Welcome the 2006 Class of Hematology/ Medical Oncology Fellows

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&and the winner is& Welcome the 2006 Class of Hematology/ Medical Oncology Fellows A Division of Cancer Medicine Information Exchange VOL. 3 NO. 2 2006 (Continued on page 4) Ricardo Alvarez, M.D.

Residency: University of Texas Health Science Center 4Houston M.D.: Universidad Nacional de la Plata,Argentina Dr.Alvarez expresses a strong interest in academic oncology,having already served as section chief at a large public hospital in Argentina,where he established a tumor registry.In addition,he worked as a clinical research associate for an oncology practice in Houston and authored or co-authored several articles published in peer-reviewed journals.Dr.Alvarez 9s primary inter- ests are conducting drug development trials,learning molecular laboratory techniques,and increasing his clinical knowledge of both solid tumor and leukemia management.After presenting to the American Society of Hematology (ASH) his research on myelofibrosis in CML,he said, cI expect to publish future data produced by the protocols I generate and I 9m looking forward to extending my medical writing to include text chapters and review articles. dAn evaluator referred to him as an cabsolute star. dAnother wrote, cI am confident that he could become an independent investigator in a very short time. d " Lauren Averett, M.D. Residency: Johns Hopkins University M.D.: Baylor College of Medicine ... more. less.

Dr.Averett 9s passion for the physician-scientist track began during her one-year fellowship at the National Cancer Institute, where she learned it was possible to use cDNA microarrays to study lymphoma tissue samples to predict which patients would respond to I t was the notification they were all waiting to receive. Thirteen of the brightest future oncologists were invited in May to join our Hematology/ Medical Oncology Fellowship Program. It was quite an honor to be selected as 220 candidates applied. Fifty-seven were called in for interviews, making the selection process take several weeks. Several members of the new class were drawn to oncology for personal reasons 4the loss of a loved one to the disease or because of a surprising response from a patient during their medical rotations or residencies. A few have worked as chief residents and have already published in prestigious journals. Their nominators speak of them as promising, driven, inquisitive, and thorough. chemotherapy based on the genes expressed in their tumors.The work was published in the New England Journal of Medicine. cI was fascinated that my team 9s investigation could have a direct impact on clinical practice, d she recalled. Dr.Averett has not determined which cancer she will focus on but she knows what types of questions interest her, such as how genetic data from tumor profiling projects can be used to develop new targets and additional markers that will allow doctors to screen for occult disease and moni- tor treatment response. Her evaluators said, cShe is impressive, has the intellectual gifts to succeed in academic medicine, and should be classified as a 8can 9t miss 9 when considering candidates. dAnother said Dr.Averett has the medical knowledge, interper- sonal skills with patients, and a spark that puts her on par with the best and brightest young physicians he 9s ever supervised. " Fadi Braiteh, M.D. Residency: Hospital of St. Raphael,Yale University School of Medicine M.D.: St. Joseph University in Beirut, Lebanon The start of Dr. Braiteh 9s fellowship will not be the beginning of his work at M. D.Anderson. He spent the past two years as a clinical fellow in the Phase I Program. He was also a Palliative Care and Symptom Management fellow in 2003-2004.A Ph.D. student at The University of Texas School of Biomedical Sciences, Dr. Braiteh wants a career as a Citation for Excellence Winners were: Administration: Mark Choate, systems analyst services manager, Cancer Medicine Administrative Office Administrative Support: Susana Mendoza, unit services coordinator,Ambulatory Treatment Center Advanced Clinical Practice: Maxine Burnett, advanced practice nurse, Genitourinary Medical Oncology Clinical Nursing Practice: Kavin Hanzik, clinical nurse, Palliative Care Center Clinical Research: Rabia Khan, research data coordinator, Gastrointestinal Medical Oncology Communications, Education, and Information Services: Jerry Gilbert, systems analyst II, Cancer Medicine Administrative Office Financial Services: Flora May Partisala, financial analyst,Thoracic/Head & Neck Medical Oncology Laboratory Research: Qinghua Yu, senior research assistant, Molecular Therapeutics We 9ll have photos and more on the winners in the next issue of DoCMessages, coming out later this summer. Deory Melliza, clinical nurse in the Ambulatory Treatment Center, was named the DoCM Third Exemplary Employee during the 2006 Recognition and Awards Program, held May 18th. After 25 years at M. D.Anderson, he still looks forward to coming to work every day to help patients. C ancer Medicine Division Head Waun Ki Hong, M.D., will have a direct hand in shaping the policies of the American Society of Clinical Oncology starting in August when he joins the Board of Directors. A member of the organization since 1974, he recently described some of the issues he wants to help ASCO tackle during his tenure. One is procuring additional money that would give the current pool of physician-scientists more dedicated time to conduct translational research. Dr. Hong wants to secure more government, pharma- ceutical, and philanthropic resources that can be used to fund additional Young Investigator Awards and Career Development Awards to cgrow d future generations of oncologists. It 9s a desire that coincides with his goal for more division fellows and young faculty members to receive these competitive awards. He added that improving the way research is disseminated is also worth tackling because, cFar more research data are being presented at the annual meeting than clinicians can hope to digest and apply to practice. The society should develop more efficient methods for timely distribution. d Although ASCO 9s membership is quite diverse 4representing medical, surgical, pediatric, and radiation oncologists, as well as cancer survivors 4Dr. Hong believes it can be better. cIt is imperative that represen- tation on all committees and educational programs better reflect all specialties and the society 9s growing international membership. d Overcoming the huge challenge of getting adequate payment for cancer treatment remains a goal for ASCO 9s members, particularly at the community level where approximately 90 percent of the nation 9s cancer treatment is provided. cThey are at a disadvantage when it comes to accessing new drugs and obtaining reimbursement from third-party payers, d said Dr. Hong, who wants the society to be out front in promoting policies through the Centers for Medicare and Medicaid Services (CMS) and the NCI to ensure equity in access. Dr. Hong will serve on the board for three years. Gabriel Hortobagyi, M.D., chair of Breast Medical Oncology, began his term as president in June. 2 DoCMessages " Vol. 3 No. 2 2006 A Message From Waun Ki Hong,M.D.,Head,Division of Cancer Medicine Dr. Hong Looks Toward Future As He Joins ASCO Board The first six external advisory board (EAB) meetings were held from January through May, 2006. Three national experts in each field were invited to evaluate patient care, research, and education and training based typically on a full day of presentations and question-and-answer sessions. At the end of each session, the evaluators met with division- and depart- ment-level executives to advise on scientific and programmatic direction. For more about the EAB program in general, see the summer 2005 issue of DoCMessages on the DoCM web site. Cross-cutting issues that evaluators raised in most sessions included: " Sufficient protected time to develop true translational researchers and physician scientists and to allow junior faculty to do original research. " Institution of a backup position for key personnel to ensure continuity of critical programs and laboratories. " Prioritization and realistic planning of clini- cal trials to ensure adequate patient accrual. " Access to tissue banks and patient databases. " Ability to study biomarkers and targeted therapies, with access to microarray technology. " Adequate collaboration outside the depart- ment and division to ensure patient accrual to clinical trials. " Adequate collaboration between basic scientists and clinical investigators. The Palliative Care and Rehabilitation Medicine EAB, held January 27th, impressed evaluators with the extremely rapid clinical growth of the Symptom Control & Palliative Care Section since the department 9s inception in 1999. The number of MD faculty and APNs doubled over the past five years and corre- spondingly, faculty clinical time rose from 55% to 77%, which severely constrains time avail- able for education and research activity. The board recommended hiring four or five physi- cians to accommodate further clinical growth while also giving them protected time to develop research careers. The oncology fellows have given outstanding reviews of their mandatory four-week rotation in palliative care, in which they participate in hospice, outpatient, and inpatient palliative care. The EAB recommended expanding the one-year palliative care fellowship to a second year focusing on research to develop academic clin- ical researchers. Despite the dearth of funding available for palliative care research, the department 9s publication output is impressive and collaboration is strong with other research programs at M. D. Anderson. The board recommended identifying additional non-government sources of funding such as foundation and philanthropic sources. The board also recommended marketing the benefits of palliative care to patients and their families institution-wide. The Blood and Marrow Transplantation (BMT) EAB, held March 27th and 28th, particularly commended the GMP laborato- ry, with its capacity to generate cell-based targeted therapeutics, as the critical center- piece for BMT. Evaluators identified cellular therapeutics as the department 9s most important priority for the future. They recognized, however, that cell therapy research is difficult to staff and fund through peer-reviewed sources. cTranslational research is a word, not an event, without a major commitment to basic science, d noted Robert Negrin, M.D. The evaluators recommended recruiting more experts in cancer stem cell biology while recognizing the difficulty in finding and attracting the best translational researchers. They want to see the GMP lead national training in cell manipulation, and recommended that M. D. Anderson dramatically increase annual funding for project support to stay ahead of the competition. cIf cell therapy becomes standard of care for anything, this is what M. D. Anderson will become known for, d commented Lee Nadler, M.D. cIf you frame it that way, a million dollar investment is like spending a nickel. You are investing in a paradigm shift. d They also view the cell bank of leukemia samples as a major national resource and recommended adding myeloma and other disease samples. The evaluators also recommended strengthening relationships and collaboration with the Department of Leukemia as well as with pharmacogenomics investigators through the Kleberg Center for Molecular Therapeutics. They saw a need to expand and apply new therapeutic concepts to the lymphomas, particularly innovations emerg- ing from immunology and developmental chemotherapy in multi-institutional trials. Investigators will continue to chip away at the main immunologic barrier: how to make transplants safer and more effective by increasing graft vs. leukemia or other disease response while decreasing graft-vs.-host disease and its associated mortality and morbidity. Controlled expansion in clinical research was advised, while implementing a system for prioritizing and supporting critical core stud- ies to ensure their completion. The board emphasized the need to discourage clinical growth at the expense of clinical impact. The Community Clinical Oncology Program (CCOP) EAB, held March 29th, recommended collaborating more with External Advisory Board Meetings Suggest Future Directions B E A External Advisory Board 3 DoCMessages " Vol. 3 No. 2 2006 M. D. Anderson behavioral scientists to do more control trials in symptom management focusing on pain, fatigue, and depression; to survey assessment of quality of life; as well as to evaluate cancer control protocols after they close. The evaluators suggested encouraging medical oncology fellows and junior faculty to do cancer control trials while rewarding faculty participation in CCOP trials. The CCOP will design future trials based on the needs and preferences of physicians specific to their community practices. The program 9s director, Michael Fisch, M.D., recommends taking the advice of a boy with AIDS quoted in USA Today , December 1, 2004, to, cDo all you can with what you have in the time you have in the place you are. d The need for community outreach was empha- sized to determine whether a study is relevant to the patient treatment needs of a specific community as well as their capacity to accrue enough patients in a given trial. Christopher Logothetis, M.D., chair, Genitourinary Medical Oncology proposed to the EAB, held March 31st, that the department aims to improve the efficiency of their clinical investigations, steer away from anatomy-based classification driving therapeutic options, and increase their proportion of translational facul- ty. Toward these goals, faculty focus has shifted in the past five years from 29 to 50 percent basic science faculty. Noting the marked increase in new junior faculty, the evaluators recommended strengthening mentorship of new recruits. They also recommended expanding collaborations with basic scientists outside the department. The clinical prostate program with its biologic model and emphasis on the epithelial-stromal interaction was esteemed as a major strength of the department. They considered the human vascular map project a strong translational science initiative focused on the interface between prostate cancer progression and tumor vascularization. The board advised more scien- tific collaboration between the department and SPORE investigators based in the Department of Urology to further develop an advanced disease bladder program. They felt that clinical and scientific development of the renal cell car- cinoma program and germ cell tumor program would particularly benefit from collaboration and recruitment, as would genomics initiatives. The Leukemia EAB, held April 19th, revered the department 9s clinical research program, particularly commending the high rate, 80 per- cent, of patients enrolling in clinical trials, and the department 9s involvement in the most sig- nificant clinical advances in leukemia over the last 15 years. cThere is nothing in the United States in the field of leukemia, and perhaps even in the larger oncology world, that matches the depth, breadth, or efficiency in which this department conducts its clinical research efforts, d commented the EAB in their review. cNo other group comes close to matching the productivity of this group in the conduct and presentation of new therapeutic approaches for leukemia. d However, the board would like to see better focusing and prioritization of clinical trials. Although the board recognized the department 9s collaborations with top scientists outside the institution, they would like to see growth in basic and translational research through more collaboration with basic science departments at M. D. Anderson as well as founding of a hematopoietic cancer insti- tute, with additional laboratory space allocated, combining basic with clinical investigators. Additional lab space along with recruitment of more basic science faculty dedicated to leukemia research would also enable adequate training and mentoring of junior faculty. The board felt that the Hematology/ Medical Oncology Fellowship Program could provide a pool of applicants if they are mentored toward readiness for junior faculty appointments with a basic science and translational research focus. The Sarcoma EAB, held April 24th, praised this department for its international leadership in treatment of sarcomas, with half of patients coming from outside Texas, but wanted to see more money spent on molecular biology and translational research. The board also com- mended clinical research faculty for being among the few medical oncologists at M. D. Anderson to enter patients onto Phase III multi-center trials. They recommended increasing emphasis on correlative, translation- al, and biologic research, and commended the department for recent efforts to bolster its research component by hiring a junior level physician scientist and a clinical trials investi- gator. At the forefront are their studies of genomic aberrations and imatinib therapy and resistance in gastrointestinal stromal tumors (GIST). The board recommended recruiting and providing laboratory space for a well-estab- lished investigator in sarcoma biology, who will also mentor new junior faculty. Other recommendations included getting an inter- institutional SPORE, and attracting fellowship program trainees to specialize in sarcoma, since there is a nationwide shortage of sarcoma medical oncologists. cI can 9t name ten other sarcoma programs in the world like this one, d board member Laurence Baker, D.O. comment- ed. Lee Helman, M.D. from NCI added, cThis is one of only two or three places in the world where one can specialize in sarcoma. M. D. Anderson is the cornerstone for develop- ing the field of Sarcoma Medical Oncology. d The Gastrointestinal Medical Oncology EAB, held May 3rd, will be covered in the next issue of DoCMessages, along with Neuro-Oncology (July 24th) and Melanoma (August 11th). 3 By Carol Howland External Advisory Board Members Blood and Marrow Transplantation Lee Nadler, M.D. Harvard Medical School Dana-Farber Cancer Institute Boston, MA Robert Negrin, M.D. Stanford University Medical Center Stanford, CA Richard O 9Reilly, M.D. Memorial Sloan-Kettering Cancer Center New York, NY Community Clinical Oncology Program Patrick Loehrer, M.D. Indiana University Walther Cancer Institute Indianapolis, IN Charles Loprinzi, M.D. Mayo Clinic Rochester, MN Carol Moinpour, PhD Southwest Oncology Group Seattle,WA Genitourinary Medical Oncology William Kaelin, Jr., M.D. Harvard Medical School Dana-Farber Cancer Institute Boston, MA Derek Raghavan, M.D., F.A.C.P. Cleveland Clinic Taussig Cancer Center Cleveland Clinic Foundation Cleveland, OH Owen Witte, M.D. Department of Microbiology, Immunology, and Molecular Genetics University of California, Los Angeles Los Angeles, CA Leukemia Gary Gilliland, M.D. Harvard Medical School Brigham & Women 9s Hospital Boston, MA Ching-Hon Pui, M.D. St. Jude Children 9s Research Hospital Memphis,TN David Scheinberg, M.D., Ph.D. Memorial Sloan-Kettering Cancer center New York, NY Charles Schiffer, M.D. Barbara Ann Karmanos Cancer Institute Wayne State University Detroit, MI Palliative Care and Rehabilitation Medicine Janet Abrahms, M.D. Dana Farber Cancer Institute Boston, MA Robin Fainsinger, M.D. Royal Alexandra Hospital Edmonton,Alberta, Canada Kathleen Foley, M.D. Memorial Sloan-Kettering Cancer Center New York, NY Sarcoma Laurence Baker, D.O. University of Michigan Medical School Ann Arbor, MI Jonathan Fletcher, M.D. Harvard Medical School Brigham & Women 9s Hospital Boston, MA Lee Helman, M.D. Center for Cancer Research National Cancer Institute Bethesda, MD cIf you frame it that way, a million dollar investment is like spending a nickel. You are investing in a paradigm shift. d 3 Dr. Lee Nadler 4 DoCMessages " Vol. 3 No. 2 2006 Medical Oncology Fellows continued from page 1 B y far, the June 9 graduation ceremony for the 2006 class of Hematology/Medical Oncology Fellows was the biggest in division history. Sixteen doctors received cer- tificates of completion of their advanced training at a dinner at the Houstonian Hotel Club & Spa in the Galleria area. This year, Dr. Hong named Emil J. Freireich, M.D. an cHonorary First Fellow d to commemorate the 40th annual graduation and for being there when the program began. Other faculty members pre- sented with awards were Gordon Mills, M.D., Ph.D., for mentorship; and Robert Wolff, M.D, for leadership. Earlier in the evening, the fel- lows gave Michael Fisch, M.D., an award for teaching. Education and Training 3 By Maxsane Mitchell physician-scientist where he can combine patient care with research, particularly to create innovative clini- cal trial designs, explore new endpoints for response, and develop new therapies 4especially for patients suffering from advanced metastatic cancer. Evaluators believe Dr. Braiteh will become a leader among physician-scientists. cHe has excellent clinical skills, has a caring personality that is appreciated by patients and their families, and is able to research difficult diagnoses and translate the information into actual treatment for patients 4particularly those suffering from complex pain and end-of-life issues. d Dr. Braiteh 9s outstanding research at M. D.Anderson has already earned him two awards 4the Tenth Trainee Recognition Day, Berlex Oncology Award in Patient Oriented Research 2006, and a 2006 ASCO Foundation Merit Award. " Vince Cataldo, M.D. Residency: Louisiana State University M.D.: Louisiana State University Dr. Cataldo is interested in academic oncology where he will be able to offer patients the latest in therapy and teach future oncologists. He is particularly interested in Leukemia as a subspecialty. Dr. Cataldo 9s evalua- tors said he has always performed beyond expectations, has superb interpersonal relations with his patients, and enthusiastically researches the latest in current and trial treatments to present patients with every option. " Jennifer Cultrera, M.D. Residency: Jackson Memorial Hospital M.D.: University of Miami Dr. Cultrera was in a car accident that prevented her from enrolling in med- ical school when she originally intended. She had to first spend a year in a rehabilitation program learn- ing how to walk properly again. She recalls the tremendous teamwork of doctors, nurses, and therapists who helped her through it all. cI will strive to attain that level of professionalism throughout my life. d During her recov- ery, she entered a Ph.D. program 4 where her study of CML patients and the induction of the CD95 receptor using interleuken-2 on blast cells sparked an interest in hematology and oncology. cThese fields are undergoing a renaissance where dis- coveries are being unraveled. In an era when molecular genetic approaches are revolutionizing medi- cine, these areas stand poised to gain benefits, d said Dr. Cultrera. Evaluators said of her work ethic, cShe always volunteers to take on the most com- plex cases and shows a great deal of empathy toward patients. She works hard, has a solid depth of knowledge of hematology and oncology, and is expected to have a productive career in these fields. d " Don Gibbons, M.D., Ph.D. Residency: Baylor College of Medicine Ph.D. & M.D.: Albert Einstein College of Medicine Dr. Gibbons believes the big issue fac- ing new physicians is whether to be practitioners of current knowledge or to create new knowledge. cI firmly embrace the latter and view a career in academic medicine as the best way to achieve balance as both a physician and a scientist. d He was bitten by the research bug during his Master 9s pro- gram, where he studied the function of chaperonins and published three first author papers in the Journal of Biological Chemistry. In another project, he coordinated the work of three labs in New York and France to determine the mechanism by which unique mem- brane proteins facilitate virus entry into target cells. cUsing the information, it 9s now possible to test ways to prevent infection by viruses such as dengue, West Nile, and St. Louis encephalitis, d Dr. Gibbons noted. Evaluators describe him as having an analytical mind, one who takes creative approaches to his research and writing, and a thorough physician who has a superb bedside manner. cDon has a longstanding inter- est in pursuing an academic career in hematology/oncology, with an emphasis on research. He 9s the rare individual who truly combines an impressive research foundation with incredibly strong clinical and interper- sonal skills. d " Wei Lin, M.D. Residency: Massachusetts General Hospital M.D.: Harvard Medical School Dr. Lin spent the first 12 years of his life at the largest cancer center in Beijing. He was not a patient; he was the son of two medical residents who lived at the adjoining housing complex. As a child, he played in the courtyard where patients strolled with their own kids. cI enjoyed talking to the patients and I wanted to do something to improve their welfare, d said Dr. Lin. With an undergraduate degree in physics, he wants to be involved in translational research that would combine basic science and clinical medicine to advance molecular imag- ing. cTechnologic innovations have permitted imaging the metabolic activ- ities of neoplasms with FDG-PET. But current advances in our understanding of tumor biology suggest a far greater use of this tool, d he said. cFor example, we can use radio-labeled antibodies to examine the expression of cell-surface receptors in vivo . d Evaluators refer to him as scholarly. cPatients who have Dr. Lin on their team will receive the best care. He has a truly multi-dimensional intellect, that rare person who is as comfortable in the theoretical as well as the practical realm. d " Petros Nikolinakos, M.D. Residency: Cook County Hospital M.D.: University of Debrecen, Hungary Dr. Nikolinakos did his residency at one of the busiest public hospitals in the country with heavy outpatient clinics and inward rotation, but he still found time to create an academic program for the interns and students. He also served an additional year as chief resident and contributed to three peer-reviewed articles, including one in the New England Journal of Medicine about the difficult diagnosis of a myeloma patient. Evaluators applaud his meticulous patient care, evaluation of test results, and grace under pressure.After working at a small hospital in rural Nebraska, Dr. Nikolinakos wants more training in hematology and oncology. cI have gained the most satisfaction from the relation- ships that I have built with oncology patients.They face a humbling and unique set of problems that require competent and compassionate care. d " Vijay Peddareddigari, M.D. Residency: Albert Einstein Medical Center M.D.: All India Institute, New Delhi, India Dr. Peddareddigari 9s interest in becoming an oncologist began when he was in medical school and his grandfather was diagnosed with advanced lung cancer. There was ultimately little that could be done for him. cThe ordeal left me shaken, angry, and insecure.Years later my grand- father 9s brother died from the same cancer. d He decided that combining strong clinical skills and laboratory cancer research was the best way to someday be in a position to give hope. Dr. Peddareddigari has been interested in everything from basic science applications Class of 2006 Hematology/Medical Oncology Fellows Graduate 5 DoCMessages " Vol. 3 No. 2 2006 to gene and cell therapy to bio-nan- otechnology. He is currently seeking a patent on a serum and gelling agent composition that can be used in medical, surgical,and wound repair applications. During his residency,Dr.Peddareddigari spent a month at M.D.Anderson 9s Thoracic Center,working under the supervision of Katherine Pisters,M.D. Evaluators throughout his career say Dr.Peddareddigari is a lateral thinker who has the capability of becoming a great physi- cian-scientist. cHe is very motivated. d " Sarina Piha-Paul, M.D. Residency: Baylor College of Medicine M.D.: Louisiana State University Dr. Piha-Paul envisions a medical career that combines clinical practice with research in hematology/oncology, head and neck cancers, and palliative care. She came to that decision in her third year of medical school when she was assigned to an inpatient oncology serv- ice for two weeks. Dr. Piha-Paul was most affected by a 43-year-old woman with stage IV breast cancer, which had metastasized to her brain. cWe talked about how much time she had left and how much she would regret not seeing her eight-and eleven-year-old daughters grow up, d recalled Dr. Piha-Paul. cSomething in my soul shifted into place and I knew that oncology was a field I should dedicate my life to. d Evaluators refer to the former chief resident as intellectually curious, a leader, possess- ing excellent procedural skills, and having a laser-like focus on patient care. Her previous work also includes helping to produce a patient education video discussing cancer diagnosis. " Alfonso Quintas-Cardama, M.D. Residency: Albert Einstein College of Medicine M.D.: University Santiago School of Medicine, Spain Like a couple of his new classmates, Dr. Quintas-Cardama has previous experience at M. D.Anderson, as he completed a rotation in Leukemia during his residency and recently fulfilled a one-year term as a fellow in the same department, where he has focused largely on clinical investigation of chron- ic myelogenous leukemia (CML) and lab research in B-cell malignancies. He is a 2006 ASCO Young Investigator Award recipient whose funds will support his efforts to develop prognostic factors and a vaccine for CML patients. cThe sense of unity and cooperation that drives M. D.Anderson 9s pursuit is inspiring, d Dr. Quintas-Cardama said. His evalua- tors believe he will have no trouble achieving his goals. cHe brims with interest, is an excellent clinical physi- cian, and has an enormous drive for research. He has never wavered from the beginning about having a career in leukemia research. d " Ronjay Rakkhit, M.D. Residency: Baylor College of Medicine M.D.: Medical University of South Carolina Dr.Rakkhit chose oncology after seeing the quality of care his mother received during her treatment for breast cancer 4a disease that ultimately took her life when she was just in her 40 9s. cI took this impression to medical school, d he said.Dr.Rakkhit is particularly inter- ested in prostate cancer and has participated in an investigation with Genitourinary Medical Oncology on the clinical outcome of patients with prostate ductal adenocarcinoma after radical prostatectomy.He has gone on medical missions to Calcutta, India. Evaluators believe any patient will be well-served by Dr.Rakkhit because he is very adept at performing examina- tions,eliciting from patients relevant information about their symptoms and deciding on a course of treatment based on that information,and he always seeks out research opportunities to advance the field. " Tomasz Srokowski, M.D. Residency: Washington University M.D.: Washington University School of Medicine Dr. Srokowski emigrated from Poland after he earned a four-year physical therapy degree. cI decided I didn 9t want to practice in a socialized health- care system, but I still loved helping patients, so I moved to the U.S. in search of a better life, d he said. Dr. Srokowski then spent another two years in pre-med studies before gaining admission to medical school. During his residency rotations, he was drawn to medical oncology. cI value learning about the patients 9 diseases, but also learning about their life stories, their families, and the way they cope with their illnesses. d He is inter- ested in a career in academic medicine where he can be involved in patient care, clinical research, and teaching. Dr. Srokowski said he wants to do more studies on hematologic and lymphoid malignancies, as well as disorders of hemostasis such a Hemolytic Uremic Syndrome. Evaluators believe he will have a productive career.They describe him as a tenacious person who possesses considerable fortitude. " M edical oncology fellows on clinical rotation at LBJ Hospital shared emotional stories about terminally ill patients who died in their care. The dialogue was part of Schwartz Center Rounds, held in January. The forums are named after healthcare attorney Kenneth Schwartz, who died at the age of 40, less than a year after he was diagnosed with advanced lung cancer. Appreciative of the medical care he received, Schwartz said what meant most to him was the empathy and compassion from providers who took the time to answer his questions, just sat with him, and always made him feel like they were committed to making sure his quality of life was the best it could be. After his death in 1995, his friends and family started an educational program to teach these principals throughout the healthcare industry. M. D. Anderson uses the Rounds as an opportunity to take care of its healers by providing emotional support and a means to instruct them on how to communicate better with patients and their families. It is attended by physicians, nurses, and social workers. One of the cases presented at Rounds came from Scott Kopetz, M.D. He talked about a 28-year-old male patient who was diagnosed with a nonseminomatous germ cell tumor in his chest. Dr. Kopetz ordered an intense regimen of chemotherapy to try to shrink the tumor enough to make the remainder resectable. The treatment took its physical toll, but on top of that the man wanted to shoulder the emotional burden alone for a while by not sharing the seriousness of his condition with his wife and family. cIt just made everything harder, d recalled Dr. Kopetz, who said the man eventually decided to tell his wife everything. Other problems in the case included the lack of privacy for doctor-patient consultation at the busy hospital, obstacles in the healthcare system because he was uninsured, and he had started missing appointments. cI had personal guilt that I didn 9t push harder to help him get through the system. When the cancer spread to one of his lungs I began 8foreshadowing 9 a prognosis with less curative options such as hospice, d Dr. Kopetz said, adding that he reached that decision after the patient endured 10 cycles of chemotherapy with no improvement. He said the father of a two-year-old son understood the prognosis, but would not discuss it. The doctor asked the group to make suggestions on how to elicit a response from a patient who understands his situation but refuses to talk about it. The patient ultimately opened up enough to discuss pain manage- ment that included a trip to the emergency room, where he was supposed to receive palliative medication to ease his suffering in his last hours. Unfortunately, there was a mix-up with the staff and the man was sent home, where he died. His wife appeared at the hospital a few days later. cI thought she was coming to rail against me, but she really valued what we were able to do for her husband. She thanked me for doing my best and for the way I interacted with them. d Martin Raber, M.D., clinical professor of Gastrointestinal Medical Oncology, applauded Dr. Kopetz for showing such compassion that the man 9s wife went out of her way to thank him. cThat means the family didn 9t feel like you abandoned them. d Dr. Kopetz was encouraged to acknowledge to himself that part of why he may have been so affected by the case was because the patient was close to his own age. Another suggestion when delivering bad news was to give the patient the impression that you have all the time in the world for him, no matter the setting. Dr. Raber also encour- aged all the doctors on the panel to not be afraid to inquire about the patient 9s spiritual beliefs about death. cSometimes talking to them about the next step in the journey may help relieve emotional and mental suffering. d Another physician commented that while it is important that patients be aware of their status, it is not necessary to tell them at every visit how dire their condition is 4because they live with their symptoms every day and can appreciate for themselves that things are not getting better. cMake it clear that you 9re available to answer questions at a later time 4and move on. d Robert Wolff, M.D., associate professor of Gastrointestinal Medical Oncology and director of the Hematology/ Medical Oncology Fellowship Program, agreed. He said it 9s important to be careful about exactly what is said during the cdeath talk d because the patient may interpret that as being deserted. cWhen a situation reaches that point in my clinic, I tell patients the therapeutic options are limited now and that they need to go home and think about it, and I will meet with them again to talk about what is next. This gives them time to prepare themselves. d Dr. Wolff said. 3 By Maxsane Mitchell Schwartz Center Rounds 4 Taking Care of Our Caregivers Accolades 3 By Maxsane Mitchell 6 DoCMessages " Vol. 3 No. 2 2006 M ary Beth Rios still remembers as if it were yesterday the time she spent as a patient at M. D. Anderson back in 1980. She had surgery to remove a benign pituitary tumor. cI was patient number 150714, d she recalled. cHaving to admit to yourself and the people in your life that something was wrong 4and then having to depend on others for help 4was awful for me. So when I see my patients today, I don 9t have to imagine how they feel. I know they are probably feeling the same way I did. That 9s why I try to do my best for them every day, d said Rios, a research nurse manager in Leukemia and the win- ner of the 2006 Ethel Fleming Arceneaux Outstanding Nurse Oncologist Award. It was pre- sented on June 19th along with a $15,000 check. Waun Ki Hong, M.D., head, Division of Cancer Medicine, is very proud of the work Rios is doing for M. D. Anderson patients. cShe is a hard-working, highly dedicated and effective research nurse, d he said, recalling that Rios was honored in 2004, when she received a DoCM Citation for Excellence Award in Clinical Research. Rios was also a finalist for the Arceneaux award in 2005 and 2004. It is considered one of the most prestigious at M. D. Anderson as it recognizes registered nurses who provide superior hands-on care to patients. Fifteen nurses were nominated throughout the institution this year 4three of them from the division. The other two nominees were Pauline Dieringer, senior research nurse, Genitourinary Medical Oncology; and Oguna Taylor, clinical care coordinator, Lymphoma/ Myeloma Center. One of Rios 9s 12 nominations came from a current patient 4an internal medicine physician from Boston who was diagnosed last year with myelodysplasia, a hematological disorder preceding acute Mary Beth Rios Wins Ethel Fleming Arceneaux Outstanding Nurse Oncologist Award M.D.Anderson Recognizes Dedicated Nurses May 9-13 BMT Staffing Model Presented at ONS Congress I t all started with a question: How do you plan for adequate staffing of pre-trans- plant nurse coordinators in one of the busiest Blood and Marrow Transplantation Centers in the country? To determine the answer, division managers launched a study. Their abstract was accepted for presentation at the 31st Annual Congress of the Oncology Nursing Society in May. Debra Adornetto-Garcia, clinical admin- istrative director for BMT; Bill Kersten, clinical business manager; Eric Koval, lead transplant coordinator; and Larry Vines, senior improvement advisor in Performance Improvement co-authored, cCreating a Staffing Model for RN Blood and Marrow Transplantation Coordinators in the Pre-trans- plant Phase of the Blood and Marrow Transplantation Journey. d The staffing model demonstrates to coordinators and their supervisor the optimal number of patients each of them can effectively manage. cWhen I asked the attendees at ONS if any of them had a staffing model for coordina- tors, they said no, but they 9re receptive to the idea. Two approached me for help in developing a model for their treatment centers, d said Adornetto-Garcia. She myeloid leukemia. cI had been completely discouraged by what I read in medical literature. My wife is also a physician and she too under- stood the lethal implications, but after Ms. Rios and I talked for two hours, I began to feel that something positive might happen here, d said Herman K. Gold, M.D. He was impressed with how his doctor, Hagop Kantarjian, M.D., chair of Leukemia, respectfully communi- cated with Rios as an equal who also exquisitely understood the illness and ordeal he faced. cI am now in complete remission. My wife and I are aware of how far above and beyond the call of duty Mary Beth went on our behalf 4always helping us put lab results in perspective, helping us understand data on trial drugs, and taking our frequent calls, d said Dr. Gold. Another patient wrote that after four-and-a-half years of being in remission, she received an alarming lab report five days before her wedding. Leigh Gates made a frantic call to Rios and read her blood results. cShe was a calming voice and reassured me that everything was fine. She recommended that I get another test before my trip. I did, and my counts were back to normal. I apologized for calling her on her cell phone and Mary Beth told me to always contact her if I ever had a question or a concern. I will never forget that conversation. d That is typical of her commitment to patients, according to Rios 9s supervisor, Dr. Kantarjian. A few years ago, they worked together for two months to enroll 130 people in a multi-center study of STI-571. The drug was ultimately approved by the FDA and mar- keted as Gleevec. Once registered, the patients had to be examined, monitored, and cared for. cMary Beth did this with skill and devo- tion, as well as handling at least 20 calls daily from other patients who wanted to get on the drug, d Dr. Kantarjian noted. cOn audit of (our) studies, no ineligible patients were registered and no protocol violations were found. Nationally, 15 percent of patients registered at other institutions were found to be ineligible, d he continued. cThe standards Mary Beth has set have become a hallmark of excellence recognized throughout the division. d added that her department uses the model each month to study volume and complexity of patients and to look for trends of needs. Neuro-Oncology APNs Contribute to Manual C ongratulations to several advanced practice nurses in the Department of Neuro- Oncology who co-authored five chapters in the Clinical Manual for the Oncology Advanced Practice Nurse , 2nd edi- tion. The book was released last May at the Oncology Nursing Society 9s (ONS) 31st World Congress in Boston. Terri Armstrong, D.S.N., A.P.N., R.N., Neuro-Oncology, wrote the chapters with six other M. D. Anderson nurses. She said the text in the new book is considered to be the caccepted standard reference for M. D. Anderson, Memorial-Sloan Kettering Cancer Center in New York, and several other institutions, d commented Dr. Armstrong. cThis manual is the most up-to-date resource on the care, diagnosis, and management of cancer patients, d she said, mentioning the other six clinicians who contributed chapters to the manual: "Neurotoxicity: Eva Lu Lee, M.S.N., R.N. "Brain Metastases: Laurel Westcarth, M.S.N., R.N. " Peripheral Neuropathy: Kathleen Grisdale, R.N. "Meningitis: Charlita Pacana, M.S.N., R.N. "Seizures: Sur Min, M.S.N., R.N., and Karen Baumgartner, B.S.N., R.N. The manual is available through the ONS Publishing Division. The cost is $80 for members and $130 for non-members. Palliative Nurses Write the Book on Caring for Patients and their Families P roviders from the Palliative Care Center have released a book offering hope and helpful instructions to clinical nurses caring for patients who suffer the emotional and physical effects of cancer. M. D. Anderson 9s Guide to Palliative Care for Nurses covers a variety of topics ranging from pain relief methods, treatment options for nausea and vomiting, and how to assess the family of a dying patient, to recognizing and reducing the stress of caring for terminally ill patients and how to better function at one 9s optimum performance capacity. Patricia Ewert Flannagan, M.S.N., R.N., clinical nurse specialist and Eduardo Bruera, M.D., professor and chair, edited the book that was written by M. D. Anderson employees. 7 DoCMessages " Vol. 3 No. 2 2006 Fatigue Drug and Nursing Telephone Intervention Under Study in New R01 Grant in Palliative Care E duardo Bruera, M.D., chair of Palliative Care and Rehabilitation Medicine, is the principal investigator of the department 9s first R01 grant from the National Cancer Institute (NCI), worth 1.5 million dol- lars. The clinical trial will examine the combined effects of methylphenidate and nursing telephone intervention (NTI) on reducing fatigue in advanced cancer patients. During the four-year trial, 212 patients will be accrued from M. D. Anderson and LBJ Hospital, where division fellows and attending physicians provide oncolo- gy medical care. cA grant of this size is a big deal for us because less than one percent of the National Cancer Institute 9s budget supports this area of research. We 9re very excited, d said Dr. Bruera. The idea for testing to see if personal interaction between caregiver and provider makes a difference in lowering symptom intensity and creating a higher quality of life came about after Dr. Bruera and others reviewed prior fatigue man- agement studies that indicated patients found a daily phone call to be extremely beneficial. cThis led us to believe telephone intervention might provide a therapeutic effect on symptoms. d Trial patients will be separated into four arms consisting of those who will receive methylphenidate and NTI; patients given a placebo and NTI; those receiving the drug without NTI; and those taking a placebo but receiving no phone calls from a research nurse. Dr. Bruera said the study has potentially short- and long-term benefits. It may help advanced cancer patients to have more energy to participate in their treatment or to enjoy family activities, especially when their remaining lives may be short. Additionally, providers will begin to see more cases where cancer cannot be cured, but can be treated as a chronic illness. cThe trial is one of the mechanisms we hope will balance our attempts to eradicate the cancer and to provide palliative care for those who can survive with it long-term. d Cord Blood Bank Accredited, Adds Ben Taub I n late February, the Cord Blood Bank (CBB) was accredited by FACT- NETCORD for a three-year term, making it one of only four facilities in the country and one of eleven in the world. The accreditation applies to all services and facilities at M. D. Anderson that were inspected for cord blood collection, processing, testing, banking, selection, and release limit- ed to allogeneic non-directed donations. The National Marrow Donor Program (NMDP) accredited the program in November and gave the CBB a $250,000 award. Chris Garcia, program manager, said the money is being used to purchase equipment and supplies, as well as hire more staff to collect and process cords. The lab has now acquired 1,800 cord blood units from consenting maternity patients at the Woman 9s Hospital of Texas. That number will rise dramatically now that the institution has reached a similar agreement with Ben Taub General Hospital. Corliss Denman, department administrator for BMT, said the contract with Ben Taub further ensures an ethnically diverse bank, increasing the chances that an appropriate match can be found for a given patient. CBB person- nel have found their first match for an M. D. Anderson patient; however, no transplantation has occurred to date. Yung Taking over Editorship of Neuro-Oncology Journal W.K. Alfred Yung, M.D., chair of the Department of Neuro-Oncology, will become editor-in-chief of Neuro-Oncology in July. David James, Ph.D. from the University of California at San Francisco will be the co-editor. Duke University Press will continue to publish the journal, but the editorial office will be moved to M. D. Anderson 9s Scientific Publications department. Neuro-Oncology has been the Society of Neuro-Oncology 9s official periodical since 1997. It contains peer-reviewed articles, abstracts of annual meetings, and society announcements. cI feel privileged and honored to have been chosen by the society. I hope I can continue the growth curve and bring the journal to the next level, d said Dr. Yung, whose goals include turning the quar- terly publication into a monthly some time in 2007. Neuro-Oncology in 2005 earned an Institute for Scientific Information (ISI) Journal Impact Factor of 4.150, meaning articles published in that year were cited an average of four times. It ranks 30th among the top 40 cancer journals, ahead of the British Journal of Cancer. cNeuro-Oncology is a young journal and already considered the authority in the field, but we want to increase its impact factor, as well as increase the number of manuscripts accepted from Europe and Asia because they are doing some very good studies there, too, d commented Dr. Yung. His term will last for seven years. Doescher Promoted to Management Analyst E ric Doescher 9s responsibilities have expanded following a promotion from operations manager to management analyst, effective April 16. He now has more responsibility for providing financial oversight of the budget for the After Hours/Hospitalist Program and managing the budgetary aspects of our Hematology/Medical Oncology program at LBJ. cI 9m grateful for all of the opportunities to grow professionally at M. D. Anderson. In the year-and-a-half that I have been here, division administrator Wendy Austin has been very supportive 4she encourages me to try new things and doesn 9t limit my interest in taking on more responsibility to become involved in new initiatives in the DoCM, d said Doescher, whose office and telephone extension will remain the same. He will continue to be housed in the DoCM Administrative Office on the 11th floor at the Faculty Center. American Cancer Society Honors Bruera D r. Bruera accepted the 2006 Lane Adams Quality of Life Award from the American Cancer Society in May during a ceremony in Atlanta, where the agency has its headquarters. Dr. Bruera was one of only ten providers in the entire country to be recognized for making a difference through innova- tion, leadership, and providing passionate, skilled care to cancer patients and counsel to their families. Awardees came from many backgrounds including medicine, oncology nursing, social work, and community activism. Russell Receives Staff Educator of the Month Award N ancy Russell, Dr. P.H., senior health education specialist in the Integrative Medicine Program, is very proud of the work she does to educate patients and clinicians about complementary cancer therapies 4and we 9re proud of her for receiving the institu- tion 9s Staff Educator of the Month Award for May! The 21-year veteran employee manages the Complementary and Integrative Medicine Resources (CIMER) Internet site, which receives thousands of hits every month and has won numerous awards. The person who nominated Dr. Russell said she has an endless fund of knowledge and exuberance. When she joined the Integrative Medicine Program in 1995, Dr. Russell intensified her commitment to helping people deal with the challenges of cancer and its treatment. Her work is more than just a job, as she has lost three loved ones to the disease. cTherapies that were previously dismissed are now treated with respect, with some even offered at M. D. Anderson through its Place& of wellness. I feel honored to be able to contribute to this mission, d she said. Accolades 8 Research Highlights T he first Keystone Symposium on Melanoma in more than ten years was held on January 18-23 in Santa Fe, N.M. It was organized by Patrick Hwu, M.D., chair of Melanoma and Elizabeth Grimm, Ph.D., professor of Experimental Therapeutics, to provide a casual setting where researchers, clinicians, patient advo- cates, and representatives from pharmaceutical companies and government agencies could talk about new ideas and challenges involved in advancing the field. About 150 people attended, some from as far away as England and Australia. They focused their discussions on three main areas: immune therapy against melanoma; anti-vascular approaches to melanoma; and melanoma signal transduction and the use of small molecules to target signaling path- ways. cNone of these exciting areas alone is likely to have a significant impact on the disease. That 9s why a multi-disciplinary approach will become more important if we 9re going to go beyond what we 9re doing now, d said Dr. Hwu. Several investigators from across the country and international guests from England and Australia present- ed abstracts on melanoma treatment options and prevention. The group also said the lengthy process to gain approval from the FDA and the enormous cost of drug development were the biggest challenges to more successful translational research. cWe all want to do things as safely as possible for our patients, but governmental regulations have become burdensome and redundant, d Dr. Hwu com- mented. cClearly, more streamlining is necessary. d Attendees added that on top of the stringent government regulation, the amount of money coming from federally- funded agencies has been decreasing annually, making it more important to pur- sue new funding sources such as previously untapped philanthropic support. Planning this winter meeting was a two-year process, including application to the Keystone Organization, which only accepts 40 meetings a year. 3 By Maxsane Mitchell Melanoma Symposium Stresses Need for New, Effective Targeted Therapies cT he incidence of melanoma has been increasing dramatically over the past six decades, creating an urgent need for effective novel therapies, d said Patrick Hwu, M.D., chair, Department of Melanoma Medical Oncology. He was co- chair with Merrick Ross, M.D., Surgical Oncology, of an interactive symposium April 29th in Houston on cMelanoma: An Update on Diagnosis and Treatment. d Other presenters from Melanoma Medical Oncology were Agop Bedikian, M.D., Wen-Jen Hwu, M.D., Ph.D., and Kevin Kim, M.D. Medical oncology discussions primarily surrounded use of immunothera- pies such as interferon and vaccines, biochemotherapy, and development of new targeted agents. Dr. Wen-Jen Hwu noted that randomized trials of chemotherapy, immunotherapy (except vaccines), and chemoimmunotherapy have shown no survival benefit for stages I-III melanoma. However, she presented compelling evidence that treating high-risk patients who have stage III malignant melanoma with interferon-alpha (IFN- ± 2b) after surgery prolongs relapse-free and overall survival, which led to FDA approval of this treatment. She also presented the finding by Suhendan Ekmekcioglu, Ph.D., Experimental Therapeutics, that inducible nitric oxide synthase (iNOS) expression is an aggressive tumor phenotype predicting poor prognosis for survival in stage III metastatic melanoma. Visiting speakers Vernon Sondak, M.D., from the H. Lee Moffitt Cancer Center and Research Institute, and William Sharfman, M.D., Johns Hopkins School of Medicine, debated the pros and cons of considering interferon-alpha standard of care for adju- vant treatment of melanoma. While Dr. Sondak concluded that high-dose interfer- on has a beneficial impact on the natural history of melanoma, he cautioned that we need to do better because, cThere is cur- rently no way to tell who doesn 9t need therapy, who will benefit from therapy, and who will have toxicity from therapy. d Dr. Sharfman countered that because high- dose interferon 9s overall survival benefit is unclear, it should not be considered the standard of care, but instead offered as an option to a select subgroup of patients. Dr. Patrick Hwu demonstrated how the cellular immune system can be activat- ed to induce significant tumor regression in some patients. In a mouse model, he found the best anti-tumor responses and survival rates with vaccines that combine both dendritic cells and T-lymphocyte cells, which he plans to study next in humans with metastatic melanoma. Other strategies to improve anti-tumor immune responses include giving multiple serial immuniza- tions at earlier stages of melanoma, enhancing thymic activity, and utilizing adoptive cell therapy with antigen-specific T-cells. There are numerous genetic and epigenetic indications that dysregulation of the Ras/Raf/MAPK and PI3K/PTEN/AKT/mTOR signal pathways is involved in the survival, proliferation, and invasion of malignant melanoma, noted Dr. Kevin Kim. cA therapeutic strategy of combining small molecules targeting different transduction pathways is the way to go, d he concluded. A promising example is the phase I/II trial of BAY 43-9006 (inhibiting the MAPK pathway) and temsirolimus (inhibiting mTOR ). After reviewing the current standard of care for treatment of metastatic melanoma 4consisting of single agent chemotherapy, combination chemotherapy, and chemotherapy combined with immunotherapy 4 Dr. Bedikian concluded that there is no universally accepted standard therapy for management of unresectable metastatic melanoma. cThere is a dire need to discover new effective drugs, d he said. cA strong effort should be made to have patients participate in clinical trials. d 3 By Carol Howland DoCMessages " Vol. 3 No. 2 2006 Keystone Symposium on Melanoma Held International Conference Addresses New Approaches to Treating MDS E lihu Estey, M.D., and Hagop Kantarjian, M.D., Department of Leukemia, chaired an international confer- ence on cNew Approaches to Biology and Treatment of MDS d held April 28, 2006 at M. D. Anderson. Additional speakers from the DoCM were Jean-Pierre Issa, M.D., Leukemia, and Jeffrey Molldrem, M.D., Blood and Marrow Transplantation. Myelodysplastic syndrome (MDS), a pre- leukemic disorder in which the bone marrow does not produce enough mature white blood cells, red blood cells, and platelets, often trans- forms to acute myeloid leukemia (AML). However, as Dr. Estey noted, distinguishing between the two can be difficult, and most patients die before transformation to AML. The very Elihu Estey, M.D. 9 Research Highlights AACR Symposia Herald More Targeted Approaches to Cancer Treatment T he DoCM was well represented at the 97th American Association for Cancer Research (AACR) Annual Meeting held April 1-5, 2006. Among the DoCM faculty chairing international, multi-institutional symposia were Scott Lippman, M.D., chair, Thoracic/Head and Neck Medical Oncology, leading the symposium on Molecular Targets for Cancer Prevention; Roy Herbst, M.D., Ph.D., Thoracic/ Head and Neck Medical Oncology, session leader for the minisymposium on Novel Agents and New Technologies; Ralph Zinner, M.D., Thoracic/Head and Neck Medical Oncology, co-session leader of the minisymposium on Prognostic and Predictive Factors; and James Abbruzzese, M.D., chair of Gastrointestinal Medical Oncology, leading a Meet the Experts Sunrise Session on Novel Targets For Pancreatic Cancer Therapeutics. The symposium on Molecular Targets for Cancer Prevention focused on interven- tions to prevent or delay carcinogenesis by developing drugs that target transla- tion initiation, TGF-beta signaling, and reactive stroma, as well as by harnessing the host immune response to premalig- nancy. Carmen Behrens, M.D. and coworkers in Thoracic/Head and Neck Medical Oncology also presented evidence that the up-regulation of the basic fibroblast growth factor (bFGF) signaling pathway may provide a novel target for early detection and chemopre- vention of non-small-cell lung cancer. FDA Approves Decitabine for MDS T he FDA approved decitabine for the treatment of myelodysplastic syndrome (MDS) on May 3, 2006. cThis approval is a major advance in our fight against MDS, d said Hagop Kantarjian, M.D., chair, Department of Leukemia. Before approval of decitabine, there was only one approved therapy for MDS. cDecitabine can reduce or eliminate the need for patients with MDS to receive blood transfusions, d said Dr. Kantarjian, also the clinical investigator for the decitabine clini- cal development program for MDS and acute myelogenous leukemia. Department of Leukemia Drs. Oki (medical oncology fellow), Kantarjian, Ravandi-Kashani, Cortes, Garcia-Manero, DoCMessages " Vol. 3 No. 2 2006 immature stem cells have lost their genomic stability in MDS, and escape from apoptosis 4normal, programmed cell death 4 resulting in very low blood cell counts and bone mar- row failure. MDS tends to occur in older adults. Thanks to the better understanding of the biology of MDS that was not available a few years ago, molecular defects have been mapped that can be targeted by novel drugs. These include abnormal signaling pathways and epigenetic silencing of genes that would normally deter malignancy. Dr. Estey explained that therapeutic strate- gies differ according to whether the MDS is considered low risk or high risk due to a higher proportion of blasts (immature blood cells). Dr. Molldrem described a promising treatment for low-risk MDS 4the PR1 peptide vaccine, which elicits cytotoxic T-lymphocytes that react to the peptide to possibly target and kill MDS. Previous studies have shown that active PR1-specific immune responses that kill leukemia are associated with remission. Therefore, studies are underway to determine whether the PR1 peptide vaccine can be used in low-risk MDS to elicit PR1-cytotoxic T-lymphocyte immunity, and whether, in turn, this immune response will produce a clinical response. High-risk patients at M. D. Anderson have the same treatment options as those with AML, but the high-intensity chemother- apy used in AML has not offered any survival advantage in MDS over supportive care due to high rates of resistance to therapy and treatment-related mortality. As an alterna- tive, Dr. Estey discussed the feasibility of using less toxic, lower-intensity targeted ther- apies such as hypomethylating agents, histone deacetylase (HDAC) inhibitors, and aurora kinase inhibitors. The best treatment strate- gy for each patient can then be determined by randomizing them to a high intensity chemotherapy regimen such as clofarabine plus cytarabine or a low intensity treatment such as decitabine, then keeping responders on the initial regimen while switching those who fail to a different treatment regimen, he explained. cDNA methylation is believed to play a major role in the progression of MDS, and inhibitors of DNA methylation such as decitabine and azacytidine are among the most active agents in fighting this disease, d said Dr. Issa in his presentation on epigenet- ics. His research team identified distinct clusters of hypermethylated genes in different patients that correspond to progression-free and overall survival. Multi-institutional studies demonstrated that the CpG island methylation phenotype in MDS particularly confers poor prognosis for survival. Dr. Kantarjian 9s studies of low-dose decitabine showed that leukemia cells did not decrease right away; instead, responses occurred slowly over a few months and improved over time. Viewing these findings as evidence of an epigenetic rather than a cytotoxic response mechanism, Dr. Issa recommended combining drugs that target different epigenetic gene silencing mecha- nisms. These drugs would act synergistically to re-activate expression of the genes that were silenced by malignant stem cells. He also advised studying combinations of epigenetic therapy with biologic, pro-apop- totic, and immune therapies such as vaccines, as well as agents that can reverse resistance to chemotherapy. cAberrant methylation is a powerful prognostic factor in MDS, d Dr. Issa concluded. cDrugs that inhibit DNA methylation are very active in MDS and appear to work via epigenetic mechanisms. d cThanks mostly to decitabine 4to hypomethylating therapies 4survival of MDS improved after 2000, d said Dr. Kantarjian. Two hypomethylating agents have been approved by the FDA for treat- ment of MDS 45-azacytidine and more recently, decitabine, which is ten times more poten

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