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MANAGEMENT OF ADULTS WITH WILMS TUMOR

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MANAGEMENT OF ADULTS WITH WILMS TUMOR Powered By Docstoc
					    MANAGEMENT OF ADULTS
      WITH WILMS TUMOR

                 Max J Coppes, MD, PhD, MBA

                    •Senior Vice President &
          Chair, Center for Cancer and Blood Disorders
       Children’s National Medical Center, Washington, DC

        •Professor of Oncology, Medicine and Pediatrics
            Georgetown University, Washington DC


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             WILMS TUMOR IN ADULTS

    • >19 years of age
    • <1% of renal tumors
    • Unexpected diagnosis after nephrectomy for
      presumed RCC
    • No standard therapy
    • Literature suggest outcome inferior to Wilms tumor
      in children
    • Recent literature suggest outcome much better if
      treated according to SIOP or NWTSG protocols

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                WILMS TUMOR IN ADULTS


    • Primarily seen by urologists
    • Referred to oncologists
    • Consultation pediatric oncologist
      –   NWTSG (now RT of COG)
      –   SIOP
      –   GOPGH
      –   UKCCSG
      –   AIEOP
      –   Brazilian POG


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                          Position paper by the Nephroblastoma Committee of the International
                              Society of Paediatric Oncology (SIOP) and the Renal Tumors
                                Committee (RTC) of the Children’s Oncology Group (COG)


    • Heidi Segers & Marry M. van den Heuvel-Eibrink, Department of Pediatric Oncology/Hematology, Sophia Children’s
      Hospital, Rotterdam, The Netherlands
    • Max J Coppes & Jeff Dome, Center for Cancer and Blood Disorders, Children’s National Medical Center, Washington,
      DC, USA
    • Christophe Bergeron, Centre Léon Bérard / Institut d’hémato-oncologie Pédiatrique, Lyon, France
    • Beatriz de Camargo, Pediatric Hematology Oncology Program, Rio de Janeiro, Brazil
    • Gemma Gatta, Evaluative Epidemiolgy Unit, Istituto Nazionale dei Tumori, Milano, Italy
    • Norbert Graf, Department of Pediatric Hematology and Oncology, University Hospital for children, Homburg, Germany
    • Paul Grundy, Departments of Pediatrics and Oncology, Edmonton, Alberta, Canada
    • John A. Kalapurakal, Department of Radiation Oncology, Northwestern University, Chicago, USA
    • Jan de Kraker, Department of Pediatric Oncology, AMC, Amsterdam, The Netherlands
    • Elizabeth J. Perlman, Department of Pathology and Laboratory Medicine, Children's Memorial Medical Center, Chicago,
      USA
    • Harald Reinhard, Asklepios Hospital, Pediatric Haematology and Oncology, Sankt Augustin, Germany
    • Filippo Spreafico, Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
    • Gordan Vujanic, Department of Histopathology, School of Medicine Cardiff University, HeathPark, Cardiff, U.K
    • Anne B. Warwick, Division of Pediatric Hematology/Oncology, Medical College of Wisconsin, Milwaukee, USA
    • Kathy Pritchard-Jones, UCL Institute of Child Health & Great Ormond Street Hospital, London, U.K




4
    Review available data




5
                              Age and Gender

                                                Median age
                        N          F/M
                                                 (range)

        Arrigo , 1990   27           -        24 yrs (16-74)

        Kattan , 1994   22         14/8       24 yrs (16-40)

         Mitry , 2004   133        69/64      34 yrs (15->60)

    Terenziani , 2004   17         11/6      17 ½ yrs (16-29)

     Reinhard , 2004    27         12/15     25.4 yrs (15-62)

    Kalapurakal, 2004   23         13/10    21.9 yrs (16.3-51.3)

         Izawa , 2008   128          -        26 yrs (15-73)

              TOTAL     377       119/103      Range:15-73



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                                                Stage

                         I       II       III    IV     V         Unknown

    Arrigo , 1990       6        5        4      11     155%
                                                                            43%-70%
    Kattan , 1994       4        8        3      7          45%

                             15 localized
    Mitry , 2004                                 14     -           89
                        15 regional extension

    Terenziani , 2004            8        4      5      53%

    Reinhard , 2004     6        2        9      10     70%

                                                        43%
    Kalapurakal, 2004   5        8        6      4




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                                  Histology

                             Favorable           Unfavorable

        Arrigo , 1990            23             4 (all stage IV)
                        No difference between
        Kattan , 1994         21               1
                        children and adults but
         Mitry , 2004   diagnosis in adults often
                              NA              NA
                        missed (15-20% misclassified)
    Terenziani , 2004            16                    1

     Reinhard , 2004    Intermediate risk: 25    High risk: 2

    Kalapurakal, 2004            23




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               Presentation adult Wilms tumor



    •   Abdominal or flank pain
    •   Malaise, weight loss
    •   Hematuria
    •   Hyperstension




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                    Period     EFS     OS (5 y) Mean follow-up
       Arrigo
     1979-1987     1979-1987    NA       67%        2 years

       Kattan
     1973-1992     1973-1992   41%       55%       8 ½ years

       Mitry
     1983-1994     1983-1994    NA      47.3%       5 years

     Terenziani
     1983-2001     1983-2001   45%      62.4%       11 years

      Reinhard
     1994-2001     1994-2001   57%       83%        4 years

     Kalapurakal
     1988-2001     1988-2001   77.3%    82.6%       5 years
       Izawa
     1973-2006     1973-2006    NA       68%       4 ½ years

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                          Treatment
     • Varied, but usually conform pediatric therapies,
       i.e.
        – AMD/VCR for stage I and II disease
        – AMD/VCR/DOX/XRT for stage III and IV
          disease
     • Several patients probably under-staged (no
       lymph node biopsy) and therefore undertreated
     • Several delay in starting post-nephrectomy
       therapy


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              Effect of delayed postoperative therapy


     Number       Start    5-year EFS             5-year OS
               treatment



       10      < 30 days     60%                     80%
                            (+/- 15%)               (+/- 12%)

                            14.3%                   28.6%
       7
               > 30 days    (+/- 13%)               (+/- 17%)



                            p = 0.02               p = 0.05

                             Terenziani et al., Cancer 101:289-93, 2004


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     Outcome and Gender




                 Mitry et al: Eur J Cancer 42:2363-8, 2006


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                           Toxicity

 • Increased incidence of neurotoxicity
   secondary to VCR
     – Up to 48% of patients @ grade 3/4!
 • Incidence of hepatotoxicty (VOD) in adults
   unclear (3-13%)
     – Recommendation to watch for liver enzymes and
       thrombocytopenia.




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                                      Recommendations

 Pre treatment investigations

 •   History in combination with
      –   personal history of congenital abnormalities or syndrome
      –   family history of early onset cancer
 •   Clinical examination (in particular blood pressure and any asymmetries and/or genito-
     urinary malformations)
 •   Laboratory investigations
      –   full blood and coagulation studies (to exclude acquired von Willebrand disease)
      –   urea and creatinine, electrolytes (sodium, potassium, calcium, magnesium, bicarbonate, chloride
          and phosphate)
      –   liver functions tests
      –   Urine analysis: dip stick for protein
 •   Radiological investigations (staging)
      –   Chest X-ray
      –   Abdominal ultrasound to assess tumor extension, IVC extension and state of opposite kidney
      –   CT scan of chest, abdomen, pelvis (where possible and without introducing treatment delay)



15
                       Recommendations

 Surgery

 • At nephrectomy: adequate sampling of renal perihilar lymph
   nodes, even if these appear macroscopically normal.
   However, while suspicious lymph nodes should be excised
   regardless of location, no need for formal lymph node
   dissection
 • Delivery of the whole and fresh nephrectomy specimen to
   the pathologist for assessment of the integrity of the tumor
   capsule.



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                     Stage I favorable histology Wilms tumor
                         (after immediate nephrectomy)




     AMD
     VCR


     Week       1   2   3   4   5   6   7   8   9   10   11 12   13   14   15
                                                    16           19
                                                    22


      AMD = 1.5 mg/m2 iv bolus (max 2 mg)
      VCR = 1.5 mg/m2 iv bolus (max 2 mg)




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               Stage II/III and IV (complete response)FH Wilms tumor
                             (after immediate nephrectomy)




     AMD
     VCR
     DOX
      XRT              xxxxxxx
     Week         1    2   3     4   5    6   7    8    9    10   11 12   13   14   15
                                                             16           19
                                                             22           25

      AMD = 1.5 mg/m2 iv bolus (max 2 mg)
      VCR = 1.5 mg/m2 iv bolus (max 2 mg)
      DOX = 50 mg/m2 iv infusion (omit until 7 days after XRT)
      XRT = 15Gy in 10 fractions



18
               Stage IV FH (slow response) + any UH Wilms tumor
                         (after immediate nephrectomy)


     VP16
     CARBO
     CYCLO
     DOX
        XRT             xxxxxxx
     Week           1    2    3    4     5    6    7        8   9   10   11   12   13   14   15
                                   16              19               22             25
                                   28              31               34

      VP16 = 150 mg/m2 iv in 1 hour
      Carbo = 200 mg/m2 iv in 1 hour
      Cyclo = 450 mg/m2 iv in 1 hour
      DOX = 50 mg/m2 iv 4-6 hours, just after first Cyclo
      XRT = 15Gy in 10 fractions

19
                        Summary


 • Very rare
 • Need to get correct diagnosis + start therapy
   in time, i.e. within 30 days of surgery
 • Follow recommended protocol
 • Watch for neurotoxicity and hepatotoxicity




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