to what I already read about the previous studies that had looked at this and those patients that had shown it wasn't effective. In addition, you have heard that radiosensitive tissues, bone marrow, get destroyed with 100 to 300 rads, certainly 400 or 500 rads. You have also heard that radioresistant tumors like GI cancer and breast, the ones that were treated here, take thousands of rads to kill the tissue, to kill the cancer. So it was not medically reasonable, it was not scientifically reasonable to think that giving someone 300 rads half body or 150 rads whole body would in any way touch the radioresistant malignant spread of cancer without wiping out their bone marrow first. The dose differences between radioresistant and radiosensitive are quite high, thousands versus hundreds. So there wasn't a medical rationale and scientific rationale, and that fact was noted in 1942. I am not telling you something that I figured out last week. I am telling you something that was published. This scientific rationale, this medical thinking, was published by Craver in 1943. Dr. STEPHENS. May I reply again to your question about my own specialty not being medicine? Mr. PORTMAN. Sure. Dr. STEPHENS. May I do so? Mr. PORTMAN. Yes, ma'am. Dr. STEPHENS. It relates to my recommendation that we have common citizens on all boards that decide how hospitals and universities and medical services shall be organized. If we can't do that, we are not a democracy, in my opinion. I am an English professor, all right. Medicine is not a magic science. It is not a body of knowledge different from all other bodies of knowledge that only certified people can understand. Mr. PORTMAN. I appreciate that response. I asked that question, in the context of your statement as to the patients being terminally ill or not, which is in my mind a medical issue and a diagnostic issue. We asked about-where it said the patients had not agreed, on page 26 of the ad hoc report, you see something about two patients did not agree to be treated. That is what I was referring to. Dr. STEPHENS. May I say that I am extremely happy that I have been able to work lately with Dr. Egilman, because, of course, I am not a physician. There is a great deal I don't know about cancer. Mr. PORTMAN. Thank you very much. Mr. BRYANT. Thank you very much for your testimony. At this time we will ask our fourth panelist to come forward, which consists of Dr. Eugene Saenger, Professor Emeritus of Radiology, University of Cincinnati. Dr. Saenger, thank you very much for being here today. At this time, we would ask you to proceed. STATEMENT OF EUGENE SAENGER, M.D., PROFESSOR EMERITUS OF RADIOLOGY, UNIVERSITY OF CINCINNATI Dr. SAENGER. Thank you, Mr. Chairman. There is a great deal to respond to in this hearing, and I will begin by stressing the important points that we wish to bring out concerning our work. One purpose of the study was the treatment of patients with far advanced cancer to whom the goal was the relief of pain, shrinkage of cancer and improvement in well-being. A second purpose was to study the systematic effects of radiation on the patient, the systemic effects. The third and most important, treatment was given only if benefit to the patient was anticipated. Patients were chiefly from the General Hospital. Selection was based only on the presence of advanced cancer and where no other therapy was considered to be as or more effective than the available chemotherapy. Race, IQ or socioeconomic standing were not selection factors. Treatment was paid for by the Cincinnati General Hospital and the National Institutes of Health. No Department of Defense funds were used for treatment or patient care or decisions regarding therapy or patient reimbursement. Patients were told that the treatment might help them and were cautioned that it might not. Some patients chose not to be treated. There was nothing secret about our work. There was nothing secret as to its being conducted. There was nothing secret about the findings obtained. The primary goal of the study was to improve the treatment and general clinical management by increasing, if possible, survival of patients with advanced cancer and palliation of symptoms. In addition, observations in laboratory tests were carried out to seek effects of radiation on cancer patients and on the changes that could be ascribed to radiation. The background for this project originated in my observations over the previous 20 years that cancer patients treated with radiation might be benefited by more careful evaluation of the effects of this kind of treatment. The scientific indications that these goals might be achievable were based on two levels of evidence, one from animal studies and one from human studies. Animal studies indicated better tumor regression by localized radiation followed by total body irradiation for lymphoma and carcinoma in mice. Human studies for treatment of advanced cancer, for far advanced solid tumors prior to 1960 suggested the value of total body radiation. It was employed in several American medical centers and internationally. Treatment was given with success in relieving pain, shrinking tumors and, in some cases, prolonging survival. A major reason that we could begin this work resulted from several developments. First, the cobalt 60 teletherapy unit was installed in General Hospital in 1958, the first in the State of Ohio. Harold Perry, M.D., our first full-time radiation therapist, came from Memorial Sloan-Kettering Cancer Institute in New York and was familiar with total and partial body radiation techniques. James G. Kereiakes, Ph.D., a physicist, joined the department in 1959. He performed the calculations regarding the administration of the doses prescribed by the treating physician. I believe that there could be implications of this treatment for individuals exposed to radiation under other circumstances. In 1958, I submitted an unsolicited application to DOD because there had been no studies on the metabolic effects of radiation, and funds were available. The Army recognized the importance of cancer therapy in this regard. This proposal was reviewed by J. A. Isherwood, M.D., for the Army Medical Research and Development Command. And, to quote, Any correlation of tumor response to total dose of irradiation by such means as proposed in this project would be of great value in the field of cancer. In addition, if by some means such as those proposed accurate knowledge of the total dose of radiation received could be determined, it would be of inestimable value in case of atomic disaster or nuclear warfare. Patients were not recruited. Patients were referred for this form of therapy mostly from the tumor clinic, outpatient or inpatient. I was not involved in patient selection or in determination of the extent of dose or the regions involved. These decisions were made solely by the attending physicians, internists and surgeons and by radiotherapists. There were 24 patients entered into the study who were not given total or partial body irradiation. Some were rejected because it was thought the patient would not benefit. Several patients and their families declined treatment. Some were treated by other means. In 1962, we developed for the DOD a document concerning the eligibility of patients for therapy-in 1962. And it stated, There is a reasonable chance of therapeutic benefit to the patient. The likelihood of damage to the patient is not greater than that encountered from comparable therapy of another type. The facilities for support of the patient and complication of treatment offer all possible medical services for successful maintenance of the patient's well-being. Race was not a factor in selection, only the type of cancer and extent. A statistical analysis done only after the program was terminated confirmed that the patients in this study did not differ from the patient population of the Cincinnati General Hospital. Again, IQ was not a factor in patient selection. The subject of informed consent-I believe we sort of fell in a period when there was a change in the general understanding of informed consent. In our study, informed consent for therapy was obtained by the attending physicians. In the 1940s and 1950s, informed consent was verbal, except for the general brief signed informed consent required by the hospital from all patients who were hospitalized for whatever services they required. In this project, the purpose and actual treatment and the possible outcomes were discussed with the patient and often included family members. In April, 1965, this project began the use of written informed consent 2 years before it was required in our medical center. It clearly indicated that the risks of treatment were discussed. One criticism of our work stems from the instructions of the attend personnel not to inquire concerning nausea, vomiting and diarrhea in the first few days after treatment. Since both nausea and vomiting could be induced by suggestive questions, we requested that no questions be asked as to how the patient felt within these first few days. This restriction did not in any way restrict the administration of drugs such as Compazine to relieve symptoms. Of interest is that, after treatment, 44 percent of the patients who were treated had no nausea and vomiting, 27 percent noted it for three hours or less, and 14 percent had symptoms for 6 hours or less. These responses are comparable to chemotherapy at the time. Funding. As noted earlier, most costs of treatment were paid by the Cincinnati General Hospital. This amounts to about $483,000. There were no professional costs or physicians fees for patient care. Some funding was obtained from the NIH through the General Clinical Research Center of our hospital, which was a unit funded by the NIH. The records of each patient in the hospital on that service were submitted to the NIH and approved. In addition, several of the postgraduate fellows in another NIH training grant of our department participated in this study. DOD funding was utilized solely for observation of patient symptoms and for the extensive laboratory tests carried out. DOD funds had no relation to choice of dose, choice of patient or patient care in any way. No patient was compensated or reimbursed or paid for treatment. The total DOD contract was about $671,000. Mortalities. In the group of patients who received radiation there were three categories in which there were enough patients to compare with other patients in our hospital treated differently or with comparable groups described in the refereed medical literature. The cancers were those of the breast, lung, and colon. The death rates were comparable to those treated by other means. This can be seen clearly in our 1973 paper and the graphs that are there. An important question is whether radiation was the factor leading to the early death of a patient. These patients had far advanced cancers which were growing exponentially. In the course of disease, the patients received chemotherapy and/or local radiation therapy both before and immediately after total or partial body irradiation. For these reasons, it is not possible to identify a single form of treatment or the rapid growth of cancer as being the single contributing cause of death. It most likely would be the rate of growth of cancer itself. There were 20 cases in which patients survived longer than 1 year. Except for the one patient with Ewing's sarcoma who remains alive after 25 years, the longest survivor lived 9 years. Two other relatively long survivors lived 5 years each. Palliation was successful with relief of pain in 31 percent of patients. There was decrease in tumor size in 31 percent and an increase in well-being found in 30 percent. No change was observed in 31 percent. Because of the radiation induced hematological depression, bone marrow storage and reinfusion began in 1964. With the improvement in techniques to include harvest of the marrow under general anesthesia and replacement immediately after total body irradiation, it became possible to avoid the characteristic depression of the white cells in five patients. This promising development was stopped at the time of the termination of the contract. This pioneering use of bone marrow has been and is being used today. Review by others. The UC Faculty Research Committee. Our protocol was submitted to this newly formed committee in March 1966. Provisional approval was given in 1967, with recommendations for review of therapeutic efficacy, bone marrow infusion as a supportive measure and some revisions in the study design. At no time was the project disapproved by the faculty research committee as it received exhaustive and critical reviews, and it was approved again in 1971. The ad hoc committee of the University of Cincinnati began a complete review of this project in 1971. Among the findings were that phase III studies should be initiated with better criteria for the determination of palliative effects and that bone marrow transplantation should be pursued. The study was judged to be adequate for support of the critically ill patients because of the development of skilled team management, especially with the help of a psychiatrist and psychologist, coupled with home visits. The American College of Radiology. You have already heard of the three gentlemen who visited us. This distinguished group made two visits to our hospital. Their major findings were as follows: One, the project is validly conceived, stated, executed, controlled and followed up. Two, the patient's selection based on clinical consideration conforms with good medical practice. Three, the records, publications, the patient-follow-up are voluminous and commendable. Four, the procedure used for obtaining patient consent is valid, thorough and consistent with the recommendations of the National Institutes of Health and with the practice of most cancer centers. And, five, should this project come before the Senate or one of its committees in some fashion, we would urge your support for its continuation. At the request of Senator Edward Kennedy, the Government Accounting Office reviewed the accounts of the Cincinnati General Hospital to determine whether there had been any intermingling of DOD funds used for patient care since we have pointed out from the start of our work that no DOD funds would be used for this purpose. An excerpt from the letter dated May 26, 1972, from the Comptroller General to Senator Kennedy, follows: Concerning the contract with the University of Cincinnati, officials of the Defense Nuclear Agency stated that the cost of radiation treatment and patient care have not been borne by their agency. They stated also that funds of the Defense Nuclear Agency have been used only to pay for supplementary laboratory analyses of patients who had received whole body irradiation in order for the Defense Nuclear Agency to gain information in areas that were relevant to national defense. From the National Institutes of Health, D.T. Chalkley, Ph.D., Chief, Office of Protection from Risks, was very supportive of our work. In a letter copied to Senators Nunn and Talmadge, he comments that, It is to be regretted that this incident has halted what promised to be a very significant addition to our armamentarium against metastatic cancer. He also wrote directly to Senator Nunn, pointing out that, "The patients were treated individually for the diseases that they had." |