Reprinted from The American Journal of Roentgenology, Radium Therapy and Nuclear Medicine Vol. CXVII, No. 3, March, 1973 PRINTED WHOLE BODY AND PARTIAL BODY RADIOTHERAPY By EUGENE L. SAENGER, M.D., EDWARD B. SILBERSTEIN, M.D., CINCINNATI, OHIO; DETROIT, MICHIGAN; AND MEMPHIS, TENNESSEE THE HE purpose of these investigations has been to improve the treatment and general clinical management and if possible the length of survival of patients with advanced cancer. Systemic effects of radiation therapy have been given particular attention in our work. In the period-February 19, 1960, through August 31, 1971, 85 adults were given whole or partial body radiation as therapy for far advanced cancer. This paper will report on the survival of patients in 3 categories: colon; lung; and breast. Prophylactic whole body radiation therapy was given to 3 children with localized Ewing's sarcoma and this experience will be discussed briefly. Investigations of biochemical, cytologic and psychologic tests have been reported elsewhere. 8.11.50 Our experience with the adjuvant use of autologous bone marrow will also be described. ANIMAL STUDIES The animal investigations basic to our work stem from the studies of Hollcroft et al.13-15 These authors demonstrated better tumor regression when whole body irradiation was preceded by localized radiation therapy than when localized radiation therapy was given alone both for lymphoma and carcinoma in mice. The studies of Jacobson et al.18.19 showed the impor tance of shielding of the spleen and other organs and parts of the body in preventing high dose radiation lethality in the mouse. BRIEF REVIEW OF TOTAL BODY IRRADIATION IN MAN Total body irradiation was first employed in 1923 by Chaoul and Lange.' Its use in 270 cases over the next 20 years was reviewed by Medinger and Craver." These authors found the greatest palliation in the lymphomas and myeloproliferative diseases, but also noted improvement in multiple myeloma. Thirty-five patients with advanced carcinoma or sarcoma were included in this series, most of them receiving their total body radiation between 1931 and 1933. Loeffler et al. compared total body irradiation in single doses up to 150 r with nitrogen mustard and triethylene melamine and found that neither chemotherapy nor radiotherapy differed in hematologic effects, but that the patients receiving radiation did not experience the malaise of varying severity noted by all patients receiving the chemotherapeutic agents. Subjective improvement was noted only in the radiotherapy group. Collins and Loeffler' gave total body irradiation in single exposure up to 200 roentgens and found this form of systemic therapy "a useful addition to the management of advanced cancer." The malignancies treated included lymphoma, chronic • Presented at the Seventy-third Annual Meeting of the American Roentgen Ray Society, Washington, D. C., October 3-6, 1972. From the Departments of Radiology, Internal Medicine and Radioisotope Laboratory, University of Cincinnati College of Medicine, Cincinnati, Ohio. + Radiation Therapy Department, Sinai Hospital of Detroit, Detroit. Michigan. Division of Nuclear Medicine, Department of Radiology, Universi: of Tennessee, Memphis, Tennessee. Supported in part by USPHS RR 5408, NIH General Research: Support Grant of the College of Medicine, University of Cincinnati. VOL. 117, No. 3 Whole Body Radiotherapy of Advanced Cancer Interest in total body irradiation in the treatment of Ewing's sarcoma, a tumor of children which carries a high mortality, has been aroused by reports from Milburn et al., Jenkins et al.," and Rider and Hasselback." In a small series so treated, survival appeared to be moderately improved compared to larger series treated by conventional local radiotherapy and/or ablative surgery. These groups felt further evaluation of this form of therapy to be most important. 671 Cincinnati College of Medicine and those of the National Institutes of Health. The use of formal informed consent forms in this study antedated the above requirements by 2 years. The project is reviewed and approved regularly by the above Committee. ELIGIBILITY OF PATIENTS Patients become eligible for this form of treatment if they have advanced cancer for which cure could not be anticipated. Three children with localized Ewing's tumor at Children's Hospital were given whole body radiation as part of the curative attempt after the primary tumor had been ablated with local radiotherapy. Biopsy proof of the malignancy has been established in all instances. Clinical data in Additional data have been published by the Medical Division of Oak Ridge Associated Universities,' concerning total body radiation therapy of lymphoproliferative and myeloproliferative disease. Summaries of the frequent use of total_each_case have been reviewed by several body irradiation for the therapy of leukemia appear in an article by Buckner et al. and in a comprehensive review of bone marrow transplantation by Bortin. Whole body radiation in routine clinical therapy has been and is currently used for leukemia, 2. lymphoma,-. Hodgkin's disease, polycythemia vera, cancer of breast," cancer of thyroid, cancer of prostate,10 10.31 and multiple myeloma.". Such therapy may be given by external radiation therapy (as in this particular study) or in the form of various radionuclides. STUDY DESIGN The studies reported here were initially considered as being in Phase I (to determine whether the treatment was toxic or not) and subsequently as Phase II (whether treatment appears effective or not but without controls). In reviewing these data it has been possible to find some comparable material in the literature. In one category, cancer of bronchus, comparable data were available in our institution. INFORMED CONSENT AND INSTITUTIONAL REVIEW All patients gave informed consent in accordance with directives of the Faculty Research Committee of the University of physicians to be certain that the tumor had indeed extended from its primary site and that curative therapy was not applicable. This preliminary evaluation is followed by an observation period of 7-14 days to observe the general condition of the patient and to carry out baseline laboratory tests to be as certain as possible that the condition of the patient is relatively stable. Frequently this determination is difficult since the patients have serious illnesses of long standing and often have had considerable previous therapy. Patients remain in the hospital as long as is necessary. Prior to the use of autologous bone marrow transfusion, hospitalization was occasionally as long as 8-10 weeks. Length of stay was also dependent upon the severity of the clinical manifestations stemming from the cancer. With the use of par. tial body irradiation and bone marrow infusion, hospitalization has been greatly shortened. The follow-up procedure is continuous during the lifetime of the patient. A total of 112 subjects were initially entered in the study through August 31, 1971. During the screening period of 7-14 days, 24 of them (21 per cent) were not continued in the study and did not receive whole or partial body irradiation. Chief 672 Saenger et al. MARCH, 1973 among the reasons for elimination was an thermoluminescence dosimeters. Over the indication in the pretreatment phase that course of the study, the air exposure rates some risk from wide-field radiation might at the distance indicated above varied from ensue or that another method of treatment 3 to 6 per minute. was considered preferable. In some, a very rapid progress of the disease made inclusion undesirable. The treatment was completed in 85 adults and 3 children between April 1960 and August 31, 1971. Three patients have received 2 separate courses of treatment in this program. Follow-up time for survivors is reported through August 31, 1972. PATIENT DOSIMETRY The radiation is delivered by a cobalt 60 teletherapy unit under the following exposure conditions: The beam is directed horizontally at a wall 342 cm. away with the midline of the patient at 286 cm. from the source. For whole body exposures, the radiation beam size for the 60 per cent isodose curve at the patient midline distance is a square approximately 120 cm. X120 cm. The patient is placed in the sitting position with legs_raised and head tilted slightly forward. Radiation is given by delivering half the specified exposure laterally through one side of the patient, the patient is then turned and the other half exposure delivered laterally through the other side. The combined dose of the 2 radiation fields provides a good homogeneous dose distribution through the patient. The maximum variation in lateral dose distribution was ±13 per cent for 1 patient who had a lateral trunk dimension of 36 cm. The exposure to the patient is determined using a percentage depth dose table corrected for the source-to-skin distance used for the patient. Using the corrected depth dose at patient midline (1/2 lateral dimension at the trunk in the plane of the xiphoid) and a conversion factor of 0.957 rads/roentgen for cobalt 60 gamma radiation, the midline air exposure required to give a desired midline absorbed dose in rads is calculated. The validity of this procedure was established with measurements in an Alderson Rando Phantom using For individuals receiving partial body radiation, the teletherapy collimator is used to restrict the beam. The xiphoid is used as the boundary of the field for upper and lower body exposures. The lateral dimensions of the patient in the plane of the xiphoid is again used for calculating the desired midline dose. As for the whole body exposure, the dose is delivered bilaterally. Additional information on the dosimetry aspects of this study has been published by Kereiakes et al." ANALYSIS OF SURVIVAL DATA In considering the survival data there was a lack of consistent selection bias both in recommendation that a patient be eligible for treatment and in regard to the dose. The principal investigator had no part in determination of therapy in any given case except for outlining the general principles of the therapeutic regime. The choice in the case of each patient was made by several radiation therapists, 3 having been associated with the project during the 10 year period. In addition, 2 internists have had active roles in the selection and medical care of each patient. The dose of radiation to be given was decided upon by the radiation therapist in consultation with the internist. There are 3 categories of patients (those with carcinoma of the colon, lung and breast) which are large enough to permit some analyses of survival. Each group will be discussed separately. Survival data are given in days from the diagnosis of far advanced disease, since this convention has been used frequently in the literature and permits comparison of our survival data with published reports. CANCER OF THE COLOK AND RECTUM Twenty-nine patients with this tumor comprised the largest single category (Table 1). In all cases the patients were classed VOL. 117, No. 3 Whole Body Radiotherapy of Advanced Cancer TABLE I CANCER OF COLON—ALL CASES BY LENGTH OF SURVIVAL OF ADVANCED DISEASE 673 •Study No. refers to the roster of patients described serially in Technical Reports: No. 6-15′′, 18-29",; 83-91, 93-103, 104-1119, 113-113 personal communication. 200+300 LB ",77-83", Dose in rads at the midline. Where no letter follows the dose, whole body radiation was given. LB➡lower body irradiation; UB upper body irradiation. The dividing point is the xiphoid. Median survival-327 days. as far advanced and in a few instances as terminal. Four patients were not included in the study for medical reasons, or because the patients themselves declined participation in the study. In order to make an appropriate comparison, several published series were reviewed. Series of cases of colon cancer metastatic to liver were utilized, since they were the best found by us with appropriate time periods of metastasis available for comparison. Stearns and Binkley," in 32 patients with colon cancer with liver metas tases, found a median survival time of 11 months after palliative resection of the primary tumor; in 28 of their patients in whom only biopsy or diversion was performed, the median survival was 8 months. In 353 patients with untreated colon cancer metastatic to liver, Pestana et al. reported a median survival of 9 months. Figure 1 presents an analysis of 177 patients with liver metastases and no subsequent therapy reported by Jaffe et al. There is also a group of 61 patients reported by Rapoport and Burleson" treated with 5-fluorouracil. The 22 patients in our series with proven metastatic carcinoma of the colon to the liver treated by irradiation are also shown in Figure 1. The median survival time for untreated patients was 146 days; for patients treated only with 5-fluorouracil, 255 days; and, among our patients with liver metastases, 391 days (Table 1). A life table analysis was performed and indicates that the treatment given to our patients was approximately equivalent to the group given 5fluorouracil. There was no evidence that the median survival time was shortened by total or partial body irradiation (Fig. 1). It should be appreciated that 5 of our patients had received or are receiving 5-fluorouracil in addition to the radiation therapy (3 of these with liver metastases). The median survival for the entire group of 29 patients (22 with liver metastases) was 327 days. CANCER OF THE BRONCHUS This group of 15 patients (Table 111) had far advanced disease with distant metastases at the time of treatment. The best comparison group was from our own institution reported by Horwitz et al. The median survival of the 15 patients receiving whole body irradiation was 193 days from the time of diagnosis. The median survival of 61 patients seen at Cincinnati General Hospital from December, 1961, to June, 1964, was 135 days. In 15 of the 17 cases with distant metastases excluded by Horwitz et al. from their study (see caption to Fig. 2), the median survival was 32 days. This last group of patients with distant metastases constitutes the most appropriate comparison group. When the median survival of 15 patients mentioned by Horwitz et al." is compared with the 15 •Two of the 17 patients excluded in the Horwitz et al. study were treated by whole body radiation. |