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3: 3 Source: Census, HHS Source: Census, HHS
4: 4 When you think of the core of GE Medical Business I think it is easy to understand if you just think of it as Imaging Services and Information.
Today you will see how we are evloing the business aroud each of these areas. From Anatomical to functional. In services from Maintanance to a broad focus on Hospital productivity and I Inforamtion from jst Radiolog PACS to entire clincoa inforamtion and workflow systems. An exciting growth Busiess great footprint with huge opportunity to grow
When you think of the core of GE Medical Business I think it is easy to understand if you just think of it as Imaging Services and Information.
Today you will see how we are evloing the business aroud each of these areas. From Anatomical to functional. In services from Maintanance to a broad focus on Hospital productivity and I Inforamtion from jst Radiolog PACS to entire clincoa inforamtion and workflow systems. An exciting growth Busiess great footprint with huge opportunity to grow
5: 5 The Potential of Molecular Imaging Cancer Therapy Clinical Management of Gastrointestinal Stromal Tumors: Before and After STI-571
RONALD P.DEMATTEO, MD, MICHAEL C.HEINRICH, MD, WA EL M.EL-RIFAI, MD, AND GEORGE DEMETRI, MD
Clinical response to STI-571 (Geevec) in a patient with advanced,metastatic Gastrointestinal Stromal Tumor (GIST). Response of a patient with intraperitoneal GIST before (top left) and 3 months after (bottom left) STI-571 therapy by CT and PET scan (off page right). Notice that the tumor nearly disappeared by CT imaging and became cold on the PET scan after treatment. (Prepared with the assistance of Dr.Annick van den Abbeele and Dr.Milos Janicek, Dana-Farber Cancer Institute,Boston MA.)
Background:
Gastrointestinal stromal tumor (GIST)is the most common mesenchymal neoplasm of the gastrointestinal tract. Until recently,surgery has been the only effective therapy for GIST. However, even after complete resection of tumor, many patients still eventually die of disease recurrence. Conventional chemotherapy and radiation therapy have been of limited value. Within the last few years, it was discovered that most GISTs have a gain-of-function mutation in the c-kit proto-oncogene. This results in ligand-independent activation of the KIT receptor tyrosine kinase and an unopposed stimulus for cell growth. STI-571 is a small molecule that selectively inhibits the enzymatic activity of the ABL, platelet-derived growth factor receptor, and KIT tyrosine kinases and the BCR-ABL fusion protein and is a landmark development in cancer therapy. Its clinical development marks a new era of rational and targeted molecular inhibition of cancer that
emanates from direct collaborations between scientists and clinicians. It provides proof of the principle that a specific molecular inhibitor can drastically and selectively alter the survival of a neoplastic cell with a particular genetic aberration. The advent of STI-571 has markedly altered the clinical approach to GIST. It has proven to be effective in metastatic GIST and is also under investigation as a neoadjuvant and adjuvant therapy. HUM PATHOL 33:466-477.Copyright 2002,Elsevier Science (USA).All rights reserved.
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F18-FDG-PET PROVIDES EARLY EVIDENCE OF BIOLOGICAL RESPONSE TO STI571 IN PATIENTS WITH MALIGNANT GASTROINTESTINAL STROMAL TUMORS (GIST) Annick D. Van den Abbeele1, R.D. Badawi1, M. Janicek1, C. Blanke2, H. Joensuu3, P. Roberts4, S. Silberman5, S. Dimitrijevic5, G.D. Demetri1 for the GIST Collaborative PET Study Group (1Dana-Farber Cancer Institute, Boston, MA; 2Oregon Health Sciences University, Portland, Oregon;3Helsinki University Central Hospital; 4Turku University Central Hospital; 5Finland, Novartis Oncology
RIGHT: FDG-PET studies in a patient showing extensive, highly FDG-avid, abdominal and hepatic disease at baseline. Follow-up studies demonstrate evidence of response as early as 24 hours post-initiation of STI571 therapy, continuing response at 7 days, and no evidence of FDG-avid disease on the 2 and 5.5 months follow-up scans.
1. Most GIST tumors demonstrate high glycolytic activity at baseline prior to STI571 therapy.
2. Sites of disease defined by FDG-PET at baseline correlated with areas of abnormality seen on CT. FDG-PET provided additional information regarding extent of disease.
3. Response to STI571 therapy could be demonstrated by FDG-PET as early as 24 hours following initiation of therapy.
4. In patients with stable or progressive disease, concordant findings between FDG-PET and bi-dimensional CT were seen in all but one case. The roles and correlative evaluation of FDG-PET and CT will need to be further studied prospectively to assess the respective predictive value of each test.
5. These findings suggest that the functional information provided by FDG-PET may play an important role in the early evaluation of therapies that target specific cell-signaling mechanisms, such as STI571.
(Sponsored by Novartis Oncology)
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FDG-PET versus spiral CT for evaluation of STI-571 treatment of gastrointestinal stromal tumors
AbstractNo: 3311
Citation: Proc Am Soc Clin Oncol 22: page 824, 2003
Author(s): C. A. Kristensen, A. Eigtved, B. Bjerregaard, S. Daugaard, A. K. Berthelsen, L. Rasch, H. Roed, A. Krarup-Hansen, for the Copenhagen Sarcoma Study Group; Herlev University Hospital, Herlev, Denmark; Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
Abstract: Gastrointestinal stromal tumors (GISTs) express the growth factor receptor c-kit (CD117). The c-kit specific tyrosine kinase inhibitor STI-571 (Glivec) has shown significant clinical effect in patients with GIST. The aim of this study was to compare FDG-PET and spiral CT for evaluation of patients with GIST during STI-571 treatment.
Fourteen patients consecutively referred to Departments of Oncology, Herlev University Hospital and Rigshospitalet, Copenhagen, Denmark between July 2001 and October 2002 were included. The immunohistochemical diagnosis of GIST was independently assessed by two pathologists. STI-571 doses were either 400mgx1 or 400mgx2 daily. FDG-PET and CT scans were performed before and 2-3 weeks after treatment initiation and subsequently every 8th week during treatment. Patients were treated until progression, intolerable toxicity, or death occurred or until radical surgery could be performed. The median treatment duration was 140+ days (range 41-527+ days). CT scans were evaluated according to RECIST criteria, whereas patients were considered FDG-PET responders if standardized uptake value (SUV) decreased to 2.5. Seven patients (50%) were FDG-PET responders, only four of these (28%) responded according to the CT response criteria. The median time to FDG-PET response was 21 days (range 2-40 days) compared to a median of 83 days (range 27-173 days) to the first detection of CT response (p 0.05). In the present protocol the first FDG-PET and CT scans after treatment initiation was performed after 2-3 weeks, but the FDG-PET response may occur already within the first 1-2 days (as detected in one patient scanned on day 2). In conclusion, FDG-PET identified more GIST patients responding to STI-571 and allowed significantly earlier response detection compared to spiral CT. FDG-PET scan should be part of the standard evaluation program for STI-571 treatment of GIST. Clinical Management of Gastrointestinal Stromal Tumors: Before and After STI-571
RONALD P.DEMATTEO, MD, MICHAEL C.HEINRICH, MD, WA EL M.EL-RIFAI, MD, AND GEORGE DEMETRI, MD
Clinical response to STI-571 (Geevec) in a patient with advanced,metastatic Gastrointestinal Stromal Tumor (GIST). Response of a patient with intraperitoneal GIST before (top left) and 3 months after (bottom left) STI-571 therapy by CT and PET scan (off page right). Notice that the tumor nearly disappeared by CT imaging and became cold on the PET scan after treatment. (Prepared with the assistance of Dr.Annick van den Abbeele and Dr.Milos Janicek, Dana-Farber Cancer Institute,Boston MA.)
Background:
Gastrointestinal stromal tumor (GIST)is the most common mesenchymal neoplasm of the gastrointestinal tract. Until recently,surgery has been the only effective therapy for GIST. However, even after complete resection of tumor, many patients still eventually die of disease recurrence. Conventional chemotherapy and radiation therapy have been of limited value. Within the last few years, it was discovered that most GISTs have a gain-of-function mutation in the c-kit proto-oncogene. This results in ligand-independent activation of the KIT receptor tyrosine kinase and an unopposed stimulus for cell growth. STI-571 is a small molecule that selectively inhibits the enzymatic activity of the ABL, platelet-derived growth factor receptor, and KIT tyrosine kinases and the BCR-ABL fusion protein and is a landmark development in cancer therapy. Its clinical development marks a new era of rational and targeted molecular inhibition of cancer that
emanates from direct collaborations between scientists and clinicians. It provides proof of the principle that a specific molecular inhibitor can drastically and selectively alter the survival of a neoplastic cell with a particular genetic aberration. The advent of STI-571 has markedly altered the clinical approach to GIST. It has proven to be effective in metastatic GIST and is also under investigation as a neoadjuvant and adjuvant therapy. HUM PATHOL 33:466-477.Copyright 2002,Elsevier Science (USA).All rights reserved.
______________________________________
F18-FDG-PET PROVIDES EARLY EVIDENCE OF BIOLOGICAL RESPONSE TO STI571 IN PATIENTS WITH MALIGNANT GASTROINTESTINAL STROMAL TUMORS (GIST) Annick D. Van den Abbeele1, R.D. Badawi1, M. Janicek1, C. Blanke2, H. Joensuu3, P. Roberts4, S. Silberman5, S. Dimitrijevic5, G.D. Demetri1 for the GIST Collaborative PET Study Group (1Dana-Farber Cancer Institute, Boston, MA; 2Oregon Health Sciences University, Portland, Oregon;3Helsinki University Central Hospital; 4Turku University Central Hospital; 5Finland, Novartis Oncology
RIGHT: FDG-PET studies in a patient showing extensive, highly FDG-avid, abdominal and hepatic disease at baseline. Follow-up studies demonstrate evidence of response as early as 24 hours post-initiation of STI571 therapy, continuing response at 7 days, and no evidence of FDG-avid disease on the 2 and 5.5 months follow-up scans.
1. Most GIST tumors demonstrate high glycolytic activity at baseline prior to STI571 therapy.
2. Sites of disease defined by FDG-PET at baseline correlated with areas of abnormality seen on CT. FDG-PET provided additional information regarding extent of disease.
3. Response to STI571 therapy could be demonstrated by FDG-PET as early as 24 hours following initiation of therapy.
4. In patients with stable or progressive disease, concordant findings between FDG-PET and bi-dimensional CT were seen in all but one case. The roles and correlative evaluation of FDG-PET and CT will need to be further studied prospectively to assess the respective predictive value of each test.
5. These findings suggest that the functional information provided by FDG-PET may play an important role in the early evaluation of therapies that target specific cell-signaling mechanisms, such as STI571.
(Sponsored by Novartis Oncology)
________________________________
FDG-PET versus spiral CT for evaluation of STI-571 treatment of gastrointestinal stromal tumors
AbstractNo: 3311
Citation: Proc Am Soc Clin Oncol 22: page 824, 2003
Author(s): C. A. Kristensen, A. Eigtved, B. Bjerregaard, S. Daugaard, A. K. Berthelsen, L. Rasch, H. Roed, A. Krarup-Hansen, for the Copenhagen Sarcoma Study Group; Herlev University Hospital, Herlev, Denmark; Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
Abstract: Gastrointestinal stromal tumors (GISTs) express the growth factor receptor c-kit (CD117). The c-kit specific tyrosine kinase inhibitor STI-571 (Glivec) has shown significant clinical effect in patients with GIST. The aim of this study was to compare FDG-PET and spiral CT for evaluation of patients with GIST during STI-571 treatment.
Fourteen patients consecutively referred to Departments of Oncology, Herlev University Hospital and Rigshospitalet, Copenhagen, Denmark between July 2001 and October 2002 were included. The immunohistochemical diagnosis of GIST was independently assessed by two pathologists. STI-571 doses were either 400mgx1 or 400mgx2 daily. FDG-PET and CT scans were performed before and 2-3 weeks after treatment initiation and subsequently every 8th week during treatment. Patients were treated until progression, intolerable toxicity, or death occurred or until radical surgery could be performed. The median treatment duration was 140+ days (range 41-527+ days). CT scans were evaluated according to RECIST criteria, whereas patients were considered FDG-PET responders if standardized uptake value (SUV) decreased to 2.5. Seven patients (50%) were FDG-PET responders, only four of these (28%) responded according to the CT response criteria. The median time to FDG-PET response was 21 days (range 2-40 days) compared to a median of 83 days (range 27-173 days) to the first detection of CT response (p 0.05). In the present protocol the first FDG-PET and CT scans after treatment initiation was performed after 2-3 weeks, but the FDG-PET response may occur already within the first 1-2 days (as detected in one patient scanned on day 2). In conclusion, FDG-PET identified more GIST patients responding to STI-571 and allowed significantly earlier response detection compared to spiral CT. FDG-PET scan should be part of the standard evaluation program for STI-571 treatment of GIST.
6: 6 When you think of the core of GE Medical Business I think it is easy to understand if you just think of it as Imaging Services and Information.
Today you will see how we are evloing the business aroud each of these areas. From Anatomical to functional. In services from Maintanance to a broad focus on Hospital productivity and I Inforamtion from jst Radiolog PACS to entire clincoa inforamtion and workflow systems. An exciting growth Busiess great footprint with huge opportunity to grow
When you think of the core of GE Medical Business I think it is easy to understand if you just think of it as Imaging Services and Information.
Today you will see how we are evloing the business aroud each of these areas. From Anatomical to functional. In services from Maintanance to a broad focus on Hospital productivity and I Inforamtion from jst Radiolog PACS to entire clincoa inforamtion and workflow systems. An exciting growth Busiess great footprint with huge opportunity to grow
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18: 18 Having added those biology and chemistry skills, we focus those skills on the major unmet needs developing novel biomarkers and imaging chemistries that balance high specificity with platform capability.
In cardiovascular disease,
In Cancer,
In Alzheimers disease
And in Chronic Obstructive Pulmonary Disease, the fourth leading killer,
As we built up our research team.
We went back to you and asked you where we should concentrate our efforts? What imaging markers we should we pursue? What probe chemistries had game? How do we best image these new chemistries? Early on, we went to the three NCI P50 sites. With Ralphs group, we optimized pulse sequences and analysis methods to help their Combidex prostate cancer lymph node metastases detection trial. This study was recently published in the New England Journal of Medicine. With Sam, we sponsored the UCLA Molecular Imaging Seminar Series that provided education to all interested in learning about the field and we look forward to Sams transition to Stanford. And with Memorial Sloan-Kettering, we worked in collaboration studies that fused microPET and VCT, evaluated reconstruction methods to optimize FDHT and developed semi-automated segmentation and analysis techniques for PET and SPECT. We also created an advanced neuro-imaging center with Albany Medical Center to accelerate the advancement of Alzheimer's disease imaging.
Having added those biology and chemistry skills, we focus those skills on the major unmet needs developing novel biomarkers and imaging chemistries that balance high specificity with platform capability.
In cardiovascular disease,
In Cancer,
In Alzheimers disease
And in Chronic Obstructive Pulmonary Disease, the fourth leading killer,
As we built up our research team.
We went back to you and asked you where we should concentrate our efforts? What imaging markers we should we pursue? What probe chemistries had game? How do we best image these new chemistries? Early on, we went to the three NCI P50 sites. With Ralphs group, we optimized pulse sequences and analysis methods to help their Combidex prostate cancer lymph node metastases detection trial. This study was recently published in the New England Journal of Medicine. With Sam, we sponsored the UCLA Molecular Imaging Seminar Series that provided education to all interested in learning about the field and we look forward to Sams transition to Stanford. And with Memorial Sloan-Kettering, we worked in collaboration studies that fused microPET and VCT, evaluated reconstruction methods to optimize FDHT and developed semi-automated segmentation and analysis techniques for PET and SPECT. We also created an advanced neuro-imaging center with Albany Medical Center to accelerate the advancement of Alzheimer's disease imaging.
19: 19 So, as this meeting is focused on Molecular Imaging, whats the opportunity?
As the biological understanding of disease evolves and new therapeutic and diagnostic biomarkers are discovered, there then is the opportunity to create chemistry that selectively binds to those markers and amplify their imaging signal so, ultra high sensitivity scanners can detect those signals and present a high resolution registration with anatomy.
Molecular Imaging is all about adding chemistry and biology to what we do today. Molecular biology to understand new markers of disease. And Chemistry to light up those markers so imaging and diagnostic equipment can see them. In imaging, we have the installed base of equipment to get at these markers, but the future value in diagnostics will be in the biology (disease knowledge), the chemistry and the informatics to present this information to medical practitioners
Imaging and Diagnostics that will:
assess risk earlier to intervene with preventive measures
diagnose earlier to intervene and stop chronic disease in its tracks
Diagnose more specifically and understand the patient better to select the right therapy
Deliver therapy, Monitor therapy delivery, and follow-up to measure efficacy
NOTES:
Biomarkers:
Left: Elevation of Beta-glucuronidase (GUS) prevents normal clearance of toxins and hormones and is known to be a major risk factor for both prostate and breast cancer.
Right: A number of pharmaceutical companies have inhibitors for beta-secretase in development in hopes of halting the formation of active beta-amyloid peptide in Alzheimers Disease
Diagnostic Technology:
DiscoveryVH Spect/CT
DiscoveryLS PET/CT
Signa VH/i 3T MR
PET Advance
Example Images:
3T prostate image with Spectra overlay, Hypothetical targeted chemistry confirming high choline-low citrate voxels
Genometrix gene expression arrays
Apple DATscan (L-Dopa) SPECT image (Parkinsons)So, as this meeting is focused on Molecular Imaging, whats the opportunity?
As the biological understanding of disease evolves and new therapeutic and diagnostic biomarkers are discovered, there then is the opportunity to create chemistry that selectively binds to those markers and amplify their imaging signal so, ultra high sensitivity scanners can detect those signals and present a high resolution registration with anatomy.
Molecular Imaging is all about adding chemistry and biology to what we do today. Molecular biology to understand new markers of disease. And Chemistry to light up those markers so imaging and diagnostic equipment can see them. In imaging, we have the installed base of equipment to get at these markers, but the future value in diagnostics will be in the biology (disease knowledge), the chemistry and the informatics to present this information to medical practitioners
Imaging and Diagnostics that will:
assess risk earlier to intervene with preventive measures
diagnose earlier to intervene and stop chronic disease in its tracks
Diagnose more specifically and understand the patient better to select the right therapy
Deliver therapy, Monitor therapy delivery, and follow-up to measure efficacy
NOTES:
Biomarkers:
Left: Elevation of Beta-glucuronidase (GUS) prevents normal clearance of toxins and hormones and is known to be a major risk factor for both prostate and breast cancer.
Right: A number of pharmaceutical companies have inhibitors for beta-secretase in development in hopes of halting the formation of active beta-amyloid peptide in Alzheimers Disease
Diagnostic Technology:
DiscoveryVH Spect/CT
DiscoveryLS PET/CT
Signa VH/i 3T MR
PET Advance
Example Images:
3T prostate image with Spectra overlay, Hypothetical targeted chemistry confirming high choline-low citrate voxels
Genometrix gene expression arrays
Apple DATscan (L-Dopa) SPECT image (Parkinsons)
20: 20 Having added those biology and chemistry skills, we focus those skills on the major unmet needs developing novel biomarkers and imaging chemistries that balance high specificity with platform capability.
In cardiovascular disease,
In Cancer,
In Alzheimers disease
And in Chronic Obstructive Pulmonary Disease, the fourth leading killer,
As we built up our research team.
We went back to you and asked you where we should concentrate our efforts? What imaging markers we should we pursue? What probe chemistries had game? How do we best image these new chemistries? Early on, we went to the three NCI P50 sites. With Ralphs group, we optimized pulse sequences and analysis methods to help their Combidex prostate cancer lymph node metastases detection trial. This study was recently published in the New England Journal of Medicine. With Sam, we sponsored the UCLA Molecular Imaging Seminar Series that provided education to all interested in learning about the field and we look forward to Sams transition to Stanford. And with Memorial Sloan-Kettering, we worked in collaboration studies that fused microPET and VCT, evaluated reconstruction methods to optimize FDHT and developed semi-automated segmentation and analysis techniques for PET and SPECT. We also created an advanced neuro-imaging center with Albany Medical Center to accelerate the advancement of Alzheimer's disease imaging.
Having added those biology and chemistry skills, we focus those skills on the major unmet needs developing novel biomarkers and imaging chemistries that balance high specificity with platform capability.
In cardiovascular disease,
In Cancer,
In Alzheimers disease
And in Chronic Obstructive Pulmonary Disease, the fourth leading killer,
As we built up our research team.
We went back to you and asked you where we should concentrate our efforts? What imaging markers we should we pursue? What probe chemistries had game? How do we best image these new chemistries? Early on, we went to the three NCI P50 sites. With Ralphs group, we optimized pulse sequences and analysis methods to help their Combidex prostate cancer lymph node metastases detection trial. This study was recently published in the New England Journal of Medicine. With Sam, we sponsored the UCLA Molecular Imaging Seminar Series that provided education to all interested in learning about the field and we look forward to Sams transition to Stanford. And with Memorial Sloan-Kettering, we worked in collaboration studies that fused microPET and VCT, evaluated reconstruction methods to optimize FDHT and developed semi-automated segmentation and analysis techniques for PET and SPECT. We also created an advanced neuro-imaging center with Albany Medical Center to accelerate the advancement of Alzheimer's disease imaging.
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24: 24 Share Exchange Mechanism Protects Both Amersham and GE Shareholders
25: 25 Significant Cost and Revenue Synergies
26: 26 Financial Outlook Accelerate Revenue Growth
Enhance Margin Through Synergies & Productivity
Good Cash Generation
Acquisition Impact on GE:
Non-Dilutive Year 1 Excluding In-Process R&D
$0.01 Accretive Year 2
Slight Dilution of Return on Total Capital
27: 27 Leadership Team
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