0910 - 925_DeBaere

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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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posted:7/19/2011
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