Transcript B.Gray et al

Literature
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Training Module 8 – Version 1.1

Literature
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Training Module 8 – Version 1.1
Clinical Studies
mCRC
HCC
Other Cancer
Mode of Action and Procedure
Radiation Protection
Issues of Concern
Reviews

Literature
®
Training Module 8 – Version 1.1
Published outcome data
Some words about patient collective beforehand:
SIRT is often regarded as second, third or even
fourth line treatment
The more treatments failed, the worse is the
prognosis for the patient
Comparing survival rates can therefore sometimes
be misleading
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Literature
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Training Module 8 – Version 1.1
Published outcome data
Some words about response rate beforehand:
The response is usually measured either as an
effect on a specific tumour marker (CEA or AFP) or
as a decrease in the size of the lesion(s)
It is known that the response (size of lesion) often
seems to be delayed in CT, whereas a functional
scan like PET shows quite quickly that there is a
response
Comparing response rates by tumour size can
therefore sometimes be misleading
CEA = carcinoembryonic antigen
AFP = α-fetoprotein
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Literature
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Training Module 8 – Version 1.1
Published outcome data
Some words about survival beforehand:
Especially in older studies, HAC is used as the
standard. But this local therapy does not treat any
extrahepatic disease
Often this extrahepatic disease mostly leads to the
death of the patient rather than the secondary liver
disease
Comparing survival rates can therefore sometimes
be misleading
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Training Module 8 – Version 1.1
Definitions
Median Survival – Kaplan Meier Plot
The median survival is the time at which half the subjects have died.
The example survival curve shows 50% survival at 5 months, so
median survival is 5 months.
Literature
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Training Module 8 – Version 1.1
Definitions
Hazard – Kaplan Meier Plot
The hazard is the slope of the survival curve – a measure of how rapidly subjects
are dying.
Literature
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Training Module 8 – Version 1.1
Definitions
Hazard – Kaplan Meier Plot
Treatment A
Treatment B
The hazard ratio compares two treatments. If the hazard ratio is 2.0, then the rate
of deaths in one treatment group is twice the rate in the other group. If it is 0.33,
the rate of death is one third of the rate in the other group.
Literature
®
Training Module 8 – Version 1.1
Clinical Studies
mCRC
HCC
Other Cancer
Mode of Action and Procedure
Radiation Protection
Issues of Concern
Reviews

Literature
®
Training Module 8 – Version 1.1
Clinical Studies
mCRC
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Literature
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Training Module 8 – Version 1.1
Clinical Studies
Randomized trial of SIR-Spheres plus chemotherapy vs.
chemotherapy alone for treating patients with liver metastasis
from primary large bowel cancer
B.Gray, G. Van Hazel, M.Hope, M.Burton, P.Moroz, J.Anderson, V.Gebski
Annals of Oncology 12:1711-1720, 2001
Phase III randomized trial (open for entry 1991-1997)
SIR-Spheres plus hepatic artery chemotherapy via port
74 patients with bipolar non-resectable CRC metastasis
Primary objectives: response, time to progression,
survival, quality of life and toxicity
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Training Module 8 – Version 1.1
Clinical Studies
B.Gray et al, Annals of Oncology 12:1711-1720, 2001
n=70
Randomization
4 patients weren't eligible
n=36
n=34
HAC with FUDR
SIRT +
• 12 day cycle
HAC with FUDR
• 4 weekly
• 12 day cycle
• 18 cycles
• 4 weekly
• 18 cycles
SIRT within 4 weeks after port implantation
Angiotensin injected prior to implant
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Training Module 8 – Version 1.1
Clinical Studies
B.Gray et al, Annals of Oncology 12:1711-1720, 2001
CR=complete response, PR=partial response, NC=no change, PD= progressive disease,
NA=not assessable
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Training Module 8 – Version 1.1
Clinical Studies
B.Gray et al, Annals of Oncology 12:1711-1720, 2001
CR=complete response, PR=partial response, NC=no change, PD= progressive disease,
NA=not assessable
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Literature
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Training Module 8 – Version 1.1
Clinical Studies
B.Gray et al, Annals of Oncology 12:1711-1720, 2001
CR=complete response, PR=partial response, NC=no change, PD= progressive disease,
NA=not assessable
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Literature
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Training Module 8 – Version 1.1
Clinical Studies
B.Gray et al, Annals of Oncology 12:1711-1720, 2001
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Literature
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Training Module 8 – Version 1.1
Clinical Studies
B.Gray et al, Annals of Oncology 12:1711-1720, 2001
Kaplan-Meier: Survival
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Literature
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Training Module 8 – Version 1.1
Clinical Studies
B.Gray et al, Annals of Oncology 12:1711-1720, 2001
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Literature
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Training Module 8 – Version 1.1
Clinical Studies
B.Gray et al, Annals of Oncology 12:1711-1720, 2001
 Significant greater response rate
 Significant longer time to disease progression
 Increased survival
 No increased toxicity
 No loss of quality of life
 Risk of death from progression of liver metastasis was 3.1
times higher in the control group
 One patient treated with SIR-Spheres is considered
permanently cured
 Study was basis for the pre-market approval of FDA (US)
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Training Module 8 – Version 1.1
Clinical Studies
B.Gray et al, Annals of Oncology 12:1711-1720, 2001
 Study closed prior to completion (95 patients planned)
 Statistically the study with only 74 patients is not very
powerful
 Most patients died from extra-hepatic disease
 Treatment regimen not suitable to treat any extra-hepatic
disease
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Training Module 8 – Version 1.1
Clinical Studies
Randomized Phase 2 Trial of SIR-Spheres Plus Fluorouracil/
Leucovorin
Chemotherapy
Versus
Fluorouracil/Leucovorin
Chemotherapy Alone in Advanced Colorectal Cancer
Guy Van Hazel, Anthony Blackwell, James Anderson, David Price, Paul
Moroz, Geoff Bower, Guiseppe Cardaci, Bruce Gray
Journal of Surgical Oncology 2004;88:78-85
Phase II trial with 21 patients
Systemic chemotherapy with and without SIRT (femoral
catheter)
Patients with CRC liver metastasis with and without
extra-hepatic disease
Primary objectives: response, time to progression and
toxicity
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Training Module 8 – Version 1.1
Clinical Studies
G. Van Hazel et al, Journal of Surgical Oncology 2004;88:78-85
n=21
Randomization
n=11
n=10
Systemic Chemo
SIRT +
• 5-FU/Leucovorin
Systemic Chemo
• 5 day cycle
• 5-FU/Leucovorin
• 4 weekly
• 5 day cycle
• until progression
• 4 weekly
• until progression
SIRT 3rd or 4th day of 2nd cycle
Angiotensin injected prior to implant
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Training Module 8 – Version 1.1
Clinical Studies
G. Van Hazel et al, Journal of Surgical Oncology 2004;88:78-85
Time to progressive disease
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Training Module 8 – Version 1.1
Clinical Studies
G. Van Hazel et al, Journal of Surgical Oncology 2004;88:78-85
Survival by treatment
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Training Module 8 – Version 1.1
Clinical Studies
G. Van Hazel et al, Journal of Surgical Oncology 2004;88:78-85
 Time to PD significantly longer for SIRT patients (18.6 month
versus 3.6 month)
 Significant better median survival for SIRT patients (29.4
month versus 12.8 month)
 One SIRT patient still alive at date of publication
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Training Module 8 – Version 1.1
Clinical Studies
G. Van Hazel et al, Journal of Surgical Oncology 2004;88:78-85
 Small number of patients only
However, the high response rate, long time to disease
progression and survival suggest that adding SIRT to
systemic
chemotherapy
can
improve
patient
outcome.
SIRFLOX Study
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Training Module 8 – Version 1.1
Clinical Studies
FOLFOX 4 Dose Escalation Trial
Guy Van Hazel et al
ASCO GI 2005, Florida, USA
Phase II trial with 20 patients
Systemic chemotherapy with Oxaliplatin in combination
with SIRT (femoral catheter)
Patients with CRC liver metastasis
Primary objectives: response and survival
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Training Module 8 – Version 1.1
Clinical Studies
G. Van Hazel et al, ASCO GI 2005, Florida, USA
 2 patients with complete response, 16 with partial response
and 2 with static disease. None with PD
 Median time to progression is currently 11.9 months
 For those with liver only disease the time to progression is
currently 14.9 months
 Median survival cannot be determined at that stage
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Training Module 8 – Version 1.1
Clinical Studies
Randomized Comparative Study Of FOLFOX6m Plus SIR-Spheres
versus FOLFOX6m Alone As First Line Treatment In Patients With
Non-Resectable Liver Metastasis From Primary Colorectal
Carcinoma
Peter Gibbs and Guy Van Hazel (Principal Investigator)
Unpublished – Study open to accrual
Trial with more than 300 patients
Systemic chemotherapy with and without SIRT (femoral
catheter)
Patients with CRC liver metastasis with and without
extra-hepatic disease
Primary objectives: Progression free survival at any site
and progression free survival in the liver
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Training Module 8 – Version 1.1
Clinical Studies
P. Gibbs and G. Van Hazel, Unpublished – Study open to accrual soon
n>300
Randomization
n>150
n>150
Systemic Chemo
SIRT +
• Oxaliplatin
Systemic Chemo
• Leucovorin
• Oxaliplatin
• 5-FU
• Leucovorin
• repeated 2 weekly
• 5-FU
• repeated 2 weekly
SIRT 1st week of 1st cycle
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Training Module 8 – Version 1.1
Clinical Studies
P. Gibbs and G. Van Hazel, Unpublished – Study open to accrual
 Statistical powerful study
 State of the art chemotherapy regimen
 Multicentre study
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Training Module 8 – Version 1.1
HCC
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Training Module 8 – Version 1.1
Clinical Studies
Treatment of inoperable hepatocellular carcinoma with intrahepatic
arterial yttrium-90 microspheres: a phase I and II study
W.-Y. Lau, W.-T. Leung, S. Ho, N.W.Y. Leung, M. Chan, J. Lin, C. Metreweli,
P. Johnson and A.K.C. Li
British Journal of Cancer 1994;70:994-999
Phase I and II trial with 18 patients
Patients with inoperable HCC, recruited 90-93
SIRT via port
Primary objectives: response and survival
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Training Module 8 – Version 1.1
Clinical Studies
W.-Y. Lau et al, British Journal of Cancer 1994;70:994-999
n=18
Randomization
n=8
n=8
SIRT
SIRT
< 120Gy
> 120Gy
Angiotensin injected prior to implant
Angiotensin injected prior to implant
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Training Module 8 – Version 1.1
Clinical Studies
W.-Y. Lau et al, British Journal of Cancer 1994;70:994-999
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Training Module 8 – Version 1.1
Clinical Studies
W.-Y. Lau et al, British Journal of Cancer 1994;70:994-999
 Significant better median survival for patients receiving the
higher dose (55.9 versus 26.2 weeks)
 Dose of >120Gy is recommended
 Three SIRT patients still alive after 10.4, 17.2 and 27.4
month respectively
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Literature
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Training Module 8 – Version 1.1
Clinical Studies
W.-Y. Lau et al, British Journal of Cancer 1994;70:994-999
 Small number of patients only
However, the result clearly shows the advantage of a
well dosed SIRT treatment.
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Training Module 8 – Version 1.1
Clinical Studies
mCRC
HCC
Combined Cancer
Mode of Action and Procedure
Radiation Protection
Issues of Concern
Reviews
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Literature
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Training Module 8 – Version 1.1
Clinical Experience in mCRC
Kennedy et al, USA, 208 patients
Stubbs et al, NZ, 165 patients
Gray et al, Aus, 71 patients
Lim et al, Aus, 30 patients
Poepperl et al, Germany, 23 patients
Wong et al, USA, 19 patients
Murthy, USA, 12 patients
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Literature
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Training Module 8 – Version 1.1
Published outcome data
Excellent overview on all published study data as
well as clinical experience on both, glass spheres
and SIR-Spheres
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Literature
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Training Module 8 – Version 1.1
Published outcome data
Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193
Author
Gray et al.
Year
1989
Number of Patients
10
Type of tumour
mCRC
Therapy
Y-90 alone
Dose
16.8-138.9Gy to normal liver
Result
8 of 9 with >50% reduction in CEA
Remarks
Intraoperative dosimetry
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Literature
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Training Module 8 – Version 1.1
Published outcome data
Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193
Author
Gray et al.
Year
1992
Number of Patients
29
Type of tumour
mCRC
Therapy
Y-90 ± HAC
Dose
755 – 4240 MBq
Result
70% average decrease in pretreatment CEA
45% response rate based on CT
Remarks
No significant toxicity
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Literature
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Training Module 8 – Version 1.1
Published outcome data
Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193
Author
Gray et al.
Year
2000
Number of Patients
71
Type of tumour
mCRC
Therapy
Y-90 + HAC
Dose
Average activity 2130MBq
Result
85% overall response rate
Median survival 13.5 months
Remarks
Fatal radiation hepatitis in one patient
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Literature
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Training Module 8 – Version 1.1
Published outcome data
Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193
Author
Gray et al.
Year
2001
Number of Patients
74
Type of tumour
mCRC
Therapy
HAC ± Y-90
Dose
2000 – 3000MBq
Result
72% overall response rate versus 47% (HAC)
40% higher death rate in HAC alone
Remarks
Phase III randomized trial
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Literature
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Training Module 8 – Version 1.1
Published outcome data
Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193
Author
Stubbs et al.
Year
2001
Number of Patients
50
Type of tumour
mCRC
Therapy
Y-90 + HAC
Dose
2000 – 3000MBq
Result
Median survival 24.7 / 11.4 months (without
extrahepatic / with extrahepatic disease)
Remarks
Duodenal ulceration in six patients
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Literature
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Training Module 8 – Version 1.1
Published outcome data
Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193
Author
Stubbs et al.
Year
2003
Number of Patients
100 (including 50 published earlier)
Type of tumour
mCRC
Therapy
Y-90 + HAC
Dose
2000 – 3000MBq
Result
Median survival 12.6 / 8.3 months (without
extrahepatic progression / with extrahepatic
progression at 6 month)
Remarks
Fatal radiation hepatitis in one patient
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Literature
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Training Module 8 – Version 1.1
Published outcome data
Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193
Author
Van Hazel et al.
Year
2004
Number of Patients
21
Type of tumour
mCRC
Therapy
Y-90 + Systemic Chemotherapy
Dose
1500 – 2500MBq
Result
Time to progression 18.6 months versus 3.6
months
Remarks
Phase III randomized trial
Radiation hepatitis in one patient
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Literature
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Training Module 8 – Version 1.1
Published outcome data
Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193
Author
Murthy et al.
Year
2005
Number of Patients
12
Type of tumour
mCRC
Therapy
Y-90 + Systemic Chemotherapy
Dose
Median dose 39.6mCi
Result
4/7 patients with response on CEA levels
5/12 patients with stable radiologic response
Remarks
Treatment after failure of multiple chemotherapy
regimens
Gastric ulceration in one patient
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Literature
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Training Module 8 – Version 1.1
Published outcome data
Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193
Author
Wong et al.
Year
2005
Number of Patients
19
Type of tumour
MET (metastatic)
Therapy
Y-90 alone
Dose
Median dose 76Gy
Result
15 of 19 patients with metabolic response (PET)
Remarks
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Literature
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Training Module 8 – Version 1.1
Published outcome data
Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193
Author
Lim et al.
Year
2005
Number of Patients
32 / 5
Type of tumour
mCRC / HCC
Therapy
Y-90 + Systemic Chemotherapy
Dose
Unavailable
Result
12 of 43 patients with partial response (CT)
Remarks
Severe gastric ulceration in four patients
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Literature
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Training Module 8 – Version 1.1
Published outcome data
Is there a common pattern of results?
No: All results seem to be different, because:
 different patient collectives
 different outcome measurements
Yes: Irregardless of patient collective and
outcome measurements, all SIRTEX patients
are doing extraordinary well!

Literature
®
Training Module 8 – Version 1.1
Clinical Studies
mCRC
HCC
Other Cancer
Mode of Action and Procedure
Radiation Protection
Issues of Concern
Reviews

Literature
®
Training Module 8 – Version 1.1
Published outcome data
Excellent overview on all published study data as
well as clinical experience on both, glass spheres
and SIR-Spheres

Literature
®
Training Module 8 – Version 1.1
Published outcome data
Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193
Author
Lau et al.
Year
1994
Number of Patients
18
Type of tumour
HCC
Therapy
Y-90 alone
Dose
26-409Gy to tumour
Result
50% partial response by CT scan
100% response by AFP or ferritin levels
Median survival 55.9 weeks
Remarks
Significant better survival in patients >120Gy
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Literature
®
Training Module 8 – Version 1.1
Published outcome data
Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193
Author
Lau et al.
Year
2001
Number of Patients
82
Type of tumour
HCC
Therapy
Y-90 alone
Dose
Median cumulative dose 332Gy and 268Gy
Result
Median survival 21.0 months (332Gy)
Median survival 4.5 months (268Gy)
Remarks
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Literature
®
Training Module 8 – Version 1.1
Published outcome data
Sean Garrean, N. Joseph Espat Surgical Oncology 2005;14:179-193
Author
Murthy et al.
Year
2005
Number of Patients
12
Type of tumour
mCRC
Therapy
Y-90 + Systemic Chemotherapy
Dose
Median dose 39.6mCi
Result
4/7 patients with response on CEA levels
5/12 patients with stable radiologic response
Remarks
Treatment after failure of multiple chemotherapy
regimens
Gastric ulceration in one patient

Literature
®
Training Module 8 – Version 1.1
Clinical Studies
mCRC
HCC
Other Cancer
Mode of Action and Procedure
Radiation Protection
Issues of Concern
Reviews

Literature
®
Training Module 8 – Version 1.1
Published outcome data
G. Poepperl et al. Cancer Biotherapy & Radiopharmaceuticals 2005;20:200-208
Author
Poepperl et al.
Year
2005
Number of Patients
12 / 4 / 2 / 1 / 1 / 2
Type of tumour
CRC/Breast/Pancreas/Melanoma/NET/ HCC
Therapy
Y-90 + Systemic Chemotherapy prior to SIRT
Dose
Mean activity: 2270MBq
Result
Promising responses, long term survival data to
be published
Remarks
Mild pancreatitis and gastric ulceration in one
patient each
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Training Module 8 – Version 1.1
Published outcome data
D. Rubin et al. Integrative Cancer Therapies 2004;3:262-267
Author
Rubin et al.
Year
2004
Number of Patients
1
Type of tumour
Metastatic Breast Cancer
Therapy
Y-90 + Systemic Chemotherapy prior to SIRT
Dose
-
Result
Stable disease after 13 months
Remarks
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Training Module 8 – Version 1.1
Published outcome data
D. Coldwell et al. Society of Interventional Radiology (SIR) conference
Author
Coldwell et al.
Year
2005
Number of Patients
34
Type of tumour
Metastatic Breast Cancer
Therapy
Y-90
Dose
Average dose 1.75GBq
Result
100% response (PET-Scan)
30/34 still alive after 10 months
Remarks
All patients report palliation of liver related
symptoms
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Training Module 8 – Version 1.1
Published outcome data
D. Coldwell et al. World Congress on Gastrointestinal Cancer
Author
Coldwell et al.
Year
2005
Number of Patients
84
Type of tumour
Metastatic Neuroendocrine Tumours
Therapy
Y-90
Dose
Average dose 1000Gy to tumour volume
Result
67% response (PET-Scan)
Symptom relief in symptomatic patients
Remarks
14 cases of grade 3 GI toxicity
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Training Module 8 – Version 1.1
Published outcome data
A. Kennedy et al. International Congress on Anti-Cancer Treatment
Author
Kennedy et al.
Year
2005
Number of Patients
40
Type of tumour
Metastatic Neuroendocrine Tumours
Therapy
Y-90 (Thera-Spheres or SIR-Spheres)
Dose
Average dose 36.59mCi (SIR-Spheres)
Result
3 CR, 3 SD, 34 PR
Remarks
Follow-up 2-48 months with 7 patients dod
dod = dead of disease
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Training Module 8 – Version 1.1
Published outcome data
J. King et al. World Congress on Gastrointestinal Cancer
Author
King et al.
Year
2005
Number of Patients
22
Type of tumour
Metastatic Neuroendocrine Tumours
Therapy
Y-90
Dose
-
Result
Radiological response (RECIST) at one month: 3
PR, 12 SD, 1 PD, 2 PR in one lobe
Remarks
2 patients dod at 4 and 7 months
dod = dead of disease
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Literature
®
Training Module 8 – Version 1.1
Clinical Studies
mCRC
HCC
Other Cancer
Mode of Action and Procedure
Radiation Protection
Issues of Concern
Reviews

Literature
®
Training Module 8 – Version 1.1
Mode of Action and Procedure
a MUST to READ

Literature
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Training Module 8 – Version 1.1
Mode of Action and Procedure
Murthy et al, RadioGraphics 2005; 25:41-55
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Training Module 8 – Version 1.1
Mode of Action and Procedure
Murthy et al, RadioGraphics 2005; 25:41-55
SIRT therapy principles
Thera-Spheres® versus SIR-Spheres®
Patient selection criteria
Therapy planning and workup
Clinical outcomes
Complications
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Training Module 8 – Version 1.1
Mode of Action and Procedure
a MUST to READ
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Training Module 8 – Version 1.1
Mode of Action and Procedure
Salem et al, J Vasc Interv Radiol 2006; 17:1251-1278
Technical and methodological considerations
Patient screening and selection
Vascular anatomy
Treatment process
Thera-Spheres® and SIR Spheres®
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Training Module 8 – Version 1.1
Mode of Action and Procedure
a MUST to READ
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Training Module 8 – Version 1.1
Mode of Action and Procedure
Salem et al, J Vasc Interv Radiol 2006; 17:1425-1439
Special Topics
Patient selection
Complications
Lobar versus whole liver approach
Treating patients after other other treatments
Combination with other treatments
Workup and treatment the same day?
Patients with increased lung shunting
Long-term follow up
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Training Module 8 – Version 1.1
Mode of Action and Procedure
a MUST to READ
Shows the high degree of variation in the
anatomy of the hepatic arterial bed and the
consequences with regard to SIRT
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Training Module 8 – Version 1.1
Mode of Action and Procedure
Liu et al, J Vasc Interv Radiol 2005, 16:911-935
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Literature
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Training Module 8 – Version 1.1
Mode of Action and Procedure
Shows clearly that an early response on a
treatment with SIR-Spheres can be detected by
PET scanning but not by CT.
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Training Module 8 – Version 1.1
Mode of Action and Procedure
Szyszko et al, Nuclear Medicine Communications 2007, 28:15-20
PET
CT
before treatment
after treatment
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Training Module 8 – Version 1.1
Mode of Action and Procedure
Points out the importance of a proper work-up,
gives a quite good perspective on likelihood of
side effects and how to deal with those
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Literature
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Training Module 8 – Version 1.1
Mode of Action and Procedure
Further publications on:
Blood supply of hepatic metastasis
Dose calculation via partition model
Microsphere and dose distribution within the liver
Intraoperative dosimetry
Pathologic response
Responses on PET and CT scan
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Literature
®
Training Module 8 – Version 1.1
Clinical Studies
mCRC
HCC
Other Cancer
Mode of Action and Procedure
Radiation Protection
Issues of Concern
Reviews

Literature
®
Training Module 8 – Version 1.1
Radiation Protection
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Literature
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Training Module 8 – Version 1.1
Radiation Protection
Radiation Protection in Australia Series 4, 2002
Dose limits and dose constrains
The discharge of patients following treatment
Maximum dose rate at time of discharge
Maximum activity to be administered to an
outpatient
Use of public transport by the patient
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Training Module 8 – Version 1.1
Radiation Protection
Gives a good overview of all radiation safety
aspects including exposure and doses

Literature
®
Training Module 8 – Version 1.1
Clinical Studies
mCRC
HCC
Other Cancer
Mode of Action and Procedure
Radiation Protection
Issues of Concern
Reviews

Literature
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Training Module 8 – Version 1.1
Issues of Concern
Publications on:
Portal hypertension after SIRT
Radiation induced ulceration of the stomach
Radiation pneumonitis
Extra-hepatic embolization
Serum proinflammatory cytokine response
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Literature
®
Training Module 8 – Version 1.1
Clinical Studies
mCRC
HCC
Other Cancer
Mode of Action and Procedure
Radiation Protection
Issues of Concern
Reviews

Literature
®
Training Module 8 – Version 1.1
a MUST to READ

Literature
®
Training Module 8 – Version 1.1
Review article
There are at least 15 further review article available
Highly recommended
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Literature
®
Training Module 8 – Version 1.1
Clinical Studies
mCRC
HCC
Other Cancer
Mode of Action and Procedure
Radiation Protection
Issues of Concern
Reviews
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Liver Cancer
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Training Module 8 – Version 1.1
What is most important to remember?
All clinical studies with outcome
Clinical experience published
Overview to answer specific questions
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Literature
®
Training Module 8 – Version 1.1
RECIST criteria
Complete Response (CR)
Disappearance of all known lesions on radiological grounds and
normalization of AFP for at least 4 weeks
Partial Response (PR)
Decrease of 50% or more in the tumour volume and/or a decrease of
more than 50% in AFP or ferritin level for at least 4 weeks
Static Disease (SD)
Decrease of tumour volume of less than 50% or an increase in
tumour volume of not more than 25%
Progressive Disease (PD)
Increase of tumour volume of more than 25% or the appearance of a
new lesion
Literature
®
Training Module 8 – Version 1.1
Definitions
Median Survival – Kaplan Meier Plot
The median survival is the time at which half the subjects have died.
The example survival curve shows 50% survival at 5 months, so
median survival is 6 months.
Literature
®
Training Module 8 – Version 1.1
Definitions
Hazard – Kaplan Meier Plot
The hazard is the slope of the survival curve – a measure of how rapidly subjects
are dying.
Literature
®
Training Module 8 – Version 1.1
Definitions
Hazard – Kaplan Meier Plot
The hazard ratio compares two treatments. If the hazard ratio is 2.0, then the rate
of deaths in one treatment group is twice the rate in the other group. If it is 0.33,
the rate of death is one third of the rate in the other group.