1. Radiation Protection
regarding
89Zr-cetuximab
Frank Hoebers, MD PhD
Maastro Clinic, Maastricht
MAASTRO Clinic
January 2014

2. Klik om deOutline bewerken
stijl te
• Learning Objectives
• Target audience
• Background of ARTFORCE study
• Aspects of radiation safety
• Practical guidelines for nursing and treating staff

3. Klik Learning Objectives
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The objective of this session is
to train medical personnel on
radiation safety measures for the
ARTFORCE head and neck study

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Target Audience
Personnel involved in the study:
• Nursing staff on day care unit and wards (cisplatin / cetuximab)
• Radiotherapy Technologists on linacs
• Treating physicians
• Consider to train chief-nurses of groups who will only see patients in
extra-ordinary circumstances:
– e.g. during admission of the patient to emergency room or short
stay ward
Make sure to have radiation exposure experts
available in case of possible emergencies

5. Background: Cetuximab-based therapies
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In recurrent and metastatic HNSCC:
Extreme Study: Vermorken et al., NEJM, 2008
The addition of cetuximab prolonged the median overall survival from:
7.4 months in the chemotherapy-alone group
TO
10.1 months in the group that received
chemotherapy plus cetuximab

6. Treatment ofde stijl te bewerken
Klik om locally advanced HNSSC
cisplatin / RT
cetuximab / RT
cisplatin / cetuximab / RT
RTOG 0522
n = 940:
cisplatin-cetuximab /RT vs cisplatin /RT
• PFS: 2-Y: 63% vs. 64%
• OS: 2-Y: 83% vs. 80%
• more toxicity
Pignon, 2009
Bonner, 2010
Ang, ASCO 2012

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Cetuximab
• Small improvements in outcome in combination with
chemotherapy and radiotherapy
• Adds to the toxicity profile in Chemo-RT
• Efficacy difficult to predict
Need for a selection tool to predict
cetuximab efficacy in individual patient

8. Efficacy of Cetuximab determined by
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• Presence of target (EGFR, epidermal growth factor receptor)
• Access of drug to target (pharmacokinetics/-dynamics):
• Vascular perfusion
• Interstitial pressure
• Non-target uptake in normal tissue
Role for non-invasive, in vivo imaging of uptake?

9. Radioactive labeledbewerken
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• In vivo imaging using tracer labelled to drug
• Cetuximab has long half life => select suitable tracer
•
89Zirconium:
half life 78 hours

10. 89Zr-Cetuximab
uptake in tumor models
Aerts et al. JNM 2009
•
•
Uptake present in several tumours expressing EGFR
No uptake in EGFR negative tumour

11. 89Zr-Cetuximab:
Phase I – Results
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18FDG
PET-CT
89Zr-Cetuximab
PET
J. van Loon et al. Radiotherapy and Oncology, Vol. 106, suppl 1, Febr 2013, p 57.

12. ARTFORCE study design
N = 268 patients to be recruited
in several european centres
Randomization after informed consent
89Zr-Cetuximab
Cisplatinum:
40mg/m2 weekly i.v.
+
Standard RT
Tumour + involved nodes:
35 x 2.0Gy = 70Gy
Elective nodes
35 x 1.55 = 54.25Gy
Cisplatinum:
40mg/m2 weekly i.v.
+
Redistributed RT
Tumour 50% PET:
35 x 2.0 -2.4Gy =
dose gradient 70-84Gy
Tumour other + involved nodes
35 x 2Gy = 70Gy
Elective nodes
35 x 1.55 = 54.25Gy
scan
Cetuximab:
250mg/m2 weekly i.v.
+
Standard RT
Tumour + involved nodes:
35 x 2.0Gy = 70Gy
Elective nodes
35 x 1.55 = 54.25Gy
Cetuximab:
250mg/m2 weekly i.v.
+
Redistributed RT
Tumour 50% PET:
35 x 2.0 -2.4Gy =
dose gradient 70-84Gy
Tumour other + involved nodes
35 x 2.0Gy = 70Gy
Elective nodes
35 x 1.55 = 54.25Gy

13. Imaging de stijl Zr Cetuximab
with 89 te bewerken
Klik om
89Zr-cetuximab
scan procedures:
• Administration of 60 MBq on day -7
• Scan 1 on day -3
• Scan 2 on day 1 (is also start of chemoradiotherapy)
Day
-7
-6
Administration
of 60 MBq
-5
-4
-3
Scan 1
-2
-1
1
2
Scan 2
+
Chemoradiotherapy
Starts
3
…

14. Radiation safety
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Radioactivity: general principles to reduce exposure:
• Increase the distance to the radioactive source:
• Quadratic law: double distance  reduce exposure by a factor of 4
• Reduce residence time at source

15. Practicalom de stijl te bewerkenstaff
Klik guidelines for nursing
Respect a 2-week period of radiation protection measures:
Week 1
Week 2
Week 3
Injection
Start treatment:
2nd administration:
3rd administration:
89Zr-cetuximab
RT +
Cisplatin/Cetuximab
Cisplatin/Cetuximab
Cisplatin/Cetuximab
• Cisplatin: nurses and staff at chemotherapy ward
• Cetuximab: nurses and staff at day care unit
• Radiotherapy: linac team, outpatient clinic, nurses, dieticians, etc.
• 2x PET-CT: technicians on scanner

16. Radiation safety
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• 89Zirconium: half life of 78.41 hrs.
• Radiation exposure has been estimated for personnel (nurses and RTT’s):
• Administration of cisplatin during 24 hrs. hospital stay:
7.91 uSv + 7.15 uSv
• Administration of cetuximab in day care unit:
6.97 uSv
• 5 fractions of radiotherapy on linac:
1.74 uSv
• These doses are low and within accepted limits:
• Natural background radiation per year:
+/- 2000 uSv
• Dose limit for radiological worker per year:
6000 uSv
• Dose limit for non-occupational exposure (nurses/family) per year:
1000 uSV
• Transatlantic air flight:
15-30 uSv

17. Practicalom de stijl te bewerkenstaff
Klik guidelines for nursing
• Consider to mark study patient in Electronic Patient File:
• Date of administration of 89Zr-cetuximab
• And following 2 weeks
• Appoint contact persons for questions:
• Local study P.I.
• Local Radiation Safety Authority
• Arrange for a 24x7 coverage

18. Practicalom de stijl te bewerkenstaff
Klik guidelines for nursing
Protection of nursing staff during 2-week period of guidelines
• Respect general and standard hygienic measures when in contact with
patient and wear gloves
• There is no need for mouth mask or protective glasses
Rotate nursing staff if:
• Several patients are hospitalized during the 2-week period of
radiation protection measures
• A patient needs to be hospitalized for more than 1 day
For RTT’s: no rotation necessary per se
Avoid contact between pregnant personnel and study patients during
the 2-week period!

19. Practicalom de stijl te bewerkenstaff
Klik guidelines for nursing
Protection of Fellow Patients during 2-week period of guidelines
• Planned admission < 2 days:
• No need for 1-bed room (depending on distance between beds)
• Admission > 2 days:
• Preferably 1-bed room to reduce exposure to fellow patients
• During the stay at the Emergency Room:
• Separate room: allow 1.5m distance between 2 patients
• Waiting room of radiotherapy faciltiy: no specific measures

20. Practicalom de stijl te bewerkenstaff
Klik guidelines for nursing
Body Excreta of study patients during 2-week period of guidelines
•
Urine, faeces, sputum, pus, and perspiration:
• Do not contain 89Zr-cetuximab
•
Therefore:
• Joint bathroom is allowed
• Standard procedures for cleaning are suitable (toilet, sheets, plates,
cutlery, beds, floors, etc.)
• Waste (foods, diapers, etc.) can be discarded using standard waste
containers

21. Practicalom de stijl te bewerkenstaff
Klik guidelines for nursing
Body Excreta of study patients during 2-week period of guidelines
•
Blood:
• Potential source of 89Zr-cetuximab
•
Therefore, in case of contamination of staff by blood:
• Contact local P.I. and local Radiation Safety Authority a.s.a.p.
• Rinse (skin of staff) with water

22. Practicalom de stijl te bewerkenstaff
Klik guidelines for nursing
Body Excreta of study patients during 2-week period of guidelines
•
Blood:
• Potential source of 89Zr-cetuximab
•
Therefore, in case of contamination of material by blood:
• Contact local P.I. and local Radiation Safety Authority
ASAP
• Contamination of materials: disposables / nondisposables
• E.g. gloves, sheets, gauzes, surgical equipment,
endoscopes
• Collect in separate labeled containers and keep away
from people in separate room

23. Practicalom de stijl te bewerkenstaff
Klik guidelines for nursing
Body Excreta of study patients during 2-week period of guidelines
•
Planned blood samples:
• Contact your local Clinical Chemistry and Laboratory Medicine
Department for local regulatory agreements
• Use venipuncture, not finger prick
• Label tubes and forms with appropriate adhesive stickers
• Consider transport in lead shielded container and avoid pneumatic
tube transport systems
• In most centres, analysis of radioactive bloodsamples is performed
under controlled conditions by certified staff

24. Practicalom de stijl te bewerkenstaff
Klik guidelines for nursing
Body Excreta of study patients during 2-week period of guidelines
•
Unplanned blood samples (outside office hours):
• Contact your local Clinical Chemistry and Laboratory Medicine
Department for local regulatory agreements
• Use venipuncture, not finger prick, label tubes and forms with stickers
• Consider transport in lead shielded container and avoid pneumatic
tube transport systems
• Discuss who will perform the analysis of bloodsamples at the Clinical
Chemistry Laboratory

25. Practicalom de stijl te bewerkenstaff
Klik guidelines for nursing
After venipuncture
• Discard used needles in standard needle container
• Consider not completely filled and unused tubes as contaminated and
collect and store these separately as discussed before

26. Klik om de stijl te bewerken
ARTFORCE HN trial
• Risk of radiation exposure is small in standard
controlled situations
• Adhere to the protocol
• Discuss any remaining issues with your local P.I. or
local Radiation Safety Authority