious intercurrent disease. These guidelines do not address

HD in pediatric or elderly patients or in patients with unusual

situations, such as HIV-positive or pregnant patients. Individualized

treatment may be necessary for these patients, older patients, and

patients with concomitant disease.

The guidelines begin with the diagnosis and workup of HD. The

WHO classification divides HD into two main types: classical HD and

nodular lymphocyte-predominant HD (NLPHD). Classical HD

includes nodular sclerosis (NSHD), mixed cellularity (MCHD),

lymphocyte-depleted (LDHD), and lymphocyte-rich (LRHD).

The discussion of clinical management issues starts with classical

HD (stages I-IV, nonbulky and bulky). Next, the guidelines discuss

nodular lymphocyte-predominant disease (stages I-IV). The

discussion then considers interim and end of treatment restaging,

follow-up strategies, and management of disease relapse.

In general, these guidelines emphasize the use of combined

modality therapy (abbreviated chemotherapy and limited irradiation)

in early stage nonbulky disease; combined modality therapy for the

intermediate-prognosis patients (bulky mediastinal stage II disease);

and systemic treatment with or without local field irradiation for

patients with stage III-IV disease. Consistent with NCCN philosophy,

participation in clinical trials is always encouraged.

Radiation oncologists who participated in the development of the HD

guidelines have somewhat divergent views, which are reflected in a

broad range of radiation doses for specific clinical situations and

combined modality therapy. For radiation therapy (RT) alone, which

1

2

Radiation Therapy Doses

( )Table 1

MS-1



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Hodgkin Disease TOC




is not commonly used, the range of recommended doses is 30 to 44

Gy to involved regions and 30 to 36 Gy to uninvolved sites. The

dose of 30 Gy is primarily used for excised NLPHD.

In combined modality therapy dose ranges are determined by

whether the disease is bulky or nonbulky. For patients with stages I-

IV bulky disease, a radiation dose of 20 to 36 Gy is recommended

even after they have received a full course of chemotherapy. This

recommendation reflects limited experience with the use of lower

doses in this setting. In the absence of bulky disease in patients with

stage I-IV the radiation dose could be reduced to 20 to 30 Gy. This

recommendation is based on the range of experience and practice

across NCCN institutions.

Unfavorable prognostic factors in early stage disease influence the

management guidelines. The mediastinal mass ratio identifies

patients who have a poor prognosis when treated with single-

modality therapy. A recommended measurement of mediastinal bulk

is the ratio of the maximum width of the mediastinal mass on chest

x-ray to the maximum intrathoracic diameter. A ratio exceeding one

third is unfavorable. Alternatively, mediastinal bulky disease may be

defined as greater than 35% of the thoracic diameter at the T5-T6

interspace. Another measurement of bulk is any mass greater than

10 cm, which occurs only rarely outside the mediastinum.

An erythrocyte sedimentation rate (ESR) of 50 or more is also

considered unfavorable. This is based largely on European

Organization for Research and Treatment of Cancer (EORTC) data

and the definition of unfavorable prognostic groups for their trials.

Another EORTC report analyzing prognostic factors in early stage

HD identified a poor prognostic group as having more than three

sites of disease. “B” symptoms are also considered an unfavorable

factor in patients with localized HD. The guidelines include flexibility

with respect to how the ESR or number of disease sites impacts

management.

An international collaborative effort evaluating more than 5,000

cases of advanced HD identified seven adverse prognostic factors,

each of which reduces survival rates by 7% to 8% per year. These

factors are 1) age of 45 years or older, 2) male gender, 3) stage IV

disease, 4) albumin level below 4 g/dL, 5) hemoglobin level below

10.5 g/dL, 6) white blood cell count above 15,000/mm , and 7)

lymphocytopenia (lymphocyte count below 600/mm or less than 8%

of the total white count). The number of unfavorable factors helps to

determine clinical management and predict prognosis. For instance,

if the patient has more than four unfavorable factors and advanced

disease, the use of dose-escalated BEACOPP (bleomycin,

etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine,

and prednisone) regimen may be considered as a treatment option.

Fine needle aspiration (FNA) alone is insufficient for diagnosis. Core

needle biopsy may be adequate, but the panel recommends

excisional nodal biopsy. Immunohistochemistry is recommended but

not necessary for classical HD. Immunostaining for CD15, CD30,

CD3, CD20, and CD45 is recommended for classical HD. For

nodular lymphocyte-predominant HD, the guidelines recommend

staining for CD20, CD57, CD15, CD30, CD3, and CD21.

The workup should include a thorough history and physical

examination such as “B” symptoms, EtOH intolerance, pruritus,

fatigue, patient performance status, and examination of the

lymphoid regions, spleen and liver. Standard laboratory testing

Unfavorable Factors

3

4

5

6

3

3

2

Diagnosis and Workup

MS-2



Guidelines Index

Hodgkin Disease TOC




should include a complete blood count (CBC), differential, platelets,

erythrocyte sedimentation rate (ESR), serum lactate dehydrogenase

(LDH) level, albumin, and liver and renal function tests. Chest x-ray

and chest/abdominopelvic computerized tomographic (CT) scans

are appropriate imaging studies. If the CT scan is equivocal,

positron emission tomography (PET) imaging is helpful in defining

the extent of disease. Data show that PET imaging has a high

sensitivity compared to CT in detection of both nodal disease and

organ involvement. Adequate bone marrow biopsy should be

performed on patients who have stage IB-IIB disease or higher.

Other tests should be based on specific symptoms or abnormalities

on the standard staging studies.

Additional information is useful in selected cases. Pregnancy test

should be done for women of childbearing age before treatment. For

patients with risk factors for HIV or unusual disease presentations,

an HIV test is needed. If chemotherapy or pelvic RT is contemplated

in male patients, semen cryopreservation should be done. For

premenopausal female patients, if pelvic RT is planned,

oophoropexy should be performed. In addition, a neck CT scan is

recommended in selected patients. Pulmonary functions tests

(PFTs), diffusion capacity of the lungs for carbon monoxide (DLCO),

and evaluation of ejection fraction are also useful if patients are

going to get ABVD (doxorubicin, bleomycin, vinblastine, and

dacarbazine) or BEACOPP therapy.

If splenic RT is contemplated, pneumococcal vaccine, H-flu vaccine,

and meningococcal vaccine are recommended.

The guidelines begin with consideration of classical HD. Nodular

lymphocyte predominant HD (NLPHD) has a different natural history

and response to therapy than does classical HD, especially stages I-

II. For that reason, NLPHD is addressed separately.

The guidelines stratify classical HD according to the presence of

bulky disease. For patients with nonbulky disease, the preferred

treatment is combined modality therapy. An example is

chemotherapy such as four cycles of ABVD with involved-field

irradiation (20-30Gy) (category 1). Highly selected patients who

cannot tolerate chemotherapy may be treated with RT alone, which

should include sequential treatment to the mantle and paraortic-

spleen fields (category 1) or Mantle field irradiation alone (category

2B). For highly selected patients where RT is contraindicated,

chemotherapy alone is also a treatment option (category 2B).

For patients who have bulky disease, which is almost always

mediastinal, the panel recommends routine combined modality

therapy, beginning with chemotherapy, and followed by limited

radiation. Generally, irradiation of the mediastinum, including

contiguous sites of bulky involvement and bilateral supraclavicular

areas, is sufficient. The usual dose is 30 to 36 Gy. Minimal disease

(less than 5 cm) outside that field may be left unirradiated if a full

course of chemotherapy has been administered.

The chemotherapy that NCCN panelists recommend for early stage

disease is ABVD for 4 cycles or Stanford V (mechlorethamine,

7

8,9

Clinical Management

Stage I-IIA

Classical Hodgkin Disease/Lymphoma

MS-3



Guidelines Index

Hodgkin Disease TOC




doxorubicin, etoposide, vincristine, vinblastine, bleomycin, and

prednisone) regimen for 8 weeks (2 cycles).

Complete restaging takes place at completion of chemotherapy if 4

cycles of ABVD are planned and after 4 cycles if 6 cycles are

planned. Consolidative irradiation follows. If no irradiation is given,

but the patient has achieved a complete remission (CR) or CRu

(complete remission uncertain), 2 additional cycles of chemotherapy

should be administered.

If Stanford V regimen is being used, complete restaging takes place

at the completion of chemotherapy (2 cycles). Consolidative irradia-

tion is optimally instituted within 3 weeks (30 Gy to all involved fields).

Clinical stage IB HD is uncommon, but occasional patients present

with stage IIB disease. The treatment recommended for patients

with nonbulky stage I-IIB disease is combined chemotherapy plus

RT to the involved nodal regions (category 1). Some panel members

feel that chemotherapy alone is an appropriate management option

for highly selected patients where RT is contraindicated; however,

differences of opinion exist among the panelists regarding its

suitability (category 2B).

Patients who have stage IIB disease with bulky mediastinal

involvement should be treated with chemotherapy plus involved-field

RT. Whenever possible, the high cervical regions (all patients) and

axillae (women) should be excluded from the radiation fields.

ABVD is generally administered for 4-6 cycles and the Stanford V

chemotherapy is administered for 12 weeks (3 cycles). Complete

restaging takes place at the completion of chemotherapy.

Consolidative irradiation is optimally instituted within 3 weeks (36

Gy to initial sites >5 cm).

Interim restaging of stage I-II patients should be conducted

following 4 cycles of chemotherapy, or at the end of chemotherapy if

less than 4 cycles of chemotherapy or combined modality therapy is

planned. All previous positive imaging studies need to be repeated.

If a CR or CRu is confirmed, completion of therapy is recommended.

Patients with response less than CRu should undergo a PET scan.

Positive results with either CRu or response less than CRu indicate

the need for additional chemotherapy, RT, or high-dose therapy

individualized according to sites of disease. However, completion of

planned therapy is recommended if the PET scan results are

negative. If disease is progressive or there is no response to current

therapy, a biopsy (may be a core needle biopsy) is strongly

recommended to confirm the diagnosis, and a subsequent

autologous hematopoietic stem cell transplant (AHSCT) with or

without locoregional RT is recommended.

The gold standard of chemotherapy treatment for HD is ABVD. A

randomized trial by the Cancer and Leukemia Group B (CALGB)

showed that ABVD-containing regimens (ABVD alone or alternating

MOPP/ABVD) were superior to MOPP alone. Some concern exists

regarding using ABVD in combination with full-dose irradiation of the

mediastinum because of potential overlapping toxicity of doxorubicin

and bleomycin with radiation.

On the basis of experience at the NCCN institutions, the Stanford V

regimen is also considered an acceptable drug combination for

advanced disease. This is a brief (12 weeks) intensive

chemotherapy regimen that includes mechlorethamine, doxorubicin,

etoposide, vincristine, vinblastine, bleomycin, and prednisone.

Although the regimen is dose intensive, the cumulative doses of

such drugs as mechlorethamine, doxorubicin, and bleomycin are

Stage I-IIB

Choice of Chemotherapy in Advanced Disease

10

11-13

MS-4



Guidelines Index

Hodgkin Disease TOC




significantly less than those in MOPP, ABVD, alternating, or hybrid

regimens, thereby reducing the risks of infertility, secondary

neoplasms, and cardiac and pulmonary toxicity. An integral part of

the treatment program is the incorporation of irradiation (36 Gy) to

initial sites >5 cm and spleen, if involved, after completion of

chemotherapy. This has been a very successful therapy and has

been introduced in the management of advanced disease (stage III-

IV and bulky stage II) in the E2496 intergroup trial.

Some NCCN institutions use dose-escalated BEACOPP regimen as

an alternative in selected cases for high-risk patients with an

International Prognostic Score (IPS 4). This regimen was

developed to improve treatment results by both dose and time

intensification. Results suggest that BEACOPP is a promising

treatment option for advanced HD.

Patients who present with stage III-IV disease may have any

histologic subtype. The primary treatment is chemotherapy alone

(eg, ABVD), as outlined above, or chemotherapy with RT (ie,

Stanford V). The guidelines do not include an option for high-dose

therapy "up front" for these patients. Two recent European trials

failed to show an advantage for high-dose therapy for patients

presenting with various combinations of unfavorable prognostic

factors. Systemic symptoms, age 40 years old, bulky mediastinal

involvement, elevated ESR, high serum LDH level, multiple

extranodal sites, and low hematocrit were defined as unfavorable

factors in this study.

The general concept is to restage patients whose studies are

positive at the outset. This restaging should be completed at certain

defined intervals, in keeping with the management philosophy of still

giving additional chemotherapy beyond the point of restaging, even

if the patient has a complete response.

Using ABVD or BEACOPP as an example, four cycles of

chemotherapy would be administered, followed by restaging. If a

complete response or CRu has occurred, two more cycles of ABVD

would be administered followed by, in selected cases, RT (20-36 Gy)

to bulky sites. If BEACOPP is being used, four additional cycles are

recommended. A final restaging, to confirm the stability of any minor

abnormalities, would follow the completion of chemotherapy.

Treatment would then be discontinued after a total of six cycles of

ABVD or 8 cycles of BEACOPP. For patients achieving response

less than CRu or if CRu is associated with a positive PET scan, 2

additional cycles of ABVD (maximum total of 6 cycles) or 4

additional cycles of BEACOPP (total of 8 cycles), if BEACOPP is

being used, may be considered.

If complete response or CRu is then achieved, an additional two

cycles of ABVD chemotherapy (maximum total of 8 cycles) is

completed. RT (20-36 Gy) to bulky sites may then be administered.

If BEACOPP was administered, RT (30-40 Gy) is then delivered to

initial sites of disease >5 cm. Both the Southwest Oncology Group

(SWOG) study of MOPP-BAP (bleomycin, doxorubicin, and

procarbazine) with or without radiation and the EORTC-GPMC trial

of MOPP/ABV with or without radiation routinely irradiated patients

who had achieved less than complete responses. A significant

proportion of those patients then achieved complete responses.

For patients with response less than CRu or those who has CRu

with a positive PET scan after interim restaging and no change after

secondary restaging, additional therapy, that is individualized

according to the sites of disease, is recommended. Therapy may

include secondary chemotherapy, RT, or high-dose therapy. Biopsy

≥

≥

6,14

14

15

16

Stage III-IV

MS-5



Guidelines Index

Hodgkin Disease TOC




should be performed if a patient is to be treated with high-dose

therapy.

If the Stanford V regimen is being used, restaging should be done

after the completion of chemotherapy. Radiation therapy (36Gy) to

initial sites (>5 cm) and macroscopic splenic disease should then be

administered.

Another issue relates to the use of consolidative low-dose irradiation to

all sites of disease following the completion of chemotherapy for

patients with stage III-IV HD. The SWOG randomized trial showed no

improvement in overall survival rates for those patients who received

irradiation, but the disease-free interval was prolonged, especially for

patients with bulky NSHD. The EORTC 20884 trial similarly showed

no improvement in survival or freedom from relapse for patients treated

with 25 Gy involved-field irradiation following completion of 8 cycles of

MOPP-ABV. One remaining issue, the role of consolidative irradiation

for stage III-IV disease with a “bulky” component, is being addressed in

a randomized trial of the German Hodgkin's Study Group (GHSG).

In the presence of truly progressive or no response disease, which

is very uncommon, a core needle biopsy may be warranted (if only

to confirm the diagnosis is truly HD), followed by high-dose salvage

regimens with or without locoregional RT, and autologous

hematopoietic stem cell transplant (AHSCT). Although the prognosis

in such cases is poor, and the efficacy of high-dose therapy in this

setting is not as good as in the setting of "minimal residual disease,"

this remains the best treatment option for these patients.

Nodular lymphocyte-predominant HD comprises about 4-5% of all

HD. Treatment choices for NLPHD are based on clinical stage and

presentation. For clinical stage IA, involved-field or regional RT

alone is recommended. Patients with stage IIA disease may also be

treated with involved-field or regional RT. However, some NCCN

panelists believe that chemotherapy plus involved-field radiation is

also appropriate in these cases (category 2B). For stage IA and IIA,

observation may be considered if the patient cannot tolerate RT.

Observation (category 2B) or chemotherapy with or without RT is an

appropriate option for asymptomatic patients with clinical stage III-

IVA NLPHD disease. Local RT alone is also an appropriate

treatment option for palliation purposes in this group of patients.

Rituximab is an option in selected symptomatic patients who are not

candidates for chemotherapy in patients with clinical stage III-IV

NLPHD (category 2B).

The end-of-treatment restaging occurs after an earlier restaging

process and should be performed 3 months after completion of

treatment. The treatment options are similar to those at the time of

initial restaging. Additional follow-up after completion of treatment is

recommended for patients with complete response or CRu.

Patients with response less than CRu require a PET scan. For

patients with either Cru or response less than CRu and a positive

PET scan, biopsy is recommended if lymph node is easily

accessible. In case of positive biopsy results, additional therapy

(salvage CT, RT, or high-dose therapy) that is individualized

according to the sites of disease and initial therapy, is

recommended. If lymph node is not easily accessible for biopsy,

observation is recommended until disease progression. If the PET

scan is negative, the patient may be observed.

17

2

Nodular Lymphocyte-Predominant Hodgkin Disease

End of Treatment Restaging

MS-6



Guidelines Index

Hodgkin Disease TOC




A patient with progressive disease that is confirmed by a positive

biopsy will likely go on to AHSCT with or without locoregional RT.

The guidelines for follow-up are based largely on NCCN panelists'

own clinical practices and are not supported by high-level

evidence. Interim physical examinations and blood work (including

CBC, platelets, ESR, and chemistry profile) are performed less

frequently as the length of time in between follow-ups increases,

but the examinations and laboratory tests are continued annually

after 5 years.

Interim evaluations should include consideration of pneumococcal

revaccination every 5-7 years especially if the patient has been

treated with splenic RT or had a splenectomy in the past. High-risk

patients (eg, treated with bleomycin, chest RT) should also be

considered for annual influenza vaccinations. Meningococcal and

H-flu revaccination can be considered in selected cases.

Patients who have had neck or upper mediastinal irradiation

should undergo thyroid function studies at least annually to rule

out hypothyroidism.

The panel overwhelmingly agrees that given the long-term risks of

the therapies for HD, patients should be followed by oncologists

who are aware of these risks and complications especially during

the first 5-year interval then annually due to the risk of late

complications including secondary cancers and cardiovascular

disease.

Repeat imaging studies of initially involved sites are important, as

are surveillance studies of both the chest and abdomen. Chest x-

ray or CT (category 2B for CT) should be performed every 3-6

months during the first 2-3 years, then annually depending on

clinical circumstances. Chest imaging is optional after 5 years if

the patient was treated with a non-alkylating agent, did not have

RT and no other risk factors (eg, smoking) are present.

Abdominal/pelvic CT (category 2B) is monitored every 3-12

months for the first 2-3 years, then annually up to 5 years. The

frequency and types of tests may vary depending on clinical

circumstances: age and stage at diagnosis, social habits,

treatment modality, etc.

The panel recommends that women who have been irradiated

above the diaphragm undergo routine annual mammography

beginning no later than 8 years after completion of therapy, or at

age 40, whichever occurs earlier. Counseling regarding self-breast

examination should also be provided.

The NCCN HD panel members agrees, based upon available data

on increased long-term risk of cardiac disease, to recommend

resting and stress echocardiography annually after 10 years from

treatment.

In addition to the follow-up measures outlined above, the panel

believes counseling about the issues of the survivorship period,

including long-term treatment effects, risks of second primary

tumors, cardiac disease, skin cancer, and reproduction must be an

integral part of follow-up for HD patients. Health habits and

psychosocial issues should also be discussed with a patient.

Patients with classical HD that relapses should undergo biopsy

and restaging. Restaging procedure should include bone marrow

biopsy. Cytogenetics may be considered if bone marrow

Follow-up after Completion of Treatment and Monitoring for LateEffects

Relapse

18

18

18,19

18

MS-7



Guidelines Index

Hodgkin Disease TOC




MS-8

transplantation is planned. Only in rare instances is relapse

documented on clinical grounds alone. The management of relapse

will depend on whether the primary treatment was radiation alone or

included a systemic component, such as chemotherapy or combined

modality therapy.

Patients with NLPHD may be managed according to the same

algorithm. However, some patients with NLPHD have a chronic

indolent course that may not require aggressive retreatment. These

asymptomatic patients may be observed.

Patients with classical HD whose initial treatment consisted of

radiation alone have very effective salvage potential when a

standard course of chemotherapy with or without RT is administered

(category 2B for RT), especially if the failure is outside of the initial

radiation field. Patients who achieve less than a complete

response may be candidates for high-dose therapy.

For patients treated initially with chemotherapy or combined

modality therapy, the algorithm is a bit more complicated and

therapy is more likely to be individualized. Appropriate treatment has

not been identified for patients with initial stage IA to IIA disease,

who received chemotherapy alone, and experienced failure at the

initial sites. The panel recommends an individualized approach in

this situation. For all other settings the panel recommends AHSCT

(category 1) with or without locoregional RT. Combined modality

therapy, or chemotherapy may be used for selected patients with

long disease-free interval and other favorable features.

Chemotherapy regimens should be individualized in this case.

Examples of salvage chemotherapy regimens prior to transplant

include ICE (ifosfamide, carboplatin, and etoposide), DHAP

(dexamethasone, cisplatin, high-dose cytarabine), ESHAP

(etoposide, methylprednisolone, high-dose cytarabine).

The management of HD continues to evolve. Major changes have

been incorporated into the NCCN guidelines since their inception.

Current management programs are based on comprehensive

clinical staging followed by combined modality therapy for those

patients with favorable and intermediate prognosis or chemotherapy

alone for patients with advanced disease. Relapse is uncommon,

but secondary management with peripheral stem cell transplant may

be very effective. The excellent prognosis for these patients man-

dates careful long-term follow-up to detect late treatment effects.

At the beginning of each panel meeting to develop NCCN guide-

lines, panel members disclosed financial support they have received

in the form of research support, advisory committee membership, or

speakers' bureau participation. Members of the panel indicated that

they have received support from the following: Albuquerque Area

Indian Health Board, Amgen, Biogen IDEC, Bristol-Myers Squibb,

Cancer Services of New Mexico, Genentech, Genitope Corporation,

GlaxoSmithKline, Lymphoma Research Foundation, Millennium,

NCI, National Initiative for Lymphoma Education, NIH, Novartis,

Oncomed, Ortho Biotech, Roche, and Tibotec.

Some panel members do not accept any support from industry. The

panel did not regard any potential conflicts of interest as sufficient

reason to disallow participation in panel deliberations by any

member.

Salvage Therapy

Summary

Disclosures for the NCCN Hodgkin Disease/LymphomaGuidelines Panel

20

21



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4. Henry-Amar M, Fiedman S, Hayat M et al. Erythrocyte

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REF-1



Guidelines Index

Hodgkin Disease TOC




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Recommended reading

REF-2

NCCN Clinical Practice Guidelines in Oncology™ Hodgkin ... · PDF fileRussell J....

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Transcript of NCCN Clinical Practice Guidelines in Oncology™ Hodgkin ... · PDF fileRussell J....