OPTIMIZATION OF PATIENT AND STAFF DOSES INMETABOLIC THERAPY
Joint ABR-BVS session – BHPA 2019prof. dr. Kristof Baete – MPE – head of NM [email protected]
prof. dr. Niki Bergans – RPE – head of health [email protected]
TREATMENT OPTIMIZATION AND STAFF DOSESIN MOLECULAR RADIONUCLIDE THERAPY (MRT)Joint ABR-BVS session – BHPA 2019prof. dr. Kristof Baete – MPE – head of NM [email protected]
prof. dr. Niki Bergans – RPE – head of health [email protected]
3Treatment optimization in MRT – K. Baete – BHPA 2019
Molecular radiotherapy (MRT)
4Treatment optimization in MRT – K. Baete – BHPA 2019
• Research– Clinical trials– Medical physics research
• Availability– Quantitative imaging– Treatment planning tools– New radioisotopes– Medical physics FTE
• Debates– Legislation– Reimbursement– Position papers
• Recommendations• Teaching & implementation
MIRD – Medical Internal Radiation Dosimetry
5Treatment optimization in MRT – K. Baete – BHPA 2019
• Task: put the MIRD formalism into clinical practice
• determine “source” and “target” regions– what is practically achievable and can be determined with a
reasonable accuracy from a NM measurement perspective– do not forget we are measuring human beings, patients– the aim is therapy planning and / or in vivo treatment verification– which source & target regions are important for the dosimetry
• determine the activity distribution as a function of time in the observed source region(s)
Source region, organ, tissue, …
Target region,organ, tissue, …
Good practice of clinical dosimetry reporting
6Treatment optimization in MRT – K. Baete – BHPA 2019
• EANM dosimetry committee guidance document (2011)• Description of the applied methodology is crucial• Important (technical) details should not be omitted
– specific use of all involved equipment: probes, activity meters, gamma cameras, PET, CT, gamma counters, …
– image reconstruction, analysis, quantification, … details– pharmacokinetic analysis and use of dosimetry models– internal dosimetry calculations
• Calibration of equipment – traceability of the measured activity• Investigate the achieved level of accuracy – error analysis• Multidisciplinary effort, involvement of techs, physicians, pharm,
engineers, physicists, nursing unit, … healthcare providers• Quality assurance and management of dosimetry procedures should
be coordinated by a medical physics expert
EANM – Internal Dosimetry Task Force (IDTF)
7Treatment optimization in MRT – K. Baete – BHPA 2019
• EANM dosimetry committee• Potential and Prospects• European survey (EANM-IDTF)
– Wide variation of MRT practice, including medical physics expert involvement and implementation of dosimetry-guided treatments
EANM – IDTF
8Treatment optimization in MRT – K. Baete – BHPA 2019
• Dosimetry for RNT, e.g.– 131I treatment
• benign thyroid disease• differentiated thyroid carcinoma• mIBG for neuroblastoma & NET
– 177Lu and 90Y PRRT– bone palliation (153Sm, 89Sr, …)– 223RaCl2 and 177Lu-PSMA for CRPC– 90Y-SIRT, 166Ho, …
• Effectiveness, imaging, organs-at-risk, normal tissue and target dosimetry, treatment planning, issues to consider, efficiency, …
Traceability of radionuclide calibrators
9Treatment optimization in MRT – K. Baete – BHPA 2019
Traceability of activity measurements – 99mTc
10Treatment optimization in MRT – K. Baete – BHPA 2019
• Relative use of activity measurements, but what about absolute?• Cross-calibration of Q-imaging equipment• Accuracy versus reproducibility / precision
Good practice – traceability & calibration – 111In
11Treatment optimization in MRT – K. Baete – BHPA 2019
proxy for 90Y
Administered activity – risk vs. benefit
12Treatment optimization in MRT – K. Baete – BHPA 2019
• SIRT – 90Y – pure beta emitter• remainder activity in vial and waste• geometry effects – accuracy – reproducibility• radiation protection is important, but the measures
should not be detrimental to the objectives of internal dosimetry or therapy planning
• additional imaging (CT) for therapy planning
Courtesy Carlo Chiesa
Whole-body dosimetry (131I-mIBG)
13Treatment optimization in MRT – K. Baete – BHPA 2019
• observe the administered activity over a time period using a WB counter (bio-phys. decay)
• determine the WB time-integrated activity coefficient (TIAC)
• WB absorbed dose rate model per unit activity as function of patient weight (kg)
GMNaI
131I-mIBG treatment of neuroblastoma
14Cancer Biotherapy & Radiopharmaceuticals, Vol. 20 (2), 2005
• in vivo dosimetry• 2-step treatment (fraction)• stem cell rescue• aim -> 4 Gy WB dose• dose based prescription• personalized treatment
WB dose (Gy) Activity (GBq)
131I-mIBG treatment of neuroblastoma
15Treatment optimization in MRT – K. Baete – BHPA 2019
• 123I-mIBG WB imagingpre-therapy planning
verification during therapy
Anterior
Posterior
Planar imaging in PRRT
16
• serial whole body images• conversion counts -> activity• calibration (ref. source)• application of corrections
– attenuation, scatter, DT• FIA – fraction inj. activity
15 min 4 h 24 h 48 h
Kidneys
Activity measurements
17Treatment optimization in MRT – K. Baete – BHPA 2019
• At what time points should we measure? -> Planning!
• Regression analysis, trapezoidal rule, …– Sum of exponentials
• If possible, late time points are sometimes preferred• After the last time point?
– Worst case scenario? -> physical decay assumption– Regression analysis
• Errors and residuals
High count rate -> dead time?
Low count rate -> uncertainty?
Quantification in tomography
18Treatment optimization in MRT – K. Baete – BHPA 2019
• Calibration of all involved equipment– Activity meter, well counter, …
• Conversion from image intensity (cpm/voxel) towards activity concentration (kBq/ml)
• For PET as well as for SPECT
Good practice for dosimetry
19
• Investigation of system calibration, quantitation, accuracy & precision
Beauregard et al., Cancer Imaging (2011) 11, 56-66Marin et al. EJNMMI Physics (2017) 4:7
Voxel level dosimetry
20Treatment optimization in MRT – K. Baete – BHPA 2019
• Dose-point kernel (DPK)• Monte Carlo• Absorbed dose rate map• Dose volume histogram
3D Activity Concentration
Dose Point Kernel
3D FFT 3D FFT
Multiplication in Fourier space
Inverse 3D FFT
Absorbeddose rate map
PET of SPECT+ CT + …
Monte Carlo, …
DVH
Image analysis for RNT planning
21Treatment optimization in MRT – K. Baete – BHPA 2019
• 90Y – SIRT planning• multi-modal image analysis (e.g. CBCT)• image registration, segmentation, …• voxel analysis, abs dose map, DVH, …
(A) MAA- SPECT/CT
200
kBq/
ml
0kBq
/m
l
(b) CBCTs (c) FDG-PET/CT
8 SU
V0
SUV
Healthy tissue (left lobe)Tumor (left lobe)Healthy tissue (right lobe)Tumor (right lobe)
(d) Segmentation
300 Gy < 270 Gy < 240 Gy < 210 Gy < 180 Gy < 150 Gy < 120 Gy <
90 Gy < 60 Gy < 30 Gy <
(e) Estimated iso-dose contours
Sirtex ©
PhD project – Esmaeel Rangraz – KU Leuven
22Treatment optimization in MRT – K. Baete – BHPA 2019
Conclusion
23“Nuclear Physics for Medicine”, NuPECC, 2014
• Nuclear medicine is evolving very rapidly– theranostics – personalized medicine– dose-effect relationship
• Molecular radionuclide therapy (MRT) is becoming a very sophisticated discipline
• Health Physics and Medical Physics need to (re)organize themselves to support this emerging field, quickly …
• All participators in this field, including the regulatory bodies, and the communities in general, need to be aware of the real challenges that each stakeholder is facing
RNT is booming and fast! Challenge for health physics:Look after the collective occupational dose through justification, optimization and safe practice in new radionuclide therapies (RNT) with higher occupational risk due to the amount of activity (GBq level) and type of emitter (, high energy β)
Organizational level:– Identify tools for determining the best radiation protection practices– Risk communication
Staff:– Safety education and training– Implementation of dose reduction measures
Follow-up of exposure:- Implementation of dose management and reporting tools
• use of dose constraints for personnel and patient family members– Risk awareness and perception of hospital staff, patient and his environment
N Bergans - Optimisation of staff doses in RNT BHPA-BVS-ABR joint session 2019
System of Protection in RNT
Safety measures are based on: Protection against external radiation : general principles of
time restriction, distance to the source and shielding Avoid internal and external contamination: strict working
procedures and use of personal protective clothing, regularcontamination control
Prevention of uncontrolled release of radioactive substances
Installation bound measures: dedicated workspace withcombination of shielded LAF cabinet, glove box, hot cell, material+ personnel air locks, a dedicated ventilation regime
Dedicated equipment: shielded automated dose dispensers, shielded set-up for administration
Radiation protection procedures: GLP, access control, radioactivewaste, decontamination
© UZ LeuvenN Bergans - Optimisation of staff doses in RNT BHPA-BVS-ABR joint session 2019
System of Protection in RNT
Infrastructural measures: dedicated radionuclide therapy rooms with design based on the RNT risk analysis: shielding in walls and doors, system tocollect excretory products, personnel air lock, dedicated ventilation regime, dose determining system for patient dose,…
Radiation monitoring: survey monitoring, personal dosimetry, contaminationmonitoring
N Bergans - Optimisation of staff doses in RNT BHPA-BVS-ABR joint session 2019
- Avoid direct contact with excretion products and blood.
- Always use PPE: disposable gloves and coat, if necessary overshoes, FFP3 mask.
- Washing of hands under a tap when leaving the room.
- Material possibly contaminated does not leave the room (e.g. blood pressure meter, infuse holder, material for patient care..).
- End control of room, linnen, personal belongings patient (glasses, smartphone,…) and radioactive waste by the RPO.
- If possible keep a distance of 0,5-1m from the patient, otherwise limit exposure time (e.g. 30-60min/day): these are general guidance levels and not a strict rule! Depends on which type of RNT is given - Patient care comes first!
- Monitor exposure levels of staff dosimetry and contamination control.
Safety guidelines for nursing personnel duringhospitalisation of the RNT patient
N Bergans - Optimisation of staff doses in RNT BHPA-BVS-ABR joint session 2019
Safety guidelines during synthesis and dispensing(recommendations ICRP 106)
N Bergans - Optimisation of staff doses in RNT BHPA-BVS-ABR joint session 2019
- Work out protocols for synthesis, dispensing and administration and plan carefully.
- Use of shielding devices: shielding of syringe and vial is the most important factor affecting finger dose. A 5–10 mm thick PMMA (syringe) shield should always be used for administration of high-energy beta-emitting therapy radionuclides.
- Avoid close contact with therapeutic vials: use of forceps, tweezers, shielding.
- All staff should undergo a period of intense training to practice manipulations using non-radioactive liquid prior to the RNT synthesis and dispensing.
- Finger dose monitoring should be done for any person handling >2 GBq/day, and regular monitoring should be carried out if finger doses can exceed 6 mSv/month.
- Venous cannulation prior to administration allows the injection to proceed more rapidly and minimizes the exposure time of the staff.
Result: significant reduction of dose! 2015-2017: finger doses of lab technologists preparing RNT < 30 mSv/year
Examples of good practices during synthesis, dispensing or administrationUse of syringe and vial shielding, tweezers:
Use of dedicated shielded dispensing and administration systems:
SIRT (Y-90)
© UZ Leuven
N Bergans - Optimisation of staff doses in RNT BHPA-BVS-ABR joint session 2019
How to face the challenges in RNT radioprotection?
Professionals working in the field need a forum where they can meet and discuss multiple aspects of radiation protection
The rapid technological development within medical applications is challenging: new applications, therapies and equipment can appear in clinical practice before solid evidence over their clinical benefits and the risks they imply is established
Strengthen radiation safety culture in health careRadionuclide therapy (including planning and diagnostic follow-up): prevention of incidents – return of experience – lessons learned
Exchange of scientific and technical knowledge and of experience Engage in multidisciplinary involvement of medical staff, health physics, medical physicists, manufacturers of radiological devices and radiopharmaceuticals,…
N Bergans - Optimisation of staff doses in RNT BHPA-BVS-ABR joint session 2019
How to face the challenges in RNT radioprotection?
RNT comes with “other challenges”
Discharge criteria for the patient – patient rules and info for family and friends - patient info on exposure in the ICFThe regulatory framework is on a national base, but most RNT start as international multicenter clinical trials!Dealing with the radioactive waste: optimization of the decay storage of the excreta – internal organization of radioactive waste management - long lived radionuclide impurities,…
Need for harmonization Define standards between competent authorities, professionals and manufacturers Enhance the exchange of info on good radiation protection practices and dedicated
infrastructural design for RNT Engage in multidisciplinary involvement of medical staff, health physics, medical physicists,
manufacturers of radiological devices and radiopharmaceuticals,…
N Bergans - Optimisation of staff doses in RNT BHPA-BVS-ABR joint session 2019
