Turin Bnct Moss

Turin, 23rd May 2008Accelerator Based Neutron Sources

Accelerator-based versus

Reactor-based neutron sources for BNCT –

an ISNCT perspective

Ray Moss(Secretary/Treasurer ISNCT)

Sector Leader Medical Applications, High Flux Reactor Unit,

Institute for Energy, Joint Research Centre, Petten,The Netherlands


Contents

ISNCTBNCT

HistoryStatus

Reactors or Accelerators?Future of BNCT


ISNCT

ISNCT CONSTITUTION

Article I NAME OF SOCIETYThe organization shall be called The International Society for Neutron Capture Therapy.

Article II PURPOSE OF SOCIETYThe purpose of the Society shall be to promote widespread interest in neutron capture therapy and related forms of management of cancer and other diseases with present emphasis on neutron capture therapy. This promotion includes the holding of scientific meetings and other such endeavors as seen appropriate to the Executive Board.


1st 12-14 October 1983 Cambridge, MA, USA Brownell/Fairchild 2nd 18 - 20 October 1985 Tokyo,Japan Hiroshi Hatanaka3rd 31 May - 3 June 1988 Bremen, Germany Detlef Gabel 4th 4-7 December 1990 Sydney, Australia Barry J. Allen 5th 14-17 September 1992 Columbus, OH, USA Albert J. Soloway6th 31 October - 4 November 1994 Kobe, Japan Yutaka Mishima7th 4-7 September 1996 Zurich, Switzerland Börje Larsson 8th 13-18 September 1998 La Jolla, CA, USA Fred Hawthorne 9th 2 – 6 October 2000 Osaka, Japan Keiji Kanda10th 8- 13 September 2002 Essen, Germany W. Sauerwein11th 11-15 October 2004 Boston, USA Robert Zamenhof12th 9-13 October 2006 Takamatsu, Japan Yoshi Nakagawa13th 2-7 November 2008 Florence, Italy Aris Zonta

Biennial Congresses on NCT


Committee for Standards in Dosimetry

Committee for Standards & Protocols in Clinical Trials

Committee for Standards in Treatment Planning

Committee for Financial Auditing

Committee for Standards in Accelerators

Committees on NCT


BNCT is based on the ability of the isotope 10B to capture low energy neutrons to produce two highly energetic particles with low range in tissue.

What is BNCT ?Boron Neutron Capture Therapy

gamma0.48 MeV

10B

0.84 MeV

7Li

1.47 MeV

4He(alpha)

nth


Success of BNCT requires:

a large number of 10B atoms must be localised selectively within the tumour cells

a sufficient number of thermal neutrons must reach and be captured by 10B


How to deliver thermal neutrons to the boronated tumour cells?

Possible sources of neutrons, include:

• Nuclear reactors• Accelerators• Radioisotopes (Cf 252)• Neutron Generators (D-D / D-T)

En » … MeV


Neutron Beams for BNCT

Generation 3: Next wave of US trials (epithermal neutron beams):-1. M.I.T.R.-II, 1994-1999 [18]2. BMRR, 1994-1999 [53]- In total, 71 patients

Generation 1: Early US trials:-1. Brookhaven Graphite Research Reactor (BGRR), 1951-61 [28]*2. Brookhaven Medical Research Reactor (BMRR), 1959-61 [17]3. M.I.T. Reactor, 1959-61 [18]- In total 63 patients

Generation 2: Japanese Reactors:1. Hitachi Training Reactor, 1968-75 [13]2. JRR-3 (JAERI), 1969 [1]3. JRR-4 (JAERI), 1990 … 1999 [13]4. Musashi I.T.R., 1977-89 [>100]5. Kyoto Univ. Research Reactor (KURR), 1975, 1981, 1990… [>60]6. JRR-2 (JAERI), 1990 [33]all above reactors use(d) thermal neutrons -In total, over 200 patients


Present Neutron Beams used in BNCT

2. JRR-4 (JAERI) 1998 [>10, glioma, meningioma]3. KUR, Kyoto, Japan 1998 [>50 head and neck]3. VTT, Finland 1999 [>100, now mainly head and neck]4. Rez, Czech Rep. 2000 [5, glioblastoma]5. Studsvik, Sweden 2001 [>40]6. MIT, USA 2002 [7]7. Pavia, Italy 2001 [2, extracorporeal liver]8. Bariloche, Argentina 2003 [3, skin melanoma]9. THOR, Taiwan 200810.HANORA, S. Korea 2008

Generation 4: new generation

1. HFR Petten 1997 [26-glioblastoma, 4-melanoma metastases]

With imminent closure??

ALL using nuclear research reactors


Status ???

Recent results (ICNCT 2006)

Both in Japan (Osaka University) and Finland (Helsinki), successful treatment of Head and Neck cancers.

Finns also showed good results for recurrent glioblastoma. Argentina reported on the successful treatment of multinodular skin melanoma (3 patients).

Japan reports on successful BNCT for Cutaneous and Mucosal melanoma.

Japan (Tsukuba) results of a combined photon + BNCT study (glioblastoma), the outcome is very good.

Other studies for the treatment of thyroid cancer, melanoma and head and neck cancers (all in Japan).


HFR Petten

reactor beam tube patient


Which type of cancer?

Energy of neutrons required??


Factors in beam design –

Therapeutic gain

- is defined as the ratio of the total dose in the tumour at depth to the maximum dose in the healthy tissue.

epithermal neutrons utilise the overlying tissue to lose their energy, principally through elastic scatter with hydrogen nuclei, and become thermalised


“SLOW” (THERMAL) NEUTRONS

- low penetration in tissue

- high reaction rate 10B(n, )7Li reaction

“FAST” (EPITHERMAL) NEUTRONS

- high penetration in tissue

- low reaction rate 10B(n, )7Li reaction

Prague, 11-12 Nov 2005


Dose components in tissue, due to a reactor beam

Neutron absorbed dose Dn

Gamma ray absorbed dose Dg

Nitrogen neutron capture absorbed dose DN

Boron neutron capture absorbed dose DB


• epithermal neutron flux 109 neutrons/cm2s (at the therapy position)

• neutron energy ~ 1 eV to ~ 10.0 keV

• gamma dose rate 1.0 Gy/hr

• fast neutron dose rate 0.5Gy/hr

• current:flux (J/) ratio > 0.8

Neutron beam requirements

- the parameter J/ reflects the forward directionality (degree of collimation) of the beam of neutrons, which equals 0.5 for a completely isotropic beam and 1.0 for a purely parallel beam


Present Reactor-based Neutron Beams for BNCT

Japan Atomic Energy Research Institute, Tokai , Ibaraki, JapanHFR Petten, Netherlands

MIT, Boston, USA


Examples of materials used in beam designs for BNCT at various reactors

ReactorsModerators Filters Attenuators

BMRR H2O, C Al, Cd, Al2O3 Bi

MITR-II H2O, D2O Al, S, Cd, Li Bi, poly-6Li

HFR H2O Al, Ti, S, Cd Ar, poly-B

fission plate Al2O3, Al, H2O Al, LiF3 Bi, Pb, 6Li

Mu.ITR Al, C, H2O Al, LiF3 Bi

TRIGA C, H2O LiF3 Bi, Pb

R2-0 Al, H2O/D2O Al, Li, teflon Bi, Pb, 6Li

FiR I (TRIGA) Al Fluental Bi


Examples of beam parameters for various epithermal neutron beams Reactors Epithermal Fast neutron dose Gamma dose Current/flux

neutron flux per epithermal neutron (109/cm2s) (10-13Gy/cm2) J/

BMRR 1.8 4.3 1.3 0.67MITR-II 0.2 12.5 14.0 0.55 HFR 0.33 8.6 10.3 0.98 MITR/fission plate 18.0 1.3 1.0 -BMRR/fission plate 12.0 2.8 1.0 0.78FiR I (TRIGA) 3.5 2.6 1.0 - R2-0 3.2 5.6 7.1 0.80WSU 0.96 3.3 1.6 0.77THOR, Taiwan 3.4 2.8 1.3 0.8


Is there an optimal approach ?

Many variables

Reactor type

Tumour to be treated, size, location, depth …….

Boron compound to be used ..............

Use of a variable, dynamic filter arrangement,

producing a shift in neutron energy spectrum, changing neutron intensity,a rotating beam or patient,………….

Theoretically – YesBut practically ….No

BNCT facility to suit the type of tumour to be treated



• 2 cameras (one fixed, one moveable placed on a tripod close to the patient)• 2-way intercom (communication with the observation area)• microphone (patient-to-medical staff)• 4 electro-optical laser positioning devices• lighting (special non-reflecting shades)• wash-basin, with hot warm water• anti-static, low conducting floor covering• various electrical (earthed) sockets placed around the room• aluminium storage rack

• aluminium therapy table, moveable in all 3 orthogonal directions (electrical motor to move the table in the vertical direction• a stop/start button, to initiate the procedure to start treatment• air conditioning• infra red sensors to detect presence of unauthorised personnel (causes closure of the beam shutters)• numerous micro-switches on main door and labyrinth door to detect the open/ close status of the doors• electrical interlock system.

The irradiation room has been built to reflect as close as possible, and within reason, a hospital-type environment. As such, the following items have been installed :-

The BNCT Facility at the HFR Petten


Monitoring the patient during treatment


BNCT - HFR Petten

The BNCT-Wing - arrival of patient


HFR Petten

BNCT is:• complex• performed outside a hospital environment• performed in a nuclear reactor• Not CONVENTIONAL treatment

BNCT is:• multi-disciplinary

Reactors have been and are still being used to treat patients by BNCT


Presentations at the last ICNCT 2006, Takamatsu, JapanAccelerator-based systems for BNCT

IPPE, Korkachov, RussiaHanyang University, Seoul, South KoreaTohoku University, JapanIBA – dynamitron – JapanHitachi – JapanCNEA, ArgentinaBudker INP, Novosibirsk, RussiaKURR, Kyoto, Japan

THE major problem is that nuclear reactors for BNCT use,are very unlikely to be built and located in a hospital –Accelerators already exist in hospitals!


The Medical Physics Building in Birmingham

Cyclotron vault

Dynamitron

Protons

NeutronsLi target, Beam moderator / shield


The actual treatment facility (mid 2003)

Proton beam-tube

Heavy water reservoir

FLUENTALTM moderator

Li-polythene delimiter / shield

Heavy water inlet

To pumps / chiller

Neutron source is > 1 x 1012 s-1


Birmingham, UK


In conclusion ……

Reactor-based facilities have been used, and are still being used for BNCT, for over 50 years.

Economical and logistical reasons – difficult to sustain

Accelerator-based facilities are the future of BNCT

BUT they must be able to demonstrate that the required beam characteristics can be achieved

Technology

Turin Bnct Moss