dosimetry in clinical trial design: making the...

George Sgouros PhD

Russell H Morgan Dept of Radiology amp Radiological Science

Johns Hopkins University School of Medicine

Baltimore MD

Dosimetry in Clinical Trial

Design Making the case

Disclosures

Consultant Bayer Roche

Scientific Advisory Board Orano Med

Founder Radiopharmaceutical Imaging and

Dosimetry (Rapid) LLC

Current cancer therapies

5-year survival by stageSite localized distant

Breast 99 30

Colorectal 90 14

Lung 56 5

Ovary 93 29

Pancreas 32 3

prostate 100 30SEERCancergov


bull Chemotherapy- Kill rapidly proliferating cells

After the cancer has spreadmetastasized

bull Targeted Biologic Therapy (hormonal Tx)- Inhibit signaling pathways that tumor cells are addicted

to (ie rely on to maintain cancer phenotype)

bull Immunotherapy- Overcome immune tolerance to cancer

bull Radiopharmaceutical Therapy- Kill targeted cells by localized radiation delivery

Radiopharmaceutical TherapyMolecular Radiotherapy (MRT)

Targeted Radionuclide Therapy

Radioimmunotherapy (RIT)

Agent distributes throughout body

Reacts withbinds to target cells

Cleared from non-target cells

Prolonged exposure to target cells

gives larger radiation dose to target cells

than to normal cells

Where (else) does the drug

concentrate and for how long

Radiopharmaceutical therapy

bull RPT provides targeted delivery of radiation

bull Not susceptible to resistance mechanism seen in

chemotherapy

bull Kills target cells vs inhibiting growthsurvival

pathways precludes adaptation

bull Can measure delivery of the therapeutic agent to

tumor targets and to normal organs

bull Guide escalation protocols and plan treatment


RPT agent Company Indication131I-radioiodine Jubilant Draximage Thyroid cancer131I-MIBG Progenics Adrenergic+ tumors212Pb-trastuzumab

OranoMed HER2+ tumors

212Pb-PRIT OranoMedRoche Undisclosed212Pb-antisomatostatin

OranoMedRadiomedix Somatostatin+ tumors

212Pb-aTEM1 OranoMedMorphotek TEM1+ tumors212Pb-aCD37 OranoMedNordicNanovector Leukemia131I-aCD45 Actinium Pharmaceuticals BM xplant prep225Ac-aCD33 Actinium Pharmaceuticals Leukemia90Y-microspheres VarianSirtex Hepatic malignancies90Y-microspheres BTG Hepatic malignancies


RPT agent Company Indication

Lutathera (177Lu) NovartisAAA Somatostatin+ tumors177Lu-aPSMA-R2 NovartisAAA Prostate tumor neovasc177Lu-NeoBOMB1 NovartisAAA Bombesin+ tumors177Lu-PSMA-617 Endocyte Prostate tumor neovascXofigo (223Ra) Bayer Bone metsHER2-TTC (227Th) Bayer HER2+ tumorsPSMA-TTC (227Th) Bayer Prostate tumor neovascMSLN-TTC (227Th) Bayer Mesothelin+ tumorsaCD22-TTC (227Th) Bayer LymphomaFPX-01 (225Ac) JampJFusion Pharma NSCLC pan-cancer target


bull 21 RPTs (abridged list)

bull 5 commercially availableFDA approved- 131I thyroid malignancies

- Xofigo (223Ra) castration resistant prostate cancer bone mets

- Lutathera (177Lu) somatostatin+ tumors

- Sirtex (90Y) hepatic malignancies

- Therapsheres (90Y) hepatic malignancies

bull 3 beta-emitters ndash 131I 177Lu 90Y

bull 4 alpha-emitters ndash 225Ac 227Th 212Pb212Bi 223Ra

DNA

ele

ctr

on

sA

lph

a-

part

icle

Clustered ionizations from

low-energy electron

Delta-ray electron

Single ionization

-- high probability of damage when

alpha-particle hits DNA

(DTGoodhead CERRIE Workshop 2003)

Linear Energy Transfer (LET)

Tumor-response evaluation in αRPT

Kratochwil et al JNM 2016

Tumor-response evaluation in RPT


DNA double-strand breaks

BT474 370kBq (10 uCi)213Bi-trastuzumab 1h

BT474 4Gy XRT

1h

bull dose for cell kill w betas 3-7 x alphas in vitro

bull RBE influenced by- Biological end-point

- Reference radiation

- Dosimetry methodology

Relative Biological Effectiveness (RBE)

)(

)()(

xD

xDxRBE

t

r=x = biological effect

r = reference radiation

t = test radiation

Repair Radiosensitization and RBE

Song et al MCT 2013

Potential for increased toxicity

httpwwwemaeuropaeuemaindexjspcurl=pagesnews_and_eventsnews201807ne

ws_detail_002996jspampmid=WC0b01ac058004d5c1

bull Early phase trials ndash opportunity to collect data

bull Donrsquot propose altering treatment

bull Show that dosimetry would have predicted toxicity or lack of efficacy

bull Assess patient variability

bull Apply rigorous consistent methods- 3 time-points 1st and last cycle

- Pre-therapy tracer study

- SPECTCT

bull Use collected data to validate simpler schemes

bull Be prepared to accept conclusions- Prior patient history dose-range can impact dose-response

relationship

PROVEDOSIMETRY IMPROVES TX

Biomarkers

bull Select patients most likely to respond

bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling

bull Genetic and epigenetic marker analysis

bull Must be rigorously qualifiedvalidated retrospectively or in prospective studies

bull Standardized

bull Incorporated in the design of clinical trials

Dosimetry


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry

bull

bull

bull Quantitative Imaging

bull Blood Counting

bull Dose Calculation

bull

bull

bull

Admin Activity (AA) vs Abs Dose

Wahl RL Semin Oncol lsquo03

Example of

patient

variability

Previously

demonstrated

that 75 cGy to

WB increases

RM toxicity

Is small fraction of patients that will be

undertreated worth the dosimetry effortcost

131I-anti-CD20 Ab NHL patients

Bexxar

le 200 cGy

gt 200 cGy

J Nucl Med 2014 Jul55(7)1047-53 doi 102967jnumed113136044 Epub 2014 May 19Tumor-Absorbed Dose Predicts Progression-Free Survival Following (131)I-Tositumomab RadioimmunotherapyDewaraja YK1 Schipper MJ2 Shen J3 Smith LB4 Murgic J5 Savas H6 Youssef E6 Regan D6 Wilderman SJ7 Roberson PL2 Kaminski MS8 Avram AM6

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors httpswwwnejmorgdoifull101056nejmoa1607427

by J Strosberg - 2017 - Cited by 376 - Related articles

12 Jan 2017 - Patients with advanced midgut neuroendocrine tumors who have had disease progression

during first-line somatostatin analogue therapy have limited therapeutic options This randomized controlled

trial evaluated the efficacy and safety of lutetium-177 (177Lu)ndashDotatate in patients

Red Marrow Dose vs Response Literature

Pla

tele

t Toxic

ity G

rade

(N = 109) (N = 57)

(N = 91) (N = 56)

OrsquoDonoghue et al CBR lsquo00

Red Marrow Dose vs Response MSKCC (N=36)

Pla

tele

t Toxic

ity G

rade


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

Effect of Chemotherapy Mitomycin

0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150

Admin ActviitySA (mCim2)

0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


w mito

wo mito

00

01

02

03

04

05

06

07

08

P-G

W-

DC

W-G

P-

DC

W-A

DC

W-T

TN

P-T

TN

P-A

DC

wo mytomycin

w mytomycin

RM Dose Correlation Coefficients (r)

mitomycin

mitomycin

Dosimetry 34

Dose Standard volume (Gy)

20 30 40

Cre

atinin

e c

leara

nce lossy

ear

( b

aselin

e)

0

20

40

60

Correlation between kidney dose (Gy)

and creatinine clearance lossyear ( baseline) N=18

Kidney volumes measured by CT

cortex (70)

Standard kidney volumes

Kidney dose CT volume (Gy)

0 10 20 30 40 50

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60

R=054p= 002

Importance of organ volume in self irradiation

UNIVERSITE CATHOLIQUE DE LOUVAINBarone et al JNM lsquo05

Dosimetry 35

Correlation between BED

and creatinine clearance lossyear

Biologic Effective Dose (Gy)

0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001

UNIVERSITE CATHOLIQUE DE LOUVAIN

Barone R Borson-Chazot F Valkema R et al J Nucl Med 2005 Jan46 Suppl 199S-106S

Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes

Processing Monte Carlo

Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart

MIRD Pamphlet 23 Quantitative SPECT for Patient-Specific

3-D Dosimetry in Radionuclide Therapy JNM 2012

153Sm-EDTMP ndash Xbeam Therapy

Pediatric patient population153Sm emits bminus with a half-life

of 467 h and 103 keV

photon

Escalation protocols ndash patients

treated with 12 mCikg and

50 mCikg (myeloablative)

and imaged with planar

images for dosimetry

Median survival was 79 days ndash

2 patients (out of 14) had

longer survival times (990

and 1472 days)

Loeb et al Cancer rsquo09

Hobbs et al Phys Med Biol rsquo10


Senthamizhchelvan et al J Nucl Med rsquo11

Sm-135 osteosarcoma RPT

Srinivasan et al JNM rsquo12

Absorbed Dose (21 Gy) EUD (6 Gy) threshold for PD vs SD

p lt 005

Absorbed Dose EUD vs Response



Confirms PD vs SD results

Tumor Volume Reduction vs AD EUD

p lt 0031 p lt 0023

Combined modality Therapybull Osteogenic Sarcoma

bull XRT for inoperable tumors

bull XRT limited if close to spinal cord (SC)

bull Combine w 153Sm (RPT)

bull uarr tumor dose SC dose

bull Adjust for dose-rates ( )( )( )

RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT

G T D t dt D w e dwD

minus minus= Hobbs et al IJROBP rsquo10

3 Combined RPT-XRT

Ideandash XRT can deliver precise amounts of radiation to

regions of interest (ROIs) but limited by adjacent organ at risk (eg spinal cord)

ndash RPT highly conformal - delivers dose to all tumor sites including micro-metastases

How ndash The combination XRT with RPT requires accurate

3-D dose calculations to avoid toxicity and evaluate potential efficacy

ndash Deliver RPT (12 mCikg) and make 3D dose map in 3D-RD convert to external beam AD values and import into XRT software and include in treatment plan Hobbs et al IJROBP rsquo10

Protocol(a) 18F-MISO PETCT for baseline

b Stem cell collection for autologous transplant

c CT-sim used for both XRT and RPT treatment planning

d Low dose 153Sm-EDTMP (1 mCikg)

e SPECTCT imaging at 4 24 and 48 h image reconstruction and dosimetry calculations

f High dose 153Sm-EDTMP determined by dosimetry (max 20 mCikg)

g High dose imaging at 4 24 and 48 h image reconstruction and dosimetry calculations

h Autologous stem cell transplant (recovery)

i IMRT plan add fusion of low + high dose maps

(j) 18F-MISO PETCT for treatment response

RPT-XRT AD equivalence

AD from XRT fractionated

AD from RPT over time

What about biological equivalence

Use BED as a bridge

(Equivalent linear dose compared to the linear-quadratic absorbed dose with a repair term)

Equivalence depends on dose per fraction d

+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT

Hobbs et al IJROBP rsquo10

Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions

bull RPT dosimetry is the ideal biomarker

bull Mechanism of action is well understood

bull Needed measurements are known

bull Patient-specific dosimetry tools are available

bull Response data from radiotherapy



bull Calculate radiation dose to tumors normal organs


Need to overcome prior history- 2nd chance

Implement standardized validated activity

quantification and dosimetry methods in early

phase clinical trials to gather rigorous

evidence that dosimetry will improve patient

care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs

Senthamil Srinivasan

Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko

Disclosures

Consultant Bayer Roche

Scientific Advisory Board Orano Med

Founder Radiopharmaceutical Imaging and

Dosimetry (Rapid) LLC



Breast 99 30

Colorectal 90 14

Lung 56 5

Ovary 93 29

Pancreas 32 3























chemotherapy
























DNA

ele

ctr

on

sA

lph

a-

part

icle


low-energy electron

Delta-ray electron

Single ionization











BT474 4Gy XRT

1h






)(

)()(

xD

xDxRBE

t



t = test radiation


Song et al MCT 2013










- SPECTCT



relationship


Biomarkers


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry

bull

bull


bull Blood Counting


bull

bull

bull



Example of

patient

variability

Previously

demonstrated

that 75 cGy to

WB increases

RM toxicity




Bexxar

le 200 cGy

gt 200 cGy








Pla

tele

t Toxic

ity G

rade

(N = 109) (N = 57)

(N = 91) (N = 56)



Pla

tele

t Toxic

ity G

rade


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


w mito

wo mito

00

01

02

03

04

05

06

07

08

P-G

W-

DC

W-G

P-

DC

W-A

DC

W-T

TN

P-T

TN

P-A

DC

wo mytomycin

w mytomycin


mitomycin

mitomycin

Dosimetry 34


20 30 40

Cre

atinin

e c

leara

nce lossy

ear

( b

aselin

e)

0

20

40

60




cortex (70)



0 10 20 30 40 50

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60

R=054p= 002



Dosimetry 35




0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001



Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko



Breast 99 30

Colorectal 90 14

Lung 56 5

Ovary 93 29

Pancreas 32 3























chemotherapy
























DNA

ele

ctr

on

sA

lph

a-

part

icle


low-energy electron

Delta-ray electron

Single ionization











BT474 4Gy XRT

1h






)(

)()(

xD

xDxRBE

t



t = test radiation


Song et al MCT 2013










- SPECTCT



relationship


Biomarkers


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry

bull

bull


bull Blood Counting


bull

bull

bull



Example of

patient

variability

Previously

demonstrated

that 75 cGy to

WB increases

RM toxicity




Bexxar

le 200 cGy

gt 200 cGy








Pla

tele

t Toxic

ity G

rade

(N = 109) (N = 57)

(N = 91) (N = 56)



Pla

tele

t Toxic

ity G

rade


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


w mito

wo mito

00

01

02

03

04

05

06

07

08

P-G

W-

DC

W-G

P-

DC

W-A

DC

W-T

TN

P-T

TN

P-A

DC

wo mytomycin

w mytomycin


mitomycin

mitomycin

Dosimetry 34


20 30 40

Cre

atinin

e c

leara

nce lossy

ear

( b

aselin

e)

0

20

40

60




cortex (70)



0 10 20 30 40 50

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60

R=054p= 002



Dosimetry 35




0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001



Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko






















chemotherapy
























DNA

ele

ctr

on

sA

lph

a-

part

icle


low-energy electron

Delta-ray electron

Single ionization











BT474 4Gy XRT

1h






)(

)()(

xD

xDxRBE

t



t = test radiation


Song et al MCT 2013










- SPECTCT



relationship


Biomarkers


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry

bull

bull


bull Blood Counting


bull

bull

bull



Example of

patient

variability

Previously

demonstrated

that 75 cGy to

WB increases

RM toxicity




Bexxar

le 200 cGy

gt 200 cGy








Pla

tele

t Toxic

ity G

rade

(N = 109) (N = 57)

(N = 91) (N = 56)



Pla

tele

t Toxic

ity G

rade


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


w mito

wo mito

00

01

02

03

04

05

06

07

08

P-G

W-

DC

W-G

P-

DC

W-A

DC

W-T

TN

P-T

TN

P-A

DC

wo mytomycin

w mytomycin


mitomycin

mitomycin

Dosimetry 34


20 30 40

Cre

atinin

e c

leara

nce lossy

ear

( b

aselin

e)

0

20

40

60




cortex (70)



0 10 20 30 40 50

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60

R=054p= 002



Dosimetry 35




0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001



Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko



















DNA

ele

ctr

on

sA

lph

a-

part

icle


low-energy electron

Delta-ray electron

Single ionization











BT474 4Gy XRT

1h






)(

)()(

xD

xDxRBE

t



t = test radiation


Song et al MCT 2013










- SPECTCT



relationship


Biomarkers


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry

bull

bull


bull Blood Counting


bull

bull

bull



Example of

patient

variability

Previously

demonstrated

that 75 cGy to

WB increases

RM toxicity




Bexxar

le 200 cGy

gt 200 cGy








Pla

tele

t Toxic

ity G

rade

(N = 109) (N = 57)

(N = 91) (N = 56)



Pla

tele

t Toxic

ity G

rade


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


w mito

wo mito

00

01

02

03

04

05

06

07

08

P-G

W-

DC

W-G

P-

DC

W-A

DC

W-T

TN

P-T

TN

P-A

DC

wo mytomycin

w mytomycin


mitomycin

mitomycin

Dosimetry 34


20 30 40

Cre

atinin

e c

leara

nce lossy

ear

( b

aselin

e)

0

20

40

60




cortex (70)



0 10 20 30 40 50

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60

R=054p= 002



Dosimetry 35




0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001



Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko







BT474 4Gy XRT

1h






)(

)()(

xD

xDxRBE

t



t = test radiation


Song et al MCT 2013










- SPECTCT



relationship


Biomarkers


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry

bull

bull


bull Blood Counting


bull

bull

bull



Example of

patient

variability

Previously

demonstrated

that 75 cGy to

WB increases

RM toxicity




Bexxar

le 200 cGy

gt 200 cGy








Pla

tele

t Toxic

ity G

rade

(N = 109) (N = 57)

(N = 91) (N = 56)



Pla

tele

t Toxic

ity G

rade


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


w mito

wo mito

00

01

02

03

04

05

06

07

08

P-G

W-

DC

W-G

P-

DC

W-A

DC

W-T

TN

P-T

TN

P-A

DC

wo mytomycin

w mytomycin


mitomycin

mitomycin

Dosimetry 34


20 30 40

Cre

atinin

e c

leara

nce lossy

ear

( b

aselin

e)

0

20

40

60




cortex (70)



0 10 20 30 40 50

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60

R=054p= 002



Dosimetry 35




0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001



Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko






)(

)()(

xD

xDxRBE

t



t = test radiation


Song et al MCT 2013










- SPECTCT



relationship


Biomarkers


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry

bull

bull


bull Blood Counting


bull

bull

bull



Example of

patient

variability

Previously

demonstrated

that 75 cGy to

WB increases

RM toxicity




Bexxar

le 200 cGy

gt 200 cGy








Pla

tele

t Toxic

ity G

rade

(N = 109) (N = 57)

(N = 91) (N = 56)



Pla

tele

t Toxic

ity G

rade


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


w mito

wo mito

00

01

02

03

04

05

06

07

08

P-G

W-

DC

W-G

P-

DC

W-A

DC

W-T

TN

P-T

TN

P-A

DC

wo mytomycin

w mytomycin


mitomycin

mitomycin

Dosimetry 34


20 30 40

Cre

atinin

e c

leara

nce lossy

ear

( b

aselin

e)

0

20

40

60




cortex (70)



0 10 20 30 40 50

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60

R=054p= 002



Dosimetry 35




0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001



Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko


Song et al MCT 2013










- SPECTCT



relationship


Biomarkers


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry

bull

bull


bull Blood Counting


bull

bull

bull



Example of

patient

variability

Previously

demonstrated

that 75 cGy to

WB increases

RM toxicity




Bexxar

le 200 cGy

gt 200 cGy








Pla

tele

t Toxic

ity G

rade

(N = 109) (N = 57)

(N = 91) (N = 56)



Pla

tele

t Toxic

ity G

rade


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


w mito

wo mito

00

01

02

03

04

05

06

07

08

P-G

W-

DC

W-G

P-

DC

W-A

DC

W-T

TN

P-T

TN

P-A

DC

wo mytomycin

w mytomycin


mitomycin

mitomycin

Dosimetry 34


20 30 40

Cre

atinin

e c

leara

nce lossy

ear

( b

aselin

e)

0

20

40

60




cortex (70)



0 10 20 30 40 50

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60

R=054p= 002



Dosimetry 35




0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001



Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko










- SPECTCT



relationship


Biomarkers


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry

bull

bull


bull Blood Counting


bull

bull

bull



Example of

patient

variability

Previously

demonstrated

that 75 cGy to

WB increases

RM toxicity




Bexxar

le 200 cGy

gt 200 cGy








Pla

tele

t Toxic

ity G

rade

(N = 109) (N = 57)

(N = 91) (N = 56)



Pla

tele

t Toxic

ity G

rade


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


w mito

wo mito

00

01

02

03

04

05

06

07

08

P-G

W-

DC

W-G

P-

DC

W-A

DC

W-T

TN

P-T

TN

P-A

DC

wo mytomycin

w mytomycin


mitomycin

mitomycin

Dosimetry 34


20 30 40

Cre

atinin

e c

leara

nce lossy

ear

( b

aselin

e)

0

20

40

60




cortex (70)



0 10 20 30 40 50

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60

R=054p= 002



Dosimetry 35




0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001



Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko

Biomarkers


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry

bull

bull


bull Blood Counting


bull

bull

bull



Example of

patient

variability

Previously

demonstrated

that 75 cGy to

WB increases

RM toxicity




Bexxar

le 200 cGy

gt 200 cGy








Pla

tele

t Toxic

ity G

rade

(N = 109) (N = 57)

(N = 91) (N = 56)



Pla

tele

t Toxic

ity G

rade


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


w mito

wo mito

00

01

02

03

04

05

06

07

08

P-G

W-

DC

W-G

P-

DC

W-A

DC

W-T

TN

P-T

TN

P-A

DC

wo mytomycin

w mytomycin


mitomycin

mitomycin

Dosimetry 34


20 30 40

Cre

atinin

e c

leara

nce lossy

ear

( b

aselin

e)

0

20

40

60




cortex (70)



0 10 20 30 40 50

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60

R=054p= 002



Dosimetry 35




0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001



Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko


bull Avoid toxicity

bull Tumor biopsy

bull Serum sampling



bull Standardized


Dosimetry

bull

bull


bull Blood Counting


bull

bull

bull



Example of

patient

variability

Previously

demonstrated

that 75 cGy to

WB increases

RM toxicity




Bexxar

le 200 cGy

gt 200 cGy








Pla

tele

t Toxic

ity G

rade

(N = 109) (N = 57)

(N = 91) (N = 56)



Pla

tele

t Toxic

ity G

rade


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


w mito

wo mito

00

01

02

03

04

05

06

07

08

P-G

W-

DC

W-G

P-

DC

W-A

DC

W-T

TN

P-T

TN

P-A

DC

wo mytomycin

w mytomycin


mitomycin

mitomycin

Dosimetry 34


20 30 40

Cre

atinin

e c

leara

nce lossy

ear

( b

aselin

e)

0

20

40

60




cortex (70)



0 10 20 30 40 50

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60

R=054p= 002



Dosimetry 35




0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001



Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko



Example of

patient

variability

Previously

demonstrated

that 75 cGy to

WB increases

RM toxicity




Bexxar

le 200 cGy

gt 200 cGy








Pla

tele

t Toxic

ity G

rade

(N = 109) (N = 57)

(N = 91) (N = 56)



Pla

tele

t Toxic

ity G

rade


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


w mito

wo mito

00

01

02

03

04

05

06

07

08

P-G

W-

DC

W-G

P-

DC

W-A

DC

W-T

TN

P-T

TN

P-A

DC

wo mytomycin

w mytomycin


mitomycin

mitomycin

Dosimetry 34


20 30 40

Cre

atinin

e c

leara

nce lossy

ear

( b

aselin

e)

0

20

40

60




cortex (70)



0 10 20 30 40 50

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60

R=054p= 002



Dosimetry 35




0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001



Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko

le 200 cGy

gt 200 cGy








Pla

tele

t Toxic

ity G

rade

(N = 109) (N = 57)

(N = 91) (N = 56)



Pla

tele

t Toxic

ity G

rade


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


w mito

wo mito

00

01

02

03

04

05

06

07

08

P-G

W-

DC

W-G

P-

DC

W-A

DC

W-T

TN

P-T

TN

P-A

DC

wo mytomycin

w mytomycin


mitomycin

mitomycin

Dosimetry 34


20 30 40

Cre

atinin

e c

leara

nce lossy

ear

( b

aselin

e)

0

20

40

60




cortex (70)



0 10 20 30 40 50

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60

R=054p= 002



Dosimetry 35




0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001



Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko







Pla

tele

t Toxic

ity G

rade

(N = 109) (N = 57)

(N = 91) (N = 56)



Pla

tele

t Toxic

ity G

rade


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


w mito

wo mito

00

01

02

03

04

05

06

07

08

P-G

W-

DC

W-G

P-

DC

W-A

DC

W-T

TN

P-T

TN

P-A

DC

wo mytomycin

w mytomycin


mitomycin

mitomycin

Dosimetry 34


20 30 40

Cre

atinin

e c

leara

nce lossy

ear

( b

aselin

e)

0

20

40

60




cortex (70)



0 10 20 30 40 50

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60

R=054p= 002



Dosimetry 35




0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001



Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko


Pla

tele

t Toxic

ity G

rade


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


w mito

wo mito

00

01

02

03

04

05

06

07

08

P-G

W-

DC

W-G

P-

DC

W-A

DC

W-T

TN

P-T

TN

P-A

DC

wo mytomycin

w mytomycin


mitomycin

mitomycin

Dosimetry 34


20 30 40

Cre

atinin

e c

leara

nce lossy

ear

( b

aselin

e)

0

20

40

60




cortex (70)



0 10 20 30 40 50

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60

R=054p= 002



Dosimetry 35




0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001



Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko

0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)


0

1

2

3

4

0 100 200 300 400 500

RM dose (rad)

0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


0

1

2

3

4

0 50 100 150

WB dose (rad)

0

1

2

3

4

0 50 100 150


w mito

wo mito

00

01

02

03

04

05

06

07

08

P-G

W-

DC

W-G

P-

DC

W-A

DC

W-T

TN

P-T

TN

P-A

DC

wo mytomycin

w mytomycin


mitomycin

mitomycin

Dosimetry 34


20 30 40

Cre

atinin

e c

leara

nce lossy

ear

( b

aselin

e)

0

20

40

60




cortex (70)



0 10 20 30 40 50

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60

R=054p= 002



Dosimetry 35




0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001



Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko

00

01

02

03

04

05

06

07

08

P-G

W-

DC

W-G

P-

DC

W-A

DC

W-T

TN

P-T

TN

P-A

DC

wo mytomycin

w mytomycin


mitomycin

mitomycin

Dosimetry 34


20 30 40

Cre

atinin

e c

leara

nce lossy

ear

( b

aselin

e)

0

20

40

60




cortex (70)



0 10 20 30 40 50

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60

R=054p= 002



Dosimetry 35




0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001



Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko

Dosimetry 34


20 30 40

Cre

atinin

e c

leara

nce lossy

ear

( b

aselin

e)

0

20

40

60




cortex (70)



0 10 20 30 40 50

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60

R=054p= 002



Dosimetry 35




0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001



Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko

Dosimetry 35




0 10 20 30 40 50 60

Cre

atin

ine c

leara

nce

lo

ssy

ear

( b

ase

line)

0

20

40

60R=093plt00001



Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko

Activity data

SPECT or PET

Anatomic data

CT (or MRI)

Input

Registration

VOIs definition

Generation of

data volumes


Calculation

Activity

(xyzt)

Density

(xyz)

Composition

(xyz)

Output

Abs dose

rate (xyzt)

Processing

- Mean dose

- Isodose

-DVH

1 2 3 4

- BED (BVH)

- EUD

3D-RD Flowchart






photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko




photon









and 1472 days)








p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko




p lt 005






p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko





p lt 0031 p lt 0023







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko







RPT RPTdGF

RPT

D G DD

d

b

b

+ =

+

( )

2

0 0

2( ) ( ) ( )

T t

t w

RPT RPT

RPT



3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko

3 Combined RPT-XRT





















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko















Use BED as a bridge



+= )(

1 i

ii

iii G

DDBED

b

+=

ii

ii

dDBED

b 1

( )2

)(2

+

+=

b

b iRPTRPT GDDEQD

RPT

XRT


Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko

Combined treatment

Xbeam and PTV

Xbeam and Sm-153

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko

Conclusions















care

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko

Acknowledgments

NIH

DOD

DOE

Rob Hobbs


Donika Plyku

Anders Josefsson

Sunju Park

Jessie Nedrow

Sanchita Roy

Alireza Karimian

Akhila Rao

Hong Song

Andy Prideaux

Yah-el Har-el

Mohana Lingappa

Karineh Shahverd

Kitiwat Khamwan

Eric Frey

Richard Wahl

Ivan Guan

Kevin Yeh

Sagar Ranka

Martin Pomper

Benjamin Tsui

James Fox

Yuchuan Wang

Hong Fan

Ron Mease

David Huso

Kathy Gabrielson

Zaver Bhujwalla

Barjor Gimi

VP Chacko

dosimetry in clinical trial design: making the...

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