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Selective Internal RadioTherapy Irene A. Burger, MD Pärnu (Estonia), October 6 – 10, 2014 Radiology and Nuclear Medicine Department University Hospital Zurich Switzerland

Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

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Page 1: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Selective Internal RadioTherapy

Irene A. Burger, MD

Pärnu (Estonia), October 6 – 10, 2014

Radiology and Nuclear Medicine Department

University Hospital Zurich

Switzerland

Page 2: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Y-90 Radioembolization of the liver

• Yttrium-90 radiotherapy was investigated for cancer therapy since the 1960s

• 1977 first publications for internal radioembolization of liver metastasis in humans (Grady et al)

Page 3: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Resin Glass

Trade name SIR-Spheres Theraspheres

Manufacturer andlocation

Sirtex Medical, Lane Cove, Australia

MDS Nordion, Kanata, Canada

Diameter 20-60 µm 20-30 µm

Specific gravity 1.6 g/dL 3.6 g/dL

Activity per particle 50 Bq/1.4 nCi 2500 Bq/67.6 nCi

Number of micro-spheres per 3 GBqvial

40-80 million 1.2 million

Material resin with bound yttriumglass with yttrium in matrix

SIRT – technical aspects:

Page 4: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Therapy with 90-Yttrium

Spheres

FDG-PET/CT

Step 1 – Imaging and Planning Step 2 – Therapy Step 3 – Control

Control with Bremstrahlen

Scan

Y-90 Radioembolization of the liver

Tc MAA Scan

Page 5: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Normal

80%

Tumor

minimal

Tumor

~100%

Normal

20%

Pfortader A. Hepatica

Afferent

O2 O2

Y-90 SIRT: Principle mechanism

Page 6: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Liver tolerance & tumor sensitivity

Curative Doses: Adenocarcinoma

RILD – Radiation-Induced Liver Disease

Preoperative Radiation: Rectal Ca

20Gy: 30 40 50 60 70 1009080

SIRT

Kennedy A et al. Int J Rad Oncol Biol Phys 2004; 60: 1520–1533.

Page 7: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

> 120 Gy

> 120 Gy

<25Gy

Y-90 SIRT: Principle mechanism

1000 Gy Dose Volume

Micro dosimetrie Explantat

Page 8: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Y-90 SIRT: Clinical set up

Page 9: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

SIRT - overview:

New technical aspects:• Patient work up • Patient selection• Vascular redistribution• Radiation exposure of the interventional team

Clinical outcome data:• Metastasized colorectal carcinoma• Unresectable hepato- or cholangiocellular carcinoma• Neuroendocrine liver metastasis

Page 10: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Patient work up:

• Dose calculation: using MRI or ceCT volumetry• Diagnostic angiography with embolization of

gastrointestinal vessels• MAA-hepatic angiography for detection of reflux,

pulmonary shunt• Optional FDG PET/CT: extrahepatic disease & extent of

metabolic active liver disease

Page 11: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

𝐷𝑜𝑠𝑒 𝐺𝐵𝑞 = 𝐵𝑆𝐴 m2 − 0.2 +𝑇𝑢𝑚𝑜𝑟 𝑉𝑜𝑙𝑢𝑚𝑒

𝑇𝑢𝑚𝑜𝑟& 𝐿𝑖𝑣𝑒𝑟 𝑉𝑜𝑙𝑢𝑚𝑒*

Y-90 SIRT: Dose calculation

Liver

Volume1600 1000 500

Tumor

Volume300 300 300

Dose

GBq/mCi

1.7275

46.7

1.84

49.7

2.14

57.8

Caution with small livers esp. after chemotherapy

- RILD -

we have to establish more precise models for dosimetry

*Ehrhardt et al. Therapeutic use of Y-90 micorspheres. Int J Radiat Appl Instrum Part B Nmucl Med Biol 1987;14:233-42.

Giammarile et al. EANM Guidelines, EJNMMI 2011;38:1393-1406

Page 12: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Patient selection:

Official guidelines:• Live expectancy of at least 4 months• Not pregnant

Relative contraindications:• Ascites or signs of liver failure (Bilirubin > 2.0 mg/dl)• Child score > B • High extra-hepatic tumor burden• Renal failure• Excessive shunting to the lungs (> 20%)• Previous radiotherapy to the liver

Page 13: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Patient selection:

With selection of patients that will respond well the outcome of SIRT could be improved.

Tumors with high arterial perfusion should have a better response than lesions with low arterial enhancement.

Page 14: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Patient selection: Can we predict outcome?

38 patients underwent FDG PET/CT and perfusion ceCT prior to SIRT: • Liver metastasis on ceCT• High arterial perfusion with

45.2 /100 ml/min• Also on angiography the

lesions are hypervascular• CT 134 days after SIRT –

significant reduction in size

Morsbach et al, Investigative Radiology 2013;48:787-794

Page 15: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Patient selection: Can we predict outcome?

Other patients with low arterial perfusion (e.g. 8.9/100 ml/min) showed no reduction in tumor size

Significant correlation of arterial perfusion and responders vsnon responders to SIRT :

Morsbach et al, Investigative Radiology 2013;48:787-794

Page 16: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Patient selection: Can we predict outcome?

There was a correlation between arterial tumor perfusion and relative tumor size reduction

Morsbach et al, Investigative Radiology 2013;48:787-794

There was also an association between high arterial perfusion prior to SIRT and overall survival (p = 0.028)

Page 17: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Patient selection: Can we predict outcome?

Higher correlation between response and arterial tumor perfusion compared to other ceCT or 99mTC-MAA parameters:

AUCArt. Perfusion 0.971* (p<0.001)

Art. HU 0.866* (p=0.001)

Port.V. HU 0.796MAA ratio 0.402

Morsbach et al, European Radiology 2014;24:1455-1465

Page 18: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Patient selection: vascular redistribution

“Radioembolization of Hepatic Tumors: Flow Redistribution After the Occlusion of Intrahepatic Arteries.”

To avoid multiple SIRT injections occlusion of segmental hepatic arteries => A flow redistribution through intrahepatic collaterals. • In 24 of 27 (89%) patients with HCC or liver metastasis sufficient

vascular redistribution after occlusion of Seg II/III or Seg IV artery could be observed.• In 16 patients flow redistribution could be shown on subsequent

MAA scans. • In 8 patients redistribution was observed on therapy angiography

after mean 16 days (range 11-26).

Lauenstein et al, Röfo 2011;183: 1058-1064

Page 19: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Patient selection: vascular redistribution

Lauenstein et al, Röfo 2011;183: 1058-1064

Vascular redistribution can be helpful for:• Therapy of segments

that are supplied by aberrant arteries

• Therapy of patients with vascular variants

• Therapy of lesions in different segments without changing catheter position

Page 20: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Radiation exposure to staff:

• SIRT therapy with 90-Y causes exposure to high energy ß- radiation if not shielded with acrylic glass:

Page 21: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Radiation exposure to staff:

• Extension of acrylic glass coverage to protect the hands of the interventional physician:

PERPLEX Plus AG, Zürich

Page 22: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

µS

v/h

(D

ose

in

1 m

dis

tan

ce

)

Radiation exposure to staff:

• Preliminary results showed a reduction of radiation exposure of about 60% with additional acrylic glass protection:

Without With

Page 23: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Y-90 SIRT: Therapy control scan

90YBremsstrahlen SPECT/CT:+ Cheap, available- Low resolution- not quantitative

90Y PET/CT :+ higher spatial resolution+ quantitative images- Higher costs

Lhommel et al, EJNMMI 2009; 36: 1696Gates et al, JNM 2011;52:72-76

Bremsstrahlung Scan90Y PET scan18F-FDG PET scan

Page 24: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Y-90 SIRT: Therapy control scan

With courtesy Dr. Michael Wissmeyer, HUG Switzerland

99mTc MAA SPECT/CT scan 90Y PET/MR scan

The gain in resolution should increase the accuracy of the dose distribution calculations of tumors and surrounding tissues

Page 25: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

SIRT – clinical context:

cancer treatment

today

Nuclear Medicine

Medical Oncology

Hepatology

Surgery

Radiation Oncology

Intervent. Radiology

Page 26: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

SIRT – current options:

Tumor board

StereotacticRadiation

Chemotherapy

MicrowaveAblation

CTX Perfusion

PEI

Nano KnifeResection

RFA

TACE

Embolisation

SIRT

Page 27: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

AE Incidence Characteristics Prevention/Action

Fever >50% mild onset on Tx day normally nonefor up to 1 week required

Abdominal ~50% acute onset during Tx may require narcoticpain ~10% grade 3–4 self-limiting; normally <24 h > oral analgesia

Nausea ~40% highest in Tx-experienced; prophylactic anti-emetics<5% grade 3–4 normally <24 h

Fatigue ~40% onset in 1st month post- adequate nutrition & <5% grade 3–4 SIRT, normally subsides hydration;

within 2 weeks prophylactic oral steroids

Abnormal ~20–40% particularly in combination none normallyLFTs 1–6% grade 3–4 with chemo or HCC/cirrhosis; required

transient; resolves indays (ALT, AST), weeks

(bilirubin) or months (alb.)

SIRT: side effects - risks

Page 28: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

SAE Incidence Characteristics Prevention/action

Radiation ~5–10% non-target administration; meticulous technique &gastritis or 1–2% grade 3–4 immediate, severe occlusion of GI arteries;duodenitis unremitting pain prophylactic PPI for 1 mo

Radiation <1% non-target administration; meticulous technique &pancreatitis immediate, severe occlusion of GI arteries

unremitting pain

Radiation <1% non-target administration; various technicalcholecystitis right upper quadrant pain approaches; may require

cholecystectomy

Radiation- <1% excess radiation to normal liver; appropriate dose;Induced Liver onset typically 30–90 d post-SIRT; dose reduction inDisease (RILD) permanently elevated LFTs, portal patients with reduced

hypertension, eventual fibrosis hepatic reserve

SIRT: side effects - risks

Page 29: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

SIRT – clinical aspects:

Indications:• Metastasized colorectal carcinoma (mCRC); First, second or

third line, salvage therapy• Unresectable hepato- or cholangiocellular carcinoma (HCC

/ CCC)• Neuroendocrine liver metastasis

Page 30: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

RESULTS – STUDIESMETASTASIZED COLORECTAL CARCINOMA

(mCRC)

Page 31: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

SIRT – clinical outcome: mCRC

FIRST LINE:• Liver dominant or liver only metastasized colorectal

cancer: First line FOLFOX vs SIRT/FOLFOX or 5FU • 5 studies with overall over 100 patients • significant increase of overall survival for FOLFOX/SIRT.

• FOLFOX 16 - 19 months• SIRT/FOLFOX 29 - 38 months

Gray et al. Ann Oncol 2001;12:1711–20. van Hazel et al. J Surg Oncol 2004;88:78–85Sharma et al. J Clin Oncol 2007;25:1099–106. Kosmider et al. J Vasc Interv Radiol 2011;

22:780-786. Tie et al. ESMO, Ann Oncol 2010;21(Suppl 8): Abs. 698.

Page 32: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

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0

0.2

0.4

0.6

0.8

1

0 6 12 18 24 30 36Months from randomisation

Pro

port

ion s

urv

ivin

g

van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85.

Hazard Ratio 0.33 (95% CI 0.12–0.91)P =0.025

12.8 months5FU/LV

29.4 months5FU/LV + SIR-Spheres

Median Survivaln = 21

First line mCRC: SIRT/5FU vs 5/FU

Page 33: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Eligible Patients:

•Unresectable liver-only or liver-predominant metastatic CRC

•No prior chemotherapy for mCRC

•Fit for combination therapy and SIRT

SIR-Spheres †

Secondary endpoints: ٠ PFS in liver٠ Overall survival٠ Response rate٠ Quality of life٠ Recurrence rate٠ Toxicity and safety

Primary endpoint: Progression-free survival (PFS)

Sponsor: Sirtex

PIs: Prof. Peter Gibbs; Prof. Guy van Hazel

Status: Enrolment complete (March 2013)

Stratify:

•Presence of extra-hepatic metastases

•Degree of liver involvement

•Institution

•Use of bevacizumabFOLFOX6m + bevacizumabC1

FOLFOX6m* +bevacizumabC4

Randomise1:1

n = >450

Multiple SIRTEX Studies completed: e.g.

Page 34: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

SIRT – clinical outcome: mCRC

SECOND or THIRD LINE:• Limited data• 2 studies with overall over 50 patients • significant increase of overall survival for FOLFOX/SIRT.

• 2nd Irinotecan 6 - 10 months• 3rd Panitumumab 8 - 10 months• SIRT/Irinotecan 12 - 17 months

van Hazel et al. J Clin Oncol 2009;27:4089–95. Cove-Smith, Wilson. WCGIC 2011; Abs P-0150.Schoemaker et al. Brit J Cancer 2004;91:1434–41. Van Cutsem et al. Brit J Cancer

2005;92:1055–62.

Page 35: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

SIRT – clinical outcome: mCRC

Salvage therapy:• Best data available• Over 12 studies with up to 600 patients, overall over

1300 patients • significant increase of overall survival for SIRT compared

to historical controls of non responders.• SIRT 10 - 14 months• Historical controls 5 - 7 months

Kennedy et al. Int J Radiat Oncol Biol Phys 2006; 65:412-425

Page 36: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

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mCRC: rectal cancer therapy refractory

ceCT scan - pre

99mTc-MAA scan ceCT perfusion scan 4 weeks later

90Y SPECT

Page 37: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

Nuclear Medicine, University Hospital Zurich

Baseline ceCT scanpre-SIRT

ceCT scan 2 months post-SIRT

mCRC: inoperable metastasis

90Y Injection & SPECT

Page 38: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

RESULTS – STUDIESHEPATOCELLULAR CARCINOMA

Page 39: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

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SIRT – clinical outcome: HCC

FIRST LINE:• Patients with unresectable HCC • 2 studies with overall over 70 patients • significant increase of overall survival for SIRT.

• Supportive care / active therapy 8 months• SIRT 14- 16 months

D'Avola et al . Hepato-gastroenterology 2009; 56: 1683–1688.Lau et al, British Journal of Cancer 1994; 70: 994–999.

Page 40: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

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Control group: 43 8 months

SIR-Spheres microspheres 35 16 months

n Median Survival

P < 0.001

supportive care only

active treatment

0

1.0

0.75

0.5

0.25

Act

uarial Surv

ival

0 126 18 24 30 36

Months after Diagnosis

42

First line HCC: SIRT/Supportive care

D'Avola et al . Hepato-gastroenterology 2009; 56: 1683–1688.

Page 41: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

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72 yo man with recurrent HCC

SIRT: 1.6 GBq/43.2 mCi(right liver)

CT follow up after 4 we and 6 months

A total of 5 lesions: all with very high arterial perfusion.

Page 42: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

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SIRT – clinical outcome: HCC

FIRST- or SECOND LINE to ADVANCED DISEASE :• Patients with unresectable HCC, not suitable for liver

transplant. • 8 studies with overall over 700 patients • significant increase of overall survival for SIRT for patients

with advanced HCC:• Placebo 7.9 months• Sorafenib 10.7 months• SIRT 14-16 months

Sangro et al, Am J Clin Ocncol 2011;34:422-431

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68 Yo woman with recurrent HCC

2 months later SIRT II: 0.8 GBq/21.6 mCi(Seg VII)

SIRT I: 1.2 GBq/32.4 mCi(Seg IV)

MRI 5 months after 2. injection.

Page 44: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

RESULTS – STUDIESCOLANGIOCELLULAR CARCINOMA

Page 45: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

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SIRT – clinical outcome: CCC

AGRESSIVE, CHEMO-REFRACTORY DISEASE : • 8 studies with overall over 100 patients • Prospective study with unresectable patients that failed

chemotherapy :• 24% response rate (RECIST) • 48% stable disease (RECIST)

Saxena et al, Ann Surg Oncol 2010; 17:484-491

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48 yo with CCC

Dynamic ceCT

before SIRT

Dynamic ceCT

6 weeks after SIRT

FDG PET/CT

before SIRT MRI 8 weeks

after SIRT

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Follow up MRI 36 months post Therapy:

no evidence of recurrence

48 yo with CCC

Page 48: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

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Pre

Post

SIR

T +

3 x

Cis

/Gem

34 yo with CCC: SIRT with Cis/Gemzar

Page 49: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

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34 yo with CCC: R0 resection

MRI 5 months post

therapy no evidence

for recurrence

Page 50: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

RESULTS – STUDIESNEUROENDOCRINE LIVERMETASTASIS

Page 51: Selective Internal RadioTherapy - Human Health Campus...van Hazel et al. Journal of Surgical Oncology 2004; 88: 78–85. Hazard Ratio 0.33 (95% CI 0.12–0.91) P=0.025 5FU/LV 12.8

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SIRT – clinical outcome: NET

LIVERMETASTASES NEUROENDOCRINE TUMORS: • Commonly high arterial perfusion• Overall better response rate compared to TACE or

chemotherapy.

Kennedy et al, Am J Clin Oncol 2008;31:271-9

Investigator n ORR SD Median Survival

>1st-line to treatment-refractory disease

Kennedy 148‡ 63.2% 22.7% 70 mo median

King 34 50% 14.7% 59% at 35.2 mo

Saxena 48 54% 23% 35 mo

Cao 58‡ 39.2% 27.4% 36 mo

Meranze 10 40% 60% 70% at 28 mo

Jakobs 25‡ 20.8% 75% 96% at 12 mo

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Only one retrospective trial with 46 patients with NET (G1/G2) – 19 SIRT patients versus 27 TACE patients

SIRT: 26% CR 51% PR 15% SD 8% PD TACE: 13% CR 59% PR 8% SD 21% PD

PFS: SIRT 44 months versus TACE 12 months (p = 0.015)

Both therapies were well tolerated without significant difference in overall survival after a follow up of 104 months.

mNET: SIRT vs TACE

Yuhsin V. Wu et al. J Clin Oncol 30, 2012 (4;300)

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Primary SIRT therapy with 1.7 GBq/45.9 mCi, ambulantPartial response over 16 months, scheduled for 2nd therapy now

39 yo woman, pancreatic NET

Pre-SIRT:

4 we - ceCT

6 mo – FDG PET

(G2 16% MIB, N0, M1 (hep)

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Nuclear Medicine, University Hospital Zurich

SIRT – Conclusion:

Potential technical improvements:- Adequate dose administration- Patient selection – predicting response with perfusion CT- Vascular redistribution – reducing SIRT interventions- Improved Therapy control with 90Y-PET

Clinical outcome:- Promising results have been published especially for

mCRC, HCC and CCC. - The large multicenter trials SIRveNIB, SIRFLOX and SIR-

KRAS closed 2013. Results will be presented at ASCOM 2015.

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Nuclear Medicine, University Hospital Zurich

Thank you!