Pulmonary Metastasis From

OsteosarcomaMulti-factorial analysis of survival

at first lung involvement

Ali Aljubran, Martin Blackstein

for the University of Toronto Musculoskeletal Oncology Group

INTRODUCTION

The cure rate of non-metastatic cases has improved from 20% (Pre chemotherapy era) to 65%.

Recurrence still occurs in approximately 30%. More than 80% of all relapses involve the lungs. Complete surgical resection is the only potential

curative treatment. Single institute review.

PATIENTS AND METHODS

Osteosarcoma patients (1988-2003).

Variables at the first lung involvement , e.g. RFI, multiplicity and laterality of lesions and size of the largest nodule are all analyzed. Peri operative chemotherapy was also analyzed.

Statistical methods: Post lung metastasis survival PLMS was calculated from the date of the first lung metastasis to the date of death or last follow-up.

RESULTS

247 Total

1988-2003

Synchronous Mets

38 (15.4%)

M0 at presentation

209 (84.6%)

RESULTS

247 Total

1988-2003

Synchronous Mets

38 (15.4%)

M0 at presentation

209 (84.6%)

MetachronousMets

56(26.8%)

No relapse145

(69.4%)

Total 94

Isolated LR8 (3.8%)

RESULTS

Med. FU 2.7y

247 Total

1988-2003

Synchronous Mets

38 (15.4%)

M0 at presentation

209 (84.6%)

MetachronousMets

56(26.8%)

Isolated LR8 (3.8%)

No relapse145

(69.4%)

Isolated Bone9

LungLung+/-others

8585

Total 94

DOD58

(68.2%)AWED

12(14.1%)

ANED15

(17.6%)

Characteristics

85 patients No. (%)

Follow up

(onset of lung mets)

Median 2.7 year,(Range 0.1 y -16.25 y)

Age at 1st lung mets Median 29,(Range 14-77)

Gender MaleFemale

53 (62.4)32 (37.6)

% Necrosis(Primary tumor)

≥ 90%<90%No pre-op chemo

26 (30.6)48 (56.5)11 (12.9)

RFI before 1st relapse(52 pts- metachronous

lung met)

≤ 12 months>12 monthsNot applicable

28 (53.9)23 (44.2)1 (1.9)

Lung surgery

No surgery1 surgery2 surgeries3 surgeries4 surgeriesUnknown

34 (40)23 (27.1)11 (12.9) 47 patients10(11.8) (55.3)3 (3.5)4 (4.7)

Variables related to 1st lung involvement

( only the operated cases, 47pts)..

Number of lung metastases

1-3≥ 4Unknown

18 (38.3)25 (53.2)4 (8.5)

Laterality

BilateralUnilateralUnknown

32 (68.1)12 (25.5)3 (6.4)

Size of the largest nodule

>1 cm≤ 1cmUnknown

20 (42.5)13 (27.7)14 (29.8)

Peri-op chemotherapy

Status of resection

YesNoUnknown

CompleteIncompleteUnknown

21 (44.7)25 (53.2)1 (2.1)

35 (74.5)5 (10.6)7 (14.9)

85 patients: 3 year PLMS: 30%

0 5 10 15

0.0

0.2

0.4

0.6

0.8

1.0

Years from the first lung metastasis to death

Su

rviv

al sin

ce

th

e fir

st lu

ng

me

tasta

sis

n = 85

3 year PLMS: Synchronous mets: 30 % Metachronous mets: 30 %

0 5 10 15

0.0

0.2

0.4

0.6

0.8

1.0

Years from the first lung metastasis to death

Su

rviv

al s

ince

the

firs

t lu

ng

me

tast

asi

s

Synchronous , n = 33Metachronous , n = 52

Logrank p-value = 0.79

3 year PLMS: NO lung surgery: 16 % lung surgery: 38 %

0 5 10 15

0.0

0.2

0.4

0.6

0.8

1.0

Years from the first lung metastasis to death

Su

rviv

al sin

ce

th

e fir

st lu

ng

me

tasta

sis

No surgery , n = 34Surgery , n = 47

Logrank p-value = 0.00023

3 year PLMS: 1-3 lesions: 69 % ≥ 4 lesions: 18 %

0 5 10 15

0.0

0.2

0.4

0.6

0.8

1.0

Years from the first lung metastasis to death

Su

rviv

al sin

ce

th

e fir

st lu

ng

me

tasta

sis

Number of lesions >=4 , n = 25Number of lesions 1-3 , n = 18

Logrank p-value <0.0001

3 year PLMS: Unilateral: 55 % Bilateral: 32 %

0 5 10 15

0.0

0.2

0.4

0.6

0.8

1.0

Years from the first lung metastasis to death

Su

rviv

al s

ince

the

firs

t lu

ng

me

tast

asi

s

Unilateral , n = 12Bilateral , n = 32

Logrank p-value = 0.091

3 year PLMS: ≤ 1 cm: 67 % > 1 cm: 34 %

0 5 10 15

0.0

0.2

0.4

0.6

0.8

1.0

Years from the first lung metastasis to death

Su

rviv

al s

ince

the

firs

t lu

ng

me

tast

asi

s

Size of the largest nodule <=1 cm , n = 13Size of the largest nodule >1 cm , n = 20

Logrank p-value = 0.072

3 year PLMS: No chemo: 39 % Chemo: 33 %

0 5 10 15

0.0

0.2

0.4

0.6

0.8

1.0

For the operated patientsYears from the first lung metastasis to death

Su

rviv

al s

ince

the

firs

t lu

ng

me

tast

asi

s

No peri-operative chemo , n = 25Peri-operative chemo , n = 21

Logrank p-value = 0.63

DISCUSSIONLATEST LARGE SERIES

Study No. of patients

Conclusions/Prognostic factors

COSS Group;JCO, Jan 2005

436257: >18y422 operated

Median FU is 1.2 year. 3 year PRS is 29 %.Long time to relapse, unilaterality and no pleural involvement are important prognostic factors.

Ferrari et al;JCO, Feb 2003

136Age®: 5-47y114 operated

3 year PRS is 33 %.RFI, size and number of lesions.No support for adjuvant chemo after complete metastectomy.

Meyer et al; Cancer, Jan 1987

5939 operated

Sex and number of nodules have impact on survival.

Belli et al;Cancer, Jun 1989

4420 operated

5 year OS is 37%.Post metastectomy chemotherapy probably prevent new lung lesion.

Carter et al;Thorax, Oct 1991

4325 operated

5 year PRS is 20%.Location of lesions ( one lobe or different lobes).DFI, No. and laterality of lesions not important.

CONCLUSION

This is a large series from single center that primarily includes adult patients with median follow up of 2.7 years.

The 3 year PLMS is 30% which is comparable to previous large studies.

Surgical resection doubled the survival at 3 years. Both Synchronous and Metachronous lung metastasis have

similar survival. Lung nodules of <4, size ≤ 1cm and unilaterality are

favorable prognostic factors. The use of chemotherapy with the resection did not appear

to affect the survival.

ACKNOWLEDGMENT

Anthony GriffinMelania Pintilie

THANK YOU