be considered an adverse prognostic factor in patients ...€¦ · Rambam Health Care Campus and Technion, Haifa, Israel Rebecca Lopez-Alonso, Tania Mashiach, Elinor Barzilai,Michal

Rambam Health Care Campus and Technion,

Haifa, Israel

Rebecca Lopez-Alonso, Tania Mashiach, Elinor Barzilai, Michal Weiler-Sagie, Eldad J. Dann

Should a bulky mediastinal mass measuring >7 cm be considered an adverse prognostic factor in

patients with advanced Hodgkin lymphoma and a negative interim PET/CT ?

“Humani nihil a se alienum putabat”

“Nothing of humanity was foreign to

him”

• The introduction of PET/CT in the staging and treatment evaluation algorithm changed the concept of therapy for many patients with advanced Hodgkin disease (HD).

• In the German HD9 study for advanced HD, 71% of patients (pts) were treated with radiation therapy (RT) for the initial mass measuring ≥5 cm.

• In the HD15 study, only 11% of pts underwent RT, i.e., those with a residual mass of ≥2.5 cm and a positive PET/CT at the end of therapy.

• This dramatic change in the strategy was demonstrated to be successful in terms of progression-free survival (PFS) in pts treated with 6 cycles of escalated BEACOPP (EB).

• However, the validity of this approach excluding RT from the management of pts receiving a less intensive regimen based on interim PET results is unclear. The GITIL study, the intergroup study and the H2 study omitted RT to a bulky mediastinal mass. But is there a cutoff that marks an increased risk for thoracic mediastinal mass?

• The current analysis included patients with stage IIB III/IV HD treated between 2001-2010 who underwent baseline CT or PET/CT.

The current study has evaluated if a bulky disease is an adverse prognostic factor in patients receiving the

following treatment regimens:

•Initiation with escalated BEACOPP and its adjustment to ABVD or standard BEACOPP, based on negative interim PET/CT.

•Initiation with ABVD therapy and its up-grading to escalated BEACOPP based on positive interim PET/CT.

•Omitting radiation therapy based on the end-of-therapy negative PET/CT.•We assessed the relapse rate of patients with mass 0-7 , 7-9.9,≥ 10 cm

BULKY Size <7 70 9 12.9

. 7-9.9 28 7 25.0

. 10+ 22 5 22.7

Copyright ©2007 American Society of Hematology. Copyright restrictions may apply.

Dann, E. J. et al. Blood 2007;109:905-909

Risk adapted therapy based on predefined risk factors and early assessment based on interim PET/CT

Aim : To achieve progression free survival in both high risk and low risk patients and ameliorate chemotherapy based on

PET/CT

Israel H2 trial: advanced stages of HL

2 x ABVD

IPS 0-2

PETNegative

Positive

2 x esc. BEACOPP

PETNegative

Positive

2 x esc. BEACOPP

PET

Negative

2 x esc. BEACOPP

PET

Negative

2 x esc. BEACOPP(+ RT)

Positive + progression

Salvage

Positive + progression

Salvage

4x ABVD

IPS 3-7

The data included measurements of the largest diameter either of the biggest single mass or conglomerate of lymph nodes in the axial and coronal planes in the staging

PET/CT and in the latest PET/CT performed

1a:

axial view of a PET/CT image without iodine-based

intravenous contrast media shows

measurement of an anterior mediastinal mass in

station 3a (prevascular).

1b:

coronal reconstruction of the

previous PET/CT image shows

measurement of the mass in its

biggest coronal diameter.

Disease free survival of patients with bulky and non-bulky disease

BULKY Size <7 70 9 12.9

. 7-9.9 28 7 25.0

. 10+ 22 5 22.7

Non mediastinal HL (all) 40 4 10.0

Mediastinal HL non bulky (<7cm) 45 7 15.6

Mediastinal HL bulky (7+ cm) 35 10 28.6

All patients N relapse %

Non mediastinal HL (all) 33 2 6.1 0.083 1.00

Mediastinal HL non bulky (<7cm) 37 5 13.5 0.312 2.33

Mediastinal HL bulky (7+ cm) 25 7 28.0 0.035 5.43

PET2 -POSITIVE 25 7 28.0 0.032 5.59

N relapse % p HR

N relapse, %

Multivariate Cox regression analysis and 5-y DFS±SE

P value Adjusted 95.0% CI for HR 5-y DFS±SE

HR Lower Upper

3 factors

Non-mediastinal HL

(all)

0.083 1 0.938±0.04

Mediastinal HL,

non-bulky (<7cm)

0.312 2.33 0.45 12.01 0.85±0.06

Mediastinal HL,

bulky (7+ cm)

0.035 5.43 1.13 26.14 0.69±0.1

PET2 -POSITIVE 0.032 5.59 1.16 26.96 0.71±0.09

For patients with IPS ≥ 3, treatment

was initiated with escalated BEACOPP

IPS ≥ 3

For patients with IPS 0-2 treatment

was initiated with ABVD

IPS 0-2

Pts Events %

IPS 0-2.

.

.

Non-mediastinal HL (all) 14 2 14.3

Mediastinal HL, non-bulky (<7cm) 17 2 11.8

Mediastinal HL bulky (7+ cm) 15 6 40.0

PET2 -POSITIVE 8 1 12.5

. Other 66 10 15.2

IPS 3+.

.

.

Non-mediastinal HL (all) 19 0 0.0

Mediastinal HL, non-bulky (<7cm) 20 3 15.0

Mediastinal HL, bulky (7+ cm)

10 1 10.0

PET2 -POSITIVE 17 6 35.3

Conclusions

Masses located in the mediastinum, measuring more than 7 cm in any of the planes, have a negative prognostic effect; thus, the cutoff of 7 cm can be used to describe bulky disease in the mediastinum.

The location of the mass has shown to be a prognostic factor: bulky masses (>7 cm) located in the mediastinum are associated with a 5-time increase in the risk of progressive disease (HR 5.4, p=0.03).

Positive interim PET has an HR for progression of 5.59, p=0.03

The relapse rate in patients with thoracic bulky disease >7 cm is substantially reduced if therapy is initiated with EB.

These findings are awaiting more extensive evaluation in a much larger cohort of patients.