SIRT in metastatatic colorectal cancer   

Dr. med. Stefan Pluntke Center of Micro-Invasive Tumor Therapies

Kliniken Essen-Mitte   

Surgery provides a chance for long-term survival

► Surgery is the standard of care in patients with colorectal liver metastases providing a chance for long-term survival

► but only 20% of theses patient are eligible for surgery

Rationale of intraarterial therapies

► Background

► Normal hepatic blood supply > 80% portal circulation < 20% arterial circulation ► Liver metastases > 80% arterial circulation < 20% portal circulation

(Segall 1926; Breedis & Young 1954)

SIRT Selective Internal Radiotherapy

SIRT Selektive Interne Radiotherapy

► Yttrium 90

► pure β-Emitter (Electron) ► Halftime 64,2 h ► after 13 days 97,5% of radiation is done ► max. depth of radiation in soft tissue 11 mm ► mean dephth 2,5 mm

Microembolic SIRT

External Beam Dose RangesWith SIRT, dosing is higher than what has been historically provided

through external beam radiation therapy

Kennedy AS et al. Int J Radiat Oncol Biol Phys. 2004;60(5):1552-63.

SIRT Rationale Minimal damage to adjacent normal tissues due to

rapid radiation dose fall-off

Kennedy AS et al. Int J Radiat Oncol Biol Phys. 2004;60(5):1552-63.

SIRT Rationale (cont’d) Minimal damage to adjacent normal tissues due to

rapid radiation dose fall-off

3D Microdosimetry 100 Gy 1000 Gy

Kennedy AS et al. Int J Radiat Oncol Biol Phys. 2004;60(5):1552-63.

First-Line Therapy

The SIRFLOX/FOXFIRE Global Trial

SIRFLOX/FOXFIRE Global Trial design

SIRFLOX/FOXFIRE Global Trial

SIRFLOX/FOXFIRE Global

SIRFLOX/FOXFIRE Global

SIRFLOX/FOXFIRE Global

SIRFLOX/FOXFIRE Global

Second Line

EPOCH-Trial

A Phase III Clinical Trial of Evaluating TheraSphere™ in Patients with Metastatic Colorectal Carcinoma of the Liver

who have Failed First Line Chemotherapy

EPOCH trial design 2nd Line mCRC

Salvage -Therapy

46 Patients (23 Arm A/21 Arm B)

Median TTLP 2,1 Mo vs 5,5 Mo p 0,003 Median TTP 2,1 Mo vs 4,5 Mo p 0,03

OS 7,3 Mo vs 10,0 Mo p 0,8 n.s.

Publication Population No. of patients

Outcomes (mCRC patients) Safety (overall cohort)

Lewandowski et al. (2014)

• Unresectable liver metastases from CRC refractory to standard of care

214 • OS: 10.6 mo • Grade ≥3 lymphocyte (44%), bilirubin (11%), albumin (10%), alkaline phosphatase (11%)

• No gastric ulcers or pneumonitis

Benson et al. (2013)

• Unresectable liver metastases refractory to standard of care

151 (mCRC: 58)

• ORR (RECIST): 5.2% • PFS: 2.9 mo • OS: 8.8 mo

• Grade ≥3 pain (12.8%), alkaline phosphatase (8.1%), deaths (7.4%), bilirubin (5.3%), lymphopenia (4.1%), ascites (3.4%), vomiting (3.4%)

• GI ulcer: n = 1 (0.7%)

Mulcahy et al. (2009)

• Unresectable, chemorefractory liver metastases from CRC

72 • ORR (WHO): 40.3% • ORR (PET): 77% • Median TTHP: 15.4

mo • OS: 14.5 mo

• Grade ≤2 transient fatigue (61%), nausea (21%), abdominal pain (25%)

• Grade ≥3 bilirubin (12.6%) • GI ulcer: n = 1 (Gr 1/2 or 1.4%)

Sato et al. (2008)

• Unresectable, chemorefractory liver metastases

137 (mCRC: 51)

• OS: 457 d (15 mo) • 1- yr OS: 53.7% • 2-yr OS: 26.7%

• Fatigue (56%), abdominal pain (26%), nausea (23%)

• Grade ≥3 bilirubin (4%) • GI ulcer (n = 1 or 0.7%), radiation-

induced cholecystitis (n = 1), bilomas (n = 2), hepatic abscess (n = 1)

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TheraSphere® Clinical Outcomes in mCRC

• A 12-year prospective study conducted at a large, comprehensive cancer care centre with significant expertise in locoregional therapies

– 214 patients treated with TheraSphere® between November 2001 and January 2013 – Median survival was 10.6 months from first 90Y treatment

TheraSphere ® may have a role in the treatment of unresectable and refractory mCRC patients who have limited therapeutic options

Lewandowski RJ, Memon K, Mulcahy MF, et al. Twelve-year experience of radioembolization for colorectal hepatic metastases in 214 patients: survival by era and chemotherapy. Eur J Nucl Med Mol Imaging. 2014;41:1861-1869.

TheraSphere® Clinical Outcomes in mCRC

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• Prospective, multicentre, open-label phase II trial investigating safety and efficacy of TheraSphere® in patients with unresectable liver metastases refractory to standard of care therapies,

– 151 patients treated between January 2007 and October 2009 of which 61 were mCRC patients

8.8 10.5 11.8

Benson AB, Geschwind JF, Mulcahy MF, et al. Radioembolisation for liver metastases: results from a prospective 151 patient multi-institutional phase II study. Eur J Cancer 2013;49:3122-3130.

TheraSphere ® resulted in survival benefit in mCRC patients refractory to current standard of care therapies

Annals of Oncology 27: 1386–1422, 2016 doi:10.1093/annonc/mdw235

2016

Guidelines metastatic colorectal cancer The Toolbox

Annals of Oncology 27: 1386–1422, 2016 doi:10.1093/annonc/mdw235

Conclusion • SIRT seems to be an option in later therapy-lines

in metastatic colorectal cancer • ESMO Guidelines support the use of SIRT • Patient selection is crucial • SIRT should be performed in experienced

centers • SIRT is not SIRT!

Dies ist eine Überschrift Über maximal zwei Zeilen

Dr. Max Müller-Mustermann

Dr. Stefan Pluntke

Thank you for attention

www.mikromed.org