Determination of The Potential Indications of Hadronthérapie ...
POTENTIAL INDICATIONS OF HADRONTHERAPY IN THE SARCOMAS ANALYSIS OF THE LITERATURE Dr Marie Pierre SUNYACH Dr Pascal POMMIER Centre Lon Brard Dr Emmanuel AMSELLEM Facult Lannec Lyon, France Carbon Ions - Perspective Rationnal Balistic Bragg peak Biological 2 to 3 times more efficient than photon From GSI, Darmstadt, Germany
Hadrontherapy Centers (Carbon Ions) Existing Centers 1994: National Institute for Radiological Science (Japan) 1997: GSI, Darmstadt (Germany) 2001: Hyogo Ion Beam Medical Center (Japan) In development (Europe) Germany (Heidelberg) Italia (CNAO TERA, Pavi) Austria (Medaustron, Baden Vienna)
France (ETOILE, Lyon) The Medical Project The medical project Determine the potential indications of carbon ions. First tumor types studied Head and neck Sarcoma Glioma Objectives To define the situations in which an increased dose (using carbon ions) could be efficient To define the survival and local control expected when the best treatment is used
To evaluate the risk of toxicities This is not an exhaustive review of litterature Definition of the best treatment Established treatments Standard treatments Treatments assessed by randomized studies Treatment established by consensus Innovative treatments Treatments with no validation No Established treatments for those indications 2002 - 2003 Local Working Groups Screening of all topographies and
histologies to identify a priori any potential indication for Hadrontherapy The potential indications tables Indications (topo, stage, pathology..) Standard and concurrent therapies Organ ICD-O2 Localisation Further cr ite ria se le ction Curr ent tr etame nt ; graduate d list of concurr ent t reatme nt t o car bon E y e, Brain & CNS C70 Me ni ng ioma (all l oc al isations) Ino perable b eg nin men ing ioma Pho ton s; IMRT, Pro ton s E y e, Brain & CNS C70
Me ni ng ioma (all l oc al isations) Beg n in men ig ioma wit h risks o f su rg ica l s equ elae Pho ton s; IMRT, Pro ton s E y e, Brain & CNS C70 Me ni ng ioma (all l oc al isations) Ma lig nan t men in gio ma Gr 2-3 Pho ton s; IMRT, Pro ton s E y e, Brain & CNS C72 Ne uri noma Ino pe rab le Pho ton s;
IMRT, Pro ton s E y e, Brain & CNS C72 Ne uri noma E y e, Brain & CNS C71 Low g rade gli oma with bad pr onosti c : 40 ye ar old, volumi nous tumor, symptoms, i noper able E y e, Brain & CNS C71 Low g rade gli oma with bad pr onosti c : 40 ye ar old, volumi nous tumor, symptoms, i noper able
E y e, Brain & CNS C71 Low g rade gli oma with bad pr onosti c : 40 ye ar old, volumi nous tumor, symptoms, i noper able E y e, Brain & CNS C71 Gl ioblas toma Ris ks of su rgic al se qu ela e++ Pho ton s; IMRT, Pro ton s (3) st 1 st ep : p os t RT tumo r re laps e
with p ro gre ss ion un de r ch emoth era py Pho ton s; Prot on s (8 ) (3) nd 2 s tep : inop e rab le tu mor not prev iou sly irrad iate d and progres siv e u nd er che mo th era py Pho ton s; Prot on s (8 ) (3) 2003 2006 Evidence based medicine approach (methodologists) screening and analysis of all relevant literature (HT & conc. Therapies) rd
3 ste p : po st -ope ra tiv e RT 1s t st ep : p os t RT t umor relaps e with p ro gre ss ion un de r ch emoth era py Pho ton s; Prot on s (8 ) Pho ton s; Chemo ra dio the rap y Epidemiological landscape Cancer registry (FRANCIM) and One day survey in French radiation oncology departments International experts 2003 2006 - Validation of the indications for HT (P. and/or C) - Estimation of the therapeutic gain & priorities - Prospective trials A portfolio of multicenter clinical trials Clinical Trial n 1 for hadronthrapie zegqergqeomfhmlqejheqtjheqojhoqejthojetphjqsetophjpqejthoqjethjqethjqptjohqrotjhpqtjhopjqtpohjqet hjpotjhopqtjhopsjthpojsrthojqpetohjqopetjhqopetjhqopejthqopejthopqejthopjqethopjqpetohjpqojhqojethpoqjet
Carbon ions Surgery Osteosarcoma chondrosarcoma Inoperable R2 Limbs Neutrons+chemotherapy Photons+chemotherapy Carbon Ions Osteosarcoma Chondrosarcoma R2 inoperable Others than limbs Neutrons+chemotherapy Photons+chemotherapy Carbon Ions Protons Chordoma Skull base cervical Protons
Chordoma Sacrum Protons Chondrosarcoma Skull base cervical Protons chondrosarcoma Lombar sacrum Protons Neutrons Plan Soft tissue sarcoma R1 and R2 Osteosarcoma and Chondrosarcoma Skull base Chondrosarcoma and Chordoma
STS: 1524 identified references 21 analysed in the final document 1524 References 135 selectionnated 1389 Exclusions (abstract) : Language No indication about treatments Review:Nb of pts < 10 Publication before 1970 Children Animals Resction R0 114 Exclusions (article) No clinical data Resection R0 No RTE RTE < 50 Gy Nb < 10 pts No indication about treatment Dosimetric studies 21 definitively selectionnated STS R1 (extremity or axial) TREATMENT Toxicity
OS LC DFS Zagars 2003 N=254 Photons: Med Doses: 64 Gy No information LC 10y:73%(67%-79%) DFS 10y:49%(43-56%) Schmitt G 1989 N=104 Photons 40 Gy Neutrons 6.3nGy No information LC 5y:77%(68-85%) DFS 5y:65%(55-74%) STS R1: proposition
R1 definitive and never resectable Hadrontherapy will not replaced good surgery Objective of Carbon Ions To decrease local recurrence to near 0 % Non randomized phase II STS R2 / unresecable (extremity /axial) Authors Years Treatment Toxicity OS LC DFS Schwartz 2001 Neutrons 4.8-22 nGy +/- Photons 10-60 Gy 15% late severe
OS 3y:46%(26-66%) DFS 3y:36%(24-50 %) STS R2 or unresecable proposition R2 definitive and never resecable Hadrontherapy will not replaced good surgery Non randomized phase II trial Photontherapy : Neutrontherapy : LC 10 % LC 60% Objective : at least 50% local control with few toxicities
Unresecable tumor or recurrence with oligo metastasis can be treated in this group Retroperitonal STS Gilbeau TREATMENT OS LC Photons +/Associated CT R0 Overall survival 2 y. : 93% 5 y.: 83% LR relapse free survival 2 y. : 100 % 5 y. : 53% Photons +/Associated CT R1 Overall survival 2 y. : 84% 5 y. : 46%
LR relapse free survival 2 y. : 55% 5 y. : 32% Retroperitonal STS Proposition Post-operative irradiation is not a standard treatment Improving local control is needed Non randomized Phase II for R2 or unresecable tumor. Osteosarcoma, Chondrosarcoma (Limbs or Sacrum): 1635 identified references 11 analysed in the final document 1635 References 114 selectionnated 1521 Exclusions (abstract): Langage No indication about treatment Review: Nb of pts < 10 Publication before 1970
103 Exclusions (article): No clinical data Resection R0 No RTE RTE < 50 Gy Nb < 10 pts No indication about treatment 11 definitively selectionnated Chondrosarcoma R2 or unresecable Bubach Munzenrider 1990 N=18 1999 Spine N=17 Treatment Toxicity Neutrons 16 nGy
Neutrons 18-26 32% Carbon Ions 52.8 GyE-57,6 GyE + chemotherapy 6 grade 3 Osteo n=16 Kamada 2002 osteosarcoma N=15 OS LC DFS Osteosarcoma OS 3.2y :53% (27-79%) LC 3.2y : 73% (12-92%) Osteosarcoma OS 4y : 11% (0.3-48%) LC 4y : 22% (3-60%) Osteosarcoma OS 3y 45% (7-83%) LC3y 73% (44-99%) R2 or Unresectable Osteosarcoma and
Chondrosarcoma: Proposition Phase II Stratification according to histology and tumor grade Unresecable tumor or recurrence with oligo metastasis can be treated in this group Chordoma of the skull base, Chondrosarcoma of the Skull base: 1077 identified references 19 analysed in the final document 1077 References 119 selectionnated 958 Exclusions (abstract): Language No indication about treatment Review: Nb of pts < 10 Publication before 1970 100 Exclusions (article): No clinical data Resection R0 No RTE RTE < 50 Gy Nb < 10 pts No indication
about treatment 19 definitively selectionnated Skull Base Chordoma TREATMENT Toxicity OS LC DFS Munzenrider 1999 N=290 Protons 66-83 CGE OS 5y :80% LC 5y :73% Noel 2003 N=47 Protons 67 CGE 49%
TREATMENT Breteau Orleans 1998 N=12 Munzenrider 1999 N=85 Photons 40 Gy Neutrons 15-25 Protons 66-83 CGE OS LC DFS LC 4y: 61% OS 4y: 54 % LC 5y: 69% OS 5y: 80% Skull of base Chordoma and Chondrosarcoma Skull Base Chordoma
Encouraging Local Control Phase II randomized Study: Proton/Carbon Skull Base Chondrosarcoma Association surgery and protontherapy Excellent results This is not an indication for Carbon ions Excepted for large tumor volume Summary Difficulty to assess the efficiency of standard treatments to be compared with carbon ions Small studies Few homogenous series of patients treated with adequate doses of radiation therapy
Survival data not reported by subgroup of treatments Indications Interest Evaluation STS R1 Excepted retroperitoneal A Phase II STS R2 MO M+ Excepted retroperitoneal A Phase II Retroperitoneal R2 unresecable Phase II
A Osteosarcoma Chondrosarcoma M0/M+ R2 unresecable Limbs Others Phase II A Chondrosarcoma Skull base B Proton Chordoma Skull base A Protons vs Carbon Chordoma Sacrum
Protons vs Carbon A Physic rationnal Pic de Bragg Protons, light ions Pic de Bragg tal Projet mdical Hadronthrapie Objectif: projet mdical franais et europen* commun pour lhadronthrapie (protons carbone) Principes: Multidisciplinarit (oncologues , chirurgiens, spcialistes dorganes, anapaths, pidmiologistes, ..) Fonde sur une analyse rigoureuse de la littrature et lavis dexperts indpendants * ENLIGHT ERANET Schema of the analysis of literatture To do the synthesis of literature in selectionnated situations
To define the survival and local control expected when the best treatment is used This is not an exhaustive review of litterature To present this document to a group of experts Validation of the potential indications Stratification of those indications To define the modality of evaluation List of clinical situations to be evaluated Report sudmitted to a group of experts Studies research : type of tumors type of treatments charateristic of studies Medline Cochrane data base institutionnal web sites Reference manager Selection of
studies -summary -integral text Document Definitive list of potential indications
Integrate more broadly with other College of Engineering Courses Hybrid and embedded software systems have natural applications in mechanical engineering, civil and environmental engineering, and bioengineering. Make hybrid and embedded systems a legitimate concentration, with its own prelim exam and...
The Origin of Asteroids. Images of the Asteroid Vesta show a complex surface, including a large impact crater. Meteorite probably fragmented from Vesta. Distribution: S-type asteroids in the outer asteroid belt; C-type asteroids in inner asteroid belt may reflect temperatures...
Symmetric block cipher, key lengths up to 256 bits. Openly designed by public competition (1997-2000) ... Salting appends several unique characters to each account password before running it though a cryptographic function, a process that blunts the value of rainbow...
Management as a daily activity as well as a distinct role. ... (Boddy:150) Process, content and context all relevant. Processes can be seen as planning, learning, or political. The 'strategy loop' involves making sense, making choices, making things happen and...
Herbalife TS-257-HC-2016-Delhi. Mitsubishi TS-647-ITAT-2014-Delhi. Amendment to be construed retrospective. Similar amendment not made to Section 40(a)(iii) Can payer treat himself as agent of payee non resident, file a return claiming non taxability of impugned sum?
Facts linked to child neglectChildren from low-income families are 4 times more likely to experience mental health problems than children from higher-income families.(Morrison Gutman et al., 2015) 75% of adults with a diagnosable mental health problem experience the first symptoms...
Beacon Health Options. 1P. ... Loss of primary . caregiver/caregiver disability. Changes in physical or mental health status . ... in" socially may give rise to episodes of anxiety and depression. 23J. Autism Spectrum Disorder: Cognitive Functioning:
Historic legislation updating the nutrition standards in the NSLP & SBP for the first time in 15 years. ... Egg Sandwich on an English Muffin. 2 oz eq grain from bread, egg = extra. 2 grain food items; egg is...
Ready to download the document? Go ahead and hit continue!