VHL and clear cell Renal Cell Carcinoma. Expression profiling reveals cell of origin. Renal Cell Carcinoma (RCC) Title. VHL syndrome hallmark cancer:

Save this PDF as:
 WORD  PNG  TXT  JPG

Size: px
Start display at page:

Download "VHL and clear cell Renal Cell Carcinoma. Expression profiling reveals cell of origin. Renal Cell Carcinoma (RCC) Title. VHL syndrome hallmark cancer:"

Transcription

1 VHL and clear cell Renal Cell Carcinoma Gene expression profiles in renal cell carcinoma October 23, 2014 VHL syndrome hallmark cancer: Clear cell renal cell carcinoma (ccrcc) VHL mutations also a hallmark of sporadic ccrcc Title VHL mutation HIF stabilization and gene expression changes associated with the hypoxia response. W. Kimryn Rathmell, MD, PhD Renal Cell Carcinoma (RCC) Expression profiling reveals cell of origin Originates in the renal cortex Most common solid lesion occurring in the kidney (80 85% of all primary renal neoplasms) Diseased Kidney 3 Cancer Genome Atlas Consortium, Nature,

2 VHL/HIF Regulatory Pathway GLUT1 PDK LDHA Glycolysis HIF1α HIFβHIF1α BNIP3 Apoptosis HIF1α PDGF FLT1 VEGF Angiogenesis MMP2 CXCR4 HIF2α Invasion Metastasis HIFβHIF2α HIF2α CCD1 TGFα OCT4 Proliferation Dedifferentiation Outline Gene expression profiles in clear cell renal cell carcinomas. Validating a prognostic signature in RCC. Exploring gene expression profiles in VHL syndrome RCC tumors. Sporadic VHL mutant tumors express HIF1 and HIF2, or HIF2 alone. Gene expression patterns show HIF specific variability HIF1 drives glycolytic genes, mtor pathway HIF2 drives genes involved in cell cycle and DNA damage. Overlap in angiogenesis and motility targets. Gordan et al, Cancer Cell, 2008 Gordan et al, Cancer Cell,

3 Using gene expression to identify tumor subgroups. cca and ccb K=3, K=4 still fall into two groups cca (classical angiogenic), ccb (bad) Validation in a historical dataset 3

4 Extent of Disease at Diagnosis Most cancers of the kidney and renal pelvis are diagnosed when the disease is still localized to the primary site Metastatic Spread 20% Loco-regional Spread 19% Unknown 5% Localized Disease 56% Determining Prognosis: Anatomic Extent of Disease Most consistent factor used to determine RCC prognosis Probability of Survival year Cancer-specific Survival Based on TNM Stage Log Rank P Value<.001 Stage IV (N=318) Stage I (N=185) Stage II (N=57) Stage III (N=83) Months of Postsurgery TNM Stage 5-year Cancerspecific Survival Stage I 91 ± 2.5% Stage II 74 ± 6.9% Stage III 67 ± 6.1% Stage IV 32 ± 3.2% National Cancer Institute. SEER Stat Fact Sheets. Available at: Accessed August 28, Reprinted with permission from Tsui KH, et al. J Urol. 2000;163: cca/ccb predicts for cancer specific and overall survival outcomes Validation dataset reveals a small distinct tumor set Brannon, et al, Eur Urol,

5 Cluster 3 are highly divergent from cca and ccb in metabolic genes. VHL mutants in both cca and ccb Brannon, et al, Eur Urol, 2012 Brannon, et al, Eur Urol, 2012 Developing a clinic tool: ClearCode34 95 clear cell tumors Prognostic value of ClearCode34 evaluated in TCGA LAD and ConsensusCluster analysis Set aside arrays with non-concordant assignments 72 arrays (microarray standard set) (69 tumors, 3 replicates) 43 cca arrays (42 tumors, 1 replicate) 29 ccb arrays (27 tumors, 2 replicates) Prediction Analysis for Microarrays (PAM) Predictive biomarkers: ClearCode34 Recurrence-free Survival cca ccb (n=205) (n=175) No. of events Median RFS, months HR, 2.3; 95% CI, 1.6 to 3.3; P=4.3e Time cca ccb Cancer-Specific Survival cca ccb (n=205) (n=175) No. of events Median CSS, months HR, 2.9; 95% CI, 1.6 to 5.6; P= cca ccb 5

6 Prognostic value of ClearCode34 validated in UNC cohort Prognostic value of ClearCode34 validated in TCGA Recurrence-Free Survival cca ccb cca ccb (n=69) (n=88) No. of events Median RFS, months HR, 2.1; 95% CI, 1.3 to 3.4; P=.001 Cancer-Specific Survival cca ccb (n=69) (n=88) No. of events 7 25 Median CSS, months HR, 3.0; 95% CI, 1.3 to 7.0; P=.005 cca ccb Abbreviation: HR, hazard ratio Subtype cca was used as reference in univariate and multivariate analysis. $ Stage I was used as reference in univariate and multivariate analysis. Stage was encoded as an ordinal variable with three levels. Grade 1 and 2 were combined and used as reference in univariate and multivariate analysis. Grade was encoded as an ordinal variable with three levels. Integrated prognostic models can evaluate risk outcomes RCC Algorithms for cancer-specific survival Group Risk Score Low Intermediate High >1.5 Recurrence-free Survival Low Risk (N=98) Intermediate Risk (N=140) High Risk (N=28) Log-rank P=3.04e-09 Time Cancer-Specific Survival Low Risk Intermediate Risk High Risk Log-rank P=2.03e-08 UCLA Integrated Staging System (UISS) 6

7 ClearCode34 Model outperforms established algorithms C-index i i C - C n - d n ex d ex UISS ClearCode34 UISS Model SSIGN ClearCode34 SSIGN ClearCode34 Model Model Change in in chi-squared statistic C h ange C h ange i n C i n h i C -squared h i -squared S t a S t is t a t ic t i s t i c * * * CC34Model->UISS UI->Model Model->SS SS->Model CC34Model->SSIGN ClearCode34 Summary ClearCode34 can accurately classify ccrcc tumors Prognostic value of cca/ccb classification validated in a TCGA and UNC cohort Integrated model for recurrence-free and cancerspecific survival constructed using ccrcc subtypes and traditional clinical variables stage and grade. This classifier adds value to predicting cancerspecific survival above and beyond established algorithms. How do we know this is meaningful for VHL patients? *VHL disease tumors and sporadic ccrccs (the majority VHL mutated) are not distinguishable by gene expression. TCGA includes 14 tumors from VHL patients: 2 class comparison reveals NO significantly different upregulated genes, 209 significantly downregulated. VHL cases in the TCGA A mixture of cca and ccb TCGA Sample ID ClearCode34 Status Grade Size (cm) T Stage N Stage M StatusStage KIRC TCGA A3 xxxx cca G2 3 T1a NX M0 Stage I KIRC TCGA A3 xxxx cca G3 4.9 T1b N0 M0 Stage I KIRC TCGA A3 xxxx ccb G2 4 T1a N0 M0 Stage I KIRC TCGA AK xxxx G2 5.5 T1 N0 M0 Stage I KIRC TCGA AK xxxx cca G2 12 T3b N0 M0 Stage III KIRC TCGA AK xxxx cca G2 7.5 T2 N0 M0 Stage II KIRC TCGA AK xxxx G3 6.5 T3b N1 M0 Stage III KIRC TCGA AK xxxx ccb G3 11 T2 NX M0 Stage II KIRC TCGA AK xxxx cca G2 7 T1b NX M0 Stage I KIRC TCGA AK xxxx G2 9 T2 N0 M1 Stage IV KIRC TCGA AK xxxx G2 6 T1b NX M0 Stage I KIRC TCGA AK xxxx ccb G3 5.5 T3a NX M0 Stage III KIRC TCGA AK xxxx cca G2 4 T1a NX M0 Stage I KIRC TCGA AK xxxx cca G3 9 T2 N0 M0 Stage II 7

8 Summary The hypoxia gene expression signature dominates VHL mutated RCC, but many other pathways emerge. The expression profile matches ccrcc to the early proximal tubule. Tumor expression profiles can reveal relevant biology and aid in disease prognosis. Rathmell Lab Kate Hacker, PhD Alex Arreola, PhD Samira Brooks Zufan Debebe, PhD Sneha Sundaram, PhD Catherine Fahey Adam Sendor Rathmell Lab Past Members Rose Brannon, PhD Oishee Sen Shufen Chen, MD, PhD Lance Cowey, MD Caroline Martz Lee, MD, PhD Tricia Wright, PhD Neal Rasmussen, PhD Translational Pathology Laboratory Genomics Core, Tissue Procurement Facility Acknowledgments Rutgers Gyan Bhanot, PhD Anupama Reddy, PhD Joel Parker, PhD UNC Biomedical Research Imaging Center Weili Lin, PhD Amir Khandani, MD Julia Fielding, MD The Cancer Genome Atlas Particularly: Chad Creighton, Marston Linehan, Richard Gibbs, Kenna Shaw Clinical TCGA Partiularly: James Hsieh, Ari Hakimi, Toni Chouieri Funding: AACR INNOVATOR Award, NIH (TCGA), NIH (K24), V Foundation for Cancer Research 8

Successes and Limitations of Targeted Therapies in Renal Cell Carcinoma

Successes and Limitations of Targeted Therapies in Renal Cell Carcinoma g Tumor Res. Basel, Karger, 2014, vol 41, pp 98 112 (DOI: 10.1159/000355906) Successes and Limitations of Targeted Therapies in Renal Cell Carcinoma Marc Pracht Dominik Berthold Medical Oncology Unit,

More information

NEOPLASMS OF KIDNEY (RENAL CELL CARCINOMA) And RENAL PELVIS (TRANSITIONAL CELL CARCINOMA)

NEOPLASMS OF KIDNEY (RENAL CELL CARCINOMA) And RENAL PELVIS (TRANSITIONAL CELL CARCINOMA) NEOPLASMS OF KIDNEY (RENAL CELL CARCINOMA) And RENAL PELVIS (TRANSITIONAL CELL CARCINOMA) Merat Esfahani, MD Medical Oncologist, Hematologist Cancer Liaison Physician SwedishAmerican Regional Cancer Center

More information

Carcinoma papilar renal, cromófobo y otras histologías. Maria José Méndez Vidal Servicio de oncología Medica Hospital Reina Sofía Córdoba

Carcinoma papilar renal, cromófobo y otras histologías. Maria José Méndez Vidal Servicio de oncología Medica Hospital Reina Sofía Córdoba Carcinoma papilar renal, cromófobo y otras histologías. Maria José Méndez Vidal Servicio de oncología Medica Hospital Reina Sofía Córdoba Europe 121 629 new cases RCC 2012, 75 676 affected men Slide 3

More information

Histologic Subtypes of Renal Cell Carcinoma

Histologic Subtypes of Renal Cell Carcinoma Histologic Subtypes of Renal Cell Carcinoma M. Scott Lucia, MD Associate Professor Chief of Genitourinary and Renal Pathology Director, Prostate Diagnostic Laboratory Dept. of Pathology University of Colorado

More information

Multiple Primary and Histology Site Specific Coding Rules KIDNEY. FLORIDA CANCER DATA SYSTEM MPH Kidney Site Specific Coding Rules

Multiple Primary and Histology Site Specific Coding Rules KIDNEY. FLORIDA CANCER DATA SYSTEM MPH Kidney Site Specific Coding Rules Multiple Primary and Histology Site Specific Coding Rules KIDNEY 1 Prerequisites 2 Completion of Multiple Primary and Histology General Coding Rules 3 There are many ways to view the Multiple l Primary/Histology

More information

Translocation Renal Cell Carcinomas: Molecular insights and Future Directions

Translocation Renal Cell Carcinomas: Molecular insights and Future Directions Translocation Renal Cell Carcinomas: Molecular insights and Future Directions Gabriel G. Malouf, MD, PhD Assistant professor Department of medical oncology Pitié-Salpêtrière Hospital, Paris, France Background

More information

KIDNEY FUNCTION RELATION TO SIZE OF THE TUMOR IN RENAL CELL CANCINOMA

KIDNEY FUNCTION RELATION TO SIZE OF THE TUMOR IN RENAL CELL CANCINOMA KIDNEY FUNCTION RELATION TO SIZE OF THE TUMOR IN RENAL CELL CANCINOMA O.E. Stakhvoskyi, E.O. Stakhovsky, Y.V. Vitruk, O.A. Voylenko, P.S. Vukalovich, V.A. Kotov, O.M. Gavriluk National Canсer Institute,

More information

Cancer Genomics: What Does It Mean for You?

Cancer Genomics: What Does It Mean for You? Cancer Genomics: What Does It Mean for You? The Connection Between Cancer and DNA One person dies from cancer each minute in the United States. That s 1,500 deaths each day. As the population ages, this

More information

Robert Bristow MD PhD FRCPC

Robert Bristow MD PhD FRCPC Robert Bristow MD PhD FRCPC Clinician-Scientist and Professor, Radiation Oncology and Medical Biophysics, University of Toronto and Ontario Cancer Institute/ (UHN) Head, PMH-CFCRI Prostate Cancer Research

More information

TNM staging and prognosis. Alexandru Eniu, MD, PhD Medical Oncologist Department of Breast Tumors Cancer Institute Ion Chiricuţă Cluj-Napoca, Romania

TNM staging and prognosis. Alexandru Eniu, MD, PhD Medical Oncologist Department of Breast Tumors Cancer Institute Ion Chiricuţă Cluj-Napoca, Romania TNM staging and prognosis Alexandru Eniu, MD, PhD Medical Oncologist Department of Breast Tumors Cancer Institute Ion Chiricuţă Cluj-Napoca, Romania The Basics of TNM Staging Premises: Cancers of the same

More information

What is Cancer? Cancer is a genetic disease: Cancer typically involves a change in gene expression/function:

What is Cancer? Cancer is a genetic disease: Cancer typically involves a change in gene expression/function: Cancer is a genetic disease: Inherited cancer Sporadic cancer What is Cancer? Cancer typically involves a change in gene expression/function: Qualitative change Quantitative change Any cancer causing genetic

More information

Renal Cell Carcinoma (Event Driven)

Renal Cell Carcinoma (Event Driven) Brochure More information from http://www.researchandmarkets.com/reports/2365661/ Renal Cell Carcinoma (Event Driven) Description: The Renal Cell Carcinoma market is highly lucrative. We anticipate that

More information

Histopathology and prognosis in renal cancer

Histopathology and prognosis in renal cancer Histopathology and prognosis in renal cancer Granular cell Granular cell Granular cell Granular cell Clear cell Chromophobe cell Papillary type 2 Luca Mazzucchelli Istituto cantonale di patologia, Locarno

More information

SECOND PRIMARY BREAST CANCERS FOLLOWING HAEMATOLOGIC MALIGNANCIES A CASE SERIES STUDY FARAH TANVEER PGY 3 DR.MEIR WETZLER DR.

SECOND PRIMARY BREAST CANCERS FOLLOWING HAEMATOLOGIC MALIGNANCIES A CASE SERIES STUDY FARAH TANVEER PGY 3 DR.MEIR WETZLER DR. SECOND PRIMARY BREAST CANCERS FOLLOWING HAEMATOLOGIC MALIGNANCIES A CASE SERIES STUDY FARAH TANVEER PGY 3 DR.MEIR WETZLER DR. TRACEY O CONNOR RESEARCH QUESTON Patients with previously diagnosed hematologic

More information

RENAL CANCER PATHOLOGY WHAT REALLY MATTERS? STEWART FLEMING UNIVERSITY OF DUNDEE

RENAL CANCER PATHOLOGY WHAT REALLY MATTERS? STEWART FLEMING UNIVERSITY OF DUNDEE RENAL CANCER PATHOLOGY WHAT REALLY MATTERS? STEWART FLEMING UNIVERSITY OF DUNDEE MAJOR PARADIGM SHIFT IN EARLY 1990S IN UNDERSTANDING RENAL CANCER Molecular differential pathology of renal cell tumours

More information

Something Old, Something New.

Something Old, Something New. Something Old, Something New. Michelle A. Fajardo, D.O. Loma Linda University Medical Center Clinical Presentation 6 year old boy, presented with hematuria Renal mass demonstrated by ultrasound & CT scan

More information

CABOZANTINIB VERSUS EVEROLIMUS IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA: RESULTS OF A RANDOMISED PHASE III TRIAL (METEOR)

CABOZANTINIB VERSUS EVEROLIMUS IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA: RESULTS OF A RANDOMISED PHASE III TRIAL (METEOR) CABOZANTINIB VERSUS EVEROLIMUS IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA: RESULTS OF A RANDOMISED PHASE III TRIAL (METEOR) This late-breaking abstract was presented on 26 th September 215 in Presidential

More information

Gleason Score. Oncotype DX GPS. identified for. about surveillance. time to get sophisticated

Gleason Score. Oncotype DX GPS. identified for. about surveillance. time to get sophisticated patient: MARK SMITH PSA 6.2 Gleason Score 6 Oncotype DX GPS 8 identified for active surveillance time to get sophisticated about surveillance Accurate prediction of prostate cancer risk is needed at the

More information

Renal Cell Carcinoma: Prognostic Factors and Patient Selection

Renal Cell Carcinoma: Prognostic Factors and Patient Selection european urology supplements 6 (2007) 477 483 available at www.sciencedirect.com journal homepage: www.europeanurology.com Renal Cell Carcinoma: Prognostic Factors and Patient Selection Arie S. Belldegrun

More information

Beyond the PSA: Genomic Testing in Localized Prostate Cancer

Beyond the PSA: Genomic Testing in Localized Prostate Cancer Beyond the PSA: Genomic Testing in Localized Prostate Cancer Kelvin A. Moses, MD, PhD Vanderbilt University Medical Center Wednesday, December 2, 2015 5:00 p.m. ET/2:00 p.m. PT About ZERO ZERO s mission

More information

Independent Validation of the Prognostic Gene Expression Ratio Test in Formalin Fixed, Paraffin Embedded (FFPE) Mesothelioma Tumor Tissue Specimens

Independent Validation of the Prognostic Gene Expression Ratio Test in Formalin Fixed, Paraffin Embedded (FFPE) Mesothelioma Tumor Tissue Specimens Independent Validation of the Prognostic Gene Expression Ratio Test in Formalin Fixed, Paraffin Embedded (FFPE) Mesothelioma Tumor Tissue Specimens Assunta De Rienzo, Ph.D. 1, Robert W. Cook, Ph.D. 2,

More information

Department of BioScience Technology Chung Yuan Christian University 2015/08/13

Department of BioScience Technology Chung Yuan Christian University 2015/08/13 Department of BioScience Technology Chung Yuan Christian University 2015/08/13 Cancer Cells Cancer, the 1st leading cause of death, is an example of a disease that arises from abnormalities in cell function

More information

From Immunotherapy of Cancer to the Discovery of Kidney Cancer Genes

From Immunotherapy of Cancer to the Discovery of Kidney Cancer Genes ISSN 2154-4006 The Genetic Basis of Human Disease zbar Colloquium series on Series Editor: Michael Dean, Ph.D., Head, Human Genetics Section, Senior Investigator, Laboratory of Experimental Immunology

More information

Renal Cell Carcinoma: Advances in Diagnosis B. Iványi, MD

Renal Cell Carcinoma: Advances in Diagnosis B. Iványi, MD Renal Cell Carcinoma: Advances in Diagnosis B. Iványi, MD Department of Pathology University of Szeged, Hungary ISUP Vancouver Classification of Renal Neoplasia Am J Surg Pathol 37:14691489, 2013 13 histologic

More information

Oncological outcome of surgical treatment in 336 patients with renal cell carcinoma

Oncological outcome of surgical treatment in 336 patients with renal cell carcinoma 窑 Original Article 窑 Chinese Journal of Cancer Oncological outcome of surgical treatment in 336 patients with renal cell carcinoma Zhi Ling Zhang,2, Yong Hong Li,2, Yong Hong Xiong 3, Guo Liang Hou,2,

More information

micrornas Non protein coding, endogenous RNAs of 21-22nt length Evolutionarily conserved

micrornas Non protein coding, endogenous RNAs of 21-22nt length Evolutionarily conserved microrna 2 micrornas Non protein coding, endogenous RNAs of 21-22nt length Evolutionarily conserved Regulate gene expression by binding complementary regions at 3 regions of target mrnas Act as negative

More information

Komorbide brystkræftpatienter kan de tåle behandling? Et registerstudie baseret på Danish Breast Cancer Cooperative Group

Komorbide brystkræftpatienter kan de tåle behandling? Et registerstudie baseret på Danish Breast Cancer Cooperative Group Komorbide brystkræftpatienter kan de tåle behandling? Et registerstudie baseret på Danish Breast Cancer Cooperative Group Lotte Holm Land MD, ph.d. Onkologisk Afd. R. OUH Kræft og komorbiditet - alle skal

More information

Surgical Management of Kidney Cancer. Adam R. Metwalli, M.D. Urologic Oncology Branch National Cancer Institute

Surgical Management of Kidney Cancer. Adam R. Metwalli, M.D. Urologic Oncology Branch National Cancer Institute Surgical Management of Kidney Cancer Adam R. Metwalli, M.D. Urologic Oncology Branch National Cancer Institute Background Cancer of the Kidney 95% of cases refers to Renal Cell Carcinoma (RCC) 5% refers

More information

Targeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma

Targeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma The Use of Kinase Inhibitors: Translational Lab Results Targeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma Sheelu Varghese, Ph.D. H. Richard Alexander, M.D.

More information

Developments in Biomarker Identification and Validation for Lung Cancer

Developments in Biomarker Identification and Validation for Lung Cancer Developments in Biomarker Identification and Validation for Lung Cancer Alexandre Passioukov, MD, PhD Alexandre.Passioukov@eortc.be Contents Introduction Lung cancer pathogenesis NSCLC treatment options

More information

Renal cell carcinoma and body composition:

Renal cell carcinoma and body composition: Renal cell carcinoma and body composition: Results from a case-control control study Ryan P. Theis, MPH Department of Epidemiology and Biostatistics College of Public Health and Health Professions University

More information

A new score predicting the survival of patients with spinal cord compression from myeloma

A new score predicting the survival of patients with spinal cord compression from myeloma A new score predicting the survival of patients with spinal cord compression from myeloma (1) Sarah Douglas, Department of Radiation Oncology, University of Lubeck, Germany; sarah_douglas@gmx.de (2) Steven

More information

The TV Series. www.healthybodyhealthymind.com INFORMATION TELEVISION NETWORK

The TV Series. www.healthybodyhealthymind.com INFORMATION TELEVISION NETWORK The TV Series www.healthybodyhealthymind.com Produced By: INFORMATION TELEVISION NETWORK ONE PARK PLACE 621 NW 53RD ST BOCA RATON, FL 33428 1-800-INFO-ITV www.itvisus.com 2005 Information Television Network.

More information

Temporal Trends in Demographics and Overall Survival of Non Small-Cell Lung Cancer Patients at Moffitt Cancer Center From 1986 to 2008

Temporal Trends in Demographics and Overall Survival of Non Small-Cell Lung Cancer Patients at Moffitt Cancer Center From 1986 to 2008 Special Report Temporal Trends in Demographics and Overall Survival of Non Small-Cell Lung Cancer Patients at Moffitt Cancer Center From 1986 to 2008 Matthew B. Schabath, PhD, Zachary J. Thompson, PhD,

More information

Classificazione anatomo-patologica nei RCC Matteo Brunelli. Department of Pathology and Diagnostic, University di Verona, Italy

Classificazione anatomo-patologica nei RCC Matteo Brunelli. Department of Pathology and Diagnostic, University di Verona, Italy Classificazione anatomo-patologica nei RCC Matteo Brunelli Department of Pathology and Diagnostic, University di Verona, Italy WHO 2004 AFIP 2004 = ISUP Vancouver Classification 2013 5 newentities 3 emerging

More information

Future Directions in Cancer Research What does is mean for medical physicists and AAPM?

Future Directions in Cancer Research What does is mean for medical physicists and AAPM? Future Directions in Cancer Research What does is mean for medical physicists and AAPM? John D. Hazle, Ph.D., FAAPM, FACR President-elect American Association of Physicists in Medicine Professor and Chairman

More information

Report series: General cancer information

Report series: General cancer information Fighting cancer with information Report series: General cancer information Eastern Cancer Registration and Information Centre ECRIC report series: General cancer information Cancer is a general term for

More information

Prognostic and Predictive Factors in Oncology. Mustafa Benekli, M.D.

Prognostic and Predictive Factors in Oncology. Mustafa Benekli, M.D. Prognostic and Predictive Factors in Oncology Mustafa Benekli, M.D. NCI Definitions ESMO Course -Essentials of Medical Oncology -Istanbul 2 Prognostic factor: NCI Definition A situation or condition, or

More information

Targeted Molecular Therapy for Renal Cell Carcinoma: Impact on Existing Treatment Paradigms

Targeted Molecular Therapy for Renal Cell Carcinoma: Impact on Existing Treatment Paradigms Targeted Molecular Therapy for Renal Cell Carcinoma: Impact on Existing Treatment Paradigms Wolfram Samlowski, MD For a CME/CEU version of this article please go to www.namcp.org/cmeonline.htm, and then

More information

Kidney Cancer Research: Developing a New Vision for the Future

Kidney Cancer Research: Developing a New Vision for the Future Kidney Cancer Research: Developing a New Vision for the Future A symposium for young investigators, hosted by the Kidney Cancer Association, September 7, 2011 Introduction Since the founding of the Kidney

More information

Renal Cancer: Symptoms, diagnosis, pathology & prognosis

Renal Cancer: Symptoms, diagnosis, pathology & prognosis Renal Cancer: Symptoms, diagnosis, pathology & prognosis Mark Johnson Consultant Urological Surgeon Newcastle upon Tyne Hospitals NHS Foundation Trust Plan for today: How renal tumours present What investigations

More information

The Molecular Diagnostic Market and development of personalized molecular tests

The Molecular Diagnostic Market and development of personalized molecular tests The Molecular Diagnostic Market and development of personalized molecular tests Dr. Iris Simon Sr. Director Research & Development, Agendia NV, Amsterdam NL and Irvine CA Agendia - Who are we Molecular

More information

Systems Biology: A Personal View XV. Network Medicine. Sitabhra Sinha IMSc Chennai

Systems Biology: A Personal View XV. Network Medicine. Sitabhra Sinha IMSc Chennai Systems Biology: A Personal View XV. Network Medicine Sitabhra Sinha IMSc Chennai Diseases, Genes and Networks http://learn.genetics.utah.edu/ Now that we have the ability to sequence entire genomes, can

More information

Tumori rari del rene: trattamento per stadio ed istologia Dr. Camillo Porta

Tumori rari del rene: trattamento per stadio ed istologia Dr. Camillo Porta Tumori rari del rene: trattamento per stadio ed istologia Dr. Camillo Porta S.C. di Oncologia Medica, Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia Non-Clear Cell Renal Cell Carcinoma (nccrcc) nccrcc

More information

The Value of Patient Advocacy in Laboratory Research--Making an Impact on Metastatic Breast Cancer Through the Rapid Autopsy Program

The Value of Patient Advocacy in Laboratory Research--Making an Impact on Metastatic Breast Cancer Through the Rapid Autopsy Program The Value of Patient Advocacy in Laboratory Research--Making an Impact on Metastatic Breast Cancer Through the Rapid Autopsy Program Lillie Shockney, RN., BS., MAS Administrative Director, Johns Hopkins

More information

Cancer Staging. Introduction. Overview

Cancer Staging. Introduction. Overview Many Hearts Many Minds One Goal Volume 2 Number 3 May 2005 Cancer Staging bt Maureen MacIntyre, Director, Surveillance and Epidemiology Unit, Cancer Care Nova Scotia and Dr. Eva Grunfeld, Clinician Scientist

More information

The WHO Classification of Renal Tumors and Common Issues in TNM Staging for Renal Cell Carcinoma

The WHO Classification of Renal Tumors and Common Issues in TNM Staging for Renal Cell Carcinoma The WHO Classification of Renal Tumors and Common Issues in TNM Staging for Renal Cell Carcinoma Steven Shen, M.D.,Ph.D. Staff Pathologist and Assistant Member The Methodsit Hospital and Research Institute

More information

Nuevas tecnologías basadas en biomarcadores para oncología

Nuevas tecnologías basadas en biomarcadores para oncología Nuevas tecnologías basadas en biomarcadores para oncología Simposio ASEBIO 14 de marzo 2013, PCB Jose Jimeno, MD, PhD Co-Founder / Vice Chairman Pangaea Biotech SL Barcelona, Spain PANGAEA BIOTECH BUSINESS

More information

A912: Kidney, Renal cell carcinoma

A912: Kidney, Renal cell carcinoma A912: Kidney, Renal cell carcinoma General facts of kidney cancer Renal cell carcinoma, a form of kidney cancer that involves cancerous changes in the cells of the renal tubule, is the most common type

More information

2. Background This was the fourth submission for everolimus requesting listing for clear cell renal carcinoma.

2. Background This was the fourth submission for everolimus requesting listing for clear cell renal carcinoma. PUBLIC SUMMARY DOCUMENT Product: Everolimus, tablets, 5 mg and 10 mg, Afinitor Sponsor: Novartis Pharmaceuticals Australia Pty Ltd Date of PBAC Consideration: November 2011 1. Purpose of Application To

More information

Examples of The Cancer Genome Atlas (TCGA) Analyses in GenePool

Examples of The Cancer Genome Atlas (TCGA) Analyses in GenePool Examples of The Cancer Genome Atlas (TCGA) Analyses in 1. RNA-Seq 2. mirna-seq 3. Protein Expression 4. Somatic Mutations 5. Copy Number 6. DNA Methylation RNA-Seq All primary tumor samples (1,097 of 1,218)

More information

BRAF as a prognostic marker in papillary thyroid cancer

BRAF as a prognostic marker in papillary thyroid cancer 12 Congresso Nazionale AME Molecular markers in thyroid cancer: current role in clinical practice BRAF as a prognostic marker in papillary thyroid cancer Dott. ssa Cristina Romei Sezione di Endocrinologia

More information

Prevalenza delle mutazioni TMEM127 nel feocromocitoma sporadico

Prevalenza delle mutazioni TMEM127 nel feocromocitoma sporadico Prevalenza delle mutazioni TMEM127 nel feocromocitoma sporadico Giuseppe Opocher Veneto Institute of Oncology and Department of Medical and Surgical Sciences, University of Padova, Italy Sympathetic paraganglia

More information

Metastatic Renal Cell Carcinoma Risk According to Tumor Size

Metastatic Renal Cell Carcinoma Risk According to Tumor Size Metastatic Renal Cell Carcinoma Risk According to Tumor Size R. Houston Thompson, Jennifer R. Hill, Yuriy Babayev, Angel Cronin, Matt Kaag, Shilajit Kundu, Melanie Bernstein, Jonathan Coleman, Guido Dalbagni,

More information

Seton Medical Center Hepatocellular Carcinoma Patterns of Care Study Rate of Treatment with Chemoembolization 2007 2012 N = 50

Seton Medical Center Hepatocellular Carcinoma Patterns of Care Study Rate of Treatment with Chemoembolization 2007 2012 N = 50 General Data Seton Medical Center Hepatocellular Carcinoma Patterns of Care Study Rate of Treatment with Chemoembolization 2007 2012 N = 50 The vast majority of the patients in this study were diagnosed

More information

Kidney Cancer OVERVIEW

Kidney Cancer OVERVIEW Kidney Cancer OVERVIEW Kidney cancer is the third most common genitourinary cancer in adults. There are approximately 54,000 new cancer cases each year in the United States, and the incidence of kidney

More information

The Ontario Cancer Registry moves to the 21 st Century

The Ontario Cancer Registry moves to the 21 st Century The Ontario Cancer Registry moves to the 21 st Century Rebuilding the OCR Public Health Ontario Grand Rounds Oct. 14, 2014 Diane Nishri, MSc Mary Jane King, MPH, CTR Outline 1. What is the Ontario Cancer

More information

Issued: September 2013. NICE diagnostics guidance 10. www.nice.org.uk/dg10

Issued: September 2013. NICE diagnostics guidance 10. www.nice.org.uk/dg10 Gene expression profiling and expanded immunohistochemistry tests for guiding adjuvant chemotherapy decisions in early breast cancer management: MammaPrint, Oncotype DX, IHC4 and Mammostrat Issued: September

More information

Breast and Lung Cancer Biomarker Research at ASCO: Changing Treatment Patterns

Breast and Lung Cancer Biomarker Research at ASCO: Changing Treatment Patterns July 2013 Edition Vol. 7, Issue 7 Breast and Lung Cancer Biomarker Research at ASCO: Changing Treatment Patterns By Julie Katz, MPH, MPhil Biomarkers played a prominent role in the research presented in

More information

Surgical Margins and follow up of Squamous Cell Carcinoma. Steve Keohane

Surgical Margins and follow up of Squamous Cell Carcinoma. Steve Keohane Surgical Margins and follow up of Squamous Cell Carcinoma Steve Keohane Poor registration Well established projected increase in incidence for next 2 decades Significant morbidity but relatively low mortality

More information

Malignant Lymphomas and Plasma Cell Myeloma

Malignant Lymphomas and Plasma Cell Myeloma Malignant Lymphomas and Plasma Cell Myeloma Dr. Bruce F. Burns Dept. of Pathology and Lab Medicine Overview definitions - lymphoma lymphoproliferative disorder plasma cell myeloma pathogenesis - translocations

More information

RCC accounts for 3% of all malignant tumors and now

RCC accounts for 3% of all malignant tumors and now Prognostic Value of Thrombocytosis in Renal Cell Carcinoma Karim Bensalah, Emmanuelle Leray, Patricia Fergelot, Nathalie Rioux-Leclercq, Jacques Tostain, François Guillé and Jean-Jacques Patard* From the

More information

9. Discuss guidelines for follow-up post-thyroidectomy for cancer (labs/tests) HH

9. Discuss guidelines for follow-up post-thyroidectomy for cancer (labs/tests) HH 9. Discuss guidelines for follow-up post-thyroidectomy for cancer (labs/tests) HH Differentiated thyroid cancer expresses the TSH receptor on the cell membrane and responds to TSH stimulation by increasing

More information

Pathologic Assessment Of The Breast And Axilla After Preoperative Therapy

Pathologic Assessment Of The Breast And Axilla After Preoperative Therapy Pathologic Assessment Of The Breast And Axilla After Preoperative Therapy W. Fraser Symmans, M.D. Associate Professor of Pathology UT M.D. Anderson Cancer Center Pathologic Complete Response (pcr) Proof

More information

Public-Private Partnerships in early phase clinical research: Spurring access to innovative therapeutics

Public-Private Partnerships in early phase clinical research: Spurring access to innovative therapeutics EPAAC WP8 Research Forum - 2 July, Sofitel Hotel Europe, Brussels Public-Private Partnerships in early phase clinical research: Spurring access to innovative therapeutics JY Blay, Past President EORTC

More information

Il percorso diagnostico del nodulo tiroideo: il ruolo dell analisi molecolare

Il percorso diagnostico del nodulo tiroideo: il ruolo dell analisi molecolare Il percorso diagnostico del nodulo tiroideo: il ruolo dell analisi molecolare Maria Chiara Zatelli Sezione di Endocrinologia Direttore: Prof. Ettore degli Uberti Dipartimento di Scienze Mediche Università

More information

Medullary Renal Cell Carcinoma Case Report

Medullary Renal Cell Carcinoma Case Report Bahrain Medical Bulletin, Vol. 27, No. 4, December 2005 Medullary Renal Cell Carcinoma Case Report Mohammed Abdulla Al-Tantawi MBBCH, CABS* Abdul Amir Issa MBBCH, CABS*** Mohammed Abdulla MBBCH, CABS**

More information

CHAPTER 2: UNDERSTANDING CANCER

CHAPTER 2: UNDERSTANDING CANCER CHAPTER 2: UNDERSTANDING CANCER INTRODUCTION We are witnessing an era of great discovery in the field of cancer research. New insights into the causes and development of cancer are emerging. These discoveries

More information

Balancing Big Data for Security, Collaboration and Performance

Balancing Big Data for Security, Collaboration and Performance Balancing Big Data for Security, Collaboration and Performance Sai Balu Lineberger Cancer Center UNC Chapel Hill Oct 14, 2014 About UNC Oldest Public University -1793 Top 5 Public University. 46th World

More information

microrna Signatures in Cancer E. ROBERT WASSMAN, MD, FAAP, FACMG CHIEF MEDICAL OFFICER, ROSETTA GENOMICS

microrna Signatures in Cancer E. ROBERT WASSMAN, MD, FAAP, FACMG CHIEF MEDICAL OFFICER, ROSETTA GENOMICS microrna Signatures in Cancer E. ROBERT WASSMAN, MD, FAAP, FACMG CHIEF MEDICAL OFFICER, ROSETTA GENOMICS 1st International Congress on Controversies in Personalized Oncology (CONPO) BARCELONA, SPAIN MARCH

More information

A New Biomarker in Prostate Cancer Care: Oncotype Dx. David M Albala, MD Chief of Urology Crouse Hospital Syracuse, NY

A New Biomarker in Prostate Cancer Care: Oncotype Dx. David M Albala, MD Chief of Urology Crouse Hospital Syracuse, NY A New Biomarker in Prostate Cancer Care: Oncotype Dx David M Albala, MD Chief of Urology Crouse Hospital Syracuse, NY Learning Objectives Review the current challenges in the prediction and prognosis of

More information

BACKGROUND. Evidence exists to suggest a pattern of increasing early diagnosis

BACKGROUND. Evidence exists to suggest a pattern of increasing early diagnosis 78 Renal Cell Cancer Stage Migration Analysis of the National Cancer Data Base Christopher J. Kane, MD 1,2 Katherine Mallin, PhD 3 Jamie Ritchey, MPH 3 Matthew R. Cooperberg, MD, MPH 4 Peter R. Carroll,

More information

Rulex s Logic Learning Machines successfully meet biomedical challenges.

Rulex s Logic Learning Machines successfully meet biomedical challenges. Rulex s Logic Learning Machines successfully meet biomedical challenges. Rulex is a predictive analytics platform able to manage and to analyze big amounts of heterogeneous data. With Rulex, it is possible,

More information

Vad är bioinformatik och varför behöver vi det i vården? a bioinformatician's perspectives

Vad är bioinformatik och varför behöver vi det i vården? a bioinformatician's perspectives Vad är bioinformatik och varför behöver vi det i vården? a bioinformatician's perspectives Dirk.Repsilber@oru.se 2015-05-21 Functional Bioinformatics, Örebro University Vad är bioinformatik och varför

More information

Changes in Breast Cancer Reports After Second Opinion. Dr. Vicente Marco Department of Pathology Hospital Quiron Barcelona. Spain

Changes in Breast Cancer Reports After Second Opinion. Dr. Vicente Marco Department of Pathology Hospital Quiron Barcelona. Spain Changes in Breast Cancer Reports After Second Opinion Dr. Vicente Marco Department of Pathology Hospital Quiron Barcelona. Spain Second Opinion in Breast Pathology Usually requested when a patient is referred

More information

Does my patient need more therapy after prostate cancer surgery?

Does my patient need more therapy after prostate cancer surgery? Does my patient need more therapy after prostate cancer surgery? Contact the GenomeDx Patient Care Team at: 1.888.792.1601 (toll-free) or e-mail: client.service@genomedx.com Prostate Cancer Classifier

More information

INTRODUCTION: CASE REPORT:

INTRODUCTION: CASE REPORT: Balekuduru Chaitanya et SYNCHRONOUS OCCURRENCE OF PAPILLARY RENAL CELL CARCINOMA AND TRANSITIONAL UROTHELIAL CELL CARCINOMA OF URINARY BLADDER a case report S. Rajasekhar Reddy 1, Balekuduru Chaitanya*

More information

Research in IBD at University of Colorado Denver

Research in IBD at University of Colorado Denver Research in IBD at University of Colorado Denver Blair Fennimore, MD Assistant Professor of Medicine Division of Gastroenterology and Hepatology UCH Crohn s and Colitis Center Mucosal Inflammation Program

More information

LUNG CANCER the new Staging System G.KIROVA TOKUDA HOSPITAL SOFIA

LUNG CANCER the new Staging System G.KIROVA TOKUDA HOSPITAL SOFIA LUNG CANCER the new Staging System G.KIROVA TOKUDA HOSPITAL SOFIA STAGING SYSTEM Provides standardized nomenclature for exchanging information Groups patients according to the biologic behavior of their

More information

Epithelial Ovarian Cancer

Epithelial Ovarian Cancer Epithelial Ovarian Cancer Fred Ueland, MD University of Kentucky Gynecologic Oncology Risk Factors Incessant ovulation Early menarche, late menopause, low parity Family history Acquired genetic mutations

More information

Incidental Detection of Renal Cell Carcinoma is an Independent Prognostic Marker: Results of a Long-Term, Whole Population Study

Incidental Detection of Renal Cell Carcinoma is an Independent Prognostic Marker: Results of a Long-Term, Whole Population Study Incidental Detection of Renal Cell Carcinoma is an Independent Prognostic Marker: Results of a Long-Term, Whole Population Study Helga Bjork Palsdottir, Sverrir Hardarson, Vigdis Petursdottir, Armann Jonsson,

More information

Case Number: RT2009-124(M) Potential Audiences: Intent Doctor, Oncology Special Nurse, Resident Doctor

Case Number: RT2009-124(M) Potential Audiences: Intent Doctor, Oncology Special Nurse, Resident Doctor Renal Cell Carcinoma of the Left Kidney Post Radical Surgery with pt4 Classification with Multiple Lung and Single Brain Metastases: the Role and Treatment Consideration of Radiotherapy Case Number: RT2009-124(M)

More information

Renal Pathology Update. Sundus Hussein MD, FRCPC

Renal Pathology Update. Sundus Hussein MD, FRCPC Renal Pathology Update Sundus Hussein MD, FRCPC Case History A 45 year old male with incidentally discovered a 3.5 x 3.9 x 2.7 cm renal mass Handling partial nephrectomy Handling partial nephrectomy

More information

Effective Health Care Program

Effective Health Care Program Comparative Effectiveness Review Number 152 Effective Health Care Program Treatment of Nonmetastatic Muscle-Invasive Bladder Cancer Executive Summary Background Nature and Burden of Nonmetastatic Muscle-Invasive

More information

Center for Causal Discovery (CCD) of Biomedical Knowledge from Big Data University of Pittsburgh Carnegie Mellon University Pittsburgh Supercomputing

Center for Causal Discovery (CCD) of Biomedical Knowledge from Big Data University of Pittsburgh Carnegie Mellon University Pittsburgh Supercomputing Center for Causal Discovery (CCD) of Biomedical Knowledge from Big Data University of Pittsburgh Carnegie Mellon University Pittsburgh Supercomputing Center Yale University PIs: Ivet Bahar, Jeremy Berg,

More information

Challenges in gastric, appendiceal and rectal NETs Leuven, 29.11.2014

Challenges in gastric, appendiceal and rectal NETs Leuven, 29.11.2014 Challenges in gastric, appendiceal and rectal NETs Leuven, 29.11.2014 Prof. Dr. Chris Verslype, Leuven Prof. Dr. Aurel Perren, Bern Menue Challenges: 1. Gastric NET 2. Appendiceal NET 3. Rectal NET SEER,

More information

A 70-year old Man with Pleural Effusion

A 70-year old Man with Pleural Effusion Mesothelioma Diagnosis: Pitfalls and Latest Updates S Klebe and DW Henderson Recommendations Indisputable malignant cells on cytomorphological criteria which demonstrate a mesothelial phenotype, which

More information

Background. t 1/2 of 3.7 4.7 days allows once-daily dosing (1.5 mg) with consistent serum concentration 2,3 No interaction with CYP3A4 inhibitors 4

Background. t 1/2 of 3.7 4.7 days allows once-daily dosing (1.5 mg) with consistent serum concentration 2,3 No interaction with CYP3A4 inhibitors 4 Abstract No. 4501 Tivozanib versus sorafenib as initial targeted therapy for patients with advanced renal cell carcinoma: Results from a Phase III randomized, open-label, multicenter trial R. Motzer, D.

More information

CONTEMPORARY MANAGEMENT OF RENAL ANGIOMYOLIPOMA

CONTEMPORARY MANAGEMENT OF RENAL ANGIOMYOLIPOMA CONTEMPORARY MANAGEMENT OF RENAL ANGIOMYOLIPOMA Stephen A. Boorjian, MD Professor of Urology Vice Chair of Research Director, Urologic Oncology Fellowship Department of Urology Mayo Clinic, Rochester,

More information

4/9/2012. Understanding the definition of Tumor Deposits. Guidance for pathologists on documenting TD. Utilizing the new N1c category

4/9/2012. Understanding the definition of Tumor Deposits. Guidance for pathologists on documenting TD. Utilizing the new N1c category Contributors: Carolyn Compton, MD, PhD J. Milburn Jessup, MD Leslie H. Sobin, MD Mary Kay Washington, MD, PhD Christian Wittekind, MD AJCC Cancer Staging Manual Seventh Edition UICC TNM Classification

More information

PARANEOPLASTIC SIGNS AND SYMPTOMS OF RENAL CELL CARCINOMA: IMPLICATIONS FOR PROGNOSIS

PARANEOPLASTIC SIGNS AND SYMPTOMS OF RENAL CELL CARCINOMA: IMPLICATIONS FOR PROGNOSIS 0022-5347/03/1705-1742/0 Vol. 170, 1742 1746, November 2003 THE JOURNAL OF UROLOGY Printed in U.S.A. Copyright 2003 by AMERICAN UROLOGICAL ASSOCIATION DOI: 10.1097/01.ju.0000092764.81308.6a PARANEOPLASTIC

More information

Metastatic Cancer: Questions and Answers. Key Points

Metastatic Cancer: Questions and Answers. Key Points CANCER FACTS N a t i o n a l C a n c e r I n s t i t u t e N a t i o n a l I n s t i t u t e s o f H e a l t h D e p a r t m e n t o f H e a l t h a n d H u m a n S e r v i c e s Metastatic Cancer: Questions

More information

Avances en biología molecular en gliomas de alto grado

Avances en biología molecular en gliomas de alto grado Avances en biología molecular en gliomas de alto grado Dra. Avelina Tortosa Campus Ciencies de la Salut Bellvitge IDIBELL-Universitat de Barcelona atortosa@ub.edu Goal: to profile a large cohort of GBMs

More information

Personalized Predictive Medicine and Genomic Clinical Trials

Personalized Predictive Medicine and Genomic Clinical Trials Personalized Predictive Medicine and Genomic Clinical Trials Richard Simon, D.Sc. Chief, Biometric Research Branch National Cancer Institute http://brb.nci.nih.gov brb.nci.nih.gov Powerpoint presentations

More information

Outline. Predictive Assays in Radiation Therapy Immunotherapy in Cancer Treatment. Introduction. Current clinical practice

Outline. Predictive Assays in Radiation Therapy Immunotherapy in Cancer Treatment. Introduction. Current clinical practice Predictive Assays in Radiation Therapy Immunotherapy in Cancer Treatment Radiation Biology Outline Introduction: Predictive assays in radiation therapy Examples for specific tumors Immunotherapy Summary

More information

Regulatory Issues in Genetic Testing and Targeted Drug Development

Regulatory Issues in Genetic Testing and Targeted Drug Development Regulatory Issues in Genetic Testing and Targeted Drug Development Janet Woodcock, M.D. Deputy Commissioner for Operations Food and Drug Administration October 12, 2006 Genetic and Genomic Tests are Types

More information

Luis D. Carcorze Soto, MD PGY-3

Luis D. Carcorze Soto, MD PGY-3 Luis D. Carcorze Soto, MD PGY-3 Peritoneal Surface Malignancies Peritoneum Patient Selection Operative Technique HIPEC EPIC Primary: Primary Peritoneal Carcinoma Malignant Peritoneal Mesothelioma Metastatic:

More information

Measures of Prognosis. Sukon Kanchanaraksa, PhD Johns Hopkins University

Measures of Prognosis. Sukon Kanchanaraksa, PhD Johns Hopkins University This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike License. Your use of this material constitutes acceptance of that license and the conditions of use of materials on this

More information

Genomic Medicine The Future of Cancer Care. Shayma Master Kazmi, M.D. Medical Oncology/Hematology Cancer Treatment Centers of America

Genomic Medicine The Future of Cancer Care. Shayma Master Kazmi, M.D. Medical Oncology/Hematology Cancer Treatment Centers of America Genomic Medicine The Future of Cancer Care Shayma Master Kazmi, M.D. Medical Oncology/Hematology Cancer Treatment Centers of America Personalized Medicine Personalized health care is a broad term for interventions

More information

Theories on Metastasis: Innovative Thinking An Advocacy Perspective

Theories on Metastasis: Innovative Thinking An Advocacy Perspective Theories on Metastasis: Innovative Thinking An Advocacy Perspective Project LEAD Workshop NBCC Annual Advocacy Conference 2011 Musa Mayer AdvancedBC.org 1 The Big Question If we want to end death from

More information