Pediatric electron intraoperative radiotherapy:results and innovations

Felipe A. CalvoESTRO

Hospital General Universitario Gregorio Marañon Madrid, Spain

2017

IOeRT in pediatric cancer: results and innovations

• The context: pediatric radiotherapy

• The fundaments: IORT electrons

• The data: clinical experiences

• Innovative developments

Cancer cure: pediatric oncology patients… unexpected biology

3

4

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

Cancer Survivors: the evidence! 

10.397 cancer survivors3.034 siblingsLeukemia/Lymphoma 46%CNS                                         12%Sarcoma                                30%Willms/Neuroblastoma 4%

Cancer survivors: the evidence… 

TOXICITY   ‐ HYPOFRACTIONATION

AGE  ‐ FIXATION FOR INMOVILITATION

ORGANIZATIONAL CONSTRAINTS   ‐ ANAESTHESIA

MULTIDISCIPLINAR PROTOCOLS ARE  “RIGID”

LOW INVOLVEMENT OF RADIATION ONCOLOGIST

LIMITS FOR RADIOTHERAPY IN CHILDREN

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

IOeRT in pediatric cancer: results and innovations

• The context: pediatric radiotherapy

• The fundaments: IORT electrons

• The data: clinical experiences

• Innovative developments

Fundamentals: description

Vision guided RT

Fingers (tactile) guided RT

Surgical guided RT

“Sapientia et Doctrina”: 2016 IOERT recomendations

Cervix: marginal resectionRectal: T4 & recurrentPancreas: close/positive marginsSarcomas: extremity, trunk,H &N, retroperitonealEndometrial: recurrentAnal canal: recurrent

Breast: PBI with IOERT single dose

• Pubmed Data Review From 1997 to 2012• 858 IORT papers from 207 journals; 281 medical institutions from 32 countries.

IF vs topic / cancer site

1997 – 2013 IF evolution

IOeRT: dosimetric advantages and registration

> 150 dosimetric configurations available

Practica clínica en cáncer de páncreas IOeRT

IOeRT in pediatric cancer: results and innovations

• The context: pediatric radiotherapy

• The fundaments: IORT electrons

• The data: clinical experiences

• Innovative developments

HDR BRACHYTHERAPYMSKCC

ELECTRON IRRADIATIONMayo Clinic

Heidelberg UnivOhio State Univ

HGU Gregorio Marañon

PEDIATRIC CANCER AND INTRAOPERATIVE RADIOTHERAPY

Treatment Strategy: Dose–escalation vs Dose‐de‐escalation

IOERT boost + EBRT  (+/‐ Hypofractionated)vsIOERT alone (exclusive RT component)

10 – 20 Gy + 50 Gy vs 15 – 25 Gy

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%)

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. 

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 350–355

18 pts1 local failureMFT 60 months6 significant morbidity

METHODS :1. 1986 – 1998, 23 patients2. IOERT: 4 – 16 MeV, 7 – 16 Gy (10 Gy median)

3. RESULTS :

4. 18p total resection6p (26%) recurrences5. No long‐term survivors in 5 patients with subtotal resection6. IOERT alone offers a good local control after R0. 7. If tumor residual, EBRT is mandatory. 

IOERT: HIGH RISK PEDIATRIC NEUROBLASTOMAHaas‐Kogan et al. Int J Radiat Oncol Biol Phys 2000;47:985‐92 

No EBRT

Hospital General Universitario Gregorio MarañonMadrid, Spain

1995‐2017>1.500 IOERT procedures

3% pediatric cancer patients

Data reported:

Extremity sarcomas (IJROBPh 2015)Ewing + Rhabdo (IJROBPH 2016)Miscellaneous (abstract)Osteosarcoma (Radiother Oncol 2016)

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)                                1500‐2000 cGy

> 150 dosimetric configurations available

Practica clínica en cáncer de páncreas IOeRT

• 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 8850• 10 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 01/1995 ‐12/2010

IOERT program: 954 cases

Energy 4 – 18 MeV

Total Doses 500 – 1250 cGy

Applicator size 5 – 15 cm

Fields 1 – 2

EBRT Doses (15 p) 2000 – 5000 cGy

• “Boost” with IOERT in unresected or high risk areas of residual tumors• Anatomic areas:

• extremities: 12 p• intra‐abdominal: 17 p• intra‐ thoracic: 7 p

IOERT

TREATMENT

CHEMOTHERAPY: 29/33 patients

EBRT: 16/33 patients

SURGERY: ‐ R0: 29/36 IORT

‐ R+: 7/36 IORT

OTHER TREATMENTSOTHER TREATMENTS

NEUROBLASTOMA: 67.5%

SARCOMA: 60%

EWING: 57%

LOCAL CONTROL: HISTOLOGYLOCAL CONTROL: HISTOLOGY

• Median follow‐up: 60 months (range 3‐173)

• 14 local recurrences (+14 distant)

11 DWD5 AWD17 NED

LOCAL RECURRENCE‐FREE SURVIVAL (5 y)

62 %

LOCAL RECURRENCE‐FREE SURVIVAL (5 y)

62 %

RESULTSRESULTS

OVERALL SURVIVAL 2010 analysisOVERALL SURVIVAL 2010 analysis

No EBRT

+ EBRT

neuroblastoma IV (5)& 

recurrent sarcoma (6)

72 patients (1985‐2015)

Pooled‐analysis CUN + HGUGM IOERT 15‐20 Gy

EBRT 30% (R+)

neoCT 60%

Non‐respondersR1

Size >5cm, R+ for local controlcompesates histology adversity

R1… survival!

37 Ewing / 34 RMS

Recurrent

R1

24%LR @ 10 y

disease status (recurrent), R+ for local controlcompensates R1 if NAT responder

IOeRT in pediatric cancer: results and innovations

• The context: pediatric radiotherapy

• The fundaments: IORT electrons

• The data: clinical experiences

• Innovative developments

Radioterapia intraoperatoria (electrones):  I + D +i HGUGM/UC3/UCM/HPC

virtualsurgery virtual simulation

invivo

dosimetry

intraoperativeimaging

automaticdoking

safety

surgicalnavigation beam

navigationclinical data base

laparoscopic

stereotacticroom

image guided surgery

approaches

2006

2018

8 grants

729.851 eur

Productivity

>20 pub > 1q > 64 IF 1 patent 9 PhD Thesis

miniaturizationoptical traking

3D doseestimation

results

Tumor‐bed

assessement

specimenCT

opticregistration

3D

sarcoma: tumor bed + 3D + TLDs

50

Tumor(3D printing)

Tumor bed(3D printing)

TLDs

sarcoma: simulation / registration process

51

sarcoma: post‐CT model 3D

Tumor bed

TLD

sarcoma: 2D dose estimation on 3D CT images

53

Plataforma casos IOERT

56https://www.rsna.org/tfs.aspx

IOERT platform• Software (free)

• Teaching File System (TFS) • Medical Imaging Resource Community (RSNA MIRC)

• Information in private server• Chart• Images• Vídeos…

• Public access login + password57

e‐learning IOeRT

Registering dataRepository of casesClinical consultation

Technical recommendations

Learning‐curve implementationR & D cooperation

Shareing knowledge: global practice

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…