Massachusetts General Hospital Cancer Center Thematic Priorities 2012 Allocation Report

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1 Massachusetts General Hospital Cancer Center Thematic Priorities 2012 Allocation Report Providing the finest, personalized care to every patient is central to the Massachusetts General Hospital Cancer Center s mission. Clinicians in 24 disease specific programs work hand-in-hand with researchers in the laboratory to advance findings and improve the treatments provided to patients. At the heart of the center is a commitment to foster innovation and excellence in all facets of its work. This approach has led US News & World Report to recently name Mass General as America s best hospital, and recognize the Cancer Center, once again, as one of the finest centers in the field. Given increasing economic pressures and decreasing support from the National Institutes of Health, Cancer Center leadership created the Priorities Fund to accelerate novel scientific discovery and better serve patients. Fueled by unrestricted philanthropy, this resource provides vital seed funding for high-risk, high-reward laboratory science; innovative clinician-led studies; and new patient support and wellness initiatives. Grants from the Priorities Fund are allocated across five thematic areas, which reflect the Cancer Center s comprehensive approach to patient care and research. This report highlights projects recently supported by the Priorities Fund.

2 Discovering the fundamental causes of cancer as a guide to prevention, early detection and treatment The Priorities Fund grants to support basic research are vital to enable our scientists to probe new and far reaching areas of cancer medicine, explains Daniel A. Haber, MD, PhD, director of the Cancer Center. Two Priorities Fund grants have been awarded to the MGH Center for Cancer Research, one for the purchase of a new confocal microscope system and the other for computational biology consultative services. Confocal laser scanning microscopy is a powerful technique for obtaining extremely high-resolution, threedimensional optical images of biological specimens. The instrument enables researchers to track individual molecules or groups of molecules inside living cells, which is critical for understanding the differences between healthy cells and tumor cells, and for identifying new targets for cancer therapy. At least 15 different laboratories will use the new system for studies ranging from tracking novel signaling pathways in zebrafish to capturing and identifying circulating tumor cells from the blood of cancer patients. Today s advanced research technologies molecular imaging, genomics, proteomics are generating vast quantities of complex information. Computational biologists have the skills to help researchers maximize the benefits of every experiment through careful planning and the development of new tools for analyzing and interpreting data. Their input speeds the search for new cancer genes, for better strategies for cancer diagnosis, and for more effective, less toxic cancer therapies. A Priorities Fund grant will enable more researchers and centers to benefit from this specialized service.

3 Targeting early cancers through precision surgery and focused radiation Support from the Priorities Fund is enabling us to pursue new and innovative ways to eradicate tumors in their primary site to not only control localized growth but also to prevent metastases, states Jay Loeffler, MD, chief of Radiation Oncology. Magnetic resonance imaging (MRI) is a technique that has long been able to provide detailed images of internal structures of the body, and particularly soft tissues. However, this technique is not as accurate as desired in precisely identifying cancerous tumors. Giulia Fulci, PhD, and a multidisciplinary team are developing a new strategy to detect tumor tissues with a higher degree of specificity and sensitivity using a technology called amide proton transfer (APT). Amide protons are desirable because they interact with water molecules, thereby amplifying the signal. Dr. Fulci and her team s goal is to show that APT-MRI can identify smaller formations of living cancerous tumors than standard MRI techniques, allowing for earlier detection. If successful, the team plans to conduct pilot studies in patients. Glioblastomas are the most deadly form of brain tumor, despite the current optimal multimodal therapy strategy. Recently, a group of cancer stem cells have been isolated from glioblastomas that have properties of adult stem cells, including self renewal. Samuel Rabkin, PhD, and his team are investigating the role played by glioblastoma stem cells (GSCs) with alterations in DNA repair pathways in enabling therapy resistance and contributing to the growth of tumors. Defects in DNA repair genes are associated with increased cancer risk. Understanding DNA repair capabilities in GSCs may lead to therapeutic strategies that enhance radiation effects. Lumpectomy surgery following a breast cancer diagnosis has been show to be as effective as a mastectomy in longterm breast cancer recurrence rates. The key is achieving clear lumpectomy margins; however many patients require additional procedures to ensure optimal results. Utilizing a Priorities Fund grant, Barbara Smith, MD, PhD, and her colleagues are studying the use of 3D breast reconstruction techniques to better understand the microanatomy of primary breast tumors and their patterns of growth. Moreover, they will compare the results of 3D reconstruction to traditional pre-operative procedures and imaging. The overall goal is to gain new and valuable insights into the tumor microanatomy to improve lumpectomy outcomes. Soft tissue sarcomas are a relatively rare cancer affecting 10,000 individuals in the US each year. The typical treatment protocol includes surgery and radiation. Local recurrence of the disease is high, especially if adjacent to blood vessels or nerves. Sam Yoon, MD, is studying the use of combining drugs that target the tumor vasculature with radiation therapy. He previously demonstrated that the drug bevacizumab improves outcomes. For this study, he will utilize pazopanib, doxorubicin and radiation, and aim to determine the proper dosing of the drugs when administered concurrently to improve treatment results.

4 Targeting complex and advanced cancers through smart drugs Seed funding through the Priorities Fund is accelerating our clinician-scientists ability to develop personalized treatments for cancer, explains José Baselga, MD, PhD, associate director of the Cancer Center. Cesar Castro, MD, and his colleagues are investigating the use of Micro-Nuclear Magnetic Resonance (μnmr), a novel MRI-based technology that can detect specific molecular markers, as a possible alternative to standard tumor biopsies. The key to Dr. Castro s approach is incorporating the use of circulating tumor cell technology on four protein targets in patients with metastatic gynecologic cancers to potentially detect cancers earlier and treat them more effectively using targeted therapies than with routine pathology. Preliminary results in this observational study have been very promising and it is being expanded to incorporate additional patients. Glioblastoma is the most common primary brain tumor in adults. Recently, a mutation in the enzyme isocitrate dehydrogenase 1 (IDH1) has emerged as a potential driver of the disease. Andrew Chi, MD, PhD, and his colleagues are aiming to validate this mutation as a therapeutic target using recently established glioblastoma stem-like cell cultures and traditional human cell lines. This team s goal is to understand the degree of enzyme inhibition needed to stop or slow cancer development. This will help to speed new treatments to patients. Acute myeloid leukemia (AML), which forms inside bone marrow, is one of the most common types of leukemia among adults. Long-term survival outcomes from this disease are low, and outside of chemotherapy, no new treatments are currently available. Amir Fathi, MD, and David Sykes, MD, PhD, are each utilizing a Priorities Fund grant to study the roots of this disease. Dr. Fathi s research is focusing on genes encoding isocitrate dehydrogenase (IDH), an important enzyme in cellular metabolism. Patients with IDH-mutant AML have elevated levels of 2-HG, a metabolite that typically presents at very low levels in human tissues. The aim of Dr. Fathi s work is to determine whether an elevated 2-HG level is associated with an increased rate of disease relapse following chemotherapy. Additionally, he is studying whether patients with IDH solid tumors have elevated serum levels of 2-HG. Dr. Sykes is investigating the role and clinical relevance of prostacyclin agonists, drugs used in the treatment of pulmonary hypertension, in the treatment of AML. The potential use of prostacyclin drugs is especially appealing as they have been previously approved by the FDA and are well-tolerated by patients.

5 Accelerating the delivery of research discoveries to people with cancer Grants from the Priorities Fund provide critical support for our first-in-human clinical trials; findings from these trials become the foundation for the definitive studies that establish new drug treatments for cancer, states Bruce Chabner, MD, director of Clinical Research. A Priorities Fund grant was awarded to support and sustain the clinical trial efforts in the Henri and Belinda Termeer Center for Targeted Therapies. The center oversees and manages the translation of laboratory research into innovative first-in-human clinical trials. Over the past several years, the number of Phase I, II, and III clinical trials has tripled, which holds the potential to speed the delivery of novel therapies to patients. The Termeer Center capitalizes on the unique capabilities of the Cancer Center s Translational Research Laboratory and Center for Molecular Therapeutics to design targeted smart drugs to attack genetic abnormalities in a tumor s unique make-up. The goal is to develop more effective, less toxic treatments to improve patients quality of life.

6 Providing a world of care: treating the patient, supporting the family and educating the community Our clinicians ability to offer the finest care and support services to patients and families affected by a cancer diagnosis is core to our mission. Their efforts are tremendously advanced by the support from the Priorities Fund, says Debra Burke, RN, associate chief nurse of the Cancer Center. Multiple myeloma is a rare cancer of the bone marrow. Every other month, Jill Burke, NP, Lauren Leavit, MA, and Amy Corveleyn, MSW, host an education and support group for patients, family members, friends and caregivers affected by this disease. Mass General was the first cancer center to establish a group of this nature, drawing patients from other hospitals to attend meetings. A Priorities Fund grant was awarded to enable the multiple myeloma support group to continue throughout A Priorities Fund grant was awarded to the Maxwell V. Blum Cancer Resource Room to expand the library of information on new treatments and clinical trials offered at the Cancer Center. Led by Sally Hooper, MSW, LICSW, the expansion of printed materials available to patients will ensure individuals and family members affected by a cancer diagnosis have the latest information on treatment options to aid decision making. Support programs specifically for youth and young adults affected by cancer are incredibly rare. The HOPES Program in partnership with NextStep, an offshoot of the Hole in the Wall Gang, received a Priorities Fund grant to host a four day conference for 25 young cancer survivors (ages 16 to 24). The retreat was held in August and helped to foster positive social support, leadership skills and advocacy, self-management techniques and above all, encourage laughter, relaxation and positive experiences. Inga Lennes, MD, will be leading a study to investigate the effectiveness of incorporating early survivorship care with routine oncology care for individuals with newly diagnosed lung and gastrointestinal cancers. The study aims to develop a new model of oncology care that addresses physical and psychosocial issues to aid patient transition into primary care after treatment and ultimately improve patient mood and overall quality of life, as well as reduce anxiety. A Priorities Fund grant was awarded to the Pediatric Oncology unit to support the Take Good Care Pack program. In the program, children with cancer, their siblings and parents each receive a customized backpack containing important educational information and therapeutic resources to promote family communication and assist in understanding and coping with the child s cancer diagnosis and treatment.

7 Providing a world of care: treating the patient, supporting the family and educating the community (cont.) Sanja Percac-Lima, MD, PhD and Sarah Oo, MSW, are leading an important effort to improve cancer care and screening, and decrease disparities for patients in the MGH Primary Care Network. The TopCare program utilizes patient navigators to identify and track patients at MGH eligible for preventive cancer screening, focusing on breast, cervical, and colorectal cancers, and assist them in obtaining necessary tests and follow up appointments. A Priorities Fund grant was awarded to continue this program through next year. William Pirl, MD, MPH, and a multidisciplinary team are launching a unique educational series for oncology nurses based on dialectical behavior therapy to improve patient care. This four-part program, supported by a Priorities Fund grant, aims to provide oncology nurses with the skills and techniques necessary to cope with some of the most difficult and emotionally challenging nursing situations, including patient psychiatric issues, extreme suffering and end-of-life care. Oncology Chaplain Katrina Scott, MDiv, BCC, has been awarded a Priorities Fund grant to launch the Dignity Therapy program. For this therapeutic intervention, patients with life-threatening or life-altering prognoses are invited to engage in guided conversations addressing issues and memories that are important. The program is based on three core tenets meaning, value and relationships. The conversations are recorded and become a written narrative that patients can share with family members and loved ones. It has been shown that African American women have higher rates of death from breast cancer compared to Caucasians. Karen Winkfield, MD, PhD, is leading a faith-based outreach initiative to educate black families in the greater Boston area about breast cancer. This community-based program aims to reduce healthcare disparities by teaching clergy and lay-persons in black churches the skills needed to provide the best breast health and to offer information on local resources pertaining to screening and follow-up care.