Progress in Cancer Treatment

Lecture by Thomas J. Fahey Jr.

Thomas J. Fahey Jr., Senior Vice President, Clinical Program Development at the Memorial Sloane Kettering Cancer Center in New York, gave a lecture for employees at the Norwegian Radium Hospital and the National Hospital on April 29th, addressing the concept "Comprehensive Cancer Center". The title of his talk was "Progress in cancer treatment". The lecture took place at the National Hospital.
PROGRESS IN CANCER TREATMENT
Thomas J. Fahey Jr., MD

The creation of the first cancer hospital on 106th Street and Central Park West in New York in 1894 was the catalyst that led to the systematic and intense study of malignancies, and the consolidation of clinical cancer treatment by pioneers such as Bradley Coley and James Ewing. It was in the French gothic building called the New York Cancer Hospital that those with similar interests and goals were brought together and were provided the space, environment and the impetus to attack cancer on multiple fronts. If that building had not been built, James Ewing may have made his mark as a great Professor of Pathology at Cornell, but Ewing was so eccentric that he may have not survived in the stilted academic environment of a medical school and his great work describing Neoplastic Diseases might never have been written.

Under Ewings leadership the concept of organizing teams of medical experts, skilled in different anatomical disciplines, into specialized services, evolved. This ultimately led to the development of surgical subspecialties that are now recognized internationally. In 1902, only 6 years after the discovery of x-rays by Roentgen in Germany, the use of x-ray as a cancer therapy was pioneered in this first cancer hospital. It was also there in 1903 that Dr. William Coley first experimented with a crude type of immunotherapy in the form of bacterial vaccines. It was there in 1915 that Dr. James Ewing, working in partnership with the farsighted James Douglas, a wealthy mining engineer, established a radium department, which laid the foundation for the development of radiotherapy as a treatment of cancer in the United States. In 1917 one-third of the world’s supply of radium was in the Memorial Hospital building, given to it by James Douglas. In 1918, Ewing published the first textbook of cancer pathology, titled “Neoplastic Diseases”, which established the first systematic and comprehensive basis for diagnosing human cancer.

In the early 20’s the first radiation research laboratory in the United States was established at Memorial. It was visited by Marie Curie in 1921. An automatic radon plant produced radon “seeds”, encapsulated in gold, which were the forerunners of interstitial radiotherapy or “brachytherapy”. It was in the old Memorial Hospital that supervoltage radiation was first pioneered with a teletherapy radium machine.

In the 1930’s, parallel with developments in the field of radiotherapy at the hospital, the surgical services, particularly the Head and Neck Service under Hayes Martin, and the Gastric and Mixed Tumor Service under George Pack, became outstanding training programs for young surgeons from all parts of the world, who came to learn the new radical techniques in surgery that were curing patients previously considered to be incurable.

In the 30’s, in a move that one must consider almost visionary, and made possible by a grant of land by Mr. John D. Rockefeller, Jr., the hospital moved into a new building on the east side of Manhattan adjacent to the Cornell Medical College and Rockefeller Institute for Medical Research. In 1939 the new 12 story structure on 68th Street became the largest of all institutions devoted to cancer and allied diseases, with the only cancer ward for children in the world. In that year the first one million volt x-ray tube was installed in the new Memorial Hospital building and Dr. Ewing retired as Director and was replaced by Dr. Cornelius Rhoads.

New avenues in research were opened. The major ones were: the investigation of steroid metabolism in relationship to carcinogenesis; the beginning of the investigation of agents which exercised an inhibitory action on cancer cells in vitro and the translation of these observations to treatment of patients; and the study of the metabolic aspects of certain types of cancer and then translating these metabolic studies into methods which made it possible for the cancer patient to undergo more radical major procedures, in an attempt to cure cancer by both surgery and radiologic means. The effect of nutrition on carcinogenesis was first studied by Dr. Rhoads and Suguira in 1940.

After World War II, a $10 million dollar gift by Mr. Alfred Sloan and Mr. Charles Kettering to the hospital was the next step in the development of the comprehensive cancer center model. This gift was for a basic research institute devoted exclusively to the cancer problem. In these laboratories the preeminent cancer chemotherapy program at Memorial was developed in the late 1940’s under the direction of Drs. Rhoads, Stock, Karnofsky, Burchenal and Phillips. In this first Sloan-Kettering Institute building methods were devised to permit many human cancers to grow in laboratory animals allowing our scientists to test the effects of chemotherapeutic agents on human cancer cells away from the human hosts. In the early 50’s in this building Ernst Wynder demonstrated the link of lung cancer, and later cancer of the oral cavity, pharynx, and bladder to cigarette smoking.

It was in this Sloan-Kettering Institute that an analgesic study section was developed in 1952 which pioneered the development of assay methods for analgesic drug evaluation. The analgesic properties of narcotic antagonists were demonstrated there, and this led to the development of potent analgesics with lower abuse potential. In the early 50’s, in these laboratories, surgeons and biochemists together studied the nutrition and physiology of patients undergoing radical cancer surgery. Many of the intravenous and feeding regimens which we now consider routine were pioneered here at the time by Drs. Randall, Pack, McNeer, Schwartz, Bodansky and Roberts.

There were many firsts in this Sloan-Kettering building in the 50’s. Some
regard the development of methods for screening and testing chemotherapeutic agents as one of the greatest contributions of the institute. From 1945 on, over 30,000 chemicals, and more than 70,000 preparations, were screened by methods developed at SKI, and many of the active chemotherapeutic agents used today were detected, synthesized and developed. An observation by Dr. Min Chu Li in 1954, that a high level of circulating hormone fell rapidly after treating metastatic choriocarcinoma with methotrexate was the first time patients with a disseminated metastatic human cancer were cured by chemotherapy.

The laboratories in the SKI building in the 1950’s were incredibly productive. The use of serum transaminase and other blood enzymes to evaluate cardiac and liver diseases were developed there. Dr. John Laughlin and his staff developed the first computerized radiation treatment planning system. New anticancer compounds were synthesized in the organic chemistry laboratories there under the direction of Dr. Fox. The relationship of viruses to some forms of cancer was strengthened by the discovery that a virus in mice caused rapidly progressive leukemia. In the biochemistry labs automated techniques for the assay of various enzymes were developed, which led to their widespread use throughout the world to help detect cancer and monitor its treatment. The development of automated cytology procedures also occurred at that time.

In 1964, a new Kettering laboratory building provided the space and the facilities for more sophisticated investigation into the basic biological mechanisms of cancer. It was there in 1965 that institute scientists were able to identify the gene which was a major determinent in the susceptibility of mice to leukemia. Evidence that a herpes virus might be involved in the development of nasal cancer was found by institute scientists in 1966.

Closer collaboration between the basic scientists and the clinicians could be seen in the late 60’s with the investigation of the enzyme L-Asparaginase which became useful in treating childhood leukemia. In 1968, in this new Kettering building the first cyclotron in a cancer center was installed. This cyclotron permitted on-site production of a variety of biologically important short lived radioisotopes, and the development of labeling methods for biologically important compounds for use in tumor localization and metabolic studies, and this allowed the development of PET technology for imaging cancer in humans that is now a reality.

In 1969 a new outpatient building was opened, allowing the rapid development of ambulatory cancer treatment plans. In 1973, the opening of a new Memorial Hospital building with 600 beds with only single or double rooms, 18 operating suites and a bone marrow transplant unit was the cornerstone for rebuilding a modern cancer center.

In 1980, Dr. Paul Marks became the new President of the Center, and was the first CEO of all three corporations – the hospital, the research institute and the cancer center which coordinated the clinical and basic research arms of the institution. Under his leadership, the Radiation Oncology Department was completely rebuilt into the largest in the world with 20 linear accelerators all integrated with computer links for treatment planning and quality control- 10 at the main hospital and 10 more in satellite treatment centers in the suburbs around Manhattan. A separate Comprehensive Breast Cancer Center was built, a 300,000 square foot new basic research laboratory named for John D. Rockefeller, with a library and education center, a new 10 story ambulatory center with a hotel above, a separate center to receive and triage international patients and a new center for prostate and urologic cancers.

In 2000, Dr. Marks retired to his laboratory and was succeeded by Dr. Harold Varmus, a Nobel Laureate for genetics who had been Director of the National Institutes of Health for 6 years prior to coming to Memorial Sloan-Kettering Cancer Center. Dr. Varmus will oversee the new direction in biomedical cancer research, understanding genetic mechanisms controlling the development of cancers, which will finally give us the means to know which persons are at high risk for cancer, and the new tools to prevent and control cancer, which I believe we will see in this century. In the meantime, the exciting advances in radiologic and computer technology will allow us to detect, observe and treat malignancies much earlier in their development, enhancing our ability to cure more patients than ever thought possible even 10 years ago.