HISTORY OF IORT

1
Milan-Eliot randomized trial results first
analysis
Roberto Orecchia, MD Madrid 11 June 2008
2
The first trial of X-ray therapy for cancer of
the breast (painting by George Chicotot, 1908,
Musée de lAssistance Publique, Paris)
3

Mid 1990s Dedicated Linacs
IOERT
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EIO Milan / ELIOT experience

• Dose-escalation study (7/1999-4/2000)
• Phase-II study at 21 Gy (5-11/2000)
• Randomized study ELIOT vs WBI (11/2000 and now
  closed)
• Nipple-sparing mastectomy (3/2002 and
  currently ongoing)
• ELIOT boost plus AWBI for under 48
• 
  
  (6/2004 and currently ongoing)
• . Out
  Trials patients

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First unfavourable event
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ELIOT side effects
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ELIOT doseDave - Dmin - Dmax (21 Gy - 90
isodose)

• Dave at surface 19,87 Gy
  (SD ? 0,51)
• Dmin / Dmax at surface 18,66 / 20, 53
  Gy
• Dave at tumor 22,53 Gy (SD ? 2,26)
• Dmin / Dmax at tumor 7,84 / 23,33 Gy
• 85 - 94 coverage

8
Model used to predict radiation effects

• D (1/2 ) ?(?/?)2 4D2 Gy (?/? 2)0.5 - ?/??
• D22.5 Gy (?/? 10 Gy) EBRT (D2 Gy 60)

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EBRT/BRT/IORT BED values
BED nd 1 d/(?/?) ?/? 10 for
early-responding tissue ?/? 4 for tumor
control/telangectasia ?/? 2 for
late-responding tissue
10
Dose Response relationship

• For 50 Gy more than 80 of patients have
  excellent result, the probability decrease to 70
  for 60 Gy, 45 for 70 Gy, and less than 20 for
  80 Gy
• Above 50 Gy an increase in upward nipple
  retraction of about 1 mm and of 0.5 mm in medial
  retraction are noted per additional 1 Gy dose
• For 50 Gy no patients had more than 4 cm nipple
  retraction, the incidence becomes 3 for 60 Gy,
  8 for 70 Gy, and 20 for 80 Gy

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Irradiated Volume

• 2 fold boost volume increase results in an 11
  reduction of the tolerance dose for fibrosis

12
ELIOT randomized trial
ACUTE and LATE TOXICITY

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Acute Subjective Toxicity Distribution of
patients symptoms according to Numeric Rating
Scale Symptom Scores () ITCHING
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Acute Subjective Toxicity Distribution of
patients symptoms according to Numeric Rating
Scale Symptom Scores () BURNING
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Acute Subjective Toxicity Distribution of
patients symptoms according to Numeric Rating
Scale Symptom Scores () PAIN
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ERT Late Toxicity () (CTCAE - v3.0)
G0
G1
G2
G3
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ELIOT Late Toxicity () (CTCAE - v3.0)
G0
G1
G2
G3
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Late Toxicity Common Terminology Criteria for
Adverse Events v3.0 (CTCAE)
BREAST
ERT ELIOT
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Late Toxicity Common Terminology Criteria for
Adverse Events v3.0 (CTCAE)
TUMOR BED
ERT ELIOT
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Late Toxicity (Lyponecrosis) (CTCAE - v3.0)
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LYPONECROSIS
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ELIOT randomized trial
QUALITY CONTROL ASSURANCE

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Main references

• Rapporti ISTISAN 03/1, www.iss.it
• AAPM TG 48, IJROBP 33, 1995
• AAPM TG 72, Med Phys 33, 2006
• citations

IORT
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2-D dose distribution

• radiochromic films
• silicon detectors

IORT
25
In vivo dosimetry

• entrance dose (dmax) derived by surface
  measurements
• 2 radiochromic films in a sterile thin envelope
• negligible field perturbation
• 24-72 hrs (48 hrs pref.) post-irradiation time
• temperature dependence 5
• estimated overall uncertainty (1 SD) 4

IORT
26
Measured vs expected dose (based on isodose chart
and gland thickness measured by surgeon using a
needle and ruler)
SPATIAL INFORMATION also evaluation of disc
alignment score 1 (bad) to 4 (excellent)
IORT
27
Stray radiation produced by patients tissues
varies, according to the angle from the axis, in
intensity and energy its intensity is strongly
reduced to safe values by a lead shield in the
direction of the beam and by 3 mobile barriers
around the operating table Angolo di diffusione
microSv/100impulsi radiazione diffusa

0
156.5
100
30
22.6
14
45
12.4
8
60
5.1
3
90
2.0
1.3
135
0.3
0.2
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15
35
50
restricted areas during irradiation
OR
50
Adjacent OR
Beam stopper
25
10
50
Area 1 floor below OR 20
Mobile Linac
30
80
35
10
25
50
Control panel
50
5
10
25
Stray radiation outside the operating room
(OR)(exposure rates expressed in microSv/hour)
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ELIOT. Breast CTV
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Electrons Energies

• 4 MeV 2.8
• 5 MeV 8.7
• 6 MeV 9.7
• 7 MeV 27
• 8 MeV 12.4
• 9 MeV 33.4
• 10 MeV 6.1

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Applicators
0.3 51.5 37.4 10
0.2 0.2
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Angles Applicators
63.9 23.2 12.9
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ELIOT randomized trial
COSMETIC OUTCOME EVALUATION

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ELIOT randomized trial
EFFECTIVENESS OTHER RELATED ISSUES

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NIO, Budapest Phase study (1998-2004)

• Tumor bed alone (HDR 5.2 Gy x 7 fx/4 days or
  50 Gy e-)
• vs conventional WBRT (50 Gy/25 fx)
• age 40 years or more (since 2001)
• unifocal disease
• size lt 2 cm
• clear margins
• N0 or pN0 (micromts lt2mm)
• histological grade lt 3
• technically suitable for implant (2-3 plane
  implants in 98)

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NIO, Budapest Phase study (1998-2004)

• Tumor bed alone vs WBRT
• LR 5.5 (6/127) 4.4
  (4/128) p0.65
• CSS 98.2
  96.9 p0.66
• DFS 85.9
  90.7 p0.21
• OS 97.0
  96.0 p0.68
• Ex/Good 79.2
  59.2 p0.001
• G2-3 late effects 25.0
  23.1 p0.43
• 
  
• 5-y Actuarial Results

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Partial Breast Irradiation (PBI) Ongoing
Randomized Trials

• NSABP B-39/RTOG 0413 study3D-CRT (10 fr/4
  Gy/10 days or 3.4 Gy BID) - Mammosite (10 fr/3.4
  Gy/5 days) - Multicatheter interstitial BRT
  (LDR/HDR)

• GEC/ESTRO Breast Working Group Study Tumor bed
  alone (HDR 30.3-32 Gy x 7-8 fx/4 days or PDR
  50/0.6 Gy) vs WBRT (50-50.4 Gy 10 Gy e-)

• TARGIT Tumor bed alone (X-ray 20 Gy x 1) vs WBRT
  (conventional RT)

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Thank you!