Chronicles of CFS™

Part 1:

In the Beginning
By Jaclyn Silverman

A small group of physicians who treated cancer patients came to the first Chemotherapy Foundation Symposium in a conference room at Mount Sinai Hospital in 1972, the year that oncology was first recognized as a subspecialty by the American Board of Internal Medicine.

Symposium founder, Ezra Greenspan, MD, was a practicing oncologist before the word chemotherapy could be found in any dictionary. He created the meeting to bring the emerging developments in cancer therapeutics to physicians treating cancer patients. It was an early stage in an odyssey that paved the way for the extraordinary progress being made today.

A Wartime Paradox
Paradoxically, the deadly agents of two world wars were the starting point for development of a legion of life-saving drugs to be used in other battles for survival. The era of cancer chemotherapy began when naval personnel were exposed to mustard gas during military action in World War II. They had unknowingly participated in the first clinical trial of a cancer drug. US Army studies of related agents had demonstrated the therapeutic efficacy of mustard compounds in treating lymphomas. Not long after that aminopterin, a compound related to the vitamin folic acid, was found to produce remissions in childhood leukemia. The chemotherapy arsenal slowly grew to include many agents developed and tested in government and industry sponsored clinical trials.

A steady stream of FDA-approved drugs flowed from the pipelines of major pharma in the years ahead. Powerful weapons were needed to combat many types of cancer, but magic bullets were hard to find.Following his internship and residency at Mount Sinai School of Medicine, Greenspan, then a fledging oncologist with an innovative bent, worked with Sidney Farber and other scientists at the laboratories of the National Cancer Institute. They were to gain renown in the first government sponsored War on Cancer initiated by Richard Nixon authorized by the National Cancer Act of 1971.

Greenspan joined the faculty at Sinai when cancer was being treated as a growth to be excised with surgery (the more extensive the better was the thinking at the time). How tumor cells proliferated with deadly efficiency through the bloodstream was not understood. It took Greenspan’s iconoclastic will to break through the wall of resistance to the systemic therapies that proved the first effective treatment of common cancers. He was a maverick who overcame the hostility of his peers and a skeptical medical establishment to gain recognition as one of the early advocates for combination therapy.

Greenspan’s first paper documenting patients’ dramatic responses, submitted with before-and-after photos to the Annals of Internal Medicine, was rejected by peer reviewers because, they alleged, he wasn’t treating cancer, or had reversed the order of progression photos, or, they argued, if the paper was accurate, the regimen would be too difficult for clinicians to follow. Five years later, Greenspan was invited by the American College of Physicians to present his results at their golden anniversary meeting. Empirical evidence was proving that cancer was a treatable disease. A landmark paper published in the Journal of the Mount Sinai Hospital in 1968 proved the effectiveness of combination chemotherapy in achieving remissions and longer survival. The first part of the struggle was over. There was new hope for cancer patients.

Greenspan went into private practice in New York City (the office was next door to the home of Jacqueline Kennedy) along with partner physicians Seymour Cohen, Martin Weiner, Lynn Ratner, Michael Goldsmith, and Wilma Bulkin—notably one of the first female oncologists. Soon, terminal breast and ovarian cancer patients who were willing to undergo innovative therapies as a last ditch hope for survival were referred to Greenspan by other clinicians.

With attitudes changing, the potential of newer drugs was recognized, but there was no pipeline. Government did little to help, and investigators in medical institutions had minimal support. He recognized the need for action.

The Chemotherapy Foundation
In 1968, Greenspan founded The Chemotherapy Foundation as a not-for-profit organization to support innovative cancer researcher at major medical centers. Contributions by patients and their families provided crucial seed money for investigators pursuing therapeutic goals that would build new models for cancer care. Greenspan named Shirley Cox as executive director, a position she holds today. This was the start of Greenspan’s extraordinary career with a singular goal of sustaining and extending the lives of cancer patients. In 1972, the Chemotherapy Foundation Symposium Innovative Cancer Therapy for Tomorrow®, became the professional education arm of the foundation—a bridge connecting basic science to oncology practice. The symposium for many years functioned as a conduit bringing the work of the researchers and results of the few clinical trials supported by the NCI to generations of oncologists treating patients.

Starting Out
Interviewing for the position of conference coordinator in 1972 I stressed my ability to work with little supervision. The value of my editorial and marketing background overcame my lack of medical or scientific background. Supported by his mercurial mentoring, I had a key role in launching the Chemotherapy Foundation Symposium. A productive relationship began then continuing for over 32 years until his death in 2004. Unlike most of his colleagues of that time, Greenspan respected women as partners. I was fortunate to have a key role in what became a career spanning half a lifetime.

Although not a professional colleague, I shared the thoughts and very controversial viewpoints of a extraordinary person. Dr Greenspan called me his secretary (administrative assistant title came into fashion later), but treated me like a junior partner who was teachable. Genuinely excited over any new therapy that showed promise, he told me of the resistance and skepticism he met when he introduced the concepts combination chemotherapy. I am very fortunate that his legacy is being carried on although I no longer have a role.

Time to move on. A medical education team bringing new insights to match the challenges ahead is managing the Symposium. As I recall the personal satisfaction I experienced in the long years I worked with Ezra, I am grateful that the mission continues in able hands. I hope that I can make an equally significant contribution working to advance the programs of The Chemotherapy Foundation.

The Division of Medical Oncology at Mount Sinai headed by Greenspan was established in the North Pavilion on Fifth Avenue and 99th Street in New York City. Greenspan and Holland worked out any potential conflicts amicably when James Holland came from Roswell Park to head up the Department of Neoplastic Diseases. Of the generation of oncologists who were trained in Holland’s fellowship program, many presented at the Symposium. Holland and Emil Frei launched the Cancer and Leukemia Group B studies in 1956. Rapid acceleration in development of new cancer therapies motivated Greenspan to broaden the continuing medical education opportunities for oncologists. Emerging advances enlarged the lexicon in conventional oncology practice. We invited the trailblazers and those who followed in their tracks to attend the Symposium. Innovative Cancer Therapy for Tomorrow aka The Greenspan Meeting became a multi-specialty cancer conference. It encapsulated the one-stop learning experience for practicing oncologists saving them an investment of time and money participating in multiple conferences and specialty meetings. Registration grew exponentially as I was able to use Internet as a resource to capture new audiences.

Program Design: A Durable Format
Programming was focused on practical applications in the treatment of specific tumor types. Compilations of relevant data for clinicians were presented in sequential talks grouped by specialty. Discussion of therapeutic innovation was always emphasized. In the early years, the Symposium was a one-man operation. Greenspan’s prescience in selection of speakers whose work became milestones in the evolution of cancer medicine was legendary.

Oncologists require realistic assessments of new developments on the clinical horizon. We were then learning to differentiate drugs with promise for wide scale use across specialty borders from those whose benefit was limited to one type of cancer.

The reports were enthusiastic. We were making a difference for so many patients in a world where so little was known about treating cancer. Attendees often expressed appreciation for the great learning opportunity and the knowledge of advances that would help their patients. Most rewarding was hearing these words from those who proved their appreciation by coming back every year.

I was frequently contacted for help in getting visas from our embassies abroad in many countries. Usually, a letter of invitation from the chair and a copy of the program was sufficient. But not always. Two women oncologists from Mongolia who wanted to come never made it despite my best efforts. We couldn’t convince the consular official that the women weren’t using the Symposium as a ruse to enter and stay in the United States. To my knowledge, neither inner nor outer Mongolia was ever represented at the meeting.

US registrants came in great numbers along with groups from France, Italy, Spain, and other European countries. We welcomed an increasing number of delegates from Asia and Africa every year. The little oncology meeting grew to a large conference of about 2,000 in the Marriott Marquis ballroom.

Part 2:

Where and When
For those who question the chronology, beginning in 1972 the Symposium was held biennially for ten years. It became an annual event to meet the increasing demand from the oncology community for additional learning resources. It is the thirty fourth Symposium that is being held in 2016 and the opportunity to share experience with colleagues. We, in turn, became better able to identify gaps in performance that selection of topics and speakers based on solid evidence in clinical trials could remedy.

After the initial meeting at Sinai, for convenience of faculty and attendees we moved to mid-Manhattan hotels, outgrowing the Barbizon Plaza, the Hilton, Sheraton Plaza, Crowne Plaza before landing at the Marriott ten years ago, where at long last we have the space to accommodate the needs of commercial exhibitors. Some will remember a time when three sponsoring companies shared inadequate space at one table and display materials ordered in error were shipped back with dispatch. What never changed was the calibre and character of the meeting over four decades.

The Symposium broadened its scope in when it became a two-day and then a three-day cancer conference. It was extended to four days when a program for nurses and pharmacists was added. No competing satellite sessions set up conflicts of interest for attendees.

Programming and Practice
Compliance with all Professional guidelines
Under the watchful eyes of CME director Alfie Truchan and, Associate Chair Dr. Edward Ambinder conflicts of interest were monitored.

There was an increasing demand from the oncology community for an opportunity to pool and share experience with colleagues. We became better able to identify gaps in performance that selection of topics and speakers based on solid evidence in clinical trials could remedy. We recognized the differing needs of community and academic based clinicians.

It has always been a challenge to keep oncologists informed of promising developments in a field crowded with data and differing interpretations of same. Chairs and a Clinical Advisory Board of top ranking specialists in hematology, GI, GYN, breast, ovarian, prostate, renal and other neoplasms recommended topics and speakers. Symposium program development based on evidence in clinical trials and best practices strengthened standards of care. Sequential sessions covered the common types of cancer. Advances in technology applied to oncology practice were explored.

The Symposium has had outstanding success using CME as a vehicle for transmission of the advances in treatment that are making significant improvements in patient outcomes, known as Translation Therapy. Presentations by investigators with the hands-on knowledge acquired through participation in clinical trials provide the guidance increasingly needed in employing complicated new treatment regimens.

Q&A exchanges in realtime, surveys, outcome analysis, and reports in the literature document the value of this educational activity.

Special Audiences
Topics and speakers met the needs of the supporting staff whose collaboration contributes to patient welfare. Physicians were encouraged to foster these relationships.

Nurses, NP’s and PA’s who traveled from afar attended the four-day event. Nursing professionals located in the New York regional area were more likely to register for only the Saturday session.. When we learned that Pharmacists had limited opportunities to gain CME, we made arrangements for their accreditation, although the accreditation process was extremely complicated in their specialty.

Pediatric Oncologists appreciated a special session with speakers whose presentations were designed for their patient populations. Childhood cancers, mostly in hematology, often treated successfully had consequences in adulthood.

Featured Events
Breakfast with the Professors began each conference day. Gourmet box lunches were brought into auditorium for the mid-day sessions.

Evening events gave speakers more leeway. But, I will admit to starting the applause when the slides kept coming and lectures went way over the time allotted, so that dinner could, be served to our hungry audience.

Ezra Greenspan Memorial Lecture
To honor his major work, a leading oncologist was selected every year by Franco Muggia for this role. Breast cancer continues to be the focus of investigators’ zeal.

Keystone Speaker
Norman Wolmark, who provided eloquent commentary on unique topics, gave us historical perspectives and provocative points of view. Dr Wolmark was a colleague of Bernard Fisher who worked with him on landmark studies for many years. I appreciated the recognition he gave me in acknowledging any suggestions I had made.

The post-ASCO timing in November is an opportunity for faculty, who presented preliminary data six months earlier, to report on final results of major studies. Many oncologists who attend both meetings gain earlier access to trial results benefiting patients whose progression is slowed and longer survival is achieved.

The many oncologists attending both conferences enjoy the advantages of a one-stop meeting with no breakout sessions, a format that enables them to listen to all the speakers without having to pick and chose between talks in their specialty, and spend time and energies scuttling between conference rooms in varied locations.

Management and Monitors
Franco Muggia, Professor, Department of Medicine at the NYU Langone Medical Center, has had a long career as a practicing clinician and participant in the Symposium for many years. He is currently Medical Director of The Chemotherapy Foundation. His many publications evidence his deeply-based knowledge of gynecological oncology. Edward Ambinder, MD, Clinical Professor of Medicine, Hematology and Medical Oncology, Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, holds an influential position at ASCO, and is known for his involvement and knowledge of practice issues and as a proponent of practical uses of technology by oncologists. They took over leadership roles of the Symposium on Ezra Greenspan’s death in 2004.

Important voices and key leaders in their specialty fields shaped the agenda and served as moderators, a role with the important responsibility of keeping the program on schedule.

While Dr. Greenspan was in charge, he had control on the podium. No faculty members would brook his displeasure. He had a firm hand. Later there were occasions when over-enthusiastic speakers did not respect designated time slots. Resulting cancellation of scheduled presentations were disturbing to audience and faculty. Overtime conflicted with other hotel events. Faculty members hereafter were given the joint responsibility more or less successfully. We had bells and whistles to help. In many ways Dr Greenspan was a hard act to follow.

Moderators included Larry Norton, MSKCC (a protégé of Dr. Greenspan during his early Fellowship days at Sinai), whose significant contributions to the conceptual understanding of breast cancer are well known, Harold Burstein, a program advisor and co-chair of the session, Jordan Berlin and Howard Hochster, who organized and participated in the GI session. Janice Gabrilove and Kanti Rai, hematologists, and Howard Burris guided us in selection of faculty for decades. William Oh, the Ezra Greenspan Professor and a director of the Tisch Cancer Center at Sinai, organized the GU talks. Chandra Belani and Roman Perez-Soler were the lung cancer chairs. Larry Leichman, NYU, was a valued advisor for the GI session. Tamar Safra from Tel Aviv partnering with Franco Muggia presented views on alternative therapies for GYN cancers. Dr. Safar is now caring for cancer patients in China.

Precision Medicine
Leading the Way
Custom-tailored treatment was how Dr. Greenspan referred to the differing regimens he employed based on his unique ability to perceive particular psychological characteristics in individual patients. Many years later, when genes and other variables were identified as markers for selection of treatment strategies, targeted therapies were developed.

Part 3:

Milestones and Trailblazers
Epilogue: Looking Backward and Ahead
Biotherapies, Oncogenomics, Precision Therapy, Immunotherapy, Molecular Therapies, Vaccines, targeted therapies and other advances are achieving new breakthroughs in the control of cancers. Clinical trials are underway. Outcomes that bring us closer to success are eagerly anticipated.

Past and Present
Paul Carbone, Gionna Bonadonna, (Adriamycin), Barnett Rosenberg (Platinum), Douglass Tormey, Stephen Carter (NCI), Richard Cooper, Judah Folkman, Bernard Fisher, Hellstroms from Sweden, James Holland, Emil Frei, Joseph Bertino, Charlotte Friend, Joseph Bertino, George Demetri, Craig Jordan, Richard Pazdur, Larry Norton, Franco Muggia, Edward Ambinder, Pierre Band, Dennis Slamon, Brian Drucker (Gleevec), Eric Rowinsky, Norman Wolmark, Leonard Price (Royal Marsden), Mace Rothenberg, Hagop Kantarjian, Howard Burris, Larry Norton, Kanti Rai and a host of other clinical investigators have made important contributions to cancer therapeutics.

In 1984 Ezra Greenspan and Franco Muggia presented the first Breast Cancer Chemoprevention Conference advocating clinical trials of the newly introduced anti-estrogen tamoxifen for high-risk women. They knew that an agent to prevent recurrence was the miracle drug for women living in fear, although the commercial sponsor ICI (premerger with AstraZeneca) was wary of this benefit claim in marketing the agent. The meeting was widely promoted and well attended, but with no participation by the pharmaceutical company. Ezra Greenspan, with colleague and ally Franco Muggia were marching ahead of the crowd.

It was a surgeon from Pittsburgh, Bernard Fisher, who proved that lumpectomies could replace mutilating surgery for early breast cancers. His studies saved countless women from the trauma of disfigurement. He presented the NSABP studies results at the Symposium in 1976 and at other cancer conferences thereafter.

Dr. Greenspan often expressed concerns that the clinical trials would not happen in his lifetime. Fortunately, he was around to see the NSABP studies that showed unequivocally longer survival and fewer recurrences compared to the control group.

He was out of the mainstream again in advising his patients to stay on the drug for five years or more. Later studies were to prove his wisdom. Anti-estrogen agents since introduced have proved equally or more effective.

About Dr. Fisher: Many will remember how his name was maligned when a published study included data from one Canadian investigator who had altered surgery dates in order to enroll lapsed patients. It took some time and stressful experience before the injustice was recognized, and with the support of colleagues he went on to achievements that repaired a very unfairly damaged reputation. Sadly, those who accomplished the most were the easiest target.

Judah Folkman introduced angiogenesis, a revolutionary theory that postulated growth of tumors through capillary blood vessels. His work presented at the Symposium in 1997 led to a new field of research. A kind and gentle man, he took the time to explain the theory to me (a scientific know-nothing) when I invited him to speak at the 1997 Symposium. A Judah Folkman lecture in his honor became an annual event during the meeting for a few years following his death.

With support from The Chemotherapy Foundation, clinical investigators are new ground. Oncologists employing the emerging therapies presented to oncologists at the Symposium created by Greenspan and at other cancer meetings have gained better patient outcomes. In this way, Greenspan’s mission of empowering oncologists from the US and throughout the world with a continuing flow of information on new agents, clinical trials, and the experience and guidance of thought leaders is continuing.

As empirical evidence is amassed showing how many types of cancer can be controlled and even cured, attendees at CME meetings from diverse practice settings are encouraged to inform their patients of improved treatment options and the value of enrollment in clinical trials. As new health care options emerge, greater understanding of the challenges facing patients and care providers will be needed.

The Symposium was the professional education arm of the Foundation Symposium designed to provide practical guidance to clinicians challenged to keep up with all new developments in treatment of their patients. It continues in the vanguard of educational activities for oncologists and hematologists.

Falsification of data for career advancement is an uncommon occurrence. Most who choose a specialty with a patient population experiencing frequent unfortunate outcomes have worthy goals. Proving benefits of new agents based on rigid criteria took resolve and relentless energy. Overcoming bureaucratic hurdles to gain FDA approval for release of agents for one type of cancer was the first step. The Symposium was often the platform presenting results of trials broadening applications of specific agents to a wider spectrum of tumors. An aura of respect gained over time by so many investigators who introduced major findings to a Symposium audience enhanced credibility for and acceptance of new therapies.

The damage caused by emphasis on wrongdoers is reflected in an image of cancer research subjected to constant negativity in congress and press, a factor that has influenced the guidelines for support of professional education. The tide may turn again, but lack of funding for cancer education is a disservice for patients who need life saving drugs employed efficiently and effectively.

Epilogue: Looking Backward and Ahead
In the 2009 economic downturn and unfavorable political climate, industry’s retreat from support of live CME increased. Income from educational grants declined precipitously. We could no longer cover the costs of this labor-intensive educational event, nor was the Foundation able to do so without curtailing their research grant program.

Our skeletal team had been running the Symposium for over forty years. But all good things must come to an end. Hennessy Associates, through their educational affiliate Physicians Education Resource (PER), gave the Symposium a second life to continue its role in the oncology community. This how and why the Symposium is now one of the many leading cancer conferences here and abroad under the management of PER.

Franco Muggia. Professor, Department of Medicine at the NYU Langone Medical Center and Edward Ambinder, MD, Clinical Professor of Medicine, Hematology and Medical Oncology, Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, who took over leadership of the Symposium when Ezra Greenspan died in 2004, continued as Chairs and provided guidance for several years.

The Team
Accolades should be shared. Always ready to take on daily tasks and any crisis with enthusiasm and efficiency were Roch McDowell, Ricardo Somarriba, Maureen Furlan, and Alfie Truchan, Jeanette Cotto and Leonson Stapleton of Sinai CME.

While clinical investigators use new agents and delivery systems resulting in better oiutcomes, the Symposium continues to empower those who care for cancer patients from the US and throughout the world by winnowing out the most consequential and credible from the ever-mounting influx of reports on new agents, clinical trials, and the experience and guidance of thought leaders. The Symposium will build on the past in going forward to a greater future for the The Greenspan Meeting.

The Chemotherapy Foundation is a 501(c)(3) not-for-profit charitable, educational,

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