A Year in Review/A Look to the Future 2011

Bold New Options Pioneering the Next Generation of Cancer Care

OUR MISSION To advance knowledge and to rapidly translate discovery into exceptional cancer care.

OUR VISION As a cornerstone of Massachusetts General Hospital, a world-leading academic medical center, we will bridge scientific discovery and clinical care to conquer cancer. We will set the standard for excellence in personalized care for patients and their families.

Noopur Raje, MD, Director, Center for Multiple Myeloma with patient

TABLE OF CONTENTS

Shahin Tabatabaei, MD, urologic surgeon

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From the Director

3 Celebrating the Old and the New This year marks Massachusetts General Hospital’s bicentennial and the opening of a new building.

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Basic Science Genetically engineered mouse models facilitate development of safer, more effective cancer therapies.

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From Bench to Bedside Cutting-edge therapies provide hope for patients with advanced melanoma.

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New Programs and Initiatives New center speeds translation of scientific understanding to patient treatments.

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Serving our Community Social, educational and philanthropic events improve the lives of cancer patients and their families.

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Growing the Future of Cancer Care Celebrating the Future of Mass General Cancer Center and the individuals who are making it happen.

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Centerpieces Awards, achievements and prime-time television series showcase the compassion and expertise of Mass General Cancer Center clinicians.

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A Year in Review: By the Numbers Facts-at-a-glance demonstrate how we serve the cancer community.

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Looking Forward

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FROM THE DIRECTOR

CANCER CENTER LEADERSHIP

Daniel A. Haber, MD, PhD Director, Cancer Center

José Baselga MD, PhD Chief, Division of Hematology Oncology Associate Director, Cancer Center

David P. Ryan, MD Clinical Director, Cancer Center

Mara G. Bloom, JD Executive Director, Cancer Center

Bruce A. Chabner, MD Director of Clinical Research, Cancer Center

Jay S. Loeffler, MD Chief, Radiation Oncology

Sally Mason Boemer Senior Vice President, Cancer Center

Debra A. Burke, RN Associate Chief Nurse, Cancer Center

Kenneth K. Tanabe, MD Chief, Surgical Oncology

Howard J. Weinstein, MD Chief, Division of Pediatric Hematology Oncology MassGeneral Hospital for Children

Dear Friends, Over the past year, our understanding of what causes cancer improved dramatically. Progress occurred hand-in-hand with development of bold, new diagnostic and treatment approaches now being offered to patients. These breakthroughs took place in a challenging economic climate, where success depends on early support of the discoveries most likely to translate into safe, effective clinical care. At the Massachusetts General Hospital Cancer Center, our ability to remain at the forefront of advances in cancer treatment is rooted in our capacity to envision and plan for future generations of cancer therapies. This effort extends from our basic science laboratories to our clinical research teams and on to the Cancer Center leadership. We focus our recruitment, research and program development efforts on the single goal of improving care for cancer patients. Much of our progress occurs out of the public eye; this issue of Synergy highlights those advances. But we have one very visible sign of progress: The Lunder Building, scheduled to open this summer. This building, with its two floors devoted to the needs of cancer patients and their families, will enable our multidisciplinary care teams to deliver the most innovative, personalized care in a specially designed, high-tech facility. I hope you will enjoy learning about other advances in these pages. Over the past year, we have made headway in understanding the cellular changes that lead to cancer and launched studies of dual-targeted therapies that disable two cancer-causing pathways. These studies move us closer to overcoming the treatment resistance that invariably occurs with single-targeted agents. We have initiated trials combining different types of therapy, potentially adding power to one of the most significant breakthroughs in advanced melanoma, the BRAF inhibitors. Coupled with these stories are examples of ways in which we have enhanced technology for detecting cancer, developed methods for matching a patient’s tumor to the drug most likely to shrink it, offered promising new drugs and innovative surgical approaches to patients in need, and improved the lives of cancer survivors. This momentum would not have been possible without your generous support. Thanks to you, we are advancing confidently toward our vision of bridging scientific discovery and clinical care to conquer cancer and setting the standard for excellence in personalized care. We hope you enjoy this issue of Synergy.

Daniel A. Haber, MD, PhD Director, Cancer Center

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Celebrating the Old and the New This year marks the Massachusetts General Hospital bicentennial. For the past two centuries, Mass General has been a leader in health care innovation, in groundbreaking research, and in forging deep connections with the community. Another milestone will be celebrated this year as well: The opening of the state-of-the-art Lunder Building this summer. The ninth and tenth floors of the building were designed specifically for cancer patients, integrating features to improve patient comfort and care. Each floor contains spacious, private patient rooms, family/multipurpose consult rooms, a comfortable family lounge, and an infusion suite. A central pathway bisects the floor, providing natural light and a view of the atrium. While each patient floor has a similar layout, specific features have been incorporated on individual floors to accommodate particular care needs. For example, specialized air handling on the tenth floor helps minimize the risk of infection for bone marrow transplant and other patients. Lunder 10 will also include a satellite pharmacy to provide chemotherapy production for inpatients. Other architectural and technological features will facilitate communication among multidisciplinary care teams. ●

Above: A Lunder Building patient room, top, and an exterior hallway looking out on the atrium. Left, a state-of-the-art operating room.

Mass General’s proud past and exciting future are demonstrated in the architecture of the new Lunder Building, left, and the 188-year-old Bulfinch Building.

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BASIC SCIENCE

Of Mice and Medicine Genetically engineered mouse models create new understanding of how cancer develops and progresses

Developing new targeted cancer therapies depends on a precise understanding of how cancer cells differ from normal cells. Some of this knowledge derives from comparisons of cancer cells and healthy human cells in a test tube, but cancer is a disease of whole organisms. To truly understand how cancer cells escape the body’s normal growth control mechanisms – leading to primary human tumors or cancer metastases – scientists in the Center for Cancer Research at the Massachusetts General Hospital Cancer Center generate and study carefully defined laboratory models, including genetically engineered mouse strains that replicate some or all of the processes leading to human cancer.

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BASIC SCIENCE

Recent Mass General Cancer Center studies using genetically engineered “transgenic” mice have produced important new insights into the origins of pancreatic, colon, liver and kidney cancer. These studies have revealed potential new directions for cancer therapy, explained why one promising drug failed in a phase II “We created the Jacqueline clinical trial, and have Saldana Pancreatic Cancer suggested a new strategy for advancing the field of stem Research Fund to support cell therapy. “Transgenic mouse strains Dr. Bardeesy’s research provide extremely important because we believe he is on tools for cancer research,” the right track to find a cure.” says Daniel Haber, MD, PhD, director of the Mass General — Jacqueline Saldana, cancer survivor Cancer Center. “When a genetic study in humans reveals that changes, or mutations, in a particular gene are associated with a certain type of cancer, we can produce mouse strains that carry the same genetic changes. If these genetic changes also cause cancer in the mice, we have the opportunity to conduct experiments to identify Left to right, Jacqueline Saldana, Nabeel Bardeesy, PhD, the gene’s function and Senior Development Director Kelly Clark and Jaime Vazquez determine how its protein product interacts with other substances in the cell. For example, is the protein part of a growthpromoting pathway or does it typically act to suppress abnormal growth?”

Haber explains that such information is vital to developing new therapies. If a mutation causes overactivity of a growth-promoting gene, then a relevant transgenic mouse strain could provide a resource for testing drugs that block that overactivity. Conversely, if a mutation disables a pathway responsible for suppressing abnormal growth, a relevant mouse model could provide insights into alternative ways of achieving the same result. These experiments provide answers to questions that could not be addressed in any other way.

Early Detection in Pancreatic Cancer Work by Nabeel Bardeesy, PhD, in pancreatic cancer provides a good example. Although scientists have identified a set of gene mutations that are often present in pancreatic ductal adenocarcinoma (PDAC) – one of the most lethal forms of cancer – these discoveries have done little to improve the efficacy of treatment. Bardeesy is developing separate mouse strains carrying all of the different genetic variations implicated in PDAC to characterize how each mutation is involved in the initiation and development of the disease. These mouse models are helping Bardeesy determine which gene mutations are significant drivers of pancreatic cancer, and thus important targets for new therapies, and which are simply bystander mutations. The models also provide important information about potential responses to therapy. For example, a pancreatic tumor with a mutation in a growth-promoting RAS gene may respond to a particular type of therapy, while a tumor that contains a RAS mutation plus some other mutation may not. Such information ultimately will lead to a broader range of targeted drugs for pancreatic cancer. ➤

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Left to right, Rushika Perera, PhD, Julien Fitamant, PhD, and Nabeel Bardeesy, PhD, of the Bardeesy Lab

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BASIC SCIENCE

“Without the funding I received from private foundations, my research could not have happened. Young investigators rely on donors to help them establish labs and produce the results that will qualify them for grants.” — Raul Mostoslavsky, MD, PhD

Andrea McClatchey, PhD, and her colleagues uncovered the role of a novel gene in kidney and liver cancer.

Bardeesy’s investigations with transgenic mice also are providing a foundation for blood tests and imaging studies that will enable physicians to detect human pancreatic cancer earlier, when it might be more responsive to therapy, as well as to track recurrences of the disease. Additionally, Bardeesy is studying the behavior of cancer stem cells in pancreatic cancer. While these cells represent only a small fraction of the total tumor burden, they are notoriously resistant to both traditional chemotherapy and targeted drugs. Recently, Bardeesy developed a method that appears to convert pancreatic cancer stem cells into cells that are sensitive to chemotherapy, providing another possible route for gaining traction in the battle against this devastating disease.

The Right Targets in Colon Cancer

The Haigis lab explores gene variations that help hone targeted therapies for colon cancer.

Kevin Haigis, PhD, of the Center for Cancer Research at the Mass General Cancer Center, uses mouse models to explore why certain promising drugs have failed to produce positive results in colon cancer therapy, and to identify new treatment strategies that might be more effective.   Haigis’ lab focuses on the RAS family of proteins, which are involved in transmitting growth-promoting signals from outside a cell to the cell nucleus. Mutations in certain RAS genes can produce abnormal protein products that

prompt the cells to engage in growth-promoting behavior even in the absence of external signals. These mutations cause unregulated growth. RAS mutations are common in many different types of human cancer.   The Haigis laboratory has used mouse models with mutations in different RAS genes to explore how RAS proteins interact in normal and abnormal cells. The results have produced new insights into the origins of colon cancer. For example, showing that a particular growth-related pathway involving the protein KRAS is important in embryonic development of the colon, but not in the development of colon cancer. These findings explained why a particular drug failed to help colon cancer patients – it was targeting the wrong RAS pathway – and led to important insights about how to target the right pathway.

New Uses for Existing Drugs in Liver and Kidney Cancer Research in the laboratory of Andrea McClatchey, PhD, of the Center for Cancer Research at the Mass General Cancer Center, demonstrates how studies of mouse models sometimes produce surprising results. McClatchey developed a mouse strain with a liver-specific mutation in the neurofibromatosis type 2 (NF2) gene with the goal of understanding how the protein product of the NF2 gene, called Merlin, functions as a tumor suppressor. Much to her surprise, the mice in her study developed both of the two most common types of liver cancer, hepatocellular carcinoma and cholangiocarcinoma. These results were unexpected, especially given the historical difficulty of creating genetically defined mouse models of liver cancer. In fact, McClatchey’s work represented the first demonstration that a single gene mutation could produce both major forms of liver cancer. She also demonstrated that disruption of the NF2 gene in the mouse kidney could cause kidney cancer.  

The loss of Merlin in these NF2-mutant mice led to overactivity of a protein called epidermal growth factor receptor (EGFR). Improper regulation of EGFRs had been observed in numerous cancers, but never before connected with disruption of the NF2 gene. Targeted drugs that block mutant EGFRs have been shown to prolong the lives of patients with a variety of different EGFR gene mutations.   McClatchey’s work suggested that these drugs also might be effective in liver and kidney cancer in the absence of EGFR mutations. She is pursuing this line of reasoning in her mouse models; the results could lead to new applications of the drug erlotinib and related compounds in human cancer therapy. McClatchey also is trying to learn more about the mechanisms through which Merlin affects EGFR activity. In the liver cancer mouse model, she discovered that loss of Merlin function can cause overproduction of immature liver progenitor cells. Previous studies have shown that abnormal proliferation of these cells can cause liver cancer. One clue to the mechanisms involved may be that the Merlin protein generally resides on the cell surface where cells come into contact with other cells. McClatchey suspects that in normal adult tissues, Merlin may play a role in preventing improper cell division and related EGFR activity associated with cell-to-cell communication.

Cell Metabolism and Cancer Raul Mostoslavsky, MD, PhD, of the Center for Cancer Research at the Mass General Cancer Center, studies mouse models that lack a protein called SIRT6, which is known to play a role in switching off, or silencing, the expression of other genes. Initially, his goal was to learn more about the impact of SIRT6 on normal cell growth and metabolism. In fact, when he began his studies of SIRT6, he was not focused on cancer. His focus broadened, however, when he began thinking about the results of his mouse experiments in the context of research studies conducted by Nobel Laureate Otto Warburg at the beginning of the 20th century.   ➤

Raul Mostoslavsky, MD, PhD, explores the mechanics of cell respiration to understand how gene mutations lock cells in an environment conducive to growth.

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BASIC SCIENCE

SIRT6-deficient mice appear relatively normal at birth, but they die of severe hypoglycemia – very low blood sugar – within four weeks. Mostoslavsky determined that these mice die because their cells are unable to switch back and forth between the two major forms of energy metabolism utilized by mammalian cells. The most efficient way for mammalian cells to produce energy is to burn sugar in the presence of oxygen (aerobic glycolysis), a process known as mitochondrial respiration. However, when oxygen is scarce normal cells can switch to a back-up or survival mechanism called anaerobic glycolysis. Anaerobic glycolysis generates less ATP, the cell’s energy For investigators at the Center currency, than mitochondrial respiration and causes a build-up for Cancer Research and other of lactate (Lactate build-up is responsible for the muscle leading medical research soreness associated with prolonged centers, mouse models exercise). Mostoslavsky discovered provide a vital bridge between that his transgenic mice died because, in the absence of SIRT6, new concepts in biomedical they could not switch from glycolysis back to respiration. research and applications. These findings led Mostoslavsky to recall the work of Warburg, who almost 90 years ago reported that cancer cells, unlike healthy cells, appeared to prefer anaerobic to aerobic glycolysis. Mostoslavsky hypothesized that mutations in the SIRT6 gene may create an environment conducive to tumor growth. In future studies utilizing the SIRT6 mutant mice, he will explore whether drugs capable of re-activating a mutant SIRT6 gene might inhibit cancerous growth by enabling cells to regain normal metabolic functions.

Innovations in Stem Cell Research Transgenic mice also are proving to be vital tools for the development of the new field of stem cell therapy. Scientists believe that stem cells – cells that have the capacity to develop into any cell type in the body – may hold great promise for treating a host of human diseases, including cancer. However, the development of stem cell therapies has been slowed by the technical challenges of controlling tissue-specific differentiation and by controversies over the use of embryonic stem cells (ESCs) derived from very early embryos.   One strategy for overcoming the ESC controversy has been to explore the use of potential alternatives. Induced pluripotent stem cells (iPSCs) are adult cells that have been returned to a stem cell-like state through exposure to a small number of specific gene products. Many questions remain, however, about whether iPSCs will have the same therapeutic potential and safety profile as ESCs.   Konrad Hochedlinger, PhD, of the Center for Cancer Research at the Mass General Cancer Center and the Harvard University Department of Stem Cell and Regenerative Biology, is conducting pioneering studies to answer these questions. He and his colleagues have developed genetically matched mouse strains derived from ESCs and iPSCs. Studies of these matched strains have revealed differences in DNA structure that affect pre- and post-natal development. Understanding the reasons for these differences and how they might affect the long-term viability of tissues derived from iPSCs will be crucial to the future of this important new field. Transgenic mouse models enable researchers to study unexpected outcomes from clinical trials and to assess the impact of new discoveries from human genetics. For investigators at the Center for Cancer Research and other leading medical research centers, mouse models provide a vital bridge between new concepts in biomedical research and applications. ●

CENTERPIECES

Konrad Hochedlinger, PhD, studies the viability of modified adult stem cells as an alternative to embryonic stem cells in therapies.

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Back to Life

Collaborations speed new treatments to clinics and patients back to their daily lives

PHOTO: Carol Dragon ©2010

Broadway producer Debra Black was diagnosed with stage II melanoma more than four years ago. Although her treatment was physically and emotionally difficult, she counts herself as one of the lucky ones because her disease was treatable. Historically, most patients with advanced-stage melanoma face a grim prognosis. Today, however, a targeted therapy called PLX4032 is extending the lives of patients battling this disease.

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“I feel lucky every single day,” says stage II melanoma survivor Debra Black, shown here with her family.

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Breakthroughs in Melanoma Treatment

Donald Lawrence, MD, left, and Keith Flaherty, MD

Approximately half of all patients with advanced melanoma have a mutation in the BRAF gene, which produces a protein vital to normal cell growth. This mutation is acquired or spontaneous, not inherited, and is present only in cancerous cells. Ordinarily the gene switches on and off in response to the body’s needs but, when mutated, the gene is permanently on, over-producing a protein that leads to unchecked cell growth. PLX4032 attaches to the defective protein, stopping its destructive behavior. Two clinical trials of the drug by Keith Flaherty, MD, director of developmental therapeutics for the Massachusetts General Hospital Cancer Center, produced astounding results: More than half of the patients receiving the medication experienced a shrinkage or disappearance of their tumors. Patients lived an average of seven months without progression of their disease, a phenomenal extension in a group of patients who experience, on average, only a two-month reprieve with chemotherapy. “This response is gratifying,” says Flaherty, “especially when you consider that as many as 90 percent of patients with this mutation have a positive response early in their treatment, and that traditional chemotherapies gave us only a 10 percent response. But there is still work to be done.” Flaherty and other melanoma specialists at the Mass General Cancer Center are probing the same questions that face clinical researchers investigating other targeted therapies: What’s different in the patients who have the mutation but do not respond to PLX4032? How can doctors know up front who will respond, so they can direct them to the right treatment? And what about the patients with advanced melanoma and no BRAF mutation?

For Flaherty, ongoing work to answer these questions includes a next generation clinical trial that combines a BRAF inhibitor with another drug that blocks a different component of the same pathway. This approach has been validated in human melanoma cells in the laboratory and is now being offered to patients with advanced melanoma at the Mass General Cancer Center and other locations. Flaherty is also readying a clinical trial of a BRAF inhibitor and an inhibitor of a secondary pathway believed important in melanoma. “These types of combinations,” he says, “will potentially help responses last longer.” Mass General Surgical Oncologist Jennifer Wargo, MD, is taking a different approach against BRAF-mutated melanomas, proposing to unite targeted agents with immunotherapy. Immunotherapy has, for the past decades, been the most effective weapon in the anti-melanoma arsenal. It works by revving up immune cells, called T cells, to fight the disease. One FDA-approved form of immunotherapy for metastatic melanoma, interleukin-2 (IL2), leads to a complete regression of disease in eight percent of patients. In another 15 percent of patients, IL2 causes some shrinkage or disappearance of disease. A second form of immunotherapy available to Mass General Cancer Center patients through clinical trials, ipilimumab, has been recently approved by the FDA for use in patients with advanced melanoma because of its ability to produce long-lasting responses. In conjunction with Mass General Cancer Center colleagues, Wargo has performed pre-clinical studies that provide solid evidence that combining BRAF-targeted therapy and immunotherapy may significantly improve responses. “The BRAF mutation appears to allow melanomas to essentially hide from the immune system,” she says. “Our work shows that BRAF inhibitors improve the ability of T cells to recognize and kill melanoma cells.” Her proposal to combine PLX4032 with immunotherapy, either ipilimumab or IL2, is intended to merge

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the benefits of both therapeutic approaches, increasing the likelihood of permanent disease regression in patients with BRAF mutations. The excitement over BRAF inhibitors extends beyond melanoma. Because BRAF mutations are present in other cancers, clinical researchers at the Mass General Cancer Center are extending knowledge of BRAF-inhibitors to patients with cancers other than melanoma. “The idea is that we can treat cancer based on its genetic fingerprint no matter where it originally arose,” says Donald Lawrence, MD, clinical director of the Mass General Cancer Center Melanoma Program. Lawrence is leading a multi-center clinical trial using BRAF-inhibitors in patients with lung, colon, thyroid, ovarian or other cancers that are positive for the BRAF mutation. Targeted therapies are also being combined with the other standard melanoma treatment approaches, surgery and radiation, to improve care at all stages of disease. Kenneth Tanabe, MD, chief of the Division of Surgical Oncology and deputy clinical director of the Mass General Cancer Center, says that “It will be interesting to see if these agents are beneficial in increasing the number of patients who are cured with surgery,” the first line of defense for melanoma. Mutation status, along with other microscopic features of tumors, also helps multidisciplinary teams determine how aggressively a tumor needs to be treated. Characteristics associated with low rates of metastasis or better outcomes, for example, could tell surgeons that lesions can be safely removed with smaller margins between cancerous and healthy tissue, thus reducing scarring. These advances are exciting for people affected by melanoma as well as for doctors and researchers. They are particularly gratifying for Debra Black, whose diagnosis made her recognize the scarcity of effective treatments for advanced melanoma. In conjunction with her husband, Leon Black, she decided to accelerate progress toward a cure. Working with Michael Milken, who established the Prostate Cancer Foundation in 1993, and the Milken Institute, the Blacks founded

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the Melanoma Research Alliance (MRA). Since its inception in 2007, MRA has provided more than $22 million for research in melanoma prevention, diagnosis and treatment. Last year, MRA honored Flaherty; David Fisher, MD, PhD, chief of the Mass General Dermatology Service, director of the Melanoma Program in the Mass General Cancer Center, and director of the Cutaneous Biology Research Center; Hensin Tsao, MD, PhD, clinical director of the Mass General Melanoma and Pigmented Lesion Center, and director of the Mass General “Private donations help us Melanoma Genetics Program; and colleagues at other establish the necessary academic melanoma centers with a $2 million award, one of infrastructure to facilitate the largest grants given to date the study of common genetic by the MRA. The investigators will establish a consortium of mutations across different cancer centers that have led cancer types. This research clinical trials of PLX4032 to share information and conduct helps speed treatments studies aimed at overcoming to patients by translating resistance to BRAF targeted therapies and developing discoveries in one cancer to new melanoma treatments. another cancer.” Milken’s Prostate Cancer Foundation has contributed — Keith Flaherty, MD, Director, generously to cancer research Developmental Therapeutics at the Mass General Cancer Center, including the work of Matthew Smith, MD, PhD, director of the Genitourinary Malignancies Program. “BRAF inhibitors are a wonderful breakthrough, but the effect is temporary,” says Debra Black. “Studies like the ones underway at the Mass General Cancer Center are our greatest hope.” ●

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Adventure of a Lifetime Kim Lohnes knew her family had a high incidence of breast and ovarian cancer, so she was vigilant about keeping her semi-annual screening appointments. Nevertheless, when a routine vaginal ultrasound revealed enlarged ovaries that were most likely cancerous, she had difficulty thinking of herself as a cancer patient. “I looked healthy. I felt healthy,” she recalls. But subsequent testing revealed her cancer had already spread throughout her abdomen, so she consulted John Schorge, MD, FACS, director of gynecologic oncology at the Mass General Cancer Center, about the best way to combat her disease. Many surgeons are reluctant to operate on women with very advanced ovarian cancer because of the disease’s tendency to spread into areas where it is difficult to remove. But Schorge and his colleagues, who perform nearly 100 of these operations each year, suggest surgery as the first line of treatment because it gives patients the greatest chance of overcoming their John Schorge, MD, FACS disease. In addition, says Schorge, the world-class resources at Mass General are readily available to help patients recover. Lohnes signed on for the aggressive approach, undergoing an operation that removed her ovarian and abdominal tumors and lymph nodes. The procedure included placement of an intraperitoneal catheter for future chemotherapy administration. She also entered a clinical trial led by Mass General Cancer Center Oncologist Carolyn Krasner, MD, involving two drugs (carboplatin and paclitaxel) administered through the intraperitoneal catheter, in addition to intravenous administration of a third drug, bevacizumab. More than a year after finishing treatment, Lohnes is cancer free and off on the adventure of a lifetime. Her trip includes a safari in Serengeti National Park, relaxing on the beaches of Zanzibar, and five months of volunteer work in orphanages and health clinics in Africa. “I’ve wanted my whole life to go to Africa to help in whatever capacity I can,” says Lohnes, who has also volunteered in South Korea. “My cancer journey is what made me realize that every day is the perfect day to do the things you really want to do.” ●

After combating aggressive ovarian cancer, Kim Lohnes fulfilled a life-long dream of volunteering in Africa.

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One Pill Fights Ovarian Cancer For years, all women with advanced ovarian cancer received identical chemotherapy regimens. In many cases, the approach is very effective … for a while. But then, says Michael Birrer, MD, PhD, director of gynecologic medical oncology at the Massachusetts General Hospital Cancer Center, the tumor returns. Timing of the recurrence varies from one patient to another, and the tumors themselves look different under the microscope. Armed with this knowledge and recent advances in the understanding of the genetics of ovarian cancer, Birrer has made it his mission to uncover the reasons behind these differences so doctors can do a better job of matching tumor to treatment. More than 90 percent of ovarian cancers originate on the surface cells of the ovaries known as epithelial cells. Today, ovarian epithelial tumors are sub-typed as serous, endometrioid, mucinous, clear cell, or other, rarer forms of the disease; they are further classified as either low-grade or high-grade cancer. Low-grade tumors grow more slowly and tend to have a better prognosis than high-grade tumors. By categorizing ovarian cancers in this way, doctors now know that outcomes differ by tumor type and even within tumor type. Fifteen percent of women with malignant serous tumors, for example, don’t respond to the standard chemotherapy regimen at all. As scientists make headway in understanding the molecular differences that may explain this lack of response, Birrer applies this knowledge in clinical trials to help prolong the effectiveness of anti-cancer treatments. In one recent clinical trial, Birrer used a targeted drug that disables proteins causing uncontrolled cell growth in women with

low-grade ovarian tumors. The drug, he says, “is a single agent, it’s oral, easy to take, and it had a significant response rate.” As part of a second, multi-center trial, he is studying the effects of a different drug, usually used in gastrointestinal tumors, on mucinous tumors. The reason, he says, is that mucinous tumors, while very rare in the ovaries, are frequently seen in the gastrointestinal tract. Another area of interest involves the subset of women with serous tumors whose disease does not respond to traditional chemotherapies. Studies of ovaries removed prophylactically from women with BRCA1 or BRCA2 mutations reveal that serous tumors have a defect in the mechanisms used in cell repair. This discovery led to the use of a form of targeted therapy known as PARP inhibitors for ovarian cancers. Cells can function without PARP, a DNA repair enzyme, as long as other genes controlling the same process are functional. But cells with mutated BRCA1 or BRCA2 genes as well as non-functional PARP will die. At the Mass General Cancer Center and other locations, PARP inhibitors are available in clinical trials for women with BRCA1 or BRCA2-related ovarian cancers, and the response rate has been, according to Birrer, “remarkably high.” Specific figures will be released at the end of the trial. Interestingly, continues Birrer, “Probably 40 percent to 50 percent of patients with recurrent serous tumors and no family history of BRCA mutations also experience a positive tumor response to PARP inhibitors.” Birrer’s belief is that these women have gene changes similar to BRCA mutations. Women with ovarian cancer being treated at the Mass General Cancer Center now have their tumors screened for BRCA-like mutations. Patients whose tumors have these characteristics will receive standard chemotherapy plus a PARP inhibitor.

As progress continues on treatment for diagnosed ovarian cancers, Birrer and his colleagues are also working on an early detection test for ovarian cancer. Ovarian cancer is usually advanced at diagnosis; discovering it at an earlier stage would greatly increase the chances of successful outcomes. Steven Skates, PhD, a Mass General biostatistician, collaborated with several Mass General Cancer Center physicians in the development of a new algorithm that can help detect ovarian cancer early. The approach uses CA125, a protein found in the serum of women, which had previously been used as a Michael Birrer, MD, PhD screening tool. In the past, however, doctors had used a cutoff approach: A CA125 level below 35 was considered normal; 35 or higher signaled the possibility of cancer. The screen was not particularly helpful in identifying women with increased risk for ovarian cancer. What Skates determined is that every woman has her own normal for CA125. Tracking the level over time and watching for increases is a much more accurate way of determining if a woman is developing ovarian cancer. This approach is being studied in clinical trials with promising initial results. Birrer and Skates are currently collaborating on a number of studies designed to find new protein markers that may be even more effective than CA125 if used in conjunction with the algorithm, to aid in the early detection of ovarian cancer. ●

Medical Oncologist Jennifer Temel, MD, second from right, and palliative care physician Vicki Jackson, MD, MPH, right, collaborated on a study that showed early introduction of palliative care along with standard treatment extends lives.

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Palliative Care Extends Life “When my mother was diagnosed with lung cancer, my brothers, my father and I were in uncharted territory,” says Jay Monahan, senior vice president of business development for the PGA TOUR and co-founder of the non-profit organization Golf Fights Cancer. In recognition of the care, education and support Dr. Jennifer Temel provided to Joanne and the Monahan family, Golf Fights Cancer donated financial resources to establish the Joanne Monahan Cancer Fund. This fund supports Dr. Temel’s palliative care research.

Joanne Monahan

Patients, family members and even some doctors confuse palliative care, which is intended to help patients with a serious disease live as well as they can for as long as they can, with hospice care, which provides supportive care near the end of life. As a result, patients are reluctant to request palliative care, believing that to do so signals that they are no longer fighting their disease. But a study led by Jennifer Temel, MD, clinical director of the Center for Thoracic Cancers at the Massachusetts General Hospital Cancer Center, dispels that belief by showing that patients with metastatic lung cancer who received early and continuous palliative care along with standard cancer treatments lived nearly three months longer than those with the same disease and standard treatment alone. The patients receiving early palliative care also reported improved quality of

life and less depression than the other group, despite comparable use of antidepressants. Palliative care has been integrated into outpatient oncology at the Mass General Cancer Center for more than a decade. According to Vicki Jackson, MD, MPH, chief of the Palliative Care Program, “The palliative care team includes doctors, nurses, nurse practitioners, social workers and chaplains who work with the oncology team to help patients make the most of their lives. You want to continue your weekly golf game? We’ll try to help you feel better so you can do that. You want to take a trip to Paris? We’ll help figure out if that’s reasonable and, if it is, we’ll help ensure you enjoy it.” The goal for 2011, says David Ryan, MD, clinical director of the Mass General Cancer Center, is to integrate palliative care specialists early in outpatient care across all cancer types. ●

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A New Badge of Courage Thirteen-year-old Tristan Morris loves hockey, basketball and American history, especially World War II. On a recent trip to the National World War II Museum in New Orleans, he educated other museum visitors about minute details of the war, including the types of weapons used. But seven years ago, the weapons surrounding Tristan weren’t museum artifacts, they were the artillery needed to combat anaplastic astrocytoma of the spine. The prognosis, says Tristan’s father Jim, was bleak.

Unlike photon beams, which pass through tumors and affect neighboring tissue, proton beams release all their energy within a tumor.

The Morrises traveled from New Jersey to the MassGeneral Hospital for Children Cancer Center and the Massachusetts General Hospital Cancer Center, where Tristan received six weeks of proton beam therapy. Compared to photon therapy, protons inflict less damage on surrounding healthy organs. This feature reduced threats to Tristan’s health posed by traditional radiation and helped minimize side effects. Three years later, when a small lesion appeared in Tristan’s brain, another round of proton beam therapy helped fight the disease while sparing his cognitive functioning. “Medulloblastoma, one of the most common forms of pediatric brain cancer, is frequently curable using a combination of surgery, radiation to the brain and spine, and chemotherapy,” says Pediatric Radiation Oncology Director Torunn Yock, MD, MCH. But the stakes are high: Children suffer debilitating treatment side effects that can include intellectual impairment; hearing loss;

diminished stature; long-term cardiac, lung and digestive problems; and, in females, a risk of infertility. Most of these side effects are related to radiation. The younger the patient is irradiated, the greater the cost to the developing tissues and thus to the maturing brain. Knowing that these side effects are related to the way traditional radiation beams consisting of photons impact tissue surrounding tumors, Yock and pediatric radiation oncologist Nancy Tarbell, MD, conducted a study of 59 pediatric medulloblastoma patients using proton radiotherapy instead of photon radiotherapy. In this type of cancer, we treat the whole brain and the spine to destroy any tumor cells that have entered the spinal fluid,” explains Yock. “Then we give a higher boost of radiation to the original tumor site.” With proton radiotherapy, all the energy is released before the beam leaves the tumor, thus sparing internal organs. The primary benefit of proton therapy in the boost part of this treatment is that the dose can be more accurately placed, which decreases the impact on the rest of the brain. Based on a median follow-up period of two years, researchers are seeing positive results. Patients still have some relative decline in neurocognitive abilities, but declines are measurably less in pediatric patients who

BENCH TO BEDSIDE

have had proton therapy. Fewer patients suffered profound hearing loss with proton therapy than with the form of conventional radiation least toxic to hearing, intensity-modulated radiation therapy. Finally, only 29 percent of patients receiving proton therapy required hormone replacement to date. This outcome compares favorably to the 50 percent to 70 percent of pediatric patients receiving conventional radiation treatments for medulloblastoma who need replacement therapy to overcome hormonal deficiencies. “Proton therapy makes so much sense for kids,” says Tarbell. “But it’s very complex. There’s a short window during which we can get these patients under treatment, and there are technical issues relating to dose that we’ve had to overcome. Fortunately we have long-term, in-depth experience using protons in children. In fact, we began in the 1970s and continue to treat children from all over the world.” For the Morris family, who are giving back to the MassGeneral Hospital for Children Cancer Center through financial support and service on the Mass General Cancer Center Leadership Council, expertise was only one part of care. According to Jim Morris, “We were touched deeply by the level of caring, concern and compassion that everyone displayed for our son, for us, and for other patients and families. The care kept our son healthy and helped us during a very difficult time.” Meanwhile Tristan continues fighting his disease with courage. He doesn’t let some paralysis in his leg stop him from engaging in the activities he loves. Nor have his treatments impeded his cognitive abilities, as those other visitors to the World War II Museum discovered. ●

Cancer survivor and basketball fan Tristan Morris leaves treatment side effects on the sidelines.

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Tests and Technology Preserve Lifestyle Massachusetts General Hospital Cancer Center clinicians work in multidisciplinary teams to help minimize the effects of genitourinary cancer therapies so that patients and families can return quickly and safely to their normal lives. Progress is ongoing as specialists in fields from physics to chemistry and from engineering to molecular biology share their knowledge and experience to avoid or alleviate the repercussions of cancer treatment.

Left to right, Chin-Lee Wu, MD, PhD, W. Scott McDougal, MD, and Aria Olumi, MD, work together to improve care and outcomes for patients with genitourinary cancer.

The first step toward minimizing the effects of treatment ideally occurs at diagnosis. Currently, doctors lack sufficient information to help them definitively determine which men with prostate cancer need aggressive treatment and which can be actively monitored. Existing guidelines clearly establish men on each end of the spectrum: Those with high-volume, localized cancer who require therapy (surgery or radiation) and those with low-volume disease who do not. But a great many men fall in the gray area, where their choices are treatments that may risk bowel, bladder and potency dysfunction, or opting for a watchful waiting approach and face sleepless nights wondering if their disease has spread. Most patients select a form of therapy, an understandable choice given the stakes. But, says Chin-Lee Wu, MD, PhD, a pathologist specializing in genitourinary cancers, “We may be over-treating patients.” Recent research by Wu and W. Scott McDougal, MD, chief of the Department of Urology, in collaboration with researchers at bioTheranostics, Inc., details a pattern of gene activity characteristic of aggressive prostate cancer. The study compared gene profiles of tumors from 191 men with mid-range prostate

cancer with the survival and disease recurrence of these men over a two-decade span. The comparison yielded a set of 29 genes that strongly correlate with prostate cancer progression. A clinical test performed at diagnosis could detect the activity of these genes and help separate men needing prostatectomy from those who can be monitored. The test requires further study before it is integrated into clinical practice. A similar study is ongoing in bladder cancer which, says McDougal, bears some relevant similarities to prostate cancer: Doctors are forced to recommend that patients with mid-range disease have their bladders removed because they lack sufficient indicators to determine which cancers are at risk of progression. “Some of these patients could be losing their bladder unnecessarily,” McDougal says. He is using tumor samples and outcome data to develop a gene profile usable as a prognostic test. Whenever possible, surgeons remove only the diseased part of an organ, leaving healthy tissue untouched. But this approach can cause disfigurement or decrease in function, leading Mass General urologists to research more precise surgical and focused radiation techniques as well as reconstruction procedures. “We’ve pioneered the development of a number of techniques in the preservation of penile function and length through precision surgery,” says McDougal. “By moving healthy tissue to repair the surgical site,

we are able to improve outcomes in sexual and urinary function and appearance.” Even in cases where patients avoid losing an organ to disease, cancer treatments may occasionally cause enough tissue damage that the organ must be removed. This is particularly true in patients receiving radiation therapy for pelvic tumors, including rectal, bladder, prostate, cervical, or uterine cancer. About ten percent of these patients develop bladder or rectal bleeding, which is usually controllable with simple lifestyle changes. But in a small percentage of cases, cauterization is required to stop bleeding. Unfortunately, cauterization creates additional problems, including scabbing, scarring, recurrent bleeding and a reduced ability to store urine. Some of these patients ultimately have their bladder removed. A new approach by Shahin Tabatabaei, MD, a urologist at Mass General, avoids these outcomes. Tabatabaei used GreenLight™ laser technology instead of traditional cauterization methods on 20 patients with this progressive form of bladder bleeding. GreenLight laser has been used successfully in men with benign enlargement of the prostate, and Tabatabaei has more than six years of experience with this technology. Applying his understanding of the physics of the GreenLight beam – different wave lengths penetrate the cell in different ways – Tabatabaei sealed bleeding vessels during an outpatient procedure without causing scabbing or scarring. In a presentation of his results at the 2010 American Urological Association meeting, Tabatabei reported that most patients were cured of their bleeding after one treatment, and none experienced side effects. “We use the intellectual, technological, biological and clinical resources of our world-class institution to discover and develop the most effective and least invasive approaches to cancer prevention, monitoring and treatment,” says Aria Olumi, MD, director of urology research. “We want our patients safe. We also want them happy.” ● Shahin Tabatabaei, MD, uses advanced laser techniques to stop uncontrolled bleeding associated with radiation therapy.

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BENCH TO BEDSIDE

FDA Approves 3-D Breast Tomosynthesis Approximately half of all women have dense breast tissue that can mask breast cancer on a mammogram, making accurate mammograms a challenge for radiologists and resulting in nerve-wracking false positives or follow-up tests for women. Recently, the Food and Drug Administration (FDA) approved a new

Elizabeth Rafferty, MD, helped pioneer breast tomosynthesis, which was recently approved by the FDA.

technology pioneered by the Mass General Breast Imaging Division, three-dimensional (3D) breast tomosynthesis. The new machine takes a series of 15 digital images of the breast at different angles. The images are compiled by computer, creating a highly focused 3D image that makes small cancers easier to find, even in dense breast tissue. “3D tomosynthesis gives both doctor and patient more confidence with interpreting images,” says Elizabeth Rafferty, MD, director of the division. “With this technology, we can find cancers earlier and reduce the number of follow-up procedures required by false positives.” This technology may replace conventional mammograms in the future. ●

Overcoming Treatment Obstacles Cancer and cancer treatment can cause low blood platelet counts, leaving patients susceptible to excessive bleeding or disruption in other cell processes. As a result, these patients must interrupt chemotherapy or receive lower doses, compromising the benefits of their therapy. Some patients will require platelet transfusions. The ideal solution is a drug that increases platelet count, just as other drugs are available to stimulate growth in red blood cells and white blood cells. Recent work in the lab of David Kuter, MD, DPhil, director of the Center for Hematology at the Massachusetts General Hospital Cancer Center, brings doctors a significant step closer to that solution. In a trial led by Kuter in the mid 90s, a molecule called thrombopoetin demonstrated the ability to increase the platelet count in most study participants. However, in a small number of participants, the drug paradoxically caused the opposite reaction, low platelets, making it inappropriate for use in patients. Since then, Kuter has worked with pharmaceutical partners Amgen and GlaxoSmithKline to develop a new group of drugs that mimics the function of thrombopoetin but that is structurally different. He tested one of the new drugs in patients with a rare autoimmune disease, idiopathic thrombocytopenic purpura (ITP) which causes low platelets. Results of the trial paved the way to recent FDA approval of an injected form of the evolved thrombopoetin for ITP. According to Kuter, “This discovery means there is a thrombopoetin that can increase cancer patients’ platelets.” He is currently leading studies that will help verify the utility of the drugs to cancer patients. ●

Big Success with Small Incisions Throughout the Massachusetts General Hospital Cancer Center, surgeons are investigating instrumentation and surgical techniques that allow them to use a minimally invasive approach rather than large incisions. Laparoscopic surgeries, or surgeries using multiple small incisions rather than one large one, reduce post-operative pain and return patients to their normal lifestyles more quickly. Most important, however, stresses Gynecologic Oncologist David Boruta II, MD, is that the less invasive approach treats the disease just as well as established methods. Boruta and Mass General colleagues Whitfield Growdon, MD, and John Schorge, MD, FACS, are pioneering efforts to further improve upon the benefits of laparoscopic surgery in women with endometrial cancer. The first step in treatment of this cancer involves surgical removal of the uterus, fallopian tubes and ovaries. Lymph nodes from the abdomen and pelvis are also often removed to look for metastases. The traditional laparoscopic approach in performing these procedures involves five incisions. Boruta wanted to develop a technique to accomplish all of this through only one tiny incision. Meeting the challenge required both negotiating with industry representatives to find the ideal instruments and choreographing the intricate movements of the surgical team. Although the team has performed the single-incision surgery on only a few patients so far, Boruta is hopeful. “The number of lymph nodes retrieved using the single-incision technique has been similar to what we’ve seen historically with the five-incision technique,” he says. “Most patients leave the hospital the day after surgery, require very little pain medication, and get back to their regular activities quickly.” Boruta looks forward to further development of this technique, noting that it may be especially beneficial for obese patients or those who will need radiation or chemotherapy following surgery. Boruta and his colleagues also perform single-incision laparoscopic removal of tubes and ovaries in women with gene mutations such as BRCA1 and BRCA2, which increase their risk for ovarian cancer. These surgeries are done for women in their mid 30s and 40s who often are already facing difficult decisions about mastectomy. “Being able to tell them that we can hopefully protect them from ovarian cancer and at the same time hide the surgical incision within their belly button is exciting for us and comforting for them,” says Boruta. The Mass General Cancer Center is one of only a handful of medical centers in the United States performing single-incision surgeries in gynecologic oncology. ● David Boruta II, MD, is developing techniques for performing gynecologic oncology surgery through a single, tiny incision.

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NEW PROGRAMS AND INITIATIVES

Where the Future Begins New options deliver the next generation of cancer care

pioneering a new generation of cancer care requires facilitating collaboration among highly specialized clinicians and scientists, maximizing the use of evolving technologies, and ensuring patients continue to receive the highest quality, compassionate care.

NEW PROGRAMS AND INITIATIVES

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Dual-Targeted Therapies Deliver a One-Two Punch The Mass General Cancer Center is uniquely positioned to lead the development of the next generation of targeted agents effective in combating cancer. This strength arises from extensive clinical experience treating both rare and common cancers, research expertise in the discovery and understanding of cancer-causing cellular pathways, and advanced technology that facilitates screening for cancer-related genetic mutations in patient tumors. The new Center for Targeted Therapeutics, led by José Baselga, MD, PhD, chief of Hematology Oncology, associate director of the Mass General Cancer Center, and incumbent in the Bruce Chabner Chair in Hematology Oncology, capitalizes on these resources to ensure rapid translation of scientific advances into clinical availability of the safest and most effective therapies. The Center focuses on basic and translational research aimed at further identifying cancer-related gene activity and developing new treatments. Through a portfolio of clinical trials, the Center offers these emerging therapies, including new drugs for treatment-resistant cancers and innovative dual-targeted therapies. Dual-targeted therapies are combinations of agents that affect two separate cancer-causing pathways. In addition to targeted therapies, the trials offer treatments that activate the body’s immune response to fight cancer and that cut off formation of the blood vessels that feed tumor growth. “The work done within the Center for Targeted Therapeutics provides the foundation from which we will develop the tools to conquer cancer,” Baselga says. “This early research is under-supported by funding agencies. Without the support of private donations, it simply cannot occur.” Baselga brings his extensive international experience in the development of targeted cancer drugs to the Center. Currently, he and fellow Mass General Cancer Center researchers are testing a two-in-one antibody designed to target two sites

that play significant roles in regulating tumor growth, as well as studying agents that inhibit a pathway known as PI3K. Inhibiting this pathway, Baselga and his colleagues believe, will interfere with a tumor’s ability to survive and grow. Baselga is also principal investigator for an international phase II trial of a dual-targeted therapy in breast cancer patients. This study compares a combined therapy with the current standard of care in women with breast cancer whose disease has not responded to earlier treatment. A phase I study showed that patients tolerated the combination therapy well, and that more than 40 percent of patients experienced positive antitumor activity. The dual-targeted therapy seems particularly effective in estrogen-receptor-positive breast cancer patients. “Coordinating the tremendous “The work done within resources and research efforts of the Mass General Cancer Center through the Center for Targeted the Center for Targeted Therapeutics Therapeutics provides the allows us to speed development of innovative new treatments and foundation from which we delivery of these therapies into the will develop the tools to clinical setting,” says Baselga. “ Our focus is on the next generation of conquer cancer.” targeted therapies, combinations of — José Baselga, MD, PhD drugs that deliver a one-two punch to cancer cells. Integrating this approach with techniques for selecting patients most likely to benefit from new therapies and methods for determining early response to therapy will help conquer cancer.” ●

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NEW PROGRAMS AND INITIATIVES

Expertise with a Personal Touch

Nurse Director Barbara Cashavelly, MSN, RN, AOCN, notes that the inpatient oncology nurse practitioner service provides both familiar faces and specialized round-the-clock care for cancer patients.

When Deanne Dorn was admitted to Massachusetts General Hospital with advanced metastatic lung cancer, she and her husband, Barry, knew she was very sick. They also knew who they wanted by her side: Nurse Practitioner Jeanne Vaughn, who had cared for Deanne on an outpatient basis since her diagnosis seven years earlier. The new Inpatient Oncology Nurse Practitioner Service at the Mass General Cancer Center helped make that continuity of care possible. Nurse practitioners (NPs) have been a valued part of the Mass General Cancer Center’s outpatient multidisciplinary disease centers for more than a decade; NPs have served on inpatient care teams as well, but not in a unified or structured service. Beginning last June, Vaughn and nine other nurse practitioners were the first NPs selected for the Inpatient Oncology NP Service. This new service covers 14 beds and cares for patients needing disease management, symptom management, and/or supportive care for melanoma, gastrointestinal, thoracic or genitourinary cancers. The inpatient NPs provide care to these patients 24/7, make clinical decisions, and facilitate communication and coordination with the patient’s inpatient and outpatient care teams. In the past, these patients were cared for by the inpatient medical residents. According to Panos Fidias, MD, medical director of the Inpatient Oncology Unit, the Inpatient NP Oncology Service represents a model that is novel for inpatient care anywhere in the country. “The service provides continuous inpatient care at a time when residents are required to spend more time in outpatient clinics,” he says. “These NPs have been specially trained in the medical and oncologic skills needed by our patients, and they are trained in supportive care.”

Also important is the communication continuum provided by the service. NPs help ensure that information about changes in medication is transmitted back to the patient’s primary oncologist and that follow-up appointments are made in the appropriate time frame. They also facilitate coordination of any support needed at home. Critically ill patients or those needing more specialized care are admitted to the medical or intensive care units. In the first six months, the new service showed a surprising benefit: A reduction in the length of hospital stay by nearly two days. “The NPs are continuously on the floor, capable of independently evaluating and managing cancer patients,” says Nurse Director Barbara Cashavelly, MSN, RN, AOCN. “That’s going to mean more effective and more efficient care.” An additional benefit to patients is that, unlike residents, NPs do not rotate to a different service. Patients who are readmitted to the service will see the same familiar faces. When the new Lunder Building opens later this year, the Inpatient Oncology NP Service will expand to 28 beds and will include patients with leukemia or who have received bone marrow transplantation. Nurse practitioners covering these patients will have training specific to those conditions. Vaughn had transitioned to an inpatient oncology NP role by the time Deanne Dorn was admitted, and was able to provide support and care for patient and family before Deanne succumbed to her disease. According to her husband Barry, a physician who practices at Winchester Hospital, the experience was very difficult but was eased by Jeanne, who treated Deanne like the special person she was. Vaughn, he felt, had truly become part of the family. “Jeanne could connect with Deanne and connect with the family,” Dorn says. “She always made Deanne feel comfortable, informed and special.” ●

Nurse Practitioner Jeanne Vaughn was a familiar face, a comforting presence, and an experienced care provider during Deanne Dorn’s cancer journey. “Her concern,” says Deanne’s husband Barry Dorn, MD, “is always, first and foremost for the patient.”

SERVING OUR COMMUNITY

Reach Out and Touch Fun and Funds for Children with Cancer For the third consecutive year, members of the Boston Bruins raised money for children with cancer treated at the MassGeneral Hospital for Children Cancer Center by allowing fans or young cancer patients to shave their heads as part of Cuts for a Cause. On March 31, 2010, staff from Barbershop Lounge supervised the activity. Howard Weinstein, MD, chief of Pediatric Hematology Oncology at the MassGeneral Hospital for Children Cancer Center, Fred “Toucher” Toettcher, Rich Shertenlieb and Adolfo Gonzalez of the Toucher and Rich show on 98.5 “The Sports Hub” also suited up and had their heads shaved. Held at upscale Irish pub Ned Devine’s, the Cuts for a Cause event raised $25,000. Funds supported art and music therapy (through the HOPES Program) for patients at the MassGeneral Hospital for Children Cancer Center.

Photo: Sherly Lanzel

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Bruins player Shawn Thornton and MassGeneral Hospital for Children’s Howard Weinstein, MD, suit up for a new haircut in support of pediatric cancer patients.

Howard Weinstein, MD, David Ortiz and Bill Taylor, general manager, Four Seasons Hotel Boston

Members of various police departments also work tirelessly to support pediatric patients and their families. Cops for Kids with Cancer sponsors motorcycle rallies, golf tournaments, 5K races and a hockey tournament. Funds raised through these events provide emergency assistance to families struggling to make ends meet while caring for a child in treatment. “Our goal is to help these families in their time of need,” says retired Superintendentin-Chief of the Boston Police Department Robert Faherty, who is chairman of Cops for Kids with Cancer. Donations also support programs that build friendships and support among parents and children coping with cancer, including an annual harbor cruise aboard a Boston Police Department patrol boat. Prior to the August 12, 2010 cruise, participating families were treated to a car and motorcycle police escort through the city. “The only one who gets an escort like that,” says Faherty, “is the president of the United States.” For more information on Cops for Kids with Cancer, visit www.copsforkidswithcancer.org. The 2010 Run of Hope marked the 25th anniversary of run host, the Four Seasons Hotel Boston. Held last year for the first time with the David Ortiz Children’s Fund, the Run of Hope included a 5K run, 2K walk and raffle aimed to raise funds for pediatric cancer care and research at the MassGeneral Hospital for Children. Participants had the opportunity to sign up with celebrity coaches this year to help them train. Among the coaches were Isadore Sharp, founder, chairman and CEO of Four Seasons Hotels & Resorts; the Red Sox’s “Big Papi,” David Ortiz; and Howard Weinstein, MD, from the MassGeneral Hospital for Children Cancer Center.

SERVING OUR COMMUNITY

The 2010 run, held June 12, attracted nearly 600 participants and raised close to $80,000. This year’s event is June 11. For more information on The Four Seasons Run of Hope, visit www.fourseasonsrunofhope.com. When 14-year-old Christina DelRosso, winner of the 2010 National American Miss Massachusetts Junior Teen competition, met with pediatric patients being treated at the MassGeneral Hospital for Children Cancer Center, she made them feel like royalty. The boys were knighted, the girls were crowned, and every child received a book and a stuffed animal. But DelRosso’s visit gave the children a gift that went far beyond an afternoon of pageantry: She gave them a glimpse of the future of childhood cancer survivors. Christina was diagnosed with neuroblastoma at the age of two and a half. The connection, says Christina’s mother, Beth, made a big difference to both children and parents at the event. Christina had another reason for wanting to give back to the Mass General Cancer Center as well: Her uncle, Daniel Ford, was treated for urethral cancer at the Cancer Center. To honor his memory, the Ford family established the Dan Ford Foundation. Every year in April, hundreds of runners participate in a road race to raise money. Proceeds are directed to the Fund for Families at the MassGeneral Hospital for Children Cancer Center to help families in need during their child’s treatment. The foundation’s mission and format is fitting for her brother, says Beth, because Dan was a competitive athlete who loved children. The 2011 race was held Saturday, April 30, 2011. For more information, visit www.danfordroadrace.com.

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Teaming up to Kick Cancer The New England Patriots Charitable Foundation joined forces with the Mass General Cancer Center and other local cancer hospitals to raise awareness of cancer risk factors and screening options. The season-long initiative included distribution of educational materials, messages to fans, and televised public service announcements featuring Patriots players. Each home game focused on awareness for a different type of cancer. During halftime of the final game of the season, cancer survivors and caregivers were honored by three-time Super Bowl Champion and cancer survivor Joe Andruzzi. The campaign also included visits by current Patriots players and alumni to cancer patients at Mass General and other participating hospitals.

New England Patriots safety Patrick Chung brightens the day for a young cancer patient.

Celebrating Relationships Last September, the Bone Marrow Transplant and Leukemia Program hosted a reunion for families, patients and staff. The event attracted more than 300 attendees. “There is probably no better way to honor our patients than to celebrate their successes and to reconnect with them and their families in a social setting,” says Karen Ballen, MD, director of the Leukemia Program. Patients undergoing bone marrow transplantation are often hospitalized for months and followed over a lifetime. It’s an intense journey for everyone involved, says Ballen, who acknowledges the team of staff members who volunteered their time to ensure the event was a success. “Seeing patients several years out was a treat for the staff, and I think the patients enjoyed seeing us in our jeans instead of our scrubs.”

➤

Karen Ballen, MD

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SERVING OUR COMMUNITY

Empowerment through Education Anniversary Walk On June 20, 2010, the North Shore Cancer Walk celebrated its 20th anniversary. The date was an important one for Walk Chair Mark Forziati: It marked the 20th anniversary of his father’s death from cancer. The event attracted thousands of participants, raising a record $913,000 to support the Mass General/North Shore Cancer Center and renovation of the inpatient oncology unit at Salem Hospital. Under Forziati’s stewardship, the event expanded to include a 5K run and a “Taste of the North Shore” featuring food from ten of the North Shore’s finest restaurants, music by the Evan Goodrow jazz trio, and an auction sponsored by General Electric. The 2011 Walk, slated for June 26, will be chaired by Kevin Noyes, director of compliance at Danversbank and director of the Danversbank Charitable Foundation, Inc. Danversbank Foundation is presenting sponsor of the Walk for the five-year period ending 2012. The partnership between the Mass General/ North Shore Cancer Center in Danvers and the Mass General Cancer Center in Boston was further strengthened through educational seminars in prostate and breast cancers. Held at the Danvers center and open to the public, the seminars featured talks by specialists from both facilities. Plans are in the works for additional seminars this year. For more information about the June 26 event, please visit www.northshorecancer walk.org.

Kevin Noyes

Mark Forzioti

Each year, the Massachusetts General Hospital Cancer Center partners with cancer-related foundations to provide educational symposia for patients and families. One of these, held in July 2010, addressed advances in the field of ovarian cancer in conjunction with the Gynecologic Cancer Foundation. The free full-day course, held at Mass General’s Simches Research Center, included an explanation of the biology of ovarian cancer, updates in screening and early detection, surgical issues, an explanation of clinical trials and new treatments being offered to treat ovarian cancer, and the meaning of CA 125 levels. The event was attended by 117 patients, family members and friends. In conjunction with the Caring for Carcinoid Foundation, the Mass General Cancer Center hosted an “Ask the Expert” day that outlined the importance of clinical trials and self-advocacy during treatment for carcinoid, which is a neuroendocrine cancer that occurs in the gastrointestinal tract and lungs. Presenters and expert panel members also covered surgical and medical management, basic research, and supportive care for neuroendocrine tumors. The Caring for Carcinoid Foundation was established by carcinoid patient Nancy Lindholm to support leading scientists whose research will lead to a cure for this disease. The Jennifer Hunter Yates Sarcoma Foundation brings together cancer experts and sarcoma patients, family members, and friends for a day of information sharing and support. Mass General Cancer Center experts from medical oncology, radiation oncology, pathology and relevant surgical subspecialties updated attendees on current and emerging treatments, as well as provided background information on the disease and its causes. Last year’s event, the fourth “Meet the Experts in Sarcoma” gathering, drew a crowd of about 90 participants. This year’s conference was Saturday, April 16, and featured presentations by more than a dozen Mass General Cancer Center physicians. For more information, please contact Donna Silva at [email protected].

SERVING OUR COMMUNITY

In October 2010, the Mass General Cancer Center and the Melanoma Research Foundation presented a full day of melanoma education for patients and caregivers. Physicians and researchers from Mass General talked about risk factors, prevention strategies, recognizing the difference between a mole and melanoma, new therapies, survivorship issues, and the future of melanoma care. “The focus was on empowering patients, their families and their caregivers,” says Krista Rubin, MS, RN, FNP-C, a nurse practitioner in the Center for Melanoma and in the Dermatology Department. “The goal was to arm attendees with information so that they understand the diagnosis and the treatments being offered.” The event included ample opportunity to ask questions of the experts.

The annual survivorship conference combines education, friendship, relaxation and fun with plenty of time for individual questions.

New Program Meets Survivors’ Needs In June 2010, the Mass General Cancer Center launched the Survivorship Program to meet the medical, emotional, educational and psychosocial needs of cancer survivors. This program helps cancer survivors treated at any hospital receive supplementary care for issues that may arise long after active treatment has ended. The Survivorship Program comprises a clinic where Elizabeth Davis, MD, a specialist in internal medicine and psychiatry, assesses the needs of individual patients and develops a personalized treatment plan that draws on Mass General’s wide array of established services. Treatment may include referral to other resources within the Survivorship Program such as psychiatric oncology, social work services, spiritual counseling, the Blum

Cancer Resource Room, HOPES Wellness Program, and the Network for Patients and Families. According to Inga Lennes, MD, Survivorship Program director, patients from the community and from almost every disease center within the Mass General Cancer Center have been seen in the Survivorship Clinic in the past year. In upcoming years, the Clinic will integrate new communication technologies and continue honing programming to promote wellness and improve quality of life for patients. The Clinic will bridge the gap between the patient’s oncologist and primary care physician, and study the long-term physical and emotional impact of cancer treatment.

Information and Support Since 1995, the Mass General Cancer Center has held an annual Celebrating Cancer Survivorship conference, initiated and organized by volunteers of the Network for Patients and Families. During the morning session of the 2010 conference, Daniel Haber, MD, PhD, director of the Mass General Cancer Center, welcomed the group, and Leif Ellisen, MD, PhD, co-executive director of the Translational Research Laboratory, provided information on genotyping and targeted therapies. Afternoon workshops led by Mass General social workers, physical and occupational therapists, physicians and other specialists addressed self advocacy for caregivers; coping with cancer as a chronic illness; maintaining intimacy and sexual health after cancer treatment; and tips for nutrition, meditation, complementary therapies and exercise for cancer survivors. The patient and family panel, says Sally Hooper, MSW, LICSW, director of the Blum Cancer Resource Room and the Network for Patients and Families, includes people of different ages with a range of experiences with cancer to provide benefit for all conference attendees. The day ended with cake, ice cream, and a performance of a cappella music by The Wicked Pitches, whose group member, Lee Jaffe, is an administrative manager in the Cancer Center. This year’s conference was Saturday, April 9, and was generously sponsored by Golf Fights Cancer, a non-profit organization committed to making a positive impact for patients and their families in the fight against cancer.

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GROWING THE FUTURE OF CANCER CARE

It Takes a Village

Conquering cancer requires commitment from all of us Dear Friends, Philanthropy is closely entwined with progress in the fight against cancer. Particularly in academic medicine – where other funding sources are becoming increasingly scarce – philanthropy plays a key role in fueling scientific discovery and speeding the translation of these discoveries to patient care. If we are to continue making the kind of progress you have read about in the pages of this magazine, we need your help. The Mass General Cancer Center is uniquely situated to turn new understanding of the biological underpinnings of cancer into effective therapies by bringing together the best and brightest scientific minds and the most experienced and compassionate clinicians. With your help, we can ensure that these individuals have the resources they need to grow the future of cancer care without delay. The Mass General Cancer Center is in the midst of a $350 million fundraising campaign, part of the hospital-wide $1.5 billion capital campaign: the Campaign for the Third Century of MGH Medicine. We are raising support for integrated laboratory and clinical research, quality-of-life enhancing support programs, medical education opportunities for the next generation of caregivers, outreach and education programs to share knowledge and improve care around the world, a new state-of-the-art care facility, and other initiatives that strengthen the Mass General Cancer Center’s ability to deliver exceptional care to our patients and their families. We will only succeed with the help of many. There is strength in numbers – scientists, physicians, caregivers, patients, advocates, volunteers, philanthropists and friends – and we invite you to join us in whatever capacity you are able. Individuals and groups highlighted in this magazine illustrate unique and meaningful ways to participate in our fight against cancer. To those and others like them who have supported the cancer cause, thank you. Our incredible progress would not be possible without the extraordinary support of our friends. At such a crucial moment in science and with so much at stake, we must rally together. Will you join us? Sincerely,

Sara S. Kelly Senior Managing Director Development and Cancer Center Campaign

GROWING THE FUTURE OF CANCER CARE

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How to Make a Gift Partner with us in the fight against cancer You can support the Massachusetts General Hospital Cancer Center in a number of ways, and we invite you to partner with us to help advance the fight against cancer. Whether you contribute financial support, time, energy or compassion, you will enhance our community in a valuable and meaningful way. Through your participation, you show commitment to our mission – advancing cancer care and ultimately the eradication of this disease.

Vital Support Comes in Many Forms Funding opportunities within the Mass General Cancer Center range from research initiatives and clinical trials, to educational opportunities for nurses and physicians, to wellness and supportive-care programs for patients and families. Unrestricted gifts are vitally important to the success of the Mass General Cancer Center as well: The acceleration of breakthrough research and advancement of patient care hinges on the availability of these resources. You can make a gift to the Mass General Cancer Center in a variety of ways, including: • Outright gift (cash) • Gift of securities • Matching gifts from your employer

Planned Giving Donors often choose to make a contribution in the form of gifts that provide them and/ or their beneficiary income for life. These arrangements can give donors significant tax benefits. This invaluable support builds a

foundation of hope for Mass General Cancer Center patients – those who come to us in search of excellent care today and those who will come in the future.

Tribute Giving A gift to the Mass General Cancer Center is a meaningful and enduring gesture to remember a loved one, honor a friend or family member, or thank an outstanding caregiver.

Organize a Fundraising Event The Mass General Cancer Center is grateful to the dedicated volunteers who work tirelessly to build support for the hospital by finding new ways to engage the community and help raise funds. To learn how to kick-start your event, please call the Development Office and inquire about our Third Party Events Program.

Participate in the one hundred Attend and/or sponsor the Mass General Cancer Center’s annual fundraiser, the one hundred, honoring 100 individuals and groups whose diligence and discoveries, philanthropy and passion have helped advance the fight against cancer. Funds raised at the gala support the Mass General Cancer Center’s patient care, research, education and community outreach programs. To learn more or to nominate someone for the one hundred, please visit theonehundred.org.

Thank You for Your Support! Countless caregivers, scientists, volunteers and philanthropists contribute their energy, talent, passion and financial support to help

Strength in Numbers M ass general cancer center campaign

the Mass General Cancer Center provide the best possible care to patients and their families. This dedicated community is what makes the Mass General Cancer Center truly exceptional and a place of hope for patients from across the country and around the world.

Contact Us The Development Office is a resource for you. Contact us at 617-726-2200 or [email protected] to learn more about how you can help patients and families at the Mass General Cancer Center. Massachusetts General Hospital Cancer Center Development Office 165 Cambridge Street, Suite 600 Boston, MA 02114 massgeneral.org/cancer/support

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the one hundred:

A Preview of the 2011 Awardees the one hundred is the Massachusetts General Hospital Cancer Center’s signature fundraising event, honoring 100 individuals and groups whose diligence and discoveries, philanthropy and passion have helped advance the fight against cancer. The annual dinner is an opportunity to recognize unsung heroes of the cancer community as well as raise funds for the Mass General Cancer Center’s research, patient care, education and community outreach programs. We are pleased to share with you five stories of this year’s the one hundred honorees. To see the complete list and stories please visit www.theonehundred.org .

Ario Nour When six-year-old Ario arrived at Mass General’s Francis H. Burr Proton Therapy Center to begin treatment for his brain tumor, he announced that he did not want to sleep and did not want needles. The staff worked together to help Ario achieve his goal of anesthesia-free treatment. Since then, he has taught other children how to have treatments without sedation, and one of his protégées trained a six-year-old girl to have sedative-free treatment. Now that child is teaching another patient. With his kindness, happy spirit and knack for teaching, Ario has helped other children avoid side effects and gain self-esteem and courage at a challenging time.

Shyamala Maheswaran Devoted to research on breast cancer, Shyamala Maheswaran, PhD, brings her passion and expertise to the Center for Cancer Risk Assessment, where she serves as scientific director, and to her laboratory, which investigates the molecular mechanisms governing the development and growth of tumors of the mammary gland. She is also co-directing a multidisciplinary team to isolate circulating tumor cells from the blood of patients with cancer. In May 2009, the group received a three-year “Dream Team” research grant of $15 million from Stand Up To Cancer, the entertainment industry’s charitable initiative to accelerate development of groundbreaking cancer treatments.

GROWING THE FUTURE OF CANCER CARE

James McIntyre, MD James McIntyre, MD, director of radiation oncology at the Mass General/North Shore Cancer Center in Danvers, Massachusetts, inspires confidence in his patients with his warm and positive manner as well as with his expertise, honed by more than two decades of clinical experience and published research. Writes one patient, “My wife and I feel as though we owe my life to him. His medical knowledge is excellent, his treatments are spot-on and his exceptional bedside manner just completes the entire package.”

On Wednesday, June 1, 2011, the 4th annual the one hundred dinner takes place at the Westin Boston Waterfront, where we recognize the contributions of Ario Nour, Shyamala Maheswaran, Heather Unruh, Evelyn Malkin, James McIntyre, and others. Nominations are open for the fifth annual the one hundred to be held in 2012. We welcome your recommendations of those who have contributed to the Mass General Cancer Center or to the greater cancer community, whether in large ways or small. The nomination deadline is December 31, 2011. For more information about the one hundred or to nominate someone for 2012, please visit theonehundred.org or call Raquel Morales at 617-724-2818.

Evelyn Malkin, LICSW Before her retirement, pediatric social worker Evelyn Malkin, LICSW, was often the first person to meet young patients and their families as they arrived for treatment at Francis H. Burr Proton Therapy Center. She had a special way of putting both children and parents at ease, providing them with love and support while simultaneously identifying and meeting their varied needs during a difficult time. For twenty-five years, she enhanced the overall excellence of care for young patients and their families.

Heather Unruh Heather Unruh, co-anchor of Boston’s ABC affiliate, WCVB-TV Channel 5, aired a series on the station’s news magazine that wove together stories of patients and families coping with lung cancer – including her own mother’s battle – with reports on the cutting-edge science of lung cancer treatment. Her deep understanding of the disease and her great gift as a communicator have positively impacted the well-being of her audience and transformed public perception of this disease and its victims.

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Support During Transition Jazzy Support for Music and Art Therapy Mike Caruso is a jazz musician and cancer survivor. So when he completed treatment for leukemia at the Massachusetts General Hospital Cancer Center, he used his talent to raise money to help other cancer patients. On October 30, 2010, Caruso, his family, friends and a jazz sextet – headed by Caruso on jazz guitar – hosted the Jazz2Cure concert in Framingham, Massachusetts. Event proceeds supported a program that was a positive influence for Caruso while he was in treatment: Music and art therapy through the Mass General Cancer Center’s HOPES Program. The Cancer Center’s music therapist Lorrie Kubicek, MT-BC, joined the sextet as lead vocalist, and many physicians and staff from Mass General attended in support of Mike and Lorrie’s efforts. The donation from Jazz2Cure enabled the music and art therapists to add iPads with music and art applications to their trove of creative tools. Caruso and Jazz2Cure previously supported the purchase of laptops for patient and family use on the inpatient bone marrow transplant unit, as well as Wii systems which are being used by patients and caregivers for low-impact physical therapy. For more information about Jazz2Cure, please visit www.mikecarusomusic.com.

Joanne Chang signs a copy of her book for Friends board member Laryn Gardner.

In December 2010, the Massachusetts General Hospital Cancer Center HOPES Program received a LIVESTRONG® Community Impact Project Award from the Lance Armstrong Foundation. The funding from this grant has enabled the Mass General Cancer Center to pilot a program designed to empower people with cancer in their transitional period following treatment. The six-week “Cancer Transitions” program includes support groups, education, nutrition and physical exercise. It also addresses other medical management, psychosocial and quality of life issues, complementing and enhancing the offerings of the Survivorship Program at the Mass General Cancer Center. The program will be offered at Mass General/ North Shore Cancer Center in the fall of 2011. For more information, please contact the HOPES Program at 617-724-6737.

Books ‘n’ Brew The Friends of the Massachusetts General Hospital Cancer Center held their 18th annual fundraiser on November 18, 2010 at the John Joseph Moakley U.S. Courthouse. Kelley Tuthill – WCVB-TV reporter, cancer survivor and dedicated advocate – emceed the event, which raised $260,000 for the Mass General Cancer Center. Local authors Joanne Chang, Barbara Lynch, Shonda Schilling and Granville Toogood signed copies of their books, donating a portion of the proceeds to the Friends. Additional activities included beer tasting by Pretty Things Beer and Ale Project and tours of the courthouse. For the past 25 years, the Friends group has provided funding for support and education programs at the Mass General Cancer Center, including the Maxwell V. Blum Cancer Resource Room, HOPES Program, and a financial assistance fund for patients and families. To become involved, please call Amy Fontanella at 617-724-6426. The 2011 Friends fundraiser will be held on November 17 at the Moakley Courthouse.

GROWING THE FUTURE OF CANCER CARE

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Skiing for a Cure Peter Newton was a husband, father and avid outdoorsman when melanoma ended his life at age 46. Newton loved to ski, and for many years he served on the Sugarbush Ski Patrol. To honor his active life and battle against melanoma, family and friends established Peter’s FUNd Racer, a fundraising ski race at Sugarbush Resort in Warren, Vermont. March 4-5, 2011 marked the 12th annual event. The race, which is open to skiers of all ages and abilities, has raised more than $400,000 for the Melanoma Research Fund at the Massachusetts General Hospital Cancer Center. David Newton, Peter’s brother and founder of Peter’s FUNd Racer, says, “We want to channel the passion that Peter had for life into raising awareness about this disease and pursuing research that will bring new hope to thousands of patients and their families.”

Foundation Brings HOPES to North Shore Susan de Vries, a wife and mother of three, lost her five-year battle with breast cancer in 2006. Following her death, de Vries’ closest friends established the Sue de Vries Cancer Foundation to continue de Vries’ mission of creating a community of caring and understanding for those whose lives are touched by cancer. A North Shore-based group, the foundation wasted no time getting involved when the Mass Susan de Vries General/North Shore Cancer Center opened in Danvers in June 2009. The foundation provided a significant gift to make wellness resources available to patients and families at the Mass General/North Shore Cancer Center. The gift enabled the HOPES Program, previously based solely at the Mass General Cancer Center’s downtown location, to expand to the Danvers facility. The HOPES Program focuses on improving the quality of life and well-being of patients, their families and friends through free wellness and complementary services such as massage and acupuncture, education and support services. Since this initial gift, the Sue de Vries Cancer Foundation continues to support the HOPES Program at the Mass General/North Shore Cancer Center.

A Day at Sea Luxury watch company Officine Panerai and Sail 4 Cancer, a nonprofit organization that helps individuals and families affected by cancer enjoy the healing powers of the sea, joined forces in 2010 to provide patients and caregivers with a restorative day of sailing. For six consecutive years, Officine Panerai has been title sponsor of an annual competition of vintage and classic yachts. In 2010, the watch company celebrated the completion of the first-ever vintage and classic racing circuit for North America by giving back to host communities through the respite sails. Massachusetts General Hospital Cancer Center patients, families and caregivers set sail under balmy skies on August 18 and October 8, 2010, launching out of Corinthian Yacht Club in Marblehead, Massachusetts. Paula Gauthier, LICSW, a social worker in the Maxwell V. Blum Cancer Resource Room and coordinator of the Network for Patients and Families, reported that “everyone was refreshed and inspired by the beauty of the sea around us.”

Pedaling in Pursuit of Childhood Cancer Now in its 9th year, the Granite State Quest (GSQ) is a 50- or 100-mile bicycle ride through southern New Hampshire that benefits the Center for Pediatric Hematology and Oncology at the MassGeneral Hospital for Children. On July 10, 2010, the one-day event started and finished at the Timberland Company in Stratham, New Hampshire, with more than 100 cyclists and 20 volunteers riding and working throughout a day of rain showers. “A few raindrops did not dampen the spirits and commitment of the riders,” says Howard Weinstein, MD, chief of MassGeneral Hospital for Children Pediatric Hematology and Oncology and one of the cyclists. On November 5, Bruce Taylor, founder of the GSQ, presented Weinstein with a check for $117,475 to advance childhood cancer research and care. The next GSQ will take place on July 9, 2011. For more information, contact Bruce Taylor at 603-773-1345 or visit www.granitestatequest.org.

Photo: Ann Marie Kane

From left, Sam Ebb, Max Ebb, David Ebb, MD, Bruce Taylor and Alex Taylor helped raise funds for childhood cancer.

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News from the Cancer Center 2010 Awards, publications and honors

Mass General Researchers Find Mutation Linked to Cancers Has Role in Stem Cell Survival A collaboration between the laboratories of David Scadden, MD, director of the Massachusetts General Hospital Center for Regenerative Medicine and co-director of the Harvard Stem Cell Institute; and Nabeel Bardeesy, PhD, scientist at the Mass General Center for Cancer Research, led to significant progress in understanding the role of a master regulator of cell metabolism. The finding, published in the December 2, 2010 issue of Nature, opens the door to studies of the relationship of the gene, LKB1, to cancer development by linking LKB1 to normal metabolism and growth control in hematopoietic stem cells (HSCs), which give rise to all blood cell types. “Imagine cells as automobiles,” says Scadden. “Cars have traditionally been very different on the outside but with essentially the same engine inside. Cells were viewed the same way. We knew they had very different functions, but believed they all had the same basic energy generation plant keeping them going.” This study demonstrates that stem cells are David Scadden, MD different from other cells types and points to how energy generation, a concept long thought to be straightforward in cells, can be different for different cell types. In normal cells, LKB1 mutation disrupts metabolism and affects the cell’s sense of polarity, causing chaos within the cell. In HSCs, the mutation disrupts functioning of the mitochondria, which help supply energy to the cell as well as play a role in other functions like signaling, cellular differentiation and cell death. Mutated HSCs also result in a brief burst of cell proliferation, after which cells lose viability, and are associated with elevated fatty acid levels. Bardeesy and other cancer researchers have linked the LKB1 mutation to the development of cancer, particularly pancreatic cancer, by inserting the mutated LKB1 gene into normal cells and discovering that cancer arises. How different tissues generate energy is an emerging area in both cancer and stem cell research. Scientists believe these studies can provide new avenues to possibly starve cancer cells or feed stem cells. Stephanie Xie, PhD, from Scadden’s lab and Sushma Gurumurthy, PhD, from Bardeesy’s lab led the study. ●

Joining Forces for Seamless Care For years, teams of clinicians at the Mass General Cancer Center and Massachusetts Eye and Ear Infirmary (MEEI) have successfully collaborated to provide multidisciplinary care for patients with cancers of the head and neck. As a result of a new relationship between the two institutions, administrative and technological impediments have been leveled, making the relationship even more seamless. The improvements are all behind the scenes, says Mass General Cancer Center Medical Oncologist and Medical Director of the Center for Head and Neck Cancers Lori Wirth, MD. But now care team members in both facilities can view patient medical records and imaging results regardless of where the patient was seen. Administrative barriers to sharing patients have also been removed. “Donors help us study rare and uncommon types of cancer,” says Wirth. “These diseases don’t have the support of large foundations, yet they are devastating to the families who face them. What we are now learning is that understanding the risks, treatment possibilities and outcomes of these rare cancers can help inform other, more common types of disease.” ●

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Cancer Center Chair Honors Bruce Chabner, MD The Massachusetts General Hospital Cancer Center established an endowed chair last year to honor Bruce Chabner, MD. Chabner is director of clinical research at the Mass General Cancer Center and has been a pioneer and a leader in the field of oncology for close to 40 years. The first incumbent of the Chabner Chair is Hematology Oncology Chief and Cancer Center Associate Director José Baselga, MD, PhD. Chabner joined Mass General in 1995 as chief of the Division of Hematology Oncology and clinical director of the Massachusetts General Hospital Cancer Center. Under his leadership, the Division of Hematology Oncology has grown ten-fold in faculty numbers and expanded to comprise an integrated multidisciplinary system of disease centers that attracts patients worldwide. Previously, Chabner led cancer drug discovery efforts at the National Cancer Institute (NCI). In his 26-year tenure there, he directed the national cancer treatment clinical trials research program, established the first intramural laboratory for the study of cancer drugs in humans, and led key drug development efforts, contributing significantly to the development of high-dose chemotherapy regimens and to standard therapies for lymphoma still utilized in cancer treatment today. He served for 13 years as director of NCI’s Division of Cancer Treatment. In 2006, President George W. Bush appointed Chabner to a Bruce Chabner, MD six-year term on the NCI’s National Cancer Advisory Board; Chabner currently chairs the board. The founding editor-in-chief for The Oncologist, Chabner is widely published and has mentored and trained many of the cancer research leaders in both industry and academia in the United States and abroad. The first incumbent of the Chabner Chair, Baselga is an internationally recognized physician-researcher whose studies are focused on targeted cancer therapies. He has led development of a number of targeted agents used to combat cancers with deregulated growth factor receptors, including breast cancer, lung cancer, melanoma and others. Currently, Baselga is spearheading international trials of combined therapies with the goal of impeding resistance to targeted agents. He has established the Center for Targeted Therapeutics at the Mass General Cancer Center to coordinate and expand early clinical trials across disease centers and to focus on identifying predictive biomarkers that will help match an individual patient’s tumor profile to therapy. The Chabner Chair was funded through the generosity of many friends and Martin Murphy, MD, and his wife, Ann (shown here with donors, including Martin Murphy, MD, and his wife, Ann. The Murphys met Davi-Ellen Chabner, left) helped spearhead efforts to Chabner when he headed Drug Discovery and Development at the NCI and establish the Bruce Chabner Chair. maintain a continuing friendship as well as a professional relationship. Their role in making the chair possible is intended to honor the man they view as “a caring and compassionate physician, a clear and critical thinker, a superb scientist, and an exemplary role model for the scores of fellows he has trained over the years and who now head cancer centers and academic departments all over the world.” ●

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Redesigned Circulating Tumor Cell (CTC) Chip Reveals Rare Cell Clumps

The newest generation of the circulating tumor cell (CTC) chip, above, isolated a cluster of CTCs from a patient with metastatic prostate cancer, below. No other method for sequestering these rare cells has captured clumps of tumor cells.

A redesigned microchip-based technology for capturing circulating tumor cells (CTCs), the second-generation CTC Chip has trapped rare, small clusters of circulating tumor cells. According to Shannon Stott, PhD, of the Massachusetts General Hospital Center for BioMicroElectroMechanical Systems (BioMEMS), no previous method for capturing CTCs has ever found such clumps of tumor cells. Stott is co-lead author of a paper published online in Proceedings of the National Academy of Sciences (PNAS) announcing the revamped chip technology. “These clusters may have broken off from the original tumor, or they might represent proliferation of CTCs within the circulation,” says BioMEMS Center Director Mehmet Toner, PhD. Senior author of the PNAS paper, he adds that “further study of these clusters could provide valuable insight into the metastatic process.” Toner co-leads the CTC Chip project with Daniel Haber, MD, PhD, director of the Mass General Cancer Center, who says the new technology “will enable increasingly sophisticated analyses of metastasis and support clinical research in targeted cancer therapies.” The updated chip, called the HB-(herringbone) Chip, provides more comprehensive and more easily accessible data from the rare cancer cells than its predecessor, the CTC Chip, which was also developed at the Mass General Cancer Center. The new device facilitates the increased production needed to conduct larger clinical studies. The national Stand Up To Cancer campaign, spearheaded by the Entertainment Industry Foundation and the American Association for Cancer Research, supported early development of this cancer analysis technology with a $15 million grant. This early funding enabled the Mass General Cancer Center to assemble a multi-institutional “Dream Team” that includes researchers from the Mass General Cancer Center, MIT, Memorial Sloan-Kettering Cancer Center, Dana-Farber Cancer Institute, and MD Anderson Cancer Center. A new collaboration with Johnson & Johnson, announced in January 2011, will support development of a third-generation device designed for mass production. The new device, when completed and tested, will make circulating tumor cell analysis more readily available to physicians and their patients. ●

CENTERPIECES

New Targeted Drug Shows Promise against Lung Tumors In a recent clinical trial led by the Massachusetts General Hospital Cancer Center and involving eight other cancer centers, a potential new targeted therapy demonstrated the ability to halt or reverse the growth of certain forms of non-small-cell lung cancer, the leading cause of cancer death in the United States. In the October 2010 issue of the New England Journal of Medicine, a multi-institutional research team led by Jeffrey Clark, MD, and Eunice Kwak, MD, PhD, of the Mass General Cancer Center reported that crizotinib, an inhibitor of the ALK and MET genes, shrank the tumors of more than half of those patients whose cancer was driven by alterations in the ALK gene. Crizotinib halted tumor growth in another one-third of patients. A phase III clinical trial is now enrolling patients, and research is also underway to develop the next generation of ALK inhibitors. More information is available by calling the Mass General Cancer Center at 877-789-6100 or visiting massgeneral.org/cancertrials. Prospective tumor genotyping has made it possible for research on crizotinib to proceed much more quickly than it did for other targeted therapies, such as erlotinib, another lung cancer drug. “The Mass General Cancer Center already had the infrastructure in place to screen tumors for molecular abnormalities, so we were poised to test for ALK rearrangement,” Kwak explains.  That screening capability enabled researchers to identify patients whose tumors might be expected to respond to the treatment.  “By allowing us to determine an individual’s potential responsiveness to a treatment based on known mutations, diagnostic testing of cancer tumors will improve treatment decision making and lead to improved clinical outcomes,” adds A. John Iafrate, MD, PhD, of the Mass General Pathology Service, senior author of the study and co-director of the Mass General Translational Research Lab. ●

ABC’s “Boston Med” Features Cancer Center Surgeons The “Boston Med” series that drew a national audience and critical acclaim last summer featured two Massachusetts General Hospital Cancer Center surgeons, William Curry, MD, and David Berger, MD, and offered viewers a very personal perspective on how physicians and patients move through the experience of cancer surgery. Curry, the neurosurgeon and brain cancer expert, whose 29-year-old patient, Ron Haynes, had a tumor in his sinus cavity, was candid about the surgical risks when the film crew interviewed him just before the procedure. “The tumor is right between the eyes,” he said. “It’s near the olfactory nerve, and is on the verge of invading the brain. If you miscalculate, if you interpret the anatomy wrong, the patient could go blind.” Haynes, the divorced father of a young boy, woke up after the surgery a bit agitated but clear-headed, with no serious side effects. A year later, Haynes was back on his feet, proud to be dating the “perfect girl,” and sharing a game of candlepin bowling with his son. In a subsequent episode, viewers watched as Berger, a colorectal and gastrointestinal surgeon and director of the Mass General Colorectal Surgery Center, met with patient Tom Alden to inform him that he had colon cancer requiring treatment. Weeks later, Alden’s relief about surviving the surgery turned to disappointment when Berger told him that he needed chemotherapy: Pathology reports showed the cancer had spread to his lymph nodes. Fortunately, Alden’s treatment was also successful. A year after concluding chemotherapy, he was back in his garden, reflecting on having survived cancer. “Dr. Berger caught it just in time,” he said. “Over a year ago, I was thinking about dying. Now I’m thinking about living.” ●

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Each year, the Institute of Medicine (IOM) of the National Academies elects up to 65 new members and five foreign associates, chosen for their professional achievements and for their willingness to actively consult on IOM initiatives. This year, two Massachusetts General Hospital physician-scientists joined the membership of the IOM: Mass General Cancer Center Director Daniel Haber, MD, PhD, Howard Hughes Medical Institute investigator and Kurt Isselbacher/Peter Schwartz Professor of Medicine at Harvard Medical School; and Mass General Center for Systems Biology Director Ralph Weissleder, MD, PhD, professor of Systems Biology and Radiology at Harvard Medical School. The new members join more than 1,700 colleagues who donate their time to provide unbiased and authoritative health care advice to decision makers and the public.

The Scadden laboratory focuses its research on the regulation of hematopoietic stem cells — the multipotent stem cells that give rise to all the blood cell types — by the stem cell microenvironment or niche. Based on their prior work to understand the mechanisms governing normal stem cells in a healthy environment, the Scadden team began investigating the role of the niche in disease. Their research has demonstrated the primary role the micro-environment can play in the emergence of malignancy. In a finding supporting the relationship between the micro-environment and cancer development, the Scadden team reported that silencing a gene known as DICER1 in bone precursor cells induced a blood disorder that has a high risk of evolving into leukemia. Understanding this link between disease development and genetic activity reveals new targets for cancer therapies. Scadden et. al. published their study in the March 2010 issue of Nature. Scadden’s work on cell-niche interactions has also contributed to the development of stem cell therapeutics and specifically, improving stem cell transplantation.

David Scadden, MD, Wins American Society of Hematology Award

José Baselga, MD, PhD, Receives Pinedo Prize

Last December, the American Society of Hematology honored Massachusetts General Hospital Cancer Center Chief of Hematologic Malignancies David Scadden, MD, co-director of the Harvard Stem Cell Institute and the Gerald and Darlene Jordan Professor of Medicine at Harvard Medical School, at its annual meeting in Orlando, Florida. During the meeting, Scadden, who is also director of the Mass General Center for Regenerative Medicine, received the 2010 Dameshek Prize for his contributions to stem cell biology. The Dameshek Prize is awarded annually to individuals who have made important contributions in hematology during the preceding years.

At its first meeting in Boston last November, the Society for Translational Oncology (STO) awarded the 2010 Bob Pinedo Cancer Care Prize to José Baselga, MD, PhD, Hematology Oncology chief, associate director of the Massachusetts General Hospital Cancer Center, and incumbent in the Bruce Chabner Chair in Hematology Oncology. The prize honors Baselga’s exceptional contributions to advancing breast cancer research, particularly through the development of new, targeted anti-cancer agents. His keynote lecture from the conference, “Building a Vision for the Future in Development of Targeted Therapeutics,” has been published in STO’s journal, The Oncologist.

Two Cancer Center Physicians Named to Institute of Medicine

Daniel Haber, MD, PhD

Ralph Weissleder, MD, PhD

David Scadden, MD

José Baselga, MD, PhD

CENTERPIECES

Baselga was previously chairman of the Medical Oncology Service and director of the Division of Medical Oncology, Hematology and Radiation Oncology at the Vall d’Hebron Institute of Oncology in Barcelona, Spain. He was the founding director of the Vall d’Hebron Institute of Oncology and a professor of medicine at the Universidad Autónoma de Barcelona. The Pinedo Cancer Care Prize, founded in 2006, honors Professor H. M. (Bob) Pinedo, founder of the Vrije Universiteit Medical Center Cancer Center Amsterdam, who combined world-class cancer research with devotion to patients and their families. STO Co-chairman Richard Goldberg, MD, hailed Baselga’s accomplishments as a leader of research into the biology that drives cancers at the molecular level, noting that his achievements “clearly exemplify the ideals that Professor Pinedo has championed as a researcher and caregiver.” Bruce Chabner, MD, of the Mass General Cancer Center, received the first Pinedo Prize in 2006.

Anthony Zietman, MD, Assumes ASTRO Chair As president of the American Society for Radiation Oncology (ASTRO) in 2010, Massachusetts General Hospital Cancer Center Radiation Oncologist and genitourinary cancers expert Anthony Zietman,MD, directed plans for ASTRO’s 52nd annual meeting in San Diego last fall. The meeting drew an estimated 12,000 radiation oncology professionals. At the beginning of this year, Zietman assumed the role of ASTRO chair. Throughout his tenure, Zietman has emphasized the separate but related themes of treatment efficacy and treatment safety. He stressed that integration of evidence-based principles into radiation oncology practice is crucial to preserving the field’s credibility. He also highlighted the need for more rigorous professional and institutional standards to ensure continued public trust in the quality and safety of radiation treatment centers. Zietman and ASTRO are working with the American College of Radiology to strengthen the national

practice accreditation program and have called on Congress to increase regulatory oversight by passing the CARE Act, which advocates stricter standards and staffing requirements. “As a long-established leader in radiation oncology,” notes Zietman, “the Mass General Cancer Center can assure our patients that we meet the highest safety and accreditation standards. Every radiation treatment center should be able to give their patients that same assurance.”

Cancer Center Experts Author New Text Mass General breast cancer physicians have edited a new text, Breast Cancer: A Multidisciplinary Approach to Diagnosis and Management. Led by Radiation Oncologist and Mass General Cancer Center Breast Service Chief Alphonse Taghian, MD, PhD, the editorial team includes Breast Surgeon Barbara Smith, MD, PhD, director of the Mass General Hospital Breast Program, and Medical Oncologist John Erban, MD, the former clinical program director and co-director of the Gillette Center for Breast Cancer at the Mass General Cancer Center. Published in 2010 by DemosMedical, the new book offers oncologists and other clinicians a comprehensive update on the multiple dimensions of breast cancer care and quality-of-life issues. Contributing chapter authors include additional Gillette Center physicians as well as breast cancer experts from other cancer centers.

Anthony Zietman, MD

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A YEAR IN REVIEW: BY THE NUMBERS

23

The number of multidisciplinary disease centers and clinical programs that comprise the Mass General Cancer Center.

7,026

The total number of newly diagnosed cancer cases treated at the Mass General Cancer Center in 2009.

1,035

The number of clinicians participating in multidisciplinary care in our Cancer Center clinics.

46

The average age of the Mass General Cancer Center faculty/clinicians. We are exceptionally proud of the fact that several faculty who trained at our Cancer Center have subsequently assumed leadership positions at other leading national cancer centers.

35%

The percentage of female faculty practicing within the Cancer Center.

327

The total number of cancer-related clinical trials conducted at the Mass General Cancer Center during the past year, including Phase I, II and III programs.

18

The number of shared laboratory and clinical resources available to researchers at the Mass General Cancer Center. These core assets are the backbone of our research enterprise, providing state-of-the-art technologies and scientific consultative services to aid investigators in their research efforts. Shared resources include: Biostatistics Unit Cancer Pharmacology Core Center for Cancer Risk Assessment Center for Computational Discovery Center for Molecular Therapeutics Center for Outcomes Research Circulating Tumor Cell Center Edwin L. Steele Laboratory for Tumor Biology Francis H. Burr Proton Therapy Center Institute for Healthcare Policy MGH Tissue Repository Palliative Care Phase I Clinical Trials Program Molecular Profiling Laboratory Specialized Histopathology Core Tobacco Research and Treatment Center Translational Research Laboratory Tumor Imaging Metrics Core

A YEAR IN REVIEW: BY THE NUMBERS

1,400

The number of our patients whose tumors were “fingerprinted” or genotyped for specific genetic mutations in 2010; Some mutations now have identified therapies that can specifically target the “on” button in cancers, repressing cell growth. The Mass General Cancer Center Pathology Department is at the forefront of genotyping technology, developing a platform to conduct large scale screenings across all tumor types.

$28 million

The total amount of competitive National Institutes of Health/National Cancer Institute grants the Mass General Cancer Center received for cancer research in the past year.

130

The number of genetic mutations screened for in genotyping analysis at the Mass General Cancer Center.

11,480

The average volume of proton therapy treatments each year in our Francis H. Burr Proton Therapy Center. Our center is currently one of only nine proton facilities in the United States, treating cancer patients with highly precise proton beams, to minimize exposure to healthy tissue.

8,475

The number of cancer-related surgical procedures completed at the Mass General Cancer Center in 2010.

7

The Massachusetts General Hospital Cancer Center’s national rank in the 2010-11 U.S. News & World Report’s “America’s Best Hospitals” list for cancer treatment. The Cancer Center has jumped in rank from 15 to 7 in the past five years.

59,366

The number of donors contributing to the $169.7 million in philanthropic funds raised during the past five years.

410,000 The approximate total of additional square footage dedicated to cancer services within the new Lunder Building scheduled to open later this year.

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LOOKING FORWARD

Dear Friends, Massachusetts General Hospital’s bicentennial year is a particularly poignant time to contemplate the many significant ways in which we have redefined medicine and served the community during the last two centuries. Yet even as we celebrate our past achievements, the Massachusetts General Hospital Cancer Center looks to the future to ensure we are creating the clinical research programs required to overcome this disease. The next step to turning insight into more effective treatments is a massive effort to identify what makes a tumor unique and how cancer resists or overcomes therapies. Simultaneously, we need a push to create treatments that target those cellular activities and disable them. This work involves building alliances with pharmaceutical and biotechnology partners. It demands rigorous and creative research design and effective, multidisciplinary collaboration. It encompasses development of more sophisticated surgical techniques, radiation therapy, and imaging technology, as well as continuing partnership with our renowned Pathology Department. And it incorporates the need for efficiency to support our focus on moving new treatments quickly through the pipeline and into clinical trials while continuing to provide our patients with top-quality, cost-effective care. By integrating progress in each of these arenas, we have laid the groundwork for continuing success in the years ahead. Our strategic plan defines how we will continue to break new ground as we pioneer the next generation of cancer care, by concentrating our efforts on six strategic goals to guide our work: Strengthen our knowledge to conquer cancer, achieve focused clinical growth, develop strategic satellite-affiliate relationships, build a strong national brand, expand our collaborations and infrastructure, and maintain financial viability. These goals serve as our roadmap in reaching our vision: To bridge scientific discovery and clinical care to conquer cancer, while setting the standard of excellence in personalized care for patients and their families. Each of the stories you have read in this issue of Synergy illustrates how our past efforts have paved the way to our current successes. In the year ahead, we will continue to set the pace for a new generation of cancer care, demonstrating the power of our vision and the strength of our institution. We look forward to sharing our 2012 issue of Synergy, when we can introduce you to the new Lunder Building and to our progress and achievement of new milestones in our quest to conquer cancer.

José Baselga, MD, PhD Chief, Hematology Oncology Associate Director, Cancer Center

The Lunder Building, scheduled to open August, 2011, features a central atrium that brightens interior spaces with natural light. The building will house two inpatient floors for cancer patients, infusion suites, and a satellite pharmacy, plus radiation oncology.

Credits Synergy is published by the Massachusetts General Hospital Cancer Center for friends and supporters of the Cancer Center. If you have comments or would like to be added or removed from the mailing list, please contact: Massachusetts General Hospital Cancer Center Marketing Department 55 Fruit Street, LH200 Boston, MA 02114 877-726-5130 [email protected] Jodie Justofin Senior Managing Editor Kate Woodworth Editor Senior Writer Laurie Covens Michelle Filteau Eve Nichols Writers Arch MacInnes Designer and Illustrator Paul Batista Joe Ferraro Sam Riley Joshua Touster Bill Truslow Photographers Shawmut Printing Printer

Spring 2011

A Comprehensive Cancer Center An integral part of one of the world’s most distinguished academic medical centers, the Massachusetts General Hospital Cancer Center is among the leading cancer care providers in the United States. U.S. News & World Report consistently ranks the Mass General Cancer Center as one of the top ten cancer centers in the country. Its nurses were the first in Massachusetts to achieve Magnet status from the American Nurses Credentialing Center in recognition of the hospital’s exceptional nursing care. Known for providing customized, innovative treatments and compassionate care to both adults and children, the Cancer Center comprises 23 fully integrated, multidisciplinary clinical programs and a vast array of support and educational services. Its network of affiliations extends throughout New England and the southeastern U.S. The Cancer Center’s commitment to eradicating cancer is fueled by scientific investigation conducted as part of one of the largest hospital-based research programs in the nation. Through a powerful synergy between laboratory scientists and bedside physicians, the Mass General Cancer Center fosters innovation in all phases of cancer research. Physician investigators conduct nearly 400 clinical trials annually. The Massachusetts General Hospital Cancer Center is proud to be a founding member of a Harvard Medical School consortium designated by the National Cancer Institute as a comprehensive cancer center. This prestigious seven-member center forms the largest cancer research collaboration in the country. The promising new treatments developed through this partnership are revolutionizing the future of cancer medicine.

55 Fruit Street • LH-200 • Boston, MA 02114 massgeneral.org/cancer 877-726-5130

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