-Proton Beam Therapy in Paediatric Radiation Oncology - Beate Timmermann, M.D. West German Proton Therapy Centre Essen Germany
Preview Survival Toxicity Why protons? (theoretically) Experiences so far (clinically) Conclusions and Outlook
Background Survival in Paediatric Oncology has increased Quality of Life and late effects now of major concern RT still important part of the multidisciplinary concept
Survival Late Toxicity???
Price of Survival Including: Depending on: - Neurological Deficits - Growth Retardation - Endocrinology Dysbalance - Psycho-social social Impairment - Mental Retardation - Secondary Cancer etc. - Age at Diagnosis - Tumor - Dose and Volume of RT - Surgeries - Chemotherapy etc.
Age and Toxicity Wachstumsverzögerung age and growth retardation / Radiotherapie Silber et al., 1990
before and after RT in one identical twin with anaplastic Ependymoma at the age of 4 years Toxicity Source: Prof. Dr. M. Bamberg, Tübingen
Multifactorial! Sequelae (AE) OP RX Tumour (TU) Operation (OP) Chemotherapy (CX) Individual Features (IF) Radiotherapy (RX) CX AE IF TU
Why Protons?
Proton Therapy Highly conformal (dose escalation!) Few field arrangements Low integral dose Thus, potentially reduction of late effects and secondary cancer (young pts.!) Routinely performed in chordomas, chondrosarcomas, retinal tumors and paediatrics where available Requiring high precision, time consuming High costs
Proton Therapy XRT Protons (each 1 Feld) Tony Lomax, PSI
PT - XRT N. Tarbell
Proton Therapy A typical case Supratentorial ependymoma, 2.5 years, incompletly resected, CX-RX according to the HIT-trial (60 Gy)
PT - XRT Applied XRT in a child with LGG of the optical pathway RT PT
PT - XRT XRT PT Choroid-Plexus Carcinoma 2 year old girl
Emb. RMS, Boy, 7.5 J. PT - XRT -2 fields - Dose 46.8 Gy + 10.8 Gy
Rec. Desmoid, Boy, 2 yrs. PT - XRT -1 Field - Dose 50.0 Gy + 10.0 Gy
Does PT make a difference clinically? We believe it is true, But We do not have the proof yet!
Any general recommendation? Herman Suit, Gray Lecture 2001
Clinical Experiences
Proton Therapy Gantry
Proton Therapy for Children- Clinical Data? Very few Why? technical pioneering first, operated by research institutes! See following table, considering paediatric data only!
Institute, year of publication Boston, 1995 LLMU, 1997 Orsay, 1999 LLMU, 2002 Boston, 2002 Boston, 2002 Diagnose N of P. chordoma s Cranial Tu intracrani al Age (yrs.) PT, dose (Gy) LC Late Toxicity FU 18 4-18 55-75.6 78% 2 pituitary, 1 temporal lobe necrosis, 1 muscle fibrosis 28 1-18 40-70.2 24/28 1 cataract, 1 hormonal, 2 seizures 9 7-16 55-60 (PT+XRT) 72 mo 25 mo 5/7 none 2-50 mo LGG 27 2-18 55.2 21/27 1 Moyamoya, all preserved performance, all optic. Tu maintained or improved vision skull base 29 1-19 50.4-78.6 72% 1 motor weakness, 1 sensory deficit Orbital RMS 2 7, 8 50 / 55 2/2 Full visual acuity, mild enophtahlmus 3.3 yrs 40 mo 2.5 / 3.4 yrs
Institute, year of publication Orsay, 2003 Diagnose N of P. Intracrani al Tu Age (yrs.) PT, dose (Gy) 17 5-17 20 +40 (PT+XRT) LC Late Toxicity FU 92% Early tox. as expected 27 mo PSI, 2006 STS 9 Med. 1.9 PSI, 2007 STS 16 0.9-13.9 PSI, 2007 CH/CS 10 10-20 50 7/9 Acute:fine Late:? 50 12/16 Well tolerable, 1/5 myopia, orbital asym. 63.2-74 100 % Acute: Well tolerable Late: not exceeding 2 12.6 mo 1.5 yrs 36 mo Boston, 2008 Ependym. 17 1-13 52.2-59.4 86%? 26 mo Orsay, 2008 CH/CS 30 <20 68 (mean) 100/ 80% Boston, 2008 Cranioph. 24 3-14 52.2-54 100 % Vision (2), hearing (4), endocrine (7) 26.5 mo? 40.5 mo
Clinical Application 120 100 80 60 40 children patients sedated 20 0 1996 1998 2000 2002 2004 2007 2009
Established Collaborations Collaboration with Children s Hospital at University of Zürich, Pediatric Oncology ( tumor boards, chemotherapy & general care for PSI patients) Collaboration with Children s Hospital at University of Zürich, Pediatric Anaesthesiology ( providing continuous anaesthesiological care at PSI on an ambulatory basis)
Established Collaborations
Established Collaborations Since 2004 treatment of mainly very young children with CNS/Sarc. TU In collaboration with several German and European study boards Including consultant activities
Continuous Evaluation Of Therapy Results Standardized, prospective Evaluation of Treatment, doses to OARs, Toxicity and Quality of Life -> RISK-Study Study (since 2004) <-> > Exchange with LESS-Data PEDQUoL-Study (since 2005)
PT-Planning
Methods and Patients patient characteristics (n = 62) Age (dx); med. 8.1 yrs. (range, 0.1-19.0) Gender; 33 m/29 f Site; craniofacial 43 spine 15 pelvis 4 Histology; STS 39 Bone 11 Chordoma/Chs 12 Tu-size; >5 cm 31 M-stage; pos. (pulmo) 3 N-stage; pos. 2
Histologies Histology n = (total 62) subtypes RMS 31 24, embryonal 2, alveolar 5, Undiff./unclass. Chordoma 10 Ewing sarcoma 6 Chondrosarcoma 5 Osteosarcoma 4 Aneurysmatic bone cyst 2 Ektomesenchymoma 1 Desmoid 1 MPNST 1 Fibrosarcoma 1
Methods and Patients treatment characteristics Surgery; Biopsy 26 STR 24 GTR 12 Chemotherapy; any 44 during PT 38 Radiation Therapy; dose 54 Gy med. (range, 36-74) in part XRT 4 sedation 28
Results PFS Mean FU: 38 mo 12 loc. Rec. Med. time to progression 12 mo PFS at 3-yrs 78.4 %
Results OS OS at 3-yrs 83.9 %
Results early toxicity Eval. 0 1 2 3 4 5 (n=) Karnofsky 62 30 16 6 - - - skin 58 8 33 13 4 - - mucosa 47 15 14 16 2 - - Bone marrow 53 8 2 10 14 9 - eye 40 23 11 5 1 - - ear 37 32 1 4 - - - cns 36 32 2 2 - - - pns 43 43 - - - - -
Follow-Up after PT 2007 2005 DOB 05/2002 Timmermann et al.
Results late toxicity Evaluable, n= 41; In 23 patients no toxicity reported 1 2 3 4 5 specify skin 4 - - - - Fibrosis, alopecia salivary 2 - - - - Sicca syndrome endocrine 2 3 - - - GH, TSH eye 2 2 2 - - chron. Conjun., cataract ear 1 - - - - Chron. otitis cns - 2 - - 1? Mental ret., chron head aches, BS-infarction pns 1 1 - - - Neuropathy, pain Bone/joint 2 1 - - - Trismus, asymmetry
Conclusions PT is providing excellent conformal dose coverage and sparing of OARs (-> IMRT) In PT irradiated volumes are small PT thus, is reducing the integral dose (low- and medium dose level) and the risk for secondary cancer Inside the target volume all techniques carry the same risk of treatment sequelae!
Outlook PT will play a major role in pediatric oncology if available on a broader base! The younger the patient the more benefit from protons to be expected! ( and the larger the volume is?) In US and also increasingly in Germany, PT is implemented in the treatment protocols Integration in multidisciplinary framework essential! We will run proton specific trials!
Outlook: Expanding Indications Mediastinal Hodgkin s Disease = moving target Reducing the risk for SMN i.e. breast cancer?!
Treatment System Configuration 230 MeV Cyclotron Fixed Horizontal and Eye Beamlines Westgerman Proton Therapy Center Essen Gantries 1-3 PBS Nozzle Imaging devices: CT MRI PET-CT Universal Nozzle Capacity max. 2000 pats./pa Situated on the campus PBS Nozzle
Outlook For any advanced technique (and for any pediatric RT), investigations of tumor control, late effects, quality of life and secondary cancer are essential! For any conformal therapy with steep dose gradients: detailed knowledge on - target volumes and - organ tolerances (considering both, dose and volume!) is needed urgently!
Examples of a difficult decision (LGG, Case 3): What to prefere? 1 field, 2 fields or 3 fields? Should we spare the hippocampus at least at one side? GPOH, Berlin 2007
The best option is? 1F vertex 2F Lat.? 3F GPOH, Berlin 2007
Who was the patient?
THANK YOU!