Estado Actual en la Radioterapia con Protones. Dra. Berta Roth 20 de Octubre de 2017

(1)

Estado Actual en la Radioterapia

con Protones

Dra. Berta Roth

20 de Octubre de 2017

(2)

Radioterapia en 2017

Precisión

Individualización

(3)

Radioterapia ¿Que podemos hacer mejor?

• IMRT, IGRT

• Dosis por fracción • Protones

Campo

• Imágenes funcionales • Radiobiología

Target

• Nuevas drogas • Biología tumoral

• Marcadores Predictivos biológicos

Modificadores

biológicos

(4)

cost /

sophistication

precision

2D RT

IMRT

(XR Intensity modulation)

IGRT

Image guided

3D RT,

conformal stereotactic radiotherapy cyberknife tomotherapy Carbon ions protons

photons

« hadrons »

>80% radiotherapy

(5)

¿Por qué la protonterapia?

• Mayor precision en la conformación del tratamiento

• Menor dosis a tejidos sanos

• Mayor daño al DNA tumoral

• Mayor efecto en tumores hipoxicos

• Menor reparación de daño sub-letal y potencialmente

mayor daño letal

(6)

(7)

Highest Dose is near the point of beam entry. Tumor Dose is

less than the entry dose. Dose is also delivered beyond the tumor target.

Fotones

(X-Rays)

Protones

(8)

(9)



Ballistic

advantages

 No radiation beyond the Bragg Peak tumor;

 Homogeneous dose along the defined modulation

 Distal & Proximal Conformality to tumor shape (PBS)

Example: Single Field Uniform Dose using in Pencil Beam Scanning

9

(10)

(11)

(12)

(13)

(14)

(15)

Protones: Beneficios Clínicos

15

Tumor control

Toxicity

PR

OBAB

ILI

TY

DOSE OF RADIATION

Photons Protons Widening of the Therapeutic Ratio

(16)

(17)

Protones: Beneficios Clínicos

17 0 10 20 30 40 50 60 70 80 90 100

Current standard (IMRT photons) Protons P rob abili ty (%)

Complications Local tumour control

Improvement of local tumor control Prevention of complications Photons Protons

Courtesy of Prof Lagendijk

Probab

ili

ty



Mejor control local



Menores

complicaciones en

tejidos sanos



Menos dosis

integral (segundos

primarios)



De elección en

re-irradiación

(18)

(19)

19

Oct. 2015 data from a leading center in the US

(20)

(21)

(22)

(23)

(24)

23 52 60

Trial type

RCT NonRandomized, comparative others 24 Source: http://www.clinicaltrials.gov End February 2016

 135 prospective clinical trials on ClinicalTrials.gov with status of ‘ongoing and/or recruiting’

 Randomized Controlled Trials have increased to 23

 Non Randomized Studies have increased to 52

3 9 5 11 8 5 17 1 6 17 9 19 16 1 ₈

Ongoing clinical trial Total 135

ocular head and neck spine liver

pancreas esophagus, anal prostate uterus, cervix bone soft tissues lung

(25)

(26)

(27)

(28)

(29)

(30)

Portonterapia en T. Cabeza y Cuello

(31)

Proton therapy for Pediatric Tumor

31

Side Effects* Protons Photons

Restrictive Lung Disease 0% 60% Reduced exercise capability 0% 75%

Abnormal EKGs 0% 31%

Growth abnormality 20% 100%

IQ drop of 10 points at 6 years 1.6% 28.5% Risk of IQ score < 90 15% 25%

Courtesy of Newhauser et al PMB 2009

(32)

(33)

(34)

(35)

(36)

(37)

Costo Efectividad de la Protonterapia: MD Anderson

37



MD Anderson

 T. Cabeza y Cuello  50 to 60% reducción de gastrostomia

 IMPT para orofaringe es costo/efectivo

 Mama  Protones es más económico que otras técnicas conformadas de tratamiento con fotones

(38)

Costo Efectividad de la Protonterapia

38 38

CONCLUSIONS: The current results provide the first evidence-based

guide for identifying children with brain tumors who may benefit the most from Therapy with respect to endocrine dys-function. Proton-Therapy may be more cost effective for scenarios in which radiation dose

to the hypothalamus can be spared, but protons may not be cost effective when tumors are involving or directly adjacent to the hypothalamus if there is a high dose to this structure. Cancer

(39)

Costo Efectividad de la Protonterapia

39 39

CONCLUSIONS: With greatly limited amount of data, PBT offers promising cost-effectiveness for pediatric brain tumors, well-selected

breast cancers, loco-regionally advanced NSCLC, and high-risk head/neck cancers. Heretofore, it has not been demonstrated that PBT

is cost-effective for prostate cancer or early stage NSCLC. Careful

patient selection is absolutely critical to assess cost-effectiveness. Together with increasing PBT availability, clinical trial evidence, and ongoing major technological improvements … Cancer

(40)

RACIONAL DE LOS PROTONES

EN CÁNCER DE MAMA

• ES UNA ENFERMEDAD ALTAMENTE CURABLE

• PACIENTES LARGAS SOBREVIVIENTES

(41)

RT en MAMA: toxicidades cardíacas asociadas

(Darby et al., NEJM, 2013)

(42)

ANATOMIA: ARTERIAS CORONARIAS

(Nilsson, JCO, 2011)

1+2+

3 =

Right CA

5+6 =

Left main

7+8+9+10 =

Left Anterior descending

Lt Tangential fields = Lt breast/chest Wall

(43)

Altas dosis de RT en OAR

• IMN izq, LAD,

VD y VI

recibirán dosis

completa.

• IMN der, RCA

recibirá altas

dosis.

(44)

Protones en Ca Mama

44 44

IMRT PT

Reduction of Side Effects

 Reduced dose to the heart

 Reduced dose to the lung

 Reduced dose to the left anterior descending

artery

Images Courtesy of Dr. S. Both, Penn Med.

Post Mastectomy trial on-going : NCT01340495

Complication Left Breast Right Breast

Chest pain 26% 12%

Coronary art. dis. 25% 10%

Myocardial Infrac. 15% 5%

(45)

PROTONES Y PARRILLA COSTAL

(Mac Donald S et al., Rad Oncol, 2013)

PROTONS PROTONS

PROTONS

(46)

Trial RADCOMP

• Randomized control trial for protons vs photons for patientes reciving Radiation for

non-metastatic breast cancer in reducing major cardiovascular events (MCE)

• PCORI sponsored

total 1716 patients

Dose specification 45-50Gy in 1.8-2Gy fractions with o whithout tumor bed or chest wall boost

Hypothesis

For patients with locally advanced breast cancer proton therapy will reduce the 10 years MCE after radiation from 6.3% to 3.8%