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Sate of the art :
ablation of lung metastases
T. de Baère , J Palussiére
Institut Gustave Roussy – Villejuif
Institut Bergonié - Bordeaux
Lung is RF friendly
Volume of ablation for a given quantity of RF energy
Lung (13 ± 3.5 mm)
Soft tissue (9.8 ± 1.0 mm)
Kidney (7.3 ± 0.6 mm)
(Ahmed M, Radiology 2004)
Lung tissue provides high degree of thermal and electric insulation
Lung is RF friendly
Lung tumor can be fully ablated with RFA thermal destruction
VX2 lung model
(Goldberg SN, Acad Radiol 1996)
HES MIB1 PCNA
Lung allows accurate targeting
Excellent contrast (lung/tumor/needle)
3D / Multiplanar
Assess correct position
Visulaization in any plane
Tolerance of ablation
Before RF 1 month after RF
FEV1 2.2 (0.62-3.75) 2.1 (0.72-3.61)
VC 2.77 (0.8-7.9) 2.6 (0.83-5.43)
(de Baere T, Radiology 2006)
No significant changes in FEV or FVC at baseline, 1, 3, 6 ans 12 months
(Lencionni R, Lancet Onco; 2008)
Chest tube = 10%
Complication < 5%
Median hospital stay < 2 days
Single lung :
15 patients (mean age 64 years)
21 tumors 4 to 37 mm (mean 15.5 mm)
All tumors treated in a single session
Tolerance
Pneumothorax (37%), Mild intrapulmonary bleeding (31%),
minor haemoptysis (12%),
Complications:
Pulmonary infection (6%)
No mortality
Median hospital stay = 3 days
No clinical worsening of pulmonary function
94% Complete tumor ablation (med follow-up = 17.6
months)
(Hess A, Radiology 2011)
Limitations of RFA
ASFC* are present in 51% of metastases
Dist tumor - ASFC : 0.5 - 11 mm (med : 2 (S Shiono, Ann Thorac Surg 2005)
mm)
GTV : Gross Tumor Volume
CTV : Clinical Target Volume
ASFC : Aerogenous spread with floating cancer cell
def : at least 0.5 mm from the tumor
Limitations of RFA
Ablation margins matters
4% incomplete ablation if ratio surface ablation / surface tumor ≥ 4
19% incomplete ablation if ratio surface ablation / surface tumor < 4 (p=0.02)
(de Baere T, Radiology 2006)
Ablation
Day 1
(Hiraki T, Cancer 2006) Nb of tumors Effectiveness
1 year 2 years
Ablation margins matters
Ground glass opacity margin width (p=0.005)
Receiver Operator Characterixtics suggest a cut off of 4.5 mm for 100%
specificity (no recurrence)
(Gillams A CVIR 2009)
Rate of incomplete ablation
3% to 38.1% (med = 11.2%) : review 24 publications, 1.7 cm med size
(Zhu JC, Annals surg oncol. 2008)
Rate of incomplete ablation
3% to 38.1% (med = 11.2%) : review 24 publications, 1.7 cm med size
Size <=3cm (n=840) Size >3cm (n=43)
P (Zhu JC, Annals surg oncol. 2008)
value
1 year 3.8% (0.7) 16.8% (6.4)
2 years 7.1% (1.1) 27.3% (8.9)
<0.000
3 years 8.4% (1.3) 27.3% (8.9)
1
(Simon CJ, Radiology 2007)
(Gillams A, Eur Radiol 2007)
Incomplete surgical resection
2-34% ?
positive margins (R1) or local recurrence
- 15% (33/255) (A van Geel, Cancer 1996)
surgical margins
- 8% (Landreneau, EJCTS 2000)
local recurrence
- 28% (17/96) (S Shiono Ann Thorac Surg 2005, 80 : 1040-1045)
local recurrence, 15/17 safe surgical margins
Rate of incomplete ablation
Local recurrence rate All tumors ≤3cm At least 1 tumor >3cm
/patient (n=463) (n=42)
1 year 9.4% (1.5) 17.1% (6.5)
2 years 15.0% (2.0) 34.4% (9.3)
3 years 17.3% (2.3) 41.7% (10.8) 0.0008
All tumors ≤2cm At least 1 tumor >2cm
(n=350) (n=155)
1 year 7.0% (1.5) 16.9% (3.3)
2 years 12.6% (2.1) 25.6% (4.2)
3 years 14.6% (2.5) 30.3% (5.1) 0.0002
(Personal unpublished data)
Microwave
82 tumors, 35±16mm mean diam, in 50 patients
Incomplete ablation : 16% per tumor, 26 % per patients @ 1 years
Size larger than 3 cm predictive of incomplete ablation (p=0,01)
(Wolf, F Radiolohy 2008)
Disease Free interval
Factors influencing incomplete ablation
Contact with a large vessel or bronchus
Nb of tumors Effectiveness
1 year 2 years
(Hiraki T, Cancer 2006)
(Gillams A, Eur Radio 2007 EPUB)
Factors influencing incomplete ablation
Before Day 1
Occlusion of large vessels ? Other energy ?
6 Months
(de Baere T, JVIR 2011) Day 7
Factors influencing incomplete ablation
Occlusion of large vessels ? Other energy ?
Microwaves and heat sink effect
Thrombosis of vessel ≤ 2 mm
MW>90% RF = 20%
Crocetti L et al, CVIR 2010
Lung RFA follow-up imaging
Local recurence at CT follow-up
CT is most commonly used
Difficult to evaluate contrast uptake
Only morphologic analysis remains
Incomplete ablation is discovered lately
Baseline Day 1 2 months 8 months 15 months
RF End of RF
Lung RFA follow-up imaging
Local recurence at CT follow-up
CT is most commonly used
Difficult to evaluate contrast uptake
Only morphologic analysis remains
Incomplete ablation is discovered lately
Slow decrease in size of ablated tissue
2 mths 4 mths 6 mths 8 mths
Lung RFA follow-up imaging
PET/CT can depict incomplete ablation early
28 patients with 52 metastases (18 mths follow-up : 43 complete ablations)
RFA
PET If PET +
Day -1 Day +1 Day +30 Day +90
(de Andreis D, Radiology 2011)
Lung RFA follow-up imaging
PET/CT can depict incomplete ablation early
28 patients with 52 metastases (18 mths follow-up : 43 complete ablations)
PET @ day1, 1 month, 3 months
• 38 Complete ablations at PET
• 3 Equivocals at day 1 or 1 month turn to be complete ablation at 3 mths
➤ 41 true negative, 0 false negative
• 11 Incomplete ablations at PET
• (2 @ day1, 3 @ M1, 6 @ M3)
➤ 9 true positive, 2 false positive
PET at 3 months : Sensitivity 100%, specificity 89%
(de Andreis D, Radiology 2011)
Lung RFA follow-up imaging
PET nicely solve most follow-up dilemmas
But pitfalls must be known
At 1 of the 3 post RF PET (1 day, 1 month, 3 months)
• 37% of inflammatory uptake in mediastinal lymphnode
• 34% of inflammatory uptake at the site of needle path
(de Andreis D, Radiology 2011)
Lung RFA follow-up imaging
PET : Additional benefit to follow-up
No Pet uptake before treatment : 2 patients (6%)
Pas de suivi FDG/PET CT
Unexpected uptake : 9 patients (32%)
Modifcation of therapeutic
mediastinal lymph nodes 3,
RFA canceled : 4
adrenal metastasis 1,
liver metastases 4, Additional RFA : 4
abdominal lymph nodes 1, RFA & surgery : 1
thyroid metastasis 1,
lung metastases 5
(de Andreis D, Radiology 2011)
Survival metastases
55 CRC mets patients
85%@1year,
64%@2 years,
46% @ 3 years
84 to 93 % @ 1 years
62 to 80% @ 2 years (Yan TD, Ann Surg Oncol 2007)
71 CRC mets patients 18 CRC mets patients
84%@1year, 87%@1year,
62%@2 years, 78%@2 years
46% @ 3 years
(Simon CJ, Radiology 2007)
(Yamakado K, JVIR 2007)
Survival metastases
Survival metastases (Inoue M, Ann Thorac Surg 2004)
Surgery
RFA
(S Shiono Ann Thorac Surg 2005, 80 : 1040-1045)
Surgery
Indications for RFA
2-3 cm 4 cm
Small and pauci nodular tumors that fulfill criteria for lung
metastasectomy but cannot tolerate surgery
Complete ablation possible
Control of the primary tumor obtained or obtainable
No Extra Pulmonary Disease (imaging work-up)
New mets in a previously operated lung
Local recurrence at the site of surgery
Surgical candidates with small tumor(s) requiring large resection
ex :3 small mets in three different lobes
Biological unfavorable situation (short Disease Free Interval)
Metastases larger than 4 cm
Metastases close to the hilum large vessels
www.nice.org.uk :
• Role relative to other treatment not clear (multi-disciplinary meeting, research)
• RFA may be used when surgery is not appropriate for patients
with a small number of lung metastases
Conclusion
• RF is safe and well tolerated in the treatment of small lung metastases
• Safety margins are key to obtain complete tumor destruction
• RF provide 70% survival at 3 years in best series
• RF provide survival close to historical surgical series
Comparative studies are needed
• New ablation technologies might improve local efficacy for larger tumors
or tumors close to the hilum
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