RADIOTERAPIA

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RADIOTERAPIA DEI SARCOMI DELLUTERO
Alessandro COLOMBO SC Radioterapia AO Ospedale
di Lecco
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uterine sarcoma treatment

• extrafascial abdominal hysterectomy with
  bilateral salpingo - oophorectomy is the primary
  treatment for uterine sarcomas
• surgical staging is generally recommended
• no additional benefits from preoperative RT or
  more radical surgery
• the role of adiuvant treatment is uncertain

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uterine sarcoma histology

• CS carcinosarcoma (malignant mixed mesodermal or
  mixed mullerian tumor)
• LMS leyomiosarcoma
• ESS endometrial stromal sarcoma
• low grade
• high grade

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uterine sarcoma pattern of recurrence
Major FJ et al, Cancer 711702, 1993 Leath III CA
et al, Gynecol Oncol, 105630, 2007
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(No Transcript)
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uterine sarcoma guidelines NCCN
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uterine sarcoma guidelines NCCN
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uterine sarcoma guidelines NCCN
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uterine sarcoma guidelines NCCN
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uterine sarcoma guidelines NCCN
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uterine sarcoma vaginal BT
40
2 cm
100
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uterine sarcoma pelvis EBR
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uterine sarcoma pelvic EBR - IMRT
P. Georg et al. R O 8019, 2006
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uterine sarcoma whole abdominal RT

• problems
• wide volume irradiated
• organs at risk (kidney, liver, small bowel)
  
• high rates of toxicity
• limited total dose

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uterine sarcoma ESS retrospective study

• LG HG
• n. 72 31
• recurrence rate 37 38
• isolated pelvis 40 58
• total pelvis 66 58
• total abdomen 37 25
• total distant 36 25

• the utility of adjuvant radiation therapy (22
  cases) is unclear

Leath CA, 3rd et al Gynecol Oncol, 105630, 2007
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uterine sarcoma LMS retrospective study

• 208 LMS pts treated at the Mayo Clinic
  (1976-1999)
• case control analysis on 62 pts receiving or not
  pelvic RT
• significant decrease in local recurrences in RT
  group
• no statistical difference in DSS or RFS
• multivariate analysis no improved survival for
  pelvic RT
• larger prospective randomized trials are needed

Giuntoli RL et al Gynecol Oncol, 89460, 2003
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uterine sarcoma CS retrospective study

• 300 CS pts treated at MDACC (1954-1998)
• surgery alone 113
• surgery RT 160
• RT alone 27
• pelvic recurrence (5 y) 38
• distant recurrence (5 y) 54 (abdomen 55)
• lower rate of local recurrence in RT group (28
  vs 48, p 0.0002)
• no difference in OS

Callister M et al. IJROBP, 58786796, 2004
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uterine sarcoma CS retrospective study

• adjuvant pelvic RT decreased the risk of pelvic
  recurrence... however the survival rates remain
  poor because of a high rate of distant
  metastases.
• as more effective CHT is developed to control
  distant disease, the role of RT in local control
  in the pelvis may increase.
• future research should consider programs that
  integrate surgery, RT, and chemotherapy to
  maximize the probability of cure.

Callister M et al. IJROBP, 58786796, 2004
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uterine sarcoma randomized trials GOG 150
pts eligible (12/1993 3/2005) 206 CS stage I
IV Whole Abdominal Irradiation (WAI) 105 CDDP
IFX Mesna (CIM) 101
Wolfson AH et al Gynecol Oncol 107177, 2007
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uterine sarcoma randomized trials GOG 150
chronic adverse events G2 G3 G4 WAI
17 14 2 CIM 6 4
0
Wolfson AH et al Gynecol Oncol 107177, 2007
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uterine sarcoma randomized trials GOG 150

• WAI I phase (12/1993 7/1996)
• abdomen 30 Gy _at_ 1 Gy BID
• pelvis 20 Gy _at_ 1 Gy BID
• BED 44.4 Gy10
• WAI II phase (8/1996 3/2005)
• abdomen 30 Gy _at_ 1.5 Gy / d
• pelvis 19.8 Gy _at_ 1.8 Gy / d
• BED 36.3 Gy10

Wolfson AH et al Gynecol Oncol 107177, 2007
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uterine sarcoma randomized trials GOG 150

• conclusions
• no significant difference in recurrence rate or
  survival
• chronic adverse events were higher in WAI regimen
• the observed difference favor the use of
  chemotherapy in future trials

Wolfson AH et al Gynecol Oncol 107177, 2007
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uterine sarcoma randomized trials EORTC 55874
pts eligible (7/1988 7/2001) 224 LMS
99 CS 92 ESS
15 Pelvic
RT 112 observation 112
Reed N et al EJC 44808, 2008
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uterine sarcoma randomized trials EORTC 55874
chronic adverse events RT n.3 G3
Reed N et al EJC 44808, 2008
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uterine sarcoma randomized trials EORTC 55874

• no difference in OS or DFS
• increased LC for CS patients receiving RT, no
  benefit for LMS
• no indication on adjuvant RT for LMS.
• CS ? aggressive variants of endometrial
  epithelial tumours and management reflects the
  treatment of endometrial carcinomas.
• these results will help to shape future
  management and clinical trials in uterine
  sarcomas, distinguishing between LMS and CS.

Reed N et al EJC 44808, 2008
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uterine sarcoma chemoradiation

• n 5 y surv
• Total 41 49.6
• adjuvant treatment
• CHT 10 22.2
• RT 21 50.5
• sCRT 10 75.0

• 41 CS patients
• CHTIFX mesna CDDP q 21 d x 6 cycles.
• RT WPI 45-50 Gy /- BT
• sCRT IFX mesna CDDP q 21 d x 3 cycles
  followed by WPI.

Menczer J et al Gynecol Oncol 97166, 2005
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uterine sarcoma chemoradiation

• sCRT RT
• pts 18 18
• LMS 13 13
• CS, ESS 5 5
• median FU 43 87

• RT WPI 45 Gy/25 f
• sCRT ADM CDDP IFX RT

a multicentric phase III study is active in
France
Pautier, P et al, Int J Gynecol Cancer, 141112
2004
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uterine sarcoma salvage chemoradiation

• 7 pts with vaginal recurrences resected (4 ESS, 2
  CS, 1 LMS)
• RT concurrent to IFX ADM
• hemotoxicity G3 3/7 G4 4/7
• diarrhea G3 5/7
• median FU 35 m
• local control 80 at 3 y
• DFS (KM) 57 at 3 y
• survival rate 83 at 3 y

Kortmann B et al Strahlenther Onkol18231824,200
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uterine sarcoma active clinical trials

• SARC-GYN1 (Institut Gustave Roussy - Villejuif)
  IFX-ADM-CDDP concurrent to RT (phase III)
• MMC-03-02-040 (Albert Einstein Cancer Center -
  NY) sandwich IFX CDDP ?RT ? IFX CDDP (phase
  II)
• 06-063 (Dana-Farber/Brigham and Women's Cancer
  Center - Boston) oxaliplatin GEM x 3 ?RT
  (phase II)

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uterine sarcoma conclusions

• the global prognosis remains poor
• adjuvant pelvic RT increases the local control in
  CS as in endometrioid high grade carcinoma
• WAI should be abandoned
• in LMS and ESS the results are controversial
• chemotherapy and radiation may cooperate in
  increasing local control and reducing distant
  metastases
• large prospective randomized trials are needed

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uterine sarcoma palliative RT

• symptomatic recurrences
• bone or CNS metastases
• 8-30 Gy in 1-10 fractions (PS, site, volume)
• significant symptoms reduction in 70 of cases
• consider RTS

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A.O. OSPEDALE DI LECCO OSPEDALE ALESSANDRO
MANZONI
Thank you for your attention