Pediatric electron intraoperative radiotherapy: results and innovations

Transcription

1 Pediatric electron intraoperative radiotherapy: results and innovations Felipe A. Calvo ESTRO Hospital General Universitario Gregorio Marañon Madrid, Spain 2017

2 IOeRT in pediatric cancer: results and innovations The context: pediatric radiotherapy The fundaments: IORT electrons The data: clinical experiences Innovative developments

3 Cancer cure: pediatric oncology patients unexpected biology 3

4 Extreme Survivors: the real story of long term follow up 4

5 Cancer Survivors: the evidence! cancer survivors siblings Leukemia/Lymphoma 46% CNS 12% Sarcoma 30% Willms/Neuroblastoma 4%

6 Cancer survivors: the evidence

7 LIMITS FOR RADIOTHERAPY IN CHILDREN TOXICITY HYPOFRACTIONATION AGE FIXATION FOR INMOVILITATION ORGANIZATIONAL CONSTRAINTS ANAESTHESIA MULTIDISCIPLINAR PROTOCOLS ARE RIGID LOW INVOLVEMENT OF RADIATION ONCOLOGIST

8 FACTORS MAY CONTRIBUTE TO DECREASE TOXICITY REDUCTION OF THE DOSE KEEPING VOLUME DECREASE VOLUME KEEPING DOSE AND ADD CHEMOTHERAPY REDUCTION OF THE DOSE AND VOLUME DECREASE DOSE, VOLUME AND ADD CHEMOTHERAPY ONLY CHEMOTHERAPY

9 IOeRT in pediatric cancer: results and innovations The context: pediatric radiotherapy The fundaments: IORT electrons The data: clinical experiences Innovative developments

10 Fundamentals: description Vision guided RT Fingers (tactile) guided RT Surgical guided RT

11 Sapientia et Doctrina : 2016 IOERT recomendations Cervix: marginal resection Rectal: T4 & recurrent Pancreas: close/positive margins Sarcomas: extremity, trunk,h &N, retroperitoneal Endometrial: recurrent Anal canal: recurrent Breast: PBI with IOERT single dose

12 Pubmed Data Review From 1997 to IORT papers from 207 journals; 281 medical institutions from 32 countries.

13 IF vs topic / cancer site

14 IF evolution

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16 IOeRT: dosimetric advantages and registration

17 Practica clínica en cáncer de páncreas IOeRT > 150 dosimetric configurations available

18 IOeRT in pediatric cancer: results and innovations The context: pediatric radiotherapy The fundaments: IORT electrons The data: clinical experiences Innovative developments

19 PEDIATRIC CANCER AND INTRAOPERATIVE RADIOTHERAPY HDR BRACHYTHERAPY MSKCC ELECTRON IRRADIATION Mayo Clinic Heidelberg Univ Ohio State Univ HGU Gregorio Marañon

20 Treatment Strategy: Dose escalation vs Dose de escalation IOERT boost + EBRT (+/ Hypofractionated) vs Gy + 50 Gy vs Gy IOERT alone (exclusive RT component)

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22 2/1983 to 7/2003, 20 EBRT + IOERT paients locally advanced or recurrent malignancies of the extremity or abdominopelvic area. All EBRT and received IOERT doses of 7.5 to 25 Gy with 6 MeV to 15 MeV electrons. Median follow up of 11.6 years (range, 2.1 to 25.5 y), 13 patients (65%) alive NED. Gross total resection superior local control (88% vs. 67%) and survival (71% vs. 33%)

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24 Excellent Local Control and Survival After Intraoperative and External Beam Radiotherapy for Pediatric Solid Tumors: Long term Follow up of the Mayo Clinic Experience Stauder, Michael C. MD * ; Laack, Nadia N.I. MD * ; Moir, Christopher R. MD ; Schomberg, Paula J. MD * Journal of Pediatric Hematology/Oncology 33(5), July 2011, p IOERT in combination with surgery and EBRT for the management of pediatric solid malignancies provides excellent local control with reasonable toxicity, given the unfavorable medical conditions of the patient population studied. Long term survival in this population also is encouraging, particularly when GTR is achieved. These results suggest that IOERT should continue to be considered as an integral part of a multimodality regimen for pediatric solid malignancies, especially in younger patients with abdominopelvic malignancies.

25 18 pts 1 local failure MFT 60 months 6 significant morbidity

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28 IOERT: HIGH RISK PEDIATRIC NEUROBLASTOMA Haas Kogan et al. Int J Radiat Oncol Biol Phys 2000;47: METHODS : , 23 patients 2. IOERT: 4 16 MeV, 7 16 Gy (10 Gy median) No EBRT 3. RESULTS : 4. 18p total resection 6p (26%) recurrences 5. No long term survivors in 5 patients with subtotal resection 6. IOERT alone offers a good local control after R0. 7. If tumor residual, EBRT is mandatory.

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31 Hospital General Universitario Gregorio Marañon Madrid, Spain >1.500 IOERT procedures 3% pediatric cancer patients Data reported: Extremity sarcomas (IJROBPh 2015) Ewing + Rhabdo (IJROBPH 2016) Miscellaneous (abstract) Osteosarcoma (Radiother Oncol 2016)

32 Interdisciplinary Tumor Board: Pediatric Surgery Radiation Oncology ( EBRT, IORT) Pediatric Oncohematologits (Neoadjuvant +/ Adjuvant CT) Tumor Histologies: Sarcomas(Osteosarcoma, Soft tissue sarcomas, Ewing) Neuroblastoma(local advanced tumors, recurrences) Miscelaneous Doses IOERT: mac residual tumor 1250 cgy mic residual tumor 1000 cgy pediatrics 750 cgy unresected (>3 cm) cgy

33 Practica clínica en cáncer de páncreas IOeRT > 150 dosimetric configurations available

34 33 pediatrics patients (3.4%); 36 procedures Gender: 18 males / 15 females Age range: 1 month 17 years Histologies: 10 neuroblastoma N II 92, N III 95. N AR 99 7 Ewing sarcoma SEOP 95,98, 99, 01, 02, E VAIA, POG sarcomas SEOP 89, MMT5 3 fibromatosis 1 teratoma 1 nephroblastoma SIOP 1 Stage I INTERMEDIATE RISK 1 PNET SEOP 95,98, 99, 01, 02, E VAIA, POG 8850 Stages: 13 stage IV 4 recurrent disease Experience 01/ /2010 IOERT program: 954 cases

35 TREATMENT Boost with IOERT in unresected or high risk areas of residual tumors Anatomicareas: extremities:12p intra abdominal: 17 p intra thoracic: 7 p IOERT Energy Total Doses Applicator size 4 18 MeV cgy 5 15 cm Fields 1 2 EBRT Doses (15 p) cgy

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37 OTHER TREATMENTS CHEMOTHERAPY: 29/33 patients EBRT: 16/33 patients SURGERY: R0: 29/36 IORT R+: 7/36 IORT

38 LOCAL CONTROL: HISTOLOGY NEUROBLASTOMA: 67.5% SARCOMA: 60% EWING: 57%

39 RESULTS Median follow up: 60 months (range 3 173) 14 local recurrences (+14 distant) 11 DWD 5 AWD 17 NED LOCAL RECURRENCE FREE SURVIVAL (5 y) 62 %

40 OVERALL SURVIVAL 2010 analysis No EBRT + EBRT neuroblastoma IV (5) & recurrent sarcoma (6)

41 72 patients ( ) Pooled analysis CUN + HGUGM IOERT Gy EBRT 30% (R+) neoct 60% Non responders R1

42 R1 survival! Size >5cm, R+ for local control compesates histology adversity

43 disease status (recurrent), R+ for local control compensates R1 if NAT responder 37 Ewing / 34 RMS Recurrent R1 24% 10 y

44 IOeRT in pediatric cancer: results and innovations The context: pediatric radiotherapy The fundaments: IORT electrons The data: clinical experiences Innovative developments

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47 Radioterapia intraoperatoria (electrones): I + D +i HGUGM/UC3/UCM/HPC Productivity 3D dose estimation specimen CT miniaturization image guided surgery optic optical traking registration virtual surgery intraoperative imaging virtual simulation safety grants >20 pub > 1q > 64 IF 1 patent 9 PhD Thesis laparoscopic approaches results automatic doking stereotactic room in vivo dosimetry surgical navigation beam navigation Tumor bed assessement clinical data base eur

48 3D

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50 sarcoma: tumor bed + 3D + TLDs Tumor bed (3D printing) Tumor (3D printing) TLDs 50

51 sarcoma: simulation / registrationprocess 51

52 sarcoma: post CT model 3D Tumor bed TLD

53 sarcoma: 2D dose estimation on 3D CT images 53

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56 Plataforma casos IOERT 56

57 IOERT platform Software (free) Teaching File System (TFS) Medical Imaging Resource Community (RSNA MIRC) Information in private server Chart Images Vídeos Public access login + password 57

58 e learning IOeRT Registering data Repository of cases Clinical consultation Technical recommendations Learning curve implementation R & D cooperation Shareing knowledge: global practice

59 IOeRT in pediatric cancer: results and innovations 2017 The context: IOERT is feasible and optimizes EBRT The fundaments: electrons are efficient indepedent of resection status The data: positive clinical data in patients candidates to surgery and EBRT Innovative developments: LA miniaturization, in vivo dosimetry, e-learning

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