Annual Impact Report. November 2016

Transcription

1 Annual Impact Report November 2016

2 Your support helps prompt the next era of innovation. Your commitment empowers us all to imagine a world free from cancer. Alan Ashworth, PhD, FRS President, UCSF Helen Diller Family Comprehensive Cancer Center Senior Vice President for Cancer Services, UCSF Health

3 Table of Contents Letter from the President 2 Precision Cancer Medical Building 5 Molecular Oncology Initiative 9 Precise Imaging for Cancer & Therapy 13 The San Francisco Cancer Initiative 19 Center for BRCA Research 25 The Prostate Cancer Endowment 29 Investigational Trials Resource 37 The Cancer Immunotherapy Program 41 Impact Grant Awards 47 1

4 Dear Friends, The UCSF Helen Diller Family Comprehensive Cancer Center is more than a place where scientists and clinicians strive to develop leading-edge therapeutics. In 2016, our brilliant researchers and clinicians, patients and families, community groups, and government and industry partners continued to work hand in hand to transform cancer into a manageable disease and cure it when possible. I m proud to share this year s accomplishments, as well as our plans to build on these successes in the years to come. Our ambition is tangible, perhaps best represented by our UCSF Precision Cancer Medicine Building (PCMB), due to open in 2019 on our Mission Bay campus. Located just steps from both our Helen Diller Family Cancer Research Building and our UCSF Bakar Cancer Hospital, the PCMB is being designed so that all patients have timely access to precise, coordinated, evidence-based care plans that include everything from groundbreaking diagnostic tests and tumor sequencing to our extensive portfolio of clinical trials and new therapies. 2

5 In addition to focusing on the PCMB, we participated in other exciting endeavors in 2016: Faculty members Mitchel Berger, MD, and Jeffrey Bluestone, PhD, were appointed to a Blue Ribbon Panel as part of the Vice President of the United States National Cancer Moonshot Initiative: I also had the opportunity to offer input on this initiative at a recent visit to the White House. Our growing Cancer Immunotherapy Program expands access to new therapies as we explore ways to broaden their efficacy and reduce side effects. We are also one of six institutions comprising the newly established Parker Institute for Cancer Immunotherapy, a collaborative effort that will accelerate the development of breakthrough immune therapies capable of turning cancer into a curable disease: We ve expanded our state-of-the-art cancer-imaging program, to more quickly assess disease progression and treatment response, creating time to move patients to other therapies when first-line therapies fail. We ve also launched the ambitious San Francisco Cancer Initiative, partnering with the City of San Francisco, other health systems, community clinics, and a wide range of community groups on a long-term effort to reduce cancer in San Francisco. Your support helps prompt the next era of innovation. Your commitment empowers us all to imagine a world free from cancer. I am deeply grateful for your participation as we work to find new ways to diminish cancer, and to one day eradicate it altogether. Sincerely, Alan Ashworth, PhD, FRS President, UCSF Helen Diller Family Comprehensive Cancer Center Senior Vice President for Cancer Services, UCSF Health 3

6 To have one building house so many people dedicated to impacting cancer on all fronts will be a huge advantage in finding new treatments. Eric Small, MD Chief, Division of Hematology and Oncology Deputy Director, Prostate Cancer Program

7 Precision Cancer Medical Building When the UCSF Precision Cancer Medicine Building (PCMB) opens in early 2019, it will bring to fruition a facility in which all cancer patients can feel confident that they are receiving the finest care in the world a facility that tailors care based on a detailed understanding of each individual s biology and life circumstances. Just a few steps from the UCSF Helen Diller Family Cancer Research Building and UCSF Bakar Cancer Hospital the PCMB s six stories and 170,000 square feet will include 120 rooms for multidisciplinary exams, procedures, and consultations. This will make it easier for UCSF cancer patients to receive all of their care in one place, at one time. And with its location on UCSF s Mission Bay campus, the PCMB will facilitate ready collaboration among researchers, teaching faculty, clinicians, patients, and families. 5

8 Our plan is for the PCMB to be the epitome of integrated patient care. Eric Small, MD Chief, Division of Hematology and Oncology Deputy Director, Prostate Cancer Program To have one building house so many people dedicated to impacting cancer on all fronts will be a huge advantage in finding new treatments, says Eric Small, MD, chief of UCSF s Division of Hematology and Oncology and leader of the UCSF Helen Diller Family Comprehensive Cancer Center s Prostate Cancer Program. Our plan is for the PCMB to be the epitome of integrated patient care. The building will encompass the latest technology, from advanced computational tools to lasers, robotics, and advanced imaging, with room to grow built right into the design. The design will empower UCSF to accelerate the discovery of new and more precise cancer treatments. Creating the PCMB is especially urgent now because of recent game-changing advances in cancer treatment, such as immunotherapy, enhanced imaging, and genetic counseling, which we intend to bring to all of our patients. By 2024, office visits related to cancer care in Northern California are projected to increase by 33 percent, so the PCMB will play a crucial role in guaranteeing patients timely access to these treatment advances and in easing the emotional burden of dealing with a challenging disease. 6

9 UCSF PRECISION CANCER MEDICINE BUILDING UCSF RON CONWAY FAMILY GATEWAY MEDICAL BUILDING UCSF BETTY IRENE MOORE WOMEN S HOSPITAL AND UCSF BAKAR CANCER HOSPITAL UCSF BENIOFF CHILDREN S HOSPITAL Future Entrance 16 th St. 4 th St. When the PCMB opens, the floor plans include space for genetic counselors on each and every practice floor so we can truly integrate with our oncology practices, says Amie Blanco, MS, LCGC, acting director of the UCSF Cancer Genetics and Prevention Program. Our aim is to provide genetic counseling and testing on-site, the day a patient comes in. Building such a leading-edge, patient-centric medical facility is estimated to cost $250 million, with the majority of funding coming from a combination of campus investment and philanthropic contributions. Faculty members involved in planning the building s multidisciplinary programming believe investing in such a centralized facility will yield tremendous benefits for patients and their health care teams. The PCMB will make things easier on multiple levels, says Michael Korn, MD, leader of UCSF s Molecular Oncology Initiative. But the most important thing is looking at it from the patient s perspective. Our goal is to make their health care delivery efficient and accessible. We are preparing so when the PCMB s doors open, we are ready to provide care as soon as the patient shows up. That is the huge advantage of having everyone in one building and under one roof. 7

10 Our mission is to use the combined experience and intelligence of many people across UCSF to turn genomic findings into clinical recommendations for individual patients. Michael Korn, MD

11 Molecular Oncology Initiative In January 2016, UCSF launched the Molecular Oncology Initiative (MOI) to integrate molecular information found in most cancer types with the everincreasing number of therapeutics being developed in translational research and clinical practice. The UCSF Molecular Tumor Board (MTB), a group of experts that reviews molecular findings, was formed to interpret findings from the UCSF 500 gene panel assay, a pioneering sequencing test developed at UCSF to find mutations in a patient s cancer that particular medicines can attack. 9

12 These findings benefitted not only the affected patients but also their entire families. This shows we are on a very promising path that will greatly influence how we diagnose and treat cancer here. Michael Korn, MD Right now, there are only a few genes where we ve found a predictable change in the gene and can recommend treatment without hesitation, explains Korn, who s also chair of the MTB. That s why the tumor board is there to tackle this big gray zone in gene behavior and help physicians make correct diagnoses for their patients and deliver appropriate treatment. The MTB reviews findings obtained by the UCSF 500 gene panel assay, he continues. Our mission is to use the combined experience and intelligence of many people across UCSF to turn genomic findings into clinical recommendations for individual patients. The MTB takes advantage of its close collaboration with the UCSF Clinical Cancer Genomics Laboratory (CCGL), led by Boris Bastian, MD. Bastian s laboratory provides the UCSF gene panel assay, which tests tumor DNA and the patient s germline (inherited) DNA, which many commercial products do not test. The test can also provide information on inherited genetic changes that increase an individual s risk of developing cancer. 10

13 Since the inception of the MOI and MTB, more than 190 patient cases have been reviewed by the board. The UCSF 500 gene panel assay has also led to dramatic responses for some patients as a result of treatments tailored to their diseases molecular profiles. After their cases were reviewed by the MTB, their test results provided the rationale for enrolling them in clinical trials at UCSF. We were able to detect mutations in several individual patient germlines, says Korn. These findings benefitted not only the affected patients but also their entire families. This shows we are on a very promising path that will greatly influence how we diagnose and treat cancer here. 11

14 Our imaging methods can help us determine at an early stage whether treatments are having an impact, and if they are not, we can to try alternative approaches in a more timely manner than might have been possible in the past. Sarah Nelson, PhD Margaret Hart Surbeck Distinguished Professor of Advanced Imaging Director, Surbeck Laboratory for Advanced Imaging Leader, Precise Imaging for Cancer and Therapy

15 Precise Imaging for Cancer and Therapy (PICT) Imaging has been an integral component of the breast, prostate, and brain cancer programs for many years. By expanding the focus to include other cancers and forging a stronger relationship with clinicians and scientists in the Department of Radiology and Biomedical Imaging, the UCSF Helen Diller Family Comprehensive Cancer Center has created opportunities to dramatically increase avenues for collaborative research and enhance patient care. PICT enables us to take maximum advantage not only of our sophisticated imaging equipment but also our expertise in developing new technologies and methodologies to improve diagnosis and treatment monitoring, says Sarah Nelson, PhD, the Margaret Hart Surbeck Distinguished Professor of Advanced Imaging, director of the Surbeck Laboratory for Advanced Imaging, and leader of PICT. 13

16 We can help researchers answer questions about the underlying biology of a particular type of cancer and help them design new treatments that attack new targets. Sarah Nelson, PhD Imaging crucial for advanced therapies, adaptive trials, research The expanded role for imaging is tied to advances that allow it to support and refine a range of precision cancer medicine approaches. Our imaging methods can help us determine at an early stage whether treatments are having an impact, and if they are not, we can try alternative approaches in a more timely manner than might have been possible in the past, says Nelson. This is especially important for the way an increasing number of clinical trials are designed to be adaptive: They use early clinical findings to reject ineffective strategies and focus on the most promising options. With that in mind, says Nelson, The more light we can shed on what s going on in the tumor, the better. Advances in imaging technology also are essential for complementing and enhancing information supplied by genomic analyses. We are finding that you need both approaches, Nelson says. Detailed spatial information can direct you to sample tissue from the areas that are most malignant. In heterogeneous tumors, that s important because you are more likely to identify mutations that define how the tumor is going to behave. That s why image-guided biopsies are so important for making an accurate diagnosis. 14

17 The combination of advanced imaging equipment and sophisticated methods for quantitative analysis allows researchers to more accurately describe the status of the tumor and detect changes that would otherwise have been considered too small to act upon. These new methods offer more objective and precise measures of the tumor and its microenvironment, Nelson says. The vascular density, the number of cells in a region, the metabolic processes, and the mutations at work all play a role in determining which therapy might work best. She adds that imaging also helps in planning and directing more focal treatments, such as radiation therapy, focused ultrasound, and convection-enhanced delivery of chemotherapeutic agents. All of these elements provide oncologists with new information that they can use to offer more informed choices to their patients. This is especially valuable at a place like the HDFCCC, which is designed to offer patients the benefits of integrating the latest knowledge from researchers and clinicians across many disciplines. The integration plays out in multiple ways. Not only does imaging play a role in the clinical setting, it also is increasingly important in preclinical studies aimed at defining cancer mechanisms and understanding how new therapeutic approaches might affect specific metabolic or molecular pathways. We can help researchers answer questions about the underlying biology of a particular type of cancer and help them design new treatments that attack new targets, Nelson says. 15

18 A two-way research street Nelson and her colleagues are also responsible for research on the imaging modalities themselves. PICT is pushing the envelope on the use of a number of technologies and methodologies, including, for example, metabolic imaging methods using hyperpolarized [1-13C] pyruvate to help distinguish between benign and malignant tissue and to more confidently predict outcomes. The translation of this technology from preclinical systems to cancer patients has been championed here at UCSF, and we are just beginning to define how to best make use of the information that it provides, Nelson says. This work is aided by the fact that much of the state-of-the-art equipment and expertise resides side by side in the clinical facilities at Mission Bay. This can enable radiologists to take advantage of experimental techniques to enhance standard imaging exams. They are also available to support 16

19 What we are doing here is showing how these advances can have real benefits for real patients. Sarah Nelson, PhD promising new treatments such as immunotherapy, which can cause changes on standard images that mimic tumor progression and may give a false picture of the long-term impact upon the cancer. It s a two-way street for mutual benefit. A clinical trials unit might contact the imaging group requesting help to support the evaluation of a new treatment. Alternatively, imaging team members might develop a methodology they believe reveals something new and important and then identify a population of patients to determine whether the methodology is valid and can improve clinical outcomes. Such work is essential because without validation, insurance companies are not likely to reimburse providers for using these new techniques. Nelson believes that if PICT can zero in on the most effective technologies those that prevent unnecessary treatments and make new therapies more effective or efficient they can save money, as well as a substantial number of lives. What we are doing here is showing how these advances can have real benefits for real patients, she says. 17

20 The real tragedy is that up to half of cancers could be avoided if what we currently know about the causes and their prevention could be put into practice widely. Robert Hiatt, MD, PhD Associate Director, Population Sciences, UCSF Helen Diller Family Comprehensive Cancer Center

21 The San Francisco Cancer Initiative Despite many remarkable clinical advances, cancer now kills more San Francisco residents than any other cause, according to the California Department of Public Health s County Health Status Profiles There are thousands of new cancer cases and more than a thousand deaths each year from the disease. San Francisco s cancers often disproportionately strike and kill people of color and those most disadvantaged in society. They also cost San Francisco patients, families, and taxpayers hundreds of millions of dollars each year. The real opportunity is that up to half of cancers could be avoided if what we currently know about the causes and their prevention could be put into practice widely, says Robert Hiatt, MD, PhD, the Helen Diller Family Comprehensive Cancer Center s associate director of population sciences. The San Francisco Cancer Initiative (SF CAN) aims to put what we know into practice to dramatically reduce the incidence and impact of cancer across this city. SF CAN already has begun implementing a systematic and coordinated approach to improving cancer prevention and screening in San Francisco that relies on forging partnerships between UCSF and the city s health systems, government, and community leaders. The San Francisco Department of Public Health (SFDPH) recently joined the effort, as have many others, including the San Francisco Medical Society, the American Cancer Society, community clinics, community groups, and other health systems. 19

22 Our collective experience and existing working relationships create a potent catalyst for change. Robert Hiatt, MD, PhD Initial focus: Leverage advances for largest possible impact The last few years have seen remarkable advances in precision population health, data and information technology, and cancer treatments. In addition, San Francisco s exceptional diversity, reasonable size with approximately 850,000 residents, and forward-looking leadership make it a prime location for this pioneering effort. Our collective experience and existing working relationships create a potent catalyst for change, Hiatt says. Spearheaded by Alan Ashworth, Helen Diller Family Comprehensive Cancer Center president, SF CAN is expected to launch officially later this year with an intensive focus on five cancer types breast, colorectal, liver, prostate, and lung and other tobacco-induced cancers chosen because they represent nearly half of the city s cancer cases or have large disparities in onset and outcomes. For each of these cancer types, promising, evidence-based prevention and screening practices exist that can lead to fewer deaths but which are not yet being fully implemented across all population groups in San Francisco. Getting a jump start Task forces are already forming for each of the five cancers. There is leadership from community advisors and the SFDPH, while the HDFCCC forms the organizational backbone and lends crucial scientific expertise, Hiatt says. Our strategy of collective impact drawing on the commitment and integration of people who represent different groups is the only way to make headway on something so complex, and it s what makes this effort so unique. 20

23 Here are a few examples of work already being done by the task forces: Joseph Guydish, PhD, MPH, is encouraged by the work already in progress for lung and other tobaccoinduced cancers. Leveraging numerous existing partnerships, this team has split into three distinct threads, all focused on groups that are especially vulnerable to tobacco-induced cancers. Guydish, Maya Vijayaraghavan, MD, MAS, and Dorie Apollonio, MPP, PhD, are working on reducing smoking among low-income populations, including the homeless and persons enrolled in drugabuse treatment. Smoking prevalence for those in low-income, safety-net services is two to three times that in the general population, Guydish says. To date, UCSF and its partners are doing needs assessments and exploring methodologies that have worked well in other settings as well as creating new interventions. In the second thread, Pamela Ling, MD, MPH who studies the social and cultural issues that drive smoking and Danielle Ramo-Larios, PhD, are working with internet and public radio station Youth Radio to try to reduce smoking in the so-called hipster community: mostly young adults who congregate in bars and tend to smoke at higher rates than the general population. Valerie Yerger, ND, leads the third thread, which focuses on reducing smoking in San Francisco s African-American community. Studies show that African-Americans smoke at lower rates than the general population does but have higher rates of lung cancer. Some research has indicated that menthol cigarettes, which tobacco companies push hard in the African-American community, may be the culprit. Yerger is working with the city and with the African-American Health Disparity Project to see if there s a way to ban menthol cigarettes in San Francisco. Local initiatives have been successful drivers for policies like smoke-free bars, restaurants, and offices, and Yerger hopes to follow that pattern. 21

24 Tung Nguyen, MD, with a patient. The colorectal cancer task force began by focusing on increasing screening in the city s safety-net populations through the use of inexpensive, evidence-based fecal immunochemical tests. In San Francisco, screening rates in privately insured populations are already quite high, but for the city s vulnerable and underinsured patient populations, this is often not the case, says the HDFCCC s Michael Potter, MD, a family physician and researcher in the Department of Family and Community Medicine. Increasing screening rates in these groups is our most potent opportunity to reduce colorectal cancer incidence and mortality in the city. The task force, which includes stakeholders from the San Francisco Community Clinic Consortium, Zuckerberg San Francisco General (ZSFG), San Francisco Health Plan, and the American Cancer Society, plans to increase access to screening within community clinics that serve the largest pockets of unscreened adults between the ages of 50 and 75. They re beginning with a needs assessment to gather detailed information about current screening rates and practices in the community health centers. We expect to identify several opportunities to implement tailored, evidence-based approaches to individual sites. These might include staff training, improved patient-education materials, streamlined processes for outreach and follow-up, and incentives for clinical teams to achieve certain targets, says Potter, who also expects the task force can help develop more efficient processes for directing high-risk patients to ZSFG for colonoscopy. The liver cancer task force has forged partnerships with the SFDPH, community organizations, and clinical providers from multiple health systems, with an initial focus on screening and treatment for hepatitis B and hepatitis C, both of which significantly increase the risk of liver cancer. The diseases affect a broad swath of the population, but liver cancer rates in Asian and Asian-American communities are particularly high, and they are increasing rapidly in African-American, Latino, and other underserved populations. 22

25 SF CAN s broad focus on the entire life course is a unique and novel approach to cancer control. Robert Hiatt, MD, PhD For hepatitis B, the group has instituted a phone navigation line where people can have questions answered about testing, results, and follow-up care in English and Chinese. For hepatitis C, the group worked with the SFDPH to launch an End Hepatitis C campaign in July 2016 to raise public awareness. We want to get people screened but also make sure people who have hepatitis C get appropriate referrals and treatment, because it can be cured, says the HDFCCC s Tung Nguyen, MD, the Stephen J. McPhee, MD, Endowed Chair in General Internal Medicine. The task force is also: Working with the city to expand ZSFG s capacity to do liver ultrasounds to catch the disease earlier, which increases the chances for effective treatment. Initiating steps to create a referral network that will enable more people and more diverse populations to access available clinical trials for liver cancer. Creating a policy paper on ways to make treatment for hepatitis C more affordable, because existing treatments, while curative, are quite expensive. Hiatt says the task forces are doing the crucial, frontline work to implement the SF CAN vision. SF CAN s broad focus on the entire life course is a unique and novel approach to cancer control, he says. We are bringing new knowledge about the origins of cancer to what we know about effective prevention and early detection to make a difference at the population level. If we can make our impact on the cancer burden a success, our model could spread through the entire Bay Area and maybe even California and the rest of the United States. 23

26 We ve received an overwhelmingly positive response from BRCA-positive patients. We re planning to continue growing and refining our services and adding staff as our patient population expands. Pagan Morris, MPH Program Manager, Center for BRCA Research at UCSF

27 Center for BRCA Research Opened in 2015, the Center for BRCA Research at UCSF is only the second comprehensive clinic in the nation and the first on the West Coast for individuals carrying hereditary gene mutations in BRCA1 or BRCA2. These mutations are widely recognized as inheritable causes of breast and ovarian cancers, but less well known is that they also heighten the risk of pancreas and prostate cancers, as well as melanoma. The center at UCSF is one of the few to focus clinical and research activities directly on BRCA mutations, concentrating on clinical care, screening and prevention (including a laboratory science program), and education and outreach. The Hereditary Cancer Clinic within the center has the capacity to treat 150 patients and conduct up to 100 genetic counseling sessions each month. 25

28 We plan to continue our work in each of the center s core areas of focus, from growing our laboratory program and the Clinical Fellow Program to increasing the number of BRCA Challenge grants, in order to train future leaders in the field. Alan Ashworth, PhD, FRS Alan Ashworth, PhD, FRS We ve received an overwhelmingly positive response from BRCA-positive patients, says Pagan Morris, MPH, the center s program manager. We re planning to continue growing and refining our services and adding staff as our patient population expands. The Center for BRCA Research is powered by the labs of Drs. Alan Ashworth and Pamela Munster. They are conducting studies to screen for risk-modifying biomarkers that can identify carriers at high risk of developing cancer and with the most potential for responsiveness to therapy. Findings from these studies will aid in further developing clinical guidelines for prevention and management, as well as identifying genetic and other factors that modify risk for BRCA-related cancer in families. On the education front, the center recently awarded the first hematology-oncology clinical research fellowship and developed the UCSF BRCA Challenge Grant, designed to launch one research project 26

29 Pamela Munster, MD, director, Early Phase Clinical Trials Unit; and leader, Developmental Therapeutics Program, Helen Diller Family Comprehensive Cancer Center a year focused on top priorities identified by the center s steering committee. All of this is intended to support and train postdoctoral and senior researchers to pursue the most promising BRCA research projects. The BRCA Center is also working with community partners to develop and launch a regional public awareness plan. It has partnered with KinTalk.org, an educational and family communication portal where at-risk family members can securely share important hereditary genetic health information. The center has received national attention from The Wall Street Journal and NBC News. We plan to continue our work in each of the center s core areas of focus, from growing our laboratory program and the Clinical Fellow Program to increasing the number of BRCA Challenge grants, in order to train future leaders in the field, Ashworth says. 27

30 All of us and the patients we serve are grateful for the support of the Helen Diller Family Foundation and the ways it has helped us reduce the incidence and impact of prostate cancer. Peter Carroll, MD, MPH Ken and Donna Derr-Chevron Distinguished Professor in Prostate Cancer Chair, Department of Urology Associate Director, Strategic Planning and Clinical Services, UCSF Helen Diller Family Comprehensive Cancer Center

31 The Prostate Cancer Endowment The Helen Diller Family Foundation s remarkably generous endowment benefitting the Prostate Cancer Program has supported and sustained what we believe is the finest research program in the country for this disease, says Peter Carroll, MD, MPH, chair of the Department of Urology. Evidence of the program s prowess is clear in both the numbers for a second consecutive year, the UCSF urology program received more biomedical research funding from the National Institutes of Health (NIH) than any other urology program in the country and in the department s people, whose influence is both broad and deep. Our investigators have a solid foothold in many different types of research, including clinical care, symptom support, and translational science, Carroll says. They are a diverse group that represents the entire research spectrum, and the Diller Professors profiled here represent people across many departments, who continue to work in fascinating and impactful ways. All of us and the patients we serve are grateful for the support of the Helen Diller Family Foundation and the ways it has helped us reduce the incidence and impact of prostate cancer. 29

32 Nynikka Palmer, DrPH, MPH In 2016, Nynikka Palmer, DrPH, MPH, became the Helen Diller Family Professor in Community Education and Outreach for Urologic Cancer. Working primarily from Zuckerberg San Francisco General (ZSFG), Palmer seeks, through her research, to eliminate disparities in care, particularly for African-American men with prostate cancer. Studies have shown African-American men have higher death rates from the disease, are both undertreated and overtreated, and struggle to cope with the side effects of treatment. With this in mind, in October 2014, Palmer launched a prostate cancer support group for African- American men in the Oakland area, which includes those with prostate issues, the newly diagnosed, and long-term survivors. In addition to helping each other, these men have become an invaluable sounding board for Palmer s research. They are contributing to one current project, in which she is developing the use of peer navigators in the health care safety net. The navigators African-American prostate cancer survivors who can bridge the cultural gap and mistrust that often exists between African-American men and the health care system interpret information and help patients think through both the short- and long-term implications of treatment decisions. Palmer will test the peer navigator concept, which has shown good results in breast cancer settings, at two Bay Area safety-net hospitals. In addition, she and UCSF researcher Rena Pasick, DrPH, are examining a new perspective on shared decision-making and working together on a prostate cancer task force for SF CAN, the collaborative, system-wide approach to reducing San Francisco s cancer burden. Palmer hopes insights from her work also can help improve early detection and health outcomes in the African-American community. We are trying to address a huge, complex problem, but piece by piece, I believe we can change the quality of care prostate cancer patients receive and eliminate the disparities, she says. 30

33 Stacey Kenfield, ScD Stacey Kenfield, ScD, became the Helen Diller Family Professor in Population Science for Urologic Cancer in Her research aims to understand how nutritional and lifestyle changes can improve prostate cancer prevention and survival. In November 2015, a study Kenfield published in the Journal of the National Cancer Institute estimated that in the US, 47 percent of lethal prostate cancer would be preventable if men over age 60 adopted five or six habits related to diet, exercise, and smoking cessation. She is now principal investigator (PI) of a pilot study called Prostate 8 that examines whether men with prostate cancer can use a web-based program to adopt and sustain lifestyle changes that include these healthy habits. She also has a NIH R01 grant to test whether a targeted lifestyle program will modify prostate biology and deter cancer progression in men who opt for surgery. We have received positive feedback from patients in the pilot trial, especially related to the wearable activity devices and personalized lifestyle reports, says Kenfield, who also has co-authored diet and lifestyle recommendations for the Prostate Cancer Foundation. We look forward to building on the pilot work and improving the patient experience for the larger trial. Kenfield is PI or co-pi on a number of other trials crossing multiple sites, organizations, countries, and concepts to further test and refine emerging ideas about the positive effects of diet and exercise on prostate cancer prevention and progression. In addition, she directs the Movember Foundation-funded global exercise trial in metastatic prostate cancer patients, which spans more than 20 institutions in seven countries. Her work also contributes to Carroll s vision of creating a patient portal at UCSF where patients can log in, review treatment management options, and get wellness and clinical information. We are building the evidence base and translating our findings for patients, Kenfield says. It s taken us 10 years since the first studies were published. We now believe we can move forward with recommendations for what men can do outside of clinical care that can lower their risk for aggressive prostate cancer or prostate cancer progression. 31

34 Michael Rabow, MD Since being appointed the Helen Diller Family Professor in Palliative Care in 2014, Michael Rabow, MD, has continued to integrate palliative care into multiple cancer specialty clinics, including the STAND (Supportive Therapy in Androgen Deprivation) clinic for prostate cancer patients. Our work in the STAND clinic is an important model for treating cancer as a chronic disease in which we pay attention to treatment complications and a patient s entire health picture, says Rabow, who directs the Symptom Management Service at the UCSF Helen Diller Family Comprehensive Cancer Center. The STAND model has a number of elements. First, doctors from multiple disciplines see patients in one location, underlining the HDFCCC s commitment to a patient-centered approach. Second, all clinicians from palliative care specialists to oncologists learn from each other by working face-to-face with the same patient. This advances primary palliative care, where all clinicians have a knowledge and facility for treating such basic concerns as pain or symptom management or straightforward depression, Rabow says. Third, patients and clinicians do advance-care planning together to ensure patients receive care consistent with their priorities and values. With prostate cancer, there is a spectrum of response from watchful waiting to the most aggressive chemotherapy, Rabow says. Because most patients now have more options, we need a much more nuanced response to cancer that includes talk about outcomes, prognoses, side effects, and values. Rabow, his HDFCCC colleagues, and a patient advisory group are now developing a program to ensure every patient receives this type of advance-care planning. I could see people doing a first draft of advance directives as part of a group, because peers can sometimes say things to each other that a health care provider cannot, Rabow says. For all of this, we must remember that the patient, family, and community are the center of our universe. 32

35 Matthew Cooperberg, MD, MPH Named to the Helen Diller Family Professorship in Urology in 2013, Matthew Cooperberg, MD, MPH, continues to be central to numerous important efforts to reduce the burden of prostate cancer. In 2016, Cooperberg became PI on an R01 grant aimed at using micrornas blood-based biomarkers to improve risk stratification for men with prostate cancer. Working with UCSF s Robert Blelloch, MD, PhD, who is the Peter R. Carroll, MD, MPH, Distinguished Professor in Urology, and members of his lab, Cooperberg s goal is to develop a blood test that can eventually replace or at least compete with tissue-based testing. Our thinking is that blood testing is easier to repeat, less invasive, more economical, and gets around concerns about sampling in biopsies, he says. Because Blelloch s lab can now sequence an entire microrna panel, the team plans to use this ability over the next five years to develop and validate the blood test on thousands of samples that the HDFCCC has gathered over the past decade. The fact that we have these samples is a tribute to Peter Carroll s prescient vision, Cooperberg says. Even as he plunges into this latest project, Cooperberg continues his work in many other areas. The American Urological Association Quality Registry (AQUA), which he was instrumental in developing and implementing, now has more than 1 million unique urology patients in its database and is starting to yield insights into prostate cancer management trends nationwide. He also has continued his passionate advocacy for retaining prostate-specific antigen (PSA) screening, which he says is still one of the most successful biomarkers when used correctly. As part of this effort, Cooperberg serves on the SF CAN prostate cancer task force, focusing on increasing PSA screening in communities hardest hit by prostate cancer. Cooperberg is a national leader in refining the use of active surveillance, continually honing the concept through his work with CaPSURE (UCSF s Cancer of the Prostate Strategic Urologic Research Endeavor) and a related US Department of Defense-funded study. We now know, for example, that because some tumors will never metastasize, we don t need to watch these patients as carefully, he says. 33

36 Davide Ruggero, PhD In 2011, Davide Ruggero, PhD, a professor in the departments of Urology and Cellular and Molecular Pharmacology, was named the Helen Diller Family Professor in Basic Research in Urologic Cancer. Since then, his lab has generated a multitude of important findings. Ruggero and his team have focused their attention on oncogenes genes associated with the conversion of normal cells into tumor cells that increase protein synthesis and metabolic activity, which in turn induce a stressor to which cancer cells must respond to survive. This is a vulnerable point, because the increased protein-dependent stress response occurs only in cancer cells, not in normal cells, he says. In a preclinical trial with genetically engineered mouse models, we are using a pharmacogenetic approach to block the stress response, and we re finding that doing so blocks prostate tumor development. Ruggero s lab is developing a patient-derived xenograft (PDX) model to further test this concept. In PDX models, scientists implant human tumors in mice an approach considered as close as one can get to replicating human response. We have five independent prostate patient PDX models that are showing similar results when we block the stress response, he says. He hopes these findings can quickly lead to a human trial. In related work, his lab is analyzing microarrays of 250 patients to track how this specific stress response affected patients disease course. We believe a high stress response is associated with more aggressive tumors and relapse, Ruggero says a finding that, if verified, can lead to a more personalized care approach. Knowing whether a prostate cancer patient harbors these oncogenes and engages this stress response allows us to identify, segregate, and refer properly. Finally, Ruggero is working with the biotech company effector Therapeutics to develop the first compounds for regulating the protein eif4e. Last year, his lab found cancer cells hijack eif4e to fuel their growth but that reducing the protein by half in mice and human cells engendered no ill effects in normal cells while suppressing tumor growth. We now have ongoing clinical and preclinical animal trials that target the eif4e activity, he says. This is an exciting step forward. 34

37 Katsuto Shinohara, MD The clinical research of Katsuto Shinohara, MD, who was named the Helen Diller Family Professor in Clinical Urology in 2010, has enhanced access to less invasive testing and treatment techniques for patients with urologic cancers. His primary focus in the last year was on magnetic resonance imaging (MRI)-ultrasound fusion biopsy, which is now a standard of care for prostate cancer patients on active surveillance who previously have had a positive biopsy. Shinohara helped pioneer this image-guided, minimally invasive technique, which locates the cancer area using an MRI fused with an ultrasound image. This helps clinicians better identify or exclude more aggressive cancers and can help eliminate the need for repeat biopsies. In particular, we have shown MRI-fusion is good at identifying bigger and more aggressive types of cancer, which helps us quickly recommend these patients for definitive treatment, Shinohara says. It is also appropriate for the patient with a previously negative biopsy but whose PSA is rising. If there is no evidence of cancer by MRI-fusion biopsy, then we can relax and continue to follow these patients with PSA screening. Shinohara also has remained active in ongoing efforts that include improving biopsy specimen handling by replacing paper with a small cassette, which enables clinicians to send the entire length of the sample intact to pathology; and brachytherapy, which places radioactive seeds in the prostate to reduce the exposure of healthy tissue to radiation. We have been using a new ultrasound device that can show simultaneous multiple views. Though it s too early to say, it looks as though the device has allowed us to more accurately position the radioactive seed strand, he says. Shinohara also treats prostate cancer with focal cryoablation techniques. Once we accrue a hundred patients, we need about 30 more, we will publish efficacy and quality-of-life outcomes. 35

38 The Investigational Trials Resource has been remarkably responsive to the needs of our community, continually adapting and innovating, and without its leadership and responsiveness, progress would slow. The difference would be night and day. Alain Algazi, MD Assistant Professor, Cutaneous Oncology Program

39 Investigational Trials Resource Alain Algazi, MD It s not enough to have a good idea, because in clinical research, there are so many steps and so much oversight and monitoring that infrastructure becomes key, says Alain Algazi, MD, who this year initiated a clinical trial program for head and neck cancers at the HDFCCC with the help of the Investigational Trials Resource (ITR). The ITR has been remarkably responsive to the needs of our community, continually adapting and innovating, and without its leadership and responsiveness, progress would slow. The difference would be night and day, Algazi says. Eric Small, MD, deputy director and director of clinical sciences in the HDFCCC, leads the ITR. In the last year, he and his team worked with researchers throughout the HDFCC to transform the program s structure to reflect changes in our understanding of cancer and how research is organized. Even as our anatomic disease-oriented programs continue to grow, we have found better ways to integrate those trials and researchers with programs that are scientifically crosscutting, like Developmental Therapeutics, Cancer Immunotherapy, and the Center for BRCA Research, Small says. A new set of standardized procedures In brief, the ITR s careful consensus-building led to the creation of a new set of standardized procedures for enrolling patients, patient safety, and data safety across multiple trials, as well as the nuts and bolts of deciding who will do what all while keeping an eye on what benefits the most patients. Our systematic approach makes it possible for the ITR to harmonize work across the HDFCCC, create new efficiencies, and still remain flexible enough to adapt to ongoing change, Small says. 37

40 Gyn Onc Site Committee Melanoma Site Committee Thoracic Oncology Committee Breast Cancer Site Committee Developmental Therapeutics Site Committee Other Sites GU Site Committee GI Site Committee Heme/BMT Committee Sample Committee Network Web This structure is an example of how one crosscutting group works with anatomic site-specific groups through a series of trials. This integrated approach provides support in three important areas: A National Cancer Institute-mandated Protocol Review and Monitoring System provides essential scientific review and monitoring of all studies. A data and safety monitoring committee ensures patients are safe and maintains the scientific integrity of all data. A clinical research support office provides an ever-expanding array of administrative services for the researchers, including essential clinical research coordinators. In addition, Algazi says, the ITR s thoughtful approach to building working groups among young research staffers fosters greater retention, more continuity, and higher quality trials executed with greater efficiency. The process has worked so well that in 2015, clinical interventional trial accruals continued to increase to 1,191 patients. Interventional Annual Accrual Summary NUMBER OF PATIENTS ENROLLED

41 Speeding new treatments to patients Algazi is one of many grateful researchers. We ve been seeing patients in head and neck oncology for four or five years, but until this year, there s been virtually no research effort, he says. The ITR was essential to making it happen. Its processes enabled us to quickly hire staff, apply resources, and get a viable and approved program up and running that builds on UCSF s strengths. The patient benefits are immediate, as multiple studies have shown that enrollment in trials correlates with better clinical outcomes. In the head-and-neck group s first year, it initiated five studies including an innovative pilot using gene therapy to stimulate anti-tumor immune responses, which has shown signs of being an effective treatment as well as several trials in collaboration with the Cancer Immunotherapy Program. Small notes that when cancer clinicians moved to Mission Bay last year, it furthered cross-pollination among diverse research teams. When the Precision Cancer Medicine Building opens in 2019, it will significantly accelerate the movement from discovery to therapy and dramatically enhance what the ITR can do to facilitate these processes. We are designing a building that truly reflects programmatic goals, he says. To have so many people side by side in one unit will be an unprecedented opportunity to really make visible this concept of integrated care. 39

42 Our goal is to have a clinical study or therapy available for every patient referred to us. Lawrence Fong, MD Efim Guzik Distinguished Professor in Cancer Biology Co-leader, Cancer Immunotherapy Program

43 The Cancer Immunotherapy Program The UCSF Helen Diller Family Comprehensive Cancer Center is a leader in developing and refining cancer immunotherapies, which over the last few years have achieved a durable response in a number of different cancers. These therapies use the body s immune system to fight cancer. In 2015, to leverage its leadership role and drive next steps in developing these therapies, the HDFCCC created the UCSF Cancer Immunotherapy Program, which pairs a high-powered research effort with a state-of-the-art clinic and approximately 20 faculty members across different disease groups and departments. 41

44 Direct patient care offers new hope In the UCSF Cancer Immunotherapy Clinic (CIC), expert UCSF hematologists and oncologists from all cancer sub-specialties work together to bring patients and their families an extensive and growing menu of treatments, including cancer vaccines, cellular therapies, and other investigational agents. Our goal is to have a clinical study or therapy available for every patient referred to us, says Lawrence Fong, MD, Efim Guzik Distinguished Professor in Cancer Biology and co-leader of the Cancer Immunotherapy Program. Robert Thistle, 70, pictured above, is one such patient. Thistle has been battling metastatic kidney cancer since he was diagnosed more than a decade ago. Originally, surgery appeared to have removed the entire tumor, but in 2012, a bone metastasis was discovered in his upper arm. That also seemed to have been successfully treated, but two years later, tumor nodules were discovered in his lungs. While Thistle was reviewing alternatives to standard treatment that might have fewer side effects, Fong was looking for potential candidates for a clinical trial. In January 2015, Thistle began treatment at UCSF with an experimental checkpoint inhibitor drug. He then received a commercially available treatment that targets blood-vessel growth in tumors, as well as an experimental immunotherapy drug. By August, the nodules had shrunk to below their original size. Thistle was able to resume his normal life with the help of regular immunotherapy infusions at UCSF. Now 70, he says, I try to be more alive in each moment. 42

45 We ve already published a study where we showed we are inducing immune responses that target prostate cancer prior to surgical resection. Lawrence Fong, MD Expanding patient access Immunotherapies have emerged as a standard of care for a number of common cancers, including melanoma and cancers of the prostate, lung, blood, bladder, and kidney. Nevertheless, Fong says, the therapies don t work as well for everybody as they have for Thistle, and they can cause side effects. Scientists are now racing to better understand which immunotherapies will be effective across cancer types, why they work in some people and not in others, and how to create more precise treatments that reflect individual biology, tumors, and immune system response. Our program is trying to dramatically shrink the proportion of patients who don t get any benefit and also discover combination therapies that will achieve responses without the toxicities, Fong says. Clinicians at the CIC use immunotherapies as first- or second-line treatments when possible and offer clinical studies both phase I and basket trials, which apply the therapies across disease states. In some cases, physicians prescribe the therapies alone; in others, they combine them with things like targeted therapies, chemotherapy, or radiation. In still other cases, physicians give patients immunotherapy treatment before surgical resection to activate the immune system while the cancer is still present, so it will recognize any metastases that occur post-surgery. We ve already published a study where we showed we are inducing immune responses that target prostate cancer prior to surgical resection, Fong says. Gabriel Mannis, MD, is the CIC s co-director for hematological cancers. From years of performing blood and bone marrow transplants, Mannis has acquired extensive experience with immune system modification. It s exciting that many of these new immunotherapies appear to mimic the effects of bone marrow transplant, potentially without the associated risks of graft-versus-host disease or the need for a 43

46 FPO Gabriel Mannis, MD, and Lawrence Fong, MD, explain treatment to a patient. bone marrow donor, he says. We can even envision an end to the era of traditional bone marrow transplantation. CAR-T cells a specific type of immune system cell that are removed from the patient, modified, and then reinfused, have shown exciting results in several types of blood cancers and are the key to success in this area. If we can get CAR-T cells to stick around rather than being eliminated by the body over time, we could have long-lasting remissions or cures without the need for a transplant, Mannis says. Amy Lin, MD, co-director for solid tumors, says the clinic also offers access to immunotherapies for nearly any type of solid tumor, with numerous individual studies defining what qualifies a patient for a trial. There is a lot to be learned, and that s the whole point of this type of clinic, she says. We re adding therapies, mixing therapies, studying immunology, and learning at an exponential rate. However, Mannis adds, because many of these therapies are still investigational, they need to be administered at a center with the expertise to manage the potential complications. We ve built an infrastructure designed to do just that. It s part of the strength of being at UCSF, he says. 44

47 My dream is that eventually precision immunotherapies will kill cancers outright and completely avert the need for surgery or conventional therapies. Lawrence Fong, MD Close collaboration to speed precision medicine approaches To continue refining clinicians understanding of the right therapies or right sequence of therapies, Fong says the CIC and its companion Cancer Immunotherapy Laboratory (CIL) offer patients a unique advantage that goes even beyond rare access to novel treatments. We obtain samples from every patient not just blood, but sputum, stool, or biopsies and have world-leading scientists study what s going on with the person s individual tumor and immune system so we can move toward having the right cancer therapy and right immunotherapy for every patient, says Fong. We believe this precision approach means the days when you get a diagnosis and a drug off a shelf are numbered. My dream is that eventually precision immunotherapies will kill cancers outright and completely avert the need for surgery or conventional therapies. Without the HDFCCC s support and UCSF s prominence in the field, none of this could have come to fruition, and Fong says he s excited by the potential for accelerated advances. Through the CIL, he and his colleagues collaborate with the newly created Parker Institute for Cancer Immunotherapy, where some faculty members have joint appointments, and he has forged research agreements with companies like Bristol-Myers Squibb, Amgen, Genentech, AbbVie, and Merck. These companies are working with us to specifically understand immune responses in human cancer, says Fong. We share our findings as part of different collaborations. If these innovations and collaborations can yield the hoped-for results, then many more patients can benefit as Thistle has. 45

48 The Impact Grants aim to find high-risk, high-reward projects that would not otherwise get support in the current environment. Alan Ashworth, PhD, FRS

49 Impact Grant Awards Earlier this year, the Helen Diller Family Comprehensive Cancer Center brought Shark Tank -style competition to cancer research. HDFCCC president Alan Ashworth, PhD, FRS, launched the inaugural Impact Grant Awards by asking a simple question: Do you have a wild idea that could significantly impact cancer? Entries were encouraged from anyone in the UCSF community, including students, researchers, and staff not affiliated with the HDFCCC. The Impact Grants aim to find high-risk, high-reward projects that would not otherwise get support in the current environment, Ashworth says. By easing application criteria, we received bold ideas from applicants spanning multiple disciplines and career levels at UCSF. 47

50 The six finalists in the inaugural Impact Grant Awards, with Alan Ashworth, PhD, FRS. Six finalists were chosen in a competitive selection process from a pool of 52 applicants. The ideas were judged on four criteria: Cancer relevance, novelty of approach, impact, and unlikelihood of being funded by conventional mechanisms. The competition included lively five-minute presentations from each of the six finalists, as well as extremely engaging Q&A, and provocative suggestions for future themes in each project. Immediately following the presentations, Ashworth announced two $250,000 grants. Eleni Linos, MD, MPH, DrPH, an assistant professor of dermatology at UCSF, and Stephen Francis, PhD, MS, a postdoctoral scholar in epidemiology and biostatistics, received the first UCSF HDFCCC Impact Grants. Linos pitched a project to study whether connecting with women through social media could motivate them to avoid harmful indoor tanning beds. Francis proposed a study looking at 48

51 The application process also provided an excellent mechanism for anyone at UCSF to make me personally aware of their particular research aims, something that doesn t always naturally happen. Alan Ashworth, PhD, FRS 2016 Impact Grant Award recipients Steven Francis, PhD, MS, and Eleni Linos, MD, MPH, DrPH, with Alan Ashworth, PhD, FRS. whether in utero cytomegalovirus infection is a causal factor in the development of childhood acute lymphoblastic leukemia. The Impact Grants will provide Linos and Francis the time to gather and analyze data so they can then apply for funding from conventional sources such as the NIH. Ashworth is quick to note the true impact of these grant awards goes beyond providing research projects with initial funding. The application process also provided an excellent mechanism for anyone at UCSF to make me personally aware of their particular research aims, something that doesn t always naturally happen, he says. I now have 52 excellent projects that I can share with potential philanthropic partners. This is a winning scenario for everyone, particularly in the case of our junior researchers who are just beginning their careers in cancer. Next year s Impact Grant Awards pitch sessions, scheduled for early March 2017, promise to be even more exciting, with three $250,000 research grants to be awarded. 49