Dartmouth Cancer Center Strategic Vision by FriendsofDartmouthCancerCenter

Strategic Vision

Our Mission To prevent and cure cancer, enhance survivorship, promote health equity through pioneering interdisciplinary research, and provide expert, effective, and compassionate clinical care that improves the lives of patients with cancer, their families, and our communities. We are committed to pursuing excellence in research, dynamic partnerships between our laboratories and clinics, robust outreach, and sustained engagement with communities throughout our region. Our outstanding education and training programs nurture the next generation of cancer scientists and clinicians from diverse backgrounds who will, over time, re-define cancer as we know it today.

Our Vision Dartmouth Cancer Center will discover new worlds of cancer medicine, lead efforts to prevent and cure cancer in northern New England, and contribute to solving the problems of cancer in the communities we serve and beyond, while providing the highest level of innovative and compassionate patient-centered care.

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Mary Chamberlin, MD, medical director of the Comprehensive Breast Program, consults with breast cancer study coordinator Grace Crummer (seated), who is training Plymouth State College nursing student Maya Langa, a member of the POWERED research training program.

Welcome to Dartmouth Cancer Center

Scientific Priority Areas

Immunology & Cancer Immunotherapy (ICI)

Cancer Population Sciences (CPS)

Translational Engineering in Cancer (TEC)

Cancer Signaling, Genomes, and Networks (SGNs)

Treating Cancer in Our Clinics

Radiation Oncology

Surgical Oncology

Medical and Hematologic Oncology

Diversity, Equity, Inclusion, and Belonging (DEIB)

Community Outreach and Engagement

Cancer Research Training and Education Coordination (CRTEC)

Measurement and Accountability

Philanthropy

Welcome to

Dartmouth Cancer Center Here we share with you our vision for Dartmouth Cancer Center, including: • Strategic scientific priorities. • Plans for the advancement of science by our research programs. • Clinical goals and strategies. • Integration of career advancement at all levels. • Outreach to engage investigators with perspectives and expertise from the community, all with a commitment to enhancing diversity, equity, inclusion, and belonging. As I enter my sixth year living in what I call “paradise,” I’m profoundly aware of our Cancer Center’s commitment and responsibility to the people of New Hampshire and Vermont. Whether we are long-time residents, recently returned home to Dartmouth after decades elsewhere like Section Chief of Radiation Oncology Charles Thomas, D’79 MD, or newer members like immunologist Tyler Curiel, MD, MPH, FACP, and Deputy Director Linda Vahdat, MD, MBA, we form a dedicated community focused on developing and providing the most informed cancer treatment anywhere. Over 50 years, our Cancer Center has seen tremendous growth and inevitable change incorporating progress in clinical care for patients with cancer. The organizations we are part of evolve, too. In 2022, Dartmouth Hitchcock Health became Dartmouth Health and our beloved Norris Cotton Cancer Center became the Dartmouth Cancer Center. We are forever grateful to New Hampshire Senator Norris Cotton, who secured the funds through the 1971 National Cancer Act to enable the creation of our first Cancer Center clinics and laboratories at the original Mary Hitchcock Hospital in Hanover, New Hampshire. By designating our state-of-the-art oncology clinics at Dartmouth Hitchcock Medical Center in Lebanon, NH as the "Norris Cotton Cancer Care Pavilion,” we honor his vision and activism.

Fifty years and a single vision to prevent and cure cancer unite the current and inaugural directors of Dartmouth Cancer Center, Steven Leach, MD and O. Ross McIntyre, MD.

Fifty years after making history by bringing top cancer care to the people of New Hampshire and Vermont, our Cancer Center is making history again. In early 2022, our generous supporter, Mrs. Dorothy Byrne, committed $25 million to establish The Byrne Family Cancer Research Institute. The institute strengthens Dartmouth Cancer Center's research partnerships by facilitating convergence of bright minds from diverse intellectual perspectives to solve the biggest problems in cancer science and improve life for people everywhere.

This Strategic Vision describes our priorities, progress, and plans to continue the painstaking work of unlocking solutions to cancer through prevention and treatment. The many diseases and their iterations that collectively make up this array that we call “cancer” are far more challenging than our inaugural Cancer Center director, O. Ross McIntyre, MD, speculated in 1972. We are tremendously grateful for the passion, dedication, and generosity of our community of supporters who continue to make possible our relentless pursuit and vision of a world without cancer. My heartfelt thanks also go to our team dedicated to easing the suffering of patients and families affected by cancer—you make everything possible.

Steven D. Leach, MD Director of Dartmouth Cancer Center

ACADEMIC VISION STATEMENT Dartmouth Cancer Center’s nimble research culture provides an ideal atmosphere for convergence science. Facilitated by Dartmouth’s human scale and spirit of collaboration, experts from widespread fields of science cross paths on a daily basis, igniting interdisciplinary and transdisciplinary partnerships that translate into innovative approaches, new devices and drugs, and discoveries revealed with powerful data analytics, epidemiology, applied engineering, and basic science. Our four research programs comprise Immunology & Cancer Immunotherapy; Cancer Signaling, Genomes, and Networks; Translational Engineering in Cancer; and Cancer Population Sciences. Along with 16 clinical oncology groups, they form the core of the academic ecosystem at the Dartmouth Cancer Center.

Dartmouth Cancer Center members are scientific investigators from 22 Dartmouth departments and professional schools (Geisel, Thayer, Guarini, and Arts and Sciences) and are awarded more than $47 million annually in cancer-related research grants and contracts. • 187 research projects are underway • 210 clinical trials are open and accruing participants • 100+ Dartmouth undergraduates are trained to become scientists by Dartmouth Cancer Center faculty each academic year • Dartmouth Cancer Center is the top provider of research opportunities for undergraduates at Dartmouth • 2/3 of Geisel students pursuing MD PhD joint degrees do their thesis work in a Dartmouth Cancer Center lab

AT A GLANCE

157 members

739

academic papers published in 2021

research programs • Immunology & Cancer Immunotherapy • Cancer Signaling, Genomes, and Networks • Translational Engineering in Cancer • Cancer Population Sciences

560

mentored trainees in 2021, ranging from undergraduates to post-docs and fellows

Yashi Ahmed, MD, PhD, a cell biologist who studies the cell signaling pathway that triggers colorectal cancer, working with trainees Hassina Benchabane, Ghalia Saad Siddiqui, and Zachary Spencer. 5

Introducing

Scientific Priority Areas Supported by the Byrne Family Cancer Research Institute

Dartmouth Cancer Center is the only cancer center in the U.S. fully integrated with a world-class liberal arts college and graduate schools of arts and sciences, medicine, business, and engineering, as well as an academic health system. We take a “One Dartmouth” conceptual approach, allowing us to marshal all of Dartmouth’s strengths, knowledge, collaboration, and innovation to fight cancer. The Byrne Family Cancer Research Institute at Dartmouth Cancer Center, launched with an initial gift of $25 million from Mrs. Dorothy Byrne in 2022, will continue to support the Center’s mission by investing in ambitious and forward-thinking scientific approaches predicted to have the highest impact return on investment in targeted cancer prevention, improved cancer treatment, and leveraged innovation.

Next-Generation Immunotherapy: Dramatic and Durable Dartmouth Cancer Center played a historic role in the development of the world's first immunotherapies, which, after decades of research, are now harnessing the body’s own immune system to cure once-deadly cancers. Leveraging that strength is paramount to our scientific priority of further discovery in immunology and immunotherapy. The current goal is developing next-generation immunotherapies that are well tolerated by patients while inducing dramatic and durable anti-tumor effects in their cancer.

First, we aim to define and leverage the features of memory T cells— potent immune cells whose action can result in durable and sustained cancer cures. Defining the drivers of memory T cell fitness and function across tumor and tissue environments will allow Dartmouth researchers to engineer broadly distributed, durable cell-based therapies. In the next five years, Dartmouth Cancer Center expects to advance a potent new class of therapies that successfully “seed” protective memory T cells across tissues where cancers grow and metastasize.

Second, Dartmouth investigators aim to launch a clinical experimental CAR T cell program. Clinical advances over the past five years have enabled Dartmouth Cancer Center to bring FDA-approved CAR T cell therapies to cancer patients. Meanwhile, discoveries in Dartmouth laboratories have continued to innovate and improve CAR T cells for more potent efficacy across a broader range of tumor types. Dartmouth Cancer Center will have launched 13 investigator-initiated clinical trials (IITs) in calendar year 2023. In years past, we averaged 2 IITs per year. This is a strong positive result of the Cancer Center’s investment in building infrastructure to support clinician scientists.

Third, we aim to break new ground in the delivery of “small molecule” immunotherapies for cancer. Dartmouth investigators are known for their role in designing the first large molecule antibody-based immunotherapies for cancer. However, many critical immune pathways can be modulated by treatment with small molecule drugs, which are much more amenable to oral delivery and rapid clinical translation. Based on existing pipelines and innovative preclinical studies in Dartmouth Cancer Center laboratories, we will offer a new class of small molecule immune-stimulatory drugs to treat a wide range of cancer types.

Innovation: Creating the Future of Cancer Treatment In this age of intensive specialization and complex scientific questions, Dartmouth Cancer Center promotes interdisciplinary, transdisciplinary, and convergence science to advance innovation in all four research programs. Our high capacity for innovation is buoyed by constant intellectual exchange among investigators who are motivated by the needs of the communities we serve. We designed our center’s physical and organizational structure to make connecting with other experts, accessing shared instrumentation, and interaction between scientists and clinicians virtually seamless. Recently, we launched the Dartmouth Innovations Accelerator for Cancer (DIAC), a $15 million initiative within Dartmouth’s Call to Lead campaign. Specifically funded to accelerate the development of Dartmouth’s most promising biomedical innovations in cancer, the ultimate impact of DIAC will be better prevention and treatment of cancer. A partnership between Dartmouth Cancer Center and the Magnuson Center for Entrepreneurship at Dartmouth, DIAC serves Dartmouth faculty, staff, and students engaged in translational cancer research with a training program and opportunities for funding. Documented outcomes include fostering innovation; better understanding of how to move new

drugs, devices, and diagnostics to the clinic; and help in de-risking the most promising projects through funding and mentorship. An external review panel of investors from top venture capital firms and biotech executives, often with deep Dartmouth connections, selects teams for participation in the DIAC program. Fueled by additional generous philanthropy, the Cancer Center’s Director’s Pipeline Innovation Fund supports innovative projects in basic science likely to be foundational for future translational science addressing cancer in humans.

“Dartmouth Cancer Center is clearly in the heavyweight class when it comes to developing National Cancer Institute (NCI)-funded biotech start-ups. DIAC brings together the best that Dartmouth has to offer, from the world-class research being conducted at the Cancer Center to the top-notch entrepreneurial programming put together by the Magnuson Center. By supporting promising early-stage cancer innovations, we’re playing an active role in changing the future of cancer treatments and ultimately saving lives.” – Steven D. Leach, MD Director of Dartmouth Cancer Center

DIAC AT A GLANCE FUNDING $7+ million in alumni donations $1.4 million awarded

PARTICIPATION 3 cohorts completed 35 teams 140 participants

OUTCOMES 6 startups created 5 technologies licensed $11.5+ million in follow-on funding

2023 COHORT

Arminja Kettenbach, PhD, co-director of the Cancer SGNs research program, is focused on understanding signaling by phosphoprotein phosphatases in the context of their cellular networks in normal cells and cancer.

16 projects 50 participants 7 returning teams

The Precision Prevention Initiative: Stopping Cancer Before it Starts Cancer’s toll on patients, workplaces, and communities is incalculable; it touches virtually every single family. Dartmouth Cancer Center is making promising strides in reducing the incidence of cancer through precision prevention—the art and science of individualized strategies designed to stop cancer before it starts. Individuals have different genetic predispositions, environmental exposures, and lifestyle preferences. Addressing individual risk factors represents the core of precision prevention. Using precision prevention techniques leverages patient’s differences, making it possible for their physicians to customize their cancer prevention, screening, and intervention efforts. In the Precision Prevention Initiative, multiple thriving cross-campus research collaborations will uncover how daily exposures and behaviors interact with genetics, which will provide more precise understanding of cancer risks. We can achieve major reductions in cancer incidence by addressing the top risk factors—tobacco

and alcohol use, obesity, pollutants, and infections— and understanding how they interact with behavioral, environmental and genetic factors to determine whether medical or lifestyle interventions to reduce risk will be effective. This research will lead to scalable solutions that will reduce cancer risk in our area and beyond, and in current and future generations.

Highlighted in the following pages are our four research programs and the promising science that are the central core of cancer research collaboration and innovation. The pursuit of next-generation immunotherapy, innovations of all sorts, and precision prevention strategies are best bets for cancer science with potential for impact on humans. The goal is readying scientific findings for deployment throughout the population. We aim for global impact.

Brock Christensen, PhD and Lucas Salas MD, PhD discuss their winning presentation in the Dartmouth Innovation Accelerator for Cancer competition.

ICI

Immunology & Cancer Immunotherapy (ICI) Research Program The ICI program provides an interdisciplinary environment to interrogate and understand mechanisms of anti-tumor immunity and advance novel immunotherapies for cancer patients. ICI’s resources and activities foster meaningful exchange of scientific ideas between immunologists, engineers, oncologists, and surgeons. Internal funding of early efforts in translational cancer immunology creates opportunities for innovation and dedicated philanthropy for training in cancer immunology supports student-led projects. The senior ICI team is actively involved in training and mentoring the next generation of immunologists in Dartmouth’s graduate and post-graduate programs that span the basic and clinical sciences. ICI’s leaders are focused on targeted recruiting to build the team’s already outstanding capabilities in T cell immunology and translational research. Our future includes the creation of an inaugural Center for Cancer Immunotherapy Research to support recruitment of immunologists and clinician-scientists and investments in innovative core resources.

Major Areas of ICI-Focused Research Include: • Targeting VISTA as a negative immune checkpoint • Memory T cell responses to cancer • Novel PD-1 inhibitors and small-molecule immunotherapies • CAR T cell therapy • Intratumoral immunotherapies • Myeloid cell biology in cancer

Clare Murray and Charles Ontiveros are doctoral trainees doing immunotherapy thesis research in the Curiel Lab.

ICI Directorship: • Mary Jo Turk, PhD, O. Ross McIntyre MD Professor of Medicine, Geisel School of Medicine at Dartmouth • Kenneth R. Meehan, MD, professor of medicine, Geisel School of Medicine at Dartmouth

ICI Membership: 24 Members

Immunologist Tyler Curiel, MD, MPH, FACP, is working to understand immune dysregulation, specifically immunopathogenesis, to enable development of novel therapies.

Featured Science Ongoing VISTA clinical trial

CAR T cell therapy

Unleashing the immune system has proven an effective way to enhance anti-tumor immunity to cure cancer. VISTA, a novel immune checkpoint molecule discovered by Randolph Noelle, PhD, will help to further enhance immunity against malignancies. Using an anti-VISTA antibody, VISTA is now targeted in patients at Dartmouth Cancer Center and holds promise for patients who otherwise would not have any remaining treatment options.

Since its first CAR T cell infusion in the spring of 2020, the Transplant and Cellular Therapy Program, led by Kenneth Meehan, MD, has demonstrated continued growth and is planning to infuse up to four CAR T patients each month. Today, the number of patient who would benefit from CAR T Cell Therapy far exceeds the current capacity and an expanding waiting lists exists. For these patients, CAR T therapy may provide a cure when no other therapies have succeeded.

Novel innovations in CAR T cells

Allogeneic T cells

Yina H. Huang, PhD, is developing armored CAR T cells that neutralize the toxic environment found in solid tumors.

The laboratory of Charrles Sentman, PhD, has developed novel gene and cell engine approaches to target cancer. Importantly, the allogeneic T cells can be used in any patient and avoid the well-known problem of having to match a donor to a patient before a transplant.

Overcoming treatment resistance barriers to immunotherapy This is the goal of Tyler J. Curiel, MD MPH, FACP, who focuses on the tumor microenvironment’s inhibition of treatment efficacy. Curiel is using studies of treatment resistance factors to guide development of novel earlyphase clinical trials to overcome resistance barriers.

Two drugs developed by the Curiel lab are entering trials; previous novel drugs from the team have been developed by industry/ biotechnology partners.

In-situ vaccination Using a mouse model, Steven N. Fiering, PhD, is developing novel approaches to boosting anti-tumor immunity by injecting immune stimulatory reagents directly into tumors. Engineering proteins Through the Dartmouth Innovations Accelerator for Cancer, Karl Griswold, PhD, an engineer, is working on a platform for precision protein engineering for cancer immunotherapy.

Mary Jo Turk, PhD, (second from left) studies memory T cell responses in cancer with a host of trainees, including (from left) Delaney Sullivan, Tyler Searles, and Cameron Messier.

Yina Huang, PhD, uses a multi-disciplinary approach to understand how tumorspecific memory T cells provide durable protection against cancer recurrences.

CPS

Cancer Population Sciences (CPS) Research Program The CPS program’s two overarching research goals are to establish the scientific basis for policies and interventions that reduce the incidence of cancer across the life course and to improve the delivery of cancer-related healthcare. Research questions spur investigation ranging from prevention to palliative care, with a special focus on rural populations typified by our catchment area of New Hampshire and Vermont. Dartmouth’s longstanding commitment to influencing policies and interventions includes educating regional and national policymakers about the science of cancer prevention in topics such as arsenic in well water and secondhand smoke; this is a distinction of Dartmouth Cancer Center’s CPS Research Program. Our broad-ranging CPS Research Program includes epidemiologists, quantitative biomedical scientists, and translational population scientists actively moving basic research into clinical and population settings. CPS investigates environmental and genetic cancer risk factor epidemiology, life course epidemiology, behavioral cancer risk reduction, and health care delivery research, with a particular focus on precision prevention—an identified scientific priority.

CPS Directorship: Brock Christensen, PhD, Sandra Wong, MD, MS

CPS Membership:

Featured Science Life-Course Epidemiology Knowing about an individual’s cancer risk in advance makes screening more effective across their lifespan. Some babies are born with genetic syndromes that predispose them to cancer. Management of risk can have impact, particularly if started early in life. General pediatricians can implement risk management plans, but at present, there are no national guidelines for pediatric genetic testing. Pediatric oncologist and scientist Bonnie Lau, MD, PhD, is investigating indications and strategies for babies born with such genetic syndromes to innovate educational tools for community physicians. This work will make it possible for clinicians in general pediatric practices to use genetic profiling to design and customize cancer surveillance plans for their patients. Biological Aging Assessment Brock Christensen, PhD, and Lucas Salas, MD, PhD are studying age, the most important risk factor for cancer. Using epigenetic technology, biological aging assessment is a new tool in precision prevention. This tool measures modifications (not mutations) on DNA to assess an individual’s biological age, which may be different than their chronological age. “Age acceleration” (a biological age older than chronological age) puts an individual at greater risk of cancer. However, recommendations for preventative cancer screening are determined by national task forces based on chronological age.

Physicians may be able to help manage risk by using the results of biological aging assessment to recalibrate and provide precision prevention strategies for individual patients.

47 members from 19 departments

Brock Christensen, PhD, and lab manager Hannah Stolrow discussing pan-cancer immunotherapy response in the Williamson Translational Research Building, Dartmouth Cancer Center’s newest facility at Dartmouth Hitchcock Medical Center.

Margaret Karagas, PhD, here with Cindy Takigawa ’21, seeks to identify emerging environmental exposures, host factors, and mechanisms that impact health from infancy to adult life, and to apply novel methods and technologies to understand disease pathogenesis.

Gene-Environment Interactions and Health Outcomes Cancer prevention starts before birth by preventing environmental exposure to toxins in water, air, and food. Discovery of a strong link between arsenic in drinking water and high rates of bladder cancer in New Hampshire inspired investigators in CPS, led by senior investigator Margaret Karagas, PhD, to study bladder cancer, gene–environment interactions, and related health outcomes. These studies are facilitated by the Children’s Environmental Health and Disease Prevention Research Center at Dartmouth. The center also has the largest longitudinal study of pregnancy and infant/child health of its kind in the U.S. At the national level, CPS investigation catalyzed new federal guidelines for allowable arsenic levels in baby rice cereal and prompted the State of New Hampshire to enact strict limits on arsenic and per- and polyfluoroalkyl substances (PFAS) in drinking water. PFAS chemicals are in consumer and industrial products, have contaminated groundwater in many communities in the U.S., and are linked to kidney and testicular cancer, elevated cholesterol, decreased fertility, thyroid problems, and decreased immune response to vaccines in children.

Healthcare Delivery Science

Studying cancer care across the continuum, from cancer prevention to palliative care and survivorship, is an area of focus for CPS investigators. By studying insurance claims data and electronic health record data, CPS investigator Erika Moen, PhD, is using innovative network data science methods to understand variations in care patterns and outcomes for rural and non-rural populations. Sandra Wong, MD, MS, and Anna Tosteson, ScD, are leading a multidisciplinary team that is studying rural cancer care and surgical disparities among those diagnosed with colorectal, lung, or pancreatic cancer. Gabriel Brooks, MD, MPH is studying outcomes associated with the oncology care model and has developed risk prediction tools to identify those at highest risk of hospitalization following chemotherapy. Andrew Loehrer, MD, MPH, is working with geospatial drivers of cancer care disparities and their susceptibility to health policy changes.

PFAS Exposure Occurs by:

Drinking contaminated municipal or private water.

Eating food packaged in materials that contain PFAS.

Using some stain/ water-resistant products.

Eating fish caught from water contaminated by PFAS.

Gabriel Brooks, MD, MPH, is a medical oncologist and health services researcher selected as a Dartmouth Cancer Faculty Fellow to provide him with protected time to advance his identification of patients at highest risk for hospitalization following chemotherapy.

CPS

Christine Gunn, PhD, is a health services researcher examining cancer risk communication and decisionmaking to make cancer prevention and care more accessible for marginalized populations.

Digital Health

Described as the next frontier in cancer prevention and risk assessment, digital therapeutics such as apps and wearable devices are already helping doctors and patients to understand harmful behavior and provide targeted interventions. Addiction and substance abuse are serious risk factors for cancer, and digital technology is currently providing information to help curb harmful exposure to toxins as a means of direct precision cancer prevention. Lisa Marsch, PhD, and her team are collaborating in biomedical data science and psychiatry to save lives by improving mental health and lifestyle behaviors with the use of new digital tools. Toxicity-measuring wristbands and mobile apps encourage physical activity and healthy behaviors by tracking behaviors and environmental exposures. Researchers distill the data, which provides a wealth of individualized information over time to develop a patient’s risk profile. This data will uncover biomarkers that give clinicians the ability to precisely predict and prevent

harmful outcomes and intervene in real time for increased impact on the health of individuals in our community. Sandra Wong, MD, MS, is working with the electronic medical record through eSYM, a project funded by the National Cancer Institute (NCI) as part of the Cancer Moonshot initiative, which focuses on electronically captured patient-reported outcomes in medical oncology and surgical oncology patients with gastrointestinal, thoracic, and gynecological cancers with the ultimate goal of improving symptom management for patients receiving systemic treatment or recovering from surgery. Machine Learning Machine learning, also known as artificial intelligence, leverages large and often unstructured data sets to organize and infer knowledge to improve our understanding of health and disease.

Opportunities for machine learning to help physicians work better and faster are being realized with the development of software by Saeed Hassanpour, PhD.

Lisa Marsch, PhD, and Molly Anderson, PhD, are discussing software that can measure individuals’ cancer risk via sensing technologies on mobile devices and target modifiable cancer risk factors using personalized digital interventions.

In addition to leading the Department of Surgery, Sandra Wong, MD, MS is a health services researcher with several studies about the health and surgical disparities experienced by patients with cancer living in rural areas.

His work provides advances in digital pathology, such as an augmented system for histologic classification of colon polyps that provides pathologists with a fast-moving, highly accurate system for assessing large volumes of data. Dr. Hassanpour’s work in histopathologic image classification methods development extends across multiple cancers and aims to have practical impact for cancer patients and their physicians.

New immune profiling methods will allow the development of biomarkers predictive of patients’ response to cancer immunotherapy. DIAC funding will support the transition to a lower cost and customized platform to accelerate clinical studies of therapy response.

Predicting Responses to Cancer Immunotherapy

Aligning cancer care with individual patient preferences and needs is enhanced through effective decision support tools for low-literacy populations and through the design and implementation of new care pathways that connect rural-residing cancer patients with needed services. CPS investigators Christine Gunn, PhD, Glyn Elwyn, MD, PhD, MSc, and Paul Barr, PhD, are leading studies that address these challenges. Rian Hasson, MD, MPH, has Levy Incubator and Cancer Center support to study increasing lung cancer screening in rural populations.

With support from the Dartmouth Innovations Accelerator for Cancer, Lucas Salas, MD, PhD, and Brock Christensen, PhD, are developing novel “methyl-immunomic” profiling technology for physicians to assess immune health and enable cancer immunoprevention strategies. Although a new era of cancer immunotherapy is revolutionizing treatment strategies, fewer than one in five cancer patients respond to treatment.

Patient-Centered Care for Rural Populations

TEC

Translational Engineering in Cancer (TEC) Research Program The TEC research program incorporates imaging, radiobiology, biophysics, and applied engineering approaches into the development and evaluation of new cancer diagnostic and treatment strategies. A diverse multidisciplinary group of cancer researchers, including faculty from Dartmouth’s Geisel School of Medicine and Thayer School of Engineering and Dartmouth Health’s Clinical Departments of Medicine, surgery, orthopaedics, pathology, and radiology comprise the program’s membership. TEC has institutional commitment to recruit seniorlevel faculty, including the next co-director, to work directly with current TEC director Keith Paulsen, PhD, in mentoring the junior faculty and resourcing bioengineering discovery. Key research themes continue to be molecularly guided surgery and radiation treatment monitoring and guidance, which are now being explored in the form of FLASH radiotherapy by an interprofessional team of engineers and clinician scientists. Development of a program with the Center for Surgical Innovation that uses FLASH intraoperatively to treat gliomas, other brain tumors, and head and neck cancers, among others, is under consideration and would bring together two of TEC’s research themes into an exciting new initiative. In addition to image analysis, autonomous artificial intelligence holds great promise for diagnostic, therapeutic,

Featured Science Contrast Imaging Kimberly Samkoe, PhD, is moving her innovative work in paired agent imaging into the clinic under NCI funding to support Phase 0 trials of an EGFR-targeting fluorescent agent used in concert with a second fluorophore that will increase sensitivity and contrast in imaging of head and neck and brain cancers. Priority: Innovation Through the Dartmouth Innovations Accelerator for Cancer, an outstanding array of innovations and their teams have been selected for enhanced training and funding. Recent projects and awardees include: 16

and therapy monitoring applications that generate actionable data useful in treatment protocols. Over the next 5-10 years, the TEC Research Program will expand its emerging research in FLASH by combining it with surgical image guidance and grow activities in automated image analysis and processing via machine learning, which will enable research investigations in robotic/fully automated surgical oncology. Concurrently, investigators will design molecular and physically based imaging and measurement techniques for guiding accurate and complete resection of cancers with minimal toxicity or complications post-surgery. In radiation oncology, investigators will expand efforts in radiation monitoring and guidance by engineering novel tools to image and directly measure radiation doses and key physiological/functional parameters that inform and guide the effectiveness and safety of radiotherapy delivery in cancer treatment. Promising new approaches in cellular and molecular detection and contrast have investigators developing new techniques for imaging cellular types, metabolites, proteins, or nucleotides in vivo and testing detection, or image contrast, based on the biophysical, parametric, pharmacokinetic, or pharmacologic features of tissues for applications in screening, detection, diagnosis, or management of cancer treatment.

TEC Membership: 30 members from 15 departments

FLASH Therapy Led by TEC members, P. Jack Hoopes, DVM, David Gladstone, PhD, and Brian Pogue, PhD, a team of Dartmouth bioengineers created the first reversible MeV FLASH beam for radiation therapy in cancer on a clinically commissioned linear accelerator with >100 Gy/s, and prototyped an open-source treatment planning system to expand research access. Additionally, the team invented unique technology to measure the highest dose rates and in vivo tissue oxygen transients directly. They are working with NCI support to overcome key technological barriers to demonstrate conversion to an Ultra-High Dose Rate (known as UHDR) irradiator within a clinically commissioned linear accelerator, verify per-pulse and perfraction dose rates, observe oxygen transients in vivo, and measure free radical changes in vitro.

Surgical oncologist Eric Henderson, MD, is committed to improving outcomes through discovery and innovation, including fluorescence-guided surgery, which is a nascent technology to make surgery safer and more effective by labeling important tissues, including cancers. It will ensure complete tumor removal and preservation of structures critical to patient function. Here, Dr. Henderson and resident Ilda Molloy, MD, complete a distal femoral replacement for a chondrosarcoma.

Nerve-Specific Fluorophore

Multi-Modal Exams

Eric Henderson, MD, medical director of Dartmouth Cancer Center’s Sarcoma Oncology Program, is pursuing the first-in-human clinical translation of a near-infrared, nerve-specific fluorophore, IT01-08, that binds to nerve tissue with high specificity in rodent and swine models to facilitate tissue-specific fluorescence-guided surgery in sarcoma resection procedures. The work will bring a new diagnostic agent into early clinical testing in patients through his investigator-initiated studies which are being supported by the National Institute of Health (NIH).

With the goal of reducing MRI false positives in breast imaging, Paul Meaney, PhD, and Shudong Jiang, PhD, are developing two novel technologies to be used simultaneously in diagnostic breast imaging. The first technology uses microwave and the second uses nearinfrared instrumentation, both in combination with MRI, for simultaneous, multi-modality exams.

Novel Antibodies

Reducing MRI false positives will potentially eliminate the need for contrast enhancement by supplementing the MRI scans with the new, and more specific, properties of microwave and near-infrared images.

The engineering lab led by Jiwon Lee, PhD, is developing an antibody engineering technology platform for faster development of novel therapeutic antibodies. This is Dr. Lee’s second DIAC award. 17

TEC

Cancer Signaling, Genomes, and Networks (SGNs) Research Program Cancer SGNs is a nexus for basic scientists, translational researchers, and clinicians with interests in cancer biology, cancer genomics, computational oncology, and the development of improved treatments and diagnostics. Members probe basic mechanisms of cancer genetics, cell biology, and biochemistry to drive therapeutic target discovery, validation, and clinical applications. SGNs members continue to innovate new approaches to uncover knowledge of cancer mechanisms and drug resistance. Dartmouth’s DISCOVERY supercomputer provides the computational infrastructure necessary to manage, analyze, and interpret “big data” for translational applications in cancer. Leveraging genomic and clinical data from Dartmouth Cancer Center patients, SGNs researchers can identify and deliver patient-specific therapies and locate the

unique cells within tumors that have the potential to metastasize to reign in cancer before it spreads. Faculty and trainee career development are SGNs priorities. In the next few years, SGNs plans to recruit two basic scientists and two clinician-scientists to build new translational cancer research programs at Dartmouth Cancer Center. This new talent will align with and augment our strengths in computational oncology and therapeutic target discovery and development.

SGNs Directorship: Konstantin Dragnev, MD Arminja Kettenbach, PhD

SGNs Membership: 51 members in 15 departments

PRE-CLINICAL

Cell Lines

CLINICAL

Mice

Study Molecular Mechanism Associated with Biomarker-pos. Response

Polly Trial

Featured Science Using Estrogen to Treat Breast Cancer

Targeting the “Undruggable”

An interdisciplinary team of SGNs researchers led by oncologist Gary Schwartz, MD, is developing strategies to increase the utility of estrogen therapy for metastatic breast cancer.

SGNs member Michael Cole, PhD, has been studying the cancer-causing protein MYC for over 40 years. In a promising alternative approach, Dr. Cole’s group focuses on developing agents to block MYC’s interactions with its key partnering proteins—an example of how basic science research can culminate in translational application. Propelled by an award from the Dartmouth Innovations Accelerator for Cancer, a Dartmouth Cancer Center Prouty Pilot award, and other institutional investments, the team’s technology has attracted funding from the federal government and the biotechnology sector.

Laboratory studies revealed that alternating estrogen stimulation and estrogen withdrawal was more effective than either continuous stimulation or continuous withdrawal. Testing followed in a clinical trial supported by the Dartmouth Cancer Center’s Early-Phase Trials Program. Cycling these therapies provided robust anti-cancer effects in patients, and tumor genetic profiling revealed potential biomarkers to predict tumor response. More recent laboratory findings supported by federal and philanthropic funding revealed that combining estrogen with approved drugs that disrupt DNA repair can enhance anti-cancer efficacy, offering drug combinations for clinical evaluation in the coming years. Targeting Proteins Paul Robustelli, PhD, is using state-of-the-art computer simulations coupled with experimental biophysical approaches to design drugs for hard-to-target proteins.

The neuro-oncology lab of Arti Gaur, PhD, and the chemistry lab of Glenn Micalizio, PhD, are developing novel treatment for brain cancers. Their new therapeutic compound kills cancer cells and leaves healthy cells intact. Drug Treatment for Colorectal Cancer Biologists Yashi Ahmed, PhD, and doctoral candidate Muhammad Taha discovered a novel drug target in colorectal cancer and are developing small molecules as potential drug candidates.

Arti Gaur, PhD, works alongside students enrolled in the POWERED program in the Gaur Lab. Dartmouth Cancer Center was awarded a five-year NCI grant for the Program for Oncology Workforce Education and Research Experience at Dartmouth (POWERED). The rolling two-year program will train undergraduates from NIH-specified under-represented minority groups for careers in cancer research.

Treating Cancer in Our Clinics

Sandra Wong, MD, MS, chair of the Department of Surgery, Charles Thomas ’79, MD, chief of radiation oncology, and Linda Vahdat, MD, MBA, deputy director of Dartmouth Cancer Center and chief of medical oncology lead Dartmouth Cancer Center’s care of patients at our hub in Lebanon and other sites throughout New Hampshire and Vermont.

Enhancing Our System for Cancer Care Our strong performance on key indicators, including patient satisfaction, time to first appointment, available technology, and excellence in staffing, is an advantage as we further integrate and expand our system of clinical and research operations to meet the needs of communities in our catchment area.

With enhanced system integration anchored by harmonized management systems, we are facilitating the multi-directional exchange of human, technical and data resources among all Cancer Center locations. Cancer treatment typically includes more than one of our three primary modalities (radiation, surgery, and chemotherapy) over many visits with multiple providers. By prioritizing coordinated care, we ensure smooth inter-provider communication, scheduling, billing, transfer of patient information such as test results, and collaboration among the care teams to understand the needs of each patient and their care partners.

Functional system integration is essential to providing every patient with timely and coordinated clinical care. This model for coordinated care operates at Dartmouth Cancer Center’s flagship Norris Cotton Cancer Care Pavilion at Dartmouth Hitchcock Medical Center in Lebanon and is growing throughout the network of Dartmouth Cancer Center locations.

The clinical vision is consistent: exceptional, award-winning team-based clinical care regardless of choice of location for treatment, and access to advanced Dartmouth investigator-initiated and national clinical trials and technology. Our clinic sites are Lebanon, Manchester, Nashua, Keene, and New London in New Hampshire and St. Johnsbury, Mt. Ascutney, and Bennington in Vermont.

We share the following standards throughout our Dartmouth Cancer Center locations.

Our Patients deserve the best treatment options, quality and safety, convenient access, and satisfaction.

Our People benefit from employee engagement, career development, safety, and joy in work.

Our Community strategy is population health and equity, system growth and integration, financial health, and philanthropy.

Our Academic and Research Missions form a bridge between care, education, and research.

Vision Meets Strategy The future of cancer care at Dartmouth Cancer Center is people-focused, with the distinct priority of leveraging strength at the system level to facilitate patient satisfaction. National metrics prove that patients at Dartmouth Cancer Center are among the most satisfied in the nation. With enhanced system integration, we will harmonize management tools across locations to allow seamless patient experiences. To further benefit our patients and ensure Dartmouth Cancer Center’s quality care is accessible to everyone in the catchment area of New Hampshire and Vermont, we will optimize workflows and plan new locations and methods of care to reduce median distance from home to treatment site. Key data for analyses include geospatial data of the catchment area, disease presentation in our clinics and statewide, and available options for the delivery of healthcare, including telehealth. Innovative workflow and production models will update clinical roles and management of our people. Coordinating staffing strategies throughout the catchment area will drive employee satisfaction and promote joy in work as well as excellence in treatment, while respecting flexibility. Our community is spread widely through the diverse landscapes of New Hampshire and Vermont. By developing and implementing novel cancer screening approaches specifically designed to meet the needs of dispersed rural populations and partnering with local providers for implementation, we will increase participation in life-saving cancer prevention practices such as lung cancer screening.

To increase the impact of our academic and research missions, we are committed to providing access to sufficient and appropriate clinical trials such that each patient, regardless of disease site or treatment location, can be offered a clinical trial. Augmenting the infrastructure at our ancillary treatment sites is essential to support trials at those locations. The Promise Partnership Learning Health System Is a collaborative endeavor to harness the collective knowledge, skills, and experience of leaders, clinicians, researchers, patients, and families to provide the best possible care. It focuses on optimizing patient outcomes; sustaining a diverse workforce that finds meaning and joy in their work; generating and utilizing new knowledge for care delivery; and supporting innovation, quality improvement, and research. Current initiatives include: • Engaging patients and families in serious illness conversations about what matters most to assure that their care aligns with their values. • Point-of-care dashboards of patient-generated and clinical information to support quality of care and to advance science through effective capture of patientreported outcome measures. • Quarterly oncology learning health system retreats where faculty, staff, patients, and families learn from each other to further advance cancer care.

Clinical Excellence in Action Translational science, which is the bridge between biomedical innovation and clinical practice, encompasses an essential series of activities that determine the effectiveness of a new approach. Treatment at an academic medical center applies an extra lens to the patient experience. At Dartmouth Cancer Center, the robust clinical trials system ensures every patient is considered for a trial. The finest teams of clinicians use the utmost consideration to match patients with trials designed to test new treatment approaches that are on the forefront of

medical, radiation, and surgical oncology. Clinical trials are highly regulated and participant safety is the top priority. Many participants and families are motivated to join trials that may help people with the same cancers to have more effective treatment in the future.

The pathway to changing the “standard of care” is long and staffed by dedicated clinicians, investigators, and participating patients—all in pursuit of a world with less suffering from cancer.

Rian Hasson, MD, MPH, a thoracic surgeon involved in health services research, was selected as a Dartmouth Cancer Faculty Fellow to give her protected time to focus on research. Here, Dr. Hasson meets with a patient before imaging.

AT A GLANCE

clinics in convenient locations in NH and VT

427

clinicians caring for our patients

4,629

individuals began treatment for cancer as our new patients at Dartmouth Cancer Center in 2021

24,946

patients were treated in our facilities in 2022

65,445 appointments for our patients in 2022

Radiation Oncology The Dartmouth radiation oncology clinical program is well-resourced to continue its leading-edge, patient-centric standard of care. Radiation oncology at Dartmouth Cancer Center delivers three advanced therapies not available at any other location in northern New England. In addition to being outstanding options for better treatment for patients, they are emblematic of the bright, creative, and interdisciplinary teams spanning all of Dartmouth to improve outcomes for patients with cancer. Air ionization from FLASH beam

Innovation and Clinical Trials The innovations established and nurtured in radiation oncology at Dartmouth Cancer Center are designed to lead to improved outcomes. We continue to pioneer the emerging treatment delivery technique of FLASH radiotherapy as well as novel image-guidance strategies such as Cherenkov imaging. We can start by understanding that radiation treatment is calculated as a number of units totaling the entirety of the treatment to a patient. Traditionally, some “fraction” of the whole is delivered as a part of the entire dose each time a patient has one of their treatments. The benefit of FLASH radiotherapy is that all of a radiation fraction will be delivered in less than a second instead of several minutes. This technique saves time for the patient and clinic staff. Testing in pre-clinical models (meaning not yet in regular human patients) has shown that when FLASH is used, normal tissues are spared harm from radiation. The potential to increase the therapeutic ratio (of quantity of radiation to length of time for radiation) may be a critical advantage for better patient outcomes due to less toxicity. Cherenkov imaging is another highly advanced technology which allows the radiation therapy technicians and physicians to verify proper alignment of machinery with the specific target on the patient before delivery of the actual radiation treatment. Our partnership with a local Cancer Center spin-off company, DoseOptics, has resulted in our programs in Lebanon and Keene (at Cheshire Medical Center) routinely implementing Cherenkov imaging as part of a daily quality parameter. We are extremely proud of the Dartmouth Cancer Center members, led by Brian Pogue, PhD, with David Gladstone,

PhD, and Lesley Jarvis, MD, PhD, who conceived and pioneered this technology here. Brachytherapy, which uses seed implants, is expanding with the addition of new expert providers offering HDR (highdose rate) brachytherapy to men with prostate cancer. Shauna McVorran, MD, leads this effort and will complement the current low-dose rate (LDR) brachytherapy prostate program developed by Alan Hartford, MD, PhD. Looking forward, we are ready to increase our expertise in the delivery of complex interstitial and intracavitary implants for women with advanced and/or recurrent cancer of the endometrium, cervix, vulva, or vagina. During the pandemic, radiation oncology clinics in lowresource countries were prompted to innovate quickly to prevent spread of disease and continue treatment protocols as planned. In a study funded by the National Cancer Institute, Dartmouth Cancer Center, with partnering cancer centers in twelve Latin American and Caribbean countries, surveyed innovations they developed, followed by a collaborative process to make a short list of scalable and generalizable innovations recommended for other medical emergencies. Testing innovations in the clinic is essential, and we are poised to expand our development of investigator-initiated clinical trials that involve the delivery of radiotherapy. These trials originate from some of the novel translational research focusing on biomedical engineering as well as health services research, which is the focus of four MD/PhD physician scientists on the radiation oncology. This focus on innovation, which spans device development to health

Dose-Response & Math Modeling

Clinical Data (EMR)/ Informatics

Patient Reported Outcomes (PRO)

Adaptive XRT/MRLinac (ViewRay)

Mobile Health & Telemedicine/ Informatics/ Data Science

Population/ Risk Modeling (nomogram)

SMMART (Serial Measurements of Molecular Architecture Responses to Therapy) Trial Platform

Omic Data Cherenkov

FLASH Comprehensive Radiation Oncology Model

Virtual Tumor Growth Modeling PatientDerived Xenograft

care delivery, is a core strength and presents treatment options we offer for patients and families. The future of the Dartmouth Cancer Center’s clinical radiotherapy program remains innovative and vibrant.

Education and Training The education and teaching mission is a unique strength of the undergraduate experience at Dartmouth College and extends into our radiation oncology program. First, our faculty actively teach Dartmouth undergraduates at the college. Professor P. Jack Hoopes, DVM, a senior scientist deeply involved in the discovery of FLASH and Cherenkov imaging, is the course director for Engineering 56, Introduction to Biomedical Engineering. Chief of Radiation Oncology Charles R. Thomas, MD, Mary Jo Turk, PhD, and other faculty from radiation oncology frequently trek to the Hanover campus and teach classes to undergraduates out of conviction that hearing about biomedical engineering from end-users makes it come alive. We are recruiting the next generation by making early and exciting connections.

Spatial Histopathology

Radiomics Quantitative imaging

Tavakkoli, Dartmouth valedictorian ’20, Geisel ’24, and another member of the Radiation Oncology Student Interest Group, is a recipient of a national award for his grant project, “Evaluating the Therapeutic Potential of FLASH Irradiation in Brain Tumor Treatment.”

The radiation oncology residency training program is poised to graduate its first physician resident in June 2024. Our residents are garnering multiple accolades as they establish a culture of learning excellence with our dedicated faculty. Highlights include research presentations by Gobind Gill, MD, (PGY4) at ASTRO 2021, GI Cancer Symposium 2022, and ASTRO 2022, and oral presentations by Melanie Rose, MD, (PGY3) at ASTRO 2021 and 2022 as well as at the 54th Congress of the International Society of Paediatric Oncology in Barcelona. All our residents routinely apply to attend the Vail Workshop in cancer clinical trial design and submit grants to the RSNA Research Resident/Fellow Award.

Our doors are open to medical students at Dartmouth’s Geisel School of Medicine, and their involvement is exciting and productive. The Radiation Oncology Interest Group provides a solid and welcoming connector between students and practicing radiation oncologists. This tradition goes back decades and here we have a few recent examples. Drew Bergman, Geisel ’24, leveraged his connections through the Translational Oncology Program for Scholars, which embedded him in radiation oncology following his first year, and won a national research grant for his paper, “Epigenetic Mechanisms of the FLASH Radiotherapy Effect.” Armin

Surgical Oncology

Teaching and research are key components of surgical oncology at Dartmouth Cancer Center, where investigators making improvements to current practice test innovations in the novel Center for Surgical Innovation.

The vast Department of Surgery, chaired by Sandra Wong, MD, MS, a surgical oncologist and current president of the Society of Surgical Oncology, encompasses the Section of General Surgery, which includes the Divisions of Surgical Oncology, Endocrine Surgery, and Colorectal Surgery, as well as the Sections of Neurosurgery, Ophthalmology, Otolaryngology, Pediatric Surgery, Plastic Surgery, Thoracic Surgery, Transplant Surgery, and Urology. All components of the department treat patients with cancer. Dartmouth Health surgeons affiliated with Dartmouth Cancer Center treat patients in Lebanon and at outreach clinics in Manchester and Keene.

Education and Training Surgical oncologists generously provide access to trainees and potential trainees ranging from undergraduates in the Dartmouth Cancer Scholars program to Geisel School of Medicine students in the Translational Oncology Program for Scholars. Each student is keen to question their interest in surgical oncology, and they come with personal questions about their ability to maintain a positive outlook when working with patients with cancer, to live a healthy lifestyle on the challenging schedule of a top surgeon, and to be actively involved in research while balancing a busy clinical load. Our thoughtful process to embed students with surgical oncologists results in equally thoughtful reflection by the students and comments such as, “I never knew the surgeon spent so much time getting to know the patient,” and “I could see how the doctor’s family time worked with the clinical schedule.”

On the national level, Kari Rosenkranz, MD, is on the American Board of Surgery’s General Surgery Certifying Exam Breast Committee, which determines standards for surgeons across the country. Dr. Rosenkranz led Dartmouth Cancer Center’s Breast Cancer Tumor Board weekly conference, which provides continuing medical education credit to participants, for more than ten years. We are honored to be setting national standards used for accreditation by the American College of Surgeon Commission on Cancer. One active quality improvement project is focused on creating a single point of referral and standardized care pathway for patients with melanoma to improve access to care. This assignment is closely related to population health issues in New Hampshire and Vermont, where the rates of melanoma are among the highest in the country.

Ryan Halter in lab with a device with Ethan Murphy, PhD, (standing) and Michael Koko, PhD, (seated).

Innovation and Clinical Trials Our surgical oncologists have diverse expertise and a collective drive to improve the lives of their patients with cancer. Scientific expertise ranges from basic/ translational sciences to clinical trials to health services research, and many projects are funded by the National Cancer Institute. Collaborative studies inform innovations in treatment and the delivery of care, which beget new research questions and further study. Richard Barth, MD, a surgical oncologist, is a superb example. Stymied by his inability to reliably locate a tumor based on conventional pre-surgery imaging, he invented a 3D printed bra-like cover for the tumor area and a system to guide the surgeon with landmarks interior to the breast rather than exterior. Through participation in the Dartmouth Innovation Accelerator in Cancer, he learned how to protect his intellectual property and open a company, and the device is in clinical trials across the U.S. Concurrently, he focused his concern about misuse of “leftover” prescription pain medications given to surgical oncology patients by developing trials to determine reasonable (refillable) starter prescriptions that would prevent excess medications from being available in homes. His helpful findings have been shared widely and are changing practice.

A strong cohort of surgical oncologists focuses on what they can and cannot see in the surgical field. In their world, a few cancer cells left behind can result in recurrence of disease.

They are developing and trialing new techniques for imaging both pre- and intra-operatively. Linton Evans, MD, a neurosurgeon with specialty training in neurooncology, is studying IDH1-targeted fluorescence-guided surgery of low-grade glioma; P. Jack Hoopes, DVM, works with animal and human studies of irradiation (focused on FLASH radiotherapy), preclinical imaging, and microscopy; and Florian Schroeck, MD, a urologic oncologist, is evaluating non-invasive alternatives to invasive cystoscopy with urine testing for non-muscle invasive bladder cancer surveillance. Others, including Rian Hasson, MD, MPH, Andrew Loehrer, MD, MPH, and Sandra Wong, MD, MS, focus on disparities of care in the more rural regions of our New Hampshire and Vermont catchment area. Their meta question is, what can we do to make cancer care work better for our rural patients? Their additional training in population science techniques incorporates qualitative research methods that facilitate analysis of non-numerical data. Topics include understanding provider and patient preferences for mobile lung cancer screening clinics (Hasson), geospatial drivers of cancer care disparities and their susceptibility to health policy changes (Loehrer), and disparities in access to and outcomes of cancer surgery for rural Medicare patients (Wong).

Medical and Hematologic Oncology

Pathology’s Clinical Genomics and Advanced Technology, led by Gregory Tsongalis, PhD, (left) provides rapid turnaround for tests on instruments at the forefront of science and medicine. Technicians Priscilla Carnaroli, Jennifer Barbuto, and Patrick Shannon process cervical samples on this high throughput Roche Cobas 6800.

Locations and Market Share

AT A GLANCE— COORDINATED CARE • 1 .18% of the residents of our catchment area are under our care

• 24,608 patients treated in 2021 • 86% of patients polled in Lebanon described their care as Very Good

AT A GLANCE— CLINICAL TRIALS • 349 clinical trials at Dartmouth Cancer Center • 48.5 FTE staff committed to the Office of Clinical Research

• 1 ,327 patients accrued to clinical trials annually • Clinical trials include pharmaceutical industry sponsored trials, Dartmouth investigator-initiated trials, and cooperative group trials

AT A GLANCE— INVESTING IN OUR FUTURE • 10 oncologists selected as Cancer Faculty Fellows, provided with 40% time for research

• $1M annually provided by Dartmouth Health to support the Cancer Faculty Fellows program

Our vision of cancer treatment is seamless services, including provider visits, infusion and radiation therapy, and access to clinical trials across our 14 sites in New Hampshire and Vermont. Current projects getting us toward that goal of “seamless,” otherwise known as hassle-free, involve interoperability of the electronic medical records from one location to another and limited access to clinical trials at the smaller sites. Key to success will be increasing our market share in the southern region of the twin states and leading innovation across the cancer continuum. Patient volume, as measured by new patient visits, is increasing dramatically at our Lebanon site, where five-year growth was 25.8% compared to 15.9% at our other locations. New patient visits had strong increases, especially in melanoma, up 43% in new and established patient visits when comparing 2021 and 2022. Almost all disease sites experienced double-digit growth. There is tremendous opportunity in the southern region of our NH/VT catchment area as population growth drives need for care. The advisoryboard projects a 16.5% increase in patient volume by 2030, with 3.1% specifically for the cancer service line. Like every medical center, Dartmouth Cancer Center finds staffing a challenge. Despite the attractive setting, healthy lifestyle, and competitive wages, potential newcomers find it difficult to get housing at a reasonable price. Towns and institutions across the region are addressing the housing shortage using many approaches, yet there is no immediate fix. For Dartmouth Cancer Center, mitigation strategies for staffing shortages include, again, system integration to facilitate shifting providers and patients from overcrowded facilities to those with capacity. Leveraging telehealth and better coordinated administrative systems make this possible.

Staff from the Cancer Center’s Office of Clinical Research are pictured at our base in the Rubin Building at Dartmouth Hitchcock Medical Center, which facilitates easy access to principal investigators, physicians, and study participants.

Clinical Trials and Innovation

Training the Next Generation

Cancer care at an academic medical center is different. Innovation is central to our mission. Medical and Hematologic oncology is led by Linda Vahdat, MD, MBA; she was recruited in 2022 with outstanding credentials as a clinical trialist. Dr. Vahdat describes herself as follows,

Our hematology-oncology fellowship program admits three MDs per year for a three-year training program, with plans to add a fourth trainee in 2024. The program attracts more than 700 applicants annually. The program is distinctive in its optional global oncology track, which includes significant time onsite in a low-resource country and time for training in research.

“I am a card-carrying drug developer. I have been closely involved in bringing three drugs to market for metastatic breast cancer. But what I learned early is that these drugs only prolong the inevitable, and if we really want to make a difference, we must come up with strategies for prevention—both primary prevention and secondary prevention, that is, after a tumor is diagnosed and treated.” With that finely tuned perspective and sense of purpose, she is leading a superb team. They include Konstantin Dragnev, MD, associate director for clinical trials, Sean Hobson, director of research operations, and a cadre of research nurses and clinical trial coordinators. Top priorities are smoothing access to trials for patients seen at our outreach locations, more rapid throughput for permission to open studies, and, always – more trials to meet our goal of at least one trial available to each patient. Dartmouth Cancer Center features cooperative group trials, industry-sponsored trials, and investigatorinitiated trials testing drugs and treatment strategies developed in the Dartmouth academic ecosystem. Trials for patients range from those at the very beginning of the continuum of drug development, called Phase One, that test for toxicity to Phase Four studies providing crucial information about dosing. And, there are trials for cancer survivors that study the best strategies for improving quality of life after treatment ends. Though many people bounce back after treatment, for others it can be a struggle to feel like themselves again.

Lancaster

St. Johnsbury Littleton

Plymouth

Lebanon

White River Junction

Claremont New London

Springfield

Manchester Keene Bennington Brattleboro

Nashua

Peterborough

Dartmouth Cancer Center provides cancer care services through a network of affiliate and outreach sites. Affiliates, denoted by the starred locations in the map above, utilize Dartmouth Cancer Center providers and staff to see patients and provide treatment. Care at outreach sites, denoted by squares on the map, is delivered through a collaboration between Dartmouth Cancer Center providers and local care teams who provide treatment closer to home.

Normalizing Efforts to Enhance

Diverstity, Equity, Inclusion, and Belonging (DEIB) 30

Pamela Rosato, PhD, trained as a virologist and immunologist at Dartmouth and we were fortunate to recruit her back as a principal investigator. Dr. Rosato and lab members, including Jordan Isaacs (PhD candidate) and Alexander Stanford ’24, an E.E. Just Fellow, prominently post their lab values, which challenge them to continuously listen, learn, and be a force for positive change against racism and discrimination.

A core improvement in our activist approach to DEIB is the Cancer Center’s DEIB Roundtable. Launched in 2020, the initiative is currently led by Erick Lansigan, MD, Dartmouth Cancer Center’s associate director of diversity, equity, inclusion, and belonging. In the collegial atmosphere of the DEIB Roundtable, we challenge our previously sustained efforts in diversity, equity, and inclusion.

Now, we focus on information gathering and base plans for actionable strategies on quantitative and qualitative data. In an open process, all faculty and staff are invited to the DEIB Roundtable, which meets frequently to assess efforts, identify areas for improvement, and brainstorm ideas for change. Recruiting and retention have been the primary focus, with new practices yielding measurable results in more diverse pools of talent, improved communication about diversity, and successful hiring of candidates. Related work to ensure attention to best DEIB practices in all

Dartmouth Health clinics is underway systemwide. The DEIB Roundtable serves as the connecting entity for DEIB work in concert with our parent institutions, Geisel School of Medicine and Dartmouth Health. We are very proud of the fact that the Dartmouth Cancer Center has moved quickly to prioritize inclusivity and implement new DEIB strategies. The goal is to make consideration of DEIB normative. For example, we find requiring candidates to submit DEIB statements with their application materials provides candidates and committees the opportunity to talk about diversity, equity, and inclusion related to their professional experience and our Cancer Center. There is no litmus test or “right” answer; for each candidate the DEIB statement is driven by their lived experience, values, goals and plans. In this highly competitive hiring environment, candidates have appreciated our consideration of how they have contributed to improving their workplaces.

National Support for DEIB The National Cancer Institute (NCI) of the National Institutes of Health (NIH) has prioritized efforts in increasing diversity in the pipeline of future cancer scientists and clinicians and made funding available for targeted training programs. Dartmouth Cancer Center was awarded a five-year NCI grant for the Program for Oncology Workforce Education and Research Experience at Dartmouth (POWERED). The rolling two-year program will train undergraduates from NIH-specified underrepresented minority groups for careers in cancer research. Each student is matched with a mentor and joins that lab for more than 500 hours per year of research experience and training in best practices. The “Plus” program expanded POWERED to include five students from HBCUs. Summers at Dartmouth are followed by September-May at their home institutions in class and working 10 hours a week on a cancer-related research project. One of the Plus students won second prize for their work at the 2023 NH-INBRE annual meeting.

Historically, women have made up less than 50 percent of science faculty in the U.S. This is true at Dartmouth Cancer Center, where one-third of our membership identifies as female. Female representation is trending upward, with our training programs typically more than half female. For example, in the 2021 academic year, 819 students were enrolled in the Guarini Arts & Sciences school at Dartmouth, with 401 identifying as female. Participation in a formal training program at Dartmouth Cancer Center is just the beginning for our trainees. Faculty mentors and training programs begin by finding and recruiting talent. They then follow trainees along the career development path to assist in identifying opportunities in residencies, fellowships, and faculty positions.

For generations, the concept of the “Dartmouth Family” has lifted and sustained thousands of graduates who have the lifelong advantage of connection to our ideally sized institution that takes career development as a responsibility.

Community Outreach and Engagement

The Community Outreach and Engagement (COE) initiative was established to better understand the cancer burden in New Hampshire and in Vermont and the healthcare needs of these communities, especially among rural and underserved populations, and to broaden the public participation in the care and services provided by the Cancer Center by identifying and addressing issues affecting the well-being of the communities in our catchment area.

Our outreach and engagement efforts are targeted at helping our community members become more informed and able to actively influence healthcare delivery. We gain community input through several community advisory boards that meet regularly to review our work, contribute to our efforts, and to serve as a mechanism to provide information back to communities.

Through bi-directional engagement, the COE serves as a bridge between our researchers and communities to improve the health of individuals and populations through research, engagement, and outreach activities. Our initiatives include disseminating information about new discoveries and knowledge at the community level. By collaborating with key stakeholders, community members, and Cancer Center researchers, we seek to understand the unique challenges within the catchment area in regard to cancer risks, treatment, and survivorship; to provide an opportunity for bidirectional information sharing; and to encourage our scientists to structure their research around issues that are important to the communities that we serve.

Reducing the Risk of Radon in Homes An example of our work is our concern about the health risk of radon in the home environment, because radon is the second-leading cause of lung cancer. Living in a home with high radon levels increases the risk of developing lung cancer. Radon is present in the ground and gets into buildings through the foundation. Because of the region’s geology, radon is more prevalent in our area. In fact, one in three homes in New Hampshire and one in seven homes in Vermont have radon levels that are too high. About 150 residents of our two states die annually from radon exposure.

To address this health issue, through research, we are developing and testing a web-based educational tool to encourage community members to test their home air for radon. The educational tool will be designed with input from local community members and community partners—including environmental health experts, local clinicians, medical students, real estate professionals, and others. Outreach with the tool will take place initially online and in community settings, with plans to expand into healthcare settings. Working with New Hampshire and Vermont’s state health departments, we will link community members to free radon testing kits provided by the states.

Zone 1 (red zones): Highest potential; average indoor radon levels may be greater than 4 pCi/L (picocuries per liter) Zone 2 (orange zones): Moderate potential; average indoor radon levels may be between 2 and 4 pCi/L Zone 3 (yellow zones): Low potential; average indoor radon levels may be less than 2 pCi/L Source: United States Environmental Protection Agency (EPA)

Radon can enter any home. This image shows a few ways. Source: United States Environmental Protection Agency (EPA) 33

Cancer Research

Training & Education Coordination (CRTEC)

The strategic vision for training in cancer research at Dartmouth Cancer Center is customized research-focused programs providing learners with hands-on mentored experience in science.

Our signature education and training programs range from introducing cancer science to high-school students to embedded training in cancer laboratories for undergraduates through doctoral trainees. At the post-doctoral level, career development continues well into mid-career for faculty to facilitate scientific communication and access to resources, including external funding. Aid in expanding one’s scientific scope is often the focus of clinicians transitioning to the role of

Geisel students Kristian Sogaard, Anne Dionne, Shannon Robins, and Soham Kale were selected for their promise as future physician scientists in cancer and participated in TOPS, the six-week Translational Oncology Program for Scholars. They were embedded in clinical oncology groups to accelerate their understanding of what being 34 a physician scientist is like on a daily basis.

a clinician-investigator, and our signature Cancer Faculty Fellows (CFF) program facilitates the transition. CRTEC also actively supports and coordinates with other programs that have impact on cancer training and education. In collaboration with Geisel’s Center for Program Design and Evaluation, CRTEC regularly receives mixed methods data about ongoing training for learners, consults with evaluation professionals, and prioritizes formative assessment for ongoing program improvement. Key metrics for pre-docs are underrepresented minority (URM) status and program(s) joined; a key metric for outcomes is the change in likelihood to pursue a career in cancer. To prepare investigators to lead research into complex

Associate Director of Diversity, Equity, Inclusion, and Belonging Erick lansigan, MD, with POWERED students at Dartmouth Cancer Center. Each of the ten POWERED undergraduates has a 1:1 relationship with a scientific mentor, and their labs are the scientific homes for the students for two years as the students develop as research scientists.

Signature CRTEC Programs •

The Dartmouth Cancer Faculty Fellows program supports clinicians’ transition to independence as clinical investigators.

•

The National Cancer Institute-funded Program for Oncology Workforce Education and Research Experience at Dartmouth (POWERED) is increasing the number of undergraduates from underrepresented minorities preparing for careers in cancer research.

contemporary questions in cancer science, we offer Leadership Optimization to Generate Interdisciplinary cancer science (LOGICS), an online resource of learning opportunities organized in 12 key capabilities related to General Science and Cancer Science. Dartmouth learners at every level are encouraged to collaborate with their mentors to create a customized individual development plan (known also as an IDP) and utilize LOGICS learning opportunities in a personalized manner to increase their skills in key capabilities including leadership, data analytics, immunology, and cancer clinical research.

•

The Dartmouth Cancer Scholars program gathers cancer-focused undergraduates to learn about the breadth of cancer while creating a community of highperforming future cancer professionals.

•

The Translational Oncology Program for Scholars program, funded by a Geisel endowment, allows Geisel students to take a deep dive into translational cancer research.

•

The Cancer Biology doctoral program trains PhD students for careers in cancer.

and convergence research will become increasingly embedded in other Dartmouth Cancer Center cancer research training, education, and career development programs.

With philanthropy, CRTEC is increasing the availability of funding for individual trainee research projects. Additionally, we focus on renewing external funding for training programs and seeking new grants to support opportunities for more learners.

Looking forward, the LOGICS framework of key capabilities and learning opportunities emphasizing skills needed for interdisciplinary, transdisciplinary,

Graduating with a PhD is a momentous occasion capping more than five years of training. Here, new PhD Brooke Brauer (left), savors her last day with other trainees Galini Poimenidou and Hieu Nguyen, and talks with principal investigator and their mentor Arminja Kettenbach, PhD, while brainstorming future collaborations.

Psychologist Courtney Stevens, PhD, trained at Dartmouth using many of the CRTEC resources, including CAREER to analyze her aims page and FAST TRACK to learn best practices for identifying the “what” and “how” of designing a customized plan for her ultimately successful training grant proposals. 35

Measurement &

Accountability

Christian Lytle, MS (left) coordinates operations at Dartmouth Cancer Center’s eight shared resources, including the busy Single Cell Genomics Core, led by Fred W. Kolling, PhD (right).

A live cell visualization of the spindle-like structure that segregates chromosomes during cell division with microtubule structures illuminated in green with a subsection selectively labeled in magenta. Photo by Melissa Parks using a spinning disc confocal microscope at 1000X magnification available to all in a shared resource.

Metrics and Evaluation Systems Based on the highest standards and comparison to the best in the nation, the National Cancer Institute named Dartmouth Cancer Center a “designated comprehensive cancer center,” the ultimate ranking for cancer centers. The Cancer Center has held that designation since 1990. NCI reviews the progress of our Center extensively every five years; 2024 is a review year. We have systems to track and measure progress and accountability in all strategic priority areas. They include this representative sample of methods: To track learners and their progress toward careers in cancer, we use the proprietary TRACE system to monitor learning engagement at Dartmouth Cancer Center and career milestones for more than 1,000 trainees, ranging from undergraduates to early-career faculty. Valuable information includes cohort demographics, trainees’ publications, competitive grant funding awarded, and professional status in cancer-related fields. System integration is monitored for the clinical enterprise across two states and evaluated within a Dartmouth Health paradigm that tracks goals, strategies, and tactics. Valuable information tracked includes monthly progress toward goals such as new clinical trials opened and patient satisfaction. Clinical trials, at the nexus of science and medicine, are monitored closely by professional surveillance systems, including Advarra Oncore and Forte eRegulatory, which produce data for metrics such as time to activation, data accuracy, and participants screened, consented, and accrued.

Scientific publications and presentations derived from Dartmouth Cancer Center members are surveilled with systems including PubMed, Web of Science, and Scopus. Data are tracked to monitor key metrics of inter- and intra-programmatic publications, individual and group achievement, and the impact of publications. Eight shared resources or “cores” are supported by Dartmouth Cancer Center’s P30 core grant from the National Cancer Institute. They provide high-end technology and expertise in a shared format to ensure the best use of resources. The practice of sharing core resources extends among other cancer centers to ensure national access to the best knowledge and equipment. No cancer center can have everything. Highend equipment needs constant monitoring to keep it tuned to top specifications, and usage data is critical to bolster proposals for support of equipment upgrades. Our cores are Biostatistics and Bioinformatics, Clinical Pharmacology, Genomics and Molecular Biology, Immune Monitoring and Flow Cytometry, Irradiation Pre-clinical Imaging and Microscopy, Mouse Modeling, Pathology, and Trace Element Analysis. Together, they processed 252,760 test (sample units) in 2022 and charged more than $3 million in at-cost fees for services rendered. These review processes are valuable and stringent, yet are surpassed in gravity by annual meetings with our External Scientific Advisory Board, made up of more than a dozen subject matter experts from top cancer centers in the U.S. Our annual two-day meeting with them leverages their collective experience to put our performance in context and hold us to the highest standards.

Jiwon Lee, PhD, with doctoral student Nick Curtis (left) and post-doctoral trainee Seungmin Shin (right), improved their tactics for commercializing a next-generation antibody engineering technology platform during the DIAC 10-week training and ultimately won Quinn Scholar Awards and the Stu Trembly Award for a total of $130,000 to advance their innovation.

Philanthropy The Dartmouth Cancer Center is the top philanthropic priority shared by Dartmouth College and Dartmouth Health. For over 50 years, the Dartmouth Cancer Center has been powered by the philanthropic and volunteer support of many friends and neighbors throughout our growing community. Most recently, Dartmouth Cancer Center has seen record-breaking fundraising years despite a pandemic and market downturn. A strategic focus on key priorities and collaborative team effort has raised our sights and our prospective donors’ sights about what is possible in the coming years. The combined leadership across the academic medical center along with alumni, patients, and community members has never been more cohesive and productive. At the launch of its Call to Lead Campaign, Dartmouth College announced the Cancer Center as one of its “Big Bets on Discovery.”

In the final stretch of this campaign, a landmark $25 million gift from local philanthropist Dorothy Byrne established the Byrne Family Cancer Research Institute and challenged the community to raise an additional $25 million in investment. Building on foundations of excellence, the Byrne Family Cancer Research Institute is amplifying dollars and discoveries in three key areas: Next-Generation Immunotherapy, Precision Cancer Prevention, and innovation through the Dartmouth Innovations Accelerator for Cancer. A partnership with the Magnuson Center for Entrepreneurship at Dartmouth College, the Accelerator has provided a particularly enticing engagement opportunity for alumni and friends to lend their professional expertise, personal networks, and financial support to bring Dartmouth discoveries to the world.

Dartmouth Cancer Center Director Steven Leach and Dartmouth President Sian Beilock at the 42nd annual Prouty on July 15, 2023, which raised a record-breaking $7.8 million to support life-saving research and patient support services at Dartmouth Cancer Center.

Named professorships and direct research support continue to be fundraising priorities and provide opportunities for the recruitment and retention of top talent. Donors to these endowment and current-use funds enjoy getting to know the beneficiaries and seeing the direct impact of their support.

rowing, golfing, and walking extravaganza with over 3,500 participants and 750 volunteers. The Friends also offers friendsfightingcancer.org, which provides a platform for third-party events and crowd-fundraising activities to make it easy for anyone who wants to create an activity to support the Cancer Center.

Our community is everything—from Lebanon to Manchester to Nashua to St. Johnsbury and beyond. Through the Friends of Dartmouth Cancer Center, we raise substantial funds for pivotal pilot research and patient and family services.

We are caring for our community and creating knowledge for the world. Our patients receive the most advanced, compassionate care and benefit from discoveries that will help all of us overcome cancer. We welcome all to join us in our efforts and thank every donor for their dedication to our mission.

The patient and family services offered through the Complementary Care Program are 100% funded through philanthropy. For over 40 years, the Friends of Dartmouth Cancer Center has hosted the annual Prouty—a cycling,

The annual Prouty is a highlight of the year where participants and volunteers from the region, and beyond, unite to raise funds for Dartmouth Cancer Center.

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