Novit in Radioterapia in Et Pediatrica Maurizio MASCARIN (MD) - - PDF document

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Novit in Radioterapia in Et Pediatrica Maurizio MASCARIN (MD) - - PDF document

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10/22/2018 Gemona 5 ottobre 2018 Palmanova, 30 novembre 2018 Novit in Radioterapia in Et Pediatrica Maurizio MASCARIN (MD) Elisa Coassin (MD), Irene Bassi, (TSRM), Giulio Pruch (TSRM) Federica Fedrigo (IP), Paola Pase (IP), Andrea

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Novità in Radioterapia in Età Pediatrica

1

Maurizio MASCARIN (MD)

Elisa Coassin (MD), Irene Bassi, (TSRM), Giulio Pruch (TSRM) Federica Fedrigo (IP), Paola Pase (IP), Andrea Schicariol (TSRM), Luana Tassan (IP)

AYA and Pediatric Radiation Oncology Unit C.R.O. Centro di Riferimento Oncologico – Aviano (Italy)

mascarin@cro.it Gemona 5 ottobre 2018 Palmanova, 30 novembre 2018

Activities of RT-Department 2,100 new patients / year 42,000 treatments / year 160 patients / day Human resources RT: Physician 14 Physicist 7; Dosimetrist 2 Informatics 2 Radiotherapist 19 CRO Aviano - Cancer Center

1 1 4 1

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Children 1%

Adults 97,5%

Adolescents AYA 1,5%

Cancer Incidence

Age 0-14 years: 175 cases/million/years (≈ 1380 new cases) Age 15-19 years: 270 cases/million/years (≈ 804 new cases) Age 20-24 years: 352 cases/million/years (≈ 1096 new cases) Age 25-29 years: 547 cases/million/years (≈ 1944 new cases)

Children, Adolescents and Young Adults

Italian population: Total 60.589.485

  • Italy ≤ 14 years: 8.182.584 Children
  • Italy 15-24 years: 5.895.353 Adolescent
  • Italy 24-29 years: 3.884.123 Young Adult
  • Italy 30-39 years: 7.393.662 adult

I tumori in FVG 1995-2005, Agenzia Reg Sanità - ISTAT 2012 AIRTUM, E&P 2008; AIRTUM 2014 Bleyer A et al SEER 1975-200

Age related cancer subtypes

I tumori in FVG 1995-2005, Agenzia Reg Sanità - ISTAT 2017 AIRTUM, E&P 2008; AIRTUM 2014

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1975

CRO History of Radiotherapy in children

1985

Cobalto

  • Acc. Lineare

2000 2001

Stereotassi 3D conformal

1995

PC planning

CRO History of Radiotherapy in children

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2005 2006

IORT TOMO

2005

IMRT IGRT

2012

ArcTherapy

CRO History of Radiotherapy in children

8

Linear Accelerator 6MV

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9

Multi Leaf Collimator

10

TomoTherapy

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11

40,8 19,6 17,4 4,2 3,7 2,6 2,4 2,3 7,1

SNC LINFOMA SARCOMA NB LEUCEMIA WILMS GCT ORL ALTRO

CRO Aviano – RT in Pediatric-AYA Patients

PAZIENTI ≤ 18 anni DAL MAGGIO 1995 AL MAGGIO 2018: 622 ped

% (pts recruited from June 2005 to May 2018: 299 Tomo/IMRT)

512 Pediatric - Adolescent pts 1992-2010

CRO Aviano – Tomo/IMRT in Pediatric-AYA Patients

222 TOMO pts (+77 IMRT). Median age 14 years

CNS 48% Thorax 9% Head & Neck 11% Mediastinal-Neck Nodes 19% Limbs 4% Abdomen 6% Pelvis 3%

Sedation 18 % of Tomo/IMRT pts

Median age 4 (range 1-14)

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  • 2% del totale dei pz di un reparto RT
  • Circa 2/3 dei bambini con tumore solido

avranno bisogno prima o poi della RT

  • Obiettivi della cura.
  • Rischio degli effetti collaterali
  • Problema delegabile?
  • Paziente è “NON TIPICO”

DEFINIZIONE DEL PROBLEMA DIFFICOLTÀ DI APPROCCIO QUALITA’ DELLA VITA

Radiotherapy in Pediatric Tumors

Clinical assesment

  • Time (years)

Therapy

Evaluation Reabilitation

SURGERY RADIOTHERAPY CHEMOTHERAPY

1 2 3

Pediatric Tumors and Outcome

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Risk-adapted radiotherapy

Endocrine late effects Secondary cancer SNC damage

Radiotherapy related morbidity

Host factors / Age Bone growing Organ dysfunction Esthetic damages Infertility Tumors factors Treatment factors

Risk-adapted therapy

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RT imaging “on board” Multidisciplinary Case Discussion Target and structure contouring Treatment planning

  • ptimization

Planning and treatment images co-registration Modified patient position

Treatment delivery

Patient position

What are we currently doing?

Immobilization

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Immobilization

20

https://www.google.it/search?sa=G&hl=it&q=maquina+de+raio+x+antigas&tbm

Immobilization

1959

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Halperin 1950

Immobilization

1980

Immobilization

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2000

Immobilization

Prone Supine

“old” prone position, “new” supine position

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Immobilization

Mask + shoulder

26

IGRT Image Guided Radiotherapy

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MVCT

Brain: CT Guidance

MVCT imaging fused with planning CT

IGRT and Tomo

28

TOMO CSI PROTON CSI

ROLL PITCH JAW BED deflection

IGRT and technology selection

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29

Sedation - Pt positioning - Immobilization

30

20 25 30 35 40 45 20 40 60 80 r2=0.18, p=0.018 durata sedute per paziente (minuti) % di sedute con eventi per paziente

Vi è un aumento degli eventi collaterali durante la sedazione all’aumentare della durata della stessa (28 vs 24 m’) e all’aumentare del numero progressivo delle sedazioni (>15). In 783 sedazioni con Propofol per RT ped:

  • nessuna complicazione maggiore,
  • 2 desaturazioni (0,25%),
  • 92 variazione della frequenza cardiaca (11,7%),
  • 173 complicanze minori vie aeree (22%).

LA SEDAZIONE CON PROPOFOL IN RADIOTERAPIA PEDIATRICA Mascarin M, Giergji M, Fantin D, Bortolussi R, Fabiani F, Bertuzzi C, Gigante M,Capone D, Fedrigo F, Pase P, Ros L, Bassi I, Pacenzia R, D’Ecclesia G, Bulian P,De Cicco M , Proceeding Congresso Nazionale AIEOP 2010

Durata seduta (m’) N° sedute)

Sedation with propofol in Pediatric Radiotherapy

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Target Definition

Definition of tumor treatment volume and OAR

Mascarin M et al in Posterior Fossa Tumors in Children. M. Özek , G. Cinalli, W. Maixner, C. Sainte-Rose. Editors, Springer Ed, pp363380 2015

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33

Some extra structures were generated (“tune structures”) to obtain a better optimization around the target

Mascarin M et al. Helical Tomotherapy in Children and Adolescents: Opportunities and Issues, Cancers 2011

If OARs are not contoured, the process “doesn’t matter”

OAR Organ at Risk From multimodality co-registration to IMRT

(Intensity Modulation Radiation Therapy)

NMR FET FET SpectroNMR NMR

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Tumor shrinking

Comparison between diagnostic PET and CT/RT-simulation after chemotherapy

TC pre-operatoria RNM pre-operatoria RNM post-operatoria

4,0 cm. 5,0 cm. 3,5 cm.

Ependimoma

“Tumor shrinking”

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10/22/2018 19 RT volumes planned on disease burden at the chemotherapy course (ISRT - INRT modified).

Confidential: Prof. Dr. Dieter Körholz, Prof Karin Dieckmann

Initial PET/CT LRA-qPET At the end of CT

EURONET PHL C2 Radiotherapy volumes “DECOPDAC21”

Could Radiotherapy Volumes safely reduced?

Involved Node Radiotherapy should be considered for pediatric patients with Hodgkin lymphoma since it is estimated to substantially lower the risk of severe long-term complications.

Mantle IFRT

Modified IFRT

INRT

Thyroid Lungs Heart Breast

Mantle fields IFRT Modified IFRT ISRT

Could Radiotherapy Volumes safely reduced?

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39

Postnatal tissue growth

  • J. Pfeil. Orthopäde 2002, 31:2-10

Gawade PL et al. A Systematic Review of Selected Musculoskeletal Late Effects in Surviv CC. Curr Pediatr Rev. 2014

Younger age, higher radiation dosage, and asymmetric bone radiation volume influences the detrimental effects of RT.

Pathophysiology of Bone Growth Damage

Silber et al, JCO 1990

Skeletal Loss for a radiotherapy field from T10-11 to L4-5

using a hypothetical male patient with IAS equal to 176.8

  • cm. Each point corresponds to an age when irradiated, a

dose in Gray, and SL ± 1 SD.

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Legs

HUMERUS

80% 20%

FEMUR

30% 70%

TIBIA

60% 30% Bone Development & Growth in Children

“4D Radiotherapy”

take account of Spatial-Temporal Evaluation

  • f the Target during the imaging, planning

and delivery of the radiotherapy.

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43

“4D Radiotherapy” ?

Mascarin M. – CRO Aviano

Dose Distribution

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Dose distribution Traditional vs High conformal RT

Female 15 y, HD lymphoma (14.4Gy / 8 fr, mediastinum, supraclavicular, infraclavicular)

2CC-AP

Tomo

Indications for HT

Mascarin M, Giugliano FM, Coassin E. Cancers 2011.

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Craniospinal Irradiation

Craniospinal irradiation

TOMO CSI IMRT CSI

Gy Dose 50% Dose 20% Dose 10% Gy

100% 0% 50%

PROTON CSI

Courtesy of: AtreP Trento

Dose 0%

Mascarin M et al in Posterior Fossa Tumors in Children. M. Özek , G. Cinalli, W. Maixner, C. Sainte-Rose. Editors, Springer Ed, pp363380 2015

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Mascarin M. – CRO Aviano

Head and Neck

  • NO multiple fieds, different energies, junctions
  • Easy delivering different doses at different volumes:
  • sequential boost, SIB
  • SIB lower doses surrounding high dose PTV than sequential boost
  • HT-SIB better homogeneity and sparing of OAR
  • Reduced incidence of high grade toxicity, delayed onset moderate

toxicity  prevention of treatment breaks  reduction in the total RT time

TOMO in Nasopharynx Carcinoma

Female 14 y, Nasopharynx carcinoma Mascarin M, Coassin E. Tomotherapy in Children. Pediatric Radiation Oncology. Editors: Merchant, Thomas E., Kortmann, Rolf-Dieter; Eds. Springer, April 2018.

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Sarcoma (soft tissue / bone)

Sarcoma (soft tissue/bones)

Mascarin M, Coassin E. Tomotherapy in Children. Pediatric Radiation Oncology. Editors: Merchant, Thomas E., Kortmann, Rolf-Dieter; Eds. Springer, April 2018.

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Lung irradiation

Whole lung irradiation

Mascarin M, Coassin E. Tomotherapy in Children. Pediatric Radiation Oncology. Editors: Merchant, Thomas E., Kortmann, Rolf-Dieter; Eds. Springer, April 2018.

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Lung stereotactic irradiation

Mascarin M, Coassin E. Tomotherapy in Children. Pediatric Radiation Oncology. Editors: Merchant, Thomas E., Kortmann, Rolf-Dieter; Eds. Springer, April 2018.

Whole abdominal irradiation

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Whole abdominal irradiation

  • Adequate coverage
  • Limited dose to residual kidney, spinal cord, bone marrow
  • Reduced dose to small bowel
  • Homogeneous dose along vertebral bodies

Mascarin M, Coassin E. Tomotherapy in Children. Pediatric Radiation Oncology. Editors: Merchant, Thomas E., Kortmann, Rolf-Dieter; Eds. Springer, April 2018.

Palliations

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Female, 22y, alveolar rhabdomyosarcoma, Site: Leg, PRO during CT, RT20Gy/5fr.

Palliative Intent

Tomo

Improve the Quality of Life

Female, 18 y, stage IV° Ewing/PNET

High School exit examination

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61

What are we currently doing?

Proton therapy

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PROTON Therapy

  • Protons Stop!!
  • Photons don’t stop.
  • Proton dose at depth (target)

is greater than dose at surface.

  • Photon dose at depth (target)

is less than dose at dmax.

Hoffman EK et al.. Journal of Child Neurology, 24, 11:1387-1396; 2009

64

PROTON Therapy (CNAO Pavia)

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65

PROTON Therapy (CNAO Pavia)

66

PROTON Therapy (IBA Trento)

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67

PROTON Therapy (IBA)

68

PROTON Therapy (MEVION)

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100% 0% 50%

PROTON CSI

TomoTherapy vs Proton Therapy in CSI

TOMO CSI

Gy

Mascarin M et al in Posterior Fossa Tumors in Children. M. Özek , G. Cinalli, W. Maixner, C. Sainte-Rose. Editors, Springer Ed, pp363380 2015 Proton Plan Courtesy ATREP Trento

70

Dosimetric comparison of proton and IMRT in pediatric RMS on a prospective phase II study

Ladra et al, Radiother Oncol 113:77-83, 2014

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71

Both Proton and Tomo/IMRT provided satisfactory conformation and OARs sparing in complex pediatric cases. Proton demonstrated superior target coverage, homogeneity, conformity, and OARs sparing. In some situations (small volumes, shallow depths) Tomo provided comparable results. Learning curve, not only for technology but also in pediatric oncology subset.

PROTON Therapy

The “value” of radiotherpay process

HIGH TECH: “new technologies” HIGH TOUCH: “special patient”

§ persone/giorno di trattamento RT

RT*

Ricavi €

Simulation Contouring Planning

Treatment § Anesthesia

Mammella 4420

20‛ 30’ 60’ 10’ no

Prostata 5170

30‛ 30’ 60’ 12’ no

Cerebrale 6870

40‛ 120’ 180’ (fusion) 120’ 180’ 20’ 30’

Craniospinale 7770

60‛ 180’ 240’ (fusion) 480’ 600’ 30’ 45’

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10/22/2018 37 “Receiving radiotherapy could be compared to taking an airplane flight. It can be an uncomfortable and scary process for some people, but it is often necessary to get from point A to point B”.

Radiation Offers New Cures, and Ways to Do Harm

January 24, 2010