-Proton Beam Therapy in Paediatric Radiation Oncology -

Transcription

1 -Proton Beam Therapy in Paediatric Radiation Oncology - Beate Timmermann, M.D. West German Proton Therapy Centre Essen Germany

2 Preview Survival Toxicity Why protons? (theoretically) Experiences so far (clinically) Conclusions and Outlook

3 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

4 Survival Late Toxicity???

5 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.

6 Age and Toxicity Wachstumsverzögerung age and growth retardation / Radiotherapie Silber et al., 1990

7 before and after RT in one identical twin with anaplastic Ependymoma at the age of 4 years Toxicity Source: Prof. Dr. M. Bamberg, Tübingen

8 Multifactorial! Sequelae (AE) OP RX Tumour (TU) Operation (OP) Chemotherapy (CX) Individual Features (IF) Radiotherapy (RX) CX AE IF TU

9 Why Protons?

10 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

11 Proton Therapy XRT Protons (each 1 Feld) Tony Lomax, PSI

12 PT - XRT N. Tarbell

13 Proton Therapy A typical case Supratentorial ependymoma, 2.5 years, incompletly resected, CX-RX according to the HIT-trial (60 Gy)

14 PT - XRT Applied XRT in a child with LGG of the optical pathway RT PT

15 PT - XRT XRT PT Choroid-Plexus Carcinoma 2 year old girl

16 Emb. RMS, Boy, 7.5 J. PT - XRT -2 fields - Dose 46.8 Gy Gy

17 Rec. Desmoid, Boy, 2 yrs. PT - XRT -1 Field - Dose 50.0 Gy Gy

18 Does PT make a difference clinically? We believe it is true, But We do not have the proof yet!

19 Any general recommendation? Herman Suit, Gray Lecture 2001

20 Clinical Experiences

21 Proton Therapy Gantry

22 Proton Therapy for Children- Clinical Data? Very few Why? technical pioneering first, operated by research institutes! See following table, considering paediatric data only!

23 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 % 2 pituitary, 1 temporal lobe necrosis, 1 muscle fibrosis /28 1 cataract, 1 hormonal, 2 seizures (PT+XRT) 72 mo 25 mo 5/7 none 2-50 mo LGG /27 1 Moyamoya, all preserved performance, all optic. Tu maintained or improved vision skull base % 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

24 Institute, year of publication Orsay, 2003 Diagnose N of P. Intracrani al Tu Age (yrs.) PT, dose (Gy) (PT+XRT) LC Late Toxicity FU 92% Early tox. as expected 27 mo PSI, 2006 STS 9 Med. 1.9 PSI, 2007 STS PSI, 2007 CH/CS /9 Acute:fine Late:? 50 12/16 Well tolerable, 1/5 myopia, orbital asym % Acute: Well tolerable Late: not exceeding mo 1.5 yrs 36 mo Boston, 2008 Ependym %? 26 mo Orsay, 2008 CH/CS 30 <20 68 (mean) 100/ 80% Boston, 2008 Cranioph % Vision (2), hearing (4), endocrine (7) 26.5 mo? 40.5 mo

25 Clinical Application children patients sedated

26 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)

27 Established Collaborations

28 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

29 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)

30 PT-Planning

31 Methods and Patients patient characteristics (n = 62) Age (dx); med. 8.1 yrs. (range, ) 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

32 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

33 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

34 Results PFS Mean FU: 38 mo 12 loc. Rec. Med. time to progression 12 mo PFS at 3-yrs 78.4 %

35 Results OS OS at 3-yrs 83.9 %

36 Results early toxicity Eval (n=) Karnofsky skin mucosa Bone marrow eye ear cns pns

37 Follow-Up after PT DOB 05/2002 Timmermann et al.

38 Results late toxicity Evaluable, n= 41; In 23 patients no toxicity reported specify skin Fibrosis, alopecia salivary Sicca syndrome endocrine GH, TSH eye chron. Conjun., cataract ear Chron. otitis cns ? Mental ret., chron head aches, BS-infarction pns Neuropathy, pain Bone/joint Trismus, asymmetry

39 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!

40 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!

41 Outlook: Expanding Indications Mediastinal Hodgkin s Disease = moving target Reducing the risk for SMN i.e. breast cancer?!

42 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 pats./pa Situated on the campus PBS Nozzle

43 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!

44 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

45 The best option is? 1F vertex 2F Lat.? 3F GPOH, Berlin 2007

46 Who was the patient?

47 THANK YOU!