Facilitating Lu 177 Personalized Dosimetry for Neuroendocrine Tumours CANM 2017
CANM ANNUAL SCIENTIFIC MEETING APRIL 20-23, 2017 TORONTO, ONTARIO I do not have a financial interest, arrangement or affiliation including receipt of honoraria or expenses with a commercial organization that may have a direct interest in the subject matter of my presentation.
Outline Brief Overview of NET-PRRT Trial Who are QIPCM? What is QIPCM s involvement with NET-PRRT? Using Medical Internal Radiation Dosimetry (MIRD) for Lu 177 SPECT Sensitivity Calibration and QC Walkthrough of the Dosimetry Report Generation process Some preliminary personalized dosimetry results Questions 3
NET-PRRT A Prospective Phase II, Single-Arm, Multi-Centre Study of the Efficacy and Safety of Lutetium 177 Octreotate (Lu-DOTATATE) Treatment in Patients with Somatostatin Receptor Positive Neuroendocrine Tumours (PI Dr. Wong). Ga 68 PET/CT to identify eligible patients for Lu 177 Octreotate therapy. Patients receive 4 cycles of Lu 177 Octreotate therapy based on individualized dosimetry based on SPECT-CT imaging. 4
Quantitative Imaging for Personalized Cancer Medicine
Trial Support Services Scanner QA Harmonize imaging results from multicentre clinical trials, Focus on functional imaging (4D CT, 4D PET, PET-CT, PET-MR and DCE-CT, DCE-MR) Imaging Protocol Development Mitigate the challenges of multi-site clinical trials in advance. Image Anonymization & Transfer with Centralized Storage Collect and anonymize images from multiple sites through RSNAs CTP pipeline Centralized QIPCM PACS with trial by trial permissions and audit logs. Remote Image Review & Analysis VMWare TM infrastructure in place for remote image review. Custom image analysis tools Commercial Image Processing Software available Users can install their own applications on their Windows virtual machine. 6
QICPM Architecture 7
Key Performance Indices Total # of Trials on the QIPCM Platform 30 Trials currently active 17 CTP Transfer Pipelines 37 Remote Desktops Assigned 47 Active Trials using QIPCM analysis service/tools 8/12 Patient exams on platform Images on platform Storage Capacity 466pts/1523 studies 3.0 million 60 TB 8
Active QIPCM Sites International St. Vincent s Health Australia, Adelaide, Australia Columbia University Medical Center, New York, NY UCLA, Los Angeles, CA MD Anderson, Houston, TX Canada BC Cancer Agency, Vancouver, BC CHUM, Montreal, QC Cross Cancer Center, Edmonton, AB Grand River Hospital, Kitchener, ON London Health Sciences Centre, London, ON Nova Scotia Cancer Centre Halifax, NS Odette Cancer Centre, Toronto, ON Ottawa Hospital Regional Cancer Centre, Ottawa, ON Princess Margaret Cancer Centre, Toronto, ON St Joseph s Healthcare Hamilton, Hamilton, ON Southlake Regional Cancer Centre, Newmarket, ON Toronto General Hospital, Toronto, ON 9
The QIPCM Team 10
Supporting the NET Lu 177 DOTATATE trial Study Description & Challenges 190 Patients to receive Lu-DOTATATE therapy at 4 centres in Ontario Patients receive Ga 68 PET-CT to determine eligibility Patients receive 4 cycles of Lu 177 DOTATATE Therapy based on individualized dosimetry based on SPECT-CT. QIPCM Solution Install CTP Client at each institution Work with sites to determine individual SPECT camera sensitivity Provide centralized hosting of Lu 177 SPECT-CT and Ga 68 PET imaging Provide a means to segment organs at risk from SPECT-CT images and generate personalized dosimetry report 11
Patient Identification by Ga 68 PET Most NETs express cell surface somatostatin receptors Allows therapeutic application of somatostatin analogs (SSA) Ga 68 linked to the SSA in the same manner as Lu 177 for treatment 68 Ga PET-CT will be used wherever feasible to determine whether patients are somatostatin receptor positive. 12
A very brief summary of Lu Dosimetry Dose calculations for 177 Lu-DOTATATE will be performed with the Medical Internal Radiation Dosimetry (MIRD) formalism such that: Where: D (T s): The dose to a target from a particular source organ, is the product of : : The average energy of those decays; Lu 177 : 6.65 day HL Multiple gammas 10% @ 208 kev 6% @ 113 kev 4 beta - emissions : = 134 kev T s : m T : A s : From Dr. S Breen absorbed fraction which is the fraction of energy emitted from the source ; absorbed in the target of mass The number of nuclear decays in the source (the cumulated activity); = 1 = OAR vol x 1 g/cc From SPECT. In MBq hours? 13
Converting SPECT Counts to MBq x Hr 2 Parts to this challenge Convert Counts to MBq SPECT Sensitivity from Phantom scans Convert MBq to MBqxHr SPECT is done at 4, 24 and 72 hours post injection Need to find area under the curve From Dr JM Beauregard 14
Determining Scanner Sensitivity Protocol developed by Dr. Curtis Caldwell Fill a Water Phantom with a known quantity of Lu 177 Select 6 circular 2D ROIs and record the total counts and ROI area. Determine the ratio of CPM (counts per minute) to MBq Example Lu177 injected 184.96 MBq Lu177 residual 20.96 MBq Phantom Volume 6716 cc Activity in Phantom 0.024 MBq/cc Slice 1 counts 65445 other 6 slices Total counts 382352 Total area of slices 1698 cm 2 Slice Thickness 4.42 mm Total Volume 749.75 cc Scan Duration 45 min Sensitivity 464.1 CPM/MBq 15
An overview of the personalized dosimetry process Anonymized Images Received Syringe measurements performed and compared to Nuc Med Worksheet OAR and Tumours Contoured by RT Contours Reviewed by Rad Onc Dosimetry Report Created Determine OAR Dose Determine Tumour Dose Propose next cycle injection activity Report Reviewed & signed by Rad Onc. and Medical Physicist Dose for next cycle ordered. 16
Centralized Storage of Anonymized Patient Images Each site is provided with a unique CTP (clinical trial processor) client Program designed by RSNA Anonymized Ga 68 PET and Lu 177 SPECT images sent to QIPCM via the client Anonymizes the data according to trial protocol Leave fields required for SPECT analysis Retain patient birth year/month Remove all non-essential patient information 17
SPECT QC with Standards Many factors go into the SPECT reconstruction Scatter Correction (On/Off) Scatter Window(s) Emission Window(s) Attenuation Correction (on/off) Frame Duration Number of Frames Additional outside factors such as Dose Calibrator Recalibration Each Patient is scanned with a syringe containing Lu 177 of a known concentration. Syringe measurements used to plot a control chart to check for variations in image reconstruction or external factors 18
Patient OAR contouring in MIM Trial RT receives notification that a new patient is ready for contouring RT logs in to their QIPCM Remote Desktop and launches MIM Searches for patient, selects image sets and launches workflow. 19
Contouring Walkthrough 20
Contouring Review and Report Generation Trial RT notifies the Radiation Oncologist that patient contours are ready for review. 21
Contouring Review and Report Generation 22
The Dosimetry Report OARs Bone Left Right Marrow Kidney 23
Dose Summary 24
Prescription Dose Report reviewed and signed by Radiation Oncologist & Medical Physicist Then provided to treating physician 25
Prescription & Dose Graphically 26
Results to Date Overall Accuracy Mean 0.67 Gy +/- 1.3 Gy OAR prediction within 1 Gy 24/34 (71%) Room for improvement Most outliers occur when predicting cycle 2 based on only 1 data point Changes in contouring may contribute 27
Tumour Absorbed Dose Example Tumour Absorbed Doses are also collected Next steps will involve producing detailed reports with results. 28
Challenges for Lu 177 Dosimetry Validating SPECT/CT systems from 3 different manufacturers across 4 sites to ensure correct conversion of counts to activity to dose. Creating a robust dosimetry report generation extension while also adapting to ever changing requirements and specifications. Continuously attempting to ensure that all documentation and software is up to regulatory standards for possible audits. 29
Acknowledgements QIPCM Team Members Dr. Harry Keller Dr. Ivan Yeung Tina Shek Julia Publicover Trial PI Dr. Rebecca Wong Nuclear Medicine Technologist Ed Sun Trial Physicists Dr. Stephen Breen Dr. Troy Farncombe Dr. Rob Stodilka Dr. Curtis Caldwell Dr. J.M. Beauregard CanProbe Ga 68 / Lu 177 DOTATATE production 30