Carbon Ion Radiotherapy at NIRS

Rationale, Technique, Results and Future…

Tadashi KAMADA, MD

Research Center for Charged Particle Therapy National Institute of Radiological Sciences

Chiba, JAPAN

ESTRO Teaching Course on Proton and Ions March 25-29

Uppsala, Sweden

Rationale Carbon ion beam has a definite range and the Bragg peak. In addition to this physical selectivity, ionization is enormous at the Bragg peak, while remains low at the plateau, showing biological advantages such as cell cycle independent effect.

Therefore, carbon beam could be a potentially curable armament for radio-resistant tumors with minimal normal tissue injury.

“Four Rs” in Radiobiology

From E. Hall : Radiobiology for the Radiologist

1920~1930s in Paris

Repair Redistribution Reoxygenation Repopulation

0

20

40

60

80

100

0 20 40 60 80 100 120 140 160

TUM

OR

CO

NTR

OL(

%)

DOSE (Gy)

γ-ray

Single fraction

5 Fractions 0

20

40

60

80

100

0 20 40 60 80 100 120 140 160

TUM

OR

CO

NTR

OL(

%)

DOSE (GyE)

Carbon 74 keV/ m m

Single fraction

5 Fractions

γ-ray Carbon

5 fractions

Ando et al. unpublished data at NIRS

Repair

Comparison of radiation cell survival levels in synchronized CHO cells irradiated with 4 Gy X-rays

and 2 Gy 70 keV/µm carbon ions.

Kato et al. unpublished data at NIRS

0.0001

0.001

0.01

0.1

1

0 5 10 15 20 25 30 35

Surv

ivng

frac

tion

Dose (Gy)

γ-ray

Hypoxic

Oxic

0.001

0.01

0.1

1 0 5 10 15 20 25 30 35

Surv

ivin

g fr

actio

n

Dose (GyE)

carbon

74 KeV/ hypoxic

74 KeV/ oxic

Oxygen effect

γ-ray Carbon

hypoxic oxic

Ando et al. Int J Radiat Biol 1999

Beyond “4 Rs” with C-ion Beam Low repair Cell cycle non-specific Low OER(re-ox) Low repopulation

Advantages of Fractionation ?

Hypo-fractionation matches with high LET conformal C-ion beam

Experiments with carbon ions and fast neutrons demonstrated that increasing their fraction dose tended to lower the RBE for both the tumor and normal tissues, but the RBE for the tumor did not decrease as rapidly as the RBE for the normal tissues.

These results substantiate that the therapeutic ratio increases rather than decreases even though the fraction dose is increased.

Another Biological Background for Hypofractionated Radiotherapy with Carbon Ion beams

Koike S, et al: Radiat Prot Dos. 2002;99: 405-408. Ando et al. : J.Radiat.Res. 2005;46:51-57. Denekamp J: Int J Radiat Biol. 1997;71: 681-694,.

To prove efficacy and safety of C-ion RT

Carbon Ion Clinical Trials at NIRS

a) Establish safe and precise C- ion RT technique b) Conduct phase I study ⇒ phase II study 1. Achieve local control in radio-resistant tumor 2. Demonstrate hypo-fractionation in common cancer (and conduct comparative study, if necessary)

Based on “high physical selectivity” & “biological effectiveness”

Technical aspect of carbon ion radiotherapy at HIMAC

Tech or Procedure

Immobilization Beam delivery Targeting Treatment planning Respiration gating Patch field Spacer insertion

Fixed beam line Passive beam Hitting a moving target SOBP; Dose description

Key-words

Simulation and Rehearsals Treatment Planning

CT gantry PSD

LED

Obtain CT data （Respiratory-gated）

Immobilization Devices

CT+MRI

CT+PET

Treatment Planning for Head and Neck Tumor Using Fusion Images

ACC

After RT

Before RT

Dose distributions

Fabrication of Bolus and Collimator

Collimator is made of brass

Bolus is fabricated with NC machine

3-D alignment to check accuracy

Treatment in 2007（Pats；642） Bolus≒2,500 Collimator≒1000 *MLC was also used

Trea

tmen

t Pla

nnin

g

Key-Tech for C-ion RT at NIRS

End-expiratory irradiation

Respiration gating for irradiation

Reduction of volume Minohara et al. IJROBP 47:1097-1103, 2000

50%

90%

64GyE/16Fx/4weeks

Patch Field Technique for Ion Beam

CT image 8 years after (Alive NED at 10 years)

Spacer Insertion Liposarcoma of the retroperitoneum（p/o rec) 54F

Spacer

After Gore-Tex

Colon

Before

Retroperitoneal liposarcoma

Before After 6 months

70.4 GyE/16fx with spacer

Key Tech in C-ion RT at HIMAC

• Respiration gating: 3089 patients lung, liver, pancreas, kidney, sarcoma etc • Patch field : 294 patients Head & Neck, para-spinal etc. • Spacer insertion :150 patients pelvis and abdomen

20

More than 3000 patients were treated with these techniques at NIRS.

The Image Intensifier was replaced by high resolution FPD

Treatment Room

Positioning with orthogonal projections

Horizontal Beam

Vertical Beam

I I FPD

Treatment Rooms

Room for Biological Experiments

Beam Lines for Physics Research

Ion Source Linear

Accelerators

Main Accelerator (Synchrotron)

HIMAC(Heavy Ion Medical Accelerator in Chiba)

• Ion : He ~ Ar Max energy: ~800Mev/n • Treatment room(3) Fixed vertical : room A Fixed horizontal : room C Fixed V & H : room B • The accelerated energy V. beam (290 or 350 MeV/u) H beam (290 or 400 MeV/u) • The range of C-ion beam in water 290-MeV/u : 15 cm 350-MeV/u : 20 cm 400-MeV/u : 25 cm • Maximum field size 15 cm by 15 cm

A B C

Specification of HIMAC

Sato et al. Nuclear Physics A. 1995; 588: 229—234 small

large

scatterer collimator compensator ridge filter

HIMAC Beam Delivery Techniques • Broad-beam(passive) irradiation

wobbler magnets

To produce uniform irradiation fields, a passive beam delivery system was employed. We use a pair of wobbler magnets and a scatterer. The range shifter is used for adjusting the residual range of carbon ions in the patient. The ridge filter is used to spread out the Bragg peak in the depth-dose distribution of carbon ions.

Kanai et al. IJROBP1999, 44:201-210

Irrespective of the size of SOBP, RBE value was estimated to be 3.0 at the distal part of SOBP. Ridge filter was designed to produce a physical dose gradient of SOBP so that the biological effect along SOBP became uniform. This was based on the biologic response of HSG tumor cells at 10 % survival level. The biologic response flatness along SOBP was checked by measurement of physical dose and dose-averaged LET.

Spread Out Bragg Peak in Carbon Ion Therapy at NURS

Kanai et al. Radiat Res 147:78-85,1997

0

1

2

3

4

5

6

7

0 50 100 150 200

Depth-dose profile of 12C - 290 MeV/n

Rela

tive

Dos

e [G

y or

GyE

]

Depth in Water [mm]

120 mm 100 mm80 mm

60 mm

40 mm

20 mm

Clinical Dose(GyE)

RBE=2.38

Ridge filter

3.0 0.0

0.5

1.0

1.5

2.0

2.5

-50050100150

Carbon 290 MeV/n, 60mm SOBP

HSG

HeLa

T98HT1080

HK

t heor y

Rel

ativ

e B

iolo

gica

l Dos

e

Residual Range [mm]

Biological check

SOBP

Results

The Domain of Carbon Ion Therapy

• with large proportion of hypoxic cells • do not well re-oxygenate • with broad-shouldered dose survival curves by low LET

radiation • slowly proliferating

Tumors ; biological view points for high LET beam(theoretical)

Tumors ; clinical context (practical) •empirically radio-resistant, such as sarcomas, melanoma, RCC, thyroid ca, and re-irradiation •located close to the radiosensitive organs ; para-spinal •decline other therapies such as second surgery, limb amputation, concurrent chemo-radiation etc. •unresectable or medically inoperable •All quest for better outcomes

Site ‘94 ‘95 ‘96 ‘97 ‘98 ‘99 ‘00 ‘01 ‘02 ‘03 ‘04 ’05 ‘06 ‘07 ‘08 ’09 ‘10 H＆N： All sites

Lung :Peripheral Central Locally advanced Med.L/N

Liver

Prostate: C-ion＋HR C-ion alone

B&STS

Uterus:Sqcc

Adc Brain

Skull base

Esoph: Pre-op/Radical

PK：pre-op

Radical

Rectum（P/0 rec）

Eye melanoma

Lacrimal gland

②16/4w

①18X/6w

①18x/6w ③ 16x/4w

①15x/5w

① 20x/5w

① X ray + chemo + C-ion

① 16x/4w

①

Preop, Radical (end)

① 16x/4w

② 9x/3w

③ 9x/3w

④ 9x/3w

② 12x/3w → 8x/2w → 4x/1w ③ 4x/1w

⑥ 4x/1w

②Hormone ③ High & Middle risk

Low risk

②C-ion alone ③+TMZ

② 16x/4w

② ③

① pre-op

Mucosal melanoma16x/4w

Phase I/II

Phase II

Sarcomas16x/4wks

② pre-op 8x/2w

① (5x/1w)

⑦ 16x/4w

1x/1day

④ 2x/2日

⑤ 16x/4w

①Pre-op 8x/2w ②Radical 12X/3wks

① 20x/5w

① 12x/3w

③ radical12x/3w ④+GEM

16x/4w

Protocols and Time Line of Carbon Ion Clinical Trials (1994-2010)

④ 12x/3w

Patient Distribution Enrolled in Carbon Ion Therapy at NIRS (Treatment: June 1994～July 2011)

Prostate 1382(20.9%)

CP:1057

Bone & Soft tissue 901(13.6%)

CP:666

Head & Neck 763(11.5%)

CP:440

Lung 695(10.5%)

CP:118

Liver 443(6.7%)

CP:213

P/O rectum341(5.2%

) CP:274

GYN170(2.6%)

Eye 114(1.7%)

CP:72

Pancreas 175(2.6%)

CP:1

CNS105(1.6%)

Skull Base 81(1.2%)

CP:52

Esophgus65(1.0%)

PA L/N 69(1.0%) CP:62

Lacrimal 23(0.3%)

Scanning 8(0.1%)

Re-irradiation 75(1.1%)

CP:16

Miscellaneous 1208(18.3%)

CP:538

Total 6,619

Clinical Practice： 3,509

1) C-ion RT is successful in the not treatable by other means

• Advanced Head & Neck cancers • Large skull base cancers • Post-op recurrent rectal cancer • Inoperable sarcoma • Re-irradiation after photon radiotherapy

• Lung cancer ( Single irradiation) • Liver cancer ( Two fractions) • Pancreatic cancer (8-12 fractions) • High risk prostate cancer (16 fractions)

2) Promising results are obtained in C-ion hypo- fractionated RT

Dose-fractionations determined by dose escalation studies for carbon ion RT at NIRS

6

Carbon Ion Radiotherapy for Head-and-Neck Tumors

Phase II (9602) n=360 64 or 57.6 GyE/16 fr./4 wks

April 1997～

94 95 96 97 02 03 04 05 98 99 00 01 06 07 08 09

June 1994～

Phase I/II (9301)

18 fr./4 wks

April 1996～

Phase I/II (9504)

16 fr./4 wks

～ ongoing

0 20 40 60 80 100 120 140 160 Tx T1 T2 T3 T4

Rec. after surgery Rec. after chemotherapy

Rec. after surgery & Chemo

Mizoe et al. Int J Radiat Oncol Biol Phys. 2004;60:358-364 Hasegawa et al. Int J Radiat Oncol Biol Phys. 2006;64:396-401 Yanagi et al. Int J Radiat Oncol Biol Phys. 2009;74:15-20

PRO

BABI

LITY

TIME IN MONTHS

5-year Local Control Rate ACC (129) 76% MMM(102) 76% Adeno(42) 77% SCC(20) 70%

Local Control according to Histological Type (Apr 97~Aug 09) Phase II (9602) for Malignant Head-and-Neck Tumors

Carbon Ion Radiotherapy for Head-and-Neck Tumors

Phase II (9602) n=360 64 or 57.6 GyE/16 fr./4 wks

April 1997～

94 95 96 97 02 03 04 05 98 99 00 01 06 07 08 09

June 1994～

Phase I/II (9301)

18 fr./4 wks

April 1996～

Phase I/II (9504)

16 fr./4 wks

～ ongoing

Phase II （with chemo）n=85 Malignant Melanoma

16 fr./4 wks + DAV x 5 courses

April 2001～

Phase II （high dose ）n=33 Bone & Soft Tissue

70.4 GyE/16 fr./4 wks

April 2001～

•Late recurrence in ACC with 57.6 GyE •High distant mets in melanoma •Poor local control in sarcomas with standard dose

→ 64 GyE

Local Control of ACC (n=129) according to Carbon ion Dose

57.6 GyE (n=75) 5-year; 73％

64 GyE (n=54) 5-year; 95％

TIME IN MONTHS

PRO

BABI

LITY

OF

LC

Phase II (9602) for Malignant Head-and-Neck Tumors

Combined Chemotherapy and C-ion RT for MMM

Local Control and Overall Survival of Mucosal Malignant Melanomas

TIME IN MONTHS

PRO

BABI

LITY

C-ions alone (n=102) 5-year; 76%

C-ions + DAV n=85) 5-year; 81%

PRO

BABI

LITY

C-ions alone (n=102) 3-year; 53%, 5-year; 37%

C-ions + DAV ( n=85) 3-year; 67%, 5-year; 62%

TIME IN MONTHS

Local Control Overall Survival

Five-year Survival Rates in Mucosal Malignant Melanoma of the Head & Neck

1) Gilligan D et al. Br J Radiol 1991; 64: 1147-1150. 2) Shibuya H et al. IJROBP 1992; 25: 35-39. 3) Chang AE et al. Cancer 1998; 78: 1664-1678. 4) Shah JP et al. Am J Surg 1977; 134: 531-535. 5) Patel SG et al. Head Neck 2002; 24: 247-257. 6) Lund VJ et al. Laryngoscope 1999; 109: 208-211. 7) Chaundhry AP et al. Cancer 1958; 11: 923-928.

Local Control and Overall Survival compared with Carbon Ion Dose

Bone and Soft-Tissue Sarcomas (Head & NECK) Low Dose Carbon vs. High Dose Carbon

TIME IN MONTHS

PRO

BABI

LITY

70.4 GyE (n=33) 3-year; 92%, 5-year; 79%

64 or 57.6 GyE( n=14) 5-year; 24%

PRO

BABI

LITY

70.4 GyE (n=33) 3-y; 76%, 5-y; 54%

64 or 57.6 GyE (n=14) 3-year; 43%, 5-year; 36%

TIME IN MONTHS

Local Control Overall Survival

Jingu et al. IJROBP.2011

Unresectable sacral chordoma 5 years after C-ion RT Sacral osteosarcoma

13 years after C-ion RT

Calf soft tissue sarcoma 5 years after C-ion RT

Pelvis chondrosarcoma 28 months after C-ion RT Married and had her baby

Late Skin Reaction in B & STSs

No of Pts Gr3-4 (%)

2000~2001 25 7 (28)

Total Dose : 73.6 Two direction Skin margin

70.4 or less Three direction or more Reduced skin margin

Risk factor

2002~2005 151 2 (Modified group)

Modifications

Yanagi et al.Radiotherapy and Oncology. 2010;95:60-65

Chordoma of the sacrum Case 1 Case 2 Case 3

•3% of all primary bone sarcoma (50% from sacrum bone) •Radio-chemo-resistant nature •Difficulty in surgery due to its location •Slow growing, sometimes presenting huge tumor size

Chordoma of the sacrum Case 1 Case 2 Case 3

6 years 5 years 6 years

Local Control & Survival Rate in Chordoma(sacrum & mobile spine)

No. Site treatment Local Survival of Pts. 5-year 5year 10year (new pts /y)

MGH 1) 21 S surgery 77% - 50% 1972-1992 (1.1) Sweden 2) 39 S+Sp surgery 44 84% 64% 1963-1998 (1.1)

MGH. 3) 27 S surgery 72 82 62 1982-2002 (2.7 ) + Proton

LBL 4) 14 S surgery 55 85 22 1977-1989 (1.2 ) + He-ion Mayo 5) 52 S surgery 56 74 52 1980-2001 (2.5 ) NIRS 6) 145 S+Sp C-ion 85 85 47 1996-2009.2 (11 ) 1) J Bone Joint Surg. 1998 2) Cancer.2000 3)IJROBP.2006 4) IJROBP.1993 5) J Bone Joint Surg. 2005 6)BJR. 2011

S:sacrum Sp:mobile spine

(disease free)

Factors in Re-irradiation • Regrowth of a radio-resistant clone; cancer stem-like cells? • Tumor bed effect: damage of tumor vasculatures and stromal elements(fibrosis and necrosis) - poor blood supply and impairment of local defense (immune? ) system • Low tolerance of surrounding normal tissue

High risk of serious morbidities with poor tumor control

Re-irradiation

80 70 60 50 40 30 20 10 0

1.0

.8

.6

.4

.2

0.0

Overall Survival (n=60)

Local control（n=68)

Local Control and Survival in Re-irradiation with Carbon Ion Beam

Months after C-ion

• 60 cases(68 lesions) treated Dec-’04. to Aug-’10. • X-ray Dose : 20-72 Gy(median 50 Gy) • X-ray to C-ion time : 4 - 275 months(median 31 mon.） • C-ion dose:36-70.4GyE/12-16Fr/3-4 weeks

Re-irradiation with C-ion beam

90%

70%

New insight

Cui et al. Cancer Res 71:3676-87, 2011

Carbon ion beam therapy may have an advantage over photon beam therapy by improved targeting of putative colon cancer stem–like cells.

X-ray C-ion

Control

Hypo-fractionation in C-ion RT •Pros •Similar effectiveness •Similar toxicity •Low OER and low repair in C-ion •High conformality •More patient easy •More capacity

•Cons •More toxic •Less effective •Less re-oxygenation •Less repair…etc •Small therapeutic window

phase Treatment No. 3year 5year of trial (Dose*/fx/week) of Pts local survival -1 I/II 59.4-95.4 GyE/18/6w 47 65% 41% -2 I/II 68.4-79.2GyE/9/3w 34 91% 40% -3 II 72.0 GyE /9fx/3w 50 95% 50% -4 I/II 52.8-60 GyE/4fx/1w 79 90% 36% -5 I/II 28 - 50GyE /1fx/1day 216 - -

Carbon Ion Radiotherapy, Stage I Non Small Cell Lung cancer

Single fraction treatment（4 direction）

Single Fraction Carbon ion therapy for Stage I non small cell lung cancer

Before

After ４months

Single fraction 28GyE of carbon ion for stage I non small cell lung cancer

After 58 months Alive NED (7 years)

year

Local control rate(5 y)：79% Cause-spec. survival rate(5y)：75% Overall survival rate(5y)：64%

52

Single Fraction Carbon ion therapy for Stage I non small cell lung cancer

Before After

T2N0M0 Sq.CC 71 F

NO Grade 3 Reactions in this series

Single dose of 36-46 Gy (n=121)

0

20

40

60

80

100

120

140

160

180

200

95 96 97 98 99 00 01 02 03 04 05 06 07 08 09

High risk 613(55%) Intermediate risk 307(28%) Low risk 188(17%) Total 1108

Number of Patients in Prostate Study

16f./4wks

Phase I/II Phase II

No. of Morbidity ≥ G2 Institutes Radiotherapy Dose (Gy/f) pts. Rectum GU Christie H.1) IMRT 60.0/20 60 9.5% 4.0% Princess Margaret H.2) IMRT 60.0/20 92 6.3% 10.0% Cleveland CF.3) IMRT 70.0/28 770 4.4% 5.2% Stanford U.4) SRT 36.25/5 41 15.0% 29.0% RTOG94065) 3DCRT 68.4-79.2/38-41 275 7-16% 18-29% 3DCRT 78.0/39 118 25-26% 23-28% Loma Linda U.6) Proton 75.0/39 901 3.5% 5.4% NIRS C-ion 63.0/20 216 1.9% 4.6% C-ion 57.6/16 274 0.7% 2.6% 1) JH Coote et al. IJROBP 74, 2009 2) JM Martin et al. IJROBP 69, 2007 3) PA Kupelian et al. IJROBP 68, 2007 4) CR King et al. IJROBP 73, 2009 5) JM Michalski et al. IJROBP 76, 2010 6) RW Schulte et al. Strahlenther Oncol 176, 2000

Morbidities in Prostate RT (Comparison with other RT)

Comparison with other RTx 5-year bNED in High risk group( iPSA≥20)

No. of Biochemical Institutes RTx Dose pts. NED (iPSA≥20) MDAnderson CC.1) Conventional 66-78Gy/33-39f 197 51%

Fox Chase CC.2) 3DCRT ≥76Gy/38f 232 26-63%

Cleveland CF.3) IMRT 70Gy/28f 293(High risk) 72%

Loma Linda U.4) Proton 75CGE/45f 901 45%

NIRS 5) Carbon 63-66/20, 57.6/16 222 87% 1) A Pollack et al. IJROBP 48, MR Storey et al.IJROBP 48, 2000 2) GE Hanks et al. IJROBP 46, 2000 3) PA Kupelian et al. IJROBP 68, 2007 4) JD Slater et al. IJROBP 59, 2004 5) H.Tsuji, et al. IJROBP 63, 2005

Hypofractionation in Prostate Cancer

20fr. / 5wks

Pilot study of 51.6GyE 7 pts.-recurrence after hormone therapy >>> No severe toxicity nor recurrence

Dose-escalation study >>> Recommended dose; 63.0GyE

New Clinical Trial

12fr. / 3wks

Fixed dose; 57.6GyE >>> Comparable Tumor Control with Lower Incidence of Toxicity

16fr. / 4wks

51.6GyE / 12fr. / 3wks applied to fresh cases(35pts treated)

8 years for 1 week reduction

7 years more for another 1 week reduction

Annual Patient Accrual for Carbon Ion Therapy at NIRS (Treatment: June 1994～ Augast 2011)

Clinical research

Clinical practice (40,000US$)

18

17 16 15

14 13 12

11

Fraction number/patient

1. Hypo-fractionated RT -- Reduction in fractions and time Average : 13.0 fr / 3 wks ( 750 pts treated in 2009)

Stage I Lung single fr, Hepatpma 2 fr, Prostate 12 fr, Pancreas 2. Photon- resistant and slow-growing tumors--Increased

biological effect Non-SCC (Adenoca, Adenoidcystic ca, Melanoma etc) Head and neck / Prostate / Pancreas/ Liver / Rectal ca(Pelvic rec) / Uterus Bone and soft tissue sarcoma Re-irradiation Slow-growing tumors : Renal cell cancer/ Thyroid cancer 3. Increased dose to the target near critical organs Skull base tumor / paravertebral tumor Pelvic tumors

Tsujii H: Radiother Oncol 73(Sippl 2): S41-S49,2004 Laramore GE: Seminars Oncol. 24:672-685, 1997 Linstdt: IJROBP,20:761,1991)

Tumor Types and Clinical Situations Where Carbon Ion Radiotherapy Offers a Therapeutic Advantage

~12 fr

and Future…

○3D Scanning (H&V): 2 rooms ○Rotating Gantry : 1 room

Iso-center0 1 2m

SMxQM SMy

Monitors

RGF

RSF

Wall

PRN1 PRN2

9.0 m3D Scanning

New treatment facility

HIMAC building

Hospital

Research Building for Charged Particle Therapy

Rotating Gantry

A New Project at NIRS

New Facility for C-ion Scanning

Treatment started as the clinical trial on May 17, 2011.

scatterer collimator compensator ridge filter

Beam delivery techniques

• Broad-beam irradiation

Scanning irradiation

More flexible in irradiation field shaping

wobbler magnets

scanning magnets

range shifter

63

Sep. 2010 - First beam in the scanning treatment room. Jan. 2011 - Commissioning report on the C-ion scanning treatment (170 pages) approved by the extramural review committee for Q/A. Feb. 2011 - IRB review and approval of the clinical protocol of the C-ion scanning. May. 2011 - First patient was treated. (1.5 months behind the schedule due to unstable power supply after the East Japan Earthquake)

From First Beam to First Patient in C-ion Scanning

Scanning : First patient : 5/17/’11 Patient # Site Start

＃1 Pelvis 5/17～6/14

＃2 H & N 5/25～6/21

＃3 Pelvis 5/27～6/23

＃4 H & N 6/1～6/29

＃5 Pelvis 6/15～7/12

#6 Pelvis 6/21~7/15

#7 H & N 6/28~7/22

#8 H & N 7/19~8/11

Scanning Beam Monitor in Head & Neck #2

19min/patient(Ave):shortest : 8-47min! (positioning:13min., irradiation time:1min.)

JIGS（Jidou Ichi-Gime Souchi)

Automated positioning system

Stage 0------- Basic functions and procedures (IRB approval at Feb. 2011) Stage 1------- Dose painting (IRB review : 2012?) Stage 2------- Gated scanning for Moving target (IRB review : 2013) stage 3------- Light weight rotating gantry (IRB review : 2015) Stage 4------- Small synchrotron - next term? (IRB review : 2019?)

Next Decade in C-ion Scanning

Future Direction in Prostate More Hypo-fractionation : 8 fr./2 wks 4 fr./1wk or more…. Reduce the OAR dose Urethral Dose Reduction

It can be realized with“Dose-painting by precise image guided C-ion RT with scanning”

Beam monitor (scanning treatment)

Fast Re-scanning for Moving Target

↑ Moving target

↑ Position Monitor

Single scanning

8 times rescanning

< ±2.5%

Dose error

Confirmation of the 3D fast scanning(100m/sec) technology for moving target.

Furukawa et al. Med Phys. 2010;37(11):5672-82 Furukawa et al. Med Phys. 2010;37(9):4874-9.

52m

40m

Super MINIMAC - A Future Facility

C-ion : 400 MeV/n Synchrotron : diameter 6 m Gantry : Size 8x10 m (3 rooms) : Weight 100~150 tons

NM：350 tons

SCM：100 tons

C-ion400MeV/n Gantry

Super MINIMAC : Superconducting Magnet Installed Ion Medical Accelerator in Chiba

Specification of Super MINIMAC

◆In the past 17 years, more than 6,600 patients were treated with C-ion RT at NIRS.

◆Almost 50 protocol studies (Phase I/II and Phase II) have been performed to investigate optimal irradiation techniques, dose fractionation, and to find indications for C-ion RT.

◆For various types of tumors, hypofractionated carbon ion radiotherapy (average:13.0 frs per patient) has been established with acceptable morbidities.

◆Better local control and survival are brought by carbon ion therapy in many photon resistant advanced tumors.

◆The next generation carbon therapy system has been under development to provide more advanced treatment.

Clinical Study on C-ion RT at NIRS –Summary

No dose, No effect ! (….with some biological help)

Thank you for your attention

Carbon therapy--New horizon in cancer treatment