Download - Partial Breast Irradiation PBI
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“Partial Breast Irradiation” PBI
Dr Vincent RemouchampsService de Radiothérapie Oncologique
Clinique Ste Elisabeth Namur
Belgian Breast Meeting 2010Brussels
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Plan: Partial Breast Irradiation From “maximum tolerable” to “minimum efficient”• Principles et Objectives (theory)• Methods• Carefulness et Inconvenients• Studies• Conclusions:
– Consensus USA / Europ, other experts opinions• Disgression:interest for boost (+ WBRT)
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Principle: accelerated RT on a smaller volume (tumor bed,...)
• Limited volume• Protection of healthy tissues• Larger doses• Reduction radiation time
– classical: 6.5 weeks (ou 3 weeks)– turns to 1 week or even 3 min …!– Enough to make the cover of “Le Soir” this
spring ...
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Objectives• USA, Italy: Diminish the under-use of breast
conserving surgery or of the post op radiation (in Italy, 20-50% skip RT depending on distance…)
• Reduce the duration, the cost, the side effects and discomfort of post op radiation therapy
• Improve Quality Of Life• Suppress sequencing issues with chemotherapy• Potentially improve prognosis by reducing overall
treatment duration?
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FA Vicini. J Clin Oncol 19:1993-2001, 2001. and KB Baglan. IJROBP
2001
Methods (1): Brachytherapy
• The longer follow up• 2 fractions per day, 5 days.
(10x 3.4 Gy)
• Current practice for boost• Consensus ESTRO 2010:
may be the only technique valid for recommandations
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Methods (2): IOERT Intra Operative Electrons Radio Th
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Methods (2): IOERT (electrons)• For exemple “Mobetron”
(Dutoit)• Adaptable depth• 21 Gy in 3 minutes• Lung protection• More dissection• ELIOT study in Milan
(ELectron IntraOp Ther.)• expensive: 2 second hand
machines in Belgium, 1 in UZA for boost only (validated)
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Methods (3):Low energy X Rays (50 Kv)
• “Intrabeam” (Zeiss)• “TARGIT” A and B studies• More superficial: treat 7-10
mm, 20 Gy in +- 20 min• more “Round”
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Methods (3): Low energy X Rays (50 Kv)
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Methods (4): External Beam conformal Radiation Therapy
(EBRT)
38 Gy in 10 fractions of 3.8 Gy, 2 fractions /day (1 week)
With existing machines!
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Methods (4): EBRTDose distribution
Transverse Sagittal Coronal
Biopsy Cavity
CTVPTV 100%
IDL
105% IDL
50% IDL
important volume : reported toxicities; new study in Holland
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Methods (5): Balloon Catheter‘MammoSite’
• MammoSite device (Proxima Therapeutics)
• Inflatable Balloon Placed In Lumpectomy Cavity At Surgery
• Remote Afterloading• 34 Gy (3.4 Gy X 10) en 5
jours• Toxicity if close to skin• Conflicts of interest (not
me)
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Arguments against Partial Breast Irradiation
…than (currently) supporting the classical whole breast irradiation after
breast conserving surgery
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1) STANDARD = partial surgery followed by whole breast
Radiation Therapy• 2500 patients 20 years follow up, randomised
phase 3 studies
• Evidence Based MedecineLevel I
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2) Veronesi et al, Ann Oncol. 2001;12(7):997-1003
RandomisedPatients
10 yearsIpsilateralrelapses
Quadrantectomy 299 23.5%
Quadrantectomy+ whole breastRadiotherapy
280 5.8%
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2) Veronesi et al, Ann Oncol. 2001;12(7):997-1003
• Quadrantectomies by Véronesi were large.• Correspond to tumorectomy + quadrant
irradiation• We can anticipate that post op irradiation of
quadrant only will be insuffisant
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3) What is the target volume?
• 85% of relapses in index quadrant. 15%??• Multifocality / Multicentricity exists (MRI
and pathology studies)• Published extensive clinical experience has
prouved most of these foci are controled by whole breast radiotherapy
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Schmitz AC, van den Bosch MA, Loo CE, et al Radiother. Oncol. 2010 [Epub ahead of print]
Precise correlation between MRI and histopathology - Exploring treatment margins for
MRI-guided localized breast cancer therapy.
• 64 wide local excision specimens were subjected to detailed microscopic examination. The size of the invasive (index) tumor was compared with the MRI-GTV. Subclinical tumor foci were reconstructed at various distances to the MRI-GTV.
• Subclinical disease occurred in 52% and 25% of the specimens at distances of 10mm and of 20mm, respectively, from the MRI-GTV
• A 1 cm margin undertreats up to 52 %, a 2 cm margin undertreats 25%, depending on the surgical margin… (studies: 1-2 cm, RTOG 1.5 cm)
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3) What is the target volume?
• ...• No correlation between tumor size cavity size...• 90-95% of tumors located at the edge of specimen (Stroom
IJROBP 2009)
• Van Mourik 2010: Large interobserver variability for target definition if no seroma ...
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4) About cosmesis?(External beam APBI)
• Hepsel et al, IJROBP 2009: « remarkably high moderate to severe late normal tissue effect » – 25% moderate to severe fibrosis (8% grade 3)– 18% unsatisfactory cosmetic results
• Jagsi et al, IJROBP 2009:– 21% unsatisfactory cosmetic results
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4) About cosmesis? (2)
• Skin sequelae after mamosite, intra-op, (seroma and ponctions more frequent, …)
• Brachytherapy: Poti IJROBP 2004:– > 59% grade III toxicity
(fibrosis, telangectasia, necrosis, …): pictures
– 50 % unsatisfactory cosmetic results
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5) Median follow up too short!• 2/3 of relapses after
conserving surgery are late
• The 2 randomised studies have 2 and 6.8 years median follow up (too short!).
Veronesi, Nejm 2002
Exemple:
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Different slopes: RT is preventing late relapses!!
META-ANALYSE: EBCTCG Lancet 2005; 366: 2087-2106
Long follow up is essential for adjuvant breast treatment...
BCS
BCS + RT
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6) Final histology after RT …!
• If Intra-operative– electrons– X rays– brachy perop
• If + margins or discovery of multifocality:? Re-excision? Mastectomy conversion?
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Context:• Tremendous pressure
– from patients (comfort)– from industry (sales)– from hospitals, surgeons (concurrency)
• 645 research articles, 4 published randomised studies, (+1 négative metanalysis), 38 single arm prospective studies
• 2009-2010 publication of recommendations
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Single arm studies with suboptimal selection criteria and > 4 years f- up from Polgar et al, Rad Oncol 94(3) 264, 2010
Institution Technique MedianFup
Local Recur. %(n)
Annual LR(%)
Comments
Uzsoki Brachy 12 24 (17 of 70) 2 5 cm, unk MgChristie Electrons 8 20 (69 of 353) 2.5 4 cm, unk MgCookridge Electrons 8 12 (10 of 84) 1.5 4.5 cm, N+London Brachy 7.6 15 (6 of 39) 2 4.5 cm, ILCTufts Brachy 7 9 (3 of 33) 1.3 Close M, EICGuys I Brachy 6 37 (10 of 27) 6.2 4 cm, N+Guys II Brachy 6.3 18 (9 of 49) 2.9 4 cm, N+, +MgOsaka Brachy 4.3 5 (1 of 20) 1.2 15% +Mg, EICFlorence Brachy 4.2 6 (7 of 115) 1.4 5 cm, N+, ILC
ALL 4.2-12 17 (132 of 790) 1.2-6.2
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Single arm studies with stringent selection criteria and > 4 years f- up from Polgar et al, Rad Oncol 94(3) 264, 2010
Institution Technique Median Fup Local Recur. %(n)
AnnualLR (%)
Budapest I Brachy 11.1 9 (4 of 45) 0.8WBH Brachy 9.7 5 (10 of 199) 0.52Orebro Brachy 7.2 6 (3 of 51) 0.83RTOG 9517 Brachy 7 6 (6 of99) 0.91Budapest II Brachy 6.8 4.7 (6 of 128) 0.69Oschner Brachy 6.3 2 (1 of 51) 0.32Ninewells Brachy 5.6 0 (0 of 11) 0German Brachy 5.3 3 (8 of 274) 0.55FDA Mammos. 5.2 0 (0 of 43) 0Kiel HNIO Mammos. 5 0 (0 of 11) 0Navarra Brachy 4.4 4 (1 of 26) 0.86Wisconsin Brachy/M. 4 3 (8 of 273) 0.72Kansas Brachy 4 0 (0 of 25) 0
ALL 4 – 11 years 3.8 (47 of 1236) 0-0.91
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7 Main Randomised Phase III trials:PBI versus whole breast RT
Study Technique Accrual Remarks
Targit X raysPerop
2232 Lancet 2010 ; only 20 % ofpatients followed > 4 years,1.2 % and 0.95 % relapse,median FU short (2 years)
Eliot ElectronsPerop
1822 Announced SABCS 2010
HungarianPolgar6.8 y medianFollow up
Brachy (88)/electrons in25 fractions(40)
258 Int JCO 2009 ; Local relapseWBRT 3.3%, BT 5.1%, CI0.6-2.3 % ! ! ! , methodsdiscussed
RTOGNSABP
Brachy +others
Target9000 ?
5 year results in 5-10 years !
GEC ESTRO Brachy Target1100
Awaited
IMPORT,IRMA, …
Awaited
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Local recurrence as a function of age in prospective APBI studies
AGE All studies Crude LR % (n)< 40 10.5 % (2 of 19)> 40 – 50 7.6 % (16 of 211)> 50 - 60 3.7 % (12 of 322)> 60 3.4 % (18 of 531)All age 4.4 % (48 of 1083)Follow up 5-9.7 years
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Level 4 evidence (weak): expert recommandations for “suitable”
ASTRO 2009 (USA)• > 60 y.o., no BRCA• T < 2cm, unicentric,
unifocal, inf. ductal, no ILC, no pure DCIS
• Margins >2 mm• pN0, no LVI, no EIC• no neo-adj chemo/ht
ESTRO 2010 (Europ)• > 50 y.o.• T < 3cm
• same for the rest
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Radioth Oncol, march 2010 Recommendations GEC-ESTRO
• Acceptable outside studies for very selected patients but ...
• “Gec Estro Accept no liability for …” !!!• “The validity of the statement may be limited to
multicatheter technique.”• “The 5 year results of the randomised trials …
will be available only in the next 5 to 10 years …”
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Editorial with the American recommendations
• 5 years results of random studies available in 10 years (5 years = short for adjuvant breast!)
• “Suitable” are generally older, with less aggressive tumors
• “Whole breast RT remains the gold standard… longer track of records about efficacy and safety”
• Alternative fractionation (15-16 x) or even lumpectomy alone … better supported by data”
…and the most cost effective (Suh IJROBP 2009)
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Even Orecchia admits, at the PRO-CONTRA session at Estro 2010
• 80-85 % not suitable for PBI• PBI is not standard• PBI is experimental• Late complications occurs (necrosis at
follow up mammograms)
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Conclusion:Partial Breast Irradiation?
Modify the principles of breast conserving treatment?
• Better than nothing? Not in Belgium…!• ETHICS: security ??, efficacy ??, … than:• Wait for a sufficient follow up of phase III studies• Opinion of NHS: it is experimental• St Gallen: Is it still experimental ?
Panel vote (86 % yes; 14% no)
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… and for the Boost?• Very attractive techniques
– Used for many years with brachy-therapy, if indicated (margins, treatment depth, …)
– Attracting developments in intra-op• SABCS 2009: Targit Boost n=300• 1.73% local recurrence at 5 years… (? Due to
improved targeting!?)
– But Expensive … • +- 1500 euro /patient (to compare to drugs …)• Thinking group ongoing at INAMI / RIZIV …
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Thank you for your attention!