ONS Highlights

1. ONS Highlights Carol S. Viele RN MS OCN Clinical Nurse Specialist Hematology-Oncology-Bone Marrow Transplant UCSF Associate Clinical; Professor Department of Physiological Nursing UCSF School of Nursing

2. Overview • Held in Boston, Massachusetts • April 29-May 1, 2011 • 55 sessions over 3.5 days of the meeting • Session topics included: • Infection, Sepsis Update • Clinical Trials/ Protocol Issues • International Oncology • Ethics • Preparing for the future of Oncology Nursing • BMT Toxicities • Safe Handling Issues • Genotype directed therapy • Genetics

3. Highlights in Crash Course in BMT • Presenters from Johns Hopkins, Seattle Cancer Care Alliance and Stanford University • Topics: Pulmonary Issues, Hepatic Toxicity and Hepatic GVHD and Skin Toxicity • Pulmonary Issues • Incidence 30-60% • Cause of death 60% • Diagnosis • Bronchoscopy • Lung biopsy • Risk Factors/Etiology • Aspergillus • CMV • Pneumocystisjiroveci • BronchiolitisObliterans • BOOP • DAH

4. Highlights in Crash Course in BMT • Interventions • Antibiotics • Antifungals • Antivirals • Steroids • Anxiolytics • Benzodiazepines • Dypsnea management

5. Highlights in Crash Course in BMT • Hepatic Complications • Sinusoidal obstruction syndrome • Graft versus host disease • Drug induced lung injury • Infections • Bacterial • Fungal • Viral • Cholecystitis

6. Highlights in Crash Course in BMT • Diagnostic tests • Laboratory data • Imaging • Liver biopsy • Prevention • Ursodiol • Antifungals • Antivirals • Conditioning regimens • Decreased intensity regimens • No cytoxan

7. Highlights in Crash Course in BMT • Treatments • Low dose tissue plasminogen activator • 20% response • Antithrombin III • Defibrotide • > 36 % response rate

8. Highlights in Crash Course BMT • Hepatic Graft versus Host disease • Onset 2-4 weeks post BMT • Jaundice and increased LFT’s • Staging directly related to level of bilirubin • Prevention and Treatment • Calcineurin inhibitors • Mycophenolate mofetil • Methotrexate • Ursodiol • Steroids • ATG • Sirolimus • Rapamycin • Monoclonal antibodies

9. Highlights Genotype Directed Therapy Lung Cancer • By Lecia Sequist MD, MPH • NSCL Cancer therapy • Chemotherapy- modestly successful • Molecular targeting • Key pieces to understand the cell biology of each individual’s tumor • Treatment effective against the particular biology of tumor • EGFR dysregulation • Tyrosine kinase inhibitors in lung • Gefitinib- Iressa • Erlotinib- Tarceva

10. Highlights Gene Directed Therapy Lung Cancer • Treatment: • Find EGFR mutations in patients • 10% of lung cancer patient have EGFR mutations • Response rates as high as 70% in this group of patients 1 • Based on the Mok trial US is looking at need for molecular testing of tumors • More common in: • Women • Never smokers • Little smoking history • Mok 2009 NEJM

11. Highlights Gene Directed Therapy Lung Cancer • Targeted therapy eventually develops resistance • Mass General is doing repeat biopsies to track resistance development in tumors • Initial response is usually 12 months • Looking at another pathway the MET inhibitor • Adding a MET inhibitor with Erlotinib • Another pathway is ALK translocation • First described in 2007 • Can be responsible for lung cancer progression

12. Highlights Gene Directed Therapy Lung Cancer • Crizotinib – a new agent being trialed and the target is ALK • Phase I study • 150 Patients • Dramatic responses • ? FDA approval in 2011

13. Highlights Gene Directed Therapy Lung Cancer • Future genotype directed therapy in lung cancer • KRAS • ALK • BRAF • MET • PDGFR • EGFR

14. Highlights Biology of Pediatric and Adult Cancers • John Maris MD Children’s Hospital Philadelphia • Belinda Mandrell PhD RN PNP • The future in cancer treatment is a “ personal approach” • Need to understand hereditary cancers • Genomic profiling • Practical and ethical implications

15. Highlights Biology of Pediatric and Adult Cancers • Childhood cancers • Continue to cause significant morbidity and mortality • Cure rates are stagnant • Late effects are significant • Childhood cancers represent a microcosm of cancers in general • Cancer is the leading cause of death in children except for accidents • 2/3 of children who survive have life long disabilities • 1/4 of the children who survive have significant life long disabilities such as CHF and hearing loss

16. Highlights Biology of Pediatric and Adult Cancers • Molecularly targeted agents • Increase the cure rates • Decrease the toxicity rates

17. Highlights Biology of Pediatric and Adult Cancers • Neuroblastoma • Median age at diagnosis 17 months • 15% of childhood mortality • Induces significant morbidity • 30% of cases spontaneously resolve • 50% of cases are high risk disease • Need to define the molecular targets • Genetic basis of disease • Define the oncogenic drivers of this disease

18. Highlights Biology of Pediatric and adult Cancers • Genomic profiling • ALK (Anaplastic lymphoma kinase) gene is the major familial neuroblastoma gene and is located on chromosome 2 • Occurs in 80% of familial disease • PHOX 2B occurs in 10% of Familial neuroblastoma

19. Highlights Biology of Pediatric and adult Cancers • Genomic Profiling includes: • DNA copy numbers- Single Nucleotide Polymorphism arrays • RNA copy numbers – Expression arrays • Mutations- Sequencing analysis Vision for all patients they will all have DNA sequencing done at diagnosis. As we treat patients mutations will occur and moving forward we can profile the DNA and RNA alterations

20. Highlights Biology of Pediatric and Adult Cancers • Genetic Profiling Considerations • Family history may suggest a genetic cancer syndrome • Tests need to be adequately interpreted • Consent for testing must occur • Pre and Post counseling needs to occur • Patients need to know the results may affect their ability to obtain life insurance not health insurance

21. Highlights Biology of Pediatric and Adult Cancers • Informed Consent Issues: • Clinical Implications • Importance for children • Accuracy of testing • Fees • Psychological issues • Confidentiality issues • Insurance issues

22. Questions