John P. Storaasli

Thoracic and Elective Brain Irradiation with Concomitant or Delayed Multiagent Chemotherapy in the Treatment of Localized Small Cell Carcinoma of the Lung: A Randomized Prospective Study by the Southeastern Cancer Study Group

A prospective randomized study was carried out to compare the effectiveness of concomitant or delayed multiagent chemotherapy combined with irradiation to the primary tumor and regional lymph nodes and to the brain in a group of 70 patients with histologically proven small cell undifferentiated carcinoma of the lung. Complete and partial response in both groups was comparable, and the overall survival was comparable. However, relapse‐free survival was significantly higher in patients receiving concomitant chemotherapy and irradiation in comparison with the radiotherapy alone group. Disease‐free survival was higher in the concomitant chemotherapy‐radiotherapy patients, although survival was not significantly modified, probably because of suboptimal chemotherapy. The initial intrathoracic failure rate was 40.7% in the concomitant chemotherapy‐irradiation group, compared with 53.8% in the radiotherapy‐alone patients. None of the patients receiving delayed chemotherapy following the radiotherapy recurrence showed signficant tumor response to the drugs. The incidence of distant metastasis was slightly lower in the chemotherapy groups. Brain metastases were noted in 7% of the patients in both groups. Increased intrathoracic recurrences were noted in patients with lower doses of irradiation. Nine of 13 patients treated with inadequate portals developed intrathoracic recurrences in comparison to 13 of 40 treated with adequate irradiation fields. The study emphasizes the need for intensive chemotherapy and adequate radiation therapy to improve survival of patients with small cell undifferentiated carcinoma of the lung. Additional trials are necessary to assess the role of each modality in the management of these patients.

Adenocarcinoma and mixed carcinoma of the uterine cervix: I. A clinicopathologic study

Ninety-two primary glandular neoplasms of the uterine cervix, including 51 endocervical adenocarcinomas, four endometrioid carcinomas, and 37 mixed carcinomas, were reviewed to define the biologic significance of pathologic features. Pure adenocarcinomas were found to have a better prognosis from mixed carcinomas of comparable stage (overall five-year survival rate, 49 vs. 36%). Endocervical adenocarcinomas with glandular and papillary patterns had a better prognosis than mucinous adenocarcinomas. When mixed carcinomas were separated into mature, signet-ring, and glassy-cell types, patients with the glassy-cell type had a better five-year survival rate than patients with the other types. However, the long-term prognosis was equally poor. The degree of differentiation as determined by the nuclear features was useful in predicting the outcome in patients with adenocarcinomas. Although the number of cases was small, combined surgery and radiotherapy achieved the best long-term survival for patients with pure adenocarcinomas. This was less apparent for mixed carcinomas.

TRANSFUSION OF LEUKOCYTES LABELED WITH RADIOACTIVE PHOSPHORUS.

Mechanisms involved in the failure to raise the white blood cell count by transfusion remain unknown. Previous studies (1) on the effect of transfusion of concentrated suspensions of leuko-cytes obtained from the peritoneal cavity of rabbits have confirmed the clinical observation that the white blood cell count cannot be effectively increased by transfusion. When concentrated sus-pensions of leukocytes were transfused into the venous system of the same rabbit from which they had been obtained or into other rabbits, not only was there no increase in the leukocyte count over a period of several hours, but a severe leuko-penia developed in nearly every animal. In over half the rabbits a subsequent marked leukocytosis developed in four to six hours. This investigation was undertaken to study the disappearance of leukocytes from the circulating blood by determining the radioactivity in various tissues following the transfusion of leukocytes labeled with P52. METHODS Leukocytes labeled with radioactive phosphorus were obtained by injecting a rabbit with approximately 1.0 millicurie of p82 intravenously prior to stimulating the production of leukocytes in the rabbits peritoneum. Two to seven days after injecting the radioactive phosphorus , leukocytes were obtained from the rabbits peri-toneal cavity by a modification of the method of Mudd and coworkers (2). Three hundred to 500 ml. of physio-logic saline were injected intraperitoneally in the evening and a similar amount about 15 hours later. Over-distension of the abdomen is poorly tolerated by the rabbits and may cause respiratory embarrassment and death. Four hours after the second injection of physio-logic saline the peritoneal fluid was removed through a 16 gauge needle using 5 mg. of heparin as an anticoagu-lant. This fluid was centrifuged at a speed of about 500-1000 R.P.M. for five minutes and the sediment re-suspended in Tyrodes solution so that the final concentration of cells was approximately 50,000 cells per cmm. The leukocytes prepared in this manner stained normally with Wrights stain, exhibited ameboid activity, were actively phagocytic for staphylococci and took up supravital stain (Janus green and neutral red). Approximately 90% of the cells were segmented and unsegmented neutrophils. The radioactive phosphorus was firmly bound within the cell, presumably in the nuclear nucleoprotein. In order to demonstrate this, samples of the leukocyte suspension were subjected to repeated washing with Tyrodes solution. Only negligible amounts of radioactivity could be removed by this procedure (Table I), indicating the chemically bound nature of the p82 in these …

A comparative study of blood volume in dogs.

Conclusion 1. A comparison of 3 methods for the determination of blood volume was made on 10 dogs. 2. The average blood volumes expressed as per cent of body weight for the 3 methods were: T-1824, 10.5%; for red cells tagged with P32, 9.7%; and iodinated protein, 9.4%. 3. The iodinated protein method permitted accurate determinations of plasma volumes for a much longer period after injection than did the other two methods. This method was simple and direct. It permitted calculation of the volume within a few minutes after the samples were obtained. It appeared to have a decided advantage over blood volume estimation with P32 impregnated red blood cells and the T-1824 dye method.

LENTICULAR CHANGES ASSOCIATED WITH BETA RADIATION OF THE EYE AND THEIR SIGNIFICANCE

aclinical evaluation of radiation therapy of lesions of the eye requires close co-operation between the ophthalmologist and the radiologist. The ophthalmologist in general is not qualified, without special training, to carry out radiation treatment, and the radiologist is usually not qualified to employ such therapy without a thorough knowledge of the pathogenesis of the lesion treated. This study represents a co-ordinated effort between the Departments of Radiology and Ophthalmology at Western Reserve University. Prior to 1940, gamma rays from radium and grenz rays were used in radiation therapy for various ophthalmologic conditions. In that year, Burnam and Neill (1) reported on the use of beta rays originating from radon gas, the daughter isotope of radium, contained in a glass bulb enclosed within a brass cylinder. This type of applicator was in general use until artificially produced radioactive isotopes became available. In 1950 two of the present authors (C. I T. and H. L. F.) reported on the use o...

Comparative evaluation of radioactive colloidal gold and nitrogen mustard in the treatment of serous effusions of neoplastic origin.

Since its introduction by Muller in 1949, intracavitary radioactive colloidal gold therapy for carcinomatous effusions has become an almost universally accepted mode of treatment. A substantial body of literature (1–12) attests to the fact that this isotope can be expected to control the production of neoplastic effusions in 50 to 70 per cent of all cases. Most authors have agreed that it is most effective when the primary neoplasm originates in the ovary or breast. Those who have worked with colloidal Au198 realize, however, that there are certain disadvantages inherent in its use: (a) the treatment is rather costly to the patient; (b) the short half-life and local unavailability necessitate careful planning and sometimes entail considerable delay in treatment; (c) the amount of radioactivity involved dictates certain precautions against exposure of nursing personnel which militate against optimum nursing care for the patient; (d) even with the best apparatus currently available for instillation, there i...

Detection of Intraocular Tumors with the Use of Radioactive Phosphorus

At the present time the most positive means of identifying malignant tissue is histologic examination. This is the method of choice and can be used in most situations. In the case of intraocular tumors, however, histologic confirmation is possible only after enucleation. It was therefore considered of great importance to utilize the selective localization of certain radioactive isotopes in tumors to aid in the diagnosis, in vivo, of such intraocular neoplasms. It was known from earlier work (1–6) that various tagged materials are selectively taken up by rapidly proliferating tissue and that the increased radioactivity can be detected in vivo by specialized counting procedures. Application of this general method to the problem of identification of intraocular tumors was a logical extension. The problem was essentially one of differentiating between fluid detachment of the retina and detachments resulting from underlying malignant tumors. Although it is often possible to differentiate between these conditio...

I131-labeled serum albumin: its use in the study of cardiac output and peripheral vascular flow.

During the past several years a method for measuring plasma volumes has been under investigation in our laboratory (1, 2). This method involved the use of a tagged serum protein (I131-tagged albumin) and gave promising results which appeared useful. It became obvious that the slow rate of disappearance of tagged albumin from the blood would make this a satisfactory substance for the study of vascular flow measurements. Before this could be achieved, however, it was necessary to develop a number of instruments which would make it possible to detect small amounts of radioactivity by their gamma emission and to record the events rapidly enough so that critical alterations in dilution and mixing of the radioactive albumin could be recorded. The essence of the method which will be described concerns itself with measuring and recording the manner and rate in which iodinated plasma is mixed and diffused through the blood. The character of the curve which is obtained on isolated arteries has proved suitable for q...

THE THERAPEUTIC APPLICATION OF RADIOACTIVE PHOSPHORUS WITH SPECIAL REFERENCE TO THE TREATMENT OF PRIMARY POLYCYTHEMIA AND CHRONIC MYELOID LEUKEMIA

The use of radioactive phosphorus in the treatment of disease stems from the initial studies made by Lawrence and his colleagues in 1936 (1). Since then there have been a number of reports which establish the efficacy of this form of therapy in chronic leukemia and polycythemia (2-11). These clinical reports have been issued from a number of separate institutions, indicating that independent experiences are now fairly widespread. The report by Reinhard et al. (12) is an exhaustive review of the clinical course of patients treated in this fashion. Similar studies by Doan et al. (13) and Lawrence et al. (14) add extensively to the data now available in the literature. It is our intention here to add to the clinical observations presented in the previous reports, but we wish particularly to emphasize the pertinent information available from the literature and from our own work which is the basis and rationale for such treatment. The concept of treating disease with internally distributed radioactive materials is not completely new and attempts in this direction have previously been made by introducing into the blood stream some of the naturally occurring elements, such as radium. However, the invention of the cyclotron and more recently the development of high energy nuclear reactors of the Atomic Energy Commission have given considerable impetus to this concept of therapy. This is particularly true because of the wide variety of radioactive elements which can be produced by these devices, some of which have suitable characteristics (desirable half-life, proper radiation characteristics, and satisfactory chemical properties). The rationale of treating patients with radioactive material arises from the desire to irradiate selectively certain specific tissues and to prolong

Appearance of Protein Tagged with Radioactive Iodine in Thoracic Duct Lymph

Conclusions 1. The total lymph volume is not measurable, so that the exact amount of activated protein that is present in the body lymph, following intravenous injection of iodinated protein, cannot be calculated. However, it appears from this experiment that a negligible amount is present in the thoracic duct lymph 10 minutes after injection. 2. During the first hour there is a rapid increase in the lymph content of radioactive protein followed by a more gradual rise.