Session 1: Radiobiology in therapy and space Marco Durante

0

10,000

20,000

30,000

40,000

50,000

60,000

70,000

80,000

90,000

100,000

2006 2007 2008 2009 2010 2011 2012

Total Protons Carbon He, pions, others

End  of  year   Total   Protons   Carbon  He,  pions,  others  

Tot  per  year  

2007   61855   53818   4450   3587      2008   70051   61122   5342   3587   8196  2009   76266   67097   5582   3587   6215  2010   84492   73804   7101   3587   8226  2011   93547   81121   8839   3587   9055  

Worldwide Patients Statistics yesterday 26/02/12

M.Jermann A.Mazal PTCOG

Status & Perspectives in Particle Therapy – Alejandro Mazal

Depth dose distribution for ions

U. Weber

Status & Perspectives in Particle Therapy – Alejandro Mazal

Damage complexity is largely dependent on ionisation density of the radiation

30-40% low-LET = complex

90% high-LET = complex

Simple DSB

Complex DSB

Clustered damage

1 2 30

10

20

30

40

50

60

70

80

90

100

or more

pe

rcen

tag

e o

f to

tal

number of lesions in cluster

low LET high LET

Peter O'Neill - Molecular basis for the relative biological effectiveness of densely ionizing radiation

10 µm 10 µm 10 µm

55 MeV carbon 5 × 5 µm² matrix

20 MeV protons randomly distributed

20 MeV protons 5 × 5 µm² matrix 117 protons per spot

Günther Dollinger - Low LET radiation focused to sub-micrometer shows enhanced radiobiological effectiveness (RBE)

Right Ventricle Hypertrophy

Pulmonary/Cardiac function loss Early radiation-induced

vascular damage

Limits tumor dose escalation

Pulmonary Hypertension

Early radiation-induced vascular damage

Angiostatin-converting enzyme (ACE) inhibition ameliorates pulmonary/cardiac function, but only when the heart is co-

irradiated

Sonja van der Veen, University of Groningen, The Netherlands

•  Dose deposition at 500nm around a AuNP of 100nm with a 85 keV X-ray beam. §  In water

Simulation results Dose deposition around a AuNP of 100nm

■ 7

§  With a centred AuNP

§  AuNP : Increase of the dose up to a factor 100 with quasi-isotropic diffusion.

1µm

X-ray source

Z

X

Dose (eV/g)

8e11

6e11

4e11

2e11

0

1µm

X-ray source

Dose (eV/g)

Z

X

NP

1e14

8e13

6e13

4e13

2e13

0

Rachel DELORME CEA, LIST, France

Michael Krämer

Michael Krämer

0

1

2

3

4

5

6

REI

D in

%

NASAestimate

our work NASAestimate

our work

Lunar, long (0.084 Sv)Mars, swing (1.03 Sv)Mars, surface (1.07 Sv)

Uwe Schneider,

Cancer risk above 1 Gy and the impact for space radiation protection

0.0001

0.001

0.01

0.1

1

0 20 40 60 80 100 120 140

Distance from Field Edge (cm)

Neut

ron

Dose

equ

ival

ent/

Prot

on D

ose

Hall's Paper, HCL (160 MeV)

LLUMC Snoopy Neutron Detector(250 MeV)

LLUMC CR39 Detectors (250 MeV)

Yan's Paper, HCL, Boston BonnerSpheres (160 MeV)

MPRI, Neutron Bubble detector (150Mev)

SOI Microdosimeter (225MeV)

Expon. (Hall's Paper, HCL (160MeV))

Courtesy of A. Wroe C. Rossi-LLUMC. ESTRO 2007

Ex : How potential applications and solutions can be suddenly affected: Use of passive delivery systems of proton beams for pediatric treatments

Measured Neutron Dose at LLUMC

Status & Perspectives in Particle Therapy – Alejandro Mazal

Gaboriaud & al, Curie!

Electrons!+ photons!

St.Clair & al, MGH!

IMXT!

Photons! Mira

lbel

l!

PEDIATRICS! (medulloblastoma)!!

Issues:!T.control!!Sequelae!Secondary T!Cognigtive!…!!!

Lomax & al, PSI!

Protons!

(court.Varian)

Status & Perspectives in Particle Therapy – Alejandro Mazal

Secondary Malignant Neoplasms (SMN) in particle therapy Comparison of relative radiation dose distribution with the corresponding relative risk distribution for radiogenic second cancer incidence and mortality. This 9-year old girl received craniospinal irradiation for medulloblastoma using passively scattered proton beams. The color scale illustrates the difference for absorbed dose, incidence and mortality cancer risk in different organs.

Radiation Absorbed Dose

Risk of SMN Incidence

Risk of SMN Mortality

Newhauser & Durante,

Nature Rev. Cancer 2011

In patient dosimetry (uterus dose for a pregnant woman)

Total dose < 0.3 mSv

Münter et al., Fertil Steril. 2010

Very low stray radiation

reduced risk of secondary

cancers or teratogen effects

We know how to deal with the technology, but is bulky and, mainly, too expensive

Protons stops but we do not know exactly where

Ions have a strong biological effect, but we do not know exactly the values

Thousands of patients have been treated but there are critics on the lack of clinical trials

In spite of the experience of the existing centers there are still non realistics business plans

CONCLUSIONS Status & Perspectives in Particle Therapy – Alejandro Mazal

~ 200 shifts/year for reducing uncertainty on cancer risk from 1500% to 50% in 20 years

Outlook •  Most of the uncertainty in particle therapy and

space radiation protection is due to biology, not physics

•  Physics can lead to significant technical improvements and reduced costs but biology can lead to major breakthrough

•  Hot topics are RBE, genetic background, hypofractionaction, vascular damage, nanotechnologies, adaptive TP, angiogenesis, metastasis, late effects and second cancers

•  Beamtime and easier access to facilities needed