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PET and Lymphoma. Corinne Haioun Unité Hémopathies Lymphoides Hôpital Henri Mondor Créteil, France. First and only rule: to cure the patient with first-line treatment. PET and Lymphoma : Background.

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Pet and lymphoma

PET and Lymphoma

Corinne Haioun

Unité Hémopathies Lymphoides

Hôpital Henri Mondor

Créteil, France


First and only rule: to cure the patient with first-line treatment

PET and Lymphoma : Background

  • Residual masses at the end of therapy are frequent(70% HL, 50% NHL) but only a minority of patients relapse (<20% HL, 25% NHL)

  • Patients in apparent complete remission also relapse

  • Early treatment of residual activedisease may improve survival

Need for an accurate and sensitive tool to detect residual disease


Pet and hodgkin lymphoma background
PET and Hodgkin Lymphoma treatment : Background

  • Hodgkin Lymphoma is a curable disease, with more than 75% of the patients free of disease 10 years or more after standard treatment.

  • However, nearly 15-20% of the patients treated with ABVD fail therapy either for progression or relapse.

  • FDG-PET scan could be a surrogate test for chemosensitivity, due to its ability to predict treatment outcome with an overall accuracy of 90-95%.


HD prognostic score: clinical variables treatment

Hasenclever d. NEJM 1998; 339:1506


HD prognostic score: 7y-FFP and OS treatment

7% of the patients

Hasenclever d. NEJM 1988; 339:1506


HL prognosis: from IPS to PET treatment

IntergruppoItaliano Linfomi

According to IPS

According to PET-2 (+vs.-) and IPS (0-2 vs 3-7)


PET-0: 25.03.04 treatment

PET-2: 30.06.04

Gallamini: Hematologica 2006; 91, 475-81

Gallamini: JCO 2007; 25, 3743-52

PET-6: 08.11.04

Hutchings: Blood 2006; 107, 52-59

Kostakoglu: Cancer 2006; 107:2678-87


H10 trial

1 cycle ABVD treatment

IN-RT 30 Gy

(+boost 6 Gy

résiduals)

whatever

FDG-

PET

H10 Trial

ABVD 2 cycles

The results

Favourable Group F

Randomisation

ABVD 2 cycles

négative

BEACOPP

2 cycles

esca

IN-RT 30 Gy

(+ boost 6 Gy)

FDG-

PET

ABVD 2 cycles

Hodgkin

Lymphoma

Stage I/II

positive

whatever

ABVD 2 cycles

IN-RT 30 Gy

(+boost 6 Gy

résiduels)

FDG-

PET

ABVD 2 cycles

The results

Unfavourable

Group U

Randomisation

negative

ABVD 4 cycles

2 cycles

BEACOPPesca

IN-RT 30 Gy

(+ boost 6 Gy)

FDG-

PET

ABVD 2 cycles

positive

First registration

Second

registration


The situation in Diffuse Large B-Cell Lymphoma treatment

Weber W: J.Nucl. Med 2007: 48: 1580-82.


Current questions for dlbcl patients
Current questions for DLBCL patients treatment

Role of PET to individualize treatment ?

Interim PET after 2 cycles may help stratify patients ?

Event-free survival

Overall survival

100

100

PET– (n = 54)

80

80

PET– (n = 54)

60

60

Pprobability

Probability

PET+ (n = 36)

40

40

PET+ (n = 36)

20

20

p < 0.0001

p = 0.006

0

0

0 1 2 3

0 1 2 3

Years after randomisation

Years after randomisation

Haioun C, et al. Blood 2005


Early after 2 cycles pet treatment evaluation with visual analysis
Early (after 2 cycles) PET treatment evaluation with visual analysis

  • All the sites of FDG uptake are scored in PET-0 and PET-2.

  • Each FDG uptake focus is quantified according to a score graded 1-3 (1 low, 2 moderate, 3 high) for extension and intensity

  • PET-2 negative: Negative was defined as having no residual abnormal uptake or as having a unique residual site (with an extent score of 1) associated with an intensity score of 1, whereas all the other previously hypermetabolic sites were extinguished.

  • PET-2 positive: Positive was defined as having at least one residual site (with an extent score of 1) associated with an intensity score of 2, or as having 2 or more residual sites with any extent and intensity scores.

Haioun, Blood 2005; 106: 1376-1381


Early treatment evaluation
Early treatment evaluation analysis

Before treatment

At 2 cycles

At 4 cycles

FDG-PET2 (+)

Haioun C, et al. Blood 2005; 106(4): 1376–81


Early treatment evaluation1
Early treatment evaluation analysis

Before treatment

At 2 cycles

At 4 cycles

FDG-PET2 (-)

Haioun C, et al. Blood 2005; 106(4): 1376–81


Current questions for dlbcl patients1
Current questions for DLBCL patients analysis

Role of PET to individualize treatment ?

Jerusalem et al. Haematologica, 85(6): 613-8   2000; Spaepen et al. Ann Oncol, 13(9): 1356-63   2002; Kostakoglu et al. J Nucl Med, 43(8): 1018-27   2002; Haioun C et al. Blood 2005; 106(4): 1376–81; Mickaeel et al. 2005


FDG-PET in DLBCL analysis

TN

TN +FN

(High negative predictive value): NPV=

FN

TP

TP +FP

FP

(Low positive predictive value): PPV=


Event free survival and overall survival according to response at 2 cycles on the basis of pet n 90
Event-free survival and overall survival according to response at 2 cycles onthe basis of PET (n = 90)

Overall survival

Event-free survival

100

100

PET– (n = 54)

80

PPV 50 %

NPV 74 %

Accuracy 68.5%

80

PET– (n = 54)

60

60

PET+ (n = 36)

probability of OS

Probability of EFS

40

40

median f/u: 2 years

PET+ (n = 36)

20

20

p < 0.0001

p = 0.006

0

0

0 1 2 3

0 1 2 3

Years after randomisation

Years after randomisation

Haioun C, et al. Blood 2005; 106(4): 1376–81


Activité mesurée response at 2 cycles on

C*tissulaire =

Volume du foyer

(Bq/g)

Ci*()

SUV=

dose/poids

Activité injectée

C*tissulaire

C*totale =

Poids du corps

SUV =

C*totale

(Bq/g)

Si distribution homogène, SUV = 1

=1g/cm3


  • 92 patients response at 2 cycles on

  • PET baseline and after 2 courses of CT

  • IPI 0-1: 38; IPI 2-3: 54

  • Therapy: CHOP, R-CHOP, ACVPB/ACE, R-ACVBP

Lin C.: J. Nucl. Med 2007; 48, 1626-1632


Suv based assessment versus visual analysis
SUV-based Assessment versus Visual Analysis response at 2 cycles on

SUV and EFS:

Optimal cut-off point of SUVmax reduction: 65.7%(ROC analysis)

PPV 81.3%

NPV 75.0%

Accuracy 76.1%

Lin C, Itti E. JNM 2007; 48:1626-32.


Visual analysis versus suv based assessment
Visual Analysis versus SUV-based Assessment response at 2 cycles on

SUV max Reduction

Visual Analysis

Probability of EFS (%)

n=58

PET (-)

n=76

> 65.7%

n=34

PET (+)

P < .0001

n=16

P = .009

65.7%

Months After Randomization

Linh C, Itti E. JNM 2007; 48:1626-32.


MSKCC 01-142-DLBCL: Risk Adapted Therapy response at 2 cycles onTransplant-eligible,CS IIX, III or IV age-adjusted IPI 1, 2, or 3 Risk Factors

  • Therapy interval-2 weeks with peg-filgrastim support

  • PET 10-14 days post cycle 4

  • Treatment is adapted by biopsy, not PET

  • No radiation therapy permitted except for testicular disease

  • IT methotrexate for aaHR, paranasal sinus, testis, BM

Moskowitz et al., Blood 108: Abstract 532, 2006


MSKCC 01-142-DLBCL: Risk Adapted Therapy response at 2 cycles onTransplant-eligible,CS IIX, III or IV age-adjusted IPI 1, 2, or 3 Risk Factors

Moskowitz et al., Blood 108: Abstract 532, 2006


Outcome based upon interim restaging pet scan
Outcome based upon Interim response at 2 cycles onRestaging PET scan

Interim PET does not predict EFS

Moskowitz et al., Blood 108: Abstract 532, 2006


Optimize pet interpretation

Current questions for DLBCL patients response at 2 cycles on

Optimize PET interpretation

Role of PET to individualize treatment ?

3 Readers

Anonymization

Double encryption

Time : 10 mn

Time : 10 mn

Medical Gateway

PET data sent over the internet via a dedicated

server to 3 readers: review in 48 hours


Lnh07 3b

PET Results response at 2 cycles on

PET Results

Salvage : CORAL

4+

R-ACVBP14 + MTX IT + G-CSF

MTX iv

R- IFM / VP16

AraC

A1

A1

2- /4 -

Arm A

A2

A2

MTX iv

Z-BEAM + ASCT

PET 0

PET 2

PET 4

R

PET Final

2+ /4 -

PET

PET

PET 4

PET 4

B2

B2

Arm B

2- /4 -

B1

B1

R-CHOP14 + MTX IT + G-CSF

R-CHOP14 + G-CSF

4+

Salvage : CORAL

LNH07-3B

DLBCL ; <60 years

aa-IPI = 2-3

Role of PET to individualize treatment ?


Acknowledgements

Lymphoma Unit response at 2 cycles on

Karim Belhadj

Taoufik El Gnaoui

Isabelle Gaillard

Jehan Dupuis

Frederique Kuhnowski

Radiology

Alain Luciani

Alain Rahmouni

Biostatistics

François Hémery

Eric Lepage

Nuclear Medicine

Emmanuel Itti

Eva Evangelista

Sophie Lin

Michel Meignan

Hematopathology

Christiane Copie

Karen Leroy

Philippe Gaulard

Acknowledgements


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