POTENTIAL INDICATIONS OF POTENTIAL INDICATIONS OF HADRONTHERAPY IN THE SARCOMAS HADRONTHERAPY IN THE SARCOMAS ANALYSIS OF THE LITERATURE ANALYSIS OF THE LITERATURE Dr Marie Pierre SUNYACH Dr Marie Pierre SUNYACH Dr Pascal POMMIER Dr Pascal POMMIER Centre Léon Bérard Centre Léon Bérard Dr Emmanuel AMSELLEM Dr Emmanuel AMSELLEM Faculté Laënnec Faculté Laënnec Lyon, France Lyon, France
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POTENTIAL INDICATIONS OF HADRONTHERAPY IN THE SARCOMAS ANALYSIS OF THE LITERATURE
POTENTIAL INDICATIONS OF HADRONTHERAPY IN THE SARCOMAS ANALYSIS OF THE LITERATURE. Dr Marie Pierre SUNYACH Dr Pascal POMMIER Centre Léon Bérard Dr Emmanuel AMSELLEM Faculté Laënnec Lyon, France. Carbon Ions - Perspective. Rationnal Balistic Bragg peak Biological - PowerPoint PPT Presentation
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POTENTIAL INDICATIONS OF POTENTIAL INDICATIONS OF HADRONTHERAPY IN THE SARCOMAS HADRONTHERAPY IN THE SARCOMAS
ANALYSIS OF THE LITERATUREANALYSIS OF THE LITERATURE
Existing CentersExisting Centers 1994: National Institute for Radiological Science (Japan)1994: National Institute for Radiological Science (Japan) 1997: GSI, Darmstadt (Germany) 1997: GSI, Darmstadt (Germany) 2001: Hyogo Ion Beam Medical Center (Japan)2001: Hyogo Ion Beam Medical Center (Japan)
In development (Europe)In development (Europe) GermanyGermany (Heidelberg) (Heidelberg) Italia Italia (CNAO – TERA, Pavi)(CNAO – TERA, Pavi) Austria (Austria (Medaustron, Baden –Vienna)Medaustron, Baden –Vienna) France France (ETOILE, Lyon)(ETOILE, Lyon)
The Medical ProjectThe Medical Project
The «The « medical projectmedical project » » Determine the potential indications of
carbon ions.
FFirst tumor types studied irst tumor types studied Head and neck Sarcoma Glioma
ObjectivesObjectives
To define the situations in which an increased dose To define the situations in which an increased dose (using carbon ions) could be efficient(using carbon ions) could be efficient
To define the survival and local control expected To define the survival and local control expected when the « best treatment » is usedwhen the « best treatment » is used
To evaluate the risk of toxicitiesTo evaluate the risk of toxicities
This is not an exhaustive review of litteratureThis is not an exhaustive review of litterature
DefinitionDefinition of of the the best treatmentbest treatment
Established treatments Treatments assessed by randomized studies
Standard treatments Treatment established by consensus
Innovative treatments Treatments with no validation
No Established treatments for those indications
Local Working Groups
Screening of all topographies and histologies to identify a priori any
potential indication for Hadrontherapy
“Evidence based medicine” approach (methodologists)
screening and analysis of all relevant literature (HT & conc. Therapies)
“Epidemiological landscape” Cancer registry (FRANCIM) and
“One day survey” in French radiation oncology departments
STS R1 (extremity or axial)STS R1 (extremity or axial)
TREATMENT TREATMENT ToxicityToxicity
OS OS
LCLC
DFSDFS
ZagarsZagars 20032003
N=254N=254
Photons:Photons:
Med Doses: 64 GyMed Doses: 64 Gy
No No informationinformation
LC 10y:73%(67%-79%)LC 10y:73%(67%-79%)
DFS 10y:49%(43-56%)DFS 10y:49%(43-56%)
Schmitt GSchmitt G 19891989
N=104N=104
Photons 40 GyPhotons 40 Gy
Neutrons 6.3nGyNeutrons 6.3nGy
No No informationinformation
LC 5y:77%(68-85%)LC 5y:77%(68-85%)
DFS 5y:65%(55-74%)DFS 5y:65%(55-74%)
STS R1: propositionSTS R1: proposition
R1 definitive and never resectableR1 definitive and never resectable Hadrontherapy will not replaced good surgeryHadrontherapy will not replaced good surgery
Objective of Carbon IonsObjective of Carbon Ions
To decrease local recurrence To decrease local recurrence
AuthorsAuthors YearsYears TreatmentTreatment ToxicityToxicity OS OS
LCLC
DFSDFS
SchwartzSchwartz 20012001
N=41N=41
NeutronsNeutrons
4.8-22 nGy4.8-22 nGy
+/- Photons+/- Photons
10-60 Gy10-60 Gy
15% late severe 15% late severe toxicitytoxicity
LC 4y : 61%LC 4y : 61%
DFS4y: 59%DFS4y: 59%
OS 4y: 66%OS 4y: 66%
SchmittSchmitt 19891989
N=94N=94
NeutronsNeutrons
16.8 nGy16.8 nGy
No informationNo information LC 5y : 56%(45-66%)LC 5y : 56%(45-66%)
DFS 5y:25.5%(17-35%)DFS 5y:25.5%(17-35%)
KamadaKamada 20022002
N=57N=57
Carbon ionsCarbon ions
52.3 Gy52.3 Gy
57.6 Gy57.6 Gy
6/57 6/57 LC 3y:73%(48-98%)LC 3y:73%(48-98%)
OS 3y:46%(26-66%)OS 3y:46%(26-66%)
DFS 3y:36%(24-50 %)DFS 3y:36%(24-50 %)
STS R2 or unresecable propositionSTS R2 or unresecable proposition R2 definitive and never resecableR2 definitive and never resecable
Hadrontherapy will not replaced good surgeryHadrontherapy will not replaced good surgery
Non randomized phase II trial Non randomized phase II trial
Photontherapy :Photontherapy : LC 10 %LC 10 %
Neutrontherapy :Neutrontherapy : LC 60% LC 60%
Objective : at least 50% local control with few Objective : at least 50% local control with few toxicitiestoxicities
Unresecable tumor or recurrence with oligo Unresecable tumor or recurrence with oligo metastasis can be treated in this groupmetastasis can be treated in this group
Chondrosarcoma Chondrosarcoma R2 or unresecable R2 or unresecable
TreatmentTreatment ToxicityToxicity
OS OS
LCLC
DFSDFS
BubachBubach 19901990
N=18N=18
NeutronsNeutrons
16 nGy16 nGy
29%29% LC 3y:61%(35-82%)LC 3y:61%(35-82%)
DFS 3y:33%(13-59%)DFS 3y:33%(13-59%)
OS 3y: 50%(26-74%) OS 3y: 50%(26-74%)
MunzenriderMunzenrider
19991999
SpineSpine
N=17N=17
Protons Protons 66-83 66-83 CGECGE
LC 4y : 54%LC 4y : 54%
OS 5y : 48%OS 5y : 48%
R2 or unresecable Osteosarcoma R2 or unresecable Osteosarcoma
TreatmentTreatment ToxicityToxicity OS OS
LCLC
DFSDFS
HugHug
19951995
Osteo n=15Osteo n=15
ProtonsProtons
OsteosarcomaOsteosarcoma
69.8 CGE69.8 CGE
+ Chemotherapy+ Chemotherapy
8.6%8.6%
OsteosarcomaOsteosarcoma
OS 3.2y :53% (27-79%)OS 3.2y :53% (27-79%)
LC 3.2y : 73% (12-92%)LC 3.2y : 73% (12-92%)
CohenCohen
19841984
Osteo n=16Osteo n=16
Neutrons 18-26Neutrons 18-26 32%32%
OsteosarcomaOsteosarcoma
OS 4y : 11% (0.3-48%)OS 4y : 11% (0.3-48%)
LC 4y : 22% (3-60%)LC 4y : 22% (3-60%)
KamadaKamada 20022002
osteosarcomaosteosarcoma
N=15N=15
Carbon IonsCarbon Ions
52.8 GyE-57,6 52.8 GyE-57,6 GyEGyE
+ chemotherapy+ chemotherapy
6 grade 36 grade 3 Osteosarcoma Osteosarcoma
OS 3y 45%OS 3y 45% (7-83%)(7-83%)
LC3y 73%LC3y 73% (44-99%)(44-99%)
R2 or Unresectable R2 or Unresectable Osteosarcoma and Osteosarcoma and ChondrosarcomaChondrosarcoma: : PropositionProposition
Phase II Stratification according to histology and Phase II Stratification according to histology and tumor gradetumor grade
Unresecable tumor or recurrence with oligo metastasis can Unresecable tumor or recurrence with oligo metastasis can be treated in this groupbe treated in this group
Chordoma of the skull base, Chondrosarcoma of the Skull Chordoma of the skull base, Chondrosarcoma of the Skull base:base:
1077 identified references 1077 identified references 19 analysed in the final document 19 analysed in the final document
1077 References
958 Exclusions (abstract): •Language•No indication about treatment•Review: Nb of pts < 10•Publication before 1970
Skull of base Chordoma and ChondrosarcomaSkull of base Chordoma and Chondrosarcoma
Skull Base ChordomaSkull Base Chordoma Encouraging Local ControlEncouraging Local Control
Phase II randomized Study: Proton/CarbonPhase II randomized Study: Proton/Carbon
Skull Base ChondrosarcomaSkull Base Chondrosarcoma Association surgery and protontherapyAssociation surgery and protontherapy Excellent resultsExcellent results This is not an indication for Carbon ionsThis is not an indication for Carbon ions
Excepted for large tumor volumeExcepted for large tumor volume
SummarySummary
Difficulty to assess the efficiency of standard Difficulty to assess the efficiency of standard treatments to be compared with carbon ionstreatments to be compared with carbon ions
Small studiesSmall studies
Few Few homogenous series of patients treated with homogenous series of patients treated with adequate doses of radiation therapy adequate doses of radiation therapy
Survival data not reported by subgroup of Survival data not reported by subgroup of treatmentstreatments
ChondrosarcomaChondrosarcoma Skull base Skull base BB ProtonProton
Chordoma Chordoma Skull base Skull base AA Protons vs CarbonProtons vs Carbon
ChordomaChordoma Sacrum Sacrum
AA
Protons vs CarbonProtons vs Carbon
Physic rationnalPhysic rationnal
Pic de Bragg
Pic de Bragg étalé
Protons, light ions
Projet médical Projet médical « Hadronthérapie »« Hadronthérapie »
Objectif:Objectif: projet médical français et européen* commun pour projet médical français et européen* commun pour l’hadronthérapie (protons – carbone)l’hadronthérapie (protons – carbone)
Fondée sur une analyse rigoureuse de la littérature Fondée sur une analyse rigoureuse de la littérature et l’avis d’experts indépendantset l’avis d’experts indépendants
* ENLIGHT * ENLIGHT ERANET ERANET
Schema of the analysis of literattureSchema of the analysis of literatture
To do the synthesis of liTo do the synthesis of litterature in selectionnated erature in selectionnated situationssituations
To defineTo define the survival and local control expected when the « best the survival and local control expected when the « best treatment » is usedtreatment » is used
This is not an exhaustive review of litteratureThis is not an exhaustive review of litterature
To present this document to a group of expertTo present this document to a group of expertss
Validation of Validation of the the potential indicationpotential indicationss Stratification of those indicationsStratification of those indications To define the modality of evaluationTo define the modality of evaluation
List of clinical situations
to be evaluated
Studies research :type of tumorstype of treatmentscharateristic of studies
Medline Cochrane data base institutionnal web sites