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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)
23
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
24
• 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