Student: Amin Hosseini,

Tutors:

Prof. Roberto Sacchi,

Dott. Simona Giordanengo

ANALYSIS OF THE DOSE DELIVERY

OUTPUT DATA COLLECTED IN 2012

(JAN-OCT) AT CNAO

OUTLINES

Introductions:

Hadron therapy(benifits)

CNAO( General and current activities)

Dose Delivery at CNAO( instruments and Data flow)

Methods:

Issues and solutions of measured Particles and Positions

Dose Distribution (simulations and comparisons)

Results:

Reproducibility of measured position and particles( Jan-Oct 2012)

Focus on a patient

Results of the Dose comparisons(with known uncertineties)

Prespectives and conclusion

Publications

HADRONTHERAPY

Benefits:

Physical properties of Proton:

Low dose is on surface

High dose in depth (most energy at end of range)

High precision on dose delivery (penetration depth is well defined and adjustable)

Dose to normal tissue minimized

Minimal lateral scattering and fragments effect.

To cover of the whole volume of tumor it is necessary to obtain Spread Out Bragg Peak (SOBP) as composed of numbers of Bragg peaks with different energies.

The hadrontherapy is effectively used to treat very difficult tumors that are located between or nearby vital organs at risk.

Fotoni Protoni

CNAO (NATIONAL CENTRE FOR ONCOLOGICAL HADRONTHERAPY )

first hospital in Italy(Pavia) for treating deep

seated tumors by a synchrotron accelerator.

Accelerator of CNAO:

-2electron cyclotron resonance sources run

continuously+ GSI linac+ injecting of particles in main

ring of synchrotron as high energy beam transfer.

- Beam E range: protons (60-250 Mev/u),carbon(120-

400 Mev/u), Max particles/spill=10^10(p)-4x10^8(c).

Three treatment rooms:

-Three identical horizontal lines

- One vertical line (in one of the rooms)

Clinical activities:

- On October 2011 the comissioning finished and

The Treatments on human started with protons,

- treatments on 30 patients are concluded (with proton)

- Since November 2012 treatment with Carbon ions havebeen started.

Dose Delivery(DD)

last part of accelerator, before target (include 3 sections):

Two identical scanning magnets(deviation of the beam)

Monitoring System:

- placed at a Nozzle

- Two independent boxes for safety

reference isocenter (target)

3D (X,Y,Z) ACTIVE BEAM DELIVERY

Scanning magnets

Synchrotron

Linac

Carbon source

Proton source

Monitorsystem

x

En

z

y

TARGET CHARACTERISTICS

The target in treatment planning system:

Divides to several slices (corresponding toBrag-peaks of Energy)

Each slice is subdivided into spots

definition of coordinates as ( Np,ΔX,ΔY,En)

per spot on the reference isocenter

A DOP file is created with prescribed of the spots characteristics.

The spots are engraved by beam -without switching off within spots

Positions (in transvers plan of reference isocenter) and delivered particles of total spots are recorded by a fast control system

A LOG file is created at the end of treatment as measurement of spots characteristics.

z

ISOCENTRO

Magneti scanning

Beam

ZmY=5460 mm

Zs=873.5 mm Zp=754 mm

Nozzle

X

Y

ZmX=6180 mm

L=553 mm

Inputs-outputs details of the DD

Number of Particles

Spot Positions(X,Y) in isocenter

Spot Positions(X,Y) in isocenter

Number of counts ,Number of counts of Integral 2

increased by 10 %

Spot positions in Nozzle reference system

Currents (Ix,Iy) for Scanning Magnets

K(E)* KTP*Kfit

Kx, Ky

Treatment «DOP files»

Input FPGA binary files «SLD files» (1 file/slice)

Calibrations

Bρ*F(E)+I0(E)

Output FPGA binary files (1 file/spill)«DDD files»

Delivery and Monitoring

Treatment

The SLDs and DDDs files are used for data analysis as input and output of DD

AIMS OF THE CURRENT STUDY

finding a clinically significant evaluation of the accuracy of Delivered Dose andof the performance of the delivery system (DD) at CNAO.

Two crucial parameters are: number of real delivered particles and measured positions of the spots

There are 4 issues for measuring the key parameters also four solutions

Several programs are designed for the evaluations by LabView software

The Prescribed and measured Parameters are useable for simulation of the Dose also comparisons.

Prescribed (SLD)

Counts integral 1,2Position X,Y strips

Currents X,Y

Measured(DDDs)

Counts integral 1,2Position X,Y

strips(sometimes)Currents X,Y

Comparison

ISSUE OF MEASURED POSITIONS BY STRIP.CH

Positions are measured by computing of center-of-gravity of thebeam profiles

when the number of counts are lower than ~100 or noise in strips

channels, the calculation of spot position is not performed

Since the abundance of missed spots are non-negligible, finding asolution are considered.

Solution:

-The measured current are exist for all of spots

Linear relation between measured Position by the s.ch and currentof magnetic dipoles (for bundle of spots with same Energy).

Day by Day the fit parameters are extracted

1- when there is noise in integral ch.1 and integral2decides to stop the beam for these spots. ~10%more than prescribed, are delivered to these spots

THREE ISSUES OF MEASURED PARTICLES:

0

2

4

6

0 50 100 150

% O

F SP

OTS

ST

OP

PIN

G B

Y IN

TEG

RA

L 2

FIELD N°Representation of spills by differential recorded counts vs time (in DDDs)

Time

3

cou

nts

2-Examples of Dark counts in between spills (during 3 sec)

and effects on between spills spots (critical spots) cause over/under Dose on these spots.

3-The Chopper can not stop the beam promptly(…> 100

microsecond) and affects at the last spot of each slice,

SOLUTIONS FOR EVALUATION OF REAL DELIVERED

PARTICLES :

1- spot by spot the decision of integral chambers 1 or 2 are carried out in the designed software.

2-the Dark counts are subtracted from the measured counts of the critical spots.

3- measured counts due to the chopper effects are considered.

Measured counts of the spots

(considering of the three effects)

Real delivered particles of spots

K(E)* KTP*K fit

SIMULATION AND COMPARISONS

OF DOSE DISTRIBUTIONS TO

EVALUATE THE EFFECT OF THESE

UNCERTAINTIES

After evaluation of the particles and positions:

A forward planning has been done:first with required spot characteristics (from DOP files) then with measured values

A TPS used is the IBA-INFN TPS developed by our colleagues , available in Torino as Dose Engine Kernel(DEK) to obtain dose distribution

The dose distributions are converted to DICOM format

using Gamma-index (as a relevant parameter for the dose distribution comparison) by OmniPro-I’mRT software.

The dose simulation&comparison procedures:

WHAT IS THE GAMMA-INDEX?

The gamma-index is a quantitive parameter using to compare dose distribution(prescribed with measured dose)

In IMRT with photons the gamma is computed in 2D (film ...) for comissioning of treatment planning.

At the moment, a commercial software (OmniPro-I’mRT) is used for the gamma evaluation within slices

Currently, I am involved in developing a custom algorythm for the evaluation in 3D.

RESULTS

Patient code

Total fields

Total slices

Total spills

Total spots

Min-Max spot(s) in

slices

Total prescribed particles

Total delivered particles

Min-Max E(Mev/u) From: To:

A110002 44 2945 10086 105683 1-1145 1.37299E+13 1.37305E+13 62-227 1-Feb 23-MarA110010 79 3168 3365 21682 1-214 1.00545E+12 1.00666E+12 62-143 22-Feb 11-AprA110011 67 2930 9858 23354 1_312 1.30399E+12 1.30461E+12 68_148 23-Jan 14-MarA120001 62 2502 5979 10905 1-163 7.27737E+11 7.27877E+11 62-139 30-Jan 19-MarA120002 110 4103 8717 18875 1_270 1.13623E+12 1.13711E+12 62-142 24-Jan 15-MarA120003 77 3809 5581 47198 1-413 2.01104E+12 2.01228E+12 62-150 2-Feb 27-MarA120005 71 2383 2964 6582 1_95 6.86423E+11 6.86912E+11 74-127 15-Mar 11-MayA120006 81 3454 3992 10167 1_131 8.19683E+11 8.20353E+11 62-144 15-Mar 11-MayA120008 67 4111 7565 64232 1-603 2.96127E+12 2.96346E+12 62-158 27-Mar 24-MayA120010 68 5496 7757 67579 1-794 7.28717E+12 7.29061E+12 101-222 10-Apr 31-MayA120011 63 3692 11880 36255 1-333 1.68583E+12 1.68749E+12 66-155 6-Jun 26-JulA120012 76 2312 2808 7370 1_110 6.87348E+11 6.87979E+11 74-133 2-May 20-JunA120013 73 2173 2577 5513 1_133 6.32572E+11 6.33345E+11 76-124 2-May 22-JunA120014 68 3007 3326 8973 1_150 7.68071E+11 7.69205E+11 62-148 21-May 10-JulA120015 73 6710 8034 24347 1-207 2.34661E+12 2.34989E+12 62-198 14-May 4-JulA120016 71 2781 5394 12979 1-148 8.31436E+11 8.32428E+11 62-153 31-May 18-JulA120018 144 6318 10300 14991 2-212 1.10895E+12 1.11092E+12 62-139 6-Jun 26-JulA120023 70 3340 3769 10782 1_141 8.81614E+11 8.82885E+11 62-138 13-Aug 3-Oct

PHYSICAL INFORMATION OF TREATMENTS

(JAN-OCT, 2012)

In total, 18 patients , 1365 fields analyzed

REPRODUCIBILITY OF BEAM POSITION X

0

20

40

60

80

100

2-J

an

12

-Jan

22

-Jan

1-F

eb

11

-Fe

b

21

-Fe

b

2-M

ar

12

-Mar

22

-Mar

1-A

pr

11

-Ap

r

21

-Ap

r

1-M

ay

11

-May

21

-May

31

-May

10

-Ju

n

20

-Ju

n

30

-Ju

n

10

-Ju

l

20

-Ju

l

30

-Ju

l

9-A

ug

19

-Au

g

29

-Au

g

8-S

ep

18

-Se

p

28

-Se

p

8-O

ct

18

-Oct

Frac

tio

n o

f sp

ots

(%

)

Date

Jan-Oct 2012, positions X (strip/current)

|%dX|<0.5 mm |%dX|<1 mm |%dX|<1.5 mm

dx=( measured-prescribed )X

0

20

40

60

80

100

2-J

an

12

-Jan

22

-Jan

1-F

eb

11

-Fe

b

21

-Fe

b

2-M

ar

12

-Mar

22

-Mar

1-A

pr

11

-Ap

r

21

-Ap

r

1-M

ay

11

-May

21

-May

31

-May

10

-Ju

n

20

-Ju

n

30

-Ju

n

10

-Ju

l

20

-Ju

l

30

-Ju

l

9-A

ug

19

-Au

g

29

-Au

g

8-S

ep

18

-Se

p

28

-Se

p

8-O

ct

18

-OctFr

acti

on

of

spo

ts (

%)

Date

Jan-Oct 2012, positions X (current)|%dX|<0.5 mm |%dX|<1 mm |%dX|<1.5 mm

Each point correspond to one field

0

20

40

60

80

100

2-J

an

12

-Jan

22

-Jan

1-F

eb

11

-Fe

b

21

-Fe

b

2-M

ar

12

-Mar

22

-Mar

1-A

pr

11

-Ap

r

21

-Ap

r

1-M

ay

11

-May

21

-May

31

-May

10

-Ju

n

20

-Ju

n

30

-Ju

n

10

-Ju

l

20

-Ju

l

30

-Ju

l

9-A

ug

19

-Au

g

29

-Au

g

8-S

ep

18

-Se

p

28

-Se

p

8-O

ct

18

-Oct

Frac

tio

n o

f sp

ots

(%

)

Date

Jan-Oct 2012, positions Y (strip/current)

|%dY|<0.5 mm |%dY|<1 mm |%dY|<1.5 mm

0

20

40

60

80

100

2-J

an

12

-Jan

22

-Jan

1-F

eb

11

-Fe

b

21

-Fe

b

2-M

ar

12

-Mar

22

-Mar

1-A

pr

11

-Ap

r

21

-Ap

r

1-M

ay

11

-May

21

-May

31

-May

10

-Ju

n

20

-Ju

n

30

-Ju

n

10

-Ju

l

20

-Ju

l

30

-Ju

l

9-A

ug

19

-Au

g

29

-Au

g

8-S

ep

18

-Se

p

28

-Se

p

8-O

ct

18

-Oct

Frac

tio

n o

f sp

ots

(%

)

Date

Jan-Oct 2012, positions Y (current)

|%dY|<0.5 mm |%dY|<1 mm |%dY|<1.5 mm

REPRODUCIBILITY OF BEAM POSITION Y

dY=( measured-prescribed )Y

80

85

90

95

100

2-J

an

12

-Jan

22

-Jan

1-F

eb

11

-Fe

b

21

-Fe

b

2-M

ar

12

-Mar

22

-Mar

1-A

pr

11

-Ap

r

21

-Ap

r

1-M

ay

11

-May

21

-May

31

-May

10

-Ju

n

20

-Ju

n

30

-Ju

n

10

-Ju

l

20

-Ju

l

30

-Ju

l

9-A

ug

19

-Au

g

29

-Au

g

8-S

ep

18

-Se

p

28

-Se

p

8-O

ct

18

-Oct

Frac

tio

n o

f sp

ots

wit

hin

to

lera

nce

(%

)

Date

Jan-Oct 2012,%err of delivered Protons

|%err|<0.5 |%err|<1 |%err|<2.5

-0.15

-0.1

-0.05

0

0.05

0.1

0.15

0.2

0.25

0.3

2-J

an

12

-Jan

22

-Jan

1-F

eb

11

-Fe

b

21

-Fe

b

2-M

ar

12

-Mar

22

-Mar

1-A

pr

11

-Ap

r

21

-Ap

r

1-M

ay

11

-May

21

-May

31

-May

10

-Ju

n

20

-Ju

n

30

-Ju

n

10

-Ju

l

20

-Ju

l

30

-Ju

l

9-A

ug

19

-Au

g

29

-Au

g

8-S

ep

18

-Se

p

28

-Se

p

8-O

ct

18

-Oct

% e

rro

r

Date

%err total delivered particles %err of critical spots %err of integral1,normal spots %err of integral2,normal spots %err of chopper

REPRODUCIBILITY OF THE NUMBER OF DELIVERED

PARTICLES

FOCUS ON ONE PATIENT

0

20

40

60

80

100

26

-May

29

-May

1-J

un

4-J

un

7-J

un

10

-Ju

n

13

-Ju

n

16

-Ju

n

19

-Ju

n

22

-Ju

n

25

-Ju

n

28

-Ju

n

1-J

ul

4-J

ul

7-J

ul

10

-Ju

l

13

-Ju

l

16

-Ju

l

19

-Ju

l

22

-Ju

l

Frac

tio

n o

f sp

ots

(%

)

Date

A120016, positions Y (current)

|%dY|<0.5 mm |%dY|<1 mm |%dY|<1.5 mm

0

20

40

60

80

100

26

-May

29

-May

1-J

un

4-J

un

7-J

un

10

-Ju

n

13

-Ju

n

16

-Ju

n

19

-Ju

n

22

-Ju

n

25

-Ju

n

28

-Ju

n

1-J

ul

4-J

ul

7-J

ul

10

-Ju

l

13

-Ju

l

16

-Ju

l

19

-Ju

l

22

-Ju

l

Frac

tio

n o

f sp

ots

(%

)

Date

A120016, positions X (current)

|%dX|<0.5 mm |%dX|<1 mm |%dX|<1.5 mm

80

85

90

95

100

26

-May

29

-May

1-J

un

4-J

un

7-J

un

10

-Ju

n

13

-Ju

n

16

-Ju

n

19

-Ju

n

22

-Ju

n

25

-Ju

n

28

-Ju

n

1-J

ul

4-J

ul

7-J

ul

10

-Ju

l

13

-Ju

l

16

-Ju

l

19

-Ju

l

22

-Ju

l

Frac

tio

n o

f sp

ots

wit

hin

to

lera

nce

(%

)

Date

A120016,%err of delivered Protons

|%err|<0.5 |%err|<1 |%err|<2.5

-0.05

0

0.05

0.1

0.15

0.2

0.25

26

-May

31

-May

5-J

un

10

-Ju

n

15

-Ju

n

20

-Ju

n

25

-Ju

n

30

-Ju

n

5-J

ul

10

-Ju

l

15

-Ju

l

20

-Ju

l

25

-Ju

l

% e

rro

r

Date

%err total delivered particles %err of critical spots

%err of integral1,normal spots %err of integral2,normal spots

%err of chopper

Example of the gamma index for the central slice of a single field

3% - 3 mm

100% passing rate

2% - 2 mm

97% passing rate

Reproducibility of Gamma index

γ>1

γ>1

Required Dose distribution

50.00

60.00

70.00

80.00

90.00

100.00

110.00

26-May 31-May 5-Jun 10-Jun 15-Jun 20-Jun 25-Jun 30-Jun 5-Jul 10-Jul

Gamma 3%-3mm

Gamma 2%-2mmPas

sin

g ra

te (

%)

Selection of a central slice of the cube,

PERSPECTIVE AND CONCLUSION

• Method explained, results shown (Jan-Oct 2012) and were presented at the Medical physicists at CNAO

• 4 issues with solutions

• Other effects not considered (e.g. virtual source movement ?)

• Providing a tool for the gamma in 3D

• Evaluations of the treatments by Carbon and Proton ions will carry out for next step.

Publications: (in-progress)co-author of:

*THE CNAO DOSE DELIVERY SYSTEM FOR MODULATED ION BEAM THERAPY

first author of:

* Clinical performances of the Dose Delivery System at the Italian National Center for Oncological Hadrontherapy

CONFERENCE PAPERS

1. Hosseini MA, Attili A, Capasso L, Cirio R, et al, “An Innovative Monitor System for Centro Nazionale di AdroterapiaOncologica (CNAO) in Pavia (Italy)”, 1st MEFOMP International Conference of Medical Physics,2-4 November 2011, Shiraz-Iran.

2 .S. Giordanengo, M. Donetti, M. A. Garella, M. Lavagno, L. Capasso, R. Cirio, M. A. Hosseini, A. Mairani, F. Marchetto, S. Molinelli,C. Peroni, R. Sacchi, “First patients at CNAO: operational results of the dose delivery”, 51th annual meeting of particle therapy co-operative group(PTCOG), 14-19 May 2012, Seoul-South Korea.

3. L.Capasso, M.Donetti, G.Fattori, G.Baroni, R.Cirio, M.A.Garella, S.Giordanengo,M.A.Hosseini, F.Marchetto, C.Peroni, R.Sacchi,“An organ motion compensator for the CNAO Center of Oncological Hadrontherapy”,5thAlpe-Adria Medical Physics Meeting (AAMP), 3–5 May, 2012, Trieste, Italy.

4. M. A. Hosseini, M. Donetti, M. A. Garella, S. Giordanengo, M. Lavagno, L. Capasso, R. Cirio, F. Marchetto, C. Peroni, R. Sacchi, “Evaluation of the CNAO spot scanning technique based on the first clinical deliveries”,54th annual meeting &exhibition of AAPM, 29 July –2 August 2012,Charlotte,NC,USA.

5. M. A. Hosseini, S. Giordanengo, M. A. Garella, M. Donetti, L. Capasso, F. Marchetto, A. Mirandola, S. Molinelli, C. Peroni, R. Sacchi, R. Cirio, “EVALUATION OF THE DOSE DELIVERY ACCURACY ACHIEVED IN THE FIRST YEAR OF THE CNAO CLINICAL PRACTICE ”, 52th annual meeting of PTCOG, Germany (In progress).